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Structural Neuroimaging of Anorexia Nervosa: Future Directions in the Quest for Mechanisms Underlying Dynamic Alterations.
Anorexia nervosa (AN) is a serious eating disorder characterized by self-starvation and extreme weight loss. Pseudoatrophic brain changes are often readily visible in individual brain scans, and AN may be a valuable model disorder to study structural neuroplasticity. Structural magnetic resonance imaging studies have found reduced gray matter volume and cortical thinning in acutely underweight patients to normalize following successful treatment. However, some well-controlled studies have found regionally greater gray matter and persistence of structural alterations following long-term recovery. Findings from diffusion tensor imaging studies of white matter integrity and connectivity are also inconsistent. Furthermore, despite the severity of AN, the number of existing structural neuroimaging studies is still relatively low, and our knowledge of the underlying cellular and molecular mechanisms for macrostructural brain changes is rudimentary. We critically review the current state of structural neuroimaging in AN and discuss the potential neurobiological basis of structural brain alterations in the disorder, highlighting impediments to progress, recent developments, and promising future directions. In particular, we argue for the utility of more standardized data collection, adopting a connectomics approach to understanding brain network architecture, employing advanced magnetic resonance imaging methods that quantify biomarkers of brain tissue microstructure, integrating data from multiple imaging modalities, strategic longitudinal observation during weight restoration, and large-scale data pooling. Our overarching objective is to motivate carefully controlled research of brain structure in eating disorders, which will ultimately help predict therapeutic response and improve treatment
Targeted Disruption of Shp2 in Chondrocytes Leads to Metachondromatosis With Multiple Cartilaginous Protrusions
Metachondromatosis is a benign bone disease predominantly observed in the hands and feet of children or young adults demonstrating two different manifestations: a cartilageâcapped bony outgrowth on the surface of the bone called exostosis and ectopic cartilaginous nodules inside the bone called enchondroma. Recently, it has been reported that lossâofâfunction mutations of the SHP2 gene, which encodes the SHP2 protein tyrosine phosphatase, are associated with metachondromatosis. The purpose of this study was to investigate the role of SHP2 in postnatal cartilage development, which is largely unknown. We disrupted Shp2 during the postnatal stage of mouse development in a chondrocyteâspecific manner using a tamoxifenâinducible system. We found tumorâlike nodules on the hands and feet within a month after the initial induction. The SHP2âdeficient mice demonstrated an exostosisâlike and enchondromaâlike phenotype in multiple bones of the hands, feet, and ribs as assessed by Xâray and microâcomputed tomography (CT). Histological assessment revealed the disorganization of the growth plate cartilage, a cartilaginous protrusion from the epiphyseal bone, and ectopic cartilage nodules within the bones, which is consistent with the pathological features of metachondromatosis in humans (ie, both exostosis and enchondroma). At molecular levels, we observed an abundant expression of Indian hedgehog protein (IHH) and fibroblast growth factor 2 (FGF2) and impaired expression of mitogenâactivated protein kinases (MAPK) in the affected cartilage nodules in the SHP2âdeficient mice. In summary, we have generated a mouse model of metachondromatosis that includes manifestations of exostosis and enchondroma. This study provides a novel model for the investigation of the pathophysiology of the disease and advances the understanding of metachondromatosis. This model will be useful to identify molecular mechanisms for the disease cause and progression as well as to develop new therapeutic strategies in the future. © 2014 American Society for Bone and Mineral Research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106063/1/jbmr2062.pd
Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis
Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two
The Red Sea, Coastal Landscapes, and Hominin Dispersals
This chapter provides a critical assessment of environment, landscape and resources in the Red Sea region over the past five million years in relation to archaeological evidence of hominin settlement, and of current hypotheses about the role of the region as a pathway or obstacle to population dispersals between Africa and Asia and the possible significance of coastal colonization. The discussion assesses the impact of factors such as topography and the distribution of resources on land and on the seacoast, taking account of geographical variation and changes in geology, sea levels and palaeoclimate. The merits of northern and southern routes of movement at either end of the Red Sea are compared. All the evidence indicates that there has been no land connection at the southern end since the beginning of the Pliocene period, but that short sea crossings would have been possible at lowest sea-level stands with little or no technical aids. More important than the possibilities of crossing the southern channel is the nature of the resources available in the adjacent coastal zones. There were many climatic episodes wetter than today, and during these periods water draining from the Arabian escarpment provided productive conditions for large mammals and human populations in coastal regions and eastwards into the desert. During drier episodes the coastal region would have provided important refugia both in upland areas and on the emerged shelves exposed by lowered sea level, especially in the southern sector and on both sides of the Red Sea. Marine resources may have offered an added advantage in coastal areas, but evidence for their exploitation is very limited, and their role has been over-exaggerated in hypotheses of coastal colonization
Oxy-fuel combustion of coal and biomass blends
The ignition temperature, burnout and NO emissions of blends of a semi-anthracite and a high-volatile bituminous coal with 10 and 20 wt.% of olive waste were studied under oxy-fuel combustion conditions in an entrained flow reactor (EFR). The results obtained under several oxy-fuel atmospheres (21%O2â79%CO2, 30%O2â70%CO2 and 35%O2â65%CO2) were compared with those attained in air. The results indicated that replacing N2 by CO2 in the combustion atmosphere with 21% of O2 caused an increase in the temperature of ignition and a decrease in the burnout value. When the O2 concentration was increased to 30 and 35%, the temperature of ignition was lower and the burnout value was higher than in air conditions. A significant reduction in ignition temperature and a slight increase in the burnout value was observed after the addition of biomass, this trend becoming more noticeable as the biomass concentration was increased. The emissions of NO during oxy-fuel combustion were lower than under air-firing. However, they remained similar under all the oxy-fuel atmospheres with increasing O2 concentrations. Emissions of NO were significantly reduced by the addition of biomass to the bituminous coal, although this effect was less noticeable in the case of the semi-anthracite.This work was carried out with financial support from the Spanish MICINN (Project
PS-120000-2005-2) co-financed by the European Regional Development Fund. M.V.G.
and L.A. acknowledge funding from the CSIC JAE-Doc and CSIC JAE-Pre programs,
respectively, co-financed by the European Social Fund. J.R. acknowledges funding
from the Government of the Principado de Asturias (Severo Ochoa program).Peer reviewe
Cognitive behaviour therapy versus counselling intervention for anxiety in young people with high-functioning autism spectrum disorders: a pilot randomised controlled trial
The use of cognitive-behavioural therapy (CBT) as a treatment for children and adolescents with autism spectrum disorder (ASD) has been explored in a number of trials. Whilst CBT appears superior to no treatment or treatment as usual, few studies have assessed CBT against a control group receiving an alternative therapy.
Our randomised controlled trial compared use of CBT against person-centred counselling for anxiety in 36 young people with ASD, ages 12â18. Outcome measures included parent- teacher- and self-reports of anxiety and social disability.
Whilst each therapy produced improvements inparticipants, neither therapy was superior to the other to a significant degree on any measure. This is consistent with findings for adults
Hedgehog Spin-texture and Berry's Phase tuning in a Magnetic Topological Insulator
Understanding and control of spin degrees of freedom on the surfaces of
topological materials are key to future applications as well as for realizing
novel physics such as the axion electrodynamics associated with time-reversal
(TR) symmetry breaking on the surface. We experimentally demonstrate
magnetically induced spin reorientation phenomena simultaneous with a
Dirac-metal to gapped-insulator transition on the surfaces of manganese-doped
Bi2Se3 thin films. The resulting electronic groundstate exhibits unique
hedgehog-like spin textures at low energies, which directly demonstrate the
mechanics of TR symmetry breaking on the surface. We further show that an
insulating gap induced by quantum tunnelling between surfaces exhibits spin
texture modulation at low energies but respects TR invariance. These spin
phenomena and the control of their Fermi surface geometrical phase first
demonstrated in our experiments pave the way for the future realization of many
predicted exotic magnetic phenomena of topological origin.Comment: 38 pages, 18 Figures, Includes new text, additional datasets and
interpretation beyond arXiv:1206.2090, for the final published version see
Nature Physics (2012
Impaired decisional impulsivity in pathological videogamers
Abstract
Background
Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort.
Methods
Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment.
Results
In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time.
Conclusions
We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management
Assessing Internet addiction using the parsimonious Internet addiction components model - a preliminary study [forthcoming]
Internet usage has grown exponentially over the last decade. Research indicates that excessive Internet use can lead to symptoms associated with addiction. To date, assessment of potential Internet addiction has varied regarding populations studied and instruments used, making reliable prevalence estimations difficult. To overcome the present problems a preliminary study was conducted testing a parsimonious Internet addiction components model based on Griffithsâ addiction components (2005), including salience, mood modification, tolerance, withdrawal, conflict, and relapse. Two validated measures of Internet addiction were used (Compulsive Internet Use Scale [CIUS], Meerkerk et al., 2009, and Assessment for Internet and Computer Game Addiction Scale [AICA-S], Beutel et al., 2010) in two independent samples (ns = 3,105 and 2,257). The fit of the model was analysed using Confirmatory Factor Analysis. Results indicate that the Internet addiction components model fits the data in both samples well. The two sample/two instrument approach provides converging evidence concerning the degree to which the components model can organize the self-reported behavioural components of Internet addiction. Recommendations for future research include a more detailed assessment of tolerance as addiction component
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