Muscle function in a patient with brody's disease

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Multimodal multi-center analysis of electroconvulsive therapy effects in depression: Brainwide gray matter increase without functional changes

Background: Electroconvulsive therapy (ECT) is an effective treatment for severe depression and induces gray matter (GM) increases in the brain. Small-scale studies suggest that ECT also leads to changes in brain functioning, but findings are inconsistent. In this study, we investigated the influence of ECT on changes in both brain structure and function and their relation to clinical improvement using multicenter neuroimaging data from the Global ECT-MRI Research Collaboration (GEMRIC). Methods: We analyzed T1-weighted structural magnetic resonance imaging (MRI) and functional resting-state MRI data of 88 individuals (49 male) with depressive episodes before and within one week after ECT. We performed voxel-based morphometry on the structural data and calculated fractional amplitudes of low-frequency fluctuations, regional homogeneity, degree centrality, functional connectomics, and hippocampus connectivity for the functional data in both unimodal and multimodal analyses. Longitudinal effects in the ECT group were compared to repeated measures of healthy controls (n = 27). Results: Wide-spread increases in GM volume were found in patients following ECT. In contrast, no changes in any of the functional measures were observed, and there were no significant differences in structural or functional changes between ECT responders and non-responders. Multimodal analysis revealed that volume increases in the striatum, supplementary motor area and fusiform gyrus were associated with local changes in brain function. Conclusion: These results confirm wide-spread increases in GM volume, but suggest that this is not accompanied by functional changes or associated with clinical response. Instead, focal changes in brain function appear related to individual differences in brain volume increases.publishedVersio

Hot-water immersion does not increase postprandial muscle protein synthesis rates during recovery from resistance-type exercise in healthy, young males

The purpose of this study was to assess the impact of postexercise hot-water immersion on postprandial myofibrillar protein synthesis rates during recovery from a single bout of resistance-type exercise in healthy, young men. Twelve healthy, adult men (age: 23 ± 1 y) performed a single bout of resistance-type exercise followed by 20 min of water immersion of both legs. One leg was immersed in hot water [46°C: hot-water immersion (HWI)], while the other leg was immersed in thermoneutral water (30°C: CON). After water immersion, a beverage was ingested containing 20 g intrinsically L-[1-13C]-phenylalanine and L-[1-13C]-leucine labeled milk protein with 45 g of carbohydrates. In addition, primed continuous L-[ring-2H5]-phenylalanine and L-[1-13C]-leucine infusions were applied, with frequent collection of blood and muscle samples to assess myofibrillar protein synthesis rates in vivo over a 5-h recovery period. Muscle temperature immediately after water immersion was higher in the HWI compared with the CON leg (37.5 ± 0.1 vs. 35.2 ± 0.2°C; P < 0.001). Incorporation of dietary protein-derived L-[1-13C]-phenylalanine into myofibrillar protein did not differ between the HWI and CON leg during the 5-h recovery period (0.025 ± 0.003 vs. 0.024 ± 0.002 MPE; P = 0.953). Postexercise myofibrillar protein synthesis rates did not differ between the HWI and CON leg based upon L-[1-13C]-leucine (0.050 ± 0.005 vs. 0.049 ± 0.002%/h; P = 0.815) and L-[ring-2H5]-phenylalanine (0.048 ± 0.002 vs. 0.047 ± 0.003%/h; P = 0.877), respectively. Hot-water immersion during recovery from resistance-type exercise does not increase the postprandial rise in myofibrillar protein synthesis rates. In addition, postexercise hot-water immersion does not increase the capacity of the muscle to incorporate dietary protein-derived amino acids in muscle tissue protein during subsequent recovery

Deregulated microRNAs in neurofibromatosis type 1 derived malignant peripheral nerve sheath tumors

Malignant peripheral nerve sheath tumors (MPNST) are aggressive cancers that occur spontaneously (sporadic MPNST) or from benign plexiform neurofibromas in neurofibromatosis type 1 (NF1) patients. MPNSTs metastasize easily, are therapy resistant and are frequently fatal. The molecular changes underlying the malignant transformation in the NF1 setting are incompletely understood. Here we investigate the involvement of microRNAs in this process. MicroRNA expression profiles were determined from a series of archival, paired samples of plexiform neurofibroma and MPNST. Ninety differentially expressed microRNAs were identified between the paired samples. Three downregulated microRNAs (let-7b-5p, miR-143-3p, miR-145-5p) and two upregulated microRNAs (miR135b-5p and miR-889-3p) in MPNST were selected for functional characterization. In general, their differential expression was validated in a relevant cell line panel but only partly in a series of unpaired, fresh frozen tumor samples. As part of the validation process we also analyzed microRNA expression profiles of sporadic MPNSTs observing that microRNA expression discriminates NF1-associated and sporadic MPNSTs. The role of microRNAs in cancer progression was examined in NF1-derived MPNST cell lines by transiently modulating microRNA levels. Our findings indicate that some microRNAs affect migratory and invasive capabilities and Wnt signaling activity but the effects are distinct in different cell lines. We conclude that miRNAs play essential regulatory roles in MPNST facilitating tumor progression

Is tissue still the issue? The promise of liquid biopsy in uveal melanoma

Uveal melanoma (UM) is the second most frequent type of melanoma. Therapeutic options for UM favor minimally invasive techniques such as irradiation for vision preservation. As a consequence, no tumor material is obtained. Without available tissue, molecular analyses for gene expression, mutation or copy number analysis cannot be performed. Thus, proper patient stratification is impossible and patients\u27 uncertainty about their prognosis rises. Minimally invasive techniques have been studied for prognostication in UM. Blood-based biomarker analysis has become more common in recent years; however, no clinically standardized protocol exists. This review summarizes insights in biomarker analysis, addressing new insights in circulating tumor cells, circulating tumor DNA, extracellular vesicles, proteomics, and metabolomics. Additionally, medical imaging can play a significant role in staging, surveillance, and prognostication of UM and is addressed in this review. We propose that combining multiple minimally invasive modalities using tumor biomarkers should be the way forward and warrant more attention in the coming years

Uveal Melanoma Patients Have a Distinct Metabolic Phenotype in Peripheral Blood

Uveal melanomas (UM) are detected earlier. Consequently, tumors are smaller, allowing for novel eye-preserving treatments. This reduces tumor tissue available for genomic profiling. Additionally, these small tumors can be hard to differentiate from nevi, creating the need for minimally invasive detection and prognostication. Metabolites show promise as minimally invasive detection by resembling the biological phenotype. In this pilot study, we determined metabolite patterns in the peripheral blood of UM patients (n = 113) and controls (n = 46) using untargeted metabolomics. Using a random forest classifier (RFC) and leave-one-out cross-validation, we confirmed discriminatory metabolite patterns in UM patients compared to controls with an area under the curve of the receiver operating characteristic of 0.99 in both positive and negative ion modes. The RFC and leave-one-out cross-validation did not reveal discriminatory metabolite patterns in high-risk versus low-risk of metastasizing in UM patients. Ten-time repeated analyses of the RFC and LOOCV using 50% randomly distributed samples showed similar results for UM patients versus controls and prognostic groups. Pathway analysis using annotated metabolites indicated dysregulation of several processes associated with malignancies. Consequently, minimally invasive metabolomics could potentially allow for screening as it distinguishes metabolite patterns that are putatively associated with oncogenic processes in the peripheral blood plasma of UM patients from controls at the time of diagnosis.</p

Ingestion of an ample amount of meat substitute based on a lysine-enriched,plant-based protein blend stimulates postprandial muscle proteinsynthesis to a similar extent as an isonitrogenous amount of chickenin healthy, young men

Plant-based proteins are considered to be less effective in their capacity to stimulate muscle protein synthesis when compared with animal-based protein sources, likely due to differences in amino acid contents. We compared the postprandial muscle protein synthetic response following the ingestion of a lysine-enriched plant-based protein product with an isonitrogenous amount of chicken. Twenty-four men (age 24 ± 5 years; BMI 22·9 ± 2·6 kg·m−2) participated in this parallel, double-blind, randomised controlled trial and consumed 40 g of protein as a lysine-enriched wheat and chickpea protein product (Plant, n 12) or chicken breast fillet (Chicken, n 12). Primed, continuous intravenous L-(ring-13C6)-phenylalanine infusions were applied while repeated blood and muscle samples were collected over a 5-h postprandial period to assess plasma amino acid responses, muscle protein synthesis rates and muscle anabolic signalling responses. Postprandial plasma leucine and essential amino acid concentrations were higher following Chicken (P < 0·001), while plasma lysine concentrations were higher throughout in Plant (P < 0·001). Total plasma amino acid concentrations did not differ between interventions (P = 0·181). Ingestion of both Plant and Chicken increased muscle protein synthesis rates from post-absorptive: 0·031 ± 0·011 and 0·031 ± 0·013 to postprandial: 0·046 ± 0·010 and 0·055 ± 0·015 % h−1, respectively (P-time < 0·001), with no differences between Plant and Chicken (time x treatment P = 0·068). Ingestion of 40 g of protein in the form of a lysine-enriched plant-based protein product increases muscle protein synthesis rates to a similar extent as an isonitrogenous amount of chicken in healthy, young men. Plant-based protein products sold as meat replacers may be as effective as animal-based protein sources to stimulate postprandial muscle protein synthesis rates in healthy, young individuals

Beta-alanine (Carnosyn™) supplementation in elderly subjects (60–80 years): effects on muscle carnosine content and physical capacity

The aim of this study was to investigate the effects of beta-alanine supplementation on exercise capacity and the muscle carnosine content in elderly subjects. Eighteen healthy elderly subjects (60–80 years, 10 female and 4 male) were randomly assigned to receive either beta-alanine (BA, n = 12) or placebo (PL, n = 6) for 12 weeks. The BA group received 3.2 g of beta-alanine per day (2 × 800 mg sustained-release Carnosyn™ tablets, given 2 times per day). The PL group received 2 × (2 × 800 mg) of a matched placebo. At baseline (PRE) and after 12 weeks (POST-12) of supplementation, assessments were made of the muscle carnosine content, anaerobic exercise capacity, muscle function, quality of life, physical activity and food intake. A significant increase in the muscle carnosine content of the gastrocnemius muscle was shown in the BA group (+85.4%) when compared with the PL group (+7.2%) (p = 0.004; ES: 1.21). The time-to-exhaustion in the constant-load submaximal test (i.e., TLIM) was significantly improved (p = 0.05; ES: 1.71) in the BA group (+36.5%) versus the PL group (+8.6%). Similarly, time-to-exhaustion in the incremental test was also significantly increased (p = 0.04; ES 1.03) following beta-alanine supplementation (+12.2%) when compared with placebo (+0.1%). Significant positive correlations were also shown between the relative change in the muscle carnosine content and the relative change in the time-to-exhaustion in the TLIM test (r = 0.62; p = 0.01) and in the incremental test (r = 0.48; p = 0.02). In summary, the current data indicate for the first time, that beta-alanine supplementation is effective in increasing the muscle carnosine content in healthy elderly subjects, with subsequent improvement in their exercise capacity

The effect of exercise training on the course of cardiac troponin T and i levels: Three independent training studies

With the introduction of high-sensitive assays, cardiac troponins became potential biomarkers for risk stratification and prognostic medicine. Observational studies have reported an inverse association between physical activity and basal cardiac troponin levels. However, causality has never been demonstrated. This study investigated whether basal cardiac troponin concentrations are receptive to lifestyle interventions such as exercise training. Basal high-sensitive cardiac troponin T ( cTnT ) and I ( cTnI ) were monitored in two resistance-type exercise training programs ( 12-week ( study 1 ) and 24-week ( study 2 ) ) in older adults ( ≥65 years ). In addition, a retrospective analysis for high sensitive troponin I in a 24-week exercise controlled trial in ( pre )frail older adults was performed ( study 3 ). In total, 91 subjects were included in the final data analyses. There were no significant changes in cardiac troponin levels over time in study 1 and 2 ( study 1: cTnT −0.13 ( −0.33–+0.08 ) ng/L/12-weeks, cTnI −0.10 ( −0.33–+0.12 ) ng/L/12-weeks; study 2: cTnT −1.99 ( −4.79–+0.81 ) ng/L/24-weeks, cTnI −1.59 ( −5.70–+2.51 ) ng/L/24-weeks ). Neither was there a significant interaction between training and the course of cardiac troponin in study 3 ( p = 0.27 ). In conclusion, this study provides no evidence that prolonged resistance-type exercise training can modulate basal cardiac troponin levels