bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of prolonged running on foot posture: a repeated measures study of half marathon runners using the foot posture index and navicular height
Authors: Cowley Emma , Marsden Jonathan 
Published: May 2013

AbstractBackgroundDifferent foot postures are associated with alterations in foot function, kinetics and the subsequent occurrence of injury. Little is known about changes in foot posture following prolonged weightbearing exercise. This study aimed to identify changes in foot posture after running a half marathon.MethodsFoot posture was measured using the Foot Posture Index (FPI‐6) and navicular height in thirty volunteer participants before and after running a half marathon. FPI‐6 scores were converted to Rasch logit values and means compared for these and navicular height using an ANOVA.ResultsThere was a 5 mm drop in navicular height in both feet when measured after the half marathon (P < 0.05). The FPI‐6 showed a side x time interaction with an increase in score indicating a more ‘pronated’ position in the left foot of + 2 [Rasch value + 1.7] but no change in the right foot (+ 0.4 [+ 0.76]) following the half marathon.ConclusionThe apparent differences between the FPI‐6 and navicular height on the right foot may be because the FPI‐6 takes soft tissue contour changes into consideration whilst the navicular height focuses on skeletal changes. The changes in foot posture towards a more pronated position may have implications for foot function, and therefore risk of injury; shoe fit and comfort and also the effect of therapeutic orthoses worn during prolonged running.
Sialic acid utilization by Cronobacter sakazakii
Authors: Joseph Susan , Hariri Sumyya , Masood Naqash , Forsythe Stephen 
Published: May 2013

Abstract

Background
The Cronobacter genus is composed of seven species, and can cause infections in all age groups. Of particular concern is C. sakazakii, as this species is strongly associated with severe and often fatal cases of necrotizing enterocolitis and meningitis in neonates and infants. Whole genome sequencing has revealed that the nanAKT gene cluster required for the utilisation of exogenous sialic acid is unique to the C. sakazakii species (ESA_03609–13).
Sialic acid is found in breast milk, infant formula, intestinal mucin, and gangliosides in the brain, hence its metabolism by C. sakazakii is of particular interest. Therefore its metabolism could be an important virulence factor. To date, no laboratory studies demonstrating the growth of C. sakazakii on sialic acid have been published nor have there been reports of sialidase activity. The phylogenetic analysis of the nan genes is of interest to determine whether the genes have been acquired by horizontal gene transfer.

Results
Phylogenetic analysis of 19 Cronobacter strains from 7 recognised species revealed the nanAKTR genes formed a unique cluster, separate from other Enterobacteriaceae such as E. coli K1 and Citrobacter koseri, which are also associated with neonatal meningitis. The gene organisation was similar to Edwardsiella tarda in that nanE gene (N-acetylmannosamine-6-phosphate-2epimerase) was not located within the nanATK cluster. Laboratory studies confirmed that only C. sakazakii, and not the other six Cronobacter species, was able to use sialic acid as a carbon source for growth. Although the ganglioside GM1 was also used as carbon source, no candidate sialidase genes were found in the genome, instead the substrate degradation is probably due to β–galactosidase activity.

Conclusions
Given the relatively recent evolution of both C. sakazakii (15–23 million years ago) and sialic acid synthesis in vertebrates, sialic acid utilization may be an example of co-evolution by one species of the Cronobacter genus with the mammalian host. This has possibly resulted in additional virulence factors contributing to severe life-threatening infections in neonates due to the utilization of sialic acid from breast milk, infant formula, milk (oligosaccharides), mucins lining the intestinal wall, and even gangliosides in the brain after passing through the blood–brain barrier.
Subthalamic nucleus deep brain stimulation for Parkinson’s disease: 8 years of follow-up
Authors: Li Dianyou , Cao Chunyan , Zhang Jing , Zhan Shikun , Chen Shengdi , Sun Bomin 
Published: May 2013

Abstract

Objective
The short-term benefits of bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced Parkinson’s disease (PD) are well documented, but long-term benefits are still uncertain. The aim of this study is to evaluate the outcome of 8 years of bilateral STN stimulation to PD patients.

Methods
In this study, 31 consecutive PD patients were treated with bilateral STN stimulation. Their functional status was measured using the Activities of Daily Living section of the Unified Parkinson’s Disease Rating Scale (UPDRS-ADL) at drug on (with medication) and drug off (without medication) states preoperatively and at 1, 5, and 8 years postoperatively. In addition, Levodopa equivalent doses and stimulation parameters were also assessed.

Results
After 8 years of STN stimulation, the UPDRS-ADL scores were improved by 4% at drug off status (P > 0.05) and 22% at drug on status (P < 0.05) compared with baseline; the levodopa daily doses were reduced by 28% (P < 0.05) compared with baseline; the stimulation voltage and pulse width were not changed, but the stimulation frequency was decreased remarkably compared with the 5 years of follow-up. Adverse events were observed in 6 patients, including misplacement of the electrode and skin erosion requiring further surgery. All events were resolved without permanent sequelae. 2 patients died of aspiration pneumonia 6 and 7 years after surgery.

Conclusions
The marked improvement in UPDRS-ADL scores were still observed after 8 years of bilateral STN stimulation with medication.
Innate immune response after adenoviral gene delivery into skin is mediated by AIM2, NALP3, DAI and mda5
Authors: Schulte Matthias , Sorkin Michael , Al-Benna Sammy , Stupka Jadwiga , Hirsch Tobias , Daigeler Adrien , Kesting Marco Rainer , Steinau Hans-Ulrich , Jacobsen Frank , Steinstraesser Lars 
Published: May 2013

Abstract
Methods for human skin gene therapy requires efficient and stable introduction of genes into skin cells. Transient cutaneous gene therapy is an attractive approach in the treatment of skin diseases. The ‘Achilles heel’ of adenoviral gene therapy is its immunogenicity and many aspects of adenovirus induced cutaneous immune reaction still remain unanswered, particularly the role of keratinocytes. Therefore, human keratinocytes were transfected with adenoviral DNA and cytokine expression was analyzed. Moreover, adenoviral transduction of full-skin was performed ex vivo and in vivo. We observed cytokine induction after cytoplasmatic internalization of adenoviral DNA into epidermal cells. Inhibition of AIM2, NALP3, DAI or mda5 downregulated the cytokine response. Transduction of immunocompetent mice led to a detectable transgene expression for 12 days. Re-application of the vector led to a decrease in intensity and duration of transgene expression limited to 4 days and an increased cytokine expression. In contrast, immunodeficient mice showed a reduced expression of cytokines after DNA internalization. AIM2, NALP3, DAI and mda5 are essential in the induction of an innate immune response towards adenoviral DNA. This immune reaction leads to a decrease in transduction efficiency of the vector after re-application and modulation of these receptor systems stabilizes transgene expression.
Comprehensive behavioral characterization of an APP/PS-1 double knock-in mouse model of Alzheimer's disease
Authors: Webster Scott J , Bachstetter Adam D , Van Eldik Linda J 
Published: May 2013

Abstract
Introduction
Despite the extensive mechanistic and pathological characterization of the amyloid precursor protein (APP)/presenilin-1 (PS-1) knock-in mouse model of Alzheimer's disease (AD), very little is known about the AD-relevant behavioral deficits in this model. Characterization of the baseline behavioral performance in a variety of functional tasks and identification of the temporal onset of behavioral impairments are important to provide a foundation for future preclinical testing of AD therapeutics. Here we perform a comprehensive behavioral characterization of this model, discuss how the observed behavior correlates with the mechanistic and pathological observations of others, and compare this model with other commonly used AD mouse models.

Methods
Four different groups of mice ranging across the lifespan of this model (test groups: 7, 11, 15, and 24 months old) were run in a behavioral test battery consisting of tasks to assess motor function (grip strength, rotor rod, beam walk, open field ambulatory movement), anxiety-related behavior (open field time spent in peripheral zone vs. center zone, elevated plus maze), and cognitive function (novel object recognition, radial arm water maze).

Results
There were no differences in motor function or anxiety-related behavior between APP/PS-1 knock-in mice and wild-type counterpart mice for any age group. Cognitive deficits in both recognition memory (novel object recognition) and spatial reference memory (radial arm water maze) became apparent for the knock-in animals as the disease progressed.

Conclusion
This is the first reported comprehensive behavioral analysis of the APP/PS1 knock-in mouse model of AD. The lack of motor/coordination deficits or abnormal anxiety levels, coupled with the age/disease-related cognitive decline and high physiological relevance of this model, make it well suited for utilization in preclinical testing of AD-relevant therapeutics.
Serum microRNA expression as an early marker for breast cancer risk in prospectively collected samples from the Sister Study cohort
Authors: Godfrey Ashley C , Xu Zongli , Weinberg Clarice R , Getts Robert C , Wade Paul A , DeRoo Lisa A , Sandler Dale P , Taylor Jack A 
Published: May 2013

Abstract
Introduction
MicroRNAs (miRNAs) are small, non-coding, single-stranded RNAs between 18-22 nucleotides long that regulate gene expression. Expression of miRNAs is altered in tumor compared to normal tissue; there is some evidence that these changes may be reflected in the serum of cancer cases compared to healthy individuals. This has yet to be examined in a prospective study where samples are collected before diagnosis.

Methods
We used Affymetrix arrays to examine serum miRNA expression profiles in 410 participants in the Sister Study, a prospective cohort study of 50,884 women. All women in the cohort had never been diagnosed with breast cancer at the time of enrollment. We compared global miRNA expression patterns in 205 women who subsequently developed breast cancer and 205 women who remained breast cancer-free. In addition within the case group we examined the association of miRNA expression in serum with different tumor characteristics, including hormone status (ER, PR, and HER-2) and lymph node status.

Results
Overall, 414 of 1,105 of the human miRNAs on the chip were expressed above background levels in 50 or more women. When the average expression among controls was compared to cases using conditional logistic regression, 21 miRNAs were found to be differentially expressed (P≤.05). Using qRT-PCR on a small, independent sample of 5 cases and 5 controls we verified overexpression of the 3 highest expressing miRNAs among cases, miR-18a, miR-181a, and miR-222; the differences were not statistically significant in this small set. The 21 differentially expressed miRNAs are known to target at least 82 genes; using the gene list for pathway analysis we found enrichment of genes involved in cancer-related processes. In a separate case-case analyses restricted to the 21 miRNAs, we found 7 miRNAs with differential expression for women whose breast tumors differed by HER-2 expression, and 10 miRNAs with differential expression by nodal status.

Conclusions
miRNA levels in serum show a number of small differences between women who later develop cancer versus those who remain cancer-free.
Plasma levels of mitochondrial and nuclear DNA in patients with massive pulmonary embolism in the emergency department: a prospective cohort study
Authors: Arnalich Francisco , Maldifassi Maria Constanza , Ciria Enrique , Codoceo Rosa , Renart Jaime , Fernández-Capitán Carmen , Herruzo Rafael , Garcia-Rio Francisco , López-Collazo Eduardo , Montiel Carmen 
Published: May 2013

Abstract
Introduction
Cell-free plasma mitochondrial DNA (mt-DNA) and nuclear DNA (n-DNA) are biomarkers with prognostic utility in conditions associated with a high rate of cell death. This exploratory study aimed to determine the plasma levels of both nucleic acids in patients with massive and submassive pulmonary embolism (PE) and to compare them with other biomarkers, such as heart-type fatty acid-binding protein (H-FABP) and troponin I (Tn-I)

Methods
This was a prospective observational study of 37 consecutive patients with massive PE, 37 patients with submassive PE, and 37 healthy subjects. Quantifications of plasma mt-DNA and n-DNA with real-time quantitative polymerase chain reaction (PCR), and plasma H-FABP and Tn-I by commercial assays, were done on blood samples drawn within 4 hours after presentation at the emergency department.

Results
Plasma mt-DNA and n-DNA concentrations were much higher in patients with massive PE (median, 2,970 GE/ml; interquartile range (IQR), 1,050 to 5,485; and 3,325 GE/ml, IQR: 1,080 to 5,790, respectively) than in patients with submassive PE (870 GE/ml and 1,245 GE/ml, respectively; P < 0.01) or controls (185 GE/ml and 520 GE/ml, respectively). Eighteen patients with massive PE died of a PE-related cause by day 15 of observation. Plasma mt-DNA and n-DNA values were 2.3-fold and 1.9-fold higher in the subgroup of nonsurviving patients than in survivors. H-FABP and Tn-I values were also higher in patients with massive PE who died (7.3 ng/ml and 0.023 ng/ml, respectively) than in those who survived (6.4 ng/ml, and 0.016 ng/ml, respectively). By receiver operating curve (ROC) analysis, the best cutoff values for predicting 15-day mortality were 3,380 GE/ml for mt-DNA, 6.8 ng/ml for H-FABP, 3,625 GE/ml for n-DNA, and 0.020 ng/ml for Tn-I, based on the calculated areas under the curve (AUCs) of 0.89 (95% confidence interval (CI), 0.78 to 0.99), 0.76 (95% CI, 0.69 to 093), 0.73 (95% CI, 0.58 to 0.91), and 0.59 (95% CI, 0.41 to 0.79), respectively. By stepwise logistic regression, a plasma mt-DNA concentration greater than 3,380 GE/ml (adjusted odds ratio (OR), 8.22; 95% CI, 1.72 to 39.18; P < 0.001) and a plasma value of H-FBAP >6.8 ng/ml (OR, 5.36; 95% CI, 1.06 to 27.08; P < 0.01) were the only independent predictors of mortality.

Conclusions
mt-DNA and H-FBAP might be promising markers for predicting 15-day mortality in massive PE, with mt-DNA having better prognostic accuracy.
Sleep, anxiety and fatigue in family members of patients admitted to the intensive care unit: a questionnaire study
Authors: Day Alex , Haj-Bakri Samer , Lubchansky Stephanie , Mehta Sangeeta 
Published: May 2013

Abstract
Introduction
Family members of critically ill patients often experience increased incidence of physical and mental health issues. One of the first ways family members suffer is by losing sleep. The purpose of this study is to understand sleep quality, levels of fatigue and anxiety, and factors contributing to poor sleep in adult family members of critically ill patients.

Methods
A questionnaire was designed to evaluate sleep, fatigue and anxiety during the intensive care unit (ICU) admission. We incorporated three validated instruments: General Sleep Disturbance Scale (GSDS), Beck Anxiety Index (BAI) and Lee Fatigue Scale (NRS-F). Adult family members of patients in ICU for more than 24 hours were approached for questionnaire completion. Patient demographics were recorded.

Results
The study population consisted of 94 respondents, (49.1 ± 12.9 years, 52.7% male); 43.6% were children and 21.3% were spouses of ICU patients. Sleep quality was rated as poor/very poor by 43.5% of respondents, and good/very good by 15.2%. The most common factors contributing to poor sleep were anxiety (43.6%), tension (28.7%) and fear (24.5%). Respondents' most common suggestions to improve sleep were more information regarding the patient's health (24.5%) and relaxation techniques (21.3%). Mean GSDS score was 38.2 ± 19.3, with 58.1% of respondents experiencing moderate to severe sleep disturbance. Mean BAI was 12.3 ± 10.2, with 20.7% of respondents experiencing moderate to severe anxiety. Mean NRS-F was 3.8 ± 2.5, with 57.6% of respondents experiencing moderate to high fatigue. Family members who spent one or more nights in the hospital had significantly higher GSDS, BAI and NRS-F scores. The patient's Acute Physiology and Chronic Health Evaluation (APACHE) II score at survey completion correlated significantly with family members' GSDS, BAI and NRS-F.

Conclusion
The majority of family members of ICU patients experience moderate to severe sleep disturbance and fatigue, and mild anxiety.
Limits of normality of quantitative thoracic CT analysis
Authors: Cressoni Massimo , Gallazzi Elisabetta , Chiurazzi Chiara , Marino Antonella , Brioni Matteo , Menga Federica , Cigada Irene , Amini Martina , Lemos Alessandro , Lazzerini Marco , Carlesso Eleonora , Cadringher Paolo , Chiumello Davide , Gattinoni Luciano 
Published: May 2013

Abstract
Introduction
Although computed tomography (CT) is widely used to investigate different pathologies, quantitative data from normal populations are scarce. Reference values may be useful to estimate the anatomical or physiological changes induced by various diseases.

Methods
We analyzed 100 helical CT scans taken for clinical purposes and referred as nonpathological by the radiologist. Profiles were manually outlined on each CT scan slice and each voxel was classified according to its gas/tissue ratio. For regional analysis, the lungs were divided into 10 sterno-vertebral levels.

Results
We studied 53 males and 47 females (age 64 ± 13 years); males had a greater total lung volume, lung gas volume and lung tissue. Noninflated tissue averaged 7 ± 4% of the total lung weight, poorly inflated tissue averaged 18 ± 3%, normally inflated tissue averaged 65 ± 8% and overinflated tissue averaged 11 ± 7%. We found a significant correlation between lung weight and subject's height (P <0.0001, r2 = 0.49); the total lung capacity in a supine position was 4,066 ± 1,190 ml, ~1,800 ml less than the predicted total lung capacity in a sitting position. Superimposed pressure averaged 2.6 ± 0.5 cmH2O.

Conclusion
Subjects without lung disease present significant amounts of poorly inflated and overinflated tissue. Normal lung weight can be predicted from patient's height with reasonable confidence.
3′,4′-Dimethoxyflavone and valproic acid promotes the proliferation of human hematopoietic stem cells
Authors: Kaur Kiranpreet , Mirlashari Mohammad Reza , Kvalheim Gunnar , Kjeldsen-Kragh Jens 
Published: May 2013

Abstract
Introduction
Human hematopoietic stem cells (HSCs) have been clinically used for transplantation and gene and cellular therapy for more than 4 decades. However, this use is limited because of the challenges in the ex vivo culturing of HSCs. The major hurdle is to amplify these cells without losing their self-renewing property.

Methods
In our study, we tested 3′,4′-dimethoxyflavone (3′4′-DMF) and valproic acid (VPA) on the ex vivo expansion of HSCs under both normoxic (20% O2) and hypoxic (1% O2) conditions. 3′4′-DMF is a widely used anticancer drug that acts as a competitive antagonist of the aryl hydrocarbon receptor. VPA is a potent inhibitor of histone deacetylase and is used in the treatment of neurologic disorders.

Results
Culturing HSCs (from mobilized peripheral blood) under normoxia, with 3′4′-DMF and VPA, highly preserved the CD34 positivity (3′4′-DMF, 22.1%, VPA, 20.3%) after 1 week and strongly enhanced the CD34+ cells (3′4′-DMF, 27.8 fold; VPA, 34.1 fold) compared with the control cultures (11.6% and 14.4 fold). Addition of 3′4′-DMF and VPA also resulted in more primary colonies and replating efficiency compared with control cultures. Although no significant effect was observed on the enhancement of CD34+ cells under hypoxia, the number of primary colonies was significantly higher than the control cultures.

Conclusions
Based on these findings, this study presents, for the first time, in vitro evidence for a new and relevant effect of 3′4′-DMF on human HSCs. In addition, the results suggest a potential clinical use of 3′4′-DMF and VPA in HSC therapy.
Shared polygenic contribution between childhood attention-deficit hyperactivity disorder and adult schizophrenia
Authors: Hamshere Marian L. , Stergiakouli Evangelia , Langley Kate , Martin Joanna , Holmans Peter , Kent Lindsey , Owen Michael J. , Gill Michael , Thapar Anita , O'Donovan Mick , Craddock Nick 
Published: May 2013

BackgroundThere is recent evidence of some degree of shared genetic susceptibility between adult schizophrenia and childhood attention-deficit hyperactivity disorder (ADHD) for rare chromosomal variants.AimsTo determine whether there is overlap between common alleles conferring risk of schizophrenia in adults with those that do so for ADHD in children.MethodWe used recently published Psychiatric Genome-wide Association Study (GWAS) Consortium (PGC) adult schizophrenia data to define alleles over-represented in people with schizophrenia and tested whether those alleles were more common in 727 children with ADHD than in 2067 controls.ResultsSchizophrenia risk alleles discriminated ADHD cases from controls (P = 1.04 × 104, R2 = 0.45%); stronger discrimination was given by alleles that were risk alleles for both adult schizophrenia and adult bipolar disorder (also derived from a PGC data-set) (P = 9.98 ×10−6, R2 × 0.59%).ConclusionsThis increasing evidence for a small, but significant, shared genetic susceptibility between adult schizophrenia and childhood ADHD highlights the importance of research work across traditional diagnostic boundaries.
Reducing duration of untreated psychosis: care pathways to early intervention in psychosis services
Authors: Birchwood Max , Connor Charlotte , Lester Helen , Patterson Paul , Freemantle Nick , Marshall Max , Fowler David , Lewis Shôn , Jones Peter , Amos Tim , Everard Linda , Singh Swaran P. 
Published: May 2013

BackgroundInterventions to reduce treatment delay in first-episode psychosis have met with mixed results. Systematic reviews highlight the need for greater understanding of delays within the care pathway if successful strategies are to be developed.AimsTo document the care-pathway components of duration of untreated psychosis (DUP) and their link with delays in accessing specialised early intervention services (EIS). To model the likely impact on efforts to reduce DUP of targeted changes in the care pathway.MethodData for 343 individuals from the Birmingham, UK, lead site of the National EDEN cohort study were analysed.ResultsA third of the cohort had a DUP exceeding 6 months. The greatest contribution to DUP for the whole cohort came from delays within mental health services, followed by help-seeking delays. It was found that delay in reaching EIS was strongly correlated with longer DUP.ConclusionsCommunity education and awareness campaigns to reduce DUP may be constrained by later delays within mental health services, especially access to EIS. Our methodology, based on analysis of care pathways, will have international application when devising strategies to reduce DUP.Declarations of interestNone.