Physical activity in children with Juvenile Idiopathic Arthritis compared to controls

BACKGROUND: To compare physical activity (PA) in children with juvenile idiopathic arthritis (JIA) with controls and to analyse the effect of disease specific factors on PA in children with JIA treated according to current treatment regimes. METHODS: PA was measured with a 7-day activity diary and expressed as physical activity level (PAL). Moderate to vigorous physical activity (MVPA) (hours/day) and sedentary time (hours/day) was determined. In children with JIA, medication, the number of swollen and/or painful joints, disease activity, functional ability, pain and well-being was determined. Multivariate regression analysis was performed to analyze differences in PA between JIA and controls, adjusted for influences of age, gender, season, Body Mass Index (BMI) and to analyze predictors of PA in JIA patients. RESULTS: Seventy-six children with JIA (26 boys and 50 girls, mean ± SD age 10.0 ± 1.4 years) and 131 controls (49 boys and 82 girls, mean ± SD age 10.4 ± 1.2 years) participated in this study. Children with JIA had a significantly lower PAL (0.10, p = 0.01) corrected for age, BMI, gender and season. They spent less time in MVPA (0.41 h/day, p = 0.06) and had a significantly higher mean time spent in sedentary activities (0.59 h/day, p 0.02) compared to controls. The activity level of children with JIA was related to age, gender, season, feeling of well-being and pain. CONCLUSION: Children with JIA have a lower PAL, spent less time in MVPA and spent more time on sedentary activities compared to controls despite current medical treatment and PA encouragement. TRIAL REGISTRATION: Data of the children with JIA are from the Rheumates@work study ISRCTN92733069

Angiogenesis and hypoxia in lymph node metastases is predicted by the angiogenesis and hypoxia in the primary tumour in patients with breast cancer

Hypoxia and angiogenesis are important factors in breast cancer progression. Little is known of hypoxia and angiogenesis in lymph node metastases of breast cancer. The aim of this study was to quantify hypoxia, by hypoxia-induced marker expression levels, and angiogenesis, by endothelial cell proliferation, comparing primary breast tumours and axillary lymph node metastases. Tissue sections of the primary tumour and a lymph node metastasis of 60 patients with breast cancer were immunohistochemically stained for the hypoxia-markers carbonic anhydrase 9 (CA9), hypoxia-inducible factor-1α (Hif-1α) and DEC-1 and for CD34/Ki-67. Endothelial cell proliferation fraction (ECP%) and tumour cell proliferation fraction (TCP%) were assessed. On haematoxylin–eosin stain, the growth pattern and the presence of a fibrotic focus were assessed. Hypoxia-marker expression, ECP% and TCP% in primary tumours and in lymph node metastases were correlated to each other and to clinico-pathological variables. Median ECP% and TCP% in primary tumours and lymph node metastases were comparable (primary tumours: ECP%=4.02, TCP%=19.54; lymph node metastases: ECP%=5.47, TCP%=21.26). ECP% correlated with TCP% (primary tumours: r=0.63, P<0.001; lymph node metastases: r=0.76, P<0.001). CA9 and Hif-1α expression were correlated (primary tumours P=0.005; lymph node metastases P<0.001). In primary tumours, CA9 and Hif-1α expression were correlated with DEC-1 expression (P=0.05), presence of a fibrotic focus (P<0.007) and mixed/expansive growth pattern (P<0.001). Primary tumours and lymph node metastases with CA9 or Hif-1α expression had a higher ECP% and TCP% (P<0.003); in primary tumours, mixed/expansive growth pattern and fibrotic focus were characterised by higher ECP% (P=0.03). Furthermore, between primary tumours and lymph node metastases a correlation was found for ECP%, TCP%, CA9 and Hif-1α expression (ECP% r=0.51, P<0.001; TCP r=0.77, P<0.001; CA9 and Hif-1α P<0.001). Our data demonstrate that the growth of breast cancer lymph node metastases is angiogenesis dependent and that angiogenesis and hypoxia in the primary tumour predict angiogenesis and hypoxia in the lymph node metastases. Together with previous findings in breast cancer liver metastases, which grow in 96% of cases angiogenesis independently, these data suggest that both the intrinsic growth characteristics and angiogenic potential of breast cancer cells and the site-specific tumour microenvironment determine angiogenesis and hypoxia in breast cancer

Genome-wide association and functional studies identify a role for matrix Gla protein in osteoarthritis of the hand

Objective Osteoarthritis (OA) is the most common form of arthritis and the leading cause of disability in the elderly. Of all the joints, genetic predisposition is strongest for OA of the hand; however, only few genetic risk loci for hand OA have been identified. Our aim was to identify novel genes associated with hand OA and examine the underlying mechanism. Methods We performed a genome-wide association study of a quantitative measure of hand OA in 12 784 individuals (discovery: 8743, replication: 4011). Genome-wide significant signals were followed up by analysing gene and allele-specific expression in a RNA sequencing dataset (n=96) of human articular cartilage. Results We found two significantly associated loci in the discovery set: at chr12 (p=3.5 × 10⁻¹⁰) near the matrix Gla protein (MGP) gene and at chr12 (p=6.1×10⁻⁹) near the CCDC91 gene. The DNA variant near the MGP gene was validated in three additional studies, which resulted in a highly significant association between the MGP variant and hand OA (rs4764133, Betameta=0.83, Pmeta=1.8*10⁻¹⁵). This variant is high linkage disequilibrium with a coding variant in MGP, a vitamin K-dependent inhibitor of cartilage calcification. Using RNA sequencing data from human primary cartilage tissue (n=96), we observed that the MGP RNA expression of the hand OA risk allele was significantly lowercompared with the MGP RNA expression of the reference allele (40.7%, p<5*10⁻¹⁶). Conclusions Our results indicate that the association between the MGP variant and increased risk for hand OA is caused by a lower expression of MGP, which may increase the burden of hand OA by decreased inhibition of cartilage calcification

Physiological Correlates of Volunteering

We review research on physiological correlates of volunteering, a neglected but promising research field. Some of these correlates seem to be causal factors influencing volunteering. Volunteers tend to have better physical health, both self-reported and expert-assessed, better mental health, and perform better on cognitive tasks. Research thus far has rarely examined neurological, neurochemical, hormonal, and genetic correlates of volunteering to any significant extent, especially controlling for other factors as potential confounds. Evolutionary theory and behavioral genetic research suggest the importance of such physiological factors in humans. Basically, many aspects of social relationships and social activities have effects on health (e.g., Newman and Roberts 2013; Uchino 2004), as the widely used biopsychosocial (BPS) model suggests (Institute of Medicine 2001). Studies of formal volunteering (FV), charitable giving, and altruistic behavior suggest that physiological characteristics are related to volunteering, including specific genes (such as oxytocin receptor [OXTR] genes, Arginine vasopressin receptor [AVPR] genes, dopamine D4 receptor [DRD4] genes, and 5-HTTLPR). We recommend that future research on physiological factors be extended to non-Western populations, focusing specifically on volunteering, and differentiating between different forms and types of volunteering and civic participation

Measuring Physical Activity in Juvenile Idiopathic Arthritis:Activity Diary Versus Accelerometer

OBJECTIVE: (1) To determine convergent validity of an activity diary (AD) and accelerometer (Actical brand/Phillips-Respironics) in measuring physical activity (PA) in children with juvenile idiopathic arthritis (JIA). (2) To determine how many days give reliable results. (3) To analyze effects of correcting accelerometer data for non-wear. METHODS: Patients with JIA (8-13 yrs) were recruited from 3 Dutch pediatric rheumatology centers. PA was assessed for 7 days with an AD and accelerometer, and was expressed as mean min/day of rest, light PA (LPA), moderate to vigorous PA (MVPA), and PA level (PAL). To analyze convergent validity, intraclass correlation coefficients (ICC) were calculated and paired sample Student t tests were performed. The required number of days to achieve reliable results was calculated using the Spearman-Brown prophecy formula. RESULTS: Convergent validity between AD and accelerometer was moderate for rest and PAL (ICC 0.41). ICC for LPA and MVPA were < 0.24. AD overestimated PAL and MVPA compared with the accelerometer. Wearing the accelerometer 7-19 days gave reliable PA estimates on group and individual levels. For the AD, 13-36 days were needed. Adjusting accelerometer data for non-wear resulted in a clinically relevant higher mean number of min/day spent in LPA (effect size 1.12), but not in MVPA (effect size 0.44). CONCLUSION: Convergent validity between AD and accelerometer is moderate to poor. In children with JIA, 1-week assessment with an accelerometer is sufficient to measure PA (all levels) reliably. On an individual level and for clinical use, 3 weeks are required. Additional use of AD enables correction for non-wear of accelerometer data

Muscles in motion:a randomized controlled trial on the feasibility, safety and efficacy of an exercise training programme in children and adolescents with juvenile dermatomyositis

Objective. To study for the first time in a randomized controlled trial the feasibility, safety and efficacy of an exercise training programme in children and adolescents with JDM. Methods. Patients were randomly assigned to the Intervention Group (IG; n = 14) or Waiting Control Group (WCG; n = 12). The intervention comprised an individually tailored 12-week home-based exercise programme of treadmill interval training and strength exercises. The efficacy of the IG over usual care (WCG) was examined with mixed linear regression (intention-to-treat). Effect sustainability during 12 weeks follow-up was also examined. Results. Seventy-five percent of the participants completed the intervention. Reasons for discontinuation were motivation/fatigue, recurrent infections and increasing physical complaints. No hospitalizations occurred and immune suppressive therapy remained stable or decreased in the patients who participated in the intervention. The estimated marginal means after the intervention period were significantly in favour of the IG compared with the WCG for standing long jump distance [difference between groups (95% CI): 13 cm (2-23)], the 30-s number of push-ups [8 (3-13)] and sit-ups [4 (0.4-8)], and the parent Childhood Health Assessment Questionnaire 30 + 8 score [-0.13 (-0.24 to - 0.01)] and effects sustained at follow-up. A trend was seen for the maximal oxygen uptake divided by body mass during maximal exercise treadmill testing; the IG scored 3.0 ml/kg/min (-1.3 to 7.3) higher compared with the WCG. Other outcomes (e.g. isometric muscle strength and perception of fatigue) did not differ between IG and WCG. Conclusion. Exercise training is of value in the clinical management of JDM