The Fate of Arginine and Proline Carbon in Squid Tissues

The metabolism of proline and arginine was investigated in kidney, gill, and heart of the pelagic squid, Symplectoteuthis. The rates of CO2 release from 14C-proline exceeded the rates from 14C-arginine. The metabolic rate of arginine and proline was assessed by monitoring the incorporation of arginine-derived carbon into various intermediates. Arginine was metabolized, through ornithine, to proline as well as to glutamate and various subsequent derivatives (alanine, octopine, aspartate, and carboxylic acids). The same components became labeled using 14C-proline as the starting substrate, but only the gill was capable of converting proline to arginine via the urea cycle. In addition, 14C-proline oxidation rates were high enough to exceed those of 14C-glucose in at least three tissues, kidney, heart, and inner mantle muscle

Repetitive task training for improving functional ability after stroke

<p><b>Objectives:</b> The objective of this review was to determine if repetitive task training after stroke improves global, upper, or lower limb function and if treatment effects are influenced by the amount, type, or timing of practice.</p> <p><b>Search Strategy:</b> We searched the Cochrane Stroke Trials Register (to October 2006); The Cochrane Library, MEDLINE, EMBASE, CINAHL, AMED, SportDiscus, Science Citation Index, Index to Theses, ZETOC, PEDro, and OT Seeker (all to September 2006); and OT search (to March 2006). We also searched for unpublished/non-English language trials; combed conference proceedings and reference lists; requested information on bulletin boards; and contacted trial authors.</p> <p><b>Selection Criteria:</b> Selection criteria included randomized/quasirandomized trials in adults after stroke, of interventions that included an active motor sequence performed repetitively within a single training session, a clear functional goal, and a quantifiable level of practice.</p> <p><b>Data Collection and Analysis:</b> Two authors independently screened abstracts, extracted data, and appraised trial quality. Further information was obtained from study authors. Results from individual trials were combined using meta-analytic techniques appropriate to the data extracted and the level of between-trial heterogeneity.</p> <p><b>Main Results:</b> Fourteen trials with 17 intervention-control pairs and 659 participants were included. Primary outcomes showed that treatment effects were statistically significant for walking distance (see the Figure); walking speed (standardized mean difference, 0.29; 95% CI, 0.04 to 0.53); and sit-to-stand (standardized effect estimate, 0.35; 95% CI, 0.13 to 0.56). Treatment effects were of borderline statistical significance for functional ambulation.</p&gt

Tensor electrical impedance myography identifies clinically relevant features in amyotrophic lateral sclerosis

Objective. Electrical impedance myography (EIM) shows promise as an effective biomarker in amyotrophic lateral sclerosis (ALS). EIM applies multiple input frequencies to characterise muscle properties, often via multiple electrode configurations. Herein, we assess if non-negative tensor factorisation (NTF) can provide a framework for identifying clinically relevant features within a high dimensional EIM dataset. Approach. EIM data were recorded from the tongue of healthy and ALS diseased individuals. Resistivity and reactivity measurements were made for 14 frequencies, in three electrode configurations. This gives 84 (2 × 14 × 3) distinct data points per participant. NTF was applied to the dataset for dimensionality reduction, termed tensor EIM. Significance tests, symptom correlation and classification approaches were explored to compare NTF to using all raw data and feature selection. Main Results. Tensor EIM provides highly significant differentiation between healthy and ALS patients (p < 0.001, AUROC = 0.78). Similarly tensor EIM differentiates between mild and severe disease states (p < 0.001, AUROC = 0.75) and significantly correlates with symptoms (ρ = 0.7, p < 0.001). A trend of centre frequency shifting to the right was identified in diseased spectra, which is in line with the electrical changes expected following muscle atrophy. Significance. Tensor EIM provides clinically relevant metrics for identifying ALS-related muscle disease. This procedure has the advantage of using the whole spectral dataset, with reduced risk of overfitting. The process identifies spectral shapes specific to disease allowing for a deeper clinical interpretation

Tensor electrical impedance myography identifies bulbardisease progression in amyotrophic lateral sclerosis

Objective Electrical impedance myography (EIM) is a promising biomarker for amyotrophic lateral sclerosis (ALS). A key issue is how best to utilise the complex high dimensional, multi-frequency data output by EIM to fully characterise the progression of disease. Methods Muscle volume conduction properties were obtained from EIM recordings of the tongue across three electrode configurations and 14 input frequencies (76 Hz–625 kHz). Analyses of individual frequencies, averaged EIM spectra and non-negative tensor factorisation were undertaken. Longitudinal data were collected from 28 patients and 17 healthy volunteers at 3-monthly intervals for a maximum of 9 months. EIM was evaluated against the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) bulbar sub-score, tongue strength and an overall bulbar disease burden score. Results Longitudinal changes to individual patient EIM spectra demonstrated complex shifts in the spectral shape. At a group level, a clear pattern emerged over time, characterised by an increase in centre frequency and general shift to the right of the spectral shape. Tensor factorisation reduced the spectral data from a total of 168 data points per participant per recording to a single value which captured the complexity of the longitudinal data and which we call tensor EIM (T-EIM). The absolute change in tensor EIM significantly increased within 3 months and continued to do so over the 9-month study duration. In a hypothetical clinical trial scenario tensor EIM required fewer participants (n = 64 at 50% treatment effect), than single frequency measures (n range 87–802) or ALSFRS-R bulbar subscore (n = 298). Conclusions Changes to tongue EIM spectra over time in ALS are complex. Tensor EIM captured and quantified disease progression and was more sensitive to changes than single frequency EIM measures and other biomarkers of bulbar disease. Significance Objective biomarkers for the assessment of bulbar disease in ALS are lacking. Tensor EIM enhances the biomarker potential of EIM data and can improve bulbar symptom monitoring in clinical trials

Modelling and analysis of electrical impedance myography of the lateral tongue

Objective: Electrical impedance myography (EIM) performed on the centre of the tongue shows promise in detecting amyotrophic lateral sclerosis (ALS). Lateral recordings may improve diagnostic performance and provide pathophysiological insights through the assessment of asymmetry. However, it is not known if electrode proximity to the muscle edge, or electrode rotation, distort spectra. We evaluated this using finite element-based modelling. Approach: Nine thousand EIM from patients and healthy volunteers were used to develop a finite element model for phase and magnitude. Simulations varied electrode proximity to the muscle edge and electrode rotation. LT-Spice simulations assessed disease effects. Patient data were assessed for reliability, agreement and classification performance. Main results: No effect on phase spectra was seen if all electrodes remained in contact with the tissue. Small effects on magnitude were observed. Cole-Cole circuit simulations indicated capacitance reduced with disease severity. Lateral tongue muscle recordings in both patients and healthy volunteers were reproducible and symmetrical. Combined lateral/central tongue EIM improved disease classification compared to either placement alone. Significance: Lateral EIM tongue measurements using phase angle are feasible. Such measurements are reliable, find no evidence of tongue muscle asymmetry in ALS and improve disease classification. Lateral measurements enhance tongue EIM in ALS

Multi-dimensional electrical impedance myography of the tongue as a potential biomarker for amyotrophic lateral sclerosis

Objective In amyotrophic lateral sclerosis (ALS) bulbar disease biomarkers are lacking. We evaluated a novel tongue electrical impedance myography (EIM) system, utilising both 2D and 3D electrode configurations for detection of tongue pathology. Methods Longitudinal multi-frequency phase angle spectra were recorded from 41 patients with ALS (baseline, 3 and 6 months) and 30 healthy volunteers (baseline and 6 months). ALS functional rating scale-revised (ALSFRS-R) data and quantitative tongue strength measurements were collected. EIM data were analysed for reliability (intra-class correlation coefficient; ICC) and differences between patients and volunteers ascertained using both univariate (Mann-Whitney U test) and multivariate techniques (feature selection and L2 norm). Results The device produced highly reliable data (pooled ICC: 0.836). Significant EIM differences were apparent between ALS patients and healthy volunteers (P<0.001). EIM data demonstrated a significant relationship to tongue strength and bulbar ALSFRS-R scores (P<0.015). The EIM recordings revealed a group level longitudinal change over 6 months and consistently identified patients in whom symptoms or tongue strength changed. Conclusions The novel EIM tongue system produces reliable data and can differentiate between healthy muscle and ALS-related disease. Significance Tongue EIM utilising multiple frequencies and electrode configurations has potential as a bulbar disease biomarker in ALS

Host-associated Genetic Import in Campylobacter jejuni

C. jejuni genomes have a host signature that enables attribution of isolates to animal sources

Bayesian robustness for decision making problems: Applications in medical contexts

AbstractPractical implementation of Bayesian decision making is hindered by the fact that optimal decisions may be sensitive to the model inputs: the prior, the likelihood and/or the underlying utility function. Given the structure of a problem, the analyst has to decide which sensitivity measures are relevant and compute them efficiently. We address the issue of robustness of the optimal action in a decision making problem with respect to the prior model and the utility function. We discuss some general principles and apply novel computational strategies in the context of two relatively complex medical decision making problems

Molecular profiling of breast and lung cancer in women with HIV reveals high tumor mutational burden

Objective: This study compared the mutation profile and tumor mutational burden (TMB) in women with HIV (WWH) diagnosed with lung adenocarcinoma (n = 8) or breast ductal neoplasm (n = 13) who were enrolled into the Women's Interagency HIV Study (WIHS). Design: Previous studies tended to focus on single institutions based on sample availability. This study is based on a representative, multicenter cohort that represents the racial and ethnic composition of women with HIV in the United States Methods: The study sequenced the complete human exome of n = 26 cancer samples from HIV-positive women, using Ion torrent next-generation sequencing. The study cohort was compared with a HIV-negative cohort obtained from the Genomic Data Commons Data Portal of the NCI. Results: There were no differences in known cancer mutations between breast cancer and lung cancer that developed in WWH and those that developed in HIV-negative (HIV-) women; however, WWH presented a significantly higher TMB in comparison to HIV- patients. Seventy-five percent of lung cancers and 61% of breast cancers were defined as TMB-high (more than 10 mutation/mb of DNA). Conclusion: This study affirms the recommendation that WWH be included in clinical trials of novel treatments for these cancers. Although these data are preliminary, the high TMB in WLHV suggests, paradoxically, that this immune challenged population may benefit greatly from immune checkpoint inhibitor therapies

Examining the validity of the Athlete Engagement Questionnaire (AEQ) within a Portuguese sport setting

Sport psychology literature suggests that understanding engagement levels is pivotal to promote positive sporting experiences among athletes. The purpose of this study was to examine the psychometric properties of the Athlete Engagement Questionnaire among Portuguese sport athletes. Two distinct samples of Portuguese athletes from different competitive levels were collected, and the results of a confirmatory factor analysis demonstrated a good fit of the model to the data. A review of the psychometric properties indicated that all factors showed good composite reliability, convergent validity, and discriminant validity. In addition, a multi-groups analysis showed the invariance of the model in two independent samples providing evidence of cross validity. Implications of these results for scholars and coaches are discussed and guidelines for future studies are suggested