Miracle-dz/UniFAR-FTUs huggingface dataset:
Gender Differences with High Dose Naltrexone in Cocaine and Alcohol Dependent Patients

This is a randomized, double blind, placebo-controlled clinical trial that evaluated the efficacy of a higher than typical daily dose of naltrexone (150mg/day), taken for 12 weeks, in 164 patients ( n =116 men and n =48 women) with co-occurring cocaine and alcohol dependence. Patients were stratified by gender, and then randomly assigned to naltrexone or placebo, and to either cognitive behavioral therapy, or a type of medical management. The two primary outcomes were cocaine and alcohol use. Significant gender by medication interactions were found for cocaine use via urine drug screens [3-way with time] and self-reports [2-way], for drug severity [2-way], and for alcohol use [2-way]. Type of psychosocial treatment did not affect outcomes. Thus, 150mg/day of naltrexone added to a psychosocial treatment resulted in reductions in cocaine and alcohol use, and drug severity in men, compared to higher rates of cocaine and alcohol use and drug severity in women.
Wnt/ β -catenin pathway regulates Bmp2-mediated differentiation of dental follicle cells

Background and Objectives— Bmp2-induced osteogenic differentiation has been shown to occur through the canonical Wnt/ β -catenin pathway, whereas factors promoting canonical Wnt signaling in cementoblasts inhibited cell differentiation and promoted cell proliferation in vitro . The aim of this study was to investigate whether putative precursor cells of cementoblasts, dental follicle cells (murine SVF4 cells), when stimulated with Bmp2, would exhibit changes in genes/ proteins associated with the Wnt/ β -catenin pathway. Materials and Methods— SVF4 cells were stimulated with Bmp2, and the following assays were carried out: 1) Wnt/ β -catenin pathway activation assessed by western blot, β -catenin/TCF reporter assay, and gene expression of lymphoid enhancer-binding factor-1 (Lef1), transcription factor 7 (Tcf7), Wnt inhibitor factor 1 (Wif1) and Axin2, and 2) cementoblast/osteoblast differentiation assessed by mineralization in vitro , and mRNA levels of runt-related transcription factor 2 (Runx2), osterix (Osx), alkaline phosphatase (Alp), osteocalcin (Ocn) and bone sialoprotein (Bsp) by qPCR after Wnt3a treatment and knockdown of β -catenin. Results— Wnt3a induced β -catenin nuclear translocation and upregulated the transcriptional activity of a canonical Wnt-responsive reporter, suggesting the Wnt/ β -catenin pathway functions in SVF4 cells. Activation of Wnt signaling with Wnt3a suppressed Bmp2-mediated induction of cementoblast/osteoblast maturation of SVF4 cells. However, β -catenin knockdown showed that Bmp2-induced expression of cementoblast/osteoblast differentiation markers requires endogenous β -catenin. Wnt3a down-regulated transcripts for Runx2, Alp and Ocn in SVF4 cells compared to untreated cells. In contrast, Bmp2 induction of Bsp transcripts occurred independent of Wnt/ β catenin signaling. A u t r r p t N H Conclusions— These data suggest that stabilization of β -catenin by Wnt-3a treatment inhibits Bmp2-mediated induction of cementoblast/osteoblast differentiation in SVF4 cells, although Bmp2 requires endogenous Wnt/ β -catenin signaling to promote cell maturation.
Body fat redistribution and metabolic abnormalities in HIV-infected patients on HAART: novel insights into pathophysiology and emerging opportunities for treatment

Highly active antiretroviral therapy (HAART) has contributed considerably towards decreasing morbidity and mortality from human immunodeficiency virus (HIV)-related diseases over the past two decades. At the same time, however, use of HAART has also been associated with metabolic complications including hyperinsulinemia and insulin resistance, dyslipidemia (hypertriglyceridemia, reduced high-density lipoprotein (HDL)cholesterol and increased total and low-density lipoprotein (LDL)-cholesterol concentrations), as well as body fat redistribution (lipodystrophy) [1,2]. All these metabolic abnormalities may in turn increase risk for cardiovascular disease [3].
Amino Acids and Muscle Loss with Aging1,2,3

Aging is associated with a progressive loss of muscle mass (sarcopenia), which increases the risks of injury and disability. Although the mechanisms of sarcopenia are not clearly elucidated, age-associated alterations in the muscle anabolic response to nutritional stimuli and a decline in protein intake may be significant contributing factors. The most recent findings regarding the role of nutritional intake on protein metabolism in the elderly will be reviewed. Specifically, aging is associated with changes in the muscle protein metabolism response to a meal, likely due to alterations in the response to endogenous hormones. Nonetheless, the older muscle is still able to respond to amino acids, mainly the essential and BCAAs, which have been shown to acutely stimulate muscle protein synthesis in older individuals. It is likely that this stimulatory effect of essential and BCAA is due to the direct effect of leucine on the initiation of mRNA translation, which is still present in older age, although it appears to be attenuated in aged animals. Recent data suggest that excess leucine may be able to overcome this age-related resistance of muscle proteins to leucine. For this reason, long-term essential amino acid supplementation may be a useful tool for the prevention and treatment of sarcopenia, particularly if excess leucine is provided in the supplement.
Apolipoprotein-J Prevention of Cardiac Myobalst Apoptosis Induced by Ethanol

Over-consumption of ethanol (EtOH) represents a major health problem. This study was to test the cytotoxicity of EtOH in cardiac stem cells or myoblasts, and the potential protective effect of apolipoprotein-J (ApoJ), a stress-responding, chaperone-like protein in high density lipoprotein, on EtOH-injured cardiac myoblasts. In culture, EtOH-exposed canine fetal myoblasts underwent apoptosis in a concentration- and time-dependent manner. Transduction of ApoJ by cDNA transfection markedly reduced EtOH-induced apoptosis in the cells. ApoJ expression also restored partially the mitochondrial membrane potential and prevented the release of cytochrome-c from mitochondria into cytoplasma. Thus, ApoJ serves as a cytoprotective protein that protects cardiac stem cells against cytotoxicity of EtOH.
The effect of 17 β -estradiol on intracellular calcium homeostasis in human endothelial cells

The cardiovascular effects of estrogen are mediated in part by augmenting the function of endothelial nitric oxide synthase. Endothelial nitric oxide synthase activity is dependent on many cofactors including Ca 2+ . Hence, we investigated the effect of chronic 17 β -estradiol treatment on the intracellular Ca 2+ concentration and endothelial nitric oxide synthase protein expression in the human endothelial cell line, EA.hy926, using spectrofluorometry and Western blot, respectively. Inhibiting the sarco(endo)plasmic reticulum Ca 2+ ATPase with thapsigargin caused an increase in the intracellular Ca 2+ concentration, which was higher in chronically 17 β -estradiol-treated (1 μ M, 24 h) cells loaded with Fura-2-acetoxymethyl ester compared to vehicle-treated cells, suggesting a higher endoplasmic reticulum Ca 2+ content in 17 β -estradiol-treated cells. An enhanced Ca 2+ influx pathway in chronically 17 β -estradiol-treated cells was also observed. In addition, 17 β -estradiol-treated cells expressed higher levels of endothelial nitric oxide synthase protein in comparison to vehicle-treated cells. The chronic effect of 17 β -estradiol on Ca 2+ homeostasis and endothelial nitric oxide synthase expression was attenuated with the nonselective estrogen receptor inhibitor, ICI 182,780 (10 M, analysis of the thapsigargin-evoked Ca 2+ response in chronically 17 β -estradiol-treated estrogen receptor α -knockdown cells showed no significant difference in Ca 2+ response compared to vehicle-treated estrogen receptor α -knockdown cells, indicating that the regulation of Ca 2+ homeostasis by 17 β -estradiol is mediated through an estrogen receptor α -dependent pathway. These data revealed an estrogen receptor α -dependent modulation of Ca 2+ homeostasis accompanying the enhancement of endothelial nitric oxide synthase expression in 17 β -estradiol-treated human endothelial cells.
b 1 -, b 2 - and atypical b -adrenoceptor-mediated relaxation in rat isolated aorta

1 b -adrenoceptor-mediated relaxation was investigated in ring preparations of rat isolated thoracic aorta. Rings were pre-constricted with a sub-maximal concentration of noradrenaline (1 m M ) and relaxant responses to cumulative concentrations of b -adrenoceptor agonists obtained. 2 isoprenaline propranolol 50 gave a pA 2 of 7.6. Selective b 1 - and b 2 -adrenoceptor antagonists, CGP 20712A (0.1 m M ) and ICI 118551 (0.1 m M ), respectively, produced 4 and 14 fold shifts of the isoprenaline CRC. 3 Atypical b -adrenoceptor agonists also produced concentration-dependent relaxation of aortic rings. The order of potency of the b -adrenoceptor agonists was ( 7 log EC 50 ): isoprenaline (6.25) 4 cyanopindolol (5.59) 4 isoprenaline+propranolol (5.11) 4 CGP 12177A (4.40) 4 ZD 2079 (4.24) 4 ZM 215001 (4.07) 4 BRL 37344 (3.89). Relaxation to CGP 12177A and ZM 215001 was una(cid:128)ected by propranolol (0.3 m M ). 4 SR 59230A ( 4 1 m M ) and cyanopindolol (1 m M ), b 3 -adrenoceptor antagonists, had no e(cid:128)ect on the isoprenaline (in the presence of propranolol) or CGP 12177A CRCs. Bupranolol and CGP 20712A, at m M concentrations ( b 4 -adrenceptor antagonists), inhibited responses to isoprenaline (in the presence of propranolol) and CGP 12177A. 5 In conclusion, atypical b -adrenoceptors co-exist with b 1 - and b 2 -adrenoceptors in rat aorta. Although non-conventional partial agonists and selective b 3 -adrenoceptor agonist cause relaxation, the vascular atypical b -adrenoceptor does not appear to correspond to the b 3 -adrenoceptor. There are, however, similarities with the putative b 4 -adrenoceptor. British Journal of Pharmacology (2000) 129, 637 –644
Mechanisms by which Human DNA Primase Chooses to Polymerize a NTP †

Human DNA primase synthesizes short RNA primers that DNA polymerase α then elongates during the initiation of all new DNA strands. Even though primase misincorporates NTPs at a relatively high frequency, this likely does not impact the final DNA product since the RNA primer is replaced with DNA. We used an extensive series of purine and pyrimidine analogues to provide further insights into the mechanism by which primase chooses whether or not to polymerize a NTP. Primase readily polymerized a size-expanded cytosine analogue, 1, 3-diaza-2-oxo-phenothiazine-NTP, across from a templating G but not across from A. The enzyme did not efficiently polymerize NTPs incapable of forming two Watson-Crick hydrogen bonds with the templating base with the exception of UTP opposite purine deoxyribonucleoside. Likewise, primase did not generate base-pairs between two nucleotides with altered Watson-Crick hydrogen bonding patterns. Examining the mechanism of NTP polymerization revealed that human primase can misincorporate NTPs via both template misreading and a primer-template slippage mechanism. Together, these data demonstrate that human primase strongly depends on Watson-Crick hydrogen bonds for efficient nucleotide polymerization, much more so than the mechanistically related herpes primase, and provide insights into the potential roles of primer-template stability and base tautomerization during misincorporation.
The Association of the Angiotensinogen Gene with Insulin Sensitivity in Humans: A Tagging SNPs and Haplotype Approach

Objective— The purpose of this study was to clarify the association of the angiotensinogen gene (AGT) with insulin sensitivity using SNP and haplotype analyses in a Caucasian cohort. Material and Methods— A candidate gene association study was conducted in Caucasians with and without hypertension (N=449). Seventeen single nucleotide polymorphisms (SNPs) of the AGT gene and their haplotypes were analyzed for an association with HOMA-IR. Multivariate regression model accounting for age, gender, BMI, hypertension status, study site, and sibling relatedness was used to test the hypothesis. Results— Nine of the seventeen SNPs were significantly associated with lower HOMA-IR levels. Homozygous minor allele carriers of the most significant SNP rs2493134 (GG), a surrogate for the gain of function mutation rs699 [AGT p.M268T], had significantly lower HOMA-IR levels (p=0.0001) than heterozygous or homozygous of rs699 in a subset of the population showed similar results with minor allele carriers exhibiting significantly decreased HOMA-IR levels (p=0.003). Haplotype analysis demonstrated that haplotypes rs2493137A|rs5050A|rs3789678G|rs2493134A and rs2004776G|rs11122576A|rs699T| rs6687360G were also significantly associated with HOMA-IR (p=0.0009, p=0.02) and these results were driven by rs2493134 and rs699. Conclusion— This study confirms an association between the AGT gene and insulin sensitivity in Caucasian humans. Haplotype analysis extends this finding and implicates SNPs rs2493134 and rs699 as the most influential. Thus, AGT gene variants, previously shown to be associated with AGT levels, are also associated with insulin sensitivity; suggesting a relationship between the AGT gene, AGT levels, and insulin sensitivity in humans.
An iPTH based protocol for the prevention and treatment of symptomatic hypocalcemia after thyroidectomy

Background— Symptomatic hypocalcemia after thyroidectomy is a barrier to same day surgery, and the cause of ER visits. A standard protocol of calcium and vitamin D supplementation, dependent on intact parathyroid hormone (iPTH) levels, can address this issue. How effective is it? When does it fail? Methods— We performed a retrospective review of the prospective Thyroid Database from January 2006 to December 2010. 620 patients underwent completion (CT) or total thyroidectomy (TT), and followed our post-operative protocol of calcium carbonate administration for iPTH levels ≥10pg/ml and calcium carbonate and 0.25 μ g calcitriol BID for iPTH <10pg/ml. Calcium and iPTH values, pathology and medication, were compared to evaluate protocol efficacy. A p value <0.05 was considered statistically significant. Results— Using the protocol, sixty-one (10.2%) patients were chemically hypocalcemic but never developed symptoms and twenty-four (3.9%) patients developed breakthrough symptomatic hypocalcemia. The symptomatic (SX) and asymptomatic (ASX) groups were similar with regard to gender, cancer diagnosis, and pre-operative calcium and iPTH. The symptomatic group was significantly younger (39.6 ± 2.8 vs. 49 ± 0.6 years, p=0.01), with lower post-operative iPTH levels. 33% (n=8) of SX patients had an iPTH ≤5 pg/ml vs. only 6% (n=37) of ASX patients. While the majority of patients with a PTH <5 pg/ml were asymptomatic, 62.5% (n=5) of SX patients with iPTH levels ≤5 pg/ml, required an increased in calcitriol dose to achieve both biochemical correction and symptom relief. based on post-operative iPTH levels can minimize symptomatic hypocalcemia after thyroidectomy. An iPTH ≤ 5pg/ml may warrant higher initial doses of calcitriol in order to prevent symptoms.
Predictive Control of Flexible Resources for Demand Response in Active Distribution Networks

In this paper, a model-based predictive control method is proposed for utilization of flexible resources such as battery energy storage systems and heating systems effectively to provide demand response in low-voltage distribution networks with solar photovoltaic. The contributions of this paper are twofold. First, a linear power flow method based on relaxation of branch power losses applicable to radial distribution networks is proposed and formulated. Second, a flexible resources controller that solves a multi-objective linear optimization problem in receding-horizon fashion is formulated taking into account system states, forecasts of generation, and loads. Using the proposed control algorithm, flexibility from network resources can be utilized for low-voltage network management with assurance of quality of service to the customers. Simulations are conducted for summer and winter cases on a simplified Danish low-voltage network using Matlab/Simulink to study the performance of the proposed control method. Compared to the methods in state of the art, the proposed linear power flow method is proven to be accurate for the calculation of network power flows. Simulation results also show that proposed flexible resources controller can meet the network control objectives while satisfying the network constraints and operation limits of the flexible resources.
TLR4 mediate intrauterine growth restriction after systemic C. rectus infection in mice

Summary Campylobacter rectus is associated with fetal exposure and low-birth weight in humans. C. rectus also invades placental tissues and induces fetal intrauterine growth-restriction (IUGR) in mice, along with Toll-like receptors (TLR4) overexpression, suggesting that TLR4 may mediate placental immunity and IUGR in mice. To test this hypothesis we examined the effect of in vitroTLR4 neutralization in trophoblastic proinflammatory activity and studied the IUGR phenotype in a congenic TLR4-mutant mouse strain after in vivo C. rectus infection. Human trophoblasts were pretreated with TLR4 neutralizing antibodies and infected with C. rectus; proinflammatory cytokine production was assessed by cytokine multiplexing assays. Neutralizing TLR4 antibodies significantly impaired the production of pro-inflammatory cytokines in trophoblastic cells after infection in a dose-dependent manner. We used a subcutaneous chamber model to provide a C. rectus challenge in BALB/cAnPt (TLR4 Lps-d ) and wild-type(WT) females. Females were mated with WT or TLR4 Lps-d males once/week; pregnant mice were infected at (E)7.5 and sacrificed at (E)16.5 to establish IUGR phenotypes. Maternal C. rectus infection significantly decreased fetal weight/length in infected WT when compared to sham WT controls(P<0.05, ANOVA). However, infected TLR4 Lps-d−/− mice did not show statistically significant differences in fetal weight and length when compared to WT controls(P>0.05). Furthermore, heterozygous TLR4 Lps-d −/+ fetuses showed IUGR phenotype rescue. We concluded that TLR4 is an important mediator of trophoblastic proinflammatory responses and TLR4-deficient fetuses do not develop IUGR phenotypes after C. rectus infection, suggesting that placental cytokine activation is likely to be mediated by TLR4 during low birth weight/preterm delivery pathogenesis.
Hypolipidaemic and antioxidant effect of Enicostemma littorale

Objective: T o investigate the hypolipidaemic and antioxidant effects of aqueous leaf extract of Enicostemma littorale ( E. littorale ) Blume ( E ns ) against ethanol induced hepatic injury in albino rats. Methods: M ale albino rats of six numbers in each group were undertaken for study. H ypolipidaemic and antioxidant effect of E. littorale Blume ( E ns ) aqueous leaf extract at a dosage of 250 mg/kg bw was evaluated. Results: L evels of serum and tissue cholesterol, triglycerides and free fatty acids were elevated and levels of tissue thiobarbituric acid reactive substances ( TBARS ) and lipid hydroperoxide were increased in ethanol treated rats. T he activity levels of liver antioxidant enzymes such as superoxide dismutase ( SOD ) , catalase ( CAT ) , glutathione peroxidase ( GPX ) and glutathione-s-transferase ( GST ) were decreased. A fter adiminstration of extract of E. littorale Blume, levels of cholesterol, triglycerides and free fatty acids were decreased in serum and liver tissue, levels of TBARS and lipid hydroperoxide were decreased, and liver antioxidant enzymes were increased in liver tissue. Conclusions: I t can be concluded that the aqueous leaf extract of E. littorale Blume ( E ns ) has potent restorative effect on hyperlipidaemic and oxidative stress.
Integral Geometry and Radon Transforms

1. - The Radon Transformon on Rn 1.1- Introduction 1.2- The Radon Transform: The Support Theorem 1.3- The Inversion Formula: Injectivity Questions 1.4- The Plancherel Formula 1.5- Radon Transform of Distribution 1.6- Integration over d-planes: X-Ray Transforms 1.7- Applications 2. - A Duality in Integral Geometry 2.1- Homogeneous Spaces in Duality 2.2- The Radon Transform for the Double Fibration: Principal Problems 2.3- Orbital Integrals 2.4- Examples of Radon Transforms for Homogeneous Spaces in Duality 3. - The Radon Transform on Two-Point Homogeneous Spaces 3.1- Spaces of Constant Curvature: Inversion and Support Theorems 3.2- Compact Two-Point Homogeneous Spaces: Applications 3.3- Noncompact Two-Point Homogeneous Spaces 3.4- Support Theorems Relative to Horocycles 4. - The X-Ray Transform on a Symmetric Space 4.1- Compact Symmetric Spaces: Injectivity and Local Inversion: Support Theorem 4.2- Noncompact Symmetric Spaces: Global Inversion and General Support Theorem 4.3- Maximal Tori and Minimal Spheres in Compact Symmetric Spaces 5. - Orbital Integrals 5.1- Isotropic Spaces 5.2- Orbital Integrals 5.3- Generalized Riesz Potentials 5.4- Determination of a Function from its Integral over Lorentzian Spheres 5.5- Orbital Integrands and Huygens' Principle 6. - The Mean-Value Operator 6.1- An Injectivity Result 6.2- Asgeirsson's Mean-Value Theorem Generalized 6.3- John's Indentities 7. - Fourier Transforms and Distribution: A Rapid Course 7.1-The Topology of Spaces D(Rn), E(Rn) and S(Rn) 7.2- Distribution 7.3- Convolutions 7.4- The Fourier Transform 7.5- Differential Operators with Constant Coefficients 7.6- Riesz Potentials 8. - Lie Transformation Groups and Differential Operators 8.1- Manifolds and Lie Groups 8.2- Lie Transformation Groups and Radon Transforms 9. - Bibliography 10. - Notational Conventions 11. - Index.
Evaluation of gene expression levels in the diagnosis of lung adenocarcinoma and malignant pleural mesothelioma

bir rol oynayabilir. Anah­tar­söz­cük­ler: Adenokarsinom, gen ekspresyonu, akciğer, malign, mezotelyoma. ABSTRACT Background:­ This study aims to evaluate gene expression levels in the diagnosis of lung adenocarcinoma and malignant pleural mesothelioma both which have a distinct treatment and prognosis. Methods: Between January 2012 and January 2014, 12 newly diagnosed patients with a lung adenocarcinoma, 12 patients with malignant pleural mesothelioma, and eight healthy individuals as the control group were included. After treatment of the fresh samples of lung adenocarcinoma stored at -80°C for ribonucleic acid isolation, and paraffin-embedded tissues of patients with malignant pleural mesothelioma were deparaffinized, complementary deoxyribonucleic acid synthesis and expression of 84 genes associated with deoxyribonucleic acid repair were analyzed via real-time polymerase chain reaction assay. According to the expression of tumor cells, expression of each fold change was calculated. Results:­ The BRCA1, BRCA2, CDK7, MLH3, MSH4, NEIL3, SMUG1, UNG, XRCC2, and XRCC4 genes showed more than five-fold higher expression in the patients with lung adenocarcinomas, compared to the control group. The patients with malignant pleural mesothelioma showed a five-fold higher expression in the APEX2, BRCA1, BRCA2, CDK7, MLH1, MLH3, MSH3, MSH4, NEIL3, PARP2, PARP3, PMS1, RAD50, RAD51, RAD51B, RAD51D, RAD52, RPA3, SMUG1, UNG, XPA, XRCC2, and XRCC4 genes, compared to the control group. Comparing malignant pleural mesothelioma with lung adenocarcinoma cases, we found that CDK7, MLH1, TREX1, PRKDC, XPA, PMS1, UNG, and RPA3 genes were overexpressed. Conclusion:­ Our study results showed differences between expression profiles of deoxyribonucleic acid repair genes in lung adenocarcinoma and malignant pleural mesothelioma cells. Based on our study results, we suggest that TREX1, PRKDC, and PMS1 genes may play a