An advanced glycation endproduct (AGE)-rich diet promotes accumulation of AGEs in Achilles tendon

Advanced Glycation Endproducts (AGEs) accumulate in long‐lived tissue proteins like collagen in bone and tendon causing modification of the biomechanical properties. This has been hypothesized to raise the risk of orthopedic injury such as bone fractures and tendon ruptures. We evaluated the relationship between AGE content in the diet and accumulation of AGEs in weight‐bearing animal Achilles tendon. Two groups of mice (C57BL/6Ntac) were fed with either high‐fat diet low in AGEs high‐fat diet (HFD) (n = 14) or normal diet high in AGEs (ND) (n = 11). AGE content in ND was six to 50‐fold higher than HFD. The mice were sacrificed at week 40 and Achilles and tail tendons were carefully excised to compare weight and nonweight‐bearing tendons. The amount of the AGEs carboxymethyllysine (CML), methylglyoxal‐derived hydroimidazolone (MG‐H1) and carboxyethyllysine (CEL) in Achilles and tail tendon was measured using ultraperformance liquid chromatography tandem mass spectrometry (UPLC‐MS/MS) and pentosidine with high‐pressure liquid chromatography (HPLC) with fluorescent detection. AGEs in Achilles tendon were higher than in tail tendon for CML (P < 0.0001), CEL (P < 0.0001), MG‐H1 and pentosidine (for both ND and HFD) (P < 0.0001). The AGE‐rich diet (ND) resulted in an increase in CML (P < 0.0001), MG‐H1 (P < 0.001) and pentosidine (P < 0.0001) but not CEL, in Achilles and tail tendon. This is the first study to provide evidence for AGE accumulation in injury‐prone, weight‐bearing Achilles tendon associated with intake of an AGE‐rich diet. This indicates that food‐derived AGEs may alter tendon properties and the development of tendon injuries

The effects of high frequency subthalamic stimulation on balance performance and fear of falling in patients with Parkinson's disease

<p>Abstract</p> <p>Background</p> <p>Balance impairment is one of the most distressing symptoms in Parkinson's disease (PD) even with pharmacological treatment (levodopa). A complementary treatment is high frequency stimulation in the subthalamic nucleus (STN). Whether STN stimulation improves postural control is under debate. The aim of this study was to explore the effects of STN stimulation alone on balance performance as assessed with clinical performance tests, subjective ratings of fear of falling and posturography.</p> <p>Methods</p> <p>Ten patients (median age 66, range 59–69 years) with bilateral STN stimulation for a minimum of one year, had their anti-PD medications withdrawn overnight. Assessments were done both with the STN stimulation turned OFF and ON (start randomized). In both test conditions, the following were assessed: motor symptoms (descriptive purposes), clinical performance tests, fear of falling ratings, and posturography with and without vibratory proprioceptive disturbance.</p> <p>Results</p> <p>STN stimulation alone significantly (p = 0.002) increased the scores of the Berg balance scale, and the median increase was 6 points. The results of all timed performance tests, except for sharpened Romberg, were significantly (p ≤ 0.016) improved. The patients rated their fear of falling as less severe, and the total score of the Falls-Efficacy Scale(S) increased (p = 0.002) in median with 54 points. All patients completed posturography when the STN stimulation was turned ON, but three patients were unable to do so when it was turned OFF. The seven patients with complete data showed no statistical significant difference (p values ≥ 0.109) in torque variance values when comparing the two test situations. This applied both during quiet stance and during the periods with vibratory stimulation, and it was irrespective of visual input and sway direction.</p> <p>Conclusion</p> <p>In this sample, STN stimulation alone significantly improved the results of the clinical performance tests that mimic activities in daily living. This improvement was further supported by the patients' ratings of fear of falling, which were less severe with the STN stimulation turned ON. Posturography could not be performed by three out of the ten patients when the stimulation was turned OFF. The posturography results of the seven patients with complete data showed no significant differences due to STN stimulation.</p

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to similar to 370,000 women, we identify 389 independent signals (P <5 x 10(-8)) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain similar to 7.4% of the population variance in age at menarche, corresponding to similar to 25% of the estimated heritability. We implicate similar to 250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility

Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project–imputed genotype data in up to ~370,000 women, we identify 389 independent signals (P < 5 × 10$^{−8}$) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ~7.4% of the population variance in age at menarche, corresponding to ~25% of the estimated heritability. We implicate ~250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility

Altered Triceps Surae Muscle-Tendon Unit Properties after 6 Months of Static Stretching

Introduction: This study examined the effects of 24 wk of daily static stretching of the plantarflexors (unilateral 4 × 60-s stretching, whereas the contralateral leg served as a control; n = 26) on joint range of motion (ROM), muscle–tendon unit morphological and mechanical properties, neural activation, and contractile function. Methods: Torque–angle/velocity was obtained in passive and active conditions using isokinetic dynamometry, whereas muscle–tendon morphology and mechanical properties were examined using ultrasonography. Results: After the intervention, ROM increased (stretching, +11° ± 7°; control, 4° ± 8°), and passive torque (stretching, −10 ± 11 N·m; control, −7 ± 10 N·m) and normalized EMG amplitude (stretching, −3% ± 6%; control, −3% ± 4%) at a standardized dorsiflexion angle decreased. Increases were seen in passive tendon elongation at a standardized force (stretching, +1.3 ± 1.6 mm; control, +1.4 ± 2.1 mm) and in maximal passive muscle and tendon elongation. Angle of peak torque shifted toward dorsiflexion. No changes were seen in tendon stiffness, resting tendon length, or gastrocnemius medialis fascicle length. Conformable changes in ROM, passive dorsiflexion variables, tendon elongation, and angle of peak torque were observed in the nonstretched leg. Conclusions: The present findings indicate that habitual stretching increases ROM and decreases passive torque, altering muscle–tendon behavior with the potential to modify contractile function