How accurate is your sclerostin measurement?:Comparison between three commercially available sclerostin ELISA kits

Sclerostin, bone formation antagonist is in the spotlight as a potential biomarker for diseases presenting with associated bone disorders such as chronic kidney disease (CDK-MBD). Accurate measurement of sclerostin is therefore important. Several immunoassays are available to measure sclerostin in serum and plasma. We compared the performance of three commercial ELISA kits. We measured sclerostin concentrations in serum and EDTA plasma obtained from healthy young (18-26 years) human subjects using kits from Biomedica, TECOmedical and from R&D Systems. The circulating sclerostin concentrations were systematically higher when measured with the Biomedica assay (serum: 35.5 ± 1.1 pmol/L; EDTA: 39.4 ± 2.0 pmol/L; mean ± SD) as compared with TECOmedical (serum: 21.8 ± 0.7 pmol/L; EDTA: 27.2 ± 1.3 pmol/L) and R&D Systems (serum: 7.6 ± 0.3 pmol/L; EDTA: 30.9 ± 1.5 pmol/L). We found a good correlation between the assay for EDTA plasma (r > 0.6; p < 0.001) while in serum, only measurements obtained using TECOmedical and R&D Systems assays correlated significantly (r = 0.78; p < 0.001). There was no correlation between matrices results when using the Biomedica kit (r = 0.20). The variability in values generated from Biomedica, R&D Systems and TECOmedical assays raises questions regarding the accuracy and specificity of the assays. Direct comparison of studies using different kits is not possible and great care should be given to measurement of sclerostin, with traceability of reagents. Standardization with appropriate material is required before different sclerostin assays can be introduced in clinical practice

Seasonal Variation in 25(OH)D at Aberdeen (57°N) and Bone Health Indicators- Could Holidays in the Sun and Cod Liver Oil Supplements Alleviate Deficiency?

Vitamin D has been linked with many health outcomes. The aim of this longitudinal study, was to assess predictors of seasonal variation of 25-hydroxy-vitamin D (25(OH)D) (including use of supplements and holidays in sunny destinations) at a northerly latitude in the UK (57°N) in relation to bone health indicators. 365 healthy postmenopausal women (mean age 62.0 y (SD 1.4)) had 25(OH)D measurements by immunoassay, serum C-telopeptide (CTX), estimates of sunlight exposure (badges of polysulphone film), information regarding holidays in sunny destinations, and diet (from food diaries, including use of supplements such as cod liver oil (CLO)) at fixed 3-monthly intervals over 15 months (subject retention 88%) with an additional 25(OH)D assessment in spring 2008. Bone mineral density (BMD) at the lumbar spine (LS) and dual hip was measured in autumn 2006 and spring 2007 (Lunar I-DXA). Deficiency prevalence (25(OH)

Retrospective evaluation of a local protocol used to enhance laboratory savings through minimizing the performance of alkaline phosphatase isoenzyme analysis

Background: Alkaline phosphatase isoenzyme analysis is an expensive and time-consuming laboratory test. We evaluated the effect of a locally derived screening algorithm for alkaline phosphatase isoenzyme requests on the number of alkaline phosphatase isoenzyme analyses performed, laboratory cost and patient care. Method: A total of 110 alkaline phosphatase isoenzyme analysis requests from the year 2015 were reviewed and subsequent alkaline phosphatase concentrations were monitored over a two-year period, to determine if the decision of performing/not performing alkaline phosphatase isoenzyme analysis, based on the algorithm, had an impact on patient care and laboratory cost. All alkaline phosphatase isoenzyme analysis requests with two consecutive elevated alkaline phosphatase concentrations (>upper limit of reference interval) were screened and, subject to the gamma glutamyl transferase being within the reference interval, either Bone alkaline phosphatase or 25 hydroxyvitamin D was measured depending on the age of the patient. Results: Compliance with this algorithm led to the normalization of subsequent serum alkaline phosphatase in 97% of patients without requiring alkaline phosphatase isoenzyme analysis. The cost of performing Bone alkaline phosphatase and 25 hydroxyvitamin D in-house was £778.50, while the cost of performing alkaline phosphatase isoenzyme analysis would have been £3040. This resulted in a laboratory saving of £2261.50. Conclusions: Implementation of this algorithm led to a significant reduction in alkaline phosphatase isoenzyme analysis, without compromising patient care. Total savings could be increased if 25 hydroxyvitamin D was used as a first-line test, for all patients with an elevated alkaline phosphatase and a normal gamma glutamyl transferase regardless of age. This algorithm is cost-effective and can be implemented in laboratories with 25 hydroxyvitamin D assay

High-level synthesis for medical image processing on Systems on Chip : a case study

Adaptive radiotherapy is a technique intended to increase the accuracy of radiotherapy. Currently, it is not clinically feasible due to the time required to process the images of patient anatomy. Hardware acceleration of image processing algorithms may allow them to be carried out in a clinically acceptable timeframe. This paper presents the experiences encountered using high-level synthesis tools to design an accelerated segmentation algorithm for computed tomography images targeted for implementation on a System on Chip. Hardware coprocessors and their interfaces for optimal threshold generation and 3D mean filter algorithms were synthesised from C++ functions. Hardware acceleration significantly outperformed the software only implementation. The high-level synthesis tools allowed the rapid exploration of different design options. However, hardware design knowledge was still necessary in order to interpret the results effectively

Parathyroid hormone secretion is controlled by both ionized calcium and phosphate during exercise and recovery in men

Context: The mechanism by which PTH is controlled during and after exercise is poorly understood due to insufficient temporal frequency of measurements. Objective: The objective of the study was to examine the temporal pattern of PTH, PO4, albumin-adjusted calcium, and Ca2+ during and after exercise. Design and Setting: This was a laboratory-based study with a crossover design, comparing 30 minutes of running at 55%, 65%, and 75% maximal oxygen consumption, followed by 2.5 hours of recovery. Blood was obtained at baseline, after 2.5, 5, 7.5, 10, 15, 20, 25, and 30 minutes of exercise, and after 2.5, 5, 7.5, 10, 15, 20, 25, 30, 60, 90, and 150 minutes of recovery. Participants: Ten men (aged 23 ± 1 y, height 1.82 ± 0.07 m, body mass 77.0 ± 7.5 kg) participated. Main Outcome Measures: PTH, PO4, albumin-adjusted calcium, and Ca2+ were measured. Results: Independent of intensity, PTH concentrations decreased with the onset of exercise (−21% to −33%; P ≤ .001), increased thereafter, and were higher than baseline by the end of exercise at 75% maximal oxygen consumption (+52%; P ≤ .001). PTH peaked transiently after 5–7.5 minutes of recovery (+73% to +110%; P ≤ .001). PO4 followed a similar temporal pattern to PTH, and Ca2+ followed a similar but inverse pattern to PTH. PTH was negatively correlated with Ca2+ across all intensities (r = −0.739 to −0.790; P ≤ .001). When PTH was increasing, the strongest cross-correlation was with Ca2+ at 0 lags (3.5 min) (r = −0.902 to −0.950); during recovery, the strongest cross-correlation was with PO4 at 0 lags (8 min) (r = 0.987–0.995). Conclusions: PTH secretion during exercise and recovery is controlled by a combination of changes in Ca2+ and PO4 in men

Vitamin D supplementation does not improve human skeletal muscle contractile properties in insufficient young males

Vitamin D may be a regulator of skeletal muscle function, although human trials investigating this hypothesis are limited to predominantly elderly populations. We aimed to assess the effect of oral vitamin D3 in healthy young males upon skeletal muscle function

Impact of a single oral dose of 100,000 IU vitamin D3 on profiles of serum 25(OH)D3 and its metabolites 24,25(OH)2D3, 3-epi-25(OH)D3, and 1,25(OH)2D3 in adults with vitamin D insufficiency

We investigate the effect of a high dose of vitamin D3 on circulating concentrations of 25(OH)D3 and its metabolites 24,25(OH)2D3, 3-epi-25(OH)D3, and 1,25(OH)2D3 in healthy individuals with self-perceived fatigue and vitamin D insufficiency (25(OH)D3 75 nmol/L. Among individuals who receivedvitamin D3, there were significant increases in serum concentrations of25(OH)D3 and its metabolites 24,25(OH)2D3, 3-epi-25(OH)D3, and1,25(OH)2D3 at 4 weeks; however, inter-individual variability inthese changes was substantial. Positive correlations between serum 25(OH)D3 and24,25(OH)2D3 and 3-epi-25(OH)D3, and a significant negativecorrelation between serum 1,25(OH)2D3 and 3-epi-25(OH)D3, were found4 weeks after supplementation. The 24,25(OH)2D3/25(OH)D3 and24,25(OH)2D3/1,25(OH)2D3 ratios were significantly increased,compared with baseline, in participants receiving vitamin D3. Baseline 25(OH)D3concentration was the only factor predictive of the change in 25(OH)D3 aftersupplementation.  Conclusions: Administration of a singlehigh dose of vitamin D3 leads to a significant increase in concentrations of25(OH)D3, 24,25(OH)2D3, 3-epi-25(OH)D3 and 1,25(OH)2D3;induction of the catabolic pathway predominates over the production of 1,25(OH)2D3.Due to the high inter-individual variation in the 25(OH)D3 response to supplementation,any given dose of vitamin D is unlikely to achieve optimal vitamin D status inall treated individual

Effect of carbohydrate feeding on the bone metabolic response to running

Bone resorption is increased after running, with no change in bone formation. Feeding during exercise might attenuate this increase, preventing associated problems for bone. This study investigated the immediate and short-term bone metabolic responses to carbohydrate (CHO) feeding during treadmill running. Ten men completed two 7-day trials, once being fed CHO (8% glucose immediately before, every 20 min during, and immediately after exercise at a rate of 0.7 g CHO·kg body mass-1·h-1) and once being fed placebo (PBO). On day 4 of each trial, participants completed a 120-min treadmill run at 70% of maximal oxygen consumption (VO2 max). Blood was taken at baseline (BASE), immediately after exercise (EE), after 60 (R1) and 120 (R2) min of recovery, and on three follow-up days (FU1-FU3). Markers of bone resorption [COOH-terminal telopeptide region of collagen type 1 (β-CTX)] and formation [NH2-terminal propeptides of procollagen type 1 (P1NP)] were measured, along with osteocalcin (OC), parathyroid hormone (PTH), albumin-adjusted calcium (ACa), phosphate, glucagon-like peptide-2 (GLP-2), interleukin-6 (IL-6), insulin, cortisol, leptin, and osteoprotogerin (OPG). Area under the curve was calculated in terms of the immediate (BASE, EE, R1, and R2) and short-term (BASE, FU1, FU2, and FU3) responses to exercise. β-CTX, P1NP, and IL-6 responses to exercise were significantly lower in the immediate postexercise period with CHO feeding compared with PBO (β-CTX: P=0.028; P1NP: P=0.021; IL-6: P=0.036), although there was no difference in the short-term response (β-CTX: P=0.856; P1NP: P=0.721; IL-6: P=0.327). No other variable was significantly affected by CHO feeding during exercise. We conclude that CHO feeding during exercise attenuated the β-CTX and P1NP responses in the hours but not days following exercise, indicating an acute effect of CHO feeding on bone turnover