Predictive simulations identify potential neuromuscular contributors to idiopathic toe walking.

BACKGROUND: Most cases of toe walking in children are idiopathic. We used pathology-specific neuromusculoskeletal predictive simulations to identify potential underlying neural and muscular mechanisms contributing to idiopathic toe walking. METHODS: A musculotendon contracture was added to the ankle plantarflexors of a generic musculoskeletal model to represent a pathology-specific contracture model, matching the reduced ankle dorsiflexion range-of-motion in a cohort of children with idiopathic toe walking. This model was employed in a forward dynamic simulation controlled by reflexes and supraspinal drive, governed by a multi-objective cost function to predict gait patterns with the contracture model. We validated the predicted gait using experimental gait data from children with idiopathic toe walking with ankle contracture, by calculating the root mean square errors averaged over all biomechanical variables. FINDINGS: A predictive simulation with the pathology-specific model with contracture approached experimental ITW data (root mean square error = 1.37SD). Gastrocnemius activation was doubled from typical gait simulations, but lacked a peak in early stance as present in electromyography. This synthesised idiopathic toe walking was more costly for all cost function criteria than typical gait simulation. Also, it employed a different neural control strategy, with increased length- and velocity-based reflex gains to the plantarflexors in early stance and swing than typical gait simulations. INTERPRETATION: The simulations provide insights into how a musculotendon contracture combined with altered neural control could contribute to idiopathic toe walking. Insights into these neuromuscular mechanisms could guide future computational and experimental studies to gain improved insight into the cause of idiopathic toe walking.

RNA silencing of South African cassava mosaic virus in transgenic cassava expressing AC1/AC4 hp- RNA induces tolerance.

Cassava mosaic disease (CMD), caused by geminiviruses, is a major hurdle to cassava production. Due to the heterozygous nature of cassava, breeding for virus resistance is difficult, but cassava has been shown to be a good candidate for genetic engineering using RNA interference (RNAi). T This study reports on the ability of a transgene-derived RNA hairpin, homologous to an overlapping region of the SACMV replication associated protein and putative virus suppressor of silencing protein (AC1/AC4), to confer tolerance in the CMD-susceptible model cassava cultivar 60444. Three of the fourteen transgenic lines expressing SACMV AC1/AC4 hairpin-derived siRNAs showed decreased symptoms and viral loads compared to untransformed control plants. Expression of SACMV AC1/AC4 homologous siRNAs showed that this tolerance is most likely associated with post-transcriptional gene silencing of the virus. This is the first report of targeting the overlapping AC1 and AC4 genes of SACMV conferring CMD tolerance in cassava.

Temporal evaluation of estrogenic endocrine disruption markers in smallmouth bass (Micropterus dolomieu) reveals seasonal variability in intersex.

A reconnaissance project completed in 2009 identified intersex and elevated plasma vitellogenin in male smallmouth bass inhabiting the Missisquoi River, VT. In an attempt to identify the presence and seasonality of putative endocrine disrupting chemicals or other factors associated with these observations, a comprehensive reevaluation was conducted between September 2012 and June 2014. Here, we collected smallmouth bass from three physically partitioned reaches along the river to measure biomarkers of estrogenic endocrine disruption in smallmouth bass. In addition, polar organic chemical integrative samples (POCIS) were deployed to identify specific chemicals associated with biological observations. We did not observe biological differences across reaches indicating the absence of clear point source contributions to the observation of intersex. Interestingly, intersex prevalence and severity decreased in a stepwise manner over the timespan of the project. Intersex decreased from 92.8% to 28.1%. The only significant predictor of intersex prevalence was year of capture, based on logistic regression analysis. The mixed model of fish length and year-of-capture best predicted intersex severity. Intersex severity was also significantly different across late summer and early spring collections indicating seasonal changes in this metric. Plasma vitellogenin and liver vitellogenin Aa transcript abundance in males did not indicate exposure to estrogenic endocrine disrupting chemicals at any of the four sample collections. Analysis of chemicals captured by the POCIS as well as results of screening discrete water samples or POCIS extracts did not indicate the contribution of appreciable estrogenic chemicals. It is possible that unreported changes in land-use activity have ameliorated the problem, and our observations indicate recovery. Regardless, this work clearly emphasizes that single, snap shot sampling for intersex may not yield representative data given that the manifestation of this condition within a population can change dramatically over time.

Goosefish Lophius americanus fecundity and spawning frequency, with implications for population reproductive potential.

To improve knowledge of goosefish Lophius americanus' reproductive biology, females were collected during 2009-2012 from the Mid-Atlantic Bight shelf region of the U.S. east coast. Batch fecundity increased with total length (LT ), from 229 100 to 2 243 300 mature oocytes per female (LT range: 55·5-112 cm; n = 54). This estimate of fecundity at LT is lower than one derived from a sample collected during 1982-1985. Examination of whole oocyte diameters in different months indicated that L. americanus is a serial spawner, releasing more than one egg veil per spawning season, as suspected or observed for other Lophius species. Seasonality of spawning was evident from whole oocytes and gonad histology, and from larval fish surveys spanning the U.S. north-east shelf, and confirmed a protracted (c. 6 months) spawning period. Peak spawning activity progressed northward from spring to autumn. The population-level implications of these results were explored by estimating population reproductive potential (PRP ), which considered the value of both current and future per capita reproduction using decade-specific age structure and fecundity at length. PRP is now more than 50% lower compared with the historical period (1982-1985), a result of the lower proportions of large females and reduced fecundity across all sizes. Mechanisms that could explain this loss of stock productivity are fishing-induced size-age truncation or regime shifts in egg production caused by changes in energy density of common forage species.

Tumours in white suckers from Lake Michigan tributaries: pathology and prevalence.

The prevalence and histopathology of neoplastic lesions were assessed in white sucker Catostomus commersonii captured at two Lake Michigan Areas of Concern (AOCs), the Sheboygan River and Milwaukee Estuary. Findings were compared to those observed at two non-AOC sites, the Root and Kewaunee rivers. At each site, approximately 200 adult suckers were collected during their spawning migration. Raised skin lesions were observed at all sites and included discrete white spots, mucoid plaques on the body surface and fins and large papillomatous lesions on lips and body. Microscopically, hyperplasia, papilloma and squamous cell carcinoma were documented. Liver neoplasms were also observed at all sites and included both hepatocellular and biliary tumours. Based on land use, the Kewaunee River was the site least impacted by human activities previously associated with fish tumours and had significantly fewer liver neoplasms when compared to the other sites. The proportion of white suckers with liver tumours followed the same patterns as the proportion of urban land use in the watershed: the Milwaukee Estuary had the highest prevalence, followed by the Root, Sheboygan and Kewaunee rivers. The overall skin neoplasm (papilloma and carcinoma) prevalence did not follow the same pattern, although the percentage of white suckers with squamous cell carcinoma exhibited a similar relationship to land use. Testicular tumours (seminoma) were observed at both AOC sites but not at the non-AOC sites. Both skin and liver tumours were significantly and positively associated with age but not sex.

Joint kinematic calculation based on clinical direct kinematic versus inverse kinematic gait models.

Most clinical gait laboratories use the conventional gait analysis model. This model uses a computational method called Direct Kinematics (DK) to calculate joint kinematics. In contrast, musculoskeletal modelling approaches use Inverse Kinematics (IK) to obtain joint angles. IK allows additional analysis (e.g. muscle-tendon length estimates), which may provide valuable information for clinical decision-making in people with movement disorders. The twofold aims of the current study were: (1) to compare joint kinematics obtained by a clinical DK model (Vicon Plug-in-Gait) with those produced by a widely used IK model (available with the OpenSim distribution), and (2) to evaluate the difference in joint kinematics that can be solely attributed to the different computational methods (DK versus IK), anatomical models and marker sets by using MRI based models. Eight children with cerebral palsy were recruited and presented for gait and MRI data collection sessions. Differences in joint kinematics up to 13° were found between the Plug-in-Gait and the gait 2392 OpenSim model. The majority of these differences (94.4%) were attributed to differences in the anatomical models, which included different anatomical segment frames and joint constraints. Different computational methods (DK versus IK) were responsible for only 2.7% of the differences. We recommend using the same anatomical model for kinematic and musculoskeletal analysis to ensure consistency between the obtained joint angles and musculoskeletal estimates.

Evidence of estrogenic endocrine disruption in smallmouth and largemouth bass inhabiting Northeast U.S. national wildlife refuge waters: A reconnaissance study.

Intersex as the manifestation of testicular oocytes (TO) in male gonochoristic fishes has been used as an indicator of estrogenic exposure. Here we evaluated largemouth bass (Micropterus salmoides) or smallmouth bass (Micropterus dolomieu) form 19 National Wildlife Refuges (NWRs) in the Northeast U.S. inhabiting waters on or near NWR lands for evidence of estrogenic endocrine disruption. Waterbodies sampled included rivers, lakes, impoundments, ponds, and reservoirs. Here we focus on evidence of endocrine disruption in male bass evidenced by gonad histopathology including intersex or abnormal plasma vitellogenin (Vtg) concentrations. During the fall seasons of 2008-2010, we collected male smallmouth bass (n=118) from 12 sites and largemouth bass (n=173) from 27 sites. Intersex in male smallmouth bass was observed at all sites and ranged from 60% to 100%; in male largemouth bass the range was 0-100%. Estrogenicity, as measured using a bioluminescent yeast reporter, was detected above the probable no effects concentration (0.73ng/L) in ambient water samples from 79% of the NWR sites. Additionally, the presence of androgen receptor and glucocorticoid receptor ligands were noted as measured via novel nuclear receptor translocation assays. Mean plasma Vtg was elevated (>0.2mg/ml) in male smallmouth bass at four sites and in male largemouth bass at one site. This is the first reconnaissance survey of this scope conducted on US National Wildlife Refuges. The baseline data collected here provide a necessary benchmark for future monitoring and justify more comprehensive NWR-specific studies.

Neonatal referrals to the coroner service: a short survey on current practice.

In Ireland, coroners are required by law to ascertain the details of potentially unexplained deaths. The Coroner's Acts (1962 and 2005) detail deaths which must be notified to the coroner. We surveyed current practice regarding the notification of the Coroner Service following neonatal deaths by telephone interview of senior clinical nurse managers of paediatric units with neonatal inpatients. Five of 21 units (23.8%) reported that all neonatal deaths would prompt contact with the Coroner Service, with four more units (19%) reporting that unexpected neonatal deaths would be referred. Nine units (42.9%) reported that referral was at the discretion of the consultant involved while three units (14.3%) do not refer neonatal deaths to the coroner.

Reproductive health indicators of fishes from Pennsylvania watersheds: association with chemicals of emerging concern.

Fishes were collected at 16 sites within the three major river drainages (Delaware, Susquehanna, and Ohio) of Pennsylvania. Three species were evaluated for biomarkers of estrogenic/antiandrogenic exposure, including plasma vitellogenin and testicular oocytes in male fishes. Smallmouth bass Micropterus dolomieu, white sucker Catostomus commersonii, and redhorse sucker Moxostoma species were collected in the summer, a period of low flow and low reproductive activity. Smallmouth bass were the only species in which testicular oocytes were observed; however, measurable concentrations of plasma vitellogenin were found in male bass and white sucker. The percentage of male bass with testicular oocytes ranged from 10 to 100%, with the highest prevalence and severity in bass collected in the Susquehanna drainage. The percentage of males with plasma vitellogenin ranged from 0 to 100% in both bass and sucker. Biological findings were compared with chemical analyses of discrete water samples collected at the time of fish collections. Estrone concentrations correlated with testicular oocytes prevalence and severity and with the percentage of male bass with vitellogenin. No correlations were noted with the percentage of male sucker with vitellogenin and water chemical concentrations. The prevalence and severity of testicular oocytes in bass also correlated with the percent of agricultural land use in the watershed above a site. Two sites within the Susquehanna drainage and one in the Delaware were immediately downstream of wastewater treatment plants to compare results with upstream fish. The percentage of male bass with testicular oocytes was not consistently higher downstream; however, severity did tend to increase downstream.

Health of white sucker within the St. Louis River area of concern associated with habitat usage as assessed using stable isotopes.

In Spring 2011, 200 adult white sucker were collected in four areas of the St. Louis River area of concern (AOC), located in Minnesota and Wisconsin, USA. The areas included the upper AOC as a reference area, the upper estuary, St. Louis Bay and Superior Bay. Grossly visible abnormalities were documented and preserved for microscopic analyses, as were five to eight representative pieces of liver tissue. A piece of dorsal muscle was preserved for stable isotope analyses and otoliths removed for age determination. The incidence of raised skin lesions (mucoid plaques) was high (31 %), however, microscopically only 4.5 % of the white suckers had neoplasia (papillomas). The remaining lesions were epidermal hyperplasia. Superior Bay had the lowest percentage of skin/lip lesions (10 %), while St. Louis Bay had the highest (44 %). St. Louis Bay also had the highest incidence of skin neoplasms (12 %). No hepatocellular neoplasms were documented, however bile duct tumors were observed in 4.5 % of the suckers. Foci of cellular alteration were observed in fish from all sites except the upper AOC. Stable isotope data indicated that most of the suckers relied on the St. Louis River AOC for the majority (>75 %) of their diet, indicating they were resident within the AOC and not in Lake Superior. The amount of diet obtained from the upper estuary was a significant predictor of skin lesion incidence. Hence, habitat use within the AOC appears to be an important risk factor for skin and possibly, liver lesions.

A redescription of Myxobolus inornatus from young-of-the-year smallmouth bass (Micropterus dolomieu).

During investigations of young-of-the year smallmouth bass ( Micropterus dolomieu ) mortalities in the Susquehanna River, Pennsylvania, U.S.A. and affected tributaries, raised areas were noted in the muscle in the vicinity of the caudal peduncle. The raised areas were caused by plasmodia of a myxozoan parasite. Spores found within plasmodia were similar to those of Myxobolus inornatus previously described from the caudal peduncle of fingerling largemouth bass ( Micropterus salmoides ) in Montana. Here, M. inornatus is redescribed based on histologic comparisons and spore measurements. The addition of spore photographs, line drawings, a voucher specimen, and partial small-subunit ribosomal (rSSU) DNA gene sequence are new in this study. This is also the first description of M. inornatus from smallmouth bass. The plasmodia of M. inornatus were grossly observed at the base of the caudal and dorsal fins and were 280.3 ± 33.5 (range 77.1-920.3) µm long and 320.6 ± 41.0 (range 74.85-898.4) µm wide. In some instances, plasmodia of M. inornatus were large enough to rupture the epidermis or were associated with misaligned vertebrae. The slightly pyriform spores were 11.3 ± 0.2 (range 8.6-17.4) µm in length and 8.6 ± 0.2 (range 7.1-13.7) µm wide with an iodinophilous vacuole and a sutural ridge with 8 to 10 sutural folds. The SSU rDNA gene sequence places M. inornatus in a sister group with Myxobolus osburni .

The larger exercise stroke volume in endurance-trained men does not result from increased left ventricular early or late inflow or tissue velocities.

AIM: To determine whether the larger exercise stroke volume in senior endurance-trained athletes results from an attenuation of age-related alterations in left ventricular (LV) early diastolic filling or a more vigorous late filling. METHODS: Body composition (DEXA), VO(2)peak, stroke volume (CO(2) rebreathing) and Doppler measures of early and late mitral inflow and mitral annular velocities were collected at seated upright rest and heart rate-matched exercise (100 and 120 bpm) in trained and untrained younger (18-30 years) men and trained and untrained older (60-80 years) healthy men. RESULTS: Ageing had a greater effect than training status on seated rest mitral inflow and tissue Doppler imaging parameters, as shown by a lower peak early-to-late mitral inflow velocity ratio (E/A ratio) and slower peak early mitral annular velocity (Em) in older compared with younger men. Exercise stroke volume was unaffected by healthy ageing; however, Em, an index of early LV lengthening rate and relaxation, was slower (P < 0.001), while measures of atrial systole were increased (P < 0.001) during exercise in older men. Stroke volume during exercise was larger in the trained men (P < 0.001); however, early and late mitral inflow and tissue velocities were not different between trained and untrained men. CONCLUSION: The larger exercise stroke volume in trained older male athletes does not seem to be related to faster filling or lengthening velocities during early or late filling. Thus, a larger, more compliant left ventricle in combination with an increased blood volume may explain the larger LV filling volumes in trained seniors.

Analysis of total aerobic viable counts in raw fish by high-throughput optical oxygen respirometry.

A simple, miniaturized, and automated screening assay for the determination of total aerobic viable counts in fish samples is presented here. Fish tissue homogenates were prepared in peptone buffered water medium, according to standard method, and aliquots were dispensed into wells of a 96-well plate with the phosphorescent, oxygen-sensing probe GreenLight. Sample wells were covered with mineral oil (barrier for ambient oxygen), and the plate was monitored on a standard fluorescent reader at 30°C. The samples produced characteristic profiles, with a sharp increase in fluorescence above the baseline level at a certain threshold time, which could be correlated with initial microbial load. Five different fish species were analyzed: salmon, cod, plaice, mackerel, and whiting. Using a conventional agar plating method, the relationship between the threshold time and total aerobic viable counts load (in CFU per gram) was established, calibration curve generated, and the test was validated with 169 unknown fish samples. It showed a dynamic range of 10(4) to 10(7) CFU/g, accuracy of ± 1 log(CFU/g), assay time of 2 to 12 h (depending on the level of contamination), ruggedness with respect to the key assay parameters, simplicity (three pipetting steps, no serial dilutions), real-time data output, high sample throughput, and automation. With this test, quality of fish samples, CFU-per-gram levels, and their respective time profiles were determined.

Sensory comparison of commercial low and high oxygen modified atmosphere packed sirloin beef steaks.

The objectives of this study were to investigate the effects of using commercially low and high modified atmosphere packaging (MAP) on quality characteristics of sirloin beef steaks. Gas mixtures used included 80% O(2):20% CO(2) (O(2)80), 70% O(2)/30% CO(2) (O(2)70) and 50% O(2)/30% CO(2):20% N(2) (O(2)50) and for commercial packs O(2)75 ± 5%, CO(2)25 ± 5%, <5% N(2)-(O(2)Com). All samples were packed in similar tray and packaging film formats. The experimental parameters monitored included microbiological, physiochemical and sensory measurements (naïve assessors). Microbial counts did not exceed the recommended legal ranges over the storage period. However the numbers of LAB (lactic acid bacteria) were the highest for commercially-packed samples (O(2)Com) in comparison to laboratory packaged samples (O(2)80, O(2)70 and O(2)50). Commercially-packaged samples eventually spoiled due to the occurrence of off-flavours and off-odours and subsequently were the least acceptable to sensory naïve assessors.

The effects of different cooking regimes on the cook yield and tenderness of non-injected and injection enhanced forequarter beef muscles.

The aim was to investigate the effect of different cooking regimes on the cook yield and tenderness of non-injected and brine injected (0.5% residual NaCl) bovine M. triceps brachii caput longum (TB), M. supraspinatus (SP) and M. pectoralis profundus (PP). Injected and non-injected TB, SP and PP muscle sections (400 g) were (a) conventionally oven cooked to 72 degrees C or cooked slowly (using a Delta10 programme) to 72 degrees C or (b) cooked in a water bath to 72 degrees C or cooked in a water bath to 55 degrees C and held at this temperature for 2 h before heating to 72 degrees C. In addition, injected PP muscle sections were oven cooked to 69 degrees C and held at this temperature for up to 12 h. Slow cooking using a Delta10 programme had no significant (P<0.05) effect on WBSF values of injected or non-injected SP and TB muscles but significantly (P<0.05) decreased the WBSF values of injected and non-injected PP muscles when compared to conventional cooking. Slow cooking significantly (P<0.05) increased % cook yield of injected PP, SP and TB muscles. Staged cooking significantly (P<0.05) decreased the WBSF values and had no significant effect on sensory tenderness ratings of non-injected TB, SP and PP muscles and injected PP muscles. Staged cooked injected or non-injected PP, SP and TB muscles had lower % cook yield values than those cooked straight to 72 degrees C. Increasing the cooking time of injected PP muscles at 69 degrees C to 8 and 12 h decreased % cook yield, decreased WBSF values and increased sensory tenderness ratings. It also alleviated the problem of residual chewiness which was evident in PP muscles cooked using the other regimes.

The effect of sodium lactate, potassium lactate, carrageenan, whey protein concentrate, yeast extract and fungal proteinases on the cook yield and tenderness of bovine chuck muscles.

This study evaluated the efficacy of injection with enhancement solutions containing sodium lactate (NaLac), potassium lactate (KLac), carrageenan, whey protein concentrate (WPC), yeast extract or fungal proteinases alone or in combination with NaCl at increasing the tenderness and cook yield of bovine M.supraspinatus and M. tricepsbrachii caput longum. Muscle sections (400g) were injected with enhancement solutions at an injection rate of 110% to give specific residual concentrations as follows: 0.5% NaCl; 2% NaLac; 2% KLac; 0.5% NaCl+1 or 2% NaLac; 0.5% NaCl+1% KLac; 0.5% NaCl+0.4% sodium tripolyphosphate (STPP)+2% NaLac; 0.5% NaCl+0.4% STPP, 1.5% WPC+/-0.5% NaCl, 1.0% carrageenan+/-0.5% NaCl, 0.5% yeast extract or 0.0005% and 0.001% fungal enzymes. Injection with solutions containing sodium or potassium lactates (alone or in combination with NaCl and STPP), WPC, carrageenan and yeast extract significantly (P<0.05) decreased WBSF values and increased sensory tenderness ratings, compared to non-injected controls. All of these ingredients in water also significantly (P<0.05) increased cook yield with the exception of yeast extract which had no significant effect. The fungal enzymes in a water carrier acted as effective tenderising agents in both muscles but when used at the higher level resulted in a significant decrease in percentage cook yield. Injection of the chuck muscles with these ingredients and water represents an effective method of improving their tenderness and in most cases also increasing percentage cook yield.

Medial humeral condyle fracture with an ipsilateral dislocated radial head.

We present the first reported case of a combined medial humeral condyle fracture with ipsilateral radial head dislocation. This injury was sustained by a 7-year-old girl following a fall on an outstretched hand. The operative technique is described. At 6-month follow-up, the patient had normal alignment of the limb and achieved full range of motion.

Two-year placebo-controlled trial of botulinum toxin A for leg spasticity in cerebral palsy.

BACKGROUND: The controlled evidence favoring botulinum toxin A (BtA) treatment for spasticity in cerebral palsy is based on short-term studies. METHODS: We conducted a randomized, double-blind, placebo-controlled, parallel-group study of BtA (Dysport) for leg spasticity in 64 children with cerebral palsy. For 2 years, the children received trial injections of up to 30 mu/kg every 3 months if clinically indicated. RESULTS: For the primary endpoints of Gross Motor Function Measure (GMFM) and Pediatric Evaluation of Disability Index (PEDI) scaled scores at 2 years (trough rather than peak effect), there were no differences between the mean change scores of each group. For the GMFM total score, the 95% CI of -4.81 to 1.90 excluded a 5-point difference in either direction, and a 2-point benefit with 95% confidence. There were no differences in adverse events. CONCLUSIONS: There was no evidence of cumulative or persisting benefit from repeated botulinum toxin A (BtA) at the injection cycle troughs at 1 year or 2 years. The dose was not enough to change spasticity measures and thus GMFM in this heterogeneous group. Ceiling effects in GMFM and Pediatric Evaluation of Disability Index (PEDI) may have reduced responsiveness. This finding does not deny the value, individually, of single injection cycles or prove that repeating them is unhelpful. In this regard, BtA treatment can be viewed in the same light as other temporary measures to relieve spasticity, such as oral or intrathecal agents: there is no evidence of continuing benefit if the treatment ceases. The study provides long-term, fully controlled adverse event data and has not revealed any long-term adverse effects.