The influence of 6 weeks of maximal eccentric plantarflexor training on muscle-tendon mechanics

Resistance training can influence muscle-tendon properties including strength, flexibility, stretch tolerance and muscle-tendon stiffness; however the specific influence of eccentric-only training is unknown. Therefore, the aims of the present study were to examine the effects of a 6-week maximal eccentric resistance training programme on isometric plantarflexor moment (MVC), dorsiflexion range of motion (ROM), stretch tolerance (peak passive moment), muscle and tendon stiffness and running economy. Thirteen recreationally active men (age = 20.0 ± 0.9 yr, mass = 75.9 ± 8.5 kg, height = 1.8 ± 0.1 m) volunteered for the study after giving written informed consent; ethical approval was granted from the University of Northampton. Training was performed twice weekly for six weeks and consisted of 5 sets of 12 repetitions of 3-s maximal eccentric contractions at 10°•s-1 from 20° plantarflexion to 10° dorsiflexion. Maximal isometric plantarflexor moment, dorsiflexion ROM, stretch tolerance, and muscle, tendon and muscle-tendon unit (MTU) stiffness were measured using isokinetic dynamometry, real-time ultrasound and 3D motion analyses before and after the training. Running economy (VO2) was determined at a running speed equating to 70%VO2max using online gas analysis. Repeated measures t-tests were used to determine significant differences between pre- and post-training data, significance accepted at p0.05). Analysis of ultrasound data revealed a significant decrease in muscle stiffness (20.6%; p0.05). While the training-induced increase in plantarflexor strength was expected, the substantial increases in ROM, stretch tolerance and tendon stiffness, and the reduction in passive muscle stiffness, were important and novel findings. Interestingly, when measured during passive stretch, MTU stiffness remained unchanged while tendon stiffness increased and muscle stiffness decreased. These disparate findings have clear implications for testing methodologies, and indicate that imaging techniques must be utilised in order to examine the effects of interventions on specific tissues. As the training clearly enhanced the capacity of the muscle to tolerate both tissue loading and deformation, which are commonly associated with muscle strain injury, these data have clear implications for both muscular performance and injury risk

The Role of FRMD7 in Idiopathic Infantile Nystagmus

Idiopathic infantile nystagmus (IIN) is an inherited disorder in which the nystagmus arises independently of any other symptoms, leading to the speculation that the disorder represents a primary defect in the area of the brain responsible for ocular motor control. The inheritance patterns are heterogeneous, however the most common form is X-linked. FRMD7 resides at Xq26-27 and approximately 50% of X-linked IIN families map to this region. Currently 45 mutations within FRMD7 have been associated with IIN, confirming the importance of FRMD7 in the pathogenesis of the disease. Although mutations in FRMD7 are known to cause IIN, very little is known about the function of the protein. FRMD7 contains a conserved N-terminal FERM domain suggesting that it may provide a link between the plasma membrane and actin cytoskeleton. Limited studies together with the knowledge of the function of other FERM domain containing proteins, suggest that FRMD7 may play a role in membrane extension during neuronal development through remodeling of the actin cytoskeleton

Stretching of active muscle elicits chronic changes in multiple strain risk factors

Introduction: The muscle stretch intensity imposed during 'flexibility' training influences the magnitude of joint range of motion (ROM) adaptation. Thus, stretching whilst the muscle is voluntarily activated was hypothesized to provide a greater stimulus than passive stretching. The effect of a 6-week program of stretch imposed on an isometrically-contracting muscle (i.e. qualitatively similar to isokinetic eccentric training) on muscle-tendon mechanics was therefore studied in 13 healthy human volunteers. Methods: Before and after the training program, dorsiflexion ROM, passive joint moment, and maximal isometric plantar flexor moment were recorded on an isokinetic dynamometer. Simultaneous real-time motion analysis and ultrasound imaging recorded gastrocnemius medialis muscle and Achilles tendon elongation. Training was performed twice weekly and consisted of five sets of 12 maximal isokinetic eccentric contractions at 10[degrees][middle dot]s-1. Results: Significant increases (P0.05), a significant increase in tendon stiffness (31.2%; P<0.01) and decrease in passive muscle stiffness (-14.6%; P<0.05) was observed. Conclusion: The substantial positive adaptation in multiple functional and physiological variables that are cited within the primary aetiology of muscle strain injury, including strength, ROM, muscle stiffness, and maximal energy storage, indicate that the stretching of active muscle might influence injury risk in addition to muscle function. The lack of change in muscle-tendon stiffness simultaneous with significant increases in tendon stiffness and decreases in passive muscle stiffness indicates that tissue-specific effects were elicited

Rasch analysis of the hospital anxiety and depression scale (hads) for use in motor neurone disease

<p>Abstract</p> <p>Background</p> <p>The Hospital Anxiety and Depression Scale (HADS) is commonly used to assess symptoms of anxiety and depression in motor neurone disease (MND). The measure has never been specifically validated for use within this population, despite questions raised about the scale's validity. This study seeks to analyse the construct validity of the HADS in MND by fitting its data to the Rasch model.</p> <p>Methods</p> <p>The scale was administered to 298 patients with MND. Scale assessment included model fit, differential item functioning (DIF), unidimensionality, local dependency and category threshold analysis.</p> <p>Results</p> <p>Rasch analyses were carried out on the HADS total score as well as depression and anxiety subscales (HADS-T, D and A respectively). After removing one item from both of the seven item scales, it was possible to produce modified HADS-A and HADS-D scales which fit the Rasch model. An 11-item higher-order HADS-T total scale was found to fit the Rasch model following the removal of one further item.</p> <p>Conclusion</p> <p>Our results suggest that a modified HADS-A and HADS-D are unidimensional, free of DIF and have good fit to the Rasch model in this population. As such they are suitable for use in MND clinics or research. The use of the modified HADS-T as a higher-order measure of psychological distress was supported by our data. Revised cut-off points are given for the modified HADS-A and HADS-D subscales.</p

Analysis of Granular Flow in a Pebble-Bed Nuclear Reactor

Pebble-bed nuclear reactor technology, which is currently being revived around the world, raises fundamental questions about dense granular flow in silos. A typical reactor core is composed of graphite fuel pebbles, which drain very slowly in a continuous refueling process. Pebble flow is poorly understood and not easily accessible to experiments, and yet it has a major impact on reactor physics. To address this problem, we perform full-scale, discrete-element simulations in realistic geometries, with up to 440,000 frictional, viscoelastic 6cm-diameter spheres draining in a cylindrical vessel of diameter 3.5m and height 10m with bottom funnels angled at 30 degrees or 60 degrees. We also simulate a bidisperse core with a dynamic central column of smaller graphite moderator pebbles and show that little mixing occurs down to a 1:2 diameter ratio. We analyze the mean velocity, diffusion and mixing, local ordering and porosity (from Voronoi volumes), the residence-time distribution, and the effects of wall friction and discuss implications for reactor design and the basic physics of granular flow.Comment: 18 pages, 21 figure

Six weeks of maximal eccentric knee extensor training affects muscle-tendon mechanics and muscle damage

Introduction: Strength training can influence muscle-tendon mechanics and architecture, and provide a protective effect from exercise-induced muscle damage; however more data are required describing the specific influence of eccentric training. Therefore, the aims of the present study were to examine the effect of 6 weeks of maximal eccentric knee extensor training on these properties. Methods: Thirteen recreationally active participants (age = 28.3 ± 1.7 yr, mass = 73.5 ± 14.6 kg, height = 1.7 ± 0.1 m) volunteered for the study after giving written informed consent; ethical approval was granted from the University of Northampton. Training was performed twice weekly and consisted of 5 sets of 12 repetitions of 3-s maximal knee extensor isokinetic eccentric contractions at 30°·s-1 from 180° to 90° knee extension. Maximal isometric and eccentric knee extensor moment, range of motion (ROM), stretch tolerance, VL thickness and fascicle angle, and tendon and muscle-tendon unit (MTU) stiffness were measured using isokinetic dynamometry and real-time ultrasonography before and after the training. Creatine kinase (CK) concentration and delayed onset muscle soreness (DOMS) were also measured before and 24 h after a 20-min downhill run (16° decline).  Results: A significant increase in isometric (21.6%; p<0.05) and eccentric (28.1%; p<0.01) strength, ROM (6.6°; p<0.01), stretch tolerance (83.6%; p<0.01), VL thickness (7.8%; p<0.01) and fascicle angle (9.2%; p<0.01) was found after training; changes in VL thickness and fascicle angle were strongly correlated (r=0.96: p<0.01). While no change was found in MTU stiffness (slope of the passive moment curve) using dynamometry (-5.8%; p=0.45), ultrasound data revealed a significant increase in VL tendon stiffness (8.7%; p<0.01). Although CK concentration after downhill running increased significantly before (103.2%; p<0.01) and after (42.1%; p<0.05) training, the increase in CK was significantly lower following the training (p<0.05), with subjects also reporting minimal DOMS within the knee extensors. Discussion: The substantial increases in strength were accompanied by increases in both muscle size and pennation. Moreover, significant increases in ROM and stretch tolerance were observed, indicating a dual benefit to the eccentric training. An increase in tendon stiffness was observed, which will likely impact muscle-skeleton force transfer, and ultimately influence movement capacity. However, importantly this was not accompanied by a change in whole MTU stiffness, suggesting that MTU measurements may miss tissue-specific adaptations. Finally, the attenuated CK and DOMS response after training has clear implications for both muscular performance and injury risk.  Contact: [email protected]

Design of a vehicle based system to prevent ozone loss

This project is designed to be completed over a three year period. Overall project goals are: (1) to understand the processes that contribute to stratospheric ozone loss; (2) to determine the best scheme to prevent ozone loss; and (3) to design a vehicle based system to carry out the prevention scheme. The 1993/1994 design objectives included: (1) to review the results of the 1992/1993 design team, including a reevaluation of the key assumptions used; (2) to develop a matrix of baseline vehicle concepts as candidates for the delivery vehicle; and (3) to develop a selection criteria and perform quantitative trade studies to use in the selection of the specific vehicle concept

Oligogenic genetic variation of neurodegenerative disease genes in 980 postmortem human brains.

BACKGROUND: Several studies suggest that multiple rare genetic variants in genes causing monogenic forms of neurodegenerative disorders interact synergistically to increase disease risk or reduce the age of onset, but these studies have not been validated in large sporadic case series. METHODS: We analysed 980 neuropathologically characterised human brains with Alzheimer's disease (AD), Parkinson's disease-dementia with Lewy bodies (PD-DLB), frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) and age-matched controls. Genetic variants were assessed using the American College of Medical Genetics criteria for pathogenicity. Individuals with two or more variants within a relevant disease gene panel were defined as 'oligogenic'. RESULTS: The majority of oligogenic variant combinations consisted of a highly penetrant allele or known risk factor in combination with another rare but likely benign allele. The presence of oligogenic variants did not influence the age of onset or disease severity. After controlling for the single known major risk allele, the frequency of oligogenic variants was no different between cases and controls. CONCLUSIONS: A priori, individuals with AD, PD-DLB and FTD-ALS are more likely to harbour a known genetic risk factor, and it is the burden of these variants in combination with rare benign alleles that is likely to be responsible for some oligogenic associations. Controlling for this bias is essential in studies investigating a potential role for oligogenic variation in neurodegenerative diseases

Frequency and signature of somatic variants in 1461 human brain exomes.

PURPOSE: To systematically study somatic variants arising during development in the human brain across a spectrum of neurodegenerative disorders. METHODS: In this study we developed a pipeline to identify somatic variants from exome sequencing data in 1461 diseased and control human brains. Eighty-eight percent of the DNA samples were extracted from the cerebellum. Identified somatic variants were validated by targeted amplicon sequencing and/or PyroMark® Q24. RESULTS: We observed somatic coding variants present in >10% of sampled cells in at least 1% of brains. The mutational signature of the detected variants showed a predominance of C>T variants most consistent with arising from DNA mismatch repair, occurred frequently in genes that are highly expressed within the central nervous system, and with a minimum somatic mutation rate of 4.25 × 10-10 per base pair per individual. CONCLUSION: These findings provide proof-of-principle that deleterious somatic variants can affect sizeable brain regions in at least 1% of the population, and thus have the potential to contribute to the pathogenesis of common neurodegenerative diseases.Wellcome Trus

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability