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The objective of this study is to test the hypothesis that increased muscle mass has positive effects on cardiovascular function. Specifically, we tested the hypothesis that increases in lean body mass caused by deletion of myostatin improves cardiac performance and vascular function. Echocardiography was used to quantify left ventricular function at baseline and after acute administration of propranolol and isoproterenol to assess β-adrenergic reactivity. Additionally, resistance vessels in several beds were removed, cannulated, pressurized to 60 mmHg and reactivity to vasoactive stimuli was assessed. Hemodynamics were measured using in vivo radiotelemetry. Myostatin deletion results in increased fractional shortening at baseline. Additionally, arterioles in the coronary and muscular microcirculations are more sensitive to endothelial-dependent dilation while nonmuscular beds or the aorta were unaffected. β-adrenergic dilation was increased in both coronary and conduit arteries, suggesting a systemic effect of increased muscle mass on vascular function. Overall hemodynamics and physical characteristics (heart weight and size) remained unchanged. Myostatin deletion mimics in part the effects of exercise on cardiovascular function. It significantly increases lean muscle mass and results in muscle-specific increases in endothelium-dependent vasodilation. This suggests that increases in muscle mass may serve as a buffer against pathological states that specifically target cardiac function (heart failure), the β-adrenergic system (age), and nitric oxide bio-availability (atherosclerosis). Taken together, pharmacological inhibition of the myostatin pathway could prove an excellent mechanism by which the benefits of exercise can be conferred in patients that are unable to exercise. [ABSTRACT FROM AUTHOR]

American football has unequivocally been linked to elevations in blood pressure and hypertension, especially in linemen. However, the mechanisms of this increase cannot be attributed solely to increased body weight and associated cardiometabolic risk factors (e.g.,dyslipidemia or hyperglycemia). Therefore, understanding the etiology of football-associated hypertension is essential for improving the quality of life in this mostly young population, as well as for lowering the potential for chronic disease in the future. We propose that inflammatogenic damage-associated molecular patterns (DAMPs) released into the circulation from football-induced musculoskeletal trauma activate pattern-recognition receptors of the innate immune system--specifically, high mobility group box 1 protein (HMGB1) and mitochondrial (mt)DNA which activate Toll-like receptor (TLR)4 and -9, respectively. Previously, we observed that circulating levels of these 2 DAMPs are increased in hypertension, and activation of TLR4 and -9 causes endothelial dysfunction and hypertension. Therefore, our novel hypothesis is that musculoskeletal injury from repeated hits in football players, particularly in linemen, leads to elevated circulating HMGB1 and mtDNA to activate TLRs on endothelial cells leading to impaired endothelium-dependent vasodilation, increased vascular tone, and hypertension.--McCarthy, C. G., Webb, R. C. The toll of the gridiron: damage-associated molecular patterns and hypertension in American football. [ABSTRACT FROM AUTHOR]

R1537 --> Overconsumption of dietary salt is unequivocally linked to end organ damage. We have recently observed that a high salt (HS) diet induces liver dysfunction in the form of impaired synthesis of ketone body, β‐hydroxybutyrate (βHB), in Dahl salt‐resistant (R) and salt‐sensitive (S) rats, and therefore, independent of high blood pressure. However, the molecular mechanisms as to why βHB is decreased after consuming a HS diet remains unknown. Evolutionarily, βHB is an energy source during times of nutrient scarcity. Therefore, we hypothesized that a HS diet decreases energy sensing and autophagy induction. To test this hypothesis, we treated low salt (LS)‐fed S and R rats, with the 5' adenosine monophosphate‐activated protein kinase (AMPK) and autophagy inhibitor dorsomorphin hydrochloride (DH; 25mg/kg), prior to a 24 h fast. As hypothesized, fasting increased serum βHB, and treatment with DH blocked this increase in R (mmol/L, non‐fasting: 0.38±0.05 vs. fasting: 1.11±0.09 * vs. fasting+DH 0.42±0.05, *p<0.05) and S (mmol/L, non‐fasting: 0.38±0.04 vs. fasting: 1.01±0.18* vs. fasting+DH: 0.47±0.09, *p<0.05). To test whether a HS diet was interfering with AMPK signaling, we took liver biopsies from R and S rats that had been on LS and HS diets for 8 weeks and probed for the protein expression of phospho‐AMPKThr172 after a 24 h fast. In R rats fed a LS diet, as expected, fasting induced a significant increase in phospho‐AMPKThr172 expression (Fig. 1A). However, Dahl R rats that had been on a high salt diet, fasting did not increase phospho‐AMPKThr172 (Fig. 1A). In LS‐fed S rats, we unexpectedly observed a basal downregulation of phospho‐AMPKThr172 expression that was further exacerbated by a 24 h fast (Fig. 1B). However, in support of our results in HS‐fed R rats, there was no difference in phospho‐AMPKThr172 expression between non‐fasting and fasting HS‐fed S rats (Fig. 1B). In addition to being an energy source, βHB can also serve as a signaling molecule, primarily through activation and inhibition of the G‐protein coupled receptors Gpr109a and Gpr41, respectively. Surprisingly, vasodilation to βHB was not different in mesenteric resistance arteries from Gpr109a and Gpr41 KO mice (data not shown). However, when mesenteric resistance arteries were incubated with Gpr43 inhibitor, GLPG 0974 (10 uM), vasodilation was prevented in both R [Emax(%), 48.6±1.7 vs. 26.4±1.1*, *p<0.05] and S [Emax(%), 43.2±3.5 vs. 22.6±1.8*, *p<0.05] rats relative to vehicle control. In summary, these data reveal that a HS diet impairs energy sensing and autophagy induction to reduce the synthesis of βHB. Furthermore, βHB partially exerts its vasodilatory effects through non‐canonical Gpr43. [ABSTRACT FROM AUTHOR]

Examines different theoretical and methodological approaches to youth and violence. Existence of a schism between theory and practice in contemporary critical scholarship in education; Multiple ways in which young people experience violence; Factors that have undermined schools' capacity to address the needs of contemporary youth.

Proposes a critical appraisal of main assumptions and goals of current multicultural discourses on curriculum reform in the area of race relations. Drawing from the work of Robert Connell and Paulo Freire; Critical multiculturalism; Multicultural curriculum discourses; Democratic initiatives in curriculum and pedagogical practices.