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

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

MARKERLESS MOTION CAPTURE WITH OPENCAP FOR FIELD-BASED JUMP TESTING: A FORCE TO BE RECKONED WITH?

Field-based methods to assess external kinetics are essential for regular biomechanical monitoring. The aim of this study was to examine the accuracy of ground reaction forces (GRF) estimated from segmental kinematics, measured with a markerless motion-capture system (OpenCap) during jumping. Full-body segmental kinematics were recorded for fifteen athletes during countermovement, squat, and drop jumps, and used to estimate vertical GRFs with a mechanics-based method. Across jumps, bias and limits of agreement were acceptable (\u3c15%) for 23 and 22 GRF variables, respectively. Within-athlete changes between arm-swing or leg-dominance conditions were adequately detected for multiple GRF variables. These findings show that a low-cost markerless motion-capture system (OpenCap) may be used to estimate and assess force variables of interest in field settings

Forces experienced at different levels of the musculoskeletal system during horizontal decelerations

Horizontal decelerations are frequently performed during team sports and are closely linked to sports performance and injury. This study aims to provide a comprehensive description of the kinetic demands of decelerations at the whole-body, structural, and tissue-specific levels of the musculoskeletal system. Team-sports athletes performed maximal-effort horizontal decelerations whilst full-body kinematics and ground reaction forces (GRFs) were recorded. A musculoskeletal model was used to determine whole-body (GRFs), structural (ankle, knee, and hip joint moments and contact forces), and tissue (twelve lower-limb muscle forces) loads. External GRFs in this study, especially in the horizontal direction, were up to six times those experienced during accelerated or constant-speed running reported in the literature. To cope with these high external forces, large joint moments (hip immediately after touchdown; ankle and knee during mid and late stance) and contact forces (ankle, knee, hip immediately after touchdown) were observed. Furthermore, eccentric force requirements of the tibialis anterior, soleus, quadriceps, and gluteal muscles were particularly high. The presented loading patterns provide the first empirical explanations for why decelerating movements are amongst the most challenging in team sports and can help inform deceleration-specific training prescription to target horizontal deceleration performance, or fatigue and injury resistance in team-sports athletes

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

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

The GATA-factor elt-2 is essential for formation of the Caenorhabditis elegans intestine

AbstractThe Caenorhabditis elegans elt-2 gene encodes a single-finger GATA factor, previously cloned by virtue of its binding to a tandem pair of GATA sites that control the gut-specific ges-1 esterase gene. In the present paper, we show that elt-2 expression is completely gut specific, beginning when the embryonic gut has only two cells (one cell cycle prior to ges-1 expression) and continuing in every cell of the gut throughout the life of the worm. When elt-2 is expressed ectopically using a transgenic heat-shock construct, the endogenous ges-1 gene is now expressed in most if not all cells of the embryo; several other gut markers (including a transgenic elt-2-promoter: lacZ reporter construct designed to test for elt-2 autoregulation) are also expressed ectopically in the same experiment. These effects are specific in that two other C. elegans GATA factors (elt-1 and elt-3) do not cause ectopic gut gene expression. An imprecise transposon excision was identified that removes the entire elt-2 coding region. Homozygous elt-2 null mutants die at the L1 larval stage with an apparent malformation or degeneration of gut cells. Although the loss of elt-2 function has major consequences for later gut morphogenesis and function, mutant embryos still express ges-1. We suggest that elt-2 is part of a redundant network of genes that controls embryonic gut development; other factors may be able to compensate for elt-2 loss in the earlier stages of gut development but not in later stages. We discuss whether elements of this regulatory network may be conserved in all metazoa