Efficacy of conservative treatment regimes for hip osteoarthritis - Evaluation of the therapeutic exercise regime "Hip School": A protocol for a randomised, controlled trial

<p>Abstract</p> <p>Background</p> <p>Hip osteoarthritis (hip OA) is a disease with a major impact on both national economy and the patients themselves. Patients suffer from pain and functional impairment in activities of daily life which are associated with a decrease in quality of life. Conservative therapeutic interventions such as physical exercises aim at reducing pain and increasing function and health-related quality of life. However, there is only silver level evidence for efficacy of land-based physical exercise in the treatment of hip OA. The purpose of this randomized controlled trial is to determine whether the specific 12-week exercise regime "Hip School" can decrease bodily pain and improve physical function and life quality in subjects with hip osteoarthritis.</p> <p>Methods/Design</p> <p>217 participants with hip OA, confirmed using the clinical score of the American College of Rheumatology, are recruited from the community and randomly allocated to one of the following groups: (1) exercise regime "Hip School", n = 70; (2) Non-intervention control group, n = 70; (3) "Sham" ultrasound group, n = 70; (4) Ultrasound group, n = 7. The exercise regime combines group exercises (1/week, 60-90') and home-based exercises (2/week, 30-40'). Sham ultrasound and ultrasound are given once a week, 15'. Measures are taken directly prior to (M1) and after (M2) the 12-week intervention period. Two follow-ups are conducted by phone 16 and 40 weeks after the intervention period. The primary outcome measure is the change in the subscale <it>bodily pain </it>of the SF36 from M1 to M2. Secondary outcomes comprise the WOMAC score, SF36, isometric strength of hip muscles, spatial-temporal and discrete measures derived from clinical gait analysis, and the length of the centre of force path in different standing tasks. An intension-to-treat analysis will be performed using multivariate statistics (group × time).</p> <p>Discussion</p> <p>Results from this trial will contribute to the evidence regarding the effect of a hip-specific exercise regime on physical function, pain, and health-related quality of life in patients with hip osteoarthritis.</p> <p>Trial registration</p> <p>German Clinical Trial Register DRKS00000651.</p

Role of cAMP in the promotion of colorectal cancer cell growth by Prostaglandin E2

<p>Abstract</p> <p>Background</p> <p>Prostaglandin E2 (PGE2), a product of the cyclooxygenase (COX) reaction, stimulates the growth of colonic epithelial cells. It is inferred that the abrogation of prostaglandins' growth-promoting effects as a result of COX inhibition underlies the advantageous effects of non-steroidal anti-inflammatory drugs in colorectal carcinoma (CRC). Despite this appreciation, the underlying molecular mechanisms remain obscure since cell culture studies have yielded discrepant results regarding PGE2's mitogenicity.</p> <p>Methods</p> <p>We have employed several alternative approaches to score cell proliferation and apoptosis of 4 CRC cell lines exposed to PGE2 under various conditions. To investigate the role of cAMP in PGE2's functions, activation of the cAMP pathway was assessed at different levels (changes in cAMP levels and PKA activity) in cells subjected to specific manipulations including the use of specific inhibitors or prostanoid receptor-selective agonists/antagonists.</p> <p>Results</p> <p>Our data document that the dose-response curve to PGE2 is 'bell-shaped', with nano molar concentrations of PGE2 being more mitogenic than micro molar doses. Remarkably, mitogenicity inversely correlates with the ability of PGE2 doses to raise cAMP levels. Consistent with a major role for cAMP, cAMP raising agents and pertussis toxin revert the mitogenic response to PGE2. Accordingly, use of prostanoid receptor-selective agonists argues for the involvement of the EP3 receptor and serum deprivation of HT29 CRC cells specifically raises the levels of Gi-coupled EP3 splice variants.</p> <p>Conclusion</p> <p>The present data indicate that the mitogenic action of low PGE2 doses in CRC cells is mediated via Gi-proteins, most likely through the EP3 receptor subtype, and is superimposed by a second, cAMP-dependent anti-proliferative effect at higher PGE2 doses. We discuss how these findings contribute to rationalize conflictive literature data on the proliferative action of PGE2.</p

Homeotic transformations reflect departure from the mammalian 'rule of seven' cervical vertebrae in sloths: inferences on the Hox code and morphological modularity of the mammalian neck

Background: Sloths are one of only two exceptions to the mammalian 'rule of seven' vertebrae in the neck. As a striking case of breaking the evolutionary constraint, the explanation for the exceptional number of cervical vertebrae in sloths is still under debate. Two diverging hypotheses, both ultimately linked to the low metabolic rate of sloths, have been proposed: hypothesis 1 involves morphological transformation of vertebrae due to changes in the Hox gene expression pattern and hypothesis 2 assumes that the Hox gene expression pattern is not altered and the identity of the vertebrae is not changed. Direct evidence supporting either hypothesis would involve knowledge of the vertebral Hox code in sloths, but the realization of such studies is extremely limited. Here, on the basis of the previously established correlation between anterior Hox gene expression and the quantifiable vertebral shape, we present the morphological regionalization of the neck in three different species of sloths with aberrant cervical count providing indirect insight into the vertebral Hox code. Results: Shape differences within the cervical vertebral column suggest a mouse-like Hox code in the neck of sloths. We infer an anterior shift of HoxC-6 expression in association with the first thoracic vertebra in short-necked sloths with decreased cervical count, and a posterior shift of HoxC-5 and HoxC-6 expression in long-necked sloths with increased cervical count. Conclusion: Although only future developmental analyses in non-model organisms, such as sloths, will yield direct evidence for the evolutionary mechanism responsible for the aberrant number of cervical vertebrae, our observations lend support to hypothesis 1 indicating that the number of modules is retained but their boundaries are displaced. Our approach based on quantified morphological differences also provides a reliable basis for further research including fossil taxa such as extinct 'ground sloths' in order to trace the pattern and the underlying genetic mechanisms in the evolution of the vertebral column in mammals

A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization

Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible