Intramuscular long-chain fatty acids (LCFAs) play an important role in energy production and initiation of mitochondrial oxidation of lipids. Herein, we report a natural porcine placenta steroid extract (PPSE) that stimulates transdifferentiation and lipid accumulation in bovine myogenic satellite cells (MSCs). The steroids hormones in PPSE were analyzed using enzyme-linked immunosorbant assay and presence of LCFA was established using gas chromatography. At 70 % confluent growth, cells were treated with PPSE, LCFAs, transdifferentiation cocktail and commercially available steroid hormones. The working concentrations of all chemicals were manipulated similar to PPSE. The cells were observed for morphological changes and subjected to quantitative analysis of lipid deposition on Days 2, 4, and 6 of treatment. PPSE-treated MSCs exclusively transformed into lipid-accumulated adipose-like cells (ALCs). However, myotubes or adipocytes were formed in cells treated with other chemicals. Expression of different genes was studied to ascertain the molecular mechanism involved in ALC formation. CD36, fatty acid binding protein 4, and peroxisome proliferator-activated receptor-gamma were up-regulated. The expression of CD36 was established through immunocyto-chemical analysis. A viability assay was used to confirm the effect of PPSE on proliferation of MSCs. Hence, a natural steroid extract from porcine was found as a nontoxic mixture, which induces lipid accumulation and transdifferentiation of MSCs to ALCs. From the gene expression studies, it was established that the extract works almost in homogenous manner with other lipid inducers.

Apolipoprotein AIV (apo AIV) and cholecystokinin (CCK) are satiation factors secreted by the small intestine in response to lipid meals. Apo AIV and CCK-8 has an additive effect to suppress food intake relative to apo AIV or CCK-8 alone. In this study, we determined whether CCK-8 (1, 3 or 5 µg/kg, ip) reduces food intake in fasted apo AIV knockout (KO) mice as effectively as in fasted WT mice. Food intake was monitored by the DietMax food system. Apo AIV KO mice had significantly reduced 30-min food intake following all doses of CCK-8, whereas WT mice had reduced food intake only at doses of 3 µg/kg and above. Post-hoc analysis revealed that the reduction of 10-min and 30-min food intake elicited by each dose of CCK-8 was significantly larger in the apo AIV KO mice than in the WT mice. Peripheral CCK 1 receptor (CCK1R) gene expression (mRNA) in the duodenum and gallbladder of the fasted apo AIV KO mice was comparable to WT mice. In contrast, CCK1R mRNA in nodose ganglia of the apo AIV KO mice was up-regulated relative to WT animals. Similarly, up-regulated CCK1R gene expression was found in the brainstem of apo AIV KO mice using in situ hybridization. Although it is possible that the increased satiating potency of CCK in apo AIV KO mice is mediated by up-regulation of CCK 1R in the nodose ganglia and nucleus tractus solitarius, additional experiments are required to confirm such a mechanism.

Since T cells express diverse sex steroid hormone receptors, they might be a good model to evaluate the effects of sex steroid hormones on immune modulation. Porcine testicular extract contains several sex steroid hormones and may be useful to study the effects of sex steroid hormones during T cell activation. We have examined the effects of the porcine testicular extract on T cell activation: proliferation and secretion of cytokines (IL-2 and IFN-γ) by activated T cells were severely decreased after treatment with porcine testicular extract. The extract produced an immunosuppressive effect and inhibited the proliferation of activated T cells by blocking the cell cycle transition from the G(1) phase to S phase. These effects were mediated by a decrease in the expression of cyclin D1 and cyclin E and constitutive expression of p27(KIP1) after T cell activation.

BACKGROUND: The limitations of serum testosterone (T) and estradiol (E2) measurements using non-extraction platform immunoassays (IA) are widely recognized. Switching to more specific mass spectrometry (MS)-based methods has been advocated but directly comparative data on the two methods are scarce.METHODS: We compared serum T and E2 measurements in a large sample of middle-aged/elderly men using a common platform IA and a gas chromatography (GC)-MS method, in order to assess their limitations and advantages, and to diagnose male hypogonadism. Of subjects of the European Male Aging Study (n=3,174; age 40-79 years), peripheral serum T and E2 were analyzed using established commerical platform IAs (Roche Diagnostics E170) and in-house GC-MS methods.RESULTS: Over a broad concentration range, serum T concentration measured by IA and MS showed high correlation (R=0.93, p<0.001), which was less robust in the hypogonadal range (<11 nmol/L; R=0.72, p<0.001). The IA/MS correlation was weaker in E2 measurements (R=0.32, p<0.001, at E2<40.8 pmol/L, and R=0.74, p<0.001, at E2>40.8 pmol/L). Using MS as comparator method, IA ascertained low T compatible with hypogonadism (<11 nmol/L) with 75% sensitivity and 96.3% specificity. The same parameters with IA for detection of low E2 (<40.7 pmol/L) were 13.3% and 99.3%, and for high E2 (>120 pmol/L) 88.4% and 88.6%.CONCLUSION: A validated platform IA is sufficient to detect subnormal T concentrations in the diagnosis of male hypogonadism. The IA used for E2 measurements showed poor correlation with MS and may only be suitable for the detection of high E2 in men.

Context:Late-onset hypogonadism (LOH) has been defined as a syndrome in middle-aged and elderly men reporting symptoms in the presence of low testosterone (T).Objective:The objective of the study was to seek objective biochemical and end-organ evidence of androgen deficiency in men classified as having LOH according to our previously published criteria.Design, Setting, and Participants:The design of the study included cross-sectional data from the European Male Aging Study on 2966 community-dwelling men aged 40-79 years in eight European countries.Main Outcome Measure(s):Waist circumference, body mass index, muscle mass, estimated heel bone mineral density (eBMD), hemoglobin, insulin sensitivity, physical activity, metabolic syndrome, insulin resistance index, and cardiovascular disease were measured.Results:Sixty-three men (2.1%) were classified as having LOH: 36 moderate and 27 severe. They were older and more obese than eugonadal men and had, in proportion to the graded T deficiency, lower muscle mass, eBMD, and hemoglobin, with poorer general health. Both moderate and severe LOH was associated with lower hemoglobin, mid-upper arm circumference, eBMD, physical function (measured by the Short Form-36 questionnaire), slower gait speed and poorer general health. Only men with severe LOH showed significant associations with larger waist circumference (β= 1.93cm; 0.04-3.81), insulin resistance (β= 2.81; 1.39-4.23), and the metabolic syndrome (odds ratio 9.94; 2.73-36.22) after adjustments for confounders. Men with low testosterone only (irrespective of symptoms) showed lesser magnitudes of association with the same end points.Conclusions:LOH is associated with multiple end-organ deficits compatible with androgen deficiency. These data support the existence of a syndrome of LOH in only a minority of aging men, especially those with T below 8 nmol/liter.

ABSTRACT: INTRODUCTION: Rheumatoid arthritis (RA) is associated with hypogalactosylation of immunoglobulin G (IgG). We examined whether a proxy measure for galactosylation of IgG N-glycans could predict response to therapy or was differentially impacted by methotrexate (MTX) or TNF blockade. METHODS: Using a previously-defined normal phase high-performance liquid chromatography (HPLC) approach, we ascertained the galactosylation status of whole serum N-glycans in two well-defined RA clinical cohorts, Autoimmune Biomarkers Collaborative Network (ABCoN),(n = 98) and Nested I (n = 64). The ratio of agalactosylated to monogalactosylated N-glycans in serum (sG0/G1) was determined before and during therapy with MTX or TNF inhibition, and correlated with anti-citrullinated peptide antibody (ACPA) status and clinical response as assessed by DAS28-CRP and EULAR response criteria. RESULTS: RA patients from both cohorts exhibited elevation of sG0/G1 at baseline. Improvement in clinical scores correlated with a reduction in sG0/G1 (Spearman = 0.31-0.37, P<0.05 for each cohort). However, pre-treatment sG0/G1 was not predictive of clinical response. Change in sG0/G1 was similar in MTX and TNF inhibitor groups. Corrected for disease activity, ACPA positivity correlated with higher sG0/G1. CONCLUSIONS: Baseline serum N-glycan hypogalactosylation, an index previously correlated with galactosylation of IgG N-glycans, did not distinguish patients likely to experience a favorable clinical response to MTX or TNF blockade in patients with rheumatoid arthritis. Clinical improvement was associated with partial glycan normalization. ACPA positive patients demonstrated enhanced N-glycan aberrancy compared with ACPA-negative patients.

The European Male Ageing Study (EMAS) was designed to examine the hypothesis that inter-individual and regional variability in symptomatic dysfunctions, alterations in body composition and health outcomes in ageing men can be explained by different rates of decline in anabolic hormones, the most important of which being testosterone. Between 2003 and 2005, 3369 community-dwelling men, aged between 40 and 79 years, were recruited from population-based registers in eight European centres to participate in the baseline survey, with follow-up investigations performed a median of 4.3 years later. Largely, identical questionnaire instruments and clinical investigations were used in both phases to capture contemporaneous data on general health (including cardiovascular diseases and chronic conditions), physical and cognitive functioning, mental health, sexual function, quality of life, bone health, chronic pain, disease biomarkers, hormones (sex hormones and metabolic hormones) and genetic polymorphisms. EMAS actively encourages new collaborations, data sharing for validation studies and participation in genetic study consortia. Potential collaborators should contact the principal investigator (F.C.W.W.) in the first instance.

Flow coefficients v_{n} for n=2, 3, 4, characterizing the anisotropic collective flow in Au+Au collisions at sqrt[s_{NN}]=200  GeV, are measured relative to event planes Ψ_{n}, determined at large rapidity. We report v_{n} as a function of transverse momentum and collision centrality, and study the correlations among the event planes of different order n. The v_{n} are well described by hydrodynamic models which employ a Glauber Monte Carlo initial state geometry with fluctuations, providing additional constraining power on the interplay between initial conditions and the effects of viscosity as the system evolves. This new constraint can serve to improve the precision of the extracted shear viscosity to entropy density ratio η/s.

Although temporal calibration is widely recognized as critical for obtaining accurate divergence-time estimates using molecular dating methods, few studies have evaluated the variation resulting from different calibration strategies. Depending on the information available, researchers have often used primary calibrations from the fossil record or secondary calibrations from previous molecular dating studies. In analyses of flowering plants, primary calibration data can be obtained from macro- and mesofossils (e.g., leaves, flowers, and fruits) or microfossils (e.g., pollen). Fossil data can vary substantially in accuracy and precision, presenting a difficult choice when selecting appropriate calibrations. Here, we test the impact of eight plausible calibration scenarios for Nothofagus (Nothofagaceae, Fagales), a plant genus with a particularly rich and well-studied fossil record. To do so, we reviewed the phylogenetic placement and geochronology of 38 fossil taxa of Nothofagus and other Fagales, and we identified minimum age constraints for up to 18 nodes of the phylogeny of Fagales. Molecular dating analyses were conducted for each scenario using maximum likelihood (RAxML + r8s) and Bayesian (BEAST) approaches on sequence data from six regions of the chloroplast and nuclear genomes. Using either ingroup or outgroup constraints, or both, led to similar age estimates, except near strongly influential calibration nodes. Using 'early but risky' fossil constraints in addition to 'safe but late' constraints, or using assumptions of vicariance instead of fossil constraints, led to older age estimates. In contrast, using secondary calibration points yielded drastically younger age estimates. This empirical study highlights the critical influence of calibration on molecular dating analyses. Even in a best-case situation, with many thoroughly vetted fossils available, substantial uncertainties can remain in the estimates of divergence times. For example, our estimates for the crown-group age of Nothofagus varied from 13 to 113 Ma across our full range of calibration scenarios. We suggest that increased background research should be made at all stages of the calibration process to reduce errors wherever possible, from verifying the geochronological data on the fossils to critical re-assessment of their phylogenetic position.

PURPOSE This study was conducted to perform a comparative analysis of the efficacy and safety of conventional transurethral resection of the prostate (TUR-P), transurethral resection in saline (TURIS), and TURIS-plasma vaporization (TURIS-V) when performed by a single surgeon for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS The clinical data of 73 consecutive men who underwent conventional TUR-P (39), TURIS (19), or TURIS-V (15) for BPH were retrospectively analyzed. All procedures were carried out by a single surgeon between October 2007 and April 2010. The patients were assessed preoperatively and perioperatively and were followed at 1, 3, and 6 months postoperatively. Patient baseline characteristics, perioperative data, and postoperative outcomes were compared, and major complications were recorded. RESULTS In all groups, significant improvements in subjective and objective voiding parameters were achieved and were sustained throughout follow-up. TURIS-V had the shortest operation time compared with conventional TUR-P and TURIS (p=0.211). TURIS-V significantly decreased procedural irrigation fluid volume, postoperative irrigation duration, catheter duration, and hospital stay compared with conventional TUR-P and TURIS. There were no significant differences between the groups in hemoglobin levels or serum sodium levels before and after the operations. There were three transfusions and four clot retentions in the TUR-P group, and one transfusion and one clot retention in the TURIS group. The TURIS-V group had no complications. CONCLUSIONS TURIS and TURIS-V were effective for the surgical treatment of BPH in addition to conventional TUR-P. TURIS-V was not inferior to conventional TUR-P or TURIS in terms of safety.