bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Modifiers Predisposing to Congenital Heart Disease in the Sensitized Down Syndrome Population
Authors: Li Huiqing , Cherry Sheila , Klinedinst Donna , DeLeon Valerie , Redig Jennifer , Reshey Benjamin , Chin Michael T. , Sherman Stephanie L. , Maslen Cheryl L. , Reeves Roger H. 
Published: April 2012

Background—
About half of people with Down syndrome (DS) exhibit some form of congenital heart disease (CHD); however, trisomy for human chromosome 21 (Hsa21) alone is insufficient to cause CHD, as half of all people with DS have a normal heart, suggesting that genetic modifiers interact with dosage-sensitive gene(s) on Hsa21 to result in CHD. We hypothesize that a threshold exists in both DS and euploid populations for the number of genetic perturbations that can be tolerated before CHD results.

Methods and Results—

We ascertained a group of individuals with DS and complete atrioventricular septal defect and sequenced 2 candidate genes for CHD:
CRELD1
, which is associated with atrioventricular septal defect in people with or without DS, and
HEY2
, whose mouse ortholog (
Hey2
) produces septal defects when mutated. Several deleterious variants were identified, but the frequency of these potential modifiers was low. We crossed mice with mutant forms of these potential modifiers to the Ts65Dn mouse model of DS. Crossing loss-of-function alleles of either
Creld1
or
Hey2
onto the trisomic background caused a significant increase in the frequency of CHD, demonstrating an interaction between the modifiers and trisomic genes. We showed further that, although each of these mutant modifiers is benign by itself, they interact to affect heart development when inherited together.

Conclusions—
Using mouse models of Down syndrome and of genes associated with congenital heart disease, we demonstrate a biological basis for an interaction that supports a threshold hypothesis for additive effects of genetic modifiers in the sensitized trisomic population.
Dairy Consumption and Risk of Stroke in Swedish Women and Men
Authors: Larsson Susanna C. , Virtamo Jarmo , Wolk Alicja 
Published: April 2012

Background and Purpose
Epidemiological studies of the associations of low-fat dairy and specific dairy food consumption with risk of stroke are sparse. Our aim was to examine the association between consumption of total, low-fat, full-fat, and specific dairy foods and risk of stroke in a prospective cohort study.

Methods
We followed 74 961 Swedish women and men who were free from cardiovascular disease and cancer and who completed a 96-item food frequency questionnaire in 1997. Incident cases of stroke were ascertained from the Swedish Hospital Discharge Registry.

Results

During a mean follow-up of 10.2 years, we ascertained 4089 cases of stroke, including 3159 cerebral infarctions, 583 hemorrhagic strokes, and 347 unspecified strokes. Consumption of low-fat dairy foods was inversely associated with risk of total stroke (
P
for trend=0.03) and cerebral infarction (
P
for trend=0.03). The multivariable relative risks for the highest compared with the lowest quintile of low-fat dairy consumption were 0.88 (95% CI, 0.80–0.97) for total stroke and 0.87 (95% CI, 0.78–0.98) for cerebral infarction. Consumption of total dairy, full-fat dairy, milk, sour milk/yogurt, cheese, and cream/crème fraiche was not associated with stroke risk.

Conclusions
These results suggest that low-fat dairy consumption is inversely associated with the risk of stroke.
Joint Effect of Modifiable Risk Factors on the Risk of Aneurysmal Subarachnoid Hemorrhage
Authors: Lindekleiv Haakon , Sandvei Marie S. , Romundstad Pål R. , Wilsgaard Tom , Njølstad Inger , Ingebrigtsen Tor , Vik Anne , Mathiesen Ellisiv B. 
Published: April 2012

Background and Purpose—
The joint effect of risk factors on the risk of aneurysmal SAH (aSAH) has been studied sparsely.

Methods—
We examined the potential synergism between cigarette smoking, hypertension, and regular alcohol consumption and the risk of aSAH in a prospective, population-based cohort of participants from the Nord-Trøndelag Health Study and the Tromsø Study in Norway. Interaction was assessed on additive and multiplicative scales.

Results—
We identified 122 cases of aSAH over 977 895 person-years of follow-up. Interaction was observed between current smoking and hypertension on the additive scale, (relative excess risk because of interaction, 6.40; 95% CI, 0.88–11.92, adjusted for sex and age). We found no significant interaction between hypertension and regular alcohol consumption or current cigarette smoking and regular alcohol consumption on the additive scale. No significant interaction was detected on the multiplicative scale.

Conclusions—
The joint effect of current smoking and hypertension on the risk of aSAH was stronger than was the sum of the independent effects of each factor. Persons at risk of aSAH should be advised of a markedly stronger risk for aSAH with the combination of current smoking and hypertension. In addition, the finding suggests that combining smoking cessation and blood pressure lowering may have an extra risk reduction effect on preventing aSAH.
Factors Associated With Low Moderate-to-Vigorous Physical Activity Levels in Pediatric Patients With Kawasaki Disease
Authors: Banks Laura , Lin Yahui Tammy , Chahal Nita , Manlhiot Cedric , Yeung Rae S. M. , McCrindle Brian W. 
Published: April 2012

Background/Methods We sought to determine functional health status and physical activity determinants in 27 patients with Kawasaki disease (KD; 20 males, 11 ± 3 years old). Patient physical activity data were compared with a population-based study of healthy children (Canadian Health Measures Survey). Results KD patients performed less moderate-to-vigorous physical activity (MVPA) than healthy children (males, 27 vs 61 min/d, P < .001; females, 10 vs 47 min/d, P < .001). Male KD patients performed more MVPA than female KD patients (median = 27; quartiles [Q1 15, Q3 26] min/d vs 10 [Q1 7, Q3 11] min/day, P = .009). Lower MVPA in KD patients was significantly associated with female gender; lower child self-efficacy score; lower Child Health Questionnaire (CHQ-PF50) scores for role functioning behavioral issues, physical functioning, and family cohesion; and higher CHQ-PF50 scores for self-esteem and family activity limitations. Conclusion Physical activity counseling should be a focus of management for children with a history of KD.
Intestinal Adaptation Is Stimulated by Partial Enteral Nutrition Supplemented With the Prebiotic Short‐Chain Fructooligosaccharide in a Neonatal Intestinal Failure Piglet Model
Authors: Barnes Jennifer L. , Hartmann Bolette , Holst Jens J. , Tappenden Kelly A. 
Published: April 2012

Background:Butyrate has been shown to stimulate intestinal adaptation when added to parenteral nutrition (PN) following small bowel resection but is not available in current PN formulations. The authors hypothesized that pre‐ and probiotic administration may be a clinically feasible method to administer butyrate and stimulate intestinal adaptation.Methods and Materials:Neonatal piglets (48 hours old, n = 87) underwent placement of a jugular catheter and an 80% jejunoileal resection and were randomized to one of the following treatment groups: control (20% standard enteral nutrition/80% standard PN), control plus prebiotic (10 g/L short‐chain fructooligosaccharides [scFOS]), control plus probiotic (1 × 109 CFU Lactobacillus rhamnosus GG [LGG]), or control plus synbiotic (scFOS + LGG). Animals received infusions for 24 hours, 3 days, or 7 days, and markers of intestinal adaptation were assessed.Results:Prebiotic treatment increased ileal mucosa weight compared with all other treatments (P = .017) and ileal protein compared with control (P = .049), regardless of day. Ileal villus length increased in the prebiotic and synbiotic group (P = .011), regardless of day, specifically due to an increase in epithelial proliferation (P = .003). In the 7‐day prebiotic group, peptide transport was upregulated in the jejunum (P = .026), whereas glutamine transport was increased in both the jejunum and colon (P = .001 and .003, respectively).Conclusions:Prebiotic and/or synbiotic supplementation resulted in enhanced structure and function throughout the residual intestine. Identification of a synergistic prebiotic and probiotic combination may enhance the promising results obtained with prebiotic treatment alone.
Impact of Adenotonsillectomy on High‐Sensitivity C‐Reactive Protein Levels in Obese Children with Obstructive Sleep Apnea
Authors: Chu Lijuan , Yao Hongbing , Wang Bing 
Published: April 2012

ObjectiveTo evaluate the effect of adenotonsillectomy (T&A) in obese children with obstructive sleep apnea (OSA) and to compare changes in high‐sensitivity C‐reactive protein (hs‐CRP) levels before and 6 months after T&A in obese children with OSA.Study DesignBefore and after study with planned data collection.SettingTertiary care, university‐based pediatric hospital.Subjects and MethodsSeventy‐five obese children with OSA were included. Clinical information such as the apnea‐hypopnea index (AHI), nadir oxyhemoglobin saturation (SaO2), and body mass index (BMI) were recorded. The hs‐CRP level was determined before T&A and at the 6‐month follow‐up examination.ResultsReductions in AHI (21.96 ± 9.277 before T&A vs 8.64 ± 5.997 after 6 months of T&A) and higher levels of nadir SaO2 (74.08 ± 7.860 before T&A vs 86.87 ± 5.586 after 6 months of T&A) were observed. The hs‐CRP levels were obviously correlated with BMI (r = 0.7948, P <. 001). Other than AHI (r = 0.0579, P =. 6217) in obese children, however, hs‐CRP levels showed no changes 6 months after T&A therapy.ConclusionT&A treatment improves clinical signs and symptoms in obese children but does not reduce chronic inflammation as reflected by hs‐CRP. To lower the risks of cardiovascular disease and diabetes mellitus morbidity, other treatments should be taken into account.
Posterior circulation embolism as a potential mechanism for migraine with aura
Authors: Shin Dong Hoon , Lim Tae Sung , Yong Seok Woo , Lee Jin Soo , Choi Jun Young , Hong Ji Man 
Published: April 2012

Background: Although the mechanism of migraine is regarded as a functional disorder of the brain, numerous studies have reported that migraine is closely associated with vascular system abnormalities. Case reports: We describe a 19-year-old female with recurrent migraine attacks and typical aura for 7 years. MRI showed multiple stroke lesions in the posterior circulation. Moreover, a pseudoaneurysm (1.9 ×  1.4 cm) originating from the left vertebral artery was observed on four-vessel angiography. Multiple microembolic signals (MES) were repeatedly observed in the basilar artery using 30-minute transcranial Doppler monitoring. Interestingly, MES and her typical migrainous symptoms disappeared simultaneously with removal of the pseudoaneurysm. Discussion: This case supports the fact that microemboli play a pivotal role in the development of migraine attacks.
Peripheral endothelial function and arterial stiffness in women with migraine with aura: a case-control study
Authors: Liman TG , Neeb L , Rosinski J , Wellwood I , Reuter U , Doehner W , Heuschmann PU , Endres M 
Published: April 2012

Background: Vascular dysfunction may be involved in migraine pathophysiology and contribute to the increased risk of ischemic stroke in migraine, particularly in women with migraine with aura (MA). However, data on endothelial function in MA are controversial. Here, we investigated whether systemic endothelial function and arterial stiffness are altered in women with MA, using a novel peripheral arterial tonometry device for the first time. Methods: Twenty-nine female MA patients without comorbidities and 30 healthy women were included, and carotid intima-media thickness was assessed by a standardized procedure. Endothelial function was assessed using peripheral arterial tonometry. Reactive hyperaemic response of digital pulse amplitude was measured following 5 minutes of forearm occlusion of the brachial artery. Arterial stiffness was assessed by fingertip tonometry derived and heart-rate-adjusted augmentation index. Results: No differences were found in peripheral arterial tonometry ratio (2.3 ± 0.6 vs 2.2 ± 0.8; p = 0.58) and left carotid intima-media thickness (in µm: 484 ± 119 vs 508 ± 60; p = 0.37). Women with MA had higher heart-rate-averaged augmentation index [median (interquartile range, IQR) of 5 (IQR 0.5 to 18) vs –5 (IQR −16.8 to 8.3), p = 0.005] and heart-rate-adjusted augmentation index [1 (IQR −6 to 12.5) vs −8 (IQR −20.3 to 2.5), p = 0.008] than healthy controls. Conclusion: Peripheral endothelial function is not impaired in women with MA, but they have greater arterial stiffness. This may contribute to the increased stroke risk in women with MA.
The Effects of Chlorhexidine Graft Decontamination on Tendon Graft Collagen and Cell Viability
Authors: Alomar Abdulaziz Z. , Gawri Rahul , Roughley Peter J. , Haglund Lisbet , Burman Mark 
Published: April 2012

Background: Chlorhexidine (CLX) has been reported as a popular and effective disinfectant of contaminated tendon grafts with no biomechanical sequelae; however, its biochemical effects on tendon collagen and fibroblasts remain unknown. Purpose: To determine whether CLX disinfection of contaminated tendon grafts has deleterious effects on tendon collagen or a toxic effect on fibroblast function. Study Design: Controlled laboratory study. Methods: Collagen fibrils prepared from purified bovine collagen type I were treated with various CLX concentrations (0.5%-4%) and incubation times (10-40 minutes), and the effects on fibril degradation and solubility were then examined using gel electrophoresis. Fresh bovine tendons were treated with sterile water or 2% CLX; then, fibroblast mobility and metabolic activity were evaluated using light microscopy and Alamar Blue assay, respectively. Results: No effect on collagen fibrils was observed when they were exposed to 0%, 0.5%, or 2% CLX at any exposure time. However, 4% CLX dissolved the fibrils even after short incubation times. Fibroblasts migrated out from the control tendon explants but not from explants treated with 2% CLX, and a 5-fold reduction in metabolic activity was observed throughout the tendon in explants exposed to 2% CLX, suggesting that CLX penetrated and killed cells throughout the tissue. Conclusion: Four-percent CLX caused collagen fibrils to dissolve in vitro, and tendon graft disinfection with 2% CLX was cytotoxic to the cells. Clinical Relevance: Because of its chemical effect on tendon collagen and cytotoxic effect on tendon fibroblasts, 4% CLX should not be used as a disinfectant. Two-percent CLX can be used to disinfect contaminated ACL grafts, but such treatment will drastically reduce the metabolic activity of the cells within the graft, making it similar to an acellular allograft tendon.
FrequentEGFRmutations in nonsmall cell lung cancer presenting with miliary intrapulmonary carcinomatosis
Authors: Wu Shang-Gin , Hu Fu-Chang , Chang Yih-Leong , Lee Yung-Chie , Yu Chong-Jen , Chang Yeun-Chung , Wu Jenn-Yu , Shih Jin-Yuan , Yang Pan-Chyr 
Published: April 2012

Nonsmall cell lung cancer (NSCLC) presenting with miliary intrapulmonary carcinomatosis (MIPC) is rare. We investigated the clinical characteristics and epidermal growth factor receptor (EGFR) mutation rate of NSCLC patients with MIPC at initial diagnosis.From June 2004 to December 2008, we screened newly diagnosed NSCLC patients for MIPC using image-based criteria. We recorded clinical data and analysedEGFRmutation status. For comparison, we collected specimens from stage IV NSCLC patients without MIPC tested forEGFRmutations from April 2001 to November 2008.From 3,612 NSCLC patients, 85 patients with MIPC at initial diagnosis were identified; 81 had adenocarcinoma. Of the 85 patients, 60 had specimen sequencing to detectEGFRmutation; 42 (70%) were positive. Compared with 673 stage IV patients without MIPC, patients with MIPC had higherEGFRmutation rate (p=0.036); even male smokers had a highEGFRmutation rate (91%). Multivariate analysis of prognostic factors for overall survival of the 85 patients with MIPC revealed that adenocarcinoma, absence of extrapulmonary metastasis and havingEGFRmutation were associated with longer overall survival.NSCLC patients with MIPC at initial diagnosis had higher rates of adenocarcinoma andEGFRmutation. EGFR tyrosine kinase inhibition may be the treatment of choice for NSCLC patients with MIPC at initial diagnosis among Asians.
Sputum purulence-guided antibiotic use in hospitalised patients with exacerbations of COPD
Authors: Soler Néstor , Esperatti Mariano , Ewig Santiago , Huerta Arturo , Agustí Carlos , Torres Antoni 
Published: April 2012

In patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) needing hospitalisation, sputum purulence is associated with bacteria in the lower respiratory tract. We performed a prospective non-randomised interventional pilot study applying a sputum purulence-guided strategy of antibiotic treatment and investigating the relationship between sputum purulence and biomarkers.In hospitalised patients with acute exacerbation of COPD antibiotics were restricted to those with purulent sputum. The primary end-point was rate of therapeutic failure during hospitalisation. Secondary end-points were parameters reflecting short- and long-term outcomes.We included 73 patients, 34 with non-purulent sputum. No differences were observed on therapeutic failure criteria (9% non-purulentversus10% purulent (p=0.51)). Serum C-reactive protein (CRP) was significantly increased in the purulent group at admission (11.6versus5.3, p=0.006) and at day 3 (2.7versus1.2, p=0.01). Serum procalcitonin (PCT) was similar between the groups. No differences were found in short-term outcomes. The exacerbation rate at 180 days was higher in the purulent group.These results support the hypothesis of performing a randomised trial using a sputum purulence-guided antibiotic treatment strategy in patients with acute exacerbations of COPD. CRP, but not PCT, may be a useful parameter to increase confidence of the absence of bacterial bronchial infection.
Persistent disruption of ciliated epithelium following paediatric lung transplantation
Authors: Thomas Biju , Aurora Paul , Spencer Helen , Elliott Martin , Rutman Andrew , Hirst Robert A. , O'Callaghan Christopher 
Published: April 2012

It is unclear whether ciliary function following lung transplantation is normal or not. Our aim was to study the ciliary function and ultrastructure of epithelium above and below the airway anastomosis and the peripheral airway of children following lung transplantation.We studied the ciliary beat frequency (CBF) and beat pattern, using high speed digital video imaging and ultrastructure by transmission electron microscopy, of bronchial epithelium from above and below the airway anastomosis and the peripheral airway of 10 cystic fibrosis (CF) and 10 non-suppurative lung disease (NSLD) paediatric lung transplant recipients.Compared to epithelium below the anastomosis, the epithelium above the anastomosis in the CF group showed reduced CBF (median (interquartile range): 10.5 (9.0–11.4) Hzversus7.4 (6.4–9.2) Hz; p<0.01) and increased dyskinesia (median (IQR): 16.5 (12.9–28.2)%versus42.2 (32.6–56.4)%; p<0.01). In both CF and NSLD groups, compared with epithelium above the anastomosis, the epithelium below the anastomosis showed marked ultrastructural abnormalities (median duration post-transplant 7–12 months).Ciliary dysfunction is a feature of native airway epithelium in paediatric CF lung transplant recipients. The epithelium below the airway anastomosis shows profound ultrastructural abnormalities in both CF and NSLD lung transplant recipients, many months after transplantation.
Transcriptome analysis of stem development in the tumourous stem mustard Brassica juncea var. tumida Tsen et Lee by RNA sequencing
Authors: Sun Quan , Zhou Guanfan , Cai Yingfan , Fan Yonghong , Zhu Xiaoyan , Liu Yihua , He Xiaohong , Shen Jinjuan , Jiang Huaizhong , Hu Daiwen , Pan Zheng , Xiang Liuxin , He Guanghua , Dong Daiwen , Yang Jianping 
Published: April 2012

Abstract

Background
Tumourous stem mustard (Brassica juncea var. tumida Tsen et Lee) is an economically and nutritionally important vegetable crop of the Cruciferae family that also provides the raw material for Fuling mustard. The genetics breeding, physiology, biochemistry and classification of mustards have been extensively studied, but little information is available on tumourous stem mustard at the molecular level. To gain greater insight into the molecular mechanisms underlying stem swelling in this vegetable and to provide additional information for molecular research and breeding, we sequenced the transcriptome of tumourous stem mustard at various stem developmental stages and compared it with that of a mutant variety lacking swollen stems.

Results
Using Illumina short-read technology with a tag-based digital gene expression (DGE) system, we performed de novo transcriptome assembly and gene expression analysis. In our analysis, we assembled genetic information for tumourous stem mustard at various stem developmental stages. In addition, we constructed five DGE libraries, which covered the strains Yong'an and Dayejie at various development stages. Illumina sequencing identified 146,265 unigenes, including 11,245 clusters and 135,020 singletons. The unigenes were subjected to a BLAST search and annotated using the GO and KO databases. We also compared the gene expression profiles of three swollen stem samples with those of two non-swollen stem samples. A total of 1,042 genes with significantly different expression levels occurring simultaneously in the six comparison groups were screened out. Finally, the altered expression levels of a number of randomly selected genes were confirmed by quantitative real-time PCR.

Conclusions
Our data provide comprehensive gene expression information at the transcriptional level and the first insight into the understanding of the molecular mechanisms and regulatory pathways of stem swelling and development in this plant, and will help define new mechanisms of stem development in non-model plant organisms.
Rural and Micropolitan Residence and Mortality in Patients on Dialysis
Authors: Maripuri Saugar , Arbogast Patrick , Ikizler T. Alp , Cavanaugh Kerri L. 
Published: April 2012

Summary

Background and objectives
Micropolitan and rural patients face challenges when initiating dialysis, including healthcare access. Previous studies have shown little association of nonurban residence with dialysis outcomes but have not examined the association of dialysis modality with residence location.

Design, setting, participants, & measurements
This retrospective cohort study used data from the U.S. Renal Data System. Adults who initiated maintenance dialysis between January 1, 2006, and December 31, 2007, were classified as rural, micropolitan, or urban. Early and long-term mortality and kidney transplantation were examined with Cox regression stratified by dialysis modality.

Results
Of 204,463 patients, 80% were urban; 10.2%, micropolitan; and 9.8%, rural. Micropolitan and rural patients were older, were less racially diverse, had more comorbid conditions, and were more likely to start peritoneal dialysis (PD). Median follow-up was 2.0 years. Early mortality or long-term hemodialysis (HD) mortality did not significantly differ by geographic residence. After adjustment, micropolitan and rural PD patients had higher risk for long-term mortality (hazard ratio [HR], 1.21 [95% confidence interval (CI), 1.09–1.35] and 1.12 [95% CI, 1.01–1.24], respectively) than urban PD patients. After adjustment, kidney transplantation was more likely in micropolitan and rural HD patients (HR, 1.19 [95% CI, 1.11–1.28] and 1.30 [CI, 1.21–1.40]) than urban HD patients, and micropolitan PD patients (HR, 1.31 [95%, CI 1.13–1.51]) than urban PD patients.

Conclusions
Micropolitan and rural residence is associated with higher mortality in PD patients and similar or higher likelihood of kidney transplantation among HD and PD patients. Studies examining the underlying mechanisms of these associations are warranted.