Reversal of motor-skill transfer impairment by trihexyphenidyl and reduction of dorsolateral striatal cholinergic interneurons in Dyt1 ΔGAG knock-in mice.

DYT-TOR1A or DYT1 early-onset generalized dystonia is an inherited movement disorder characterized by sustained muscle contractions causing twisting, repetitive movements, or abnormal postures. The majority of the DYT1 dystonia patients have a trinucleotide GAG deletion in DYT1/TOR1A. Trihexyphenidyl (THP), an antagonist for excitatory muscarinic acetylcholine receptor M1, is commonly used to treat dystonia. Dyt1 heterozygous ΔGAG knock-in (KI) mice, which have the corresponding mutation, exhibit impaired motor-skill transfer. Here, the effect of THP injection during the treadmill training period on the motor-skill transfer to the accelerated rotarod performance was examined. THP treatment reversed the motor-skill transfer impairment in Dyt1 KI mice. Immunohistochemistry showed that Dyt1 KI mice had a significant reduction of the dorsolateral striatal cholinergic interneurons. In contrast, Western blot analysis showed no significant alteration in the expression levels of the striatal enzymes and transporters involved in the acetylcholine metabolism. The results suggest a functional alteration of the cholinergic system underlying the impairment of motor-skill transfer and the pathogenesis of DYT1 dystonia. Training with THP in a motor task may improve another motor skill performance in DYT1 dystonia.

Attended vs unattended systolic blood pressure measurement: A randomized comparison in patients with cardiovascular disease.

Recent clinical guidelines recommend lower blood pressure (BP) goals for most patients, and recent trends have favored use of automated unattended BP measurements in the office setting to minimize observer error and white-coat effects. Patients attending a routinely scheduled CVD clinic visit were prospectively randomized to BP measured using an attended, followed by an unattended method, or vice versa, after a controlled rest period. All study BP measurements were obtained in triplicate using the automated Omron HEM-907XL BP monitor, and averaged. The outcome was difference in SBP. Routinely measured clinic BP from the same visit was extracted from the medical record, and compared with attended and unattended BP. A total of 102 patients were randomized, and mean age was 63 years, 52% female and 75% Caucasian. Attended and unattended SBP was 125.4 ± 20.4 and 122.6 ± 21.0 mm Hg, mean ± SD, respectively. Routine clinic SBP was 130.6 ± 23.6 mm Hg. Attended SBP was 2.7 mm Hg higher than the unattended measurement (95% CI 1.3-4.1; P = .0002). Routine clinic SBP was 5.2 mm Hg higher than attended SBP (95% CI 2.4-8.0; P = .0003) and 8.0 mm Hg higher than unattended SBP (95% CI 5.4-10.5; P < .0001). Attended measurement of BP is significantly higher than unattended measurement and the difference is physiologically meaningful, even in a CVD cohort with generally well-controlled hypertension. Furthermore, routine clinic SBP substantially overestimates both attended and unattended automated SBP, with important implications for treatment decisions like dose and/or drug escalation.

Decreased number of striatal cholinergic interneurons and motor deficits in dopamine receptor 2-expressing-cell-specific Dyt1 conditional knockout mice.

DYT1 early-onset generalized torsion dystonia is a hereditary movement disorder characterized by abnormal postures and repeated movements. It is caused mainly by a heterozygous trinucleotide deletion in DYT1/TOR1A, coding for torsinA. The mutation may lead to a partial loss of torsinA function. Functional alterations of the basal ganglia circuits have been implicated in this disease. Striatal dopamine receptor 2 (D2R) levels are significantly decreased in DYT1 dystonia patients and in the animal models of DYT1 dystonia. D2R-expressing cells, such as the medium spiny neurons in the indirect pathway, striatal cholinergic interneurons, and dopaminergic neurons in the basal ganglia circuits, contribute to motor performance. However, the function of torsinA in these neurons and its contribution to the motor symptoms is not clear. Here, D2R-expressing-cell-specific Dyt1 conditional knockout (d2KO) mice were generated and in vivo effects of torsinA loss in the corresponding cells were examined. The Dyt1 d2KO mice showed significant reductions of striatal torsinA, acetylcholine metabolic enzymes, Tropomyosin receptor kinase A (TrkA), and cholinergic interneurons. The Dyt1 d2KO mice also showed significant reductions of striatal D2R dimers and tyrosine hydroxylase without significant alteration in striatal monoamine contents or the number of dopaminergic neurons in the substantia nigra. The Dyt1 d2KO male mice showed motor deficits in the accelerated rotarod and beam-walking tests without overt dystonic symptoms. Moreover, the Dyt1 d2KO male mice showed significant correlations between striatal monoamines and locomotion. The results suggest that torsinA in the D2R-expressing cells play a critical role in the development or survival of the striatal cholinergic interneurons, expression of striatal D2R mature form, and motor performance. Medical interventions to compensate for the loss of torsinA function in these neurons may affect the onset and symptoms of this disease.

Short rest interval lengths between sets optimally enhance body composition and performance with 8 weeks of strength resistance training in older men.

PURPOSE: To determine if 8 weeks of periodized strength resistance training (RT) utilizing relatively short rest interval lengths (RI) in between sets (SS) would induce greater improvements in body composition and muscular performance, compared to the same RT program utilizing extended RI (SL). METHODS: 22 male volunteers (SS: n = 11, 65.6 ± 3.4 years; SL: n = 11, 70.3 ± 4.9 years) were assigned to one of two strength RT groups, following 4 weeks of periodized hypertrophic RT (PHRT): strength RT with 60-s RI (SS) or strength RT with 4-min RI (SL). Prior to randomization, all 22 study participants trained 3 days/week, for 4 weeks, targeting hypertrophy; from week 4 to week 12, SS and SL followed the same periodized strength RT program for 8 weeks, with RI the only difference in their RT prescription. RESULTS: Following PHRT, all study participants experienced increases in lean body mass (LBM) (p < 0.01), upper and lower body strength (p < 0.001), and dynamic power (p < 0.001), as well as decreases in percentage body fat (p < 0.05). Across the 8-week strength RT phase, SS experienced significantly greater increases in LBM (p = 0.001), flat machine bench press 1-RM (p < 0.001), bilateral leg press 1-RM (p < 0.001), narrow/neutral grip lat pulldown (p < 0.01), and Margaria stair-climbing power (p < 0.001), compared to SL. CONCLUSIONS: This study suggests 8 weeks of periodized high-intensity strength RT with shortened RI induces significantly greater enhancements in body composition, muscular performance, and functional performance, compared to the same RT prescription with extended RI, in older men. Applied professionals may optimize certain RT-induced adaptations, by incorporating shortened RI.

Periodized resistance training with and without supplementation improve body composition and performance in older men.

PURPOSE: To examine the effects of 12 weeks of periodized resistance training (RT) with and without combined creatine and whey protein supplementation on changes in body composition, muscular strength, and functional performance. METHODS: Twenty-two male volunteers (68.1 ± 6.1 years) were randomly assigned to one of three groups: RT plus supplementation (RTS, n = 7); RT only (RT, n = 7); or control (C, n = 8). RTS consumed 0.3 g/kg/day of creatine for 5 days followed by 0.07 g/kg/day. RTS also consumed one 35 g liquid protein ready-to-drink daily. RT and RTS trained 3 days/week. RESULTS: Following 12 weeks of training, there were no significant differences in the main measured outcome variables between RT and RTS. RTS increased relative (% change) lean body mass (LBM, 3.3 ± 3.1 %) compared with C (p = 0.01). Compared to baseline, RT increased LBM at week 6 (60.2 ± 8.3 to 61.6 ± 9.4 kg; p < 0.05), and decreased fat mass (20.8 ± 4.2 to 19.0 ± 3.9 kg; p = 0.05) and percentage body fat at week 12 (25.7 ± 3.8 to 23.8 ± 4.0 %; p = 0.05); RTS increased LBM at week 6 (p < 0.01) and week 12 (56.4 ± 4.3 to 58.2 ± 3.4 kg; p < 0.01), and decreased percentage body fat at week 12 (23.9 ± 4.4 to 22.0 ± 4.4 %; p < 0.01). In addition, compared to C, relative bench press 1-RM increased for RTS (72.4 ± 62.2 %; p < 0.01) and RT (50.1 ± 21.5 %; p = 0.05); relative leg press 1-RM increased for RTS (129.6 ± 39.4 %; p < 0.0001) and RT (112.9 ± 22.7 %; p < 0.0001); RTS increased relative Margaria stair-climbing power (38.3 ± 30.4 %; p < 0.05); and, relative 400-m walk time decreased for RT (-11 ± 9.2 %; p < 0.05) and RTS (-9.6 ± 9.4 %; p = 0.05). RT increased estimated VO2Max at week 6 (p < 0.01) and 12 (34.6 ± 1.9 to 36.4 ± 2.7 ml/kg/min; p = 0.01) compared to baseline. Lastly, RTS increased estimated VO2Max at week 12 (36.3 ± 2.7 to 37.5 ± 3.3 ml/kg/min; p = 0.05) compared to baseline. CONCLUSION: Creatine and whey protein supplementation may not provide additional benefits in older adults performing periodized RT to augment muscular and functional performance.

Influence of rest interval length on acute testosterone and cortisol responses to volume-load-equated total body hypertrophic and strength protocols.

We hypothesized that total body strength (S) and hypertrophic (H) resistance training (RT) protocols using relatively short rest interval (RI) lengths between sets will elicit significant acute increases in total testosterone (TT) and cortisol (C) in healthy young men. Six men, 26 (±2.4) years, completed 4 randomized RT sessions, after a control session (R). The S and H protocols were equated for volume load (sets × repetitions × load); S: 8 sets × 3 repetitions at 85% 1RM, H: 3 sets × 10 repetitions at 70% 1RM, for all exercises. The RI used 60 seconds (S60, H60) and 90 seconds (S90, H90). Blood was drawn preexercise (PRE), immediately postexercise (POST), 15 minutes postexercise (15 MIN), and 30 minutes postexercise (30 MIN). The H60 elicited significant increases in TT from PRE (7.32 ± 1.85 ng·ml) to POST (8.87 ± 1.83 ng·ml(-1)) (p < 0.01), 15 MIN (8.58 ± 2.15 ng·ml(-1)) (p < 0.01), and 30 MIN (8.28 ± 2.16 ng·ml(-1)) (p < 0.05). The H90 also elicited significant increases in TT from PRE (8.37 ± 1.93 ng·ml(-1)) to POST (9.90 ± 1.25 ng·ml(-1)) (p < 0.01) and 15 MIN (9.46 ± 1.27 ng·ml(-1)) (p < 0.05). The S60 elicited significant increases in TT from PRE (7.73 ± 1.88 ng·ml(-1)) to 15 MIN (8.35 ± 1.64 ng·ml(-1)) (p < 0.05), and S90 showed a notable (p < 0.10) difference in TT from PRE (7.96 ± 2.29 ng·ml(-1)) to POST (8.75 ± 2.45 ng·ml(-1)). All the protocols did not significantly increase C (p > 0.05). Using relatively short RI between RT sets augments the acute TT response to hypertrophic and strength schemes. Shortening RI within high-intensity strength RT may lead to concomitant enhancements in muscle strength and size over a longer period of training.