Kinematic algorithm to determine the energy cost of running with changes of direction

Changes of direction (CoDs) have a high metabolic and mechanical impact in field and court team sports, but the estimation of the associated workload is still inaccurate. This study aims at validating an algorithm based on kinematic data to estimate the energy cost of running with frequent 180\ub0-CoDs. Twenty-six physically active male subjects (22.4\u202f\ub1\u202f3.2\u202fyears) participated in two sessions: (1) maximum oxygen uptake (V\u307O2,max) and maximal aerobic speed (MAS) test; (2) 5-m continuous shuttle run (two 5-min trials at 50% and 75% MAS, 6-min recovery). In (2), full-body 3D-kinematics and V\u307O2 were simultaneously recorded. Actual cost of shuttle running (Cmeas) was obtained from the aerobic, anaerobic alactic and lactic components. The proposed algorithm detects "braking phases", periods of mostly negative (eccentric) work occurring at concurrent knee flexion and ground contact, and estimates energy cost (Cest) considering negative mechanical work in braking phases, and positive elsewhere. At the speed of, respectively, 1.54\u202f\ub1\u202f0.17 and 1.90\u202f\ub1\u202f0.15\u202fm\u202fs-1 (rate of perceived exertion: 9.1\u202f\ub1\u202f1.8 and 15.8\u202f\ub1\u202f1.9), Cmeas was 8.06\u202f\ub1\u202f0.49 and 9.04\u202f\ub1\u202f0.73\u202fJ\u202fkg-1\u202fm-1. Cest was more accurate than regression models found in literature (p\u202f\u202f0.05; average error: 8.3%, root-mean-square error: 0.86\u202fJ\u202fkg-1\u202fm-1). The proposed algorithm improved existing techniques based on CoM kinematics, integrating data of ground contacts and joint angles that allowed to separate propulsive from braking phases. This work constitutes the basis to extend the model from the laboratory to the field, providing a reliable measure of training and matches workload

Clinical relevance of thymidylate syntetase expression in the signet ring cell histotype component of colorectal carcinoma

Thymidylate Synthase (TS) is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU). The aim of this work was to study TS expression and the proliferation rate in the different histological types of colorectal carcinoma (CRC). 50 patients with CRC were included in this study and evaluated immunohistochemically using the monoclonal antibodies, TS106 and Ki67. 20 tumours were of the intestinal type, 15 cases were signet ring cell carcinoma (SRCCs) and 15 cases were "mixed-type", with at least two different histological components. Intestinal and mucinous histotypes were positive for TS and Ki67, while "signet ring cell" samples were negative or showed only weak and focal positivity for both the TS and Ki67 antibodies. Our results show that signet ring cells (that are also often present in intestinal and mucinous carcinomas), are in the post-mitotic phase of the cell cycle and show a low proliferation index and TS expression. As TS is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU), we can hypothesise that TS expression levels in the different histotypes of CRC could affect the potential responsiveness of these tumours to fluoropyrimidine chemotherapy, with a low efficacy being expected in signet ring cell areas

Thymidylate synthase gene promoter polymorphisms are associated with TSmRNA expressions but not with microsatellite instability in colorectal cancer

Abstract BACKGROUND: Microsatellite instability (MSI) is a biological characteristic of most tumours, being involved in 85% of hereditary non-polyposis colorectal cancer (HNPCC). It also occurs in 10-15% of sporadic colorectal cancers (CRC). HNPCC appears to be caused by germline mutations in mismatch repair (MMR) genes, which are responsible for repairing single base-pair mismatches. MSI is also associated with a better response of CRC to adjuvant chemotherapy with fluoropyrimidines. We investigated any relationship between the MSI status and the TSmRNA expression, the polymorphisms of 5-Fluorouracil (5-FU cellular target, the enzyme thymidylate synthase (TS) and TS expression evaluated by means of immunohistochemistry. MATERIALS AND METHODS: A series of 80 colorectal cancers was evaluated for MSI and polymorphisms in the 3'UTR and the 5'UTR of the TS gene by a PCR assay. TSmRNA was quantified by real-time PCR and the TS expression by immunohistochemical assay. RESULTS: There was no significant association between the polymorphisms in the TS gene and the MSI or between the TSmRNA expression and the MSI status. CRC with a 3R/3R or 2R/3R genotype showed a significantly higher TSmRNA expression than those with the 2R/2R genotype (p = 0.001 and p = 0.028, respectively). Another significant association was found between the TSmRNA expression and the TS immunohistochemical determination (p = < 0.05). No association was found between the polymorphism of the 3'UTR and the TSmRNA expression. CONCLUSION: Our data show that there is no association between MSI status and the polymorphisms in the 3' and 5' UTRs and the TS expression. Tumour samples displaying the 3R/3R or 2R/3R genotype of TS have higher TSmRNA levels than the 2R/2R genotype. Polymorphic variant of the 3'UTR does not influence the TSmRNA level. We found a relationship between the TSmRNA expression, evaluated by real-time PCR, and with the TS level determined by immunohistochemical assay. Thus, genotyping of the 5'UTR and quantification of the TSmRNA expression in human CRC could be considered as predictors for response to SFU-based chemotherapy. The evaluation of the TS expression by means of immunohistochemistry assay remains a safe and reliable assay in CRC

Clinical and Experimental Projects on Chemotherapy of Bladder Tumours

Our clinical and experimental experience with chemotherapy of bladder tumours is reviewed. The routes of drug administrations, drug dosages and combinations, are presented. Adjuvant radiotherapy and chemoprophylaxis of certain tumours are discussed.S. Afr. Med. J., 48, 631 (1974

Clinical and experimental projects on chemotherapy of bladder tumours

Click on the link to view

Dor versus Toupet fundoplication after Laparoscopic Heller Myotomy: Systematic review and Bayesian meta-analysis of randomized controlled trials

Laparoscopic Heller Myotomy (LHM) with partial fundoplication has become the treatment of choice for esophageal achalasia. However, the choice of the partial fundoplication is debated. The aim of this study was to compare outcomes for Dor and Toupet fundoplication after LHM. A systematic search of randomized controlled trials comparing Dor and Toupet fundoplication was performed using PubMed, EMBASE and Web of Science. Three studies met the inclusion criteria. Overall, 174 patients were included in the analysis. The postoperative abnormal acid reflux [pooled Risk Ratio 0.98 (95% HPD 0.54-1.80)] and dysphagia [pooled Risk Ratio 1.03 (95% HPD 0.51-2.05)] were similar comparing Dor and Toupet fundoplication. The % total time pH&nbsp; 64&nbsp;4 [estimated pooled mean difference -0.08 (95% HPD -1.04-0.90)] and DeMeester score [estimated pooled mean difference 0.51 (95% HPD -0.90-1.94)] were comparable. Additionally, the operative time [estimated pooled mean difference 0.02 (95% HPD -0.53-0.52)] and iatrogenic esophageal perforation [pooled Risk Ratio 1.05 (95% HPD 0.52-2.10)] were similar in the two groups. Dor and Toupet fundoplication after laparoscopic Heller myotomy seem comparable in term of postoperative abnormal acid exposure and dysphagia. The choice of the partial fundoplication should be left to surgeon experience and tailored on each patient

FGF4 and Retinoic Acid Direct Differentiation of hESCs into PDX1-Expressing Foregut Endoderm in a Time- and Concentration-Dependent Manner

BACKGROUND: Retinoic acid (RA) and fibroblast growth factor 4 (FGF4) signaling control endoderm patterning and pancreas induction/expansion. Based on these findings, RA and FGFs, excluding FGF4, have frequently been used in differentiation protocols to direct differentiation of hESCs into endodermal and pancreatic cell types. In vivo, these signaling pathways act in a temporal and concentration-dependent manner. However, in vitro, the underlying basis for the time of addition of growth and differentiation factors (GDFs), including RA and FGFs, as well as the concentration is lacking. Thus, in order to develop robust and reliable differentiation protocols of ESCs into mature pancreatic cell types, including insulin-producing beta cells, it will be important to mechanistically understand each specification step. This includes differentiation of mesendoderm/definitive endoderm into foregut endoderm--the origin of pancreatic endoderm. METHODOLOGY/PRINCIPAL FINDINGS: Here, we provide data on the individual and combinatorial role of RA and FGF4 in directing differentiation of ActivinA (AA)-induced hESCs into PDX1-expressing cells. FGF4's ability to affect endoderm patterning and specification in vitro has so far not been tested. By testing out the optimal concentration and timing of addition of FGF4 and RA, we present a robust differentiation protocol that on average generates 32% PDX1(+) cells. Furthermore, we show that RA is required for converting AA-induced hESCs into PDX1(+) cells, and that part of the underlying mechanism involves FGF receptor signaling. Finally, further characterization of the PDX1(+) cells suggests that they represent foregut endoderm not yet committed to pancreatic, posterior stomach, or duodenal endoderm. CONCLUSION/SIGNIFICANCE: In conclusion, we show that RA and FGF4 jointly direct differentiation of PDX1(+) foregut endoderm in a robust and efficient manner. RA signaling mediated by the early induction of RARbeta through AA/Wnt3a is required for PDX1 expression. Part of RA's activity is mediated by FGF signaling

Role of CBP and SATB-1 in Aging, Dietary Restriction, and Insulin-Like Signaling

Increased transcriptional complex activity, or pharmacological mimics of increased complex activity, predict lifespan in mice and mediate the protective effects of dietary restriction during aging