EFFECT OF FATIGUE FROM REPEATED SPRINTS ON HAMSTRING MUSCLE ACTIVATION PATTERNS DURING RUNNING

Hamstring injury has been associated with fatigue-induced reductions in activation levels during running. This study examined neuromuscular changes of the hamstring muscles as a result of fatigue following sprinting in a group of nine team sport athletes. Hamstring muscle activation, lower-limb kinematics and isokinetic eccentric hamstring strength were assessed to examine the effects of fatigue during running at five different sub-maximal speeds. As expected, there were significant increases in both Biceps Femoris (BF) and Semitendinosus (ST) activations with running speed (P \u3c 0.001). After fatigue, BF activation during late swing significantly decreased by an average of 11% (P=0.002). There was evidence in some subjects that ST activity was increased with fatigue but the increase (4%) was non-significant for the group. There was also a tendency for reduced BF activity with fatigue to be more evident at the faster speeds of running. These findings support other evidence in the literature that the lateral hamstrings (BF) are more susceptible to fatigue. In addition, there were signs of compensatory increased ST activation levels in some subjects. These effects lend support to the potential benefit of this neuromuscular assessment of the hamstrings as a useful measure of both performance and recovery

Improved generation of rat gene knockouts by target-selected mutagenesis in mismatch repair-deficient animals

BACKGROUND: The laboratory rat (Rattus norvegicus) is one of the preferred model organisms in physiological and pharmacological research, although the availability of specific genetic models, especially gene knockouts, is limited. N-ethyl-N-nitrosourea (ENU)-driven target-selected mutagenesis is currently the most successful method in rats, although it is still very laborious and expensive. RESULTS: As ENU-induced DNA damage is normally recognized by the mismatch repair (MMR) system, we hypothesized that the effectiveness of the target-selected mutagenesis approach could be improved by using a MMR-deficient genetic background. Indeed, Msh6 knockout rats were found to be more sensitive to ENU treatment and the germ line mutation rate was boosted more than two-fold to 1 mutation per 585 kb. In addition, the molecular mutation spectrum was found to be changed in favor of generating knockout-type alleles by approximately 20%, resulting in an overall increase in efficiency of approximately 2.5 fold. The improved effectiveness was demonstrated by high throughput mutation discovery in 70 Mb of sequence in a set of only 310 mutant F1 rats. This resulted in the identification of 89 mutations of which four introduced a premature stopcodon and 64 resulted in amino acid changes. CONCLUSION: Taken together, we show that the use of a MMR-deficient background considerably improves ENU-driven target-selected mutagenesis in the rat, thereby reducing animal use as well as screening costs. The use of a mismatch repair-deficient genetic background for improving mutagenesis and target-selected knockout efficiency is in principle applicable to any organism of interest

Anticarbamylated protein antibodies are associated with long-term disability and increased disease activity in patients with early inflammatory arthritis:Results from the Norfolk Arthritis Register

Objectives: Anticarbamylated protein (anti-CarP) antibodies are a novel family of autoantibodies recently identified in patients with inflammatory arthritis. The aim of this study was to investigate their association with long-term outcomes of disability and disease activity over 20 years’ follow-up in a cohort of patients with inflammatory polyarthritis (IP).  Methods: Norfolk Arthritis Register recruited adults with recent-onset swelling of ≥2 joints for ≥4 weeks from 1990 to 2009. At baseline, Health Assessment Questionnaire (HAQ) and 28 joint disease activity scores (DAS28) were obtained, and C reactive protein, rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA) and anti-CarP antibodies were measured. Further HAQ scores and DAS28 were obtained at regular intervals over 20 years. Generalised estimating equations were used to test the association between anti-CarP antibody status and longitudinal HAQ and DAS28 scores; adjusting for age, gender, smoking status, year of inclusion and ACPA status. Analyses were repeated in subgroups stratified by ACPA status. The relative association of RF, ACPA and anti-CarP antibodies with HAQ and DAS28 scores was investigated using a random effects model.  Results: 1995 patients were included; 1310 (66%) were female. Anti-CarP antibodies were significantly associated with more disability and higher disease activity, HAQ multivariate β-coefficient (95% CI) 0.12 (0.02 to 0.21), and these associations remained significant in the ACPA-negative subgroups. The associations of RF, ACPA and anti-CarP antibodies were found to be additive in the random effects model.  Conclusions: Anti-CarP antibodies are associated with increased disability and higher disease activity in patients with IP. Our results suggest that measurement of anti-CarP antibodies may be useful in identifying ACPA-negative patients with worse long-term outcomes. Further, anti-CarP antibody status provided additional information about RF and ACPA

Comprehensive single-cell genome analysis at nucleotide resolution using the PTA Analysis Toolbox

Detection of somatic mutations in single cells has been severely hampered by technical limitations of whole-genome amplification. Novel technologies including primary template-directed amplification (PTA) significantly improved the accuracy of single-cell whole-genome sequencing (WGS) but still generate hundreds of artifacts per amplification reaction. We developed a comprehensive bioinformatic workflow, called the PTA Analysis Toolbox (PTATO), to accurately detect single base substitutions, insertions-deletions (indels), and structural variants in PTA-based WGS data. PTATO includes a machine learning approach and filtering based on recurrence to distinguish PTA artifacts from true mutations with high sensitivity (up to 90%), outperforming existing bioinformatic approaches. Using PTATO, we demonstrate that hematopoietic stem cells of patients with Fanconi anemia, which cannot be analyzed using regular WGS, have normal somatic single base substitution burdens but increased numbers of deletions. Our results show that PTATO enables studying somatic mutagenesis in the genomes of single cells with unprecedented sensitivity and accuracy.</p

Adjustments with running speed reveal neuromuscular adaptations during landing associated with high mileage running training.

It remains to be determined whether running training influences the amplitude of lower limb muscle activations before and during the first half of stance and whether such changes are associated with joint stiffness regulation and usage of stored energy from tendons. Therefore, the aim of this study was to investigate neuromuscular and movement adaptations before and during landing in response to running training across a range of speeds. Two groups of high mileage (HM; >45 km/wk, n = 13) and low mileage (LM; <15 km/wk, n = 13) runners ran at four speeds (2.5-5.5 m/s) while lower limb mechanics and electromyography of the thigh muscles were collected. There were few differences in prelanding activation levels, but HM runners displayed lower activations of the rectus femoris, vastus medialis, and semitendinosus muscles postlanding, and these differences increased with running speed. HM runners also demonstrated higher initial knee stiffness during the impact phase compared with LM runners, which was associated with an earlier peak knee flexion velocity, and both were relatively unchanged by running speed. In contrast, LM runners had higher knee stiffness during the slightly later weight acceptance phase and the disparity was amplified with increases in speed. It was concluded that initial knee joint stiffness might predominantly be governed by tendon stiffness rather than muscular activations before landing. Estimated elastic work about the ankle was found to be higher in the HM runners, which might play a role in reducing weight acceptance phase muscle activation levels and improve muscle activation efficiency with running training.NEW & NOTEWORTHY Although neuromuscular factors play a key role during running, the influence of high mileage training on neuromuscular function has been poorly studied, especially in relation to running speed. This study is the first to demonstrate changes in neuromuscular conditioning with high mileage training, mainly characterized by lower thigh muscle activation after touch down, higher initial knee stiffness, and greater estimates of energy return, with adaptations being increasingly evident at faster running speeds

Identifying generalised segmental acceleration patterns that contribute to ground reaction force features across different running tasks

Objective: To support future developments of field-based biomechanical load monitoring tools, this study aimed to identify generalised segmental acceleration patterns and their contribution to ground reaction forces (GRFs) across different running tasks. Design: Exploratory experimental design. Methods: A multivariate principal component analysis (PCA) was applied to a combination of segmental acceleration data from all body segments for fifteen team-sport athletes performing accelerated, decelerated and constant low-, moderate- and high-speed running, and 90° cutting trials. Segmental acceleration profiles were then reconstructed from each principal component (PC) and used to calculate their specific GRF contributions. Results: The first PC explained 48.57% of the acceleration variability for all body segments and was primarily related to the between-task differences in the overall magnitude of the GRF impulse. Magnitude and timing of high-frequency acceleration and GRF features (i.e. impact related characteristics) were primarily explained by the second PC (12.43%) and also revealed important between-task differences. The most important GRF characteristics were explained by the first five PCs, while PCs beyond that primarily contained small contributions to the overall GRF impulse. Conclusions: These findings show that a multivariate PCA approach can reveal generalised acceleration patterns and specific segmental contributions to GRF features, but their relative importance for different running activities are task dependent. Using segmental acceleration to assess whole-body biomechanical loading generically across various movements may thus require task identification algorithms and/or advanced sensor or data fusion approaches

Substance use and psychological disorders among art and non-art university students: an empirical self-report survey

Media stories often suggest that those working in the creative arts appear to use and abuse psychoactive substances. The aim of the present study was to analyze the relationship between the use of psychoactive substances and the presence of psychological disorders among art and non-art students. Questionnaires related to these two areas were completed by 182 art students in higher education and a control group of 704 non-art university students. To assess psychoactive substance use, a structured questionnaire including the Cannabis Abuse Screening Test (CAST) and the Alcohol Use Disorders Identification Test (AUDIT) was administered to participants. Psychological disorders were assessed using the Hungarian version of the Brief Symptom Inventory (BSI) and the Global Severity Index (GSI). After analyzing the data, significant differences were found between the two groups regarding their first use of psychoactive substances. Art students' current substance use was found to be significantly more frequent compared to the control group. In relation to psychological disorders, art students scored significantly higher on three scales of the BSI (i.e., psychoticism, hostility, and phobic anxiety). Overall, a significantly higher proportion of artists were labeled as "problematic" using the GSI. The results suggest that artists have a higher risk of both substance use and experiencing psychological disorders