BACKGROUND Genetic analysis has been successful in identifying causative mutations for individual cardiovascular risk factors. Success has been more limited in mapping susceptibility genes for clusters of cardiovascular risk traits, such as those in the metabolic syndrome. METHODS We identified three large families with coinheritance of early-onset coronary artery disease, central obesity, hypertension, and diabetes. We used linkage analysis and whole-exome sequencing to identify the disease-causing gene. RESULTS A founder mutation was identified in DYRK1B, substituting cysteine for arginine at position 102 in the highly conserved kinase-like domain. The mutation precisely cosegregated with the clinical syndrome in all the affected family members and was absent in unaffected family members and unrelated controls. Functional characterization of the disease gene revealed that nonmutant protein encoded by DYRK1B inhibits the SHH (sonic hedgehog) and Wnt signaling pathways and consequently enhances adipogenesis. Furthermore, DYRK1B promoted the expression of the key gluconeogenic enzyme glucose-6-phosphatase. The R102C allele showed gain-offunction activities by potentiating these effects. A second mutation, substituting proline for histidine 90, was found to cosegregate with a similar clinical syndrome in an ethnically distinct family. CONCLUSIONS These findings indicate a role for DYRK1B in adipogenesis and glucose homeostasis and associate its altered function with an inherited form of the metabolic syndrome. (Funded by the National Institutes of Health.)

Hypertension is the major risk factor for cardiovascular diseases and is one of the primary causes of morbidity and mortality worldwide. Apelin levels and NO bioavailability are impaired in older hypertensive patients. Exercise is an effective intervention for treating hypertension. Our purpose was to evaluate the effect of high-intensity interval training on blood pressure, apelin, and NOx plasma levels in older treated hypertensive individuals. Thirty treated hypertensive subjects (61.70 ± 5.78 years, 17 males, 13 females) were randomly divided into 6 weeks of high-intensity interval training (n = 15) and control (n = 15). The exercise training was conducted for three 35-min sessions a week (1.5-min interval at 85-90% of heart rate reserve [HRR] and 2 min active phase at 50-55% of HRR). Assessment of plasma apelin, nitrite/nitrate (NOx), and endothelin-1 (ET-1) was performed before and after the intervention. At the end of the study, apelin, and NOx plasma levels increased significantly in the high-intensity interval training (HIIT) group (P = 0.021, P = 0.003, respectively). Conversely, ET-1 plasma levels significantly decreased in the training group after the intervention (P = 0.015). Moreover, there was a positive correlation between the change of plasma apelin and change of plasma NOx (r = 0. 771, P = 0.0008). In addition, there was a negative correlation between the change of plasma ET-1, change of plasma apelin (r = - 0.595, P = 0.019), and variation of NOx (r = - 0.572, P = 0.025). This study indicates that, by increasing of apelin and NOx plasma levels, HIIT may be effective in reducing blood pressure.

To the best of our knowledge, there is no published report regarding electrocardiographic diagnosis and screening of AAS abusing athletes. In the present study, we present an easy and applicable method to screen and diagnose AAS abusing among professional bodybuilders. In the presence of QTc interval < or = 380 ms in a bodybuilder, one would predict AAS abusing with 83% sensitivity and 88% specificity.

Objectives:The aim of this study was to investigate the effects of 8-week endurance and resistance exercise training on release of brain natriuretic peptide.Materials and Methods:Study population was categorized into 4 groups: Group-1 (n = 6) consisted of sedentary individuals who volunteered to complete 8-weeks of endurance exercise; Group-2 (n=6) consisted of sedentary individuals who volunteered to complete 8-weaks of resistance exercise. Three blood samples [for Terminal pro BNP (NT-Pro-BNP)] were taken before, immediately after exercise and after 8 weeks of exercise training.Results:NT-Pro BNP was significantly increased immediately after endurance exercise [from 37.9 ± 1.4 pg/ml to 52.1 ±1.5 pg/ml; P = 0.002] and was decreased to 23.2 ± 9.3 pg/ml after 8 weeks of endurance exercise [P = 0.013]. On the other hand, NT-Pro BNP showed no significant changes immediately after resistance exercise [from 26.6 ± 4.9 pg/ml to 24.1 ±4.5 pg/ml; P = 0.553]. In contrast, NT-Pro BNP was significantly increased to 39.5 ±1.6 pg/ml after 8 weeks of resistance exercise [P = 0.012].Conclusion:Endurance exercise training reduces circulating NT-Pro BNP concentration, which is likely a marker of reduced ventricular wall tension and improved myocardial function. In contrast, strength exercise induces significant increase in NT-Pro BNP, which could be partially attributed to myocardial damage.

The present study demonstrates that chronic cocaine abuse clearly produces significant decrease in the elastic properties of aorta. This effect of cocaine is related to the duration of cocaine abuse.