bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Endogenous Cannabinoid System Stimulates Glucose Uptake in Human Fat Cells via Phosphatidylinositol 3-Kinase and Calcium-Dependent Mechanisms
Authors: Pagano Claudio , Pilon Catia , Calcagno Alessandra , Urbanet Riccardo , Rossato Marco , Milan Gabriella , Bianchi Katiuscia , Rizzuto Rosario , Bernante Paolo , Federspil Giovanni , Vettor Roberto 
Published: September 2007

Abstract
Background: The endogenous cannabinoid system participates in the regulation of energy balance, and its dysregulation may be implicated in the pathogenesis of obesity. Adipose tissue endocannabinoids may produce metabolic and endocrine effects, but very few data are available in human adipose tissue and in primary human fat cells.
Experimental Design: We measured expression of type 1 and type 2 cannabinoid receptors (CNR), enzymes of cannabinoids synthesis and degradation in human omental, sc abdominal, and gluteal adipose tissue from lean and obese subjects. Furthermore, we assessed the effect of CNR1 stimulation on glucose uptake and intracellular transduction mechanisms in primary human adipocytes. Then we assessed the reciprocal regulation between CNR1 and peroxisome proliferator-activated receptor-γ (PPARγ). Finally, we tested whether leptin and adiponectin are regulated by CNR1 in human adipocytes.
Results: We found that most genes of the endocannabinoid system are down-regulated in gluteal fat and up-regulated in visceral and sc abdominal adipose tissue of obese patients. Treatment of adipocytes with rosiglitazone markedly down-regulated CNR1 expression, whereas Win 55,212 up-regulated PPARγ. Win 55,212 increased (+50%) glucose uptake, the translocation of glucose transporter 4, and intracellular calcium in fat cells. All these effects were inhibited by SR141716 and wortmannin and by removing extracellular calcium. Win 55,212 and SR141716 had no effect on expression of adiponectin and leptin.
Conclusions: These results indicate a role for the local endocannabinoids in the regulation of glucose metabolism in human adipocytes and suggest a role in channeling excess energy fuels to adipose tissue in obese humans.
Hypothalamic-Pituitary-Adrenal Axis Activity in Obese Men with and without Sleep Apnea: Effects of Continuous Positive Airway Pressure Therapy
Authors: Vgontzas A. N. , Pejovic S. , Zoumakis E. , Lin H.-M. , Bentley C. M. , Bixler E. O. , Sarrigiannidis A. , Basta M. , Chrousos G. P. 
Published: September 2007

Abstract
Context: Previous studies on the association between the hypothalamic-pituitary-adrenal axis activity and sleep apnea (SA) and obesity are inconsistent and/or limited.
Objective: In this study, we evaluated the activity of the hypothalamic-pituitary-adrenal axis in nonpsychologically distressed obese subjects with and without SA and examined the impact of continuous positive airway pressure (CPAP) in SA patients.
Design and Participants: In study I, four-night sleep laboratory recordings and serial 24-h plasma measures of cortisol were obtained in 45 obese men with and without apnea and nonobese controls. Sleep apneic patients were reassessed after 3 months of CPAP use. In study II, 38 obese men with and without sleep apnea and nonobese controls were challenged with ovine CRH administration after four nights in the sleep laboratory.
Results: The sleep patterns were similar between obese and nonobese controls. Twenty-four-hour plasma cortisol levels were highest in nonobese controls, intermediate in obese apneic patients, and lowest in obese controls (8.8 ± 0.4 vs. 8.1 ± 0.3 vs. 7.5 ± 0.3 μg/dl, P &lt; 0.05). CPAP tended to reduce cortisol levels in the apneic patients (difference −0.7 ± .4 μg/dl, P = 0.1). CRH administration resulted in a higher ACTH response in both obese groups, compared with nonobese controls; the three groups were not different in cortisol response.
Conclusions: Nonpsychologically distressed, normally sleeping, obese men had low cortisol secretion. The cortisol secretion was slightly activated by SA and returned to low by CPAP use. The low cortisol secretion in obesity through its inferred hyposecretion of hypothalamic CRH might predispose the obese to sleep apnea.
Prolonged Reactive Oxygen Species Generation and Nuclear Factor-κB Activation after a High-Fat, High-Carbohydrate Meal in the Obese
Authors: Patel Chinmay , Ghanim Husam , Ravishankar Shreyas , Sia Chang Ling , Viswanathan Prabhakar , Mohanty Priya , Dandona Paresh 
Published: September 2007

Abstract
Background: Because obesity is associated with chronic oxidative and inflammatory stress, and high-fat, high-carbohydrate meals induce significant oxidative and inflammatory stress in normal subjects, we have now hypothesized that the intake of a high-fat, high-carbohydrate meal would result in a greater and more prolonged oxidative and inflammatory stress in the obese than in normal subjects.
Methods: Ten normal-weight and eight obese subjects were given a high-fat, high-carbohydrate meal after an overnight fast. Blood samples were collected at baseline and hourly following the meal for 3 h.
Results: Reactive oxygen species generation by mononuclear cells increased significantly by 2 h in both groups but continued to increase significantly at 3 h in the obese subjects, whereas in normal subjects it returned to baseline. Levels of p47phox increased significantly (by 81 ± 26%) at 3 h in obese individuals (P &lt; 0.05), whereas there was no significant change in p47phox in normal subjects. Nuclear factor-κB DNA binding in mononuclear cells increased significantly (by 48 ± 58%, P &lt; 0.036) at 2 h but not at 3 h in normal subjects, whereas in the obese, nuclear factor-κB increased significantly at both 2 and 3 h (by 36 ± 57 and 42 ± 63%, respectively, P &lt; 0.004). Matrix metalloproteinase-9 concentrations were significantly higher in the obese at baseline (580 ± 103.9 vs. 373 ± 30.03 ng/ml, P &lt; 0.05) and increased to significantly greater concentrations after the meal than in the lean subjects.
Conclusions: High-fat, high-carbohydrate meals induced a significantly more prolonged and greater oxidative and inflammatory stress in the obese. This may contribute to the increased atherogenic risk in obesity.
Association of BRAF V600E Mutation with Poor Clinicopathological Outcomes in 500 Consecutive Cases of Papillary Thyroid Carcinoma
Authors: Lupi Cristiana , Giannini Riccardo , Ugolini Clara , Proietti Agnese , Berti Piero , Minuto Michele , Materazzi Gabriele , Elisei Rossella , Santoro Massimo , Miccoli Paolo , Basolo Fulvio 
Published: September 2007

Abstract
Context: Because very few studies have examined the correlation between BRAF mutations and clinicopathological features of papillary thyroid carcinoma (PTC), we analyzed here a large and homogeneous cohort of patients with PTC for the presence of the BRAF mutation.
Objective: We examined BRAF mutations in a consecutive series of 500 PTC patients who underwent surgery in the Department of Surgery of the University of Pisa, and we correlated the presence of the mutation with clinicopathological parameters of the patients: age, gender, tumor size, presence of tumor capsule, extrathyroidal invasion, multicentricity, presence of node metastases, and tumor class.
Design: BRAF (exon 15) mutation was examined by PCR-single strand conformational polymorphism followed by DNA sequencing in laser-capture microdissected tissue samples.
Results: In this study, BRAF mutation was found in 219 of 500 cases (43.8%). In particular, we found the most common BRAF V600E mutation in 214 cases (42.8%), BRAF K601E mutation in three cases (0.6%), BRAF VK600–1E (0.2%) in one case, whereas in one case we found a new 14-bp deletion with concomitant 2-bp insertion, VKSR600–3del and T599I, respectively. BRAF V600E was associated with extrathyroidal invasion (P &lt; 0.0001), multicentricity (P = 0.0026), presence of nodal metastases (P = 0.0009), class III vs. classes I and II (P &lt; 0.00000006), and absence of tumor capsule (P &lt; 0.0001), in particular in follicular- and micro-PTC variants. By multivariate analysis, the absence of tumor capsule remained the only parameter associated (P = 0.0005) with BRAF V600E mutation.
Conclusions: Our data suggest that BRAF V600E mutation is associated with high-risk PTC and in particular in follicular variant with invasive tumor growth.
Risk Factors for Development of Coronary Heart Disease in Patients with Acromegaly: A Five-Year Prospective Study
Authors: Bogazzi Fausto , Battolla Luigi , Spinelli Cheti , Rossi Giuseppe , Gavioli Silvia , Di Bello Vitantonio , Cosci Chiara , Sardella Chiara , Volterrani Duccio , Talini Enrica , Pepe Pasquale , Falaschi Fabio , Mariani Giuliano , Martino Enio 
Published: September 2007

Abstract
Background: Data on coronary heart disease (CHD) are scanty and matter of argument in acromegalic patients.
Objective: The objective of this study was to evaluate risk factors for development of CHD and the occurrence of cardiac events in acromegalic patients during a 5-yr prospective study.
Design: Ten-year likelihood for CHD development was estimated by the Framingham scoring system (FS); patients were stratified as having low (FS &lt; 10), intermediate (≥ 10 FS &lt; 20), or high (FS ≥ 20) risk. Coronary artery calcium content was measured using the Agatston score (AS) in all patients; those with positive AS were submitted to myocardial single-photon emission computed tomography; cardiac events were recorded during a 5-yr follow-up period.
Patients: Fifty-two consecutive patients (31 women, mean age 52 ± 11 yr) with controlled or uncontrolled acromegaly were followed prospectively for 5 yr.
Results: Thirty-seven patients (71%) had low, 14 patients (27%) had intermediate, and one patient (2%) had high CHD risk. CHD risk was unrelated to acromegaly activity or the estimated duration of disease. Among patients with FS less than 10%, 24 had AS equal to 0, eight had AS of 1 or greater and less than 100, and five had AS 100 or greater and less than 300, respectively. Among patients with FS 10 or greater and less than 20%, nine had AS equal to 0, two had AS of one or greater and less than 100, one had AS of 100 or greater and less than 300, and two had AS of 300 or greater; a patient of the latter group, having AS of 400 or greater, increased his CHD risk from 11% to 20% or more. FS or AS did not differ in patients with controlled or uncontrolled acromegaly (P = 0.981). All patients with positive AS had no single photon emission computed tomography perfusion defects. During the 5-yr follow-up period no patient developed ischemic cardiac events.
Conclusions: CHD risk in acromegalic patients, predicted by FS as in nonacromegalic subjects, is low; AS might have adjunctive role only in a subset of patients. However, most patients have systemic complications of acromegaly, which participate in the assessment of global CHD risk.
Machine vision analysis of the energy efficiency of intermodal freight trains
Authors: Lai Y-C , Barkan C P L , Drapa J , Ahuja N , Hart J M , Narayanan P J , Jawahar C V , Kumar A , Milhon L R , Stehly M P 
Published: September 2007

Intermodal (IM) trains are typically the fastest freight trains operated in North America. The aerodynamic characteristics of many of these trains are often relatively poor resulting in high fuel consumption. However, considerable variation in fuel efficiency is possible depending on how the loads are placed on railcars in the train. Consequently, substantial potential fuel savings are possible if more attention is paid to the loading configuration of trains. A wayside machine vision (MV) system was developed to automatically scan passing IM trains and assess their aerodynamic efficiency. MV algorithms are used to analyse these images, detect and measure gaps between loads. In order to make use of the data, a scoring system was developed based on two attributes - the aerodynamic coefficient and slot efficiency. The aerodynamic coefficient is calculated using the Aerodynamic Subroutine of the train energy model. Slot efficiency represents the difference between the actual and ideal loading configuration given the particular set of railcars in the train. This system can provide IM terminal managers feedback on loading performance for trains and be integrated into the software support systems used for loading assignment.
Impact of Drug Use and Comorbidities on In-Hospital Falls in Patients with Chronic Kidney Disease
Authors: Angalakuditi Mallik V , Gomes Joseph , Coley Kim C 
Published: September 2007

Background: In-hospital falls are a major problem in healthcare institutions and contribute to morbidity and mortality in this setting. Patients with chronic kidney disease (CKD) were previously found to be at higher risk for experiencing an in-hospital fall. Objective: To evaluate the association between comorbidities and drug use with the risk of in-hospital falls in adults with CKD. Methods: A retrospective case-control study was conducted in patients with CKD hospitalized between January 1, 1998, and June 30, 2003. Cases included patients who experienced an in-hospital fait, were 18 years of age or older, and had been hospitalized for more than 24 hours. For every case, 2 controls were identified and matched for CKD, age, and sex. Information about comorbidities and drug use was collected from an electronic medical data repository. Statistical tests performed were t-tests, χ2 analysis, and multivariate logistic regression, using occurrence of a fall as the dependent variable and race, comorbidities, and drug groups as covariates. Results: There were 635 fall cases that met study criteria. The mean age of patients was 68 ± 15 years, 54% were female, and 82% were white. There were 1270 matched controls with CKD who were included in the regression analysis. Comorbidities that increased the likelihood of experiencing an in-hospital fall were dementia (OR 2.63), pneumonia (OR 1.72), gastrointestinal disease (OR 1.41), and diabetes (OR 1.31). Drugs associated with an in-hospital fall were antidepressants (OR 1.65) and anticonvulsants (OR 1.52). Conclusions: Several comorbidities, especially dementia, significantly increase the risk of experiencing an in-hospital fall in patients with CKD. Drugs that place CKD patients at risk include antidepressants and anticonvulsants.
Risk of Treatment-Emergent Diabetes Mellitus in Patients Receiving Antipsychotics
Authors: Citrome Leslie L , Holt Richard IG , Zachry Woodie M , Clewell Jerry D , Orth Paul A , Karagianis Jamie L , Hoffmann Vicki Poole 
Published: September 2007

Background: Type 2 diabetes mellitus has been reported during antipsychotic treatment. Objective: To quantify the potential risk of treatment-emergent diabetes mellitus among patients receiving antipsychotic medications. Methods: The MEDLINE and Psychinfo databases were searched using the key words antipsychotic (including individual drug names), diabetes, risk, and incidence for all English-language articles published between 1966 and 2005. Risk calculations were performed using data obtained from pharmacoepidemiologic studies that met the following criteria: (1) cohort design, (2) determination of preexisting diabetes, (3) inclusion of antipsychotic monotherapy as an exposure variable, and (4) comparison with exposure to first-generation antipsychotics. Studies meeting these criteria were used to calculate incidence, attributable risk between agents, and number needed to harm. Results: A total of 25 observational pharmacoepidemiologic studies were found comparing antipsychotics on the outcome of diabetes mellitus. Sufficient information was provided in 15 of the reports to be able to estimate attributable risk, Attributable risk for individual second-generation antipsychotics relative to first-generation antipsychotics ranged from 53 more to 46 fewer new cases of diabetes per 1000 patients. Little observable difference was noted between the individual second-generation antipsychotics versus first-generation antipsychotics on this outcome. However, few of the studies controlled for body weight, race or ethnicity, or the presence of diabetogenic medications. None adjusted for familial history of diabetes, levels of physical activity, or diet, as this information is not usually available in the databases used in pharmacoepidemiologic studies. Conclusions: Based on the published pharmacoepidemiologic reports reviewed, the avoidance of diabetes as an outcome cannot be predictably achieved with precision by choice of a second- versus a first-generation antipsychotic. Risk management for new-onset diabetes requires the assessment of established risk factors such as family history, advancing age, non-white ethnicity, diet, central obesity, and level of physical activity.
Potential Interactions Between Complementary/Alternative Products and Conventional Medicines in a Medicare Population
Authors: Elmer Gary W , Lafferty William E , Tyree Patrick T , Lind Bonnie K 
Published: September 2007

Background: Despite the high prevalence of complementary and alternative medicine (CAM) product use among the elderly, little is known about the extent of concurrent CAM-conventional medicine use and the potential for adverse reactions. Objective: To determine the prevalence of CAM product use concurrent with conventional medications, prescription and nonprescription, in a Medicare population and assess the risk for adverse interactions. Methods: Retrospective analysis was performed on Cardiovascular Health Study interview data from 1994, 1995, 1997, and 1999. The prevalence of concurrent combinations of CAM products and conventional drugs was tabulated. The adverse interaction risks were categorized as unknown, theoretical, and significant. Results: Of 5052 participants, the median age was 75, 60.2% were female, 16.6% were African American, and 83.4% were white. The percent using CAM products during the 4 time periods was 6.3%, 6.7%, 12.8%, and 15.1 %, The percent using both CAM products and conventional drugs was 6.0%. 6.2%. 11.7%, and 14.4%, Of these, 294 (5.8%) individuals took combinations considered to have a significant risk for an adverse interaction. Combinations with risk were observed on 393 separate interviews. Most (379) involved a risk of bleeding due to use of ginkgo, garlic, or ginseng together with aspirin, warfarin, ticlopidine, or pentoxifylline. An additional 786 observations of combinations were considered to have some, albeit theoretical or uncertain, risk (or an adverse interaction. Conclusions: Concurrent use of CAM products and conventional medicines in a Medicare population was found to be common. Research to define the risks of combining ginkgo and garlic supplements with aspirin should be of high priority.
Grain Growth in Nanocrystalline Metal Thin Films under In Situ Ion-Beam Irradiation
Authors: Kaoumi D. , Motta A. T. , Birtcher R. C. 
Published: September 2007

Abstract
In-situ observations in a transmission electron microscope (TEM) were used to study the microstructure evolution in metal Zr, Pt, Cu, and Au nanocrystalline thin films under ion-beam irradiation. Free-standing films were prepared by sputter deposition. Samples were irradiated in-situ at the Intermediate Voltage Electron Microscope (IVEM) at Argonne National Laboratory with Ar and Kr ions to fluences in excess of 1016 ion/cm2. As a result of irradiation, grain growth was observed in all samples using Bright Field (BF) imaging in the TEM. The average grain size increased monotonically with ion fluence until it reached a saturation value. Similarly to thermal grain growth, the ion-irradiation induced grain growth curves could be best fitted with curves of the type: Dn-D0n=KΦ. The irradiations were done at temperatures ranging from 20 to 773 K. The results suggest the existence of three regimes with respect to irradiating temperature: (i) a purely thermal regime, which appears to start above the bulk coarse-grained recrystallization temperature, (ii) a thermally assisted regime where thermal diffusion and irradiation effects combine to increase the rate of grain growth relative to that resulting from either of these mechanisms alone, and (iii) an athermal regime (low-temperature regime) where irradiation can by itself cause grain growth. The transition temperature between the athermal regime and the thermally assisted regime depends on the material, but is in the range 0.14–0.22 times the melting point. The influence of the ion type was also investigated on Zr-Fe irradiated with 600 keV Kr ions versus 600 keV Ar ions.
β-Cell Mitochondria Exhibit Membrane Potential Heterogeneity That Can Be Altered by Stimulatory or Toxic Fuel Levels
Authors: Wikstrom Jakob D. , Katzman Shana M. , Mohamed Hibo , Twig Gilad , Graf Solomon A. , Heart Emma , Molina Anthony J.A. , Corkey Barbara E. , de Vargas Lina Moitoso , Danial Nika N. , Collins Sheila , Shirihai Orian S. 
Published: September 2007

OBJECTIVE—β-Cell response to glucose is characterized by mitochondrial membrane potential (ΔΨ) hyperpolarization and the production of metabolites that serve as insulin secretory signals. We have previously shown that glucose-induced mitochondrial hyperpolarization accompanies the concentration-dependent increase in insulin secretion within a wide range of glucose concentrations. This observation represents the integrated response of a large number of mitochondria within each individual cell. However, it is currently unclear whether all mitochondria within a single β-cell represent a metabolically homogenous population and whether fuel or other stimuli can recruit or silence sizable subpopulations of mitochondria. This study offers insight into the different metabolic states of β-cell mitochondria.
RESULTS—We show that mitochondria display a wide heterogeneity in ΔΨ and a millivolt range that is considerably larger than the change in millivolts induced by fuel challenge. Increasing glucose concentration recruits mitochondria into higher levels of homogeneity, while an in vitro diabetes model results in increased ΔΨ heterogeneity. Exploration of the mechanism behind heterogeneity revealed that temporary changes in ΔΨ of individual mitochondria, ATP-hydrolyzing mitochondria, and uncoupling protein 2 are not significant contributors to ΔΨ heterogeneity. We identified BAD, a proapoptotic BCL-2 family member previously implicated in mitochondrial recruitment of glucokinase, as a significant factor influencing the level of heterogeneity.
CONCLUSIONS—We suggest that mitochondrial ΔΨ heterogeneity in β-cells reflects a metabolic reservoir recruited by an increased level of fuels and therefore may serve as a therapeutic target.