2,663 research outputs found
Statins as modulators of bone formation
No full textThe use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) to reduce serum cholesterol is well described. However, the recent finding that statins have direct effects on bone was unexpected. A number of epidemiological studies have recently been published that explore the effects of statins on bone mineral density and risk of fracture in humans. Statins may act by directly stimulating the expression of bone morphogenetic protein-2 and increasing osteoblast differentiation or, like nitrogen-containing bisphosphonates, may have effects on the mevalonate pathway that leads to inhibition of osteoclast activity and osteoblast apoptosis. In addition, the demonstration that statins can inhibit inflammation and encourage angiogenesis offers other possibilities for action
Evaluating Citebase, an open access Web-based citation-ranked search and impact discovery service
No full textCitebase is a new citation-ranked search and impact discovery service that measures citations of scholarly research papers which are openly accessible on the Web, i.e. papers that are assessable continuously online. Other services, such as ResearchIndex, have emerged in recent years to offer citation indexing of Web research papers. In the first detailed user evaluation of an open access Web citation indexing service, Citebase has been evaluated by nearly 200 users from different backgrounds. The paper details the procedures used in the evaluation, and analyses the results of this study, which took place between June and October 2002. It was found that within the scope of its primary components, the search interface and services available from its rich bibliographic records, Citebase can be used simply and reliably for the purpose intended, and that it compares favourably with other bibliographic services. It is shown tasks can be accomplished efficiently with Citebase regardless of the background of the user. More data need to be collected and the process refined before it is as reliable for measuring citation impact of indexed papers. Better explanations and guidance are required for first-time users. Coverage is seen as a limiting factor, even though Citebase indexes over 200,000 papers from arXiv. Non-physicists were frustrated at the lack of papers from other sciences. The principle of citation searching of open access archives has thus been demonstrated and need not be restricted to current users. Since the evaluation, Citebase has become a featured service of the ArXiv physics eprint archives
Mixing omics: combining genetics and metabolomics to study rheumatic diseases
No full textMetabolomics is an exciting field in systems biology that provides a direct readout of the biochemical activities taking place within an individual at a particular point in time. Metabolite levels are influenced by many factors, including disease status, environment, medications, diet and, importantly, genetics. Thanks to their dynamic nature, metabolites are useful for diagnosis and prognosis, as well as for predicting and monitoring the efficacy of treatments. At the same time, the strong links between an individual's metabolic and genetic profiles enable the investigation of pathways that underlie changes in metabolite levels. Thus, for the field of metabolomics to yield its full potential, researchers need to take into account the genetic factors underlying the production of metabolites, and the potential role of these metabolites in disease processes. In this Review, the methodological aspects related to metabolomic profiling and any potential links between metabolomics and the genetics of some of the most common rheumatic diseases are described. Links between metabolomics, genetics and emerging fields such as the gut microbiome and proteomics are also discussed.</p
Effective measurement of knee alignment using AP knee radiographs
No full textThe gold standard for measuring knee alignment is mechanical axis determined using full-limb radiographs (FLR). Measurement of joint alignment using antero-posterior (AP) knee radiographs is more accessible, economical and involves less radiation exposure to the patient compared with using full-limb radiographs. The aim of this study was to compare and assess the reproducibility of knee joint axial alignment on full-limb radiographs and conventional AP knee radiographs.
Knee alignment was measured in 40 subjects (80 knees) from the TwinsUK registry. Measurement of mechanical knee alignment was from FLR, and anatomic knee alignment from weight-bearing AP knee radiographs. Reproducibility was assessed by intra-class correlation coefficients and kappa statistics. Reproducibility of knee alignment for both methods was good, with intra-observer ICC's of 0.99 for both FLR
and AP radiographs. The mean alignment angle on FLR was 178.9° (SD 2.1, range 173–183°), and 179.0° (SD 2.1, range 173–185°) on AP films. 58.8% of knees on FLR and 66.3% on AP films were of varus alignment. Good correlations were seen between results for FLR and AP radiographs, with ICC ranging from 0.87–0.92 for left and right knees, and kappa statistics of 0.65–0.74. Standard AP knee radiographs can be used to measure knee alignment with good reproducibility, and
provide comparable results to those obtained from FLR. This will facilitate measurement of knee alignment in existing cohort studies to assess malalignment as a risk factor of incident OA, and in clinical practice
Effects of body weight and fat mass on back pain - direct mechanical or indirect through inflammatory and metabolic parameters?
No full textBackground: while reports indicate the association between obesity and back pain, its mechanism is still unclear. Thus, we aimed to investigate the effects of weight and its components on back pain in middle-aged women while considering direct mechanical and indirect effects via inflammatory and metabolic parameters.Methods: we used data from the Chingford 1000 Women Study, two follow-ups seven years apart. We assessed effects of weight, body mass index (BMI), total fat mass (TFM), total lean mass (TLM) and total bone mineral density (TBMD), measured by dual-energy X-ray absorptiometry, on back pain episode. We used inflammatory (C-reactive protein, interleukin-6, and tumour necrosis factor-alpha) and metabolic parameters (systolic and diastolic blood pressure, triglyceride, high-density lipoprotein cholesterol, and fasting blood glucose) as mediators of indirect effects. We investigated associations of interest cross-sectionally and longitudinally using binary logistic regression and parallel mediation model.Results: we included 826 Chingford middle-aged women (mean age=60.7, SD=5.9) from the first used follow-up in cross-sectional and mediation analyses and 645 women that attended the follow-up seven years later, in longitudinal analyses. We found that increased weight was directly associated with increased odds of having back pain episode (OR=1.02; 95% CI 1.01-1.03), similarly as BMI (OR=1.05; 95% CI 1.02-1.08) and TFM (OR=1.03; 95% CI 1.01-1.04) consistently across the cross-sectional and longitudinal models, but not TLM or TBMD. However, we did not find consistent indirect effects of weight or its components through measured inflammatory or metabolic parameters on back pain.Conclusions: our results show that in middle-aged women, weight, BMI and TFM are directly related to back pain, indicating prominence of mechanical loading effect.</p
Predicting incident radiographic knee osteoarthritis in middle-aged women within 4 years:the importance of knee-level prognostic factors.
No full textObjective Develop and internally validate risk models and a clinical risk score tool to predict incident radiographic knee osteoarthritis (RKOA) in middle-aged women. Methods We analysed 649 women in the Chingford 1000 Women study. The outcome was incident RKOA, defined as Kellgren/Lawrence grade 0-1 at baseline and ≥2 at year 5. We estimated predictors’ effects on the outcome using logistic regression models. Two models were generated. The clinical model considered patient characteristics, medication, biomarkers, and knee symptoms. The radiographic model considered the same factors, plus radiographic factors (e.g., angle between the acetabular roof and ilium’s vertical cortex (hip α-angle)). The models were internally validated. Model performance was assessed using calibration and discrimination (area under the receiver characteristic curve, AUC). Results The clinical model contained age, quadriceps circumference, and a cartilage degradation marker (CTX-II) as predictors (AUC = 0.692). The radiographic model contained older age, greater quadriceps circumference, knee pain, knee baseline Kellgren/Lawrence 1 (versus 0), greater hip α-angle, greater spinal bone mineral density, and contralateral RKOA at baseline as predictors (AUC = 0.797). Calibration tests showed good agreement between the observed and predicted incident RKOA. A clinical risk score tool was developed from the clinical model. Conclusion Two models predicting incident RKOA within 4 years were developed; including radiographic variables improved model performance. First-time predictor hip α-angle and contralateral RKOA suggest osteoarthritis origins beyond the knee. The clinical tool has the potential to help physicians identify patients at risk of RKOA in routine practice, but should be externally validated
Pigmentation and vitamin D metabolism in Caucasians: low vitamin D serum levels in fair skin types in the UK.
No full textBackgroundVitamin D may play a protective role in many diseases. Public health messages are advocating sun avoidance to reduce skin cancer risk but the potential deleterious effects of these recommendations for vitamin D metabolism have been poorly investigated.Methodology/principal findingsWe investigated the association between 25-hydroxy-vitamin D (25(OH)D), skin type and ultraviolet exposure in 1414 Caucasian females in the UK. Mean age of the cohort was 47 years (18-79) and mean 25(OH)D levels were 77 nmol/L (6-289). 25(OH)D levels were strongly associated with season of sampling with higher levels in the spring and summer months (pConclusions/significanceContrary to previous studies across different ethnic backgrounds, this study within Caucasian UK females shows that fair skin types have lower levels of 25(OH)D compared to darker skin types with potential detrimental health effects. Public health campaigns advocating sun avoidance in fair skinned individuals may need to be revised in view of their risk of vitamin D deficiency
Blood, urine and faecal metabolite profiles in the study of adult renal disease
No full textChronic kidney disease (CKD) is a major public health burden and to date traditional biomarkers of renal function (such as serum creatinine and cystatin C) are unable to identify at-risk individuals before the disease process is well under way. To help preventive strategies and maximize the potential for effective interventions, it is important to characterise the molecular changes that take place in the development of renal damage. Metabolomics is a promising tool to identify markers of renal disease since the kidneys are involved in the handling of major biochemical classes of metabolites. These metabolite levels capture a snap-shot of the metabolic profile of the individual, allowing for the potential identification of early biomarkers, and the monitoring of real-time kidney function. In this review, we describe the current status of the identification of blood/urine/faecal metabolic biomarkers in different entities of kidney diseases including: acute kidney injury, chronic kidney disease, renal transplant, diabetic nephropathy and other disorders.</p
- …
