Gender differences in barriers to physical activity among adolescents.

BACKGROUND AND AIMS: Great attention is now being paid to effective policies and programs to promote physical activity among adolescents, girls consistently found to be less active than boys. The aim of this study was to assess gender differences in perceived barriers for physical activity practice and their relationship with physical activity levels and physical condition among adolescents. METHODS AND RESULTS: A cross-sectional study was conducted in February-April 2017 among students (n = 368) in the last year of two state high schools in Florence (Italy). Participants underwent the measurements of anthropometric parameters (height, weight, waist, and hip circumferences), blood pressure and administration of 3 standardized questionnaires (International Physical Activity Questionnaire, Mediterranean Diet Score Quiz, and Barriers to Being Active Quiz). Gender differences were assessed using a multivariate logistic regression model (adjusted for age and body mass index). The prevalence of participants who reached recommended levels was lower among girls compared to boys (OR 0.27; 95% CI 0.17-0.43). The number of perceived barriers to physical activity was higher among girls than among boys (OR 1.52; 95% CI 1.29-1.79), lack of energy for exercise and lack of willpower being the two barriers most frequently reported by girls. At multivariable adjusted logistic regression analysis, gender (female), and positivity of at least one perceived barrier (score ≥ 5) were independently selected as the main determinants of non-compliance with WHO criteria for physical activity. CONCLUSIONS: Exercise professionals should be aware of the barriers that young girls can face during exercise prescription and be able to contrast them with useful individual strategies.

Evaluation of left ventricular remodelling in young Afro-Caribbean athletes.

BACKGROUND: Cardiac adaptation to intense physical training is determined by many factors including age, gender, body size, load training and ethnicity. Despite the wide availability of ECG analysis, with a higher presence of abnormalities in different races, echocardiographic studies on young Afro-Caribean (AA) and Caucasian athletes (CA) are lacking in literature. We aimed to assess the effect in the secondary LV remodelling of load training in young AA players compared to matched CA players. METHOD: Seventy-seven AA and 53 CA matched soccer players (mean age 17.35 ± 0.50 and 18.25 ± 0.77 y) were enrolled. They were evaluated with echocardiography. A subgroup of 30 AA and 27 CA were followed up for a period of 4 years. The myocardial contractile function was evaluated by speckle-tracking echocardiographic global longitudinal strain (GLS). RESULTS: No significant differences were found in weight and height and in blood pressure response to maximal ergometer test in either group. In AA a higher level of LV remodelling, consisting in higher LV wall thickness, higher interventricular septum (IVS) and posterior wall (PW) thickness were found (IVS: 10.04 ± 0.14 and 9.35 ± 0.10 in AA and CA respectively, p < 0.001. PW: 9.70 ± 0.20 and 9.19 ± 0.10 mm in AA and CA respectively, p < 0.05). Strain data showed no significant differences between the two groups (22.35 ± 0.48 and 23.38 ± 0.69 in AA (n = 27) and CA (n = 25), respectively). At the beginning of the follow-up study AA showed a significantly higher left ventricular remodelling (IVS = 9.29 ± 0.3 and 8.53 ± 0.12 mm in AA and CA respectively, p < 0.002. PW = 9.01 ± 0.2 and 8.40 ± 0.20 in AA and CA respectively, p = 0.1). During the next four years of follow-up we observed a regular parallel increase in LV wall thickness and chamber diameters in both groups, proportionally to the increase in body size and LV mass. (IVS = 10.52 ± 0.17 and 9.03 ± 0.22 mm in AA and CA respectively, p < 0.001. PW: 10.06 ± 0.17 and 8.26 ± 0.19 mm in AA and CA respectively, p < 0.001). CONCLUSION: The study shows that the ventricular remodelling observed in AA appears to be a specific phenotype already present in pre-adolescence. These data also suggest that genetic/ethnic factors play a central role in left ventricular remodelling during the first years of life in elite athletes.

Late sodium current inhibition reverses electromechanical dysfunction in human hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM), the most common mendelian heart disorder, remains an orphan of disease-specific pharmacological treatment because of the limited understanding of cellular mechanisms underlying arrhythmogenicity and diastolic dysfunction. METHODS AND RESULTS: We assessed the electromechanical profile of cardiomyocytes from 26 HCM patients undergoing myectomy compared with those from nonfailing nonhypertrophic surgical patients by performing patch-clamp and intracellular Ca(2+) (Ca(2+)(i)) studies. Compared with controls, HCM cardiomyocytes showed prolonged action potential related to increased late Na(+) (I(NaL)) and Ca(2+) (I(CaL)) currents and decreased repolarizing K(+) currents, increased occurrence of cellular arrhythmias, prolonged Ca(2+)(i) transients, and higher diastolic Ca(2+)(i). Such changes were related to enhanced Ca(2+)/calmodulin kinase II (CaMKII) activity and increased phosphorylation of its targets. Ranolazine at therapeutic concentrations partially reversed the HCM-related cellular abnormalities via I(NaL) inhibition, with negligible effects in controls. By shortening the action potential duration in HCM cardiomyocytes, ranolazine reduced the occurrence of early and delayed afterdepolarizations. Finally, as a result of the faster kinetics of Ca(2+)(i) transients and the lower diastolic Ca(2+)(i), ranolazine accelerated the contraction-relaxation cycle of HCM trabeculae, ameliorating diastolic function. CONCLUSIONS: We highlighted a specific set of functional changes in human HCM myocardium that stem from a complex remodeling process involving alterations of CaMKII-dependent signaling, rather than being a direct consequence of the causal sarcomeric mutations. Among the several ion channel and Ca(2+)(i) handling proteins changes identified, an enhanced I(NaL) seems to be a major contributor to the electrophysiological and Ca(2+)(i) dynamic abnormalities of ventricular myocytes and trabeculae from patients with HCM, suggesting potential therapeutic implications of I(NaL) inhibition.

Adjuvant Therapy Reduces Fat Mass Loss during Exercise Prescription in Breast Cancer Survivors.

Improvements in cancer care over the years have increased the numbers of cancer survivors. Therefore, quality of life, fat mass management and physical activity are growing areas of interest in these people. After the surgical removal of a breast cancer, adjuvant therapy remains anyway a common strategy. The aim of this study was to assess how adjuvant therapy can affect the effectiveness of an unsupervised exercise program. Forty-two women were enrolled (52.0 ± 10.1 years). Assessments performed at baseline and after six months of exercise prescription were body composition, health-related quality of life, aerobic capacity by Six-Minute Walk Test, limbs strength by hand grip and chair test and flexibility by sit and reach. Statistical analyses were conducted by ANOVA tests and multiple regression. Improvements in body composition, physical fitness and quality of life (physical functioning, general health, social functioning and mental health items) were found. The percentage change in fat mass has been associated with adjuvant cancer therapy (intercept = -0.016; b = 8.629; p < 0.05). An unsupervised exercise prescription program improves body composition, physical fitness and health-related quality of life in breast cancer survivors. Adjuvant therapy in cancer slows down the effectiveness of an exercise program in the loss of fat mass.

Breast cancer: effectiveness of a one-year unsupervised exercise program.

BACKGROUND: Improvements in prevention and therapeutic strategies over the years have considerably increased the number of breast cancer survivors. Sedentary behavior is now acknowledged to be a risk factor for cancer and cancer relapse. Currently, there are different approaches to increasing the effectiveness of long-term physical activity in these patients. The aim of this study was to verify the long-term effectiveness of a home-based program for active lifestyle change in overweight breast cancer survivors. METHODS: We enrolled 43 women (age 51.5±9.9 years), who underwent an evaluation of their spontaneous physical activity levels, their baseline aerobic capacity through a 6-Minute Walking Test (6MWT), their flexibility, grip and lower limb strength, and their body composition. We repeated the measurements of these physical and anthropometric parameters six times during one year of unsupervised exercise. RESULTS: At the beginning of the program the sample showed a moderate level of spontaneous physical activity (physical activity level=1.44±0.12, steps/day=7420.3±1622.3). After being prescribed an individual exercise program, a significant reduction in BMI (T0=27.9±4.3, T5=25.8±3.0 kg/m2; P<0.001) and skinfold sum was observed (T0=99.5±25.2, T5=86.2±22.7 mm; P=0.019), with a parallel maintenance of cell mass (T0= 21.4±3.3, T5= 22.5±3.0 kg; P=0.654). The functional parameters showed an increase in lower limb muscle fitness and a reduction in diastolic blood pressure after 6 MWT (T0= 78.4±10.1, T5= 72.5±14.9 mmhg; P=0.032). CONCLUSIONS: Physical activity is recommended for cancer patients; this model of prescribing unsupervised exercise seems to ensure optimal compliance, thus allowing long-term therapeutic efficacy.

Seasonal blood pressure variation: implications for cardiovascular risk stratification.

Long-term blood pressure variations contribute to an increased risk of cardiovascular events during cold season, requiring personalized management of antihypertensive medications in a single patient, and can influence the results of clinical trials and epidemiological surveys in population studies. In addition to blood pressure values, which guide the stratification of cardiovascular risk, other cardiovascular risk factor levels also tend to be higher in the winter months and lower in the summer months. The resultant estimation of individual cardiovascular risk may thus vary depending on the season. At the patient level, only a low value in the winter should thus be considered a true measure of low cardiovascular risk, whereas low values measured in the summer do not indicate a low risk in the winter. Likewise, estimations of cardiovascular risk in population studies may vary according to the period of the year. Efforts should thus be directed at considering the potential influence of seasonal variations in establishing "normal" and "high-risk" assessment at both the patient and population levels, integrating such data into clinical practice.

Late sodium current inhibitors to treat exercise-induced obstruction in hypertrophic cardiomyopathy: an in vitro study in human myocardium.

BACKGROUND AND PURPOSE: In 30-40% of hypertrophic cardiomyopathy (HCM) patients, symptomatic left ventricular (LV) outflow gradients develop only during exercise due to catecholamine-induced LV hypercontractility (inducible obstruction). Negative inotropic pharmacological options are limited to ß-blockers or disopyramide, with low efficacy and tolerability. We assessed the potential of late sodium current (INaL )-inhibitors to treat inducible obstruction in HCM. EXPERIMENTAL APPROACH: The electrophysiological and mechanical responses to ß-adrenoceptor stimulation were studied in human myocardium from HCM and control patients. Effects of INaL -inhibitors (ranolazine and GS-967) in HCM samples were investigated under conditions simulating rest and exercise. KEY RESULTS: In cardiomyocytes and trabeculae from 18 surgical septal samples of patients with obstruction, the selective INaL -inhibitor GS-967 (0.5 µM) hastened twitch kinetics, decreased diastolic [Ca2+ ] and shortened action potentials, matching the effects of ranolazine (10µM). Mechanical responses to isoprenaline (inotropic and lusitropic) were comparable in HCM and control myocardium. However, isoprenaline prolonged action potentials in HCM myocardium, while it shortened them in controls. Unlike disopyramide, neither GS-967 nor ranolazine reduced force at rest. However, in the presence of isoprenaline, they reduced Ca2+ -transient amplitude and twitch tension, while the acceleration of relaxation was maintained. INaL -inhibitors were more effective than disopyramide in reducing contractility during exercise. Finally, INaL -inhibitors abolished arrhythmias induced by isoprenaline. CONCLUSIONS AND IMPLICATIONS: Ranolazine and GS-967 reduced septal myocardium tension during simulated exercise in vitro and therefore have the potential to ameliorate symptoms caused by inducible obstruction in HCM patients, with some advantages over disopyramide and ß-blockers.

Pathogenesis of Hypertrophic Cardiomyopathy is Mutation Rather Than Disease Specific: A Comparison of the Cardiac Troponin T E163R and R92Q Mouse Models.

BACKGROUND: In cardiomyocytes from patients with hypertrophic cardiomyopathy, mechanical dysfunction and arrhythmogenicity are caused by mutation-driven changes in myofilament function combined with excitation-contraction (E-C) coupling abnormalities related to adverse remodeling. Whether myofilament or E-C coupling alterations are more relevant in disease development is unknown. Here, we aim to investigate whether the relative roles of myofilament dysfunction and E-C coupling remodeling in determining the hypertrophic cardiomyopathy phenotype are mutation specific. METHODS AND RESULTS: Two hypertrophic cardiomyopathy mouse models carrying the R92Q and the E163R TNNT2 mutations were investigated. Echocardiography showed left ventricular hypertrophy, enhanced contractility, and diastolic dysfunction in both models; however, these phenotypes were more pronounced in the R92Q mice. Both E163R and R92Q trabeculae showed prolonged twitch relaxation and increased occurrence of premature beats. In E163R ventricular myofibrils or skinned trabeculae, relaxation following Ca2+ removal was prolonged; resting tension and resting ATPase were higher; and isometric ATPase at maximal Ca2+ activation, the energy cost of tension generation, and myofilament Ca2+ sensitivity were increased compared with that in wild-type mice. No sarcomeric changes were observed in R92Q versus wild-type mice, except for a large increase in myofilament Ca2+ sensitivity. In R92Q myocardium, we found a blunted response to inotropic interventions, slower decay of Ca2+ transients, reduced SERCA function, and increased Ca2+/calmodulin kinase II activity. Contrarily, secondary alterations of E-C coupling and signaling were minimal in E163R myocardium. CONCLUSIONS: In E163R models, mutation-driven myofilament abnormalities directly cause myocardial dysfunction. In R92Q, diastolic dysfunction and arrhythmogenicity are mediated by profound cardiomyocyte signaling and E-C coupling changes. Similar hypertrophic cardiomyopathy phenotypes can be generated through different pathways, implying different strategies for a precision medicine approach to treatment.

Continuing follow-up of malignant hypertension.

The history of accelerated (malignant) hypertension is reviewed, and unsolved problems related to the disease are illustrated, including its relationship to malignant nephrosclerosis, as well as terminology, current frequency and treatment. Over the past 25 years, out of a series of 131 patients, 53 were classified as suffering from essential malignant hypertension, the only suitable model on which the effects of pharmacological treatment on the disease can correctly be evaluated. In 2000, there were 24 survivors in our series and the maximum follow-up was 290 months. Multiple daily B.P. self-measurements allowed us to establish that pharmacological treatment was only able to approximate, to a varying degree, the conventional threshold of 140/90. Yet, despite this incomplete control over blood pressure levels, renal function was maintained in those patients whose initial creatininemia levels had not been higher than 2 mg/L. The renal protection effect of treatment was preserved even in patients who relapsed intoaccelerated disease phase one or more times over the study period.

Impact of detubulation on force and kinetics of cardiac muscle contraction.

Action potential-driven Ca(2+) currents from the transverse tubules (t-tubules) trigger synchronous Ca(2+) release from the sarcoplasmic reticulum of cardiomyocytes. Loss of t-tubules has been reported in cardiac diseases, including heart failure, but the effect of uncoupling t-tubules from the sarcolemma on cardiac muscle mechanics remains largely unknown. We dissected intact rat right ventricular trabeculae and compared force, sarcomere length, and intracellular Ca(2+) in control trabeculae with trabeculae in which the t-tubules were uncoupled from the plasma membrane by formamide-induced osmotic shock (detubulation). We verified disconnection of a consistent fraction of t-tubules from the sarcolemma by two-photon fluorescence imaging of FM4-64-labeled membranes and by the absence of tubular action potential, which was recorded by random access multiphoton microscopy in combination with a voltage-sensitive dye (Di-4-AN(F)EPPTEA). Detubulation reduced the amplitude and prolonged the duration of Ca(2+) transients, leading to slower kinetics of force generation and relaxation and reduced twitch tension (1 Hz, 30°C, 1.5 mM [Ca(2+)]o). No mechanical changes were observed in rat left atrial trabeculae after formamide shock, consistent with the lack of t-tubules in rodent atrial myocytes. Detubulation diminished the rate-dependent increase of Ca(2+)-transient amplitude and twitch force. However, maximal twitch tension at high [Ca(2+)]o or in post-rest potentiated beats was unaffected, although contraction kinetics were slower. The ryanodine receptor (RyR)2 Ca-sensitizing agent caffeine (200 µM), which increases the velocity of transverse Ca(2+) release propagation in detubulated cardiomyocytes, rescued the depressed contractile force and the slower twitch kinetics of detubulated trabeculae, with negligible effects in controls. We conclude that partial loss of t-tubules leads to myocardial contractile abnormalities that can be rescued by enhancing and accelerating the propagation of Ca(2+)-induced Ca(2+) release to orphan RyR2 clusters.