bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of age at onset of migraine with family history of migraine in children attending a pediatric headache clinic: A retrospective cohort study
Authors: Eidlitz-Markus Tal , Haimi-Cohen Yishay , Zeharia Avraham 
Published: October 2014

Aim Migraine is known to run in families and has long been considered a strongly heritable disorder. This study sought to evaluate the relationship between age at onset of pediatric migraine and family history of migraine. Methods Review of the medical files of the headache clinic of a tertiary pediatric medical center yielded 344 children with migraine for whom details on migraine in family members were available. Results Mean age of the cohort was 11.69 ± 3.49 years, and mean frequency of headache per month, 13.68 ± 11.26. Mean age at migraine onset in patients with a negative parental history was10.48 ± 3.39 years; in patients with one parent with migraine, 8.84 ± 3.72 years; and in patients with both parents with migraine, 7.32 ± 3.22 years ( p < 0.001).The duration of migraine attacks (in hours) was significantly longer in patients with any family member with migraine than in those with no family history ( p = 0.026). Conclusions Among children attending a tertiary pediatric headache clinic, migraine appears at a younger age in those with parental history of migraine than in those with a negative family history. The findings suggest that having a genetic background of migraine makes a child more susceptible to migraine earlier in life than a child without a family history.
Squatting Mechanics in People With and Without Anterior Cruciate Ligament Reconstruction
Authors: Bell David R. , Kulow Stephanie M. , Stiffler Mikel R. , Smith Mason D. 
Published: October 2014

Background: Single-legged squat mechanics change after anterior cruciate ligament (ACL) reconstruction and rehabilitation, but it is unclear if changes in squat mechanics are graft specific. Purpose: To investigate graft differences in biomechanics of the knee, hip, and trunk during the single-legged squat in patients with ACL-reconstructed knees, determine if these factors were associated with deficits in knee extension moment, and determine if subjective knee function and squat biomechanics are related. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 106 individuals were grouped based on surgical status and graft type (51 control, 34 bone–patellar tendon–bone [BPTB], 21 ipsilateral semitendinosus and gracilis autograft [ISGA]). Motion capture interfaced with force plates was used to capture single-legged squat performance in the ACL reconstructed and dominant control limbs. Variables were captured at peak knee flexion. Results: Controls exhibited greater knee extension moment ( P = .04), knee flexion ( P = .002), and hip adduction angles ( P = .04) compared with the reconstructed groups. The ISGA group demonstrated greater forward ( P = .01) and lateral ( P = .002) trunk flexion over the reconstructed limb. Summated extension moment did not differ between groups ( P = .42). Knee extension moment was correlated with lateral trunk flexion ( r = −0.31, P = .03) in the control group and knee flexion angle ( r = −0.44, P = .04) in the ISGA group. Subjective knee function scores were correlated with lateral trunk flexion ( r = −0.45, P = .008) in the BPTB group and with hip adduction angle ( r = −0.46, P = .04) and hip extension moment ( r = 0.48, P = .03) in the ISGA group. Conclusion: Knee and hip biomechanics were related to surgical status but not graft type. Increased forward and lateral trunk motion in the ISGA group may be a mechanism to protect the knee by minimizing motion during squatting or related to surgical selection bias. Secondary findings (summated extensor moments and correlations) most likely represent a strategy to shift the squat demands from the knee to the hip. Clinical Relevance: Clinicians should target these neuromuscular deficits during rehabilitation and training programs after ACL reconstruction.
Couples' experiences with early-onset dementia: An interpretative phenomenological analysis of dyadic dynamics
Authors: Wawrziczny Emilie , Antoine Pascal , Ducharme Francine , Kergoat Marie-Jeanne , Pasquier Florence 
Published: October 2014

Objective The growing interest in early-onset dementia has attracted attention to the situation and experiences of the caregiver, most often the spouse. Several qualitative studies on caregiving spouses have underlined the importance of the feeling of loss, the change of role reported by the caregiving spouses, and the strategies used to protect the person with dementia, all of which raise the question of the relational dynamics at play in these dyads. The present study on 16 couples examines the experiences of each partner, as well as the kinds of interactions taking place within the dyad and how they have evolved since the disease began. Design An interpretative phenomenological analysis was conducted on dyadic semi-structured interviews. Results Seven axes emerged from the analyses, showing that control over symptoms gradually leads to deterioration of marital interactions and to the components of marital dissolution.
Carers: The navigators of the maze of care for people with dementia—A qualitative study
Authors: Jamieson Maggie , Grealish Laurie , Brown Jo-Ann , Draper Brian 
Published: October 2014

Background Dementia is a challenge in our society, with individuals accessing services across multiple settings. Carers are navigating and delivering care services in the home. This research sought to investigate the experiences of people with dementia and their carers when transitioning home from hospital. Methods This study used a qualitative descriptive design, employing in-depth interviews with 30 carers recruited through networks known to one state branch of Alzheimer’s Australia. Emerging themes were validated in one focus group. Results During the hospital stay carers experienced a paradox: being required to deliver care yet perceiving that they were being ignored in regard to decisions about care. The time in hospital was considered by some carers to be stressful, as they were concerned about the safety of the person with dementia. Many reported that discharge home was rarely planned and coordinated. Returning home carers found re-establishing and/or accessing new services challenging, with available services often inappropriate to need. Conclusion The paradox of the care experience in the acute setting, whereby the carer was either invited, or sought, to deliver care, yet was excluded in staff decisions about that care, challenges the current communication and coordination of care. For people with dementia and their carers, there is a need for a coordinated seamless service that enables continued unbroken care and support from acute care to home. Carers also need support navigating the wide range of services available and importantly both carers and care providers may need to understand service boundaries. Recommendations This study highlights the need to acknowledge the expertise of the carer, and their need for support. Enabling a smooth discharge from hospital and support to navigate care access in the community is paramount. These experiences provide insight into gaps in service provision and modifying existing services may lead to improved experiences.
Impaired glucose tolerance alters functional ability of peripheral blood-derived mononuclear cells in Asian Indian men
Authors: Nathan Abel Arul , Charan Tej Mallu Abhiram , Chitiprolu Maneka , Rangan Shreyas , Mohan Viswanathan , Harish Ranjani , Anand Setty B , Dixit Madhulika 
Published: October 2014

Aim: To compare the adhesion, migration and endothelial differentiation potential of peripheral blood-derived mononuclear cells (PBMCs) obtained from drug-naive normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) Asian Indian men. Methods: Based on the 75-g oral glucose tolerance test, 30 NGT and 31 IGT subjects were recruited into the study. PBMCs were isolated from fasting blood using histopaque density gradient centrifugation. Isolated PBMCs were analysed for their ability to adhere to extracellular matrices, incorporation into tubular structures formed by matured endothelial cells and differentiation into endothelial cells upon 7-day culture in endothelial-specific growth medium. Results: PBMCs obtained from IGT subjects exhibit poor adherence to fibronectin and reduced incorporation into tubular structures. Migration towards stromal cell-derived factor-1α (SDF-1α) in a trans-well filter assembly was also reduced for these cells. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis revealed decreased expression of CXCR4 and β2 integrin and increased expression of arginase II in IGT subjects. No differences were observed with regard to endothelial differentiation; however, cultured PBMCs of IGT subjects had decreased intracellular nitric oxide (NO) production. Conclusion: In pre-diabetic, Asian Indian men, PBMCs exhibit defective migration and homing potential.
Featured Article: Teriflunomide, an immunomodulatory drug, exerts anticancer activity in triple negative breast cancer cells
Authors: Huang Ou , Zhang Weili , Zhi Qiaoming , Xue Xiaofeng , Liu Hongchun , Shen Daoming , Geng Meiyu , Xie Zuoquan , Jiang Min 
Published: October 2014

Triple-negative breast cancer (TNBC) is defined as a group of primary breast cancers lacking expression of estrogen, progesterone, and human epidermal growth factor receptor-2 (HER-2) receptors, characterized by higher relapse rate and lower survival compared with other subtypes. Due to lack of identified targets and molecular heterogeneity, conventional chemotherapy is the only available option for treatment of TNBC, but non-discordant positive therapeutic efficacy could not be achieved. Here, we demonstrated that these TNBC cells were sensitive to teriflunomide, which was a well-known immunomodulatory drug for treatment of relapsing multiple sclerosis (MS). Potent anti-cancer effects in TNBC in vitro, including proliferation inhibition, cell cycle delay, cell apoptosis, and suppression of cell motility and invasiveness, could be achieved with this agent. Of note, we showed that multiple signals involved in TNBC proliferation, survival, migratory, and invasive potential were under regulation by teriflunomide. Among them, we identified down-regulation of growth factor receptors to abolish growth maintenance, suppression of c-Myc, and cyclin D1 to contribute to its anti-proliferative effect, modulation of components of cell cycle to induce S-phase arrest, degradation of Bcl-xL, and up-regulation of BAX via activation of MAPK pathway to induce apoptosis, and inhibition of epithelial-mesenchymal transition (EMT) process, matrix metalloproteinase-9 (MMP9) expression, and inactivation of Src/FAK to reduce TNBC migration and invasion. The results identified teriflunomide may be of therapeutic benefit for the more aggressive and difficult-to-treat breast cancer subtype, indicating the use of teriflunomide for clinical trials for treatment of TNBC patients.
Time Lag of Glucose From Intravascular to Interstitial Compartment in Type 1 Diabetes
Authors: Basu Ananda , Dube Simmi , Veettil Sona , Slama Michael , Kudva Yogish C. , Peyser Thomas , Carter Rickey E. , Cobelli Claudio , Basu Rita 
Published: October 2014

Background and Objective: The premise of effective closed-loop insulin therapy for type 1 diabetes (T1D) relies on the accuracy of continuous interstitial fluid glucose sensing that represents the crucial afferent arm of such a system. An important determinant of sensor accuracy is the physiological time lag of glucose transport from the vascular to the interstitial space. The purpose of current studies was to determine the physiological time lag of glucose transport from the vascular to the abdominal subcutaneous interstitial space in T1D. Method: Four microdialysis catheters were inserted into the abdominal subcutaneous space in 6 T1D subjects under overnight fasted conditions. Plasma glucose was maintained at 113.7 ± 6.3 mg/dl using a continuous intravenous insulin infusion. After sequential intravenous bolus administrations of glucose isotopes, timed plasma and interstitial fluid samples were collected chronologically and analyzed for tracer enrichments. Results: We observed a median (range) time lag of tracer appearance (time to detection) into the interstitial space after intravenous bolus of 6.8 (4.8-9.8) minutes, with all participants having detectable values by 9.8 minutes. Conclusions: We conclude that in the overnight fasted state in T1D adults, the delay of glucose appearance from the vascular to the interstitial space is less than 10 minutes, thereby implying that this minimal physiological time lag should not be a major impediment to the development of an effective closed-loop control system for T1D.
Are IBD patients more likely to have a prior diagnosis of irritable bowel syndrome? Report of a case‐control study in the General Practice Research Database
Authors: Card Timothy R , Siffledeen Jesse , Fleming Kate M 
Published: October 2014

BackgroundInflammatory bowel disease (IBD) patients are sometimes first diagnosed with irritable bowel syndrome (IBS), which may be construed as a misdiagnosis.ObjectiveThe objective of this article is to determine if this occurs more than expected by chance.MethodsWe conducted a case‐control study nested in the General Practice Research Database. We selected incident cases of IBD and up to 10 matched controls for each. We assessed the proportions with IBS recorded prior to the IBD diagnosis and variation by age, sex, and calendar time. We compared proportions affected in fixed time periods and conducted conditional logistic regression to derive odds ratios.ResultsThe 20, 193 cases were three times as likely as controls to have a prior record of IBS. Fifteen per cent of IBD cases and 5% of controls had IBS coded before diagnosis with 11% having a code for IBS over one year before IBD (cf. 5% of controls) and 6% over five years earlier (cf. 3%). These figures roughly doubled if typical antispasmodic therapies were assumed to represent IBS diagnoses.ConclusionIf excess IBS diagnoses represent misdiagnoses of IBD, our results suggest that about 10% of IBD patients are misdiagnosed and in 3% of cases this may persist for five or more years.
Online Education About Herbs and Dietary Supplements
Authors: Kemper Kathi J. , Patel Sejal 
Published: October 2014

Background: Online education is increasingly used to train health professionals, but little is known about how variations in cost affect use of elective training. We assessed whether offering registration for free increased the number of modules consumed in both absolute terms (# modules consumed per person, pp) and relative terms (# modules consumed per # modules registered). Methods: We analyzed results of the ‘natural experiment’ on learner's use of the OSU Center for Integrative Health and Wellness online elective curriculum, Introduction Herbs and Dietary Supplements Across the Lifespan, in which costs varied based on monthly discounts for students, faculty, staff, alumni, and members of selected professional associations. Results: Over 7 months there were a total of 905 registrants for 8553 modules. Most (847/905, 94%) registered for free; they completed 1505 (18%) of 8344 modules for which they registered. Fewer (58/905, 6%) people paid for registration; they completed a significantly higher percentage 90/209 (43%, P < 0.001) of modules for which they registered; those who paid full, non-discount rates had the highest completion rates (62%, P < 0.001). Free and paid registrants completed about the same average number of modules per person, pp, (1.8 pp free vs.1.6 pp paid). Conclusion: Although it may not contribute to financial margins, offering free online elective training addresses the institutional mission of increasing the number health professionals trained and the number of modules consumed compared with charging for training. Additional research is needed to determine the impact of pricing on educational outcomes and ultimately on patient care.
The same site on the integrase-binding domain of lens epithelium–derived growth factor is a therapeutic target for MLL leukemia and HIV
Authors: Murai Marcelo J. , Pollock Jonathan , He Shihan , Miao Hongzhi , Purohit Trupta , Yokom Adam , Hess Jay L. , Muntean Andrew G. , Grembecka Jolanta , Cierpicki Tomasz 
Published: October 2014

Key Points
Inhibiting LEDGF interaction with a novel fragment of MLL represents an attractive approach to develop new drugs for MLL leukemias. Structural studies reveal a new pocket on the LEDGF IBD suitable for targeting by small-molecule inhibitors.
Ibrutinib treatment affects collagen and von Willebrand factor-dependent platelet functions
Authors: Levade Marie , David Elodie , Garcia Cédric , Laurent Pierre-Alexandre , Cadot Sarah , Michallet Anne-Sophie , Bordet Jean-Claude , Tam Constantine , Sié Pierre , Ysebaert Loïc , Payrastre Bernard 
Published: October 2014

Key Points
Ibrutinib affects collagen and VWF-mediated platelet activation. The bleeding diathesis correlates with defects in collagen-induced platelet aggregation and firm adhesion on VWF at arterial shear rate.
Quality of diabetes care worldwide and feasibility of implementation of the Alphabet Strategy: GAIA project (Global Alphabet Strategy Implementation Audit)
Authors: Lee James D , Saravanan Ponnusamy , Varadhan Lakshminarayanan , Morrissey John R , Patel Vinod 
Published: October 2014

Abstract

Background
The Alphabet Strategy (AS) is a diabetes care checklist ensuring “important, simple things are done right all the time.” Current audits of diabetes care in developed countries reveal wide variations in quality with performance of care processes frequently sub-optimal. This study had three components:
• an audit to assess diabetes care quality worldwide,
• a questionnaire study seeking opinions on the merits of the AS,
• a pilot study to assess the practicality of implementation of the AS in a low socioeconomic setting.

Methods
Audit data was collected from 52 centres across 32 countries. Data from 4537 patients were converted to Quality and Outcome Framework (QOF) scores to enable inter-centre comparison. These were compared to each country’s Gross Domestic Product (GDP), and Total Health Expenditure percentage per capita (THE%). The opinions of diabetes patients and healthcare professionals from the diabetes care team at each of these centres were sought through a structured questionnaire. A retrospective audit on 100 randomly selected case notes was conducted prior to AS implementation in a diabetes outpatient clinic in India, followed by a prospective audit after four months to assess its impact on care quality.

Results
QOF scores showed wide variation across the centres (mean 49.0, range 10.2–90.1). Although there was a positive relationship between GDP and THE% to QOF scores, there were exceptions. 91% of healthcare professionals felt the AS approach was practical. Patients found the checklist to be a useful education tool. Significant improvements in several aspects of care as well as 36% improvement in QOF score were seen following implementation.

Conclusions
International centres observed large variations in care quality, with standards frequently sub-optimal. 71% of health care professionals would consider adopting the AS in their daily practice. Implementation in a low resource country resulted in significant improvements in some aspects of diabetes care. The AS checklist for diabetes care is a freely available in the public domain encompassing patient education, care plans, and educational resources for healthcare professionals including summary guidelines. The AS may provide a unique approach in delivering high quality diabetes care in countries with limited resources.
Lysozyme-coated silver nanoparticles for differentiating bacterial strains on the basis of antibacterial activity
Authors: Ashraf Sumaira , Chatha Mariyam Asghar , Ejaz Wardah , Janjua Hussnain Ahmed , Hussain Irshad 
Published: October 2014

Abstract
Lysozyme, an antibacterial enzyme, was used as a stabilizing ligand for the synthesis of fairly uniform silver nanoparticles adopting various strategies. The synthesized particles were characterized using UV-visible spectroscopy, FTIR, dynamic light scattering (DLS), and TEM to observe their morphology and surface chemistry. The silver nanoparticles were evaluated for their antimicrobial activity against several bacterial species and various bacterial strains within the same species. The cationic silver nanoparticles were found to be more effective against Pseudomonas aeruginosa 3 compared to other bacterial species/strains investigated. Some of the bacterial strains of the same species showed variable antibacterial activity. The difference in antimicrobial activity of these particles has led to the conclusion that antimicrobial products formed from silver nanoparticles may not be equally effective against all the bacteria. This difference in the antibacterial activity of silver nanoparticles for different bacterial strains from the same species may be due to the genome islands that are acquired through horizontal gene transfer (HGT). These genome islands are expected to possess some genes that may encode enzymes to resist the antimicrobial activity of silver nanoparticles. These silver nanoparticles may thus also be used to differentiate some bacterial strains within the same species due to variable silver resistance of these variants, which may not possible by simple biochemical tests.
Astrocyte-specific regulation of hMeCP2 expression in Drosophila
Authors: Hess-Homeier David L. , Fan Chia-Yu , Gupta Tarun , Chiang Ann-Shyn , Certel Sarah J. 
Published: October 2014

ABSTRACT
Alterations in the expression of Methyl-CpG-binding protein 2 (MeCP2) either by mutations or gene duplication leads to a wide spectrum of neurodevelopmental disorders including Rett Syndrome and MeCP2 duplication disorder. Common features of Rett Syndrome (RTT), MeCP2 duplication disorder, and neuropsychiatric disorders indicate that even moderate changes in MeCP2 protein levels result in functional and structural cell abnormalities. In this study, we investigated two areas of MeCP2 pathophysiology using Drosophila as a model system: the effects of MeCP2 glial gain-of-function activity on circuits controlling sleep behavior, and the cell-type specific regulation of MeCP2 expression. In this study, we first examined the effects of elevated MeCP2 levels on microcircuits by expressing human MeCP2 (hMeCP2) in astrocytes and distinct subsets of amine neurons including dopamine and octopamine (OA) neurons. Depending on the cell-type, hMeCP2 expression reduced sleep levels, altered daytime/nighttime sleep patterns, and generated sleep maintenance deficits. Second, we identified a 498 base pair region of the MeCP2e2 isoform that is targeted for regulation in distinct subsets of astrocytes. Levels of the full-length hMeCP2e2 and mutant RTT R106W protein decreased in astrocytes in a temporally and spatially regulated manner. In contrast, expression of the deletion Δ166 hMeCP2 protein was not altered in the entire astrocyte population. qPCR experiments revealed a reduction in full-length hMeCP2e2 transcript levels suggesting transgenic hMeCP2 expression is regulated at the transcriptional level. Given the phenotypic complexities that are caused by alterations in MeCP2 levels, our results provide insight into distinct cellular mechanisms that control MeCP2 expression and link microcircuit abnormalities with defined behavioral deficits.