Miracle-dz/UniFAR-FTUs huggingface dataset:
Combination of Calcium Channel Blockers and Beta‐Blockers for Patients with Exercise‐Induced Angina Pectoris: Beneficial Effect of Calcium Channel Blockers Largely Determined by Their Effect on Heart Rate

The combination of calcium channel blockers and beta‐blockers is more effective for the treatment of exercise‐induced angina pectoris than beta‐blocker monotherapy. As ischemia in exercise‐induced angina is essentially preceded by an increase in heart rate, calcium channel blockers with a negative chronotropic property may perform better for this purpose than nonchronotropic compounds. A 335‐patient, 10‐week, double‐blind, parallel‐group comparison of amlodipine 5 mg and 10 mg, diltiazem 200 mg and 300 mg, and mibefradil 50 mg and 100 mg treatment added to baseline beta‐blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. All of the calcium channels blockers significantly delayed the onset of 1 mm ST‐segment depression on ETT (p < 0.001 for any treatment vs. baseline). In addition, mibefradil, in both low‐ and high‐dose treatments, produced the largest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 seconds, respectively, p < 0.003 and < 0.001; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 seconds, respectively, p < 0.001 and < 0.001). A stepwise logistic regression analysis revealed that this beneficial effect of calcium channel blockers was largely dependent on their effect on heart rate. Serious symptoms of dizziness likewise occurred significantly more frequently on mibefradil (p < 0.05 vs. diltiazem) and urged no fewer than 19 patients on mibefradil to withdraw from the trial. The authors conclude that calcium channel blockers with a negative chronotropic property provide a better delay of ischemia in patients with exercise‐induced angina, but the concomitant risk of intolerable dizziness may reduce this benefit.
Identification of a nucleoside analog active against adenosine kinase–expressing plasma cell malignancies

Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity. We found different adenosine kinase–inactivating (ADK-inactivating) alterations in all resistant clones and determined that ADK is required to phosphorylate and activate 6-ETI. Further, we observed that 6-ETI induces ATP depletion and cell death accompanied by S phase arrest and DNA damage only in ADK-expressing cells. Immunohistochemistry for ADK served as a biomarker approach to identify 6-ETI–sensitive tumors, which we documented for other lymphoid malignancies with plasmacytic features. Notably, multiple myeloma (MM) expresses high levels of ADK, and 6-ETI was toxic to MM cell lines and primary specimens and had a robust antitumor effect in a disseminated MM mouse model. Several nucleoside analogs are effective in treating leukemias and T cell lymphomas, and 6-ETI may fill this niche for the treatment of PEL, plasmablastic lymphoma, MM, and other ADK-expressing cancers.
Effects of Resistance Exercise Applied Early After Coronary Artery Bypass Grafting: a Randomized Controlled Trial

OBJECTIVE To evaluate the effects of resistance exercise applied early after coronary artery bypass grafting. METHODS It is a randomized controlled trial with 34 patients undergoing coronary artery bypass grafting between August 2013 and May 2014. Patients were randomized into two groups by simple draw: a control group (n=17), who received conventional physical therapy and an intervention group (n=17), who received, additionally, resistance exercise. Pulmonary function and functional capacity were evaluated in preoperative period and hospital discharge by spirometry and the six-minute walk test. For statistical analysis, we used the following tests: Shapiro-Wilk, Mann-Whitney, Student's t and Fisher's exact. Variables with P<0.05 were considered significant. RESULTS Groups were homogeneous in terms of demographic, clinical and surgical variables. Resistance exercise exerted no effect on pulmonary function of intervention group compared to control group. However, intervention group maintained functional capacity at hospital discharge measured by percentage of predict distance in 6MWT (54.122.7% vs. 52.515.5%, P=0.42), while control group had a significant decrease (59.211.1% vs. 50.69.9%, P<0.016). CONCLUSION Our results indicate that resistance exercise, applied early, may promote maintenance of functional capacity on coronary artery bypass grafting patients, having no impact on pulmonary function when compared to conventional physical therapy.
Endogenous Testosterone and Mortality Due to All Causes, Cardiovascular Disease, and Cancer in Men: European Prospective Investigation Into Cancer in Norfolk (EPIC-Norfolk) Prospective Population Study

Background— The relation between endogenous testosterone concentrations and health in men is controversial. Methods and Results— We examined the prospective relationship between endogenous testosterone concentrations and mortality due to all causes, cardiovascular disease, and cancer in a nested case-control study based on 11 606 men aged 40 to 79 years surveyed in 1993 to 1997 and followed up to 2003. Among those without prevalent cancer or cardiovascular disease, 825 men who subsequently died were compared with a control group of 1489 men still alive, matched for age and date of baseline visit. Endogenous testosterone concentrations at baseline were inversely related to mortality due to all causes (825 deaths), cardiovascular disease (369 deaths), and cancer (304 deaths). Odds ratios (95% confidence intervals) for mortality for increasing quartiles of endogenous testosterone compared with the lowest quartile were 0.75 (0.55 to 1.00), 0.62 (0.45 to 0.84), and 0.59 (0.42 to 0.85), respectively (P<0.001 for trend after adjustment for age, date of visit, body mass index, systolic blood pressure, blood cholesterol, cigarette smoking, diabetes mellitus, alcohol intake, physical activity, social class, education, dehydroepiandrosterone sulfate, androstanediol glucuronide, and sex hormone binding globulin). An increase of 6 nmol/L serum testosterone (≈1 SD) was associated with a 0.81 (95% confidence interval 0.71 to 0.92, P<0.01) multivariable-adjusted odds ratio for mortality. Inverse relationships were also observed for deaths due to cardiovascular causes and cancer and after the exclusion of deaths that occurred in the first 2 years. Conclusions— In men, endogenous testosterone concentrations are inversely related to mortality due to cardiovascular disease and all causes. Low testosterone may be a predictive marker for those at high risk of cardiovascular disease.
[Ten-day sequential therapy for Helicobacter pylori eradication in children: a systematic review of randomized controlled trials].

OBJECTIVE To assess the efficacy and safety of 10-day sequential therapy for Helicobacter pylori (H.pylori) eradication in children. METHODS The databases of Cochrane Central Register of Controlled Trials (CENTRAL, 2013,N01), Medline, Embase, OVID, Chinese Biological Medicine database (CBMDisc), CNKI, Chinese VIP and WANFANG (all from 2000-2013) were searched. And manual searches were performed for the relevant journals and conference proceedings. Prospective, randomized controlled trials of 10-day sequential therapy for H.pylori eradication in children were selected. The systematic review was conducted with the method recommended by The Cochrane Collaboration. RESULTS Fifteen trials with a total of 1348 patients were included for analysis. The meta-analysis showed: (1) H.pylori eradication rates: 10-day sequential therapy were superior to triple therapy (80.78% (521/645) vs 69.84% (491/703), OR 2.13, 95%CI: 1.62-2.80, P < 0.01). It was also superior to 7-day and 10-day standard triple therapy (86.03% (271/315) vs 73.77% (225/305), 79.04% (181/229) vs 65.19% (176/270); OR 2.23, 2.11; 95%CI:1.47-3.36, 1.37-3.24;both P < 0.01) . There were non-superior to 14-day standard triple therapy (73.97% (108/146) vs 70.31% (90/128), OR 1.87, 95%CI: 0.46-7.69, P = 0.38). (2) Adverse effect rate: adverse events were similar between sequential and standard triple therapies (P = 0.58). CONCLUSION The 10-day sequential therapy may be a new effective and safe option in treatment of H.pylori infections in children.
Role for Phosphoglucomutase in Vibrio fischeri-Euprymna scolopes Symbiosis

ABSTRACT Vibrio fischeri, a luminescent marine bacterium, specifically colonizes the light organ of its symbiotic partner, the Hawaiian squid Euprymna scolopes. In a screen for V. fischeri colonization mutants, we identified a strain that exhibited on average a 10-fold decrease in colonization levels relative to that achieved by wild-type V. fischeri. Further characterization revealed that this defect did not result from reduced luminescence or motility, two processes required for normal colonization. We determined that the transposon in this mutant disrupted a gene with high sequence identity to the pgm (phosphoglucomutase) gene of Escherichia coli, which encodes an enzyme that functions in both galactose metabolism and the synthesis of UDP-glucose. The V. fischeri mutant grew poorly with galactose as a sole carbon source and was defective for phosphoglucomutase activity, suggesting functional identity between E. coli Pgm and the product of the V. fischeri gene, which was therefore designated pgm. In addition, lipopolysaccharide profiles of the mutant were distinct from that of the parent strain and the mutant exhibited increased sensitivity to various cationic agents and detergents. Chromosomal complementation with the wild-type pgm allele restored the colonization ability to the mutant and also complemented the other noted defects. Unlike the pgm mutant, a galactose-utilization mutant (galK) of V. fischeri colonized juvenile squid to wild-type levels, indicating that the symbiotic defect of the pgm mutant is not due to an inability to catabolize galactose. Thus, pgm represents a new gene required for promoting colonization of E. scolopes by V. fischeri.
Positive Selection of (cid:103)(cid:100) CTL by TL Antigen Expressed in the Thymus

To elucidate the function of the mouse TL antigen in the thymus, we have derived two TL transgenic mouse strains by introducing Tla a -3 of A strain origin with its own promoter onto a C3H background with no expression of TL in the thymus. These transgenic mouse strains, both of which express high levels of Tla a -3-TL antigen in their thymus, were analyzed for their T cell function with emphasis on cytotoxic T lymphocyte (CTL) generation. A T cell response against TL was induced in Tg.Tla a -3-1, Tg.Tla a -3-2, and control C3H mice by skin grafts from H-2K b / T3 b transgenic mice, Tg.Con. 3-1, expressing T3 b -TL ubiquitously. Spleen cells from mice that had rejected the T3 b -TL positive skin grafts were restimulated in vitro with Tg.Con. 3-1 irradiated spleen cells. In mixed lymphocyte cultures (MLC), approximately 20% and 15% of Thy-1 (cid:49) T cells derived from Tg.Tla a -3-1 and Tg.Tla a -3-2, activity by TCR (cid:103)(cid:100) and coreceptors. The thymic origin of these CTL clones was indicated by the expression of Thy-1 and Ly-1 (CD5), and CD8 (cid:97)(cid:98) heterodimers in CD8 (cid:49) clones on their surfaces and by the usage of TCR V (cid:103) 4 chains in 12 of the 14 clones. Taken together, these results suggest that Tla a -3-TL antigen expressed in the thymus engages in positive selection of a sizable population of (cid:103)(cid:100) T cells.
Development of a Valid and Reliable Diabetes Empowerment Scale: An Iranian Version

Background Patient empowerment can enhance the outcomes of care such as metabolic control as well as quality of their life. This study evaluates the Iranian version for development of a valid and reliable diabetes empowerment scale. Methods Validity and reliability of Iranian version of Diabetes Empowerment Scale (DES-LF) were measured through a cross-sectional study. DES-LF was evaluated through a qualitative and quantitative study by 160 type 2 diabetic patients. Results Reliability and validity of the scale and its 3 subscales, namely, managing the psychosocial aspects of diabetes (α=0.94), assessing dissatisfaction and readiness to change (α=0.96), and setting and achieving diabetes goals (α=0.96) were approved by a psychometric analysis. Conclusion Findings approved the reliability and validity of the Iranian version of DES-LF for patient education and psychosocial interventions among Iranian people with type 2 diabetes.
A Novel Noninvasive Measurement Technique for Analyzing the Pressure Pulse Waveform of the Radial Artery

Previous noninvasive measurements of the pulse waveform of the radial artery have not employed standard positioning procedures. Here, we propose a new noninvasive measuring apparatus that has a two-axis mechanism and employs a standard positioning procedure for detecting the optimal site for accurately measuring the pressure pulse waveform (PPW). A modified sensor was designed to simultaneously measure the arterial diameter changed waveform (ADCW) and PPW. Considering the artery as a cylinder, the measured waveform would be distorted if the sensor were not at the middle of arterial width. Moreover, a blood vessel is elastic, and its compliance changes with the transmural pressure, being maximal when the transmural pressure is equal to zero. The sensor should detect the PPW with the lowest possible distortion and, hence, an analysis of the vascular geometry and an arterial model were used to design a standard positioning procedure based on the ADCW for the X and Z axes. In order to verify the resolution of the X axis scanning procedure, the echo method was used to measure the radial artery outer diameter in ten healthy subjects. The difference between the scanning width and the actual arterial diameter was 0.36 plusmn 0.23 mm (mean plusmn SD). Finally, the PPW as measured at the optimal position was used to diagnose myocardial ischemia symptoms in 60 elderly subjects whose chief complaint was chest pain, with the exercise electrocardiogram being used as a reference to compare between individuals with and without myocardial ischemia. The PPW analysis used the harmonic components in the frequency domain. We found that the fourth harmonic of the Fourier series differed significantly between the groups (p = 0.0039), which is consistent with previous studies. The results indicate that our noninvasive measurement apparatus is very suitable for analyzing the PPW of the radial artery.
Engineering mesenchymal stem cell sheets on functional polyelectrolyte multilayer substrates

Cell sheet engineering is a novel and effective means of forming tissue substitutes in regenerative medicine. This technology allows for the manufacturing of cell sheets for either direct transplantation or the assembly of three-dimensionally organized tissuemimicking structures. In the last decade, cell sheet engineering emerged as a promising alternative to injected cell delivery and biomaterial vehicles. Cell sheets manufactured on thermosensitive polymer coatings are already successfully employed in clinical applications such as human corneal reconstruction and treatment of human myocardial dysfunction. The main goal of my thesis was to develop an alternative, electrochemically responsive surface coating for the site-specific release of cell sheets by applying of micro-electrical currents. In context of my work, polyelectrolyte multilayer (PEM)-based platforms should be used for the synthesis of cell sheets composed of human stem / progenitor and end-differentiated cells. In the first part of my thesis, I determined the critical parameters for the isolation and long-term cultivation of human term placenta-derived mesenchymal stem cells (PDMSCs). My results revealed that the isolated cells were of maternal origin and possessed very high proliferation and very low mortality rates up to passage twenty. The phenotypic profile of PD-MSC-isolates fulfilled the recently defined minimal criteria for the determination of mesenchymal stem cells (MSCs) and remained constant throughout continuous sub-confluent culture. The plasticity of PD-MSCs allowed their differentiation into adipogenic, chondrogenic, and osteogenic lineages as well as endothelium. In the second part of my thesis, I designed and optimized a PEM-based platform for the growth and intact peeling of cell sheets generated from different human cell types. Therefore, I established PEM substrates of a constant thickness with variations in rigidity. As a preliminary experiment, I used the assembly composed from nine layerpairs of positively-charged poly-L-lysine (PLL) and negatively-charged hyaluronic acid (HA). The use of such polymers allowed for the construction of soft coatings and has been previously described as an attractive system for culturing different cell types. Moreover, the coating stiffness was adjusted by modulating the heterobifunctional
The Role of PGC-1α in the Development of Insulin Resistance in Skeletal Muscle - Revisited

Currently, obesity is a predominant medical condition and an important risk factor for the development of several diseases, including type 2 diabetes mellitus. Importantly, most research has indicated lipid-induced insulin resistance in skeletal muscles is a key link between the aforementioned pathological conditions. PGC-1α is a prominent regulator of myocellular energy metabolism orchestrating gene transcription programming in response to numerous environmental stimuli. Moreover, it is widely acknowledged that mitochondrial metabolism (primary metabolic target of PGC-1α) disturbances are widely acknowledged contributors to type 2 diabetes development. Therefore, it seems surprising that the exact physiological contribution of PGC-1α in the development of insulin resistance in skeletal muscle remains poorly understood. This review aims to reconcile these allegedly different findings by looking for a common denominator in the role(s) of PGC-1α in respect to lipid-induced insulin resistance in skeletal muscle. Our scrutiny of the literature indicates that interventions at the level of PGC-1α may exert beneficial effects on myocytes in respect to lipid-induced insulin resistance. The latter takes place as a result of a positive net energy balance (fatty acids oxidation surpassing their accumulation rate). Moreover, the aforementioned effects may not necessarily be limited to physically active states. They seem to occur, however, only within a physiologically observed range in muscle cells (approximately 1-fold changes in PGC-1α protein expression).
Diversity of Cnidarian Muscles: Function, Anatomy, Development and Regeneration

The ability to perform muscle contractions is one of the most important and distinctive features of eumetazoans. As the sister group to bilaterians, cnidarians (sea anemones, corals, jellyfish, and hydroids) hold an informative phylogenetic position for understanding muscle evolution. Here, we review current knowledge on muscle function, diversity, development, regeneration and evolution in cnidarians. Cnidarian muscles are involved in various activities, such as feeding, escape, locomotion and defense, in close association with the nervous system. This variety is reflected in the large diversity of muscle organizations found in Cnidaria. Smooth epithelial muscle is thought to be the most common type, and is inferred to be the ancestral muscle type for Cnidaria, while striated muscle fibers and non-epithelial myocytes would have been convergently acquired within Cnidaria. Current knowledge of cnidarian muscle development and its regeneration is limited. While orthologs of myogenic regulatory factors such as MyoD have yet to be found in cnidarian genomes, striated muscle formation potentially involves well-conserved myogenic genes, such as twist and mef2. Although satellite cells have yet to be identified in cnidarians, muscle plasticity (e.g., de- and re-differentiation, fiber repolarization) in a regenerative context and its potential role during regeneration has started to be addressed in a few cnidarian systems. The development of novel tools to study those organisms has created new opportunities to investigate in depth the development and regeneration of cnidarian muscle cells and how they contribute to the regenerative process.
Induction of Beige-Like Adipocytes in 3T3-L1 Cells

ABSTRACT There are two types of brown adipocytes: classical brown adipocytes that form the brown fat depots and beige adipocytes that emerge in the white fat depots. Beige adipocytes have a low level of uncoupling protein 1 (Ucp1) expression in the basal state, but Ucp1 expression is increased in response to β adrenergic receptor activation. The present study explored the factors responsible for the differentiation of 3T3-L1 white preadipocytes to beige adipocytes. Significant expression of Ucp1 was not detected under any tested conditions in the absence of isoproterenol (Iso), an agonist of β adrenergic receptor. Iso-induced Ucp1 expression was significantly higher in the cells treated with a mixture of triiodothyronine (T3) and 3-isobutyl-1-methylxanthine (IBMX) for days 0–8 than in the control cells. Chronic IBMX treatment was indispensable for the enhanced Iso-induced Ucp1 expression, and treatment with additional rosiglitazone (Rosi) for days 0–8 further increased the Ucp1 expression. Recently, genes were identified that are predominantly expressed in beige adipocytes, which were induced from stromal vascular cells in white fat depots. However, the expression levels of the beige adipocyte-selective genes in the adipocytes induced by the mixture of T3, IBMX and Rosi did not differ from those in the control adipocytes. The present study indicates that 3T3-L1 cells can differentiate to beige-like adipocytes by prolonged treatment with the mixture of T3, IBMX and Rosi and that the gene expression profile of the adipocytes is distinct from those previously induced from white fat depots.
An experimental and numerical investigation in elastohydrodynamic behaviour of a plain cylindrical journal bearing heavily loaded

This article is an experimental and numerical study on elastohydrodynamic behavior of a plain cylindrical journal bearing subjected to the radial loads. An experimental study conducted on the effects of applied load on the determination of the characteristics of a cylindrical journal bearing, with 100 mm diameter and a radial clearance of 0.09 mm. The bearing is made of steel backing material and babitted (88% tin) on its inner surface. Lubrication is insured using PM3 type oil which features good rheological properties as well as a large density. The operating conditions are variable, with the radial load ranging up to 10 kN and the rotational speed ranging up to 2000 r/min. The numerical analysis investigates the deformation effects on the bearing behavior. This analysis considers the impact of various parameters such as rotational speed up to 9000 r/min, radial load up to 150 kN. Finally, the numerical predictions have been validated in comparison with experimental data.