The relationship between lower limb muscle volume and body mass in ambulant individuals with bilateral cerebral palsy

Background

Individuals with cerebral palsy have smaller muscle volumes normalised to body mass than their typically developing peers. The aim of this study is to investigate the relationship between lower limb muscle volume and body mass in young people with bilateral cerebral palsy and their typically developing peers.

Methods

Twenty-five participants with bilateral cerebral palsy (aged 14.7±3.0 years, GMFCS level I-III) and 25 of their typically developing peers (aged 16.8±3.3 years) took part in this study. None of the participants had undergone orthopaedic surgery, botulinum toxin injections, or serial casting in the previous year. All participants underwent magnetic resonance imaging of both lower limbs. Nine major muscles of each lower limb were individually manually segmented and the muscle volumes calculated.

Results

Body mass and total lower limb muscle volume were significantly linearly related in both the cerebral palsy (R² = 0.75, p<0.001) and typically developing (R² = 0.77, p<0.001) groups. The slope of the relationship between muscle volume and body mass was significantly shallower in the cerebral palsy group compared to the typically developing group (p=0.007).

Conclusions

This cross-sectional study suggests that the increase in size of lower limb muscles relative to body mass is reduced in adolescents and young adults with cerebral palsy. Longitudinal studies are required to further investigate altered muscle growth trajectories in this group and their impact on long-term mobility.

     

Skeletal muscle apoptotic signaling predicts thigh muscle volume and gait speed in community-dwelling older persons: an exploratory study

Background

Preclinical studies strongly suggest that accelerated apoptosis in skeletal myocytes may be involved in the pathogenesis of sarcopenia. However, evidence in humans is sparse. In the present study, we investigated whether apoptotic signaling in the skeletal muscle was associated with indices of muscle mass and function in older persons.

Methodology/Principal Findings

Community-dwelling older adults were categorized into high-functioning (HF) or low-functioning (LF) groups according to their short physical performance battery (SPPB) summary score. Participants underwent an isokinetic knee extensor strength test and 3-dimensional magnetic resonance imaging of the thigh. Vastus lateralis muscle samples were obtained by percutaneous needle biopsy and assayed for the expression of a set of apoptotic signaling proteins. Age, sex, number of comorbid conditions and medications as well as knee extensor strength were not different between groups. HF participants displayed greater thigh muscle volume compared with LF persons. Multivariate partial least squares (PLS) regressions showed significant correlations between caspase-dependent apoptotic signaling proteins and the muscular percentage of thigh volume (R² = 0.78; Q² = 0.61) as well as gait speed (R² = 0.81; Q² = 0.56). Significant variables in the PLS model of percent muscle volume were active caspase-8, cleaved caspase-3, cytosolic cytochrome c and mitochondrial Bak. The regression model of gait speed was mainly described by cleaved caspase-3 and mitochondrial Bax and Bak. PLS predictive apoptotic variables did not differ between functional groups. No correlation was determined between apoptotic signaling proteins and muscle strength or quality (strength per unit volume).

Conclusions/Significance

Data from this exploratory study show for the first time that apoptotic signaling is correlated with indices of muscle mass and function in a cohort of community-dwelling older persons. Future larger-scale studies are needed to corroborate these preliminary findings and determine if down-regulation of apoptotic signaling in skeletal myocytes will provide improvements in the muscle mass and functional status of older persons.     

Dependence of mechanical properties of trabecular bone on plate–rod microstructure determined by individual trabecula segmentation (ITS)

Individual trabecula segmentation (ITS) technique can decompose the trabecular bone network into individual trabecular plates and rods and is capable of quantifying the plate/rod-related microstructural characteristics of trabecular bone. This novel technique has been shown to be able to provide in-depth insights into micromechanics and failure mechanisms of human trabecular bone, as well as to distinguish the fracture status independent of area bone mineral density in clinical applications. However, the plate/rod microstructural parameters from ITS have never been correlated to experimentally determined mechanical properties of human trabecular bone. In this study, on-axis cylindrical trabecular bone samples from human proximal tibia (n=22), vertebral body (n=10), and proximal femur (n=21) were harvested, prepared, scanned using micro computed-tomography (µCT), analyzed with ITS and mechanically tested. Regression analyses showed that the plate bone volume fraction (pBV/TV) and axial bone volume fraction (aBV/TV) calculated by ITS analysis correlated the best with elastic modulus (R²=0.96–0.97) and yield strength (R²=0.95–0.96). Trabecular plate-related microstructural parameters correlated highly with elastic modulus and yield strength, while most rod-related parameters were found inversely and only moderately correlated with the mechanical properties. In addition, ITS analysis also identified that trabecular bone at human femoral neck had the highest trabecular plate-related parameters while the other sites were similar with each other in terms of plate–rod microstructure.     

Cranial muscle markers: A preliminary examination of size, sex, and age effects

Most muscle marker research consists of post-cranial analyses, but some researchers examine crania to reconstruct activities. Regardless of bones examined, anthropologists know of some of the complexities surrounding muscle marker development. Here, posterior cranial muscle markers are analyzed to determine whether they are useful in reconstructing activities by examining effects that may hinder reconstructions. Additionally, upper limb muscle markers and humeral cross-sectional robusticity variables are correlated with cranial muscle markers to determine if robust individuals are generally robust due to the synergistic effects of muscle use.Cranial muscle markers of 65 prehistoric California Amerinds are scored using a five-point observer rating scale. Body mass is calculated from femoral head size; maximum cranial length and breadth are measured with a spreading caliper; and age and sex are determined through standard procedures. Upper limb muscle markers are scored on seven sites using two dimensions within a seven-point scale. Cross-sectional properties are calculated from biplanar humeral radiographs. Aggregates are created for cranial muscle markers, upper limb muscle markers, and cross-sectional robusticity.Cranial muscle markers correlate significantly with cranial length, r=0.25 and cross-sectional robusticity of humerus, r=0.29; P’s<0.05. All variables differed between sexes (Mann-Whitney=31.00-307.50, P’s<0.01). Results imply that some differences in cranial muscle markers are related to size; however, individuals with well-developed cranial muscle markers have greater upper limb robusticity possibly due to activity patterns. Sex differences remained after size controls and may relate to activity differences.     

Cross-Talk in Mechanomyographic Signals from the Forearm Muscles during Sub-Maximal to Maximal Isometric Grip Force

Purpose

This study aimed: i) to examine the relationship between the magnitude of cross-talk in mechanomyographic (MMG) signals generated by the extensor digitorum (ED), extensor carpi ulnaris (ECU), and flexor carpi ulnaris (FCU) muscles with the sub-maximal to maximal isometric grip force, and with the anthropometric parameters of the forearm, and ii) to quantify the distribution of the cross-talk in the MMG signal to determine if it appears due to the signal component of intramuscular pressure waves produced by the muscle fibers geometrical changes or due to the limb tremor.

Methods

Twenty, right-handed healthy men (mean ± SD: age  = 26.7±3.83 y; height  = 174.47±6.3 cm; mass  = 72.79±14.36 kg) performed isometric muscle actions in 20% increment from 20% to 100% of the maximum voluntary isometric contraction (MVIC). During each muscle action, MMG signals generated by each muscle were detected using three separate accelerometers. The peak cross-correlations were used to quantify the cross-talk between two muscles.

Results

The magnitude of cross-talk in the MMG signals among the muscle groups ranged from, R²_{x, y} = 2.45–62.28%. Linear regression analysis showed that the magnitude of cross-talk increased linearly (r² = 0.857–0.90) with the levels of grip force for all the muscle groups. The amount of cross-talk showed weak positive and negative correlations (r² = 0.016–0.216) with the circumference and length of the forearm respectively, between the muscles at 100% MVIC. The cross-talk values significantly differed among the MMG signals due to: limb tremor (MMG_TF), slow firing motor unit fibers (MMG_SF) and fast firing motor unit fibers (MMG_FF) between the muscles at 100% MVIC (p<0.05, η ² = 0.47–0.80).

Significance

The results of this study may be used to improve our understanding of the mechanics of the forearm muscles during different levels of the grip force.     

Application of bioelectrical impedance analysis in prediction of light kid carcass and muscle chemical composition

Carcass data were collected from 24 kids (average live weight of 12.5±5.5 kg; range 4.5 to 22.4 kg) of Jarmelista Portuguese native breed, to evaluate bioelectrical impedance analysis (BIA) as a technique for prediction of light kid carcass and muscle chemical composition. Resistance (Rs, Ω) and reactance (Xc, Ω), were measured in the cold carcasses with a single frequency bioelectrical impedance analyzer and, together with impedance (Z, Ω), two electrical volume measurements (Vol_A and Vol_B, cm²/Ω), carcass cold weight (CCW), carcass compactness and several carcass linear measurements were fitted as independent variables to predict carcass composition by stepwise regression analysis. The amount of variation explained by Vol_A and Vol_B only reached a significant level (P<0.01 and P<0.05, respectively) for muscle weight, moisture, protein and fat-free soft tissue content, even so with low accuracy, with Vol_A providing the best results (0.326⩽R²⩽0.366). Quite differently, individual BIA parameters (Rs, Xc and Z) explained a very large amount of variation in dissectible carcass fat weight (0.814⩽R²⩽0.862; P<0.01). These individual BIA parameters also explained a large amount of variation in subcutaneous and intermuscular fat weights (respectively 0.749⩽R²⩽0.793 and 0.718⩽R²⩽0.760; P<0.01), and in muscle chemical fat weight (0.663⩽R²⩽0.684; P<0.01). Still significant but much lower was the variation in muscle, moisture, protein and fat-free soft tissue weights (0.344⩽R²⩽0.393; P<0.01) explained by BIA parameters. Still, the best models for estimation of muscle, moisture, protein and fat-free soft tissue weights included Rs in addition to CCW, and accounted for 97.1% to 99.8% (P<0.01) of the variation observed, with CCW by itself accounting for 97.0% to 99.6% (P<0.01) of that variation. Resistance was the only independent variable selected for the best model predicting subcutaneous fat weight. It was also selected for the best models predicting carcass fat weight (combined with carcass length, CL; R²=0.943; P<0.01) and intermuscular fat weight (combined with CCW; R²=0.945; P<0.01). The best model predicting muscle chemical fat weight combined CCW and Z, explaining 85.6% (P<0.01) of the variation observed. These results indicate BIA as a useful tool for prediction of light kids’ carcass composition.     

Control of center of mass motion state through cuing and decoupling of spontaneous gait parameters in level walking

Can the center of mass (COM) motion state, i.e., its position and velocity relative to the base of support (BOS), which dictate gait stability, be predictably controlled by the global gait parameters of step length and gait speed, or by extension, cadence? The precise relationships among step length and gait speed, and the COM motion state are unknown, partially due to the interdependence between step length and gait speed and the difficulty in independent control of both parameters during spontaneous level walking. The purposes of this study were to utilize simultaneous audio-visual cuing to independently manipulate step length and gait speed, and to determine the extent to which the COM position and velocity can be subsequently controlled. Fifty-six young adults were trained at one of the three gait patterns in which both the step length and gait speed were targeted simultaneously. The results showed that the cuing could successfully “decouple” gait speed from step length. Although this approach did yield reliable control of the COM velocity through manipulation of gait speed (R²=0.97), the manipulation of step length yielded less precise control of COM position (R²=0.60). This latter control appears to require manipulation of an additional degree-of-freedom at the local segment level, such that the inclusion of trunk inclination with step length improved the prediction of COM position (R²=0.80).     

Local irradiation alters bone morphology and increases bone fragility in a mouse model

Insufficiency fracture following radiation therapy (RTx) is a challenging clinical problem and typical bone mass measures fail to predict these fractures. The goals of this research were to develop a mouse model that results in reduced bone strength following focal irradiation, quantify morphological and strength changes occurring over time, and determine if a positive correlation between bone morphology and strength is retained after irradiation. Right hind limbs of 13 week-old female Balb/c mice were irradiated (5 or 20 Gy) using a therapeutic X-ray unit. Left limbs served as control. Animals were euthanized at 2, 6, 12, or 26 weeks. Axial compression tests of the distal femur were used to quantify whole bone strength. Specimen-specific, non-linear finite element (FE) analyses of the mechanical tests were performed using voxel-based meshes with two different material failure models: a linear bone density–strength relationship and a non-linear ‘embrittled’ relationship. Radiation resulted in a dose dependent increase in cortical bone density and marked loss of trabecular bone, measured using micro-CT. An early (2 week) increase in bone volume was associated with an increase in bone strength following irradiation; at 12 weeks there was a loss of bone strength despite higher bone volume for irradiated limbs. There was a positive correlation between bone volume bone and strength in control (r²=0.63) but not irradiated femora (r²=0.08). FE analysis with a constant strain failure model resulted in improved prediction of bone strength for irradiated limbs (r²=0.34) and this was improved further with the embrittled material model (r²=0.46). In summary, focal irradiation leads to substantial changes in bone morphology and strength with time, where there is a decreased bone strength following irradiation in the face of increasing bone mass; FE models with a non-linear embrittled material model were most successful in simulating these experimental findings.     

Use of large web-based data to identify public interest and trends related to endangered species

Use of the Internet by an increasing number of people to search for information related to varying disciplines has led to more precise data on societal views and trends. We used web search log data from a 6-year period and examined characteristics related to public interest in endangered species. Web search data for 246 endangered species as determined by the Ministry of Environment of Korea were evaluated. Relative search volumes for species were correlated with the status of conservation practices, and a self-organizing map (SOM) was used to analyze the relationship among selected variables. The relative search volume for higher taxa, including mammals, birds, amphibians and reptiles, were ten times higher than those for other taxa. SOM clusters were mainly divided according to the rank designation of the endangered species and the existence of a conservation facility dedicated to the species. The relative search volume and amount of web materials were the highest for the most highly ranked species. A positive relationship between the relative search volume and number of printed media articles (β 2.68; R ² 0.45; p < 0.0,001) and a negative relationship between the length of the common name of a species and number of printed media articles (β ?125.7; R ² 0.48; p = 0.024) were found. The evaluation of endangered species by using web-based data can be useful to improve conservation tools, including using feedback to facilitate interaction among political, scientific, and socio-economic interests.     

Extra-Hippocampal Subcortical Limbic Involvement Predicts Episodic Recall Performance in Multiple Sclerosis

Background

Episodic memory impairment is a common but poorly-understood phenomenon in multiple sclerosis (MS). We aim to establish the relative contributions of reduced integrity of components of the extended hippocampal-diencephalic system to memory performance in MS patients using quantitative neuroimaging.

Methodology/Principal Findings

34 patients with relapsing-remitting MS and 24 healthy age-matched controls underwent 3 T MRI including diffusion tensor imaging and 3-D T1-weighted volume acquisition. Manual fornix regions-of-interest were used to derive fornix fractional anisotropy (FA). Normalized hippocampal, mammillary body and thalamic volumes were derived by manual segmentation. MS subjects underwent visual recall, verbal recall, verbal recognition and verbal fluency assessment. Significant differences between MS patients and controls were found for fornix FA (0.38 vs. 0.46, means adjusted for age and fornix volume, P<.0005) and mammillary body volumes (age-adjusted means 0.114 ml vs. 0.126 ml, P<.023). Multivariate regression analysis identified fornix FA and mammillary bodies as predictor of visual recall (R² = .31, P = .003, P = .006), and thalamic volume as predictive of verbal recall (R² = .37, P<.0005). No limbic measures predicted verbal recognition or verbal fluency.

Conclusions/Significance

These findings indicate that structural and ultrastructural alterations in subcortical limbic components beyond the hippocampus predict performance of episodic recall in MS patients with mild memory dysfunction.     

Association between individual quadriceps muscle volume/enthesis and patello femoral joint cartilage morphology

Introduction

The aim of this study was to determine the association between individual quadriceps muscle volumes and the quadriceps enthesis structures and cartilage morphology at the patellofemoral joint (PFJ).

Methods

We studied 12 cadavers (age 75 ± 5 years). For both legs, individual quadriceps muscles (vastus lateralis (VL), rectus femoris (RF), vastus intermedialis (VI) and vastus medialis (VM)) were dissected and their volumes measured. Cartilage areas at the PFJ were classified using the International Cartilage Repair Society (ICRS) score. Histological sections were evaluated at the quadriceps tendon enthesis (laterally, centrally and medially). Several variables were calculated on the binary images based on two-dimensional analysis. These were apparent bone area (BA) and apparent trabecular thickness (TH). A Spearman rank test was used to determine the strength of correlation between individual quadriceps muscles volume, the structure of the quadriceps tendon enthesis and the ICRS score.

Results

The thickness of calcified fibrocartilage tissue was significantly greater in the central part of the enthesis than both medially (P = 0.03) and laterally (P = 0.04). Uncalcified fibrocartilage was significantly thicker laterally (P = 0.04) and centrally (P = 0.02) than medially. Muscle volume was highest (P <0.05) for the VL, followed by the VI, VM and RF. There was no association between total and individual muscle volumes and ICRS or BA. However, there was a strong positive correlation (r = 0.81) between the VL/VM volume ratio and BA ratio (bone volume at the lateral part divided by bone volume at the medial part). There was a moderate positive correlation between VL/VM and ICRS (r = 0.65) and between ICRS and BA ratio (lateral/medial; r = 0.74).

Conclusions

Individual and total quadriceps volumes were not correlated with cartilage loss at the PFJ or fibrocartilage thickness. However, both VL/VM and BA ratio (lateral/medial) were positively correlated with ICRS scoring and therefore could be a tool for predicting degree of PFJ osteoarthritis severity.     

Linkage map construction using InDel and SSR markers and QTL analysis of heading traits in Brassica oleracea var. capitata L.

Cabbage heading traits are important quantitative traits that greatly affect both quality and yield of cabbage. However, the genetic control of these traits remains unclear. To detect quantitative trait loci (QTLs) associated with heading traits, a double haploid (DH) population with 196 lines was created from a cabbage hybrid 01–20 × 96–100. A genetic map with insertion–deletion and simple sequence repeat markers was constructed based on the DH population, with a total length of 934.06 cM and average interval length of 2.3 cM between adjacent markers. Field experiments in three seasons were carried out to evaluate the heading traits, including head mature period (Hm), head weight (Hw), core length (Cl), head vertical diameter (Hvd), and the ratio of Cl to Hvd (Cl/Hvd). Using the map and the trait data, 13 reliable QTLs in total were identified and 5 were found in more than one season based on the adjusted means of three seasons. Major QTLs were identified for Hm (R ² = 40.4, LOD = 14.84), Hw (R ² = 28.6, LOD = 9.83), Cl (R ² = 38.8, LOD = 15.73), Hvd (R ² = 19.2, LOD = 9.26), and Cl/Hvd (R ² = 38.8, LOD = 12.75). The most significant QTLs were Hm3.1, Cl3.1, and Cl/Hvd3.1, which were detected in three seasons with the maximum contribution rate of almost 40 %. Six active regions that harbored more than one QTL were identified on five chromosomes, and one of them contained major QTLs associated with five traits. The QTLs obtained in this study should be useful for marker-assisted selection in cabbage breeding and for understanding the genetic control of these traits.     

Alterations of treatment-naïve pelvis and thigh muscle morphology in children with cerebral palsy

Lower limb (LL) muscle morphology and growth are altered in children with cerebral palsy (CP). Muscle alterations differ with age and with severity of motor impairment, classified according to the gross motor classification system (GMFCS). Muscle alterations differ also with orthopedic intervention, frequently performed at the level of the shank muscles since an early age, such as the gastrocnemius. The aim was to investigate the alterations of treatment-naïve pelvis and thigh muscle lengths and volumes in children with GMFCS levels I and II, of varying ages.17 children with CP (GMFCS I: N = 9, II: N = 8, age: 11.7 ± 4 years), age-matched to 17 typically developing (TD) children, underwent MRI of the LL. Three-dimensional reconstructions of the muscles were performed bilaterally. Muscle volumes and lengths were calculated in 3D and compared between groups. Linear regression between muscle volumes and age were computed.Adductor-brevis and gracilis lengths, as well as rectus-femoris volume, were decreased in GMFCS I compared to TD (p < 0.05). Almost all the reconstructed muscle volumes and lengths were found to be altered in GMFCS II compared to TD and GMFCS I. All muscle volumes showed significant increase with age in TD and GMFCS I (R² range: 0.3–0.9, p < 0.05). Rectus-femoris, hamstrings and adductor-longus showed reduced increase in the muscle volume with age in GMFCS II when compared to TD and GMFCS I.Alterations of treatment-naïve pelvis and thigh muscle volumes and lengths, as well as muscle growth, seem to increase with the severity of motor impairment in ambulant children with CP.     

Electromyographic and mechanomyographic responses across repeated maximal isometric and concentric muscle actions of the leg extensors

The purpose of the present study was to examine the patterns of responses for torque, electromyographic (EMG) amplitude, EMG mean power frequency (MPF), mechanomyographic (MMG) amplitude, and MMG MPF across 30 repeated maximal isometric (ISO) and concentric (CON) muscle actions of the leg extensors. Twelve female subjects (21.1 ± 1.4 yrs; 63.3 ± 7.4 kg) performed ISO and CON fatigue protocols with EMG and MMG signals recorded from the vastus lateralis. The relationships for torque, EMG amplitude, EMG MPF, MMG amplitude, and MMG MPF versus repetition number were examined using polynomial regression. The results indicated there were decreases (p < 0.05) across the ISO muscle actions for torque (r² = 0.95), EMG amplitude (R² = 0.44), EMG MPF (r² = 0.62), and MMG MPF (r² = 0.48), but no change in MMG amplitude (r² = 0.07). In addition, there were decreases across the CON muscle actions for torque (R² = 0.97), EMG amplitude (R² = 0.46), EMG MPF (R² = 0.86), MMG amplitude (R² = 0.44), and MMG MPF (R² = 0.80). Thus, the current findings suggested that the mechanisms of fatigue and motor control strategies used to modulate torque production were similar between maximal ISO and CON muscle actions.     

Inhalable Ipratropium Bromide Particle Engineering with Multicriteria Optimization

Spray-dried ipratropium bromide (IPB) microspheres for oral inhalation were engineered using Quality by Design. The interrogation of material properties, process parameters, and critical product quality attributes interplay enabled rational product design. A 2^7–3 screening design exhibited the Maillard reaction between L-leucine (LL) and lactose at studied outlet temperatures (OT) >130°C. A response surface custom design was used in conjunction with multicriteria optimization to determine the operating design space to achieve inhalable microparticles. Statistically significant predictive models were developed for volume median diameter (p?=?0.0001, adjusted R ²? =?0.9938), span (p?=?0.0278, adjusted R ²? =?0.7912), yield (p?=?0.0020, adjusted R ²? =?0.9320), and OT (p?=?0.0082, adjusted R ²? =?0.8768). An independent verification batch confirmed the model’s predictive capability. The prediction and actual values were in good agreement. Particle size and span were 3.32?±?0.09 μm and 1.71?±?0.18, which were 4.7 and 5.3% higher than the predicted values. The process yield was 50.3%, compared to the predicted value of 65.3%. The OT was 100°C versus the predicted value of 105°C. The label strength of IPB microparticles was 99.0 to 105.9% w/w suggesting that enrichment occurred during the spray-drying process. The present study can be utilized to initiate the design of the first commercial IPB dry powder inhaler.     

The effect of resorption cavities on bone stiffness is site dependent

Resorption cavities formed during the bone remodelling cycle change the structure and thus the mechanical properties of trabecular bone. We tested the hypotheses that bone stiffness loss due to resorption cavities depends on anatomical location, and that for identical eroded bone volumes, cavities would cause more stiffness loss than homogeneous erosion. For this purpose, we used beam–shell finite element models. This new approach was validated against voxel-based FE models. We found an excellent agreement for the elastic stiffness behaviour of individual trabeculae in axial compression (R² = 1.00) and in bending (R²>0.98), as well as for entire trabecular bone samples to which resorption cavities were digitally added (R² = 0.96, RMSE = 5.2%). After validation, this new method was used to model discrete cavities, with dimensions taken from a statistical distribution, on a dataset of 120 trabecular bone samples from three anatomical sites (4th lumbar vertebra, femoral head, iliac crest). Resorption cavities led to significant reductions in bone stiffness. The largest stiffness loss was found for samples from the 4th lumbar vertebra, the lowest for femoral head samples. For all anatomical sites, resorption cavities caused significantly more stiffness loss than homogeneous erosion did. This novel technique can be used further to evaluate the impact of resorption cavities, which are known to change in several metabolic bone diseases and due to treatment, on bone competence.     

Rapid,Accurate, and Non-Invasive Measurement of Zebrafish Axial Length and Other Eye Dimensions Using SD-OCT Allows Longitudinal Analysis of Myopia and Emmetropization

Refractive errors in vision can be caused by aberrant axial length of the eye, irregular corneal shape, or lens abnormalities. Causes of eye length overgrowth include multiple genetic loci, and visual parameters. We evaluate zebrafish as a potential animal model for studies of the genetic, cellular, and signaling basis of emmetropization and myopia. Axial length and other eye dimensions of zebrafish were measured using spectral domain-optical coherence tomography (SD-OCT). We used ocular lens and body metrics to normalize and compare eye size and relative refractive error (difference between observed retinal radial length and controls) in wild-type and lrp2 zebrafish. Zebrafish were dark-reared to assess effects of visual deprivation on eye size. Two relative measurements, ocular axial length to body length and axial length to lens diameter, were found to accurately normalize comparisons of eye sizes between different sized fish (R² = 0.9548, R² = 0.9921). Ray-traced focal lengths of wild-type zebrafish lenses were equal to their retinal radii, while lrp2 eyes had longer retinal radii than focal lengths. Both genetic mutation (lrp2) and environmental manipulation (dark-rearing) caused elongated eye axes. lrp2 mutants had relative refractive errors of −0.327 compared to wild-types, and dark-reared wild-type fish had relative refractive errors of −0.132 compared to light-reared siblings. Therefore, zebrafish eye anatomy (axial length, lens radius, retinal radius) can be rapidly and accurately measured by SD-OCT, facilitating longitudinal studies of regulated eye growth and emmetropization. Specifically, genes homologous to human myopia candidates may be modified, inactivated or overexpressed in zebrafish, and myopia-sensitizing conditions used to probe gene-environment interactions. Our studies provide foundation for such investigations into genetic contributions that control eye size and impact refractive errors.     

Synthesis of dimethylcobalt(III) complexes containing trimethylphosphine and 2-formyl-phenolato- or 2-formyl-enolato(O:O) ligands

Substituted salicylaldehydes [C₆HR¹R²R³(CHO)(OH)] react with CoMe₃(PMe₃)₃ to afford 6-coordinate (cis-dimethyl)(2-formyl-phenolato)trans-bis(trimethylphosphine)cobalt(III) compounds Co[C₆HR¹R²R³(CHO)(O)Me₂](PMe₃)₂ (1: R¹ = H; R² = Me; R³ = tert-Bu; 2: R¹, R² = C₆H₄; R³ = H). Accordingly, substituted enolated malonic dialdehydes (CHO-CR⁴CR⁵-OH) react with CoMe₃(PMe₃)₃ to afford 6-coordinate (cis-dimethyl)(2-formyl-enolato)trans-bis(trimethylphosphine)cobalt(III) compounds Co[(CHO-CR⁴CR⁵-O)(Me)₂](PMe₃)₂ (3: R⁴, R⁵ = (CH₂)₂C₆H₄; 4: R⁴ = R⁵ = C₆H₅). In the molecular structure of 4, the cobalt atom is centred in an octahedral coordination geometry brought about by a six-membered chelate ring (O:O-ligand), cis-dimethyl and trans-trimethylphosphine groups. A reaction mechanism is suggested.     

Validation of a simplified method for muscle volume assessment

The present study investigated the validity of a simplified muscle volume assessment that uses only the maximum anatomical cross-sectional area (ACSA_max), the muscle length (L_M) and a muscle-specific shape factor for muscle volume calculation ( Albracht et al., 2008, J Biomech 41, 2211–2218). The validation on the example of the triceps surae (TS) muscles was conducted in two steps. First L_M, ACSA_max, muscle volume and shape factor were calculated from magnet resonance image muscle reconstructions of the soleus (SO), gastrocnemius medialis (GM) and lateralis (GL) of a group of untrained individuals (n=13), endurance (n=9) and strength trained (n=10) athletes. Though there were significant differences in the muscle dimensions, the shape factors were similar across groups and were in average 0.497±0.026, 0.596±0.030, and 0.556±0.041 for the SO, GM and GL respectively. In a second step, the shape factors were applied to an independent recreationally active group (n=21) to compare the muscle volume assessed by the simplified method to the results from whole muscle reconstructions. There were no significant differences between the volumes assessed by the two methods. In conclusion, assessing TS muscle volume on the basis of the reported shape factors is valid across populations and the root mean square differences to whole muscle reconstruction of 7.9%, 4.8% and 8.3% for SO, GM and GL show that the simplified method is sensitive enough to detect changes in muscle volume in the context of degeneration, atrophy or hypertrophy.     

Experimental and finite element analysis of the mouse caudal vertebrae loading model: prediction of cortical and trabecular bone adaptation

In this study, we attempt to predict cortical and trabecular bone adaptation in the mouse caudal vertebrae loading model using knowledge of bone’s local mechanical environment at the onset of loading. In a previous study, we demonstrated appreciable 25.9 and 11% increases in both trabecular and cortical bone volume density, respectively, when subjecting the fifth caudal vertebrae (C5) of C57BL/6 (B6) mice to an acute loading regime (amplitude of 8N, 3000 cycles, 10 Hz, 3 times a week for 4 weeks). We have also established a validated finite element (FE) model of the C5 vertebra using micro-computed tomography (micro-CT), which characterizes, in 3D, the micro-mechanical strains present in both cortical and trabecular compartments due to the applied loads. To investigate the relationship between load-induced bone adaptation and mechanical strains in-vivo and in-silico data sets were compared. Using data from the previous cross-sectional study, we divided cortical and trabecular compartments into 15 subregions and determined, for each region, a bone formation parameter ΔBV/BS (a cross-sectional measure of the bone volume added to cortical and trabecular surfaces following the described loading regime). Linear regression was then used to correlate mean regional values of ΔBV/BS with mean values of mechanical strains derived from the FE models which were similarly regionalized. The mechanical parameters investigated were strain energy density (SED), the orthogonal strains (e _x , e _y , e _z ) and the three shear strains (e _xy , e _yz , e _zx ). For cortical regions, regression analysis showed SED to correlate extremely well with ΔBV/BS (R ² =?0.82) and e _z (R ²?=?0.89). Furthermore, SED was found to predict expansion of the cortical shell correlating significantly with the regional percentage increases in cortical tissue volume (R ² = 0.92), cortical marrow volume (R ² =?0.91) and cortical thickness (R ² = 0.56). For trabecular regions, FE parameters were found not to correlate with load-induced trabecular bone morphology. These results indicate that load-induced cortical morphology can be predicted from population data, whereas the prediction of trabecular morphology requires subject-specific micro- architecture.