Eccentric exercise versus Usual-care with older cancer survivors: The impact on muscle and mobility- an exploratory pilot study

<p>Abstract</p> <p>Background</p> <p>Resistance exercise programs with high compliance are needed to counter impaired muscle and mobility in older cancer survivors. To date outcomes have focused on older prostate cancer survivors, though more heterogeneous groups of older survivors are in-need. The purpose of this exploratory pilot study is to examine whether resistance exercise via negative eccentrically-induced work (RENEW) improves muscle and mobility in a diverse sample of older cancer survivors.</p> <p>Methods</p> <p>A total of 40 individuals (25 female, 15 male) with a mean age of 74 (± 6) years who have survived (8.4 ± 8 years) since their cancer diagnosis (breast, prostate, colorectal and lymphoma) were assigned to a RENEW group or a non-exercise Usual-care group. RENEW was performed for 12 weeks and measures of muscle size, strength, power and mobility were made pre and post training.</p> <p>Results</p> <p>RENEW induced increases in quadriceps lean tissue average cross sectional area (Pre: 43.2 ± 10.8 cm²; Post: 44.9 ± 10.9 cm²), knee extension peak strength (Pre: 248.3 ± 10.8 N; Post: 275.4 ± 10.9 N), leg extension muscle power (Pre: 198.2 ± 74.7 W; Post 255.5 ± 87.3 W), six minute walk distance (Pre: 417.2 ± 127.1 m; Post 466.9 ± 125.1 m) and a decrease on the time to safely descend stairs (Pre: 6.8 ± 4.5 s; Post 5.4 ± 2.5 s). A significant (P < 0.05) group x time interaction was noted for the muscle size and mobility improvements.</p> <p>Conclusions</p> <p>This exploration of RENEW in a heterogeneous cohort of older cancer survivors demonstrates increases in muscle size, strength and power along with improved mobility. The efficacy of a high-force, low perceived exertion exercise suggests RENEW may be suited to older individuals who are survivors of cancer.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00335491">NCT00335491</a></p

Randomised controlled trial of a supervised exercise rehabilitation program for colorectal cancer survivors immediately after chemotherapy: study protocol

Background Colorectal cancer (CRC) diagnosis and the ensuing treatments can have a substantial impact on the physical and psychological health of survivors. As the number of CRC survivors increases, so too does the need to develop viable rehabilitation programs to help these survivors return to good health as quickly as possible. Exercise has the potential to address many of the adverse effects of CRC treatment; however, to date, the role of exercise in the rehabilitation of cancer patients immediately after the completion of treatment has received limited research attention. This paper presents the design of a randomised controlled trial which will evaluate the feasibility and efficacy of a 12-week supervised aerobic exercise program (ImPACT Program) on the physiological and psychological markers of rehabilitation, in addition to biomarkers of standard haematological outcomes and the IGF axis. Methods/Design Forty CRC patients will be recruited through oncology clinics and randomised to an exercise group or a usual care control group. Baseline assessment will take place within 4 weeks of the patient completing adjuvant chemotherapy treatment. The exercise program for patients in the intervention group will commence a week after the baseline assessment. The program consists of three supervised moderate-intensity aerobic exercise sessions per week for 12 weeks. All participants will have assessments at baseline (0 wks), mid-intervention (6 wks), post-intervention (12 wks) and at a 6-week follow-up (18 wks). Outcome measures include cardio-respiratory fitness, biomarkers associated with health and survival, and indices of fatigue and quality of life. Process measures are participants' acceptability of, adherence to, and compliance with the exercise program, in addition to the safety of the program. Discussion The results of this study will provide valuable insight into the role of supervised exercise in improving life after CRC. Additionally, process analyses will inform the feasibility of implementing the program in a population of CRC patients immediately after completing chemotherapy

The unsupported upper limb exercise test in people without disabilities: assessing the within-day test–retest reliability and the effects of age and gender

Purpose: To estimate the within-day test–retest reliability and standard error of measurement (SEM) of the unsupported upper limb exercise test (UULEX) in adults without disabilities and to determine the effects of age and gender on performance of the UULEX. Method: A cross-sectional study was conducted with 100 adults without disabilities (44 men, mean age 44.2 [SD 26] y; 56 women, mean age 38.1 [SD 24.1] y). Participants performed three UULEX tests to establish within-day reliability, measured using an intra-class correlation coefficient (ICC) model 2 (two-way random effects) with a single rater (ICC[2,1]) and SEM. The effects of age and gender were examined using two-factor mixed-design analysis of variance (ANOVA) and one-way repeated-measures ANOVA. For analysis purposes, four sub-groups were created: younger adults, older adults, men, and women. Results: Excellent within-day reliability and a small SEM were found in the four sub-groups (younger adults: ICC[2,1]=0.88; 95% CI: 0.82, 0.92; SEM∼40 s; older adults: ICC[2,1]=0.82; 95% CI: 0.72, 0.90; SEM∼50 s; men: ICC[2,1]=0.93; 95% CI: 0.88, 0.96; SEM∼30 s; women: ICC[2,1]=0.85; 95% CI: 0.78, 0.91; SEM∼45 s). Younger adults took, on average, 308.24 seconds longer than older adults to perform the test; older adults performed significantly better on the third test (p0.05). Conclusion: The within-day test–retest reliability and SEM values of the UULEX may be used to define the magnitude of the error obtained with repeated measures. One UULEX test seems to be adequate for younger adults to achieve reliable results, whereas three tests seem to be needed for older adults.Objectif : évaluer la fiabilité d'un test-retest en une même journée et l'erreur type de mesure (ETM) du test d'exercice des membres supérieurs sans appui (UULEX) chez des adultes sans incapacités et déterminer les effets de l'âge et du sexe sur leur exécution. Méthodologie : les chercheurs ont réalisé une étude transversale auprès de 100 adultes sans incapacités (44 hommes, d'un âge moyen de 44,2 ans [ÉT 26], et 56 femmes, d'un âge moyen de 38,1 ans [ÉT 24,1]). Les participants ont effectué trois UULEX pour établir la fiabilité du test-retest en une même journée, mesurés à l'aide du modèle 2 de coefficient de corrélation intraclasse (ICC, effets aléatoires bilatéraux) comportant un ICC(2,1) et une ETM à un seul évaluateur. Les chercheurs ont examiné les effets de l'âge et du sexe à l'aide d'une analyse de variance bifactorielle à mesures mixtes et d'une analyse de variance unifactorielle à mesures répétées. Pour les besoins de l'analyse, les chercheurs ont créé quatre sous-groupes: jeunes adultes, adultes plus âgés, hommes et femmes. Résultats : les quatre sous-groupes affichaient une excellente fiabilité en une même journée et une petite ETM (jeunes adultes: ICC[2,1]=0,88 [IC 95% : 0,82, 0,92] et ETM∼40 secondes; adultes plus âgés : ICC[2,1]=0,82 [IC 95 % : 0,72, 0,90] et ETM∼50 secondes; hommes: ICC[2,1]=0,93 [IC 95% : 0,88, 0,96] et ETM∼30 secondes; femmes: ICC[2,1]=0,85 [IC 95 % : 0,78, 0,91] et ETM∼45 secondes). En moyenne, les jeunes adultes ont effectué le test pendant 308,24 secondes de plus que les adultes plus âgés; ceux-ci ont obtenu un résultat nettement meilleur au troisième test (p0,05). Conclusion : il est possible d'utiliser la fiabilité de test-retest en une même journée et les valeurs d'ETM de l'UULEX pour définir l'importance de l'erreur obtenue lors de mesures répétées. Un UULEX semble suffire pour que les jeunes adultes obtiennent des résultats fiables, tandis que trois tests semblent nécessaires chez les adultes plus âgés

The strength of the template effect attracting nucleotides to naked DNA

The transmission of genetic information relies on Watson-Crick base pairing between nucleoside phosphates and template bases in template–primer complexes. Enzyme-free primer extension is the purest form of the transmission process, without any chaperon-like effect of polymerases. This simple form of copying of sequences is intimately linked to the origin of life and provides new opportunities for reading genetic information. Here, we report the dissociation constants for complexes between (deoxy)nucleotides and template–primer complexes, as determined by nuclear magnetic resonance and the inhibitory effect of unactivated nucleotides on enzyme-free primer extension. Depending on the sequence context, Kd´s range from 280 mM for thymidine monophosphate binding to a terminal adenine of a hairpin to 2 mM for a deoxyguanosine monophosphate binding in the interior of a sequence with a neighboring strand. Combined with rate constants for the chemical step of extension and hydrolytic inactivation, our quantitative theory explains why some enzyme-free copying reactions are incomplete while others are not. For example, for GMP binding to ribonucleic acid, inhibition is a significant factor in low-yielding reactions, whereas for amino-terminal DNA hydrolysis of monomers is critical. Our results thus provide a quantitative basis for enzyme-free copyin

Cascade of reduced speed and accuracy after errors in enzyme-free copying of nucleic acid sequences

Nonenzymatic, template-directed synthesis of nucleic acids is a paradigm for self-replicating systems. The evolutionary dynamics of such systems depend on several factors, including the mutation rates, relative replication rates, and sequence characteristics of mutant sequences. We measured the kinetics of correct and incorrect monomer insertion downstream of a primer-template mismatch (mutation), using a range of backbone structures (RNA, DNA, and LNA templates and RNA and DNA primers) and two types of 5'-activated nucleotides (oxyazabenzotriazolides and imidazolides, i.e., nucleoside 5'-phosphorimidazolides). Our study indicated that for all systems studied, an initial mismatch was likely to be followed by another error (54-75% of the time), and extension after a single mismatch was generally 10-100 times slower than extension without errors. If the mismatch was followed by a matched base pair, the extension rate recovered to nearly normal levels. On the basis of these data, we simulated nucleic acid replication in silico, which indicated that a primer suffering an initial error would lag behind properly extended counterparts due to a cascade of subsequent errors and kinetic stalling, with the typical mutational event consisting of several consecutive errors. Our study also included different sequence contexts, which suggest the presence of cooperativity among monomers affecting both absolute rate (by up to 2 orders of magnitude) and fidelity. The results suggest that molecular evolution in enzyme-free replication systems would be characterized by large "leaps" through sequence space rather than isolated point mutations, perhaps enabling rapid exploration of diverse sequences. The findings may also be useful for designing self-replicating systems combining high fidelity with evolvability

60 Ethnic differences in repolarisation patterns and left ventricular remodelling in highly trained male adolescent (14-18 years) athletes.

International audiencePurpose Studies in adult, black athletes (BA) demonstrate a high prevalence of ECG repolarisation changes and echocardiographic left ventricular hypertrophy (LVH) that may overlap with hypertrophic cardiomyopathy (HCM). The prevalence of ECG repolarisation changes and echocardiographic LVH in adolescent BA, the group most vulnerable to exercise-related sudden death from HCM, is unknown. Methods This study evaluated 219 male adolescent BA (14-18 years, inclusive) with 12-lead ECG and 2-D echocardiography. Results were compared with 1440 male adolescent WA. Athletes with T wave inversions and morphological LVH were invited for further investigation with exercise stress test, 24 h Holter and CMR. Results ST segment elevation was common in both groups but more frequent in BA (63.5% vs 14.9%, p12 mm vs only 6 (0.4%) WA (p<0.001). None of the athletes exhibited the broader phenotype of HCM on further investigation. In multivariable analysis black ethnicity was the strongest independent predictor for the presence of T wave inversions (OR 3.56, 95% CI 1.56 to 8.13, p=0.003) and LVH (OR 3.17, 95% CI 1.77 to 5.71, p<0.001). Conclusions As with adult athletes, T wave inversions and LVH were more prevalent in adolescent BA compared to WA. These findings have important implications in the pre-participation screening era, particularly in countries with a high proportion of BA competing at elite level, since extrapolation of ECG and echocardiographic criteria, solely derived from Caucasian cohorts, would result in 25.6% of BA requiring further investigations for cardiac pathology

Improved diagnosis of post-operative myocardial infarction by contrast echocardiography after coronary artery bypass graft surgery

International audienceOBJECTIVE: Contrast echocardiography is a more accurate means of assessment of left ventricular (LV) regional motion compared with non-enhanced echocardiography. Despite new tests, the diagnosis of post-operative myocardial infarction (MI) remains difficult. The aim of this study was to determine whether contrast echocardiography can facilitate this diagnosis. METHODS: We performed standard and contrast echocardiography in 79 consecutive patients before and up to 10 days after they underwent isolated coronary artery bypass graft (CABG) surgery. RESULTS: The post-operative intra- and interobserver reproducibility of echocardiographic measurements of the LV ejection fraction and wall motion score was significantly higher with than without contrast enhancement. The proportion of non-visualized LV myocardial segments was significantly greater with non-enhanced (6.6%) than with contrast (0.3%) echocardiography (P< 0.0001). The mean peak serum cardiac troponin (cTnI) concentration was significantly higher in the group of patients with new wall motion abnormalities detected with contrast-enhanced echocardiography. A correlation was found (r = -0.43, P< 0.01) between peak cTnI and changes in wall motion score only when a contrast agent was used. CONCLUSION: Contrast echocardiography facilitated the detection of new LV wall motion abnormalities after CABG. This observation, added to other markers, might facilitate the diagnosis of post-operative MI