Effect of regular physical training on age-associated alteration of body composition in men

Body composition changes with increasing age in men, in that lean body mass decreases whereas fat mass increases. Whether this altered body composition is related to decreasing physical activity or to the known age-associated decrease in growth hormone secretion is uncertain. To address this question, three groups of healthy men (n = 14 in each group), matched for weight, height and body mass index, were investigated using dual-energy X-ray absorptiometry, indirect calorimetry and estimate of daily growth hormone secretion [i.e. plasma insulin-like growth factor I (IGF-I-) levels]. Group 1 comprised young untrained subjects aged 31.0 +/- 2.1 years (mean +/- SEM) taking no regular physical exercise; group 2 consisted of old untrained men aged 68.6 +/- 1.2 years; and group 3 consisted of healthy old men aged 67.4 +/- 1.2 years undergoing regular physical training for more than 10 years with a training distance of at least 30 km per week. Subjects in group 3 had for the past three years taken part in the 'Grand Prix of Berne', a 16.5-km race run at a speed of 4.7 +/- 0.6 min km-1 (most recent race). Fat mass was more than 4 kg higher in old untrained men (P < 0.01, ANOVA) than in the other groups (young untrained men, 12.0 +/- 0.9 kg; old untrained men, 16.1 +/- 1.0 kg; old trained men, 11.0 +/- 0.8 kg), whereas body fat distribution (i.e. the ratio of upper to lower body fat mass) was similar between the three groups. The lean mass of old untrained men was more than 3.5 kg lower (P < 0.02, ANOVA) than in the other two groups (young untrained men, 56.4 +/- 1.0 kg; old untrained men, 52.4 +/- 1.0 kg; old trained men, 56.0 +/- 1.0 kg), mostly because of a loss of skeletal muscle mass in the arms and legs (young untrained men, 24.0 +/- 0.5 kg; old untrained men 20.8 +/- 0.5 kg; old trained men, 23.6 +/- 0.7 kg; P < 0.01, ANOVA). Resting metabolic rate per kilogram lean mass decreased with increasing age independently of physical activity (r = -0.42, P < 0.005). Fuel metabolism was determined by indirect calorimetry at rest. Protein oxidation was similar in the three groups. Old untrained men had higher (P < 0.001) carbohydrate oxidation (young untrained men, 13.2 +/- 1.0 kcal kg-1 lean mass; old untrained men, 15.2 +/- 1.3 kcal Kg-1; old trained men, 7.8 +/- 0.8 kcal kg-1), but lower (P < 0.05, ANOVA) fat oxidation (young untrained men, 10.1 +/- 1.2 kcal kg-1 lean mass; old untrained men, 6.5 +/- 1.0 kcal kg-1; old trained men, 13.7 +/- 1.0 kcal kg-1) than the other two groups. Mean plasma IGF-I level in old trained men was higher than in old untrained men (P < 0.05), but was still lower than that observed in young untrained men (P < 0.005) (young untrained men, 236 +/- 24 ng mL-1; old untrained men, 119 +/- 13 ng mL-1; old trained men, 166 +/- 14 ng mL-1). In summary, regular physical training in older men seems to prevent the changes in body composition and fuel metabolism normally associated with ageing. Whether regular physical training in formerly untrained old subjects would result in similar changes awaits further study.

Single Molecular Conductance of Tolanes: Experimental and Theoretical Study on the Junction Evolution Dependent on the Anchoring Group

Employing a scanning tunneling microscopy based beak junction technique and mechanically controlled break junction experiments, we investigated tolane (diphenylacetylene)-type single molecular junctions having four different anchoring groups (SH, pyridyl (PY), NH2, and CN) at a solid/liquid interface. The combination of current–distance and current–voltage measurements and their quantitative statistical analysis revealed the following sequence for junction formation probability and stability: PY > SH > NH2 > CN. For all single molecular junctions investigated, we observed the evolution through multiple junction configurations, with a particularly well-defined binding geometry for PY. The comparison of density functional theory type model calculations and molecular dynamics simulations with the experimental results revealed structure and mechanistic details of the evolution of the different types of (single) molecular junctions upon stretching quantitatively.

Early changes in biochemical markers of bone formation during teriparatide therapy correlate with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis

Summary Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. Introduction To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. Methods A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 μg/day, n = 45) and risedronate (35 mg/week, n = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. Results PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. Conclusions Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients.

Teaching Tolerance? Associational Diversity and Tolerance Formation

Tolerance is a basic democratic principle that helps civil societies cope with rising levels of diversity stemming from increased immigration and individualism. During the last decade the question of how tolerance may be fostered has dominated debates in public and academic spheres. In this article, a closer look is taken at how associational diversity relates to the formation of tolerance and the importance of associations as schools of tolerance are evaluated. The main theoretical argument follows contact theory, wherein regular and enduring contact in diverse settings reduces prejudice and thereby increases an individual’s tolerance toward objectionable groups. The empirical findings reveal a positive relationship between associational diversity and tolerance. It is observed, however, that the duration of active engagement in associations reduces this positive relation between diversity and tolerance. Accordingly, these results challenge the notion that associations serve as schools of tolerance in the long run.

Action of food preservatives on 14-days dental biofilm formation, biofilm vitality and biofilm-derived enamel demineralisation in situ

AIMS The aims of this double-blind, controlled, crossover study were to assess the influence of food preservatives on in situ dental biofilm growth and vitality, and to evaluate their influence on the ability of dental biofilm to demineralize underlying enamel over a period of 14 days. MATERIALS AND METHODS Twenty volunteers wore appliances with six specimens each of bovine enamel to build up intra-oral biofilms. During four test cycles of 14 days, the subjects had to place the appliance in one of the assigned controls or active solutions twice a day for a minute: negative control 0.9 % saline, 0.1 % benzoate (BA), 0.1 % sorbate (SA) and 0.2 % chlorhexidine (CHX positive control). After 14 days, the biofilms on two of the slabs were stained to visualize vital and dead bacteria to assess biofilm thickness (BT) and bacterial vitality (BV). Further, slabs were taken to determine mineral loss (ML), by quantitative light-induced laser fluorescence (QLF) and transversal microradiography (TMR), moreover the lesion depths (LD). RESULTS Nineteen subjects completed all test cycles. Use of SA, BA and CHX resulted in a significantly reduced BV compared to NaCl (p < 0.001). Only CHX exerted a statistically significant retardation in BT as compared to saline. Differences between SA and BA were not significant (p > 0.05) for both parameters. TMR analysis revealed the highest LD values in the NaCl group (43.6 ± 44.2 μm) and the lowest with CHX (11.7 ± 39.4 μm), while SA (22.9 ± 45.2 μm) and BA (21.4 ± 38.5 μm) lay in between. Similarly for ML, the highest mean values of 128.1 ± 207.3 vol% μm were assessed for NaCl, the lowest for CHX (-16.8 ± 284.2 vol% μm), while SA and BA led to values of 83.2 ± 150.9 and 98.4 ± 191.2 vol% μm, respectively. With QLF for both controls, NaCl (-33.8 ± 101.3 mm(2) %) and CHX (-16.9 ± 69.9 mm(2) %), negative values were recorded reflecting a diminution of fluorescence, while positive values were found with SA (33.9 ± 158.2 mm(2) %) and BA (24.8 ± 118.0 mm(2) %) depicting a fluorescence gain. These differences were non-significant (p > 0.05). CONCLUSION The biofilm model permited the assessment of undisturbed oral biofilm formation influenced by antibacterial components under clinical conditions for a period of 14 days. An effect of BA and SA on the demineralization of enamel could be demonstrated by TMR and QLF, but these new findings have to be seen as a trend. As part of our daily diet, these preservatives exert an impact on the metabolism of the dental biofilm, and therefore may even influence demineralization processes of the underlying dental enamel in situ.

Bioresorbable vascular scaffold treatment induces the formation of neointimal cap that seals the underlying plaque without compromising the luminal dimensions: a concept based on serial optical coherence tomography data.

Aims: To evaluate the implications of an Absorb bioresorbable vascular scaffold (Absorb BVS) on the morphology of the superficial plaques. Methods and results: Forty-six patients who underwent Absorb BVS implantation and 20 patients implanted with bare metal stents (BMS) who had serial optical coherence tomographic examination at baseline and follow-up were included in this analysis. The thin-capped fibroatheromas (TCFA) were identified in the device implantation regions and in the adjacent native coronary segments. Within all regions, circumferential locations of TCFA and calcific tissues were identified, and the neointimal thickness was measured at follow-up. At six to 12-month follow-up, only 8% of the TCFA detected at baseline were still present in the Absorb BVS and 27% in the BMS implantation segment (p=0.231). Sixty percent of the TCFA in native segments did not change their phenotype at follow-up. At short-term follow-up, significant reduction in the lumen area of the BMS was noted, which was higher compared to that reported in the Absorb BVS group (-2.11±1.97 mm2 vs. -1.34±0.99 mm2, p=0.026). In Absorb BVS, neointima tissue continued to develop at midterm follow-up (2.17±0.48 mm2 vs. 1.38±0.52 mm2, p<0.0001) and covered the underlying tissues without compromising the luminal dimensions (5.93±1.49 mm2 vs. 6.14±1.49 mm2, p=0.571) as it was accommodated by the expanded scaffold (8.28±1.74 mm2 vs. 7.67±1.28 mm2, p<0.0001). Conclusions: Neointimal tissue develops following either Absorb BVS or BMS implantation and shields lipid tissues. The neointimal response in the BMS causes a higher reduction of luminal dimensions compared to the Absorb BVS. Thus, Absorb BVS may have a value in the invasive re-capping of high-risk plaques.

Multidisciplinary consensus on assessment of unruptured intracranial aneurysms: proposal of an international research group.

BACKGROUND AND PURPOSE To address the increasing need to counsel patients about treatment indications for unruptured intracranial aneurysms (UIA), we endeavored to develop a consensus on assessment of UIAs among a group of specialists from diverse fields involved in research and treatment of UIAs. METHODS After composition of the research group, a Delphi consensus was initiated to identify and rate all features, which may be relevant to assess UIAs and their treatment by using ranking scales and analysis of inter-rater agreement (IRA) for each factor. IRA was categorized as very high, high, moderate, or low. RESULTS Ultimately, 39 specialists from 4 specialties agreed (high or very high IRAs) on the following key factors for or against UIA treatment decisions: (1) patient age, life expectancy, and comorbid diseases; (2) previous subarachnoid hemorrhage from a different aneurysm, family history for UIA or subarachnoid hemorrhage, nicotine use; (3) UIA size, location, and lobulation; (4) UIA growth or de novo formation on serial imaging; (5) clinical symptoms (cranial nerve deficit, mass effect, and thromboembolic events from UIAs); and (6) risk factors for UIA treatment (patient age and life expectancy, UIA size, and estimated risk of treatment). However, IRAs for features rated with low relevance were also generally low, which underlined the existing controversy about the natural history of UIAs. CONCLUSIONS Our results highlight that neurovascular specialists currently consider many features as important when evaluating UIAs but also highlight that the appreciation of natural history of UIAs remains uncertain, even within a group of highly informed individuals.

Identification of platelet function defects by multi-parameter assessment of thrombus formation.

Assays measuring platelet aggregation (thrombus formation) at arterial shear rate mostly use collagen as only platelet-adhesive surface. Here we report a multi-surface and multi-parameter flow assay to characterize thrombus formation in whole blood from healthy subjects and patients with platelet function deficiencies. A systematic comparison is made of 52 adhesive surfaces with components activating the main platelet-adhesive receptors, and of eight output parameters reflecting distinct stages of thrombus formation. Three types of thrombus formation can be identified with a predicted hierarchy of the following receptors: glycoprotein (GP)VI, C-type lectin-like receptor-2 (CLEC-2)>GPIb>α6β1, αIIbβ3>α2β1>CD36, α5β1, αvβ3. Application with patient blood reveals distinct abnormalities in thrombus formation in patients with severe combined immune deficiency, Glanzmann's thrombasthenia, Hermansky-Pudlak syndrome, May-Hegglin anomaly or grey platelet syndrome. We suggest this test may be useful for the diagnosis of patients with suspected bleeding disorders or a pro-thrombotic tendency.

Regular exercise decreases liver tumors development in hepatocyte-specific PTEN-deficient mice independently of steatosis.

BACKGROUND & AIMS Unhealthy lifestyles predispose to non-alcoholic steatohepatitis (NASH), which may further result in the development of hepatocellular carcinoma (HCC). Although NASH patients benefit from physical activity, it is unknown whether regular exercise reduces the risk of developing HCC. Therefore, we studied the effect of regular exercise on the development of HCC in male hepatocyte-specific PTEN-deficient mice (AlbCrePten(flox/flox)), which develop steatohepatitis and HCC spontaneously. METHODS Mice were fed a standardized 10% fat diet and were randomly divided into exercise or sedentary groups. The exercise group ran on a motorized treadmill for 60 minutes/day, 5 days/week during 32 weeks. RESULTS After 32 weeks of regular exercise, 71% of exercised mice developed nodules larger than 15 mm(3) vs 100% of mice in the sedentary group. The mean number of tumors per liver was reduced by exercise, as well as the total tumoral volume per liver. Exercise did not affect steatosis and had no effect on the Non-alcoholic fatty liver disease (NAFLD) Activity Score (NAS). Exercise decreased tumor cell proliferation. Mechanistically, exercise stimulated the phosphorylation of AMPK and its substrate raptor, which decreased the kinase activity of mTOR. CONCLUSIONS These data show a benefit of regular exercise on the development of HCC in an experimental model of NASH and offer a rationale for encouraging predisposed patients to increase their physical activity for the prevention of HCC.

Pattern and process: competition causes regular spacing of individuals within plant populations

1 We used simulated and experimental plant populations to analyse mortality-driven pattern formation under size-dependent competition. Larger plants had an advantage under size-asymmetric but not under symmetric competition. Initial patterns were random or clumped. 2 The simulations were individual-based and spatially explicit. Size-dependent competition was modelled with different rules to partition overlapping zones of influence. 3 The experiment used genotypes of Arabidopsis thaliana with different morphological plasticity and hence size-dependent competition. Compared with wild types, transgenic individuals over-expressed phytochrome A and had decreased plasticity because of disabled phytochrome-mediated shade avoidance. Therefore, competition among transgenics was more asymmetric compared with wild-types. 4 Density-dependent mortality under symmetric competition did not substantially change the initial spatial pattern. Conversely, simulations under asymmetric competition and experimental patterns of transgenic over-expressors showed patterns of survivors that deviated substantially from random mortality independent of initial patterns. 5 Small-scale initial patterns of wild types were regular rather than random or clumped. We hypothesize that this small-scale regularity may be explained by early shade avoidance of seedlings in their cotyledon stage. 6 Our experimental results support predictions from an individual-based simulation model and support the conclusion that regular spatial patterns of surviving individuals should be interpreted as evidence for strong, asymmetric competitive interactions and subsequent density-dependent mortality.

Inhibition of DNA polymerase reaction by pyrimidine nucleotide analogues lacking the 2-keto group

To investigate the influence of the pyrimidine 2-keto group on selection of nucleotides for incorporation into DNA by polymerases, we have prepared two C nucleoside triphosphates that are analogues of dCTP and dTTP, namely 2-amino-5-(2'-deoxy-beta-d-ribofuranosyl)pyridine-5'-triphosphate (d*CTP) and 5-(2'-deoxy- beta-d-ribofuranosyl)-3-methyl-2-pyridone-5'-triphosphate (d*TTP) respectively. Both proved strongly inhibitory to PCR catalysed by Taq polymerase; d*TTP rather more so than d*CTP. In primer extension experiments conducted with either Taq polymerase or the Klenow fragment of Escherichia coli DNA polymerase I, both nucleotides failed to substitute for their natural pyrimidine counterparts. Neither derivative was incorporated as a chain terminator. Their capacity to inhibit DNA polymerase activity may well result from incompatibility with the correctly folded form of the polymerase enzyme needed to stabilize the transition state and catalyse phosphodiester bond formation.

Incidence of Gallstone Formation and Cholecystectomy 10 Years After Bariatric Surgery.

PURPOSE Rapid weight loss is a risk factor for gallstone formation, and postoperative treatment options for gallstone formation are still part of scientific discussion. No prospective studies monitored the incidence for gallstone formation and subsequent cholecystectomy after bariatric surgery longer than 5 years. The aim of the study was to determine the incidence of gallstone formation and cholecystectomy in bariatric patients over 10 years. MATERIALS AND METHODS One hundred nine patients were observed over 10 years after laparoscopic gastric banding or gastric bypass/gastric sleeve. The incidence of gallstone formation and cholecystectomy was correlated to longitudinal changes in anthropometric parameters. RESULTS In total, 91 female and 18 male patients were examined. Nineteen patients had postoperative gallstone formation, and 12 female patients required cholecystectomy. The number needed to harm for gallstone formation was 7.1 and 2.3 cases in the banding group and gastric bypass/gastric sleeve group, respectively. The number needed to harm for cholecystectomy was 11.6 and 2.5 cases in the banding group and the gastric bypass/gastric sleeve group, respectively. Weight loss was higher in patients requiring subsequent cholecystectomy. Mean follow-up to cholecystectomy was 21.5 months with the latest operation after 51 months. CONCLUSION Female gender and rapid weight loss were major risk factors for postoperative cholelithiasis. Ultrasound examinations within 2 to 5 years are recommended in every patient, independent of bariatric procedure. Pharmacologic treatment should be considered in high risk patients within 2 to 5 years to prevent postoperative cholelithiasis. This helps to optimize patient care and lowers postoperative morbidity.

Decomposition studies of group 6 hexacarbonyl complexes. Part 1: Production and decomposition of Mo(CO)6 and W(CO)6

Chemical studies of superheavy elements require fast and efficient techniques, due to short half-lives and low production rates of the investigated nuclides. Here, we advocate for using a tubular flow reactor for assessing the thermal stability of the Sg carbonyl complex – Sg(CO)6. The experimental setup was tested with Mo and W carbonyl complexes, as their properties are established and supported by theoretical predictions. The suggested approach proved to be effective in discriminating between the thermal stabilities of Mo(CO)6 and W(CO)6. Therefore, an experimental verification of the predicted Sg–CO bond dissociation energy seems to be feasible by applying this technique. By investigating the effect of 104,105Mo beta-decay on the formation of 104,105Tc carbonyl complex, we estimated the lower reaction time limit for the metal carbonyl synthesis in the gas phase to be more than 100 ms. We examined further the influence of the wall material of the recoil chamber, the carrier gas composition, the gas flow rate, and the pressure on the production yield of 104Mo(CO)6, so that the future stability tests with Sg(CO)6 can be optimized accordingly.

Steiner’s formula in the Heisenberg group

Steiner’s tube formula states that the volume of an ϵ-neighborhood of a smooth regular domain in Rn is a polynomial of degree n in the variable ϵ whose coefficients are curvature integrals (also called quermassintegrals). We prove a similar result in the sub-Riemannian setting of the first Heisenberg group. In contrast to the Euclidean setting, we find that the volume of an ϵ-neighborhood with respect to the Heisenberg metric is an analytic function of ϵ that is generally not a polynomial. The coefficients of the series expansion can be explicitly written in terms of integrals of iteratively defined canonical polynomials of just five curvature terms.