Changes in construals of tic-producing situations following cognitive and behavioral therapy

12 clients suffering from chronic tics participated in one of two treatment programs, either a behavioral group using competing response therapy or a group using Beck-style cognitive restructuring. A repertory grid based upon the personal construct psychology of George Kelly was administered to all clients before and after treatment. The grid comprised a set of elements made up of situations with high, medium, and low risk of eliciting tics, and constructs were derived from comparisons between them. Clients' ratings of the elements on the constructs were subjected to a principal components analysis using an INGRID program. Following treatment the total variation around construct means decreased in both groups but significantly more in the cognitive group, indicating a narrowing of the difference in their perceptions of situations which formerly indicated high and low risk of inducing tics.postprin

Association entre les mouvements périodiques des jambes au cours du sommeil et l’intégrité de la matière blanche cérébrale

Les mouvements périodiques des jambes au cours du sommeil (MPJS) sont une activité motrice répétée et stéréotypée qui se caractérise par une dorsiflexion des orteils et de la cheville. Des travaux récents ont démontré une association temporelle entre les MPJS et une activation du système nerveux sympathique, qui se manifeste par une augmentation répétée de la tension artérielle et du rythme cardiaque. Avec l’âge, les MPJS pourraient donc favoriser l’apparition d’atteintes cérébrales via un processus d’artériolosclérose. Dans cette étude, trente-sept individus âgés entre 55 et 82 ans et présentant différents niveaux de sévérités de MPJS ont été inclus. Nous avons utilisé l'imagerie par résonance magnétique associée à la morphométrie basée sur les voxels et l’imagerie du tenseur de diffusion pour estimer la présence de changements en regard de la matière blanche et de la matière grise. Des analyses corrélationnelles ont été effectuées entre les marqueurs de sévérité des MPJS (indice de MPJS, intervalle inter-mouvement, durée des mouvements, association avec les micro-éveils) et les variables de neuroimagerie (hyperintensités, intégrité de la matière blanche et volume de la matière grise). Nos résultats ont démontré que des indices plus élevés de MPJS et des MPJS associés aux micro-éveils étaient associés à des réductions de l’intégrité de la matière blanche dans les régions fronto-temporo-pariétales. Une corrélation a été observée entre une réduction du volume de matière grise et un intervalle inter-mouvement plus long dans le gyrus frontal médian. Les associations observées dans notre échantillon soulèvent l’hypothèse que les MPJS puissent modifier la microstructure du cerveau et avoir un impact sur l’intégrité cérébrovasculaire chez des individus d’âge moyen ou plus âgé.Periodic leg movements during sleep (PLMS) are repeated and stereotyped nocturnal motor activity characterized by dorsiflexion of the toes and ankle. Recent studies showed a temporal association between PLMS and activation of the sympathetic nervous system, characterized by a repeated increase in blood pressure and heart rate. The PLMS might be involved in the genesis of cardiovascular damage and favor the occurrence of cerebral injuries via an arteriolosclerosis process. In the present study, thirty-seven healthy subjects aged between 55 and 82 years old were recorded for one night of in-laboratory polysomnography and participated to a brain magnetic resonance imaging (MRI) session. Regression analysis were performed between the four PLMS severity variables, namely the PLMS index (PLMSI), the average time interval between PLMS, the PLMS mean duration and the number of PLMS associated with a micro-arousal (PLMS-MA) and neuroimaging variables (white matter hyperintensities, white matter structure through diffusion tensor imaging (DTI) and gray matter volume through voxel-based morphometry (VBM). Our results showed that a higher PLMSI and PLMS-ME have been associated with reductions in white matter integrity in fronto-temporo-parietal regions. Also, reduction in grey matter volume was associated with a longer time interval between PLMS in the middle frontal gyrus. Associations observed in our sample suggest that PLMS may modify the microstructure of the brain and affect cerebrovascular integrity in middle-aged and older individuals

Machine Learning in Melanoma Diagnosis. Limitations About to be Overcome

[spa] Antecedentes: La clasificación automática de imágenes es una rama prometedora del aprendi-zaje automático (de sus siglas en inglés Machine Learning [ML]), y es una herramienta útil enel diagnóstico de cáncer de piel. Sin embargo, poco se ha estudiado acerca de las limitacionesde su uso en la práctica clínica diaria.Objetivo: Determinar las limitaciones que existen en cuanto a la selección de imágenes usadaspara el análisis por ML de las neoplasias cutáneas, en particular del melanoma.Métodos: Se dise ̃nó un estudio de cohorte retrospectivo, donde se incluyeron de forma conse-cutiva 2.849 imágenes dermatoscópicas de alta calidad de tumores cutáneos para su valoraciónpor un sistema de ML, recogidas entre los a ̃nos 2010 y 2014. Cada imagen dermatoscópica fueclasificada según las características de elegibilidad para el análisis por ML.Resultados: De las 2.849 imágenes elegidas a partir de nuestra base de datos, 968 (34%) cum-plieron los criterios de inclusión. De los 528 melanomas, 335 (63,4%) fueron excluidos. Laausencia de piel normal circundante (40,5% de todos los melanomas de nuestra base de datos)y la ausencia de pigmentación (14,2%) fueron las causas más frecuentes de exclusión para elanálisis por ML.Discusión: Solo el 36,6% de nuestros melanomas se consideraron aceptables para el análisispor sistemas de ML de última generación. Concluimos que los futuros sistemas de ML deberánser entrenados a partir de bases de datos más grandes que incluyan imágenes representativasde la práctica clínica habitual. Afortunadamente, muchas de estas limitaciones están siendosuperadas gracias a los avances realizados recientemente por la comunidad científica, como seha demostrado en trabajos recientes. [eng] Background: Automated image classification is a promising branch of machine learning (ML)useful for skin cancer diagnosis, but little has been determined about its limitations for generalusability in current clinical practice.Objective: To determine limitations in the selection of skin cancer images for ML analysis,particularly in melanoma.Methods: Retrospective cohort study design, including 2,849 consecutive high-quality dermos-copy images of skin tumors from 2010 to 2014, for evaluation by a ML system. Each dermoscopyimage was assorted according to its eligibility for ML analysis.Results: Of the 2,849 images chosen from our database, 968 (34%) met the inclusion criteriafor analysis by the ML system. Only 64.7% of nevi and 36.6% of melanoma met the inclusioncriteria. Of the 528 melanomas, 335 (63.4%) were excluded. An absence of normal surroundingskin (40.5% of all melanomas from our database) and absence of pigmentation (14.2%) were themost common reasons for exclusion from ML analysis.Discussion: Only 36.6% of our melanomas were admissible for analysis by state-of-the-art MLsystems. We conclude that future ML systems should be trained on larger datasets which includerelevant non-ideal images from lesions evaluated in real clinical practice. Fortunately, many ofthese limitations are being overcome by the scientific community as recent works show

Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

SUMO-2 and PIAS1 modulate insoluble mutant Huntingtin protein accumulation

A key feature in Huntington disease (HD) is the accumulation of mutant Huntingtin (HTT) protein, which may be regulated by posttranslational modifications. Here, we define the primary sites of SUMO modification in the amino-terminal domain of HTT, show modification downstream of this domain, and demonstrate that HTT is modified by the stress-inducible SUMO-2. A systematic study of E3 SUMO ligases demonstrates that PIAS1 is an E3 SUMO ligase for both HTT SUMO-1 and SUMO-2 modification and that reduction of dPIAS in a mutant HTT Drosophila model is protective. SUMO-2 modification regulates accumulation of insoluble HTT in HeLa cells in a manner that mimics proteasome inhibition and can be modulated by overexpression and acute knockdown of PIAS1. Finally, the accumulation of SUMO-2-modified proteins in the insoluble fraction of HD postmortem striata implicates SUMO-2 modification in the age-related pathogenic accumulation of mutant HTT and other cellular proteins that occurs during HD progression

SUMO modification of cell surface Kv2.1 potassium channels regulates the activity of rat hippocampal neurons

Voltage-gated Kv2.1 potassium channels are important in the brain for determining activity-dependent excitability. Small ubiquitin-like modifier proteins (SUMOs) regulate function through reversible, enzyme-mediated conjugation to target lysine(s). Here, sumoylation of Kv2.1 in hippocampal neurons is shown to regulate firing by shifting the half-maximal activation voltage (V1/2) of channels up to 35 mV. Native SUMO and Kv2.1 are shown to interact within and outside channel clusters at the neuronal surface. Studies of single, heterologously expressed Kv2.1 channels show that only K470 is sumoylated. The channels have four subunits, but no more than two non-adjacent subunits carry SUMO concurrently. SUMO on one site shifts V1/2 by 15 mV, whereas sumoylation of two sites produces a full response. Thus, the SUMO pathway regulates neuronal excitability via Kv2.1 in a direct and graded manner

SUMO-2 and PIAS1 Modulate Insoluble Mutant Huntingtin Protein Accumulation

SUMMARY A key feature in Huntington disease (HD) is the accumulation of mutant Huntingtin (HTT) protein, which may be regulated by posttranslational modifications. Here, we define the primary sites of SUMO modification in the amino-terminal domain of HTT, show modification downstream of this domain, and demonstrate that HTT is modified by the stress-inducible SUMO-2. A systematic study of E3 SUMO ligases demonstrates that PIAS1 is an E3 SUMO ligase for both HTT SUMO-1 and SUMO-2 modification and that reduction of dPIAS in a mutant HTT Drosophila model is protective. SUMO-2 modification regulates accumulation of insoluble HTT in HeLa cells in a manner that mimics proteasome inhibition and can be modulated by overexpression and acute knockdown of PIAS1. Finally, the accumulation of SUMO-2-modified proteins in the insoluble fraction of HD postmortem striata implicates SUMO-2 modification in the age-related pathogenic accumulation of mutant HTT and other cellular proteins that occurs during HD progression

Optimization of the Balanced Steady State Free Precession (bSSFP) Pulse Sequence for Magnetic Resonance Imaging of the Mouse Prostate at 3T

INTRODUCTION: MRI can be used to non-invasively monitor tumour growth and response to treatment in mouse models of prostate cancer, particularly for longitudinal studies of orthotopically-implanted models. We have optimized the balanced steady-state free precession (bSSFP) pulse sequence for mouse prostate imaging. METHODS: Phase cycling, excitations, flip angle and receiver bandwidth parameters were optimized for signal to noise ratio and contrast to noise ratio of the prostate. The optimized bSSFP sequence was compared to T1- and T2-weighted spin echo sequences. RESULTS: SNR and CNR increased with flip angle. As bandwidth increased, SNR, CNR and artifacts such as chemical shift decreased. The final optimized sequence was 4 PC, 2 NEX, FA 50°, BW ±62.5 kHz and took 14-26 minutes with 200 µm isotropic resolution. The SNR efficiency of the bSSFP images was higher than for T1WSE and T2WSE. CNR was highest for T1WSE, followed closely by bSSFP, with the T2WSE having the lowest CNR. With the bSSFP images the whole body and organs of interest including renal, iliac, inguinal and popliteal lymph nodes were visible. CONCLUSION: We were able to obtain fast, high-resolution, high CNR images of the healthy mouse prostate with an optimized bSSFP sequence