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

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

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

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

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

Genetic dissection of granulomatous enterocolitis and arthritis in the intramural peptidoglycan-polysaccharide-treated rat model of IBD:

Inflammatory arthropathies are common extraintestinal manifestations of inflammatory bowel diseases (IBD). As genetic susceptibility plays an important role in the etiology of IBD, we questioned how granulomatous enterocolitis and arthritis are genetically controlled in an experimental animal model displaying both conditions

Indigenous identity, natural resources, and contentious politics in Bolivia: a disaggregated conflict analysis; 2000-2011

How do natural resources and ethnic identity interact to incite or to mitigate social conflict? This article argues that high-value natural resources can act as an important catalyst for the politicization of ethnic, specifically indigenous identity, and contribute to social conflict as they limit the malleability of identity frames and raise the stakes of confrontations. We test this argument using unique subnational data from Bolivian provinces. Drawing on Bolivian newspaper reports, we code conflict events for all of the 112 provinces from 2000 to 2011. We join this conflict data with information on local ethnic composition from the census, the political representation of ethnic groups at the national level, as well as geo-spatial information on gas deposits. Using time-series cross-sectional count models, we show a significant conflict-promoting effect of the share of indigenous people in provinces with gas reserves, but not without

Photoperiodic control of seasonal growth is mediated by ABA acting on cell-cell communication

In temperate and boreal ecosystems, seasonal cycles of growth and dormancy allow perennial plants to adapt to winter conditions. We show, in hybrid aspen trees, that photoperiodic regulation of dormancy is mechanistically distinct from autumnal growth cessation. Dormancy sets in when symplastic intercellular communication through plasmodesmata is blocked by a process dependent on the phytohormone abscisic acid. The communication blockage prevents growth-promoting signals from accessing the meristem. Thus, precocious growth is disallowed during dormancy. The dormant period, which supports robust survival of the aspen tree in winter, is due to loss of access to growth-promoting signals

Berlin Registry of Neuroimmunological entities (BERLimmun): protocol of a prospective observational study

BACKGROUND: Large-scale disease overarching longitudinal data are rare in the field of neuroimmunology. However, such data could aid early disease stratification, understanding disease etiology and ultimately improve treatment decisions. The Berlin Registry of Neuroimmunological Entities (BERLimmun) is a longitudinal prospective observational study, which aims to identify diagnostic, disease activity and prognostic markers and to elucidate the underlying pathobiology of neuroimmunological diseases. METHODS: BERLimmun is a single-center prospective observational study of planned 650 patients with neuroimmunological disease entity (e.g. but not confined to: multiple sclerosis, isolated syndromes, neuromyelitis optica spectrum disorders) and 85 healthy participants with 15 years of follow-up. The protocol comprises annual in-person visits with multimodal standardized assessments of medical history, rater-based disability staging, patient-report of lifestyle, diet, general health and disease specific symptoms, tests of motor, cognitive and visual functions, structural imaging of the neuroaxis and retina and extensive sampling of biological specimen. DISCUSSION: The BERLimmun database allows to investigate multiple key aspects of neuroimmunological diseases, such as immunological differences between diagnoses or compared to healthy participants, interrelations between findings of functional impairment and structural change, trajectories of change for different biomarkers over time and, importantly, to study determinants of the long-term disease course. BERLimmun opens an opportunity to a better understanding and distinction of neuroimmunological diseases

Healable Cellulose Iontronic Hydrogel Stickers for Sustainable Electronics on Paper

The authors acknowledge the support from FCT - Portuguese Foundation for Science and Technology through the Ph.D. scholarships SFRH/BD/126409/2016 (I.C.) and SFRH/BD/122286/2016 (J.M.). The authors would like to acknowledge the European Commission under project NewFun (ERC-StG-2014, GA 640598) and project SYNERGY (H2020-WIDESPREAD-2020-5, CSA, proposal no 952169). This work was also supported by the FEDER funds through the COMPETE 2020 Program and the National Funds through the FCT - Portuguese Foundation for Science and Technology under the Project No. POCI-01-0145-FEDER-007688, reference UID/CTM/50025, project CHIHC, reference PTDC/NAN-MAT/32558/2017. The authors would also like to thank their colleagues Daniela Gomes and Ana Pimentel from CENIMAT/i3N for the SEM and DSC-TGA measurements, respectively.Novel nature-based engineered functional materials combined with sustainable and economically efficient processes are among the great challenges for the future of mankind. In this context, this work presents a new generation of versatile flexible and highly conformable regenerated cellulose hydrogel electrolytes with high ionic conductivity and self-healing ability, capable of being (re)used in electrical and electrochemical devices. They can be provided in the form of stickers and easily applied as gate dielectric onto flexible indium–gallium–zinc oxide transistors, decreasing the manufacturing complexity. Flexible and low-voltage (<2.5 V) circuits can be handwritten on-demand on paper transistors for patterning of conductive/resistive lines. This user-friendly and simplified manufacturing approach holds potential for fast production of low-cost, portable, disposable/recyclable, and low-power ion-controlled electronics on paper, making it attractive for application in sensors and concepts such as the “Internet-on-Things.”.publishersversionpublishe