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Renal cancer is a common urogenital system malignance. Novel biomarkers could provide more and more critical information on tumor features and patients' prognosis. Here, we performed an integrated analysis on the discovery set and established a three-gene signature to predict the prognosis for clear cell renal cell carcinoma (ccRCC). By constructing a LASSO Cox regression model, a 3-messenger RNA (3-mRNA) signature was identified. Based on the 3-mRNA signature, we divided patients into high- and low-risk groups, and validated this by using three other data sets. In the discovery set, this signature could successfully distinguish between the high- and low-risk patients (hazard ratio (HR), 2.152; 95% confidence interval (CI),1.509-3.069; p < 0.0001). Analysis of internal and two external validation sets yielded consistent results (internal: HR, 2.824; 95% CI, 1.601-4.98; p < 0.001; GSE29609: HR, 3.002; 95% CI, 1.113-8.094; p = 0.031; E-MTAB-3267: HR, 2.357; 95% CI, 1.243-4.468; p = 0.006). Time-dependent receiver operating characteristic (ROC) analysis indicated that the area under the ROC curve at 5 years was 0.66 both in the discovery and internal validation set, while the two external validation sets also suggested good performance of the 3-mRNA signature. Besides that, a nomogram was built and the calibration plots and decision curve analysis indicated the good performance and clinical utility of the nomogram. In conclusion, this 3-mRNA classifier proved to be a useful tool for prognostic evaluation and could facilitate personalized management of ccRCC patients.

Made available in DSpace on 2020-12-12T01:12:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01 To analyze the impact of participation in sports with different cardiorespiratory fitness (CRF) demands on changes in metabolic and cardiovascular markers in adolescents. Longitudinal study with 12 months of follow-up (Analysis of Behaviors of Children During Growth [ABCD Growth Study]). Overall, 184 adolescents (age 15.6 ± 2.1) were classified according to sports participation: non-sport (control), low CRF sports, and high CRF sports. Metabolic outcomes were total cholesterol (TC) and its fractions, triacylglycerol (TG), glucose, insulin levels, and the insulin resistance index. Cardiovascular outcomes were arterial thickness (carotid and femoral [ultrasound]), blood pressure, and resting heart rate. Adolescents engaged in sports classified as high CRF demand presented a significant increase in HDL-c (1.2 mg/dL [95%CI: −0.5 to 3.0]) when compared to the non-sport group (−2.4 mg/dL [95%CI: −4.4 to −0.5]). Regular engagement in high CRF sports was significantly related to changes in TC (β = −0.027 [95%CI: −0.048 to −0.005]), HDL-c (β = 0.009 [95%CI: 0.001 to 0.019]), LDL-c (β = −0.032 [95%CI: −0.049 to −0.016]), and glucose (β = −0.017 [95%CI: −0.025 to −0.008]), while engagement in low CRF sports was related to changes in TG (β = −0.065 [95%CI: −0.112 to −0.019]). No significant relationships for cardiovascular parameters were observed in the low CRF group, but one significant relationship was found between high CRF sports and changes in SBP (β = −0.063 [95%CI: −0.117 to −0.009]). In conclusion, engagement in sports seems to be beneficial for improvements in metabolic and cardiovascular parameters in adolescents, mainly sports with higher CRF demand. Laboratory of Investigation in Exercise - LIVE Department of Physical Education UNESP Post-Graduate Program in Physiotherapy UNESP Post-Graduate Program in Radiology Federal University of São Paulo UNIFESP Amsterdam UMC Amsterdam Public Health Research Institute Laboratory of Investigation in Exercise - LIVE Department of Physical Education UNESP Post-Graduate Program in Physiotherapy UNESP

The diffusiophoresis of a charged sphere along the axis of a circular microtube filled with an electrolyte solution is studied theoretically. The tube wall may be either nonconductive and impermeable or prescribed with a linear electrolyte concentration distribution. The electric double layers at the solid surfaces are thin, but the diffuse-layer polarization effect over the particle surface is considered. The general solutions to the electrokinetic differential equations are expressed in spherical and cylindrical coordinates, whereas the boundary conditions at the particle surface are satisfied by a collocation technique. The collocation solutions for the diffusiophoretic velocity of the particle, which are in good agreement with the asymptotic formula derived from a reflection method, are obtained for various values of the radius ratio and zeta potential ratio between the particle and the microtube and of other relevant parameters. The contributions from the diffusioosmotic flow along the tube wall and wall-corrected diffusiophoretic driving force to the particle velocity can be superimposed due to the linearity. Although the diffusiophoretic velocity in an uncharged microtube is in general a decreasing function of the particle-to-tube radius ratio and can reverse its direction, it can increase with increases in this ratio due to the competition of the wall effects of possible electrochemical enhancement and hydrodynamic retardation to the particle motion. When the zeta potentials associated with the tube and particle are equivalent, the diffusioosmotic flow induced by the tube wall dominates the diffusiophoretic motion.

In children, levels of play, physical activity, and fitness are key indicators of health and disease and closely tied to optimal growth and development. Cardiopulmonary exercise testing (CPET) provides clinicians with biomarkers of disease and effectiveness of therapy, and researchers with novel insights into fundamental biological mechanisms reflecting an integrated physiological response that is hidden when the child is at rest. Yet the growth of clinical trials utilizing CPET in pediatrics remains stunted despite the current emphasis on preventative medicine and the growing recognition that therapies used in children should be clinically tested in children. There exists a translational gap between basic discovery and clinical application in this essential component of child health. To address this gap, the NIH provided funding through the Clinical and Translational Science Award (CTSA) program to convene a panel of experts. This report summarizes our major findings and outlines next steps necessary to enhance child health exercise medicine translational research. We present specific plans to bolster data interoperability, improve child health CPET reference values, stimulate formal training in exercise medicine for child health care professionals, and outline innovative approaches through which exercise medicine can become more accessible and advance therapeutics across the broad spectrum of child health.

Objective: To evaluate the safety and efficacy of golimumab through 5 years in adults with active rheumatoid arthritis (RA) who had not previously received methotrexate (MTX). Methods: In the GO-BEFORE study, 637 MTX-naive adult patients with active RA were randomized (1:1:1:1) to placebo + MTX (group 1), golimumab 100 mg + placebo (group 2), golimumab 50 mg + MTX (group 3), or golimumab 100 mg + MTX (group 4). Inadequate responders in groups 1, 2, and 3 entered early escape at week 28 to golimumab 50 mg + MTX, golimumab 100 mg + MTX, or golimumab 100 mg + MTX, respectively; remaining patients in group 1 could cross over to golimumab 50 mg + MTX at week 52. Assessments included the American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70) response, the Disease Activity Score in 28 joints (DAS28) using C-reactive protein (CRP) level, and the modified Sharp/van der Heijde score (SHS). Efficacy was analyzed using an intent-to-treat (ITT) analysis. Pharmacokinetics and immunogenicity were evaluated at selected visits. Results: A total of 422 patients completed golimumab treatment through week 256. At week 256, 72.8%, 54.6%, and 38.0% of all patients in the full ITT population (n = 637) had an ACR20/50/70 response, respectively; 84.1% had a good or moderate DAS28-CRP response; and 72.7% had a clinically meaningful improvement in physical function. Radiographic progression was minimal in all treatment groups through week 256, and the overall mean change from baseline in SHS was 1.36. Serum trough golimumab concentrations were approximately dose proportional and maintained through week 256. Antibodies to golimumab occurred in 9.6% of patients through week 256. Infections were the most common type of adverse event (AE); 204 of 616 patients (33.1%) had ≥1 serious AE. Conclusions: Clinical efficacy with golimumab treatment was maintained through week 256 of the GO-BEFORE trial of MTX-naive RA patients. No unexpected AEs occurred; safety results through 5 years are consistent with earlier reports.

In this study, we have synthesized and characterized Li4Ti5O12 (LTO)-coated meso-carbon micro beads (MCMB) as an anode material for Li-batteries. The surface of MCMB powders was uniformly coated by the LTO nanoparticles to form a core-shell structure via a sol-gel process, followed by calcination. The average size of MCMB core was 15 μm while the thickness of LTO shell was 80 to 120 nm. We found that LTO-coated MCMB had better rate-capability and cycle life, compared with the pristine MCMB. Electrochemical impedance spectroscopy (EIS) results showed that after 40 cycles, the cell resistance of the LTO-coated MCMB electrode increased slightly, while that of the pristine MCMB electrode increased significantly. The enhanced performance of the LTO-coated MCMB electrode is attributed to the LTO coating, which suppresses the increase in the charge-transfer resistance during prolonged cycle.

Background: The food industry has shown an increased interest in the manufacture of healthier and more natural food products. By tailored processing fruit and vegetables can be used as structurants thus reducing artificial gums and stabilisers. The effect of different thermal and mechanical treatments, including high-pressure homogenisation, on the microstructural and rheological properties of carrot, broccoli and tomato dispersions was studied. As part of the rheological characterisation small oscillatory deformation as well as shear flow measurements were performed.RESULTS: Carrot and broccoli showed a different behaviour from tomato under the conditions studied. Changing the order of thermal and mechanical treatment led to microstructures with different flow properties. The resulting microstructures differed in the manner of cell wall separation: either breaking across the cell walls or through the middle lamella. High-pressure homogenisation decreased the viscosity of carrot and broccoli dispersions, while it increased the viscosity of tomato. Cryo-scanning electron microscopy showed that the cell walls of carrot and broccoli remained as compact structures after homogenisation whereas tomato cell walls were considerably swollen.CONCLUSIONS: Based on the type of vegetable, the different processes applied led to microstructures with different rheological properties. This study shows that particle size distribution, morphology and phase volume are important parameters to explain the complex relationship between rheology and microstructure for these types of systems.

Organogels based on edible oils and specific mixtures of phytosterols can serve as structured systems with a low saturated fat content. These low-SAFA organogels can be used also to create o/w emulsions. Little is known about the structures formed in these specific organogels and at the emulsion interface. We studied o/w organogels on different length scales to describe and understand their micro-structural features. Very basic processing conditions such as composition, temperature and storage time were taken into account. Two different types of structure were observed; at the smallest scale, long thin crystals are formed out of the oil phase into the continuous water phase. We propose that these are needle-like crystals. Next, tube-like structures are identified and can be visualized as tubular micelles. A model is proposed which fits the dimension (~7 nm) with the length scale of the molecular building blocks (TAGs and sterols). As edible fats from food products are enzymatically hydrolyzed in the gut prior to absorption, we also looked into the impact on the lipase reaction speed. Simple in vitro enzymatic hydrolysis experiments showed a slower enzymatic digestion. Organogel systems and emulsion made thereof have interesting food structuring properties with possible advantages in composition (low SAFA) and digestion speed.

In the Amsterdam Growth and Health Longitudinal Study (AGAHLS), a cohort of about 400 boys and girls (mean age 13 years) were followed over a period of 20 years. Over that period repeated measurements were done of body dimensions (height, weight, skinfolds), physical fitness (eight motor performance field tests: plate tapping, bent arm hang, 10 x 5 m sprint, arm pull, sit and reach, standing high jump, 10 leg lifts, 12-min endurance run, and one laboratory test to measure maximal aerobic power), and physical activity (by a cross-check interview). Three research questions were studied: (1) Is there a positive relationship between adolescent fitness (age 13-17 years) and adult physical activity (age 33 years)? (2) Do physical fitness and physical activity track from adolescence into adulthood? (3) What is the longitudinal relationship between physical fitness and physical activity? Multiple linear regression analysis showed that of the 9 physical fitness tests, only the 12-min endurance run and the maximal aerobic power during adolescence are significant (P < 0.05) predictors of adult physical activity. The effects are not influenced by biological age but by sex: only in females are the predictions significant (P < 0.05) Tracking over the period of 20 years estimated from stability coefficients showed values for physical fitness varying between 0.83 (plate tapping) to 0.38 (standing high jump and maximal aerobic power). Physical activity shows lower stability coefficients (0.35-0.29). A longitudinal linear regression technique was used to analyse the relationship between physical activity and physical fitness over the 20-year period; in this analysis corrections were made for both time-dependent (time, biological age, and cardiovascular factors) and time-independent variables (sex). All physical fitness tests show positive and significant (P < 0.05) standardized regression coefficients with physical activity, but the explained variance is less than 1%. Only maximal aerobic power has a higher explained variance of 1.8%. It can be concluded that: (1) Physical fitness in adolescence is only weakly related to adult physical activity; (2) between age 13 and 33 years, physical activity has low stability and physical fitness was higher stability; and (3) the longitudinal relationships between physical fitness and physical activity are only meaningful with maximal aerobic power.

BACKGROUND Abnormalities of upper gut motility, including a delay of gastric emptying and small bowel transit, found in patients with constipation may be secondary to factors originating in the colon or rectum as a result of faecal stasis. The aim was to determine if stimulation of mechanosensory function by rectal distension affects postprandial gallbladder emptying and release of gastrointestinal peptides participating in control of upper gut motility. MATERIALS AND METHODS Eight healthy volunteers were studied with an electronic barostat and a plastic bag positioned in the rectum. Intrabag pressure was maintained at minimal distension pressure + 2 mmHg on one occasion and on a pressure that induced a sensation of urge on the other. Gallbladder volume and plasma concentrations of cholecystokinin (CCK), pancreatic polypeptide (PP) and peptide YY (PYY) were measured before and after ingestion of a 450-kcal mixed liquid meal. RESULTS Rectal distension enhanced maximum gallbladder emptying from 66 +/- 7% to 78 +/- 5% (P < 0.05). Distension tended to increase integrated plasma PYY from 77 +/- 30 pM min to 128 +/- 40 pM min in the first hour after the meal (P = 0.08) and it suppressed integrated plasma PP from 1133 +/- 248 pM min to 269 +/- 284 pM min in the second hour (P < 0.05). Integrated plasma CCK concentrations were not significantly affected. CONCLUSION Mechanosensory stimulation of the rectum enhances postprandial gallbladder emptying and influences postprandial release of gut hormones involved in the regulation of gastrointestinal motility in healthy subjects. These mechanisms may play a role in the pathogenesis of the upper gastrointestinal motor abnormalities observed in constipated patients.

The purpose of the study was to determine the impact of nutrition and physical activity on growth and health of 228 native Bolivian prepubertal girls and boys 10-12 years of age, from high socioeconomic status (HSES) and low socioeconomic status (LSES), living at high altitude (HA) in La Paz (∼4,000 m) and at low altitude (LA) in St. Cruz (∼400 m). In the 4 years of the study, dietary information and daily physical activities were obtained with the 24-hour recall method by interviewing the child and mother. All food items were converted into grams, and nutrients were calculated by using food composition tables for Latin America. Physical activities were estimated in four intensity levels and calculated in terms of energy output. The results show that nutritional intake is influenced by socioeconomic status, but not by altitude. Overall, the energy and nutrient intake of the HSES girls and boys was significantly higher (P ≤ 0.01) than the intake of the LSES children at both altitudes; no sex effect was evident. HSES girls and boys consumed greater amounts of nutrients, especially protein and fat; they were taller but also fatter. The physical activity of LSES children was higher than that of HSES children. The lower energy intake and the higher energy expenditure of LSES children were reflected in their smaller body size. Am. J. Hum. Biol. 9:51-62 © 1997 Wiley-Liss, Inc.

Within the framework of a longitudinal study, the Amsterdam Growth and Health Study followed a group of males and females from their teens into early adulthood. Directly measured maximal oxygen uptake (VO2 max) was determined five times in 97 males and 103 females between 13 and 21 years of age during a constant speed (8 km/hr) and variable slope treadmill run to exhaustion. A change in oxygen uptake (VO2 ) of < 150 ml between the second last and final minute of the test was used as the criterion to determine the attainment of a plateau or leveling-off (LO) in VO2 . The purpose of this study was to investigate the relationship between VO2 max and the leveling-off criterion and other factors associated with the plateau phenomenon in this sample with increasing age. The VO2 max measurements over the years showed that 44-57% of males and 24-42% of females did not show a plateau. Moreover, subjects who did not reach leveling-off (no-LOs) showed slightly higher VO2 max values than subjects who reached the leveling-off criterion (LOs). These differences are significant (P < 0.05) in males from age 14.5 on, and in females only at age 21.5. Males who did not demonstrate a plateau in VO2 had a significantly higher total fat-free mass and lean leg volume (LLV) than males who demonstrated a plateau, but were not different in stature and weight. However, in females these differences were not significant. The apparent sex difference can be explained by the much smaller increase (25%) in LLV in females than in males. These results can be explained by the limitations of VO2 max by central and/or peripheral circulating factors. One possibility could be that during maximal uphill running, relatively less vasoconstriction occurs in the arterioles of larger exercising leg muscles, which permits an upward shift in VO2 and an increased demand on central oxygen transport mediated by increased peripheral metabolism. © 1994 Wiley-Liss, Inc.