Complimentary electrostatics dominate T-cell receptor binding to a psoriasis-associated peptide antigen presented by human leukocyte antigen C∗06:02.

Psoriasis is a chronic skin disease characterized by hyperproliferative epidermal lesions infiltrated by autoreactive T cells. Individuals expressing the human leukocyte antigen (HLA) C∗06:02 allele are at highest risk for developing psoriasis. An autoreactive T cell clone (termed Vα3S1/Vß13S1) isolated from psoriatic plaques is selective for HLA-C∗06:02, presenting a peptide derived from the melanocyte-specific autoantigen ADAMTSL5 (VRSRRCLRL). Here we determine the crystal structure of this psoriatic TCR-HLA-C∗06:02 ADAMTSL5 complex with a stabilized peptide. Docking of the TCR involves an extensive complementary charge network formed between negatively charged TCR residues interleaving with exposed arginine residues from the self-peptide and the HLA-C∗06:02 α1 helix. We probed these interactions through mutagenesis and activation assays. The charged interface spans the polymorphic region of the C1/C2 HLA group. Notably the peptide-binding groove of HLA-C∗06:02 appears exquisitely suited for presenting highly charged Arg-rich epitopes recognized by this acidic psoriatic TCR. Overall, we provide a structural basis for understanding the engagement of melanocyte antigen-presenting cells by a TCR implicated in psoriasis while simultaneously expanding our knowledge of how TCRs engage HLA-C.

The interplay between citrullination and HLA-DRB1 polymorphism in shaping peptide binding hierarchies in rheumatoid arthritis.

The HLA-DRB1 locus is strongly associated with rheumatoid arthritis (RA) susceptibility, whereupon citrullinated self-peptides bind to HLA-DR molecules bearing the shared epitope (SE) amino acid motif. However, the differing propensity for citrullinated/non-citrullinated self-peptides to bind given HLA-DR allomorphs remains unclear. Here, we used a fluorescence polarization assay to determine a hierarchy of binding affinities of 34 self-peptides implicated in RA against three HLA-DRB1 allomorphs (HLA-DRB1*04:01/*04:04/*04:05) each possessing the SE motif. For all three HLA-DRB1 allomorphs, we observed a strong correlation between binding affinity and citrullination at P4 of the bound peptide ligand. A differing hierarchy of peptide-binding affinities across the three HLA-DRB1 allomorphs was attributable to the ß-chain polymorphisms that resided outside the SE motif and were consistent with sequences of naturally presented peptide ligands. Structural determination of eight HLA-DR4-self-epitope complexes revealed strict conformational convergence of the P4-Cit and surrounding HLA ß-chain residues. Polymorphic residues that form part of the P1 and P9 pockets of the HLA-DR molecules provided a structural basis for the preferential binding of the citrullinated self-peptides to the HLA-DR4 allomorphs. Collectively, we provide a molecular basis for the interplay between citrullination of self-antigens and HLA polymorphisms that shape peptide-HLA-DR4 binding affinities in RA.

The molecular basis for peptide repertoire selection in the human leucocyte antigen (HLA) C*06:02 molecule.

Human leukocyte antigen (HLA)-C*06:02 is identified as the allele associated with the highest risk for the development of the autoimmune skin disease psoriasis. However, the diversity and mode of peptide presentation by the HLA-C*06:02 molecule remains unclear. Here, we describe the endogenous peptide repertoire of ∼3,000 sequences for HLA-C*06:02 that defines the peptide-binding motif for this HLA allomorph. We found that HLA-C*06:02 predominantly presents nonamer peptides with dominant arginine anchors at the P2 and P7 positions and a preference for small hydrophobic residues at the C terminus (PΩ). To determine the structural basis of this selectivity, we determined crystal structures of HLA-C*06:02 in complex with two self-peptides (ARTELYRSL and ARFNDLRFV) and an analogue of a melanocyte autoantigen (ADAMTSL5, VRSRR-abu-LRL) implicated in psoriasis. These structures revealed that HLA-C*06:02 possesses a deep peptide-binding groove comprising two electronegative B- and E-pockets that coincide with the preference for P2 and P7 arginine anchors. The ADAMTSL5 autoantigen possessed a P7-Leu instead of the P7-Arg residue, but nevertheless was accommodated within the HLA-C*06:02 antigen-binding cleft. Collectively, our results provide the structural basis for understanding peptide repertoire selection in HLA-C*06:02.

Relationship of patient-reported outcomes with MRI measures in rheumatoid arthritis.

PURPOSE: We assessed whether MRI measures of synovitis, osteitis and bone erosion were associated with patient-reported outcomes (PROs) in a longitudinal clinical trial setting among patients with rheumatoid arthritis (RA). METHODS: This longitudinal cohort of 291 patients with RA was derived from the MRI substudy of the GO-BEFORE randomised controlled trial of golimumab among methotrexate-naïve patients. Correlations between RAMRIS scores (synovitis, osteitis, bone erosion) and physical function (Health Assessment Questionnaire (HAQ)), pain and global patient scores were determined at 0, 12, 24 and 52 weeks. Correlations between interval changes were also assessed. Multivariable regression models using robust generalised estimating equations evaluated associations over all time-points and their relationship to other clinical disease activity measures. RESULTS: Greater synovitis, osteitis and bone erosion scores were positively associated with HAQ at all time-points (all p<0.05) and with pain and patient global scores at 24 and 52 weeks. Over all visits, synovitis was associated with HAQ, pain and patient global scores (p≤0.03) independent of clinical disease activity measures. Improvements in synovitis and bone erosion were also associated with improvements in PROs. Less improvement in synovitis and progression in MRI erosion at 52 weeks were both independently associated with worsening in all PROs at 52 weeks while progression on X-ray was not associated. Similar associations were observed across treatment groups. CONCLUSIONS: MRI measures of inflammation and structural damage correlate independently with physical function, pain and patient global assessments. These observations support the validity of MRI biomarkers. TRIAL REGISTRATION NUMBER: NCT00264537; Post-results.

Obesity and rates of clinical remission and low MRI inflammation in rheumatoid arthritis.

OBJECTIVES: Obesity has been proposed as a risk factor for refractory rheumatoid arthritis (RA). We evaluated the impact of obesity on achieving clinical and imaging definitions of low disease activity. METHODS: This study evaluated 470 patients with RA from GO-BEFORE and GO-FORWARD randomised clinical trials. Included patients had blinded clinical disease activity measures and MRI at baseline, 24 and 52 weeks. Synovitis, osteitis and total inflammation scores were determined using the RA MRI scoring system. Multivariable logistic regression analyses compared odds of achieving Disease Activity Score using 28 joints and C-reactive protein (DAS28-CRP) remission, low component measures, or low MRI inflammation measures at 24 weeks in patients with obesity versus no obesity. RESULTS: At 24 weeks, patients with obesity were significantly less likely to achieve DAS28(CRP) remission (OR 0.47; 95% CI 0.24 to 0.92, p=0.03). In contrast, patients with obesity had similar odds of achieving low synovitis (OR 0.94; 95% CI 0.51 to 1.72, p=0.84) and inflammation scores (OR 1.16; 95% CI 0.61 to 2.22, p=0.64) and greater odds of achieving low osteitis scores (OR 2.06; 95% CI 1.10 to 3.84, p=0.02) versus normal weight patients. CONCLUSIONS: Patients with RA and obesity have lower rates of DAS28 remission but similar rates of low MRI activity compared with patients without obesity, suggesting that obesity and its associated comorbidities can bias clinical disease activity measures. TRIAL REGISTRATION NUMBER: NCT00361335 and NCT00264550; Post-results.

Development and validation of rheumatoid arthritis magnetic resonance imaging inflammation thresholds associated with lack of damage progression.

OBJECTIVES: To determine thresholds for rheumatoid arthritis (RA) magnetic resonance imaging scores (RAMRIS) associated with a low risk of structural damage progression. METHODS: MRI of the dominant hand was performed and RAMRIS scores determined at weeks 0, 24, and 52. X-rays were performed and van der Heijde-Sharp scores (vdHS) determined. In a development cohort (n=297) the changes in MRI erosion score and vdHS score were determined over the 24-week to 52-week interval and progression was defined as change >0.5. We identified 24-week thresholds for synovitis and osteitis that provided >90% sensitivity for imaging progression over the 24 to 52-week interval. The performance of these cut-offs was tested in a validation cohort (n=217). RESULTS: In the development cohort, synovitis or osteitis scores ≤3 by 24 weeks were associated with a low probability of progression on MRI and x-ray. The coefficient for osteitis was stronger than that of synovitis in models predicting x-ray and MRI progression. Therefore, a total inflammation score was weighted on osteitis (x2). An inflammation score ≤9 was more frequently attained than DAS28 remission (64 vs. 38) and was associated with low probability of progression regardless of attainment of clinical remission. In the validation cohort, there was a low odds of MRI progression among those with low synovitis [OR 0.27 (0.086,0.82) p=0.02], osteitis [OR 0.20 (0.085, 0.49) p<0.001] and inflammation scores [OR 0.12 (0.033, 0.41) p=0.001]. CONCLUSIONS: Attainment of low MRI single-hand synovitis and osteitis is not uncommon and predicts a lack of structural progression in RA, independent of clinical remission.

Comparison of Strength Levels Between Players From Within the Same Club Who Were Selected vs. Not Selected to Play in the Grand Final of the National Rugby League Competition.

A number of studies have established that higher levels of strength and power, tested at the end of the preseason, distinguish between playing level in professional rugby league. How this may impact the ability of players to get selected for final payoff games some 30 weeks later has not been fully investigated. The purpose of this study was to compare measures of upper- and lower-body strength between players from the same professional club, designated as those 17 players who attained selection and played in the team that won the Grand Final of the National Rugby League competition (GF) and those who did not attain selection (NSGF). Players were tested and compared for 1 repetition maximum bench press and full squat strength levels at the end of the preparation period, 30 weeks before the GF, using traditional significance analysis of variance and effect size (ES) statistics. Furthermore, the players were analyzed according to the 2 broad positional playing groups of forwards (FWD) and backs (BL). The results demonstrated that overall, the GF players were stronger than NSGF players by approximately 10 and 15%, respectively, for the upper and lower body. When analyzed according to positional groupings, there were significant differences and large ES for GF forwards, who were significantly stronger, heavier, and older than NSGF FWD players. For the BL groups, the differences between the groups were not significant. Because of the intense physical collisions inherent in rugby league, it would appear that higher levels of strength afford players greater performance benefits, resiliency against injury, and greater likelihood of being selected in the most important games at the end of the season.

Validity of early MRI structural damage end points and potential impact on clinical trial design in rheumatoid arthritis.

OBJECTIVE: To evaluate the construct validity of the rheumatoid arthritis MRI score (RAMRIS) erosion evaluation as structural damage end point and to assess the potential impact of incorporation in clinical trials. METHODS: In a randomised trial of early methotrexate-naïve RA (GO-BEFORE), RAMRIS scores were determined from MRIs and van der Heijde-Sharp (vdHS) scores from radiographs, at baseline, week 12, week 24 and week 52. Progression in damage scores was defined as change >0.5. Associations of X-ray and MRI outcomes with clinical features were evaluated for convergent validity. Iterative Wilcoxon rank sum tests and tests of proportion estimated the sample size required to detect differences between combination therapy (methotrexate+golimumab) and methotrexate-monotherapy arms in (A) change in damage score and (B) proportion of patients progressing. RESULTS: Patients with early MRI progression had higher DAS28, C reactive protein (CRP) and vdHS at baseline, and higher 2-year HAQ. Associations were similar to those with 1-year vdHS progression. Differences in change in structural damage between treatment arms achieved significance with fewer subjects when 12-week or 24-week MRI erosion score was the outcome (150 patients; 100 among an enriched sample with baseline-synovitis >5) compared with the 52-week vdHS (275 patients). Differences in the proportion progressing could be detected in 234 total subjects with 12-week MRI in an enriched sample whereas 1-year X-ray required between 468 and 1160 subjects. CONCLUSIONS: Early MRI erosion progression is a valid measure of structural damage that could substantially decrease sample size and study duration if used as structural damage end point in RA clinical trials.

Greater body mass independently predicts less radiographic progression on X-ray and MRI over 1-2†years.

INTRODUCTION: Greater body mass index (BMI) has been associated with less radiographic progression in rheumatoid arthritis (RA). We evaluated the association between BMI and joint damage progression as measured by X-ray and MRI. METHODS: 1068 subjects with RA from two clinical trials of golimumab (GO-BEFORE and GO-FORWARD) had radiographs performed at weeks 0, 52 and 104 and evaluated using the van der Heijde-Sharp (vdHS) scoring system. Contrast-enhanced MRIs of the dominant wrist and hand were obtained at weeks 0, 12, 24, 52 and 104. Multivariable logistic regression evaluated the risk of radiographic progression for each BMI category (<25, 25-30, >30 kg/m(2)). Within GO-BEFORE, piecewise, robust generalised estimating equations marginal models assessed the probability of MRI erosion progression for each BMI category. Multivariable linear regression models assessed baseline associations between BMI and bone oedema (a precursor of bone erosion). RESULTS: Higher BMI category was associated with a lower probability of progression in vdHS score at weeks 52 and 104 independent of potential confounders. Higher BMI was also independently associated with a lower probability of progression in MRI erosion score over 2 years. Subjects with greater BMI demonstrated less bone oedema independent of differences in other disease severity measures, including MRI synovitis in the same joints. CONCLUSIONS: Greater BMI is associated with a lower risk of progression on X-ray and MRI over 2 years. Subjects with greater BMI also demonstrate less bone oedema at baseline. Greater BMI may indicate a less aggressive RA phenotype and aid in risk stratification.

Early MRI measures independently predict 1-year and 2-year radiographic progression in rheumatoid arthritis: secondary analysis from a large clinical trial.

OBJECTIVE: To determine if early MRI measures predict X-ray progression at 1 and 2 years in a large RA trial cohort. DESIGN: This study included 256 methotrexate (MTX)-naïve RA patients from a randomised placebo-controlled trial of golimumab (GO-BEFORE). MRIs of wrist and 2nd-5th metacarpophalangeal joints at 0, 12, 24, 52 and 104 weeks were obtained and scored using the RAMRIS system. Multivariable logistic regression examined if baseline and early change (weeks 12/24) in RAMRIS scores independently predicted progression of the van der Heijde-Sharp (vdHS) score and MRI erosion score at 1 and 2 years of follow-up. RESULTS: High baseline score and poor improvement over the first 24 weeks in synovitis (p=0.003 and p=0.003, respectively) and in bone oedema (p=0.02 and p=0.001, respectively) were independent predictors of X-ray progression at 1 year. Associations were significant or tended towards an association at 2 years. An increase in RAMRIS bone erosion >0.5 at weeks 12 and 24 also predicted X-ray progression (p<0.003). Poor 12-week improvement in bone oedema was associated with X-ray and MRI progression at 1 year (p<0.05). Regression models that incorporated baseline and 12-week and 24-week changes in MRI measures of synovitis (AUC=0.71) and bone oedema (AUC=0.70) improved the prediction of X-ray progression at 1 year above clinical disease activity alone (AUC=0.66, p<0.04). CONCLUSIONS: Baseline and early changes in MRI measures independently predicted X-ray and MRI progression at later time-points. The predictive validity established here supports potential use in shorter-duration studies to determine efficacy of RA therapies in preventing structural damage.

H. Ralph Schumacher.

Dr Schumacher was a force in rheumatology for more than half a century through his multiple roles as a researcher, clinician, mentor, and educator. He is not likely to be soon forgotten by the rheumatology community; however, it is hoped that this chapter can provide a faithful recollection that will help bring his memory to life for some and that rings true to those who knew him and learned from him.

10-year changes in upper body strength and power in elite professional rugby league players--the effect of training age, stage, and content.

The purpose of this investigation was to observe changes in maximal upper body strength and power across a 10-year period in professional athletes who were experienced resistance trainers. Six professional rugby league players were observed with test data reported according to 2 important training stages in their professional careers. The first stage (1996-1998) monitored the changes as the subjects strived to establish themselves as elite professionals in their sport. The remaining test data are from the latter stage (2000-2006), which is characterized by a longer competition schedule and shorter periods devoted to improving physical preparation. The changes in upper body strength, assessed by the 1 repetition maximum bench press and mean maximum power during bench press throws with various barbell resistances of 40-80 kg, were assessed by effect size (ES) and smallest worthwhile change (SWC) statistics. Large increases in strength and power of approximately 22-23% were reported across the 10-year period, however, only small changes (as determined by ES) in strength or power occurred after year 2000 till 2006. This result of only small changes in strength or power despite 6 years of intense resistance training was attributed to 3 main factors. Key among them are the possible existence of a "strength ceiling" for experienced resistance trainers, the Long-term Athlete Development model, and possibly an inappropriate volume of strength-endurance training from 2004 to 2005. The fact that an SWC in strength and power occurred in the year after the cessation of strength-endurance training suggests that training program manipulation is still an influencing factor in continuing strength and power gains in experienced resistance trainers.

Associations between vitamin D, disease activity, and clinical response to therapy in rheumatoid arthritis.

OBJECTIVES: Vitamin D deficiency is a potential risk factor for autoimmunity. Prior studies of the association between vitamin D levels and rheumatoid arthritis (RA) disease activity have yielded conflicting results. METHODS: Serum 25(OH)vitamin D levels were measured at baseline in 499 participants with active RA, ages 18-85 years, enrolled in a randomised clinical trial of golimumab (Go-Before Trial). Subjects were methotrexate and biologic therapy naïve. Multivariable linear regression was used to assess associations between vitamin D levels and disease activity scores (DAS28), van der Heijde-Sharp (vdHS) erosion scores, and serum inflammatory markers. Generalised estimating equations were used to evaluate the associations between vitamin D status and the response to therapy over 52 weeks, using the DAS28 and ACR response. RESULTS: Forty-eight percent of participants were vitamin D deficient, defined as serum 25(OH)vitamin D <20 ng/mL. Deficiency was not associated with greater DAS28 (ß-0.021 [95% CI -0.22, 0.18]), adjusted for age, race, sex, BMI, disease duration and glomerular filtration rate. Vitamin D deficiency was not associated with baseline vdHS scores or inflammatory markers in adjusted or unadjusted models. There was no association between baseline vitamin D deficiency and change in DAS28 (ß = -0.024 [-0.30, 0.25]), proportion meeting ACR response (OR 0.82 [0.56, 1.20]), or radiographic progression at 52 weeks (OR 0.91 [0.59-1.40]). CONCLUSIONS: Vitamin D levels were not associated with RA disease activity, inflammatory markers, or vdHS scores at baseline. Furthermore, there was no association between baseline vitamin D level and response to therapy or radiographic progression.

Within Session Exercise Sequencing During Programming for Complex Training: Historical Perspectives, Terminology, and Training Considerations.

The primary aim of this narrative review was to outline the historical genesis of resistance training strategies that incorporate high-load, low-velocity exercises and low-load, high-velocity exercises in the same training session allowing for different "exercise sequences" to be simultaneously implemented. Discrepancies between scientific works and the terminology used within contemporary sport science publications are identified. Upon review of the literature, we propose "complex training" to be considered an umbrella term with 4 different implementations, generally used to indicate a method in which movement velocity or load is altered between sets and/or exercises within the same session with the aim of improving slow and fast force expression. We propose the following terminology for said implementations: contrast training-exercise sequence with alternating high-load and low-load (higher-velocity) exercises in a set-by-set fashion within the same session (corresponding with 'contrast pairs' and 'intra-contrast rest'); descending training-several sets of high-load (e.g., back squat) exercises completed before the execution of several sets of low-load, higher-velocity (e.g., vertical jump) exercises within the same session; ascending training-several sets of low-load, higher-velocity exercises completed before several sets of high-load exercises within the same session; and French contrast training-subset of contrast training in which a series of exercises are performed in sequence within a single session: heavy compound exercise, plyometric exercise, light-to-moderate load compound exercise that maximises movement speed (i.e., external power), and a plyometric exercise (often assisted). Finally, practical applications and training considerations are presented.

Anti-Mouse CD83 Monoclonal Antibody Targeting Mature Dendritic Cells Provides Protection Against Collagen Induced Arthritis.

Antibodies targeting the activation marker CD83 can achieve immune suppression by targeting antigen-presenting mature dendritic cells (DC). This study investigated the immunosuppressive mechanisms of anti-CD83 antibody treatment in mice and tested its efficacy in a model of autoimmune rheumatoid arthritis. A rat anti-mouse CD83 IgG2a monoclonal antibody, DCR-5, was developed and functionally tested in mixed leukocyte reactions, demonstrating depletion of CD83+ conventional (c)DC, induction of regulatory DC (DCreg), and suppression of allogeneic T cell proliferation. DCR-5 injection into mice caused partial splenic cDC depletion for 2-4 days (mostly CD8+ and CD83+ cDC affected) with a concomitant increase in DCreg and regulatory T cells (Treg). Mice with collagen induced arthritis (CIA) treated with 2 or 6 mg/kg DCR-5 at baseline and every three days thereafter until euthanasia at day 36 exhibited significantly reduced arthritic paw scores and joint pathology compared to isotype control or untreated mice. While both doses reduced anti-collagen antibodies, only 6 mg/kg achieved significance. Treatment with 10 mg/kg DCR-5 was ineffective. Immunohistological staining of spleens at the end of CIA model with CD11c, CD83, and FoxP3 showed greater DC depletion and Treg induction in 6 mg/kg compared to 10 mg/kg DCR-5 treated mice. In conclusion, DCR-5 conferred protection from arthritis by targeting CD83, resulting in selective depletion of mature cDC and subsequent increases in DCreg and Treg. This highlights the potential for anti-CD83 antibodies as a targeted therapy for autoimmune diseases.

Associations between body mass, radiographic joint damage, adipokines and risk factors for bone loss in rheumatoid arthritis.

OBJECTIVE: To evaluate the association between BMI and radiographic joint damage (RJD) in RA. METHODS: van der Heijde-Sharp (vdHS) erosion scores were determined in 499 participants with RA, ages 18-85 years, while enrolled in a clinical trial of golimumab (GO-BEFORE trial). Subjects were MTX and biologic therapy naïve. Multivariable logistic regressions determined the odds of prevalent RJD (defined as vdHS score >10) according to BMI category. Longitudinal analyses evaluated the association between BMI category and progression of vdHS score over 52 weeks. Analyses in a subset of 100 participants examined the association between adipokines and vdHS scores. RESULTS: At enrolment and 52 weeks, 37.6 and 43.6% of participants had RJD. Compared with normal weight, obese subjects had lower odds of RJD [0.40 (95% CI 0.22, 0.74); P = 0.003], and underweight subjects had greater odds [3.86 (95% CI 1.66, 9.00); P = 0.002] at baseline, adjusted for demographic and disease characteristics. The baseline associations between BMI category and RJD were greater among participants with multiple risk factors for bone loss (female >50 years, smoking, glucocorticoid exposure and vitamin D deficiency); test for interaction P = 0.05. Adjustment for adiponectin levels did not attenuate the association between BMI and vdHS scores. Baseline BMI and change in weight did not independently predict radiographic progression (P > 0.1). CONCLUSIONS: Higher BMI was independently associated with less RJD and was greatest in participants with risk factors for bone loss. Future studies are needed to examine the associations between RJD, obesity, weight loss and osteoporosis.

The shared susceptibility epitope of HLA-DR4 binds citrullinated self-antigens and the TCR.

Individuals expressing HLA-DR4 bearing the shared susceptibility epitope (SE) have an increased risk of developing rheumatoid arthritis (RA). Posttranslational modification of self-proteins via citrullination leads to the formation of neoantigens that can be presented by HLA-DR4 SE allomorphs. However, in T cell-mediated autoimmunity, the interplay between the HLA molecule, posttranslationally modified epitope(s), and the responding T cell repertoire remains unclear. In HLA-DR4 transgenic mice, we show that immunization with a Fibß-74cit69-81 peptide led to a population of HLA-DR4Fibß-74cit69-81 tetramer+ T cells that exhibited biased T cell receptor (TCR) ß chain usage, which was attributable to selective clonal expansion from the preimmune repertoire. Crystal structures of pre- and postimmune TCRs showed that the SE of HLA-DR4 represented a main TCR contact zone. Immunization with a double citrullinated epitope (Fibß-72,74cit69-81) altered the responding HLA-DR4 tetramer+ T cell repertoire, which was due to the P2-citrulline residue interacting with the TCR itself. We show that the SE of HLA-DR4 has dual functionality, namely, presentation and a direct TCR recognition determinant. Analogous biased TCR ß chain usage toward the Fibß-74cit69-81 peptide was observed in healthy HLA-DR4+ individuals and patients with HLA-DR4+ RA, thereby suggesting a link to human RA.

Sex Differences in the Achievement of Remission and Low Disease Activity in Rheumatoid Arthritis.

OBJECTIVE: In rheumatoid arthritis, whether women are less likely to achieve low disease activity is unclear. We evaluated sex differences in remission and low disease activity, comparing different clinical and imaging measures. METHODS: We used data from the Veterans Affairs Rheumatoid Arthritis (VARA) registry and from 2 clinical trials. Remission and low disease activity were defined using composite scores, individual items (tender joints, swollen joints, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP] level, and evaluator/patient global assessment), and magnetic resonance imaging (MRI). In the VARA registry, we assessed the likelihood of point remission at any time during follow-up using logistic regression, and time to sustained remission (2 consecutive visits) using Cox proportional hazards models. In the clinical trials, logistic regression models evaluated the likelihood of low clinical and MRI activity at 52 weeks. RESULTS: Among 2,463 patients in VARA, women (10.2%) were less likely to be in Disease Activity Score in 28 joints (DAS28)-ESR remission in follow-up (odds ratio [OR] 0.71 [95% confidence interval (95% CI) 0.55-0.91]; P < 0.01) and had a longer time to sustained DAS28-ESR remission. This difference was not observed for DAS28-CRP, Clinical Disease Activity Index, or Routine Assessment of Patient Index Data 3. Women were more likely to achieve favorable individual components except for an ESR <30 mm/hour (OR 0.72 [95% CI 0.57-0.90]; P < 0.01). Among 353 trial participants (83.7% women), women had reduced rates of DAS28-ESR remission (OR 0.39 [95% CI 0.21-0.72]; P = 0.003) but similar rates of low MRI synovitis and osteitis. CONCLUSION: The comparison of remission rates between men and women varies based on the disease activity measure, with sex-specific differences in ESR resulting in reliably lower rates of remission among women. There were no differences in MRI measures.

Ability and validity of three different methods of assessing upper-body strength-endurance to distinguish playing rank in professional rugby league players.

To date, little study has been performed to determine the importance of upper-body strength-endurance (S-E) to success in rugby league football. Furthermore, debate exists as to which type of S-E testing, absolute resistance or relative percent S-E testing, where performance is gauged with an absolute resistance in kilograms or with a set percentage of 1 repetition maximum (1RM), respectively, would garner more informative results. To this end, 3 different methods of assessing S-E (1 relative and 2 absolute S-E) were investigated to determine their effectiveness and validity for distinguishing between rugby league players of different ranking. In study 1, 26 players of similar strength, but different playing ranking, performed a bench press test with a resistance of 60% of their 1RM to determine if any differences existed between the groups in how many repetitions could be completed with the same relative percentage resistance. The fact that no significant difference existed between the groups in repetitions performed indicated that this test of relative S-E did not differentiate playing rank in rugby league. In study 2, 38 subjects performed tests with absolute resistances of 60 and 102.5 kg (bench press repetitions-to-fatigue (BP RTF) 60 and 102.5, respectively) in an effort to determine the merits of absolute S-E testing. Both tests significantly differentiated playing rank, but on the basis of how many repetitions were performed, only the BP RTF 60 could be considered a valid test of S-E. Absolute S-E testing with a moderate resistance of 60 kg appears to be a valid and effective test for discriminating playing rank in rugby league players.

Effect of kinetically altering a repetition via the use of chain resistance on velocity during the bench press.

It is theorized that the force and velocity profile of a repetition performed during a standard barbell exercise may be altered by substituting suspended chains for some portion of the total resistance. The purpose of this study was to document the alterations in lifting velocity that occur when the bench press exercise is performed as standard (BP) or with the substitution of resistance via chains draped over the barbell (BP+CH). Thirteen professional rugby league players participated in this study as part of their usual training program. Each subject performed 2 sets of 3 repetitions under the following conditions: The BP+CH condition, where the barbell resistance of 60% 1RM (repetition maximum) was supplemented by 17.5-kg in chains draped over the barbell (total resistance was about 75% 1RM), and the BP condition, where the total resistance was the same but was constituted in the form of standard barbell weights. The BP+CH condition resulted in increases in mean and peak concentric lifting velocities of around 10% in both sets as compared to both BP sets. Eccentric peak velocities were more varied in response, but generally the addition of chain resistance could be said to allow for increased velocities. The result may be partially explained by the eccentric unloading that occurs as the chain links furl upon the floor in the latter stages of the eccentric range. This eccentric unloading precipitates a more rapid stretch-shorten cycle (SSC) transition and possibly a within-repetition postactivation potentiation (PAP) that allows the subject to utilize faster lifting velocities in the initial concentric portion, which flow through to the remainder of the concentric phase. Therefore the use of chains appears warranted when athletes need to lift heavy resistances explosively.