bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ectopic Expression of E2F1 Stimulates β-Cell Proliferation and Function
Authors: Grouwels Gael , Cai Ying , Hoebeke Inge , Leuckx Gunter , Heremans Yves , Ziebold Ulrike , Stangé Geert , Chintinne Marie , Ling Zhidong , Pipeleers Daniel , Heimberg Harry , Van de Casteele Mark 
Published: March 2010

OBJECTIVE
Generating functional β-cells by inducing their proliferation may provide new perspectives for cell therapy in diabetes. Transcription factor E2F1 controls G1- to S-phase transition during the cycling of many cell types and is required for pancreatic β-cell growth and function. However, the consequences of overexpression of E2F1 in β-cells are unknown.

RESEARCH DESIGN AND METHODS
The effects of E2F1 overexpression on β-cell proliferation and function were analyzed in isolated rat β-cells and in transgenic mice.

RESULTS
Adenovirus AdE2F1-mediated overexpression of E2F1 increased the proliferation of isolated primary rat β-cells 20-fold but also enhanced β-cell death. Coinfection with adenovirus AdAkt expressing a constitutively active form of Akt (protein kinase B) suppressed β-cell death to control levels. At 48 h after infection, the total β-cell number and insulin content were, respectively, 46 and 79% higher in AdE2F1+AdAkt-infected cultures compared with untreated. Conditional overexpression of E2F1 in mice resulted in a twofold increase of β-cell proliferation and a 70% increase of pancreatic insulin content, but did not increase β-cell mass. Glucose-challenged insulin release was increased, and the mice showed protection against toxin-induced diabetes.

CONCLUSIONS
Overexpression of E2F1, either in vitro or in vivo, can stimulate β-cell proliferation activity. In vivo E2F1 expression significantly increases the insulin content and function of adult β-cells, making it a strategic target for therapeutic manipulation of β-cell function.
Extracellular Fatty Acid Synthase: A Possible Surrogate Biomarker of Insulin Resistance
Authors: Fernandez-Real Jose Manuel , Menendez Javier A. , Moreno-Navarrete Jose Maria , Blüher Matthias , Vazquez-Martin Alejandro , Vázquez María Jesús , Ortega Francisco , Diéguez Carlos , Frühbeck Gema , Ricart Wifredo , Vidal-Puig Antonio 
Published: March 2010

CONTEXT
Circulating fatty acid synthase (FASN) is a biomarker of metabolically demanding human diseases. The aim of this study was to determine whether circulating FASN could be a biomarker of overnutrition-induced metabolic stress and insulin resistance in common metabolic disorders.

RESEARCH DESIGN AND METHODS
Circulating FASN was evaluated in two cross-sectional studies in association with insulin sensitivity and in four longitudinal studies investigating the effect of diet- and surgery-induced weight loss, physical training, and adipose tissue expansion using peroxisome proliferator–activated receptor agonist rosiglitazone on circulating FASN.

RESULTS
Age- and BMI-adjusted FASN concentrations were significantly increased in association with obesity-induced insulin resistance in two independent cohorts. Both visceral and subcutaneous FASN expression and protein levels correlated inversely with extracellular circulating FASN (P = −0.63; P &lt; 0.0001), suggesting that circulating FASN is linked to depletion of intracellular FASN. Improved insulin sensitivity induced by therapeutic strategies that decreased fat mass (diet induced, surgery induced, or physical training) all led to decreased FASN levels in blood (P values between 0.02 and 0.04). To discriminate whether this was an effect related to insulin sensitization, we also investigated the effects of rosiglitazone. Rosiglitazone did not lead to significant changes in circulating FASN concentration.

CONCLUSIONS
Our results suggest that circulating FASN is a biomarker of overnutrition-induced insulin resistance that could provide diagnostic and prognostic advantages by providing insights on the individualized metabolic stress.
Progression of Cerebral Atrophy and White Matter Hyperintensities in Patients With Type 2 Diabetes
Authors: de Bresser Jeroen , Tiehuis Audrey M. , van den Berg Esther , Reijmer Yael D. , Jongen Cynthia , Kappelle L. Jaap , Mali Willem P. , Viergever Max A. , Biessels Geert Jan ,   on behalf of the Utrecht Diabetic Encephalopathy Study Group
Published: March 2010

OBJECTIVE
Type 2 diabetes is associated with a moderate degree of cerebral atrophy and a higher white matter hyperintensity (WMH) volume. How these brain-imaging abnormalities evolve over time is unknown. The present study aims to quantify cerebral atrophy and WMH progression over 4 years in type 2 diabetes.

RESEARCH DESIGN AND METHODS
A total of 55 patients with type 2 diabetes and 28 age-, sex-, and IQ-matched control participants had two 1.5T magnetic resonance imaging scans with a 4-year interval. Volumetric measurements of total brain, peripheral cerebrospinal fluid (CSF), lateral ventricles, and WMH were performed with k-nearest neighbor–based probabilistic segmentation. All volumes were expressed as percentage of intracranial volume. Linear regression analyses, adjusted for age and sex, were performed to compare brain volumes between the groups and to identify determinants of volumetric change within the type 2 diabetic group.

RESULTS
At baseline, patients with type 2 diabetes had a significantly smaller total brain volume and larger peripheral CSF volume than control participants. In both groups, all volumes showed a significant change over time. Patients with type 2 diabetes had a greater increase in lateral ventricular volume than control participants (mean adjusted between-group difference in change over time [95% CI]: 0.11% in 4 years [0.00 to 0.22], P = 0.047).

CONCLUSIONS
The greater increase in lateral ventricular volume over time in patients with type 2 diabetes compared with control participants shows that type 2 diabetes is associated with a slow increase of cerebral atrophy over the course of years.
Hyperglycemia-Induced Platelet Activation in Type 2 Diabetes Is Resistant to Aspirin but Not to a Nitric Oxide–Donating Agent
Authors: Gresele Paolo , Marzotti Stefania , Guglielmini Giuseppe , Momi Stefania , Giannini Silvia , Minuz Pietro , Lucidi Paola , Bolli Geremia B. 
Published: March 2010

OBJECTIVE
Acute, short-term hyperglycemia enhances high shear stress–induced platelet activation in type 2 diabetes. Several observations suggest that platelets in type 2 diabetes are resistant to inhibition by aspirin. Our aim was to assess comparatively the effect of aspirin, a nitric oxide–donating agent (NCX 4016), their combination, or placebo on platelet activation induced by acute hyperglycemia in type 2 diabetes.

RESEARCH DESIGN AND METHODS
In a double-blind, placebo-controlled, randomized trial, 40 type 2 diabetic patients were allocated to 100 mg aspirin once daily, 800 mg NCX 4016 b.i.d., both of them, or placebo for 15 days. On day 15, 1 h after the morning dose, a 4-h hyperglycemic clamp (plasma glucose 13.9 mmol/l) was performed, and blood samples were collected before and immediately after it for platelet activation and cyclooxygenase-1 (COX-1) inhibition studies.

RESULTS
Acute hyperglycemia enhanced shear stress–induced platelet activation in placebo-treated patients (basal closure time 63 ± 7.1 s, after hyperglycemia 49.5 ± 1.4 s, −13.5 ± 6.3 s, P &lt; 0.048). Pretreatment with aspirin, despite full inhibition of platelet COX-1, did not prevent it (−12.7 ± 6.9 s, NS vs. placebo). On the contrary, pretreatment with the NO donor NCX 4016, alone or in combination with aspirin, suppressed platelet activation induced by acute hyperglycemia (NCX 4016 +10.5 ± 8.3 s; NCX 4016 plus aspirin: +12.0 ± 10.7 s, P &lt; 0.05 vs. placebo for both). Other parameters of shear stress–dependent platelet activation were also more inhibited by NCX 4016 than by aspirin, despite lesser inhibition of COX-1.

CONCLUSIONS
Acute hyperglycemia-induced enhancement of platelet activation is resistant to aspirin; a NO-donating agent suppresses it. Therapeutic approaches aiming at a wider platelet inhibitory action than that exerted by aspirin may prove useful in patients with type 2 diabetes.
Validity of a Single-Factor Model Underlying the Metabolic Syndrome in Children
Authors: Martínez-Vizcaíno Vicente , Martínez Montserrat Solera , Aguilar Fernando Salcedo , Martínez Sandra Serrano , Gutiérrez Ricardo Franquelo , López Mairena Sánchez , Martínez Pablo Moya , Rodríguez-Artalejo Fernando 
Published: March 2010

OBJECTIVE
We used confirmatory factor analysis to test whether a single factor might explain the clustering of the metabolic syndrome (MS) components in children.

RESEARCH DESIGN AND METHODS
We studied 1,020 children aged 10–13 years from 20 schools in Cuenca, Spain. The single-factor model included: waist circumference (WC), fasting insulin, triglyceride to HDL cholesterol ratio (Triglyl/HDL-C), and mean arterial pressure (MAP). The standardized scores of the four variables in the model were used to develop a continuous MS index.

RESULTS
Factor loadings were 0.67 for WC, 0.68 for fasting insulin, 0.57 for Triglyl/HDL-C, and 0.37 for MAP. The single-factor model also showed a good fit to the data. As compared with Adult Treatment Panel III criteria, the MS index showed strong validity in the diagnosis of MS (area under the receiver operating characteristic curve = 0.98, 95% CI 0.96–0.99).

CONCLUSIONS
A single underlying factor has acceptable validity to represent MS in children.
Online Diabetes Self-Management Program
Authors: Lorig Kate , Ritter Philip L. , Laurent Diana D. , Plant Kathryn , Green Maurice , Jernigan Valarie Blue Bird , Case Siobhan 
Published: March 2010

OBJECTIVEWe hypothesized that people with type 2 diabetes in an online diabetes self-management program, compared with usual-care control subjects, would 1) demonstrate reduced A1C at 6 and 18 months, 2) have fewer symptoms, 3) demonstrate increased exercise, and 4) have improved self-efficacy and patient activation. In addition, participants randomized to listserve reinforcement would have better 18-month outcomes than participants receiving no reinforcement.RESEARCH DESIGN AND METHODSA total of 761 participants were randomized to 1) the program, 2) the program with e-mail reinforcement, or 3) were usual-care control subjects (no treatment). This sample included 110 American Indians/Alaska Natives (AI/ANs). Analyses of covariance models were used at the 6- and 18-month follow-up to compare groups.RESULTSAt 6 months, A1C, patient activation, and self-efficacy were improved for program participants compared with usual care control subjects (P &lt; 0.05). There were no changes in other health or behavioral indicators. The AI/AN program participants demonstrated improvements in health distress and activity limitation compared with usual-care control subjects. The subgroup with initial A1C &gt;7% demonstrated stronger improvement in A1C (P = 0.01). At 18 months, self-efficacy and patient activation were improved for program participants. A1C was not measured. Reinforcement showed no improvement.CONCLUSIONSAn online diabetes self-management program is acceptable for people with type 2 diabetes. Although the results were mixed they suggest 1) that the program may have beneficial effects in reducing A1C, 2) AI/AN populations can be engaged in and benefit from online interventions, and 3) our follow-up reinforcement appeared to have no value.
Treatment of Type 2 Diabetes and Outcomes in Patients With Heart Failure: A Nested Case–Control Study From the U.K. General Practice Research Database
Authors: MacDonald Michael R. , Eurich Dean T. , Majumdar Sumit R. , Lewsey James D. , Bhagra Sai , Jhund Pardeep S. , Petrie Mark C. , McMurray John J.V. , Petrie John R. , McAlister Finlay A. 
Published: March 2010

OBJECTIVE
Diabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with metformin than other antidiabetic agents. We designed this study to determine whether this association reflects a beneficial effect of metformin or a harmful effect of other agents.

RESEARCH DESIGN AND METHODS
We performed a case-control study nested within the U.K. General Practice Research Database cohort in which diagnoses were assigned by each patient's primary care physician. Case subjects were patients 35 years or older, newly diagnosed with both heart failure and diabetes after January 1988, and who died prior to October 2007. Control subjects were matched to case subjects based on age, sex, clinic site, calendar year, and duration of follow-up. Analyses were adjusted for comorbidities, A1C, renal function, and BMI.

RESULTS
The duration of concurrent diabetes and heart failure was 2.8 years (SD 2.6) in our 1,633 case subjects and 1,633 control subjects (mean age 78 years, 53% male). Compared with patients who were not exposed to antidiabetic drugs, the current use of metformin monotherapy (adjusted odds ratio 0.65 [0.48–0.87]) or metformin with or without other agents (0.72 [0.59–0.90]) was associated with lower mortality; however, use of other antidiabetic drugs or insulin was not associated with all-cause mortality. Conversely, the use of ACE inhibitors/angiotensin receptor blockers (0.55 [0.45–0.68]) and β-blockers (0.76 [0.61–0.95]) were associated with reduced mortality.

CONCLUSIONS
Our results confirm the benefits of trial-proven anti-failure therapies in patients with diabetes and support the use of metformin-based strategies to lower glucose.
Alterations in Retinal Microvascular Geometry in Young Type 1 Diabetes
Authors: Sasongko Muhammad Bayu , Wang Jie Jin , Donaghue Kim C. , Cheung Ning , Benitez-Aguirre Paul , Jenkins Alicia , Hsu Wynne , Lee Mong-Li , Wong Tien Y. 
Published: March 2010

OBJECTIVE
To describe retinal microvascular geometric parameters in young patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS
Patients with type 1 diabetes (aged 12–20 years) had clinical assessments and retinal photography following standardized protocol at a tertiary-care hospital in Sydney. Retinal microvascular geometry, including arteriolar and venular tortuosity, branching angles, optimality deviation, and length-to-diameter ratio (LDR), were measured from digitized photographs. Associations of these geometric characteristics with diabetes duration, A1C level, systolic blood pressure (SBP), and other risk factors were assessed.

RESULTS
Of 1,159 patients enrolled, 944 (81.4%) had gradable photographs and 170 (14.7%) had retinopathy. Older age was associated with decreased arteriolar (P = 0.024) and venular (P = 0.002) tortuosity, and female subjects had larger arteriolar branching angle than male subjects (P = 0.03). After adjusting for age and sex, longer diabetes duration was associated with larger arteriolar branching angle (P ≤ 0.001) and increased arteriolar optimality deviation (P = 0.018), higher A1C was associated with increased arteriolar tortuosity (&gt;8.5 vs. ≤8.5%, P = 0.008), higher SBP was associated with decreased arteriolar LDR (P = 0.002), and higher total cholesterol levels were associated with increased arteriolar LDR (P = 0.044) and decreased venular optimality deviation (P = 0.044). These associations remained after controlling for A1C, retinal vessel caliber, and retinopathy status and were seen in subjects without retinopathy.

CONCLUSIONS
Key diabetes-related factors affect retinal microvascular geometry in young type 1 diabetes, even in those without evidence of retinopathy. These early retinal alterations may be markers of diabetes microvascular complications.
Physical Therapists' Perceptions of Ease of Care in Patients Receiving 2 Forms of Analgesia After Total Hip Arthroplasty
Authors: Bourne Michael H. , Chelly Jacques E. , Damaraju C.V. , Nelson Winnie W. , Schein Jeff R. , Hewitt David J. 
Published: March 2010

Background
Pain management modalities that facilitate patient mobility may contribute to recovery after total hip replacement (THR) surgery.

Objective
The aim of this study was to evaluate the impact of morphine intravenous (IV) patient-controlled analgesia (PCA) and the fentanyl iontophoretic transdermal system (fentanyl ITS) on physical therapists' ability to complete care tasks for patients after THR.

Design
The data were from an open-label, randomized, multicenter, active-control phase IIIb clinical trial.

Methods
The settings were 52 US-based teaching and community hospitals. The patients were ≥18 years of age (mean [SEM]: 62.8 [0.6] years in the fentanyl ITS group and 62.9 [0.6] years in the morphine IV PCA group); had an American Society of Anesthesiologists physical status of I, II, or III; and were scheduled to undergo primary unilateral THR surgery. The patients were randomized to receive analgesia for up to 72 hours via the fentanyl ITS (40 μg of fentanyl over 10 minutes for up to 6 doses per hour for 24 hours or 80 doses per system, whichever occurred first) or morphine IV PCA (1-mg bolus doses [with a 5-minute lockout interval between doses] for up to 10 doses per hour for 24 hours). All patients received the usual treatment administered by physical therapists. After each therapy session, physical therapists completed a validated Physical Therapist Ease-of-Care Questionnaire, which included time efficiency and convenience subscales (lower scores indicated more positive responses) and a satisfaction subscale (a higher score indicated a more positive response). Therapists whose average scores were ≤2 on all items of the time efficiency and convenience subscales or ≥4 on both items of the satisfaction subscale were considered responders.

Results
Higher percentages of physical therapists were responders for the fentanyl ITS than for morphine IV PCA on the subscales that assessed time efficiency (84.9% and 59.1%, respectively), convenience (86.6% and 71.2%, respectively), and satisfaction (54.3% and 30.5%, respectively). Higher percentages of physical therapists favored the fentanyl ITS than favored morphine IV PCA.

Limitations
The trial was limited by its open-label design, and physical therapists were more familiar with IV PCA than with the fentanyl ITS.

Conclusions
The findings demonstrate benefits to physical therapists of using the fentanyl ITS over morphine IV PCA in terms of time efficiency, convenience, and satisfaction.
Spondyloarthritis in a Patient With Unilateral Buttock Pain and History of Crohn Disease
Authors: Coronado Rogelio A. , Sheets Charles Z. , Cook Chad E. , Boissonnault William G. 
Published: March 2010

Background and Purpose
Patients with inflammatory spinal conditions related to spondyloarthritis are rarely seen by primary care practitioners. However, patients with a history of inflammatory bowel disease and chronic low back or buttock pain should be examined carefully for the presence of spondyloarthritis, as proper management may include referral to a rheumatologist and appropriate medical intervention.

Case Description
A 27-year-old woman with a 6-month history of posterior buttock pain was referred for physical therapy with a diagnosis of piriformis syndrome. During the second physical therapy visit, a nonmechanical source of lumbopelvic pain was suspected, and the patient was referred for medical consultation. The patient underwent evaluation by a rheumatologist and was eventually diagnosed with spondyloarthritis associated with inflammatory bowel disease.

Outcomes
The patient initiated treatment with anti-tumor necrosis factor medication to address the spondyloarthritis. Medical management resulted in significant improvement in all outcome measures.

Discussion
Clinical suspicion of spondyloarthritis is raised when specific historical, examination, and imaging findings are present. The posttest probability of spondyloarthritis is increased with the presence of inflammatory back pain and specific spondyloarthritic features, such as a positive history of inflammatory bowel disease, radiographic evidence of sacroiliitis, and improvement with anti-inflammatory medication. Referral of patients with these findings for a rheumatological evaluation is warranted, as these diseases are managed effectively with specific treatment.
Practical Application of the Nutrition Recommendations for the Prevention and Treatment of Obesity in Pediatric Primary Care
Authors: Parks Elizabeth Prout , Kumanyika Shiriki , Stettler Nicolas 
Published: March 2010

CME EDUCATIONAL OBJECTIVES

1.
Identify the nutrition recommendations for the prevention and treatment of childhood overweight and obesity.

2.
Discuss the best use of behavioral strategies to implement changes in nutrition and feeding behaviors.

3.
Define the major challenges to adhering to nutrition recommendations and provide strategies to address these challenges.
More Variations on the Sierpiński Sieve
Authors: Hare Kevin G. 
Published: March 2010

AbstractThis paper answers a question of Broomhead, Montaldi and Sidorov about the existence of gaskets of a particular type related to the Sierpiński sieve. These gaskets are given by iterated function systems that do not satisfy the open set condition. We use the methods of Ngai and Wang to compute the dimension of these gaskets.
Predicting the toxicity of major ions in seawater to mysid shrimp (Mysidopsis bahia), sheepshead minnow (Cyprinodon variegatus), and inland silverside minnow (Menidia beryllina)
Authors: Pillard David A , DuFresne Doree L , Caudle Dan D , Tietge Joseph E , Evans James M 
Published: March 2010

AbstractAlthough marine organisms are naturally adapted to salinities well above those of freshwater, elevated concentrations of specific ions have been shown to cause adverse effects on some saltwater species. Because some ions are also physiologically essential, a deficiency of these ions can also cause significant effects. To provide a predictive tool to assess toxicity associated with major ions, mysid shrimp (Mysidopsis bahia), sheepshead minnows (Cyprinodon variegatus), and inland silverside minnows (Menidia beryllina) were exposed to saline solutions containing calcium, magnesium, potassium, strontium, bicarbonate, borate, bromide, and sulfate at concentrations above and below what would be found in seawater. Solution salinity was maintained at approximately 31‰ by increasing or decreasing sodium and chloride concentrations. Logistic regression models were developed with both the ion molar concentrations and ion activity. Toxicity to all three species was observed when either a deficiency or an excess of potassium and calcium occurred. Significant mortality occurred in all species when exposed to excess concentrations of magnesium, bicarbonate, and borate. The response to the remaining ions varied with species. Sheepshead minnows were the most tolerant of both deficient and elevated levels of the different ions. Mysid shrimp and inland silverside minnows demonstrated similar sensitivities to several ions, but silverside minnow response was more variable. As a result, the logistic models that predict inland silverside minnow survival generally were less robust than for the other two species.