Epigallocatechin-3-gallate: a useful, effective and safe clinical approach for targeted prevention and individualised treatment of neurological diseases

Neurodegenerative disorders show an increasing prevalence in a number of highly developed countries. Often, these diseases require life-long treatment mostly with drugs which are costly and mostly accompanied by more or less serious side-effects. Their heterogeneous manifestation, severity and outcome pose the need for individualised treatment options. There is an intensive search for new strategies not only for treating but also for preventing these diseases. Green tea and green tea extracts seem to be such a promising and safe alternative. However, data regarding the beneficial effects and possible underlying mechanism, specifically in clinical trials, are rare and rather controversial or non-conclusive. This review outlines the existing evidence from preclinical studies (cell and tissue cultures and animal models) and clinical trials regarding preventive and therapeutic effects of epigallcatechin-3-gallate in neurodegenerative diseases and considers antioxidative vs. pro-oxidative properties of the tea catechin important for dosage recommendations

Is metabolic flexibility altered in multiple sclerosis patients?

OBJECTIVES: Metabolic flexibility is defined as ability to adjust fuel oxidation to fuel availability. Multiple sclerosis (MS) results in reduced muscle strength and exercise intolerance. We tested the hypothesis that altered metabolic flexibility contributes to exercise intolerance in MS patients. METHODS: We studied 16 patients (all on glatiramer) and 16 matched healthy controls. Energy expenditure (EE), and carbohydrate (COX) and lipid oxidation (LOX) rates were determined by calorimetry, before and after an oral glucose load. We made measurements either at rest (canopy device) or during 40 min low-grade (0.5 W/kg) exercise (metabolic chamber). We also obtained plasma, and adipose tissue and skeletal muscle dialysate samples by microdialysis to study tissue-level metabolism under resting conditions. RESULTS: At rest, fasting and postprandial plasma glucose, insulin, and free fatty acid levels did not differ between patients and controls. Fasting and postprandial COX was higher and LOX lower in patients. In adipose, fasting and postprandial dialysate glucose, lactate, and glycerol levels were higher in patients vs. controls. In muscle, fasting and postprandial dialysate metabolite levels did not differ significantly between the groups. During exercise, EE did not differ between the groups. However, COX increased sharply over 20 min in patients, without reaching a steady state, followed by an immediate decrease within the next 20 min and fell even below basal levels after exercise in patients, compared to controls. CONCLUSIONS: Glucose tolerance is not impaired in MS patients. At rest, there is no indication for metabolic inflexibility or mitochondrial dysfunction in skeletal muscle. The increased adipose tissue lipolytic activity might result from glatiramer treatment. Autonomic dysfunction might cause dysregulation of postprandial thermogenesis at rest and lipid mobilization during exercise

Dysphagia affecting quality of life in cerebellar ataxia - a large survey

Dysphagia is a common symptom in neurodegenerative disorders and is generally associated with increased mortality. In the clinical care setting of ataxia patients, no systematical and standardized assessment of dysphagia is employed. Its impact on patients' health-related quality of life is not well understood. To assess the impact of dysphagia in ataxia patients on diet, body weight, and health-related quality of life. We conducted a large survey using self-reported questionnaires for swallowing-related quality of life (Swal-QOL) and a food frequency list in combination with retrospective clinical data of 119 patients with cerebellar ataxia treated in the neurological outpatient clinic of a large German university hospital. Seventeen percent of ataxia patients suffered from dysphagia based on the Swal-QOL score. Less than 1% of all patients reported dysphagia as one of their most disabling symptoms. Dysphagia was associated with unintentional weight loss (p = 0.02) and reduced health-related quality of life (p = 0.01) but did not affect individual nutritional habits (p > 0.05; Chi-squared test). Dysphagia is a relevant symptom in cerebellar ataxia. A systematic screening for dysphagia in patients with cerebellar ataxia would be desirable to enable early diagnosis and treatment

Validity and reliability of total body volume and relative body fat mass from a 3-dimensional photonic body surface scanner

OBJECTIVE: Three-dimensional photonic body surface scanners (3DPS) feature a tool to estimate total body volume (BV) from 3D images of the human body, from which the relative body fat mass (%BF) can be calculated. However, information on validity and reliability of these measurements for application in epidemiological studies is limited. METHODS: Validity was assessed among 32 participants (men, 50%) aged 20-58 years. BV and %BF were assessed using a 3DPS (VitusSmart XXL) and air displacement plethysmography (ADP) with a BOD POD(R) device using equations by Siri and Brozek. Three scans were obtained per participant (standard, relaxed, exhaled scan). Validity was evaluated based on the agreement of 3DPS with ADP using Bland Altman plots, correlation analysis and Wilcoxon signed ranks test for paired samples. Reliability was investigated in a separate sample of 18 participants (men, 67%) aged 25-66 years using intraclass correlation coefficients (ICC) based on two repeated 3DPS measurements four weeks apart. RESULTS: Mean BV and %BF were higher using 3DPS compared to ADP, (3DPS-ADP BV difference 1.1 +/- 0.9 L, p<0.01; %BF difference 7.0 +/- 5.6, p<0.01), yet the disagreement was not associated with gender, age or body mass index (BMI). Reliability was excellent for 3DPS BV (ICC, 0.998) and good for 3DPS %BF (ICC, 0.982). Results were similar for the standard scan and the relaxed scan but somewhat weaker for the exhaled scan. CONCLUSIONS: Although BV and %BF are higher than ADP measurements, our data indicate good validity and reliability for an application of 3DPS in epidemiological studies

Dysphagia Affecting Quality of Life in Cerebellar Ataxia—a Large Survey

Dysphagia is a common symptom in neurodegenerative disorders and is generally associated with increased mortality. In the clinical care setting of ataxia patients, no systematical and standardized assessment of dysphagia is employed. Its impact on patients’ health-related quality of life is not well understood. To assess the impact of dysphagia in ataxia patients on diet, body weight, and health-related quality of life. We conducted a large survey using self-reported questionnaires for swallowing-related quality of life (Swal-QOL) and a food frequency list in combination with retrospective clinical data of 119 patients with cerebellar ataxia treated in the neurological outpatient clinic of a large German university hospital. Seventeen percent of ataxia patients suffered from dysphagia based on the Swal-QOL score. Less than 1% of all patients reported dysphagia as one of their most disabling symptoms. Dysphagia was associated with unintentional weight loss (p = 0.02) and reduced health-related quality of life (p = 0.01) but did not affect individual nutritional habits (p > 0.05; Chi-squared test). Dysphagia is a relevant symptom in cerebellar ataxia. A systematic screening for dysphagia in patients with cerebellar ataxia would be desirable to enable early diagnosis and treatment

Virtual Method for the Investigation of Dynamic Emission Formation for Gasoline Engines

Significantly reduced development times of today's powertrains as well as steadily increasing requirements regarding fuel consumption and pollutant emissions require a continuous refinement of the development methods for internal combustion engines. The presented simulation method focuses on the new and tightened approval cycles for passenger car engines; more particularly on the start-up phase as well as on sharp load changes, which lead to increased engine out emissions. The aim of this study is to create a simulation tool for the investigation and the evaluation of the emissions during the dynamic engine operation. Established simulation methods, such as Computational Fluid Dynamics (CFD), are bundled in such a way that transient processes can be simulated within a reasonable calculation time without significant loss of information. The tool is based on a 1D gas exchange simulation software. Herein, detailed reaction kinetics are used to simulate the combustion process, which also takes the thermal boundary conditions (wall temperatures) and the quality of the mixture formation into account. For this purpose, the gas exchange model is extended with a thermal network and the mixture formation process is assessed with CFD. Suitable test bench data serve to validate the whole process chain. In addition to the improvement of the CAE-based assessment for the development of virtual engines, the simulation tool should provide an understanding of the phenomena leading to emission formation under the transient engine operation. Furthermore, using such a tool can contribute to the development of alternative driving concepts like plug-in hybrid electric vehicles (PHEV) and exhaust aftertreatment systems

Strategic verbal rehearsal in adolescents with mild intellectual disabilities: A multi-centre European study

Background: There is a long-held view that verbal short-term memory problems of individuals with intellectual disabilities (ID) might be due to a deficit in verbal rehearsal. However, the evidence is inconclusive and word length effects as indicator of rehearsal have been criticised. Aim & Method: The aim of this multi-site European study was to investigate verbal rehearsal in adolescents with mild ID (n=90) and a comparison group of typically developing children matched individually for mental age (MA, n=90). The investigation involved: (1) a word length experiment with non-verbal recall using pointing and (2) ‘self-paced’ inspection times to infer whether verbal strategies were utilised when memorising a set of pictorial items. Results: The word length effect on recall did not interact with group, suggesting that adolescents with ID and MA comparisons used similar verbal strategies, possibly phonological recoding of picture names. The inspection time data suggested that high span individuals in both groups used verbal labelling or single item rehearsal on more demanding lists, as long named items had longer inspection times. Conclusions: The findings suggest that verbal strategy use is not specifically impaired in adolescents with mild ID and is mental age appropriate, supporting a developmental perspective

Computational approaches to predicting treatment response to obesity using neuroimaging

Obesity is a worldwide disease associated with multiple severe adverse consequences and comorbid conditions. While an increased body weight is the defining feature in obesity, etiologies, clinical phenotypes and treatment responses vary between patients. These variations can be observed within individual treatment options which comprise lifestyle interventions, pharmacological treatment, and bariatric surgery. Bariatric surgery can be regarded as the most effective treatment method. However, long-term weight regain is comparably frequent even for this treatment and its application is not without risk. A prognostic tool that would help predict the effectivity of the individual treatment methods in the long term would be essential in a personalized medicine approach. In line with this objective, an increasing number of studies have combined neuroimaging and computational modeling to predict treatment outcome in obesity. In our review, we begin by outlining the central nervous mechanisms measured with neuroimaging in these studies. The mechanisms are primarily related to reward-processing and include "incentive salience" and psychobehavioral control. We then present the diverse neuroimaging methods and computational prediction techniques applied. The studies included in this review provide consistent support for the importance of incentive salience and psychobehavioral control for treatment outcome in obesity. Nevertheless, further studies comprising larger sample sizes and rigorous validation processes are necessary to answer the question of whether or not the approach is sufficiently accurate for clinical real-world application

Altered expression of cyclin A 1 in muscle of patients with facioscapulohumeral muscle dystrophy (FSHD-1)

Objectives Cyclin A1 regulates cell cycle activity and proliferation in somatic and germ-line cells. Its expression increases in G1/S phase and reaches a maximum in G2 and M phases. Altered cyclin A1 expression might contribute to clinical symptoms in facioscapulohumeral muscular dystrophy (FSHD). Methods Muscle biopsies were taken from the Vastus lateralis muscle for cDNA microarray, RT-PCR, immunohistochemistry and Western blot analyses to assess RNA and protein expression of cyclin A1 in human muscle cell lines and muscle tissue. Muscle fibers diameter was calculated on cryosections to test for hypertrophy. Results cDNA microarray data showed specifically elevated cyclin A1 levels in FSHD vs. other muscular disorders such as caveolinopathy, dysferlinopathy, four and a half LIM domains protein 1 deficiency and healthy controls. Data could be confirmed with RT-PCR and Western blot analysis showing up-regulated cyclin A1 levels also at protein level. We found also clear signs of hypertrophy within the Vastus lateralis muscle in FSHD-1 patients. Conclusions In most somatic human cell lines, cyclin A1 levels are low. Overexpression of cyclin A1 in FSHD indicates cell cycle dysregulation in FSHD and might contribute to clinical symptoms of this disease

Glassy low-energy spin fluctuations and anisotropy gap in La_1.88Sr_0.12CuO₄

We present high-resolution triple-axis neutron scattering studies of the high-temperature superconductor La1.88Sr0.12CuO4 (Tc=27 K). The temperature dependence of the low-energy incommensurate magnetic fluctuations reveals distinctly glassy features. The glassiness is confirmed by the difference between the ordering temperature TN ~ Tc inferred from elastic neutron scattering and the freezing temperature Tf ~ 11 K obtained from muon spin rotation studies. The magnetic field independence of the observed excitation spectrum as well as the observation of a partial suppression of magnetic spectral weight below 0.75 meV for temperatures smaller than Tf, indicate that the stripe frozen state is capable of supporting a spin anisotropy gap, of a magnitude similar to that observed in the spin and charge stripe ordered ground state of La1.875Ba0.125CuO4. The difference between TN and Tf implies that the significant enhancement in a magnetic field of nominally elastic incommensurate scattering is caused by strictly in-elastic scattering -- at least in the temperature range between Tf and Tc -- which is not resolved in the present experiment. Combining the results obtained from our study of La1.88Sr0.12CuO4 with a critical reappraisal of published neutron scattering work on samples with chemical composition close to p=0.12, where local probes indicate a sharp maximum in Tf(p), we arrive at the view that the low-energy fluctuations are strongly dependent on composition in this regime, with anisotropy gaps dominating only sufficiently close to p=0.12 and superconducting spin gaps dominating elsewhere.Comment: 8 pages, 4 figure