Background and Objectives: Recent studies have shown the existence of a positive relationship between physical exercise, symptomatic improvement, and reduction of damage caused by comorbidities associated with autistic spectrum disorder (ASD) in children, adolescents, and adults. The aim of this systematic review with meta-analysis (SRM) was to estimate the effects of physical exercise (PE) on the stereotyped behaviors of children with a diagnosis of ASD in intervention studies. Materials and Methods: The design followed the PRISMA guidelines and the TREND statement to assess the quality of information in each study. Nine non-randomized intervention trial studies with low, moderate, and vigorous physical exercise, with a duration varying from 8 to 48 weeks and a frequency of 3 times a week, were included in the SRM. The dependent variable episodes of stereotypical behaviors was analyzed in all studies and assessed as the number of episodes demonstrated by the child in pre- versus post-exercise intervention conditions. Results: The eight studies included a total 129 children (115 males and 14 females) with an average age of 8.93 ± 1.69 years. Children with ASD showed a reduction of 1.1 in the number of occurrences of stereotypical behaviors after intervention with physical exercise. Conclusion: Evidence was found to support physical exercise as an effective tool in reducing the number of episodes of stereotypical behaviors in children diagnosed with ASD.

Increased arterial stiffness and vascular remodeling precede and are consequences of hypertension. They also contribute to the development and progression of life-threatening cardiovascular diseases. Yet, there are currently no agents specifically aimed at preventing or treating arterial stiffening and remodeling. Previous research indicates that vascular smooth muscle actin polymerization participates in the initial stages of arterial stiffening and remodeling and that LIMK (LIM kinase) promotes F-actin formation and stabilization via cofilin phosphorylation and consequent inactivation. Herein, we hypothesize that LIMK inhibition is able to prevent vasoconstriction- and hypertension-associated arterial stiffening and inward remodeling. We found that small visceral arteries isolated from hypertensive subjects are stiffer and have greater cofilin phosphorylation than those from nonhypertensives. We also show that LIMK inhibition prevents arterial stiffening and inward remodeling in isolated human small visceral arteries exposed to prolonged vasoconstriction. Using cultured vascular smooth muscle cells, we determined that LIMK inhibition prevents vasoconstrictor agonists from increasing cofilin phosphorylation, F-actin volume, and cell cortex stiffness. We further show that localized LIMK inhibition prevents arteriolar inward remodeling in hypertensive mice. This indicates that hypertension is associated with increased vascular smooth muscle cofilin phosphorylation, cytoskeletal stress fiber formation, and heightened arterial stiffness. Our data further suggest that pharmacological inhibition of LIMK prevents vasoconstriction-induced arterial stiffening, in part, via reductions in vascular smooth muscle F-actin content and cellular stiffness. Accordingly, LIMK inhibition should represent a promising therapeutic means to stop the progression of arterial stiffening and remodeling in hypertension.

To our knowledge, this is the first study to investigate the involvement of ADAM17 in causing impaired insulin-induced vasodilation in T2D. We provide evidence that ADAM17 activity is increased in the vasculature of patients with T2D and support the notion that ADAM17-mediated shedding of endothelial IRα ectodomains is a novel mechanism causing vascular insulin resistance. Our results highlight that targeting ADAM17 activity may be a potential therapeutic strategy to correct vascular insulin resistance in T2D.

We have previously demonstrated that different modalities of endurance exercise combined with lower muscle glycogen content elicit several physiological and molecular benefits in men. In this study, we hypothesized that these exercise strategies modulate monocarboxylate transporters (MCTs) and plasma lactate. We investigated MCT1 and MCT4 gene expression after two forms of exercise (i.e., once daily and twice-a-day) under low carbohydrate (CHO) availability (Acute - Study 1) and whether three weeks under once daily or twice-a-day training differentially affected plasma lactate during exercise (Chronic - Study 2). In Study 1, five participants performed a high-intensity interval exercise (HIIE) 2 h (twice-a-day) or 15 h (once daily) after exercise and diet manipulations to reduce endogenous CHO stores or without previous CHO manipulation (Control). Muscle biopsies were collected before, right after, and 3 h after HIIE. In Study 2, plasma lactate was measured during a graded exercise test before and after three weeks of once-daily (n=7) or twice-a-day training (n=7). MCT1 gene expression increased from before to after and 3-h post-HIIE only in the twice-a-day exercise (P0.05). The plasma lactate curve shifted to the right in both training approaches, without differences in lactate slope reduction between once-daily (-0.49±0.58 mmol·L-1·min-1) and twice-a-day (-0.46±0.73 mmol·L-1·min-1) exercise. In conclusion, twice-a-day training increased acute MCT1 gene expression but did not result in chronic changes in plasma lactate response during exercise.

Vascular insulin resistance is a hallmark of type 2 diabetes (T2D) and blunting of insulin‐induced dilation is its primary manifestation. Importantly, in T2D, reduced insulin‐induced dilation and blood flow to skeletal muscle significantly limits glucose uptake and contributes to impaired glucose control. However, the mechanisms underlying vascular insulin resistance in T2D remain largely unknown. Adropin is a peptide primarily secreted by the liver and brain, recently shown to regulate energy homeostasis as well as to promote systemic insulin sensitivity. Notably, circulating levels of adropin are decreased in T2D, which may contribute to impairments in vascular insulin signaling. Herein we tested the hypothesis that arterial exposure to adropin improves vascular insulin sensitivity, particularly in T2D. To test this hypothesis, femoral arteries from ~12‐week old db/db (n=5) and genetic control (db ^+/− , n=5) male mice were incubated with adropin (50 ng/mL) or vehicle for 24 hours and vasomotor responses to acetylcholine, insulin, and sodium nitroprusside (SNP) assessed thereafter via pressure myography. Consistent with our hypothesis, we show that treatment of femoral arteries from db/db mice with adropin improves insulin‐induced dilation ( P 0.05). Adropin exposure did not alter acetylcholine and SNP‐induced dilation of femoral arteries in either db/db or db ^+/− mice ( P >0.05). These findings support the notion that adropin deficiency may contribute to vascular insulin resistance in T2D.