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Mechanical loading determines bone mass and bone structure, which involves many biochemical signal molecules. Of these molecules, Mepe and Fgf23 are involved in bone mineralization and phosphate homeostasis. Thus, we aimed to explore whether mechanical loading of bone affects factors of phosphate homeostasis. We studied the effect of mechanical loading of bone on the expression of Fgf23, Mepe, Dmp1, Phex, Cyp27b1, and Vdr. Twelve-week old female rats received a 4-point bending load on the right tibia, whereas control rats were not loaded. RT-qPCR was performed on tibia mRNA at 4, 5, 6, 7 or 8 hours after mechanical loading for detection of Mepe, Dmp1, Fgf23, Phex, Cyp27b1, and Vdr. Immunohistochemistry was performed to visualise FGF23 protein in tibiae. Serum FGF23, phosphate and calcium levels were measured in all rats. Four-point bending resulted in a reduction of tibia Fgf23 gene expression by 64% (p = 0.002) and a reduction of serum FGF23 by 30% (pDmp1 and Mepe gene expression increased by 151% (p = 0.007) and 100% (p = 0.007). Mechanical loading did not change Phex, Cyp27b1, and Vdr gene expression at any time-point. We conclude that mechanical loading appears to provoke both a paracrine as well as an endocrine response in bone by modulating factors that regulate bone mineralization and phosphate homeostasis.

Background The purpose of this study was to develop a DTI-based method to quantitatively assess fiber angles and changes therein in leg muscles in order to facilitate longitudinal studies on muscle fiber architectural adaptations in healthy subjects. Methods The upper legs of five volunteers were scanned twice on the same day. The right lower legs of five volunteers were scanned twice with the ankle in three positions, i.e. -15° dorsiflexion, 0° neutral position, and 30° plantarflexion. The MRI protocols consisted of a noise scan, a 3-point mDixon scan and a DTI scan. Fiber-angle color maps were generated for four muscles in the upper legs and two muscles in the lower leg. Voxel-wise fiber angles (θ) were calculated from the angle between the principal eigenvector of the diffusion tensor and a reference line defined between the origo and insertion points of each muscle. Bland-Altman analysis, intraclass correlation coefficient (ICC), coefficient of variation (CV%), minimal detectable change (MDC), standard error (SE) and Friedman test were used for assessing the feasibility of this method and in order to have an indication of the repeatability and the sensitivity. Results Bland-Altman analysis showed good repeatability (CV% Conclusion Our method facilitates fast inspection and quantification of muscle fiber angles in the lower and upper leg muscles in rest and detection of changes in lower-leg muscle fiber angles with varying ankle angles.

Background The evidence for rehabilitation interventions poststroke lack sufficient robustness. However, variation in treatment effects across countries have been given little attention. Objective To compare two identically protocolized trials conducted in different western countries in order to identify factors that may have caused variation in secondary trial outcomes. Methods Comparative study based on individual patient data (N = 129) from two randomized controlled trials, conducted in hospitals and rehabilitation facilities in the Netherlands (N = 66) and Australia (N = 63). Patients with stroke and their caregivers were randomly allocated to an 8-week caregiver-mediated exercises intervention (N = 63; 31 Australian and 32 Dutch) or to a control group (N = 66; 32 Australian and 34 Dutch). Patient characteristics, compliance, usual care and process measures were compared across countries. We examined if study setting significantly moderated the trial outcomes: Hospital Anxiety and Depression Scale, Fatigue Severity Scale and General Self-Efficacy Scale, measured at 8- and 12 weeks follow-up. In addition, we explored if factors that were significantly different across countries caused variation in these trial outcomes. Results Most patients suffered an ischemic stroke, were in the subacute phase and participated with their partner. Dutch patients were younger (P = 0.005) and had a lower functional status (P = 0.001). Australian patients were recruited earlier poststroke (PPPP = 0.040) among Dutch controls. No effect modification was observed and trial outcomes did not change after controlling for cross-country differences. Conclusions The present study highlighted important clinical differences across countries whilst using an identical study protocol. The observed differences could result in a different potential for recovery and variation in treatment effects across trials. We argue that we can proceed faster to evaluating interventions within international pragmatic trials.

Background An early return to normal intake and early mobilization enhances postoperative recovery. However, one out of six surgical patients is undernourished during hospitalization and approximately half of the patients eat 50% or less of the food provided to them. We assessed the use of newly introduced breakfast buffets in two wards for gastrointestinal and oncological surgery and determined the impact on postoperative protein and energy intake. Methods A prospective pilot cohort study was conducted to assess the impact of the introduction of breakfast buffets in two surgical wards. Adult patients had the opportunity to choose between an attractive breakfast buffet and regular bedside breakfast service. Primary outcomes were protein and energy intake during breakfast. We asked patients to report the type of breakfast service and breakfast intake in a diary over a seven-day period. Prognostic factors were used during multivariable regression analysis. Results A total of 77 patients were included. The median percentage of buffet use per patient during the seven-day study period was 50% (IQR 0–83). Mean protein intake was 14.7 g (SD 8.4) and mean energy intake 332.3 kcal (SD 156.9). Predictors for higher protein intake included the use of the breakfast buffet (β = 0.06, p = 0.01) and patient weight (β = 0.13, p = 0.01). Both use of the breakfast buffet (β = 1.00, p = 0.02) and Delirium Observation Scale scores (β = -246.29, p = 0.02) were related to higher energy intake. Conclusion Introduction of a breakfast buffet on a surgical ward was associated with higher protein and energy intake and it could be a promising approach to optimizing such intake in surgical patients. Large, prospective and preferably randomized studies should confirm these findings.

BackgroundLittle is known about differences in the size and morphology of the right and left human tali. The present study demonstrates differences between right and left talar morphometric geometric profiles as fluctuating asymmetry in matched pairs of cadaveric specimens.MethodsIn total, 24 tali were collected in this study. All eligible tali were systematically measured with a Vernier caliper and three-dimensional laser scanner, which provided data for further analysis regarding the talar morphometric geometric profiles. Data were calculated to demonstrate differences between the right and left talar profiles using a matched-pair method, including the general size of the talus.ResultsThe average talar length was 53.5 mm, the average talar dome height was 31.2 mm, and the average talar body width was 41.3 mm. The average anterior trochlear width, middle trochlear width, posterior trochlear width, and trochlear length were 31.8, 31.2, 28.3, and 30.7 mm, respectively. Eleven matched pairs of intact tali were eligible for the matched-pair study. Paired t-tests showed significant differences in the talar dome height (P = 0.019), middle trochlear width (P = 0.027), and posterior trochlear width (P = 0.016) between the right and left tali. However, there were no significant differences in the surface area or volume between the right and left tali.ConclusionSignificant differences in the morphometric profile were found between the right and left matched pairs of tali. This basic information indicates that the profile of the contralateral talus may not be used as a single reference to reconstruct or duplicate the talus of interest in certain conditions such as talar prosthesis implantation or customized total ankle replacement.

Accurate quantification and characterization of atherosclerotic plaques with MRI requires high spatial resolution acquisitions with excellent image quality. The intrinsically better signal-to-noise ratio (SNR) at high-field clinical 7T compared to the widely employed lower field strengths of 1.5 and 3T may yield significant improvements to vascular MRI. However, 7T atherosclerosis imaging also presents specific challenges, related to local transmit coils and B1 field inhomogeneities, which may overshadow these theoretical gains. We present the development and evaluation of 3D, black-blood, ultra-high resolution vascular MRI on clinical high-field 7T in comparison lower-field 3T. These protocols were applied for in vivo imaging of atherosclerotic rabbits, which are often used for development, testing, and validation of translatable cardiovascular MR protocols. Eight atherosclerotic New Zealand White rabbits were imaged on clinical 7T and 3T MRI scanners using 3D, isotropic, high (0.63 mm3) and ultra-high (0.43 mm3) spatial resolution, black-blood MR sequences with extensive spatial coverage. Following imaging, rabbits were sacrificed for validation using fluorescence imaging and histology. Image quality parameters such as SNR and contrast-to-noise ratio (CNR), as well as morphological and functional plaque measurements (plaque area and permeability) were evaluated at both field strengths. Using the same or comparable imaging parameters, SNR and CNR were in general higher at 7T compared to 3T, with a median (interquartiles) SNR gain of +40.3 (35.3–80.1)%, and a median CNR gain of +68.1 (38.5–95.2)%. Morphological and functional parameters, such as vessel wall area and permeability, were reliably acquired at 7T and correlated significantly with corresponding, widely validated 3T vessel wall MRI measurements. In conclusion, we successfully developed 3D, black-blood, ultra-high spatial resolution vessel wall MRI protocols on a 7T clinical scanner. 7T imaging was in general superior to 3T with respect to image quality, and comparable in terms of plaque area and permeability measurements.

Diagnosing the causes of low back pain is a challenging task, prone to errors. A novel approach to increase diagnostic accuracy in medical decision making is collective intelligence, which refers to the ability of groups to outperform individual decision makers in solving problems. We investigated whether combining the independent ratings of chiropractors, chiropractic radiologists and medical radiologists can improve diagnostic accuracy when interpreting diagnostic images of the lumbosacral spine. Evaluations were obtained from two previously published studies: study 1 consisted of 13 raters independently rating 300 lumbosacral radiographs; study 2 consisted of 14 raters independently rating 100 lumbosacral magnetic resonance images. In both studies, raters evaluated the presence of "abnormalities", which are indicators of a serious health risk and warrant immediate further examination. We combined independent decisions of raters using a majority rule which takes as final diagnosis the decision of the majority of the group. We compared the performance of the majority rule to the performance of single raters. Our results show that with increasing group size (i.e., increasing the number of independent decisions) both sensitivity and specificity increased in both data-sets, with groups consistently outperforming single raters. These results were found for radiographs and MR image reading alike. Our findings suggest that combining independent ratings can improve the accuracy of lumbosacral diagnostic image reading.

Preliminary evidence from studies using quantitative sensory testing suggests the presence of central mechanisms in patients with carpal tunnel syndrome (CTS) as apparent by widespread hyperalgesia. Hallmarks of central mechanisms after nerve injuries include nociceptive facilitation and reduced endogenous pain inhibition. Methods to study nociceptive facilitation in CTS so far have been limited to quantitative sensory testing and the integrity of endogenous inhibition remains unexamined. The aim of this study was therefore to investigate changes in facilitatory and inhibitory processing in patients with CTS by studying hypersensitivity following experimentally induced pain (facilitatory mechanisms) and the efficacy of conditioned pain modulation (CPM, inhibitory mechanisms). Twenty-five patients with mild to moderate CTS and 25 age and sex matched control participants without CTS were recruited. Increased pain facilitation was evaluated via injection of hypertonic saline into the upper trapezius. Altered pain inhibition through CPM was investigated through cold water immersion of the foot as the conditioning stimulus and pressure pain threshold over the thenar and hypothenar eminence bilaterally as the test stimulus. The results demonstrated that patients with CTS showed a greater duration (p = 0.047), intensity (p = 0.044) and area (p = 0.012) of pain in response to experimentally induced pain in the upper trapezius and impaired CPM compared to the control participants (p = 0.006). Although typically considered to be driven by peripheral mechanisms, these findings indicate that CTS demonstrates characteristics of altered central processing with increased pain facilitation and reduced endogenous pain inhibition.

Context Sleep deprivation has detrimental metabolic consequences. Osteopenia and sarcopenia usually occur together and increase risk of fractures and disease. Results from studies linking sleep parameters to osteopenia or sarcopenia are scarce and inconsistent. Objective To examine the associations of sleep parameters with osteopenia and sarcopenia, considering the influence of sex and menopause. Design, setting and participants Cross-sectional analysis of 915 participants (45–65 years, 56% women, BMI 26 (range: 18–56) kg/m2) in the Netherlands Epidemiology of Obesity (NEO) study, a population-based cohort study. Sleep duration, quality, and timing were assessed with the Pittsburgh Sleep Quality Index (PSQI); bone mineral density and relative appendicular muscle mass were measured by DXA scans. Linear and logistic regressions were performed to associate sleep parameters to bone mineral density, relative appendicular muscle mass, osteopenia (t-score between -1 and -2.5) and sarcopenia (1 SD below average muscle mass). Results After adjustment for confounding factors, one unit increase in PSQI score (OR and 95% CI, 1.09, 1.03–1.14), declined self-rated sleep quality (1.76, 1.03–3.01), sleep latency (1.18, 1.06–1.31), and a one hour later sleep timing (1.51, 1.08–2.11), but not sleep duration (1.05, 0.90–1.23), were associated with osteopenia. PSQI score (1.10, 1.02–1.19) was also associated with sarcopenia; OR’s of sleep latency and later mid-sleep time with sarcopenia were 1.14 (0.99–1.31) and 1.54 (0.91–2.61), respectively. Associations were somewhat stronger in women and varied per menopausal status. Conclusions These results suggest that decreased sleep quality and a later sleep timing are risk factors for osteopenia and sarcopenia in middle aged individuals.

OBJECTIVES: The metabolic syndrome has been associated with a variety of individual variables, including demographics, lifestyle, clinical measures and physical performance. We aimed to identify independent predictors of the prevalence and incidence of metabolic syndrome in a large cohort of older adults.METHODS: The Longitudinal Aging Study Amsterdam is a prospective cohort including community-dwelling adults aged 55-85 years. Metabolic syndrome was defined according to criteria of the National Cholesterol Education Program Adult Treatment Panel III. The incidence of metabolic syndrome was calculated over a period of three years. Stepwise backward logistic regression analyses were used to identify predictors, including variables for demographics, lifestyle, clinical measures and physical performance, both in a cross-sectional cohort (n = 1292) and a longitudinal sub-cohort (n = 218).RESULTS: Prevalence and incidence of metabolic syndrome were 37% (n = 479) and 30% (n = 66), respectively. Cross-sectionally, heart disease (OR: 1.91, 95% CI: 1.37-2.65), peripheral artery disease (OR: 2.13, 95% CI: 1.32-3.42), diabetes (OR: 4.74, 95% CI: 2.65-8.48), cerebrovascular accident (OR: 1.92, 95% CI: 1.09-3.37), and a higher Body Mass Index (OR: 1.32, 95% CI: 1.26-1.38) were significant independent predictors of metabolic syndrome. Longitudinally, Body Mass Index (OR: 1.16, 95% CI: 1.05-1.27) was an independent predictor of metabolic syndrome.CONCLUSION: Four age related diseases and a higher Body Mass Index were the only predictors of metabolic syndrome in the cross-sectional cohort, despite the large variety of variables included in the multivariable analysis. In the longitudinal sub-cohort, a higher Body Mass Index was predictive of developing metabolic syndrome.

Inverse dynamics is a technique in which measured kinematics and, possibly, external forces are used to calculate net joint torques in a rigid body linked segment model. However, kinematics and forces are usually not consistent due to incorrect modelling assumptions and measurement errors. This is commonly resolved by introducing ‘residual forces and torques’ which compensate for this problem, but do not exist in reality. In this study a constrained optimization algorithm is proposed that finds the kinematics that are mechanically consistent with measured external forces and mimic the measured kinematics as closely as possible. The algorithm was tested on datasets containing planar kinematics and ground reaction forces obtained during human walking at three velocities (0.8 m/s, 1.25 and 1.8 m/s). Before optimization, the residual force and torque were calculated for a typical example. Both showed substantial values, indicating the necessity of developing a mechanically consistent algorithm. The proposed optimization algorithm converged to a solution in which the residual forces and torques were zero, without changing the ground reaction forces and with only minor changes to the measured kinematics. When using a rigid body approach, our algorithm ensures a consistent description of forces and kinematics, thereby improving the validity of calculated net joint torque and power values.