Modulatory effects of 5Hz rTMS over the primary somatosensory cortex in focal dystonia--an fMRI-TMS study.

Dystonia is associated with impaired somatosensory ability. The electrophysiological method of repetitive transcranial magnetic stimulation (rTMS) can be used for noninvasive stimulation of the human cortex and can alter cortical excitability and associated behavior. Among others, rTMS can alter/improve somatosensory discrimation abilities, as shown in healthy controls. We applied 5Hz-rTMS over the left primary somatosensory cortex (S1) in 5 patients with right-sided writer's dystonia and 5 controls. We studied rTMS effects on tactile discrimination accuracy and concomitant rTMS-induced changes in hemodynamic activity measured by functional magnetic resonance imaging (fMRI). Before rTMS, patients performed worse on the discrimination task than controls even though fMRI showed greater task-related activation bilaterally in the basal ganglia (BG). In controls, rTMS led to improved discrimination; fMRI revealed this was associated with increased activity of the stimulated S1, bilateral premotor cortex and BG. In dystonia patients, rTMS had no effect on discrimination; fMRI showed similar cortical effects to controls except for no effects in BG. Improved discrimination after rTMS in controls is linked to enhanced activation of S1 and BG. Failure of rTMS to increase BG activation in dystonia may be associated with the lack of effect on sensory discrimination in this group and may reflect impaired processing in BG-S1 connections. Alternatively, the increased BG activation seen in the baseline state without rTMS may reflect a compensatory strategy that saturates a BG contribution to this task.

Validation transculturelle de l'Oswestry disability index en français [Cross-cultural validation of the Oswestry disability index in French]

AIM: The aim of this study was to interpret and validate a French version of the Oswestry disability index (ODI), using a cross-cultural validation method. The validity and reliability of the questionnaire was assessed in order to ensure the psychometric characteristics. METHOD: The cross-cultural validation was carried out according to Beaton's methodology. The study was conducted with 41 patients suffering from low back pain. The correlation between the ODI and the Roland-Morris disability questionnaire (RMDQ), the medical outcome survey short form-36 (MOS SF-36) and a pain visual analogical scale (VAS) was assessed. RESULTS: The validity of the Oswestry questionnaire was studied using the Cronbach Alpha coefficient calculation: 0.87 (n=36). The significant correlation between the ODI and RMDQ was 0.8 (P<0.001, n=41) and 0.71 (P<0.001, n=36) for the pain VAS. The correlation between the ODI and certain subscales (physical functioning 0.7 (P<0.001, n=41), physical role 0.49 et bodily pain 0.73 (P<0.001, n=41)) of the MOS SF-36 were equally significant. The reproducibility of the ODI was calculated using the Wilcoxon matched pairs test: there was no significant difference for eight out of ten sections or for the final score. CONCLUSION: This French translation of the ODI should be considered as valid and reliable. It should be used for any future clinical studies carried out using French language patients. Complimentary studies must be completed in order to assess its sensitivity to change in the event of any modifications in the patients functional capacity.

¿La cultura es un factor que influye en la percepción de las marcas? :Caso: La imagen de marca-país de México entre los turistas españoles

Aquest treball presenta un model comparatiu d’anàlisis de la marca en base a l’inconscient col•lectiu, teoria desenvolupada per C. G. Jung (1991), adequat per Sabrine Dornelles (2010) a l’estudi de les marques comercials i contrastat en aquest treball amb la proposta d’aproximació al Perfil Arquetípic Azteca. Per aquesta raó, s’ha realitzat una revisió bibliográfica en referencia a l’objecte de l’estudi del posicionament de la marca, i en especial, dels atributs vinculats al perfil azteca. Amb l’objectiu de conèixer si la cultura influeix o no, en la percepció d’una marca, s’ha realitzat un pre-test via online amb subjectes de nacionalitat espanyola i de països d’Amèrica llatina (Argentina, Colòmbia, Equador, Perú, República Dominicana i Veneçuela) per al grup de control. 5 Els resultats han sigut tractats tant a nivell d’estadística descriptiva com a mode inferencial. Les dades amb significació p≤ 0,05 mostren els estímuls (atributs) que foren associats o no, amb la marca del país Mèxic. Mentre que l’arquetip occidental (grec) va permetre en major percentatge valorar la marca amb tots els subjectes (espanyols, mexicans i llatins) l’arquetip prehispànic no dóna significació suficient amb els espanyols i llatins, però en canvi aporta matisos en el cas dels mexicans. En referència a l’esmenta’t anteriorment , cal que el proper pas sigui millorar el perfil d’arquetipus azteca.

Concentrations of the enantiomers of fluoxetine and norfluoxetine after multiple doses of fluoxetine in cytochrome P4502D6 poor and extensive metabolizers.

Plasma concentrations of the enantiomers of fluoxetine (FLX) and norfluoxetine (NFLX) were measured at days 7, 14, and 23 of oral administration of 20 mg of racemic fluoxetine in 11 patients who were comedicated with risperidone. Eight patients were genotyped as being cytochrome P4502D6 extensive metabolizers (EMs) and three as cytochrome P4502D6 poor metabolizers (PMs). No statistically significant differences were calculated between EMs and PMs in the concentrations of (R)-FLX and (R)-NFLX for all days examined (day 23, mean +/- SD for (R)-FLX and (R)-NFLX in EMs, 16 +/- 5 and 29 +/- 20 ng/mL, respectively; in PMs, 16 +/- 1 and 20 +/- 2 ng/mL, respectively). However, concentrations of (S)-FLX and (S)-NFLX were higher and lower, respectively, in PMs as compared with EMs (day 7, p = 0.037 and p = 0.036; day 14, p = 0.014 and p = 0.014; day 23, p = 0.068 and p = 0.038). On day 23, mean (S)-FLX and (S)-NFLX in EMs were (mean +/- SD) 39 +/- 26 and 63 +/- 26 ng/mL, and in PMs they were 88 +/- 7 and 19 +/- 2 ng/mL. This study confirms the results of the single-dose studies showing that CYP2D6 is involved in the demethylation of FLX to NFLX, with a stereoselectivity toward the (S)-enantiomer. The data also clearly show that the CYP2D6 genotype has an important influence on the concentrations of the (S)- but not of the (R)-enantiomer of FLX and NFLX after multiple doses.

Comparison of early cortical networks in efficient and inefficient visual search: an event-related potential study.

Functional magnetic resonance imaging studies have indicated that efficient feature search (FS) and inefficient conjunction search (CS) activate partially distinct frontoparietal cortical networks. However, it remains a matter of debate whether the differences in these networks reflect differences in the early processing during FS and CS. In addition, the relationship between the differences in the networks and spatial shifts of attention also remains unknown. We examined these issues by applying a spatio-temporal analysis method to high-resolution visual event-related potentials (ERPs) and investigated how spatio-temporal activation patterns differ for FS and CS tasks. Within the first 450 msec after stimulus onset, scalp potential distributions (ERP maps) revealed 7 different electric field configurations for each search task. Configuration changes occurred simultaneously in the two tasks, suggesting that contributing processes were not significantly delayed in one task compared to the other. Despite this high spatial and temporal correlation, two ERP maps (120-190 and 250-300 msec) differed between the FS and CS. Lateralized distributions were observed only in the ERP map at 250-300 msec for the FS. This distribution corresponds to that previously described as the N2pc component (a negativity in the time range of the N2 complex over posterior electrodes of the hemisphere contralateral to the target hemifield), which has been associated with the focusing of attention onto potential target items in the search display. Thus, our results indicate that the cortical networks involved in feature and conjunction searching partially differ as early as 120 msec after stimulus onset and that the differences between the networks employed during the early stages of FS and CS are not necessarily caused by spatial attention shifts.

What is the relationship between fear of falling and gait in well-functioning older persons aged 65 to 70 years?

OBJECTIVE: To investigate the association between fear of falling and gait performance in well-functioning older persons. DESIGN: Survey. SETTING: Community. PARTICIPANTS: Subjects (N=860, aged 65-70y) were a subsample of participants enrolled in a cohort study who underwent gait measurements. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Fear of falling and its severity were assessed by 2 questions about fear and related activity restriction. Gait performance, including gait variability, was measured using body-fixed sensors. RESULTS: Overall, 29.6% (210/860) of the participants reported fear of falling, with 5.2% (45/860) reporting activity restriction. Fear of falling was associated with reduced gait performance, including increased gait variability. A gradient in gait performance was observed from participants without fear to those reporting fear without activity restriction and those reporting both fear and activity restriction. For instance, stride velocity decreased from 1.15+/-.15 to 1.11+/-.17 to 1.00+/-.19 m/s (P<.001) in participants without fear, with fear but no activity restriction and with fear and activity restriction, respectively. In multivariate analysis, fear of falling with activity restriction remained associated with reduced gait performance, independent of sex, comorbidity, functional status, falls history, and depressive symptoms. CONCLUSIONS: In these well-functioning older people, those reporting fear of falling with activity restriction had reduced gait performance and increased gait variability, independent of health and functional status. These relationships suggest that early interventions targeting fear of falling might potentially help to prevent its adverse consequences on mobility and function in similar populations.

Connectivity differences in brain networks.

The scenario considered here is one where brain connectivity is represented as a network and an experimenter wishes to assess the evidence for an experimental effect at each of the typically thousands of connections comprising the network. To do this, a univariate model is independently fitted to each connection. It would be unwise to declare significance based on an uncorrected threshold of α=0.05, since the expected number of false positives for a network comprising N=90 nodes and N(N-1)/2=4005 connections would be 200. Control of Type I errors over all connections is therefore necessary. The network-based statistic (NBS) and spatial pairwise clustering (SPC) are two distinct methods that have been used to control family-wise errors when assessing the evidence for an experimental effect with mass univariate testing. The basic principle of the NBS and SPC is the same as supra-threshold voxel clustering. Unlike voxel clustering, where the definition of a voxel cluster is unambiguous, 'clusters' formed among supra-threshold connections can be defined in different ways. The NBS defines clusters using the graph theoretical concept of connected components. SPC on the other hand uses a more stringent pairwise clustering concept. The purpose of this article is to compare the pros and cons of the NBS and SPC, provide some guidelines on their practical use and demonstrate their utility using a case study involving neuroimaging data.

Cytokine mRNA profile of Epstein-Barr virus-stimulated highly differentiated T cells in multiple sclerosis: a pilot study.

The reason why EBV-specific cellular immune responses are abnormal in multiple sclerosis (MS) patients is still missing. In this exploratory pilot study, we assessed IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-17, IFN-gamma, TGF-beta1 and FOXP3 mRNA expression in EBV-stimulated highly differentiated T cells (T(HD)) of MS patients and healthy controls (HC). We found increased levels of IFN-gamma and IL-4 mRNA in CD8+ T(HD) cells of MS patients. All the other tested molecules were expressed similarly in MS patients and HC. Interestingly, increased IFN-gamma and IL-4 suggest that the control of EBV replication may be insufficient in MS patients.

Augmented myocardial methionine-enkephalin in a murine model of cardiac angiotensin II-overexpression.

INTRODUCTION: The endogenous opioid system has been reported to interact with both the cardiac sympathetic and renin-angiotensin systems in exerting a local regulatory action on the heart. The goal of this investigation was to examine how cardiac levels of enkephalin production are altered in the development of normotensive primary hypertrophy due to elevated intra-cardiac angiotensin II (Ang II) production. METHODS: Atrial and ventricular methionine-enkephalin (ME) levels were measured by quantitative radioimmunoassay in 14 and 28-week-old male transgenic mice (TG1306/1R) and control mice. The TG1306/1R exhibit cardiac specific Ang II overexpression and cardiac hypertrophy, but not hypertension. RESULTS: TG1306/1R mice had significantly higher heart/body weight ratios (15-20%) than control littermates at both 14 (p=0.02) and 28 weeks (p=0.04). Relative to controls, ME content was significantly elevated (approximately two-fold) in atria and ventricles in the older 28-week TG1306/1R mice only. A significant inverse correlation between heart size and ME level was observed for 28-week TG1306/1R only. CONCLUSIONS: We have provided evidence that a marked elevation of myocardial enkephalin level is observed in the established (but not early) phase of cardiac hypertrophy associated with cardiac-specific Ang II-overexpression. This study identifies a potentially important relationship between two endogenous peptidergic signalling systems involved in the regulation of growth and function of the hypertrophic heart.

Etude des liens entre l'alexithymie, l'expérience dépressive et la dépendance interpersonnelle chez des sujets addictifs [Relationships between alexithymia, depression and interpersonal dependency in addictive subjects].

In the scientific literature, the term of addiction is currently used to describe a whole range of phenomena characterized by an irresistible urge to engage in a series of behaviors carried out in a repetitive and persistent manner despite accruing adverse somatic, psychological and social consequences for the individual. It has been suggested that subjects presenting such behaviors would share specific features of personality which support the appearance or are associated with these addictive behaviors. Dimensions such as alexithymia and depression have been particularly well investigated. The aim of this study was to explore the hypothesis of a specific psychopathological model relating alexithymia and depression in different addictive disorders such as alcoholism, drug addiction or eating disorders. Alexithymic and depressive dimensions were explored and analyzed through the statistical tool of path analysis in a large clinical sample of addicted patients and controls. The results of this statistical method, which tests unidirectional causal relationships between a certain number of observed variables, showed a good adjustment between the observed data and the ideal model, and support the hypothesis that a depressive dimension can facilitate the development of dependence in vulnerable alexithymic subjects. These results can have clinical implications in the treatment of addictive disorders.

Temporo-Parietal Junction encodes the Embodied Self: Neuro-Robotics, fMRI, and Lesion mapping.

Introduction: Neuroimaging of the self focused on high-level mechanisms such as language, memory or imagery of the self. Recent evidence suggests that low-level mechanisms of multisensory and sensorimotor integration may play a fundamental role in encoding self-location and the first-person perspective (Blanke and Metzinger, 2009). Neurological patients with out-of body experiences (OBE) suffer from abnormal self-location and the first-person perspective due to a damage in the temporo-parietal junction (Blanke et al., 2004). Although self-location and the first-person perspective can be studied experimentally (Lenggenhager et al., 2009), the neural underpinnings of self-location have yet to be investigated. To investigate the brain network involved in self-location and first-person perspective we used visuo-tactile multisensory conflict, magnetic resonance (MR)-compatible robotics, and fMRI in study 1, and lesion analysis in a sample of 9 patients with OBE due to focal brain damage in study 2. Methods: Twenty-two participants saw a video showing either a person's back or an empty room being stroked (visual stimuli) while the MR-compatible robotic device stroked their back (tactile stimulation). Direction and speed of the seen stroking could either correspond (synchronous) or not (asynchronous) to those of the seen stroking. Each run comprised the four conditions according to a 2x2 factorial design with Object (Body, No-Body) and Synchrony (Synchronous, Asynchronous) as main factors. Self-location was estimated using the mental ball dropping (MBD; Lenggenhager et al., 2009). After the fMRI session participants completed a 6-item adapted from the original questionnaire created by Botvinick and Cohen (1998) and based on questions and data obtained by Lenggenhager et al. (2007, 2009). They were also asked to complete a questionnaire to disclose the perspective they adopted during the illusion. Response times (RTs) for the MBD and fMRI data were analyzed with a 3-way mixed model ANOVA with the in-between factor Perspective (up, down) and the two with-in factors Object (body, no-body) and Stroking (synchronous, asynchronous). Quantitative lesion analysis was performed using MRIcron (Rorden et al., 2007). We compared the distributions of brain lesions confirmed by multimodality imaging (Knowlton, 2004) in patients with OBE with those showing complex visual hallucinations involving people or faces, but without any disturbance of self-location and first person perspective. Nine patients with OBE were investigated. The control group comprised 8 patients. Structural imaging data were available for normalization and co-registration in all the patients. Normalization of each patient's lesion into the common MNI (Montreal Neurological Institute) reference space permitted simple, voxel-wise, algebraic comparisons to be made. Results: Even if in the scanner all participants were lying on their back and were facing upwards, analysis of perspective showed that half of the participants had the impression to be looking down at the virtual human body below them, despite any cues about their body position (Down-group). The other participants had the impression to be looking up at the virtual body above them (Up-group). Analysis of Q3 ("How strong was the feeling that the body you saw was you?") indicated stronger self-identification with the virtual body during the synchronous stroking. RTs in the MBD task confirmed these subjective data (significant 3-way interaction between perspective, object and stroking). fMRI results showed eight cortical regions where the BOLD signal was significantly different during at least one of the conditions resulting from the combination of Object and Stroking, relative to baseline: right and left temporo-parietal junction, right EBA, left middle occipito-temporal gyrus, left postcentral gyrus, right medial parietal lobe, bilateral medial occipital lobe (Fig 1). The activation patterns in right and left temporo-parietal junction and right EBA reflected changes in self-location and perspective as revealed by statistical analysis that was performed on the percentage of BOLD change with respect to the baseline. Statistical lesion overlap comparison (using nonparametric voxel based lesion symptom mapping) with respect to the control group revealed the right temporo-parietal junction, centered at the angular gyrus (Talairach coordinates x = 54, y =-52, z = 26; p>0.05, FDR corrected). Conclusions: The present questionnaire and behavioural results show that - despite the noisy and constraining MR environment) our participants had predictable changes in self-location, self-identification, and first-person perspective when robotic tactile stroking was applied synchronously with the robotic visual stroking. fMRI data in healthy participants and lesion data in patients with abnormal self-location and first-person perspective jointly revealed that the temporo-parietal cortex especially in the right hemisphere encodes these conscious experiences. We argue that temporo-parietal activity reflects the experience of the conscious "I" as embodied and localized within bodily space.

Impact of recommendation updates in well-controlled patients on nonrecommended antiretroviral therapies: the Swiss HIV cohort study.

BACKGROUND: HIV treatment recommendations are updated as clinical trials are published. Whether recommendations drive clinicians to change antiretroviral therapy in well-controlled patients is unexplored. METHODS: We selected patients with undetectable viral loads (VLs) on nonrecommended regimens containing double-boosted protease inhibitors (DBPIs), triple-nucleoside reverse transcriptase inhibitors (NRTIs), or didanosine (ddI) plus stavudine (d4T) at publication of the 2006 International AIDS Society recommendations. We compared demographic and clinical characteristics with those of control patients with undetectable VL not on these regimens and examined clinical outcome and reasons for treatment modification. RESULTS: At inclusion, 104 patients were in the DBPI group, 436 in the triple-NRTI group, and 19 in the ddI/d4T group. By 2010, 28 (29%), 204 (52%), and 1 (5%) patient were still on DBPIs, triple-NRTIs, and ddI plus d4T, respectively. 'Physician decision,' excluding toxicity/virological failure, drove 30% of treatment changes. Predictors of recommendation nonobservance included female sex [adjusted odds ratio (aOR) 2.69, 95% confidence interval (CI) 1 to 7.26; P = 0.01] for DPBIs, and undetectable VL (aOR 3.53, 95% CI 1.6 to 7.8; P = 0.002) and lack of cardiovascular events (aOR 2.93, 95% CI 1.23 to 6.97; P = 0.02) for triple-NRTIs. All patients on DBPIs with documented diabetes or a cardiovascular event changed treatment. Recommendation observance resulted in lower cholesterol values in the DBPI group (P = 0.06), and more patients having undetectable VL (P = 0.02) in the triple-NRTI group. CONCLUSION: The physician's decision is the main factor driving change from nonrecommended to recommended regimens, whereas virological suppression is associated with not switching. Positive clinical outcomes observed postswitch underline the importance of observing recommendations, even in well-controlled patients.

Estimation of protein coding density in a corpus of DNA sequence data

A number of experimental methods have been reported for estimating the number of genes in a genome, or the closely related coding density of a genome, defined as the fraction of base pairs in codons. Recently, DNA sequence data representative of the genome as a whole have become available for several organisms, making the problem of estimating coding density amenable to sequence analytic methods. Estimates of coding density for a single genome vary widely, so that methods with characterized error bounds have become increasingly desirable. We present a method to estimate the protein coding density in a corpus of DNA sequence data, in which a ‘coding statistic’ is calculated for a large number of windows of the sequence under study, and the distribution of the statistic is decomposed into two normal distributions, assumed to be the distributions of the coding statistic in the coding and noncoding fractions of the sequence windows. The accuracy of the method is evaluated using known data and application is made to the yeast chromosome III sequence and to C.elegans cosmid sequences. It can also be applied to fragmentary data, for example a collection of short sequences determined in the course of STS mapping.

Climatic extremes improve predictions of spatial patterns of tree species.

Understanding niche evolution, dynamics, and the response of species to climate change requires knowledge of the determinants of the environmental niche and species range limits. Mean values of climatic variables are often used in such analyses. In contrast, the increasing frequency of climate extremes suggests the importance of understanding their additional influence on range limits. Here, we assess how measures representing climate extremes (i.e., interannual variability in climate parameters) explain and predict spatial patterns of 11 tree species in Switzerland. We find clear, although comparably small, improvement (+20% in adjusted D(2), +8% and +3% in cross-validated True Skill Statistic and area under the receiver operating characteristics curve values) in models that use measures of extremes in addition to means. The primary effect of including information on climate extremes is a correction of local overprediction and underprediction. Our results demonstrate that measures of climate extremes are important for understanding the climatic limits of tree species and assessing species niche characteristics. The inclusion of climate variability likely will improve models of species range limits under future conditions, where changes in mean climate and increased variability are expected.

Anti-Nogo-A Antibody Treatment Promotes Recovery of Manual Dexterity after Unilateral Cervical Lesion in Adult Primates--re-examination and Extension of Behavioral Data.

In rodents and nonhuman primates subjected to spinal cord lesion, neutralizing the neurite growth inhibitor Nogo-A has been shown to promote regenerative axonal sprouting and functional recovery. The goal of the present report was to re-examine the data on the recovery of the primate manual dexterity using refined behavioral analyses and further statistical assessments, representing secondary outcome measures from the same manual dexterity test. Thirteen adult monkeys were studied; seven received an anti-Nogo-A antibody whereas a control antibody was infused into the other monkeys. Monkeys were trained to perform the modified Brinkman board task requiring opposition of index finger and thumb to grasp food pellets placed in vertically and horizontally oriented slots. Two parameters were quantified before and following spinal cord injury: (i) the standard 'score' as defined by the number of pellets retrieved within 30 s from the two types of slots; (ii) the newly introduced 'contact time' as defined by the duration of digit contact with the food pellet before successful retrieval. After lesion the hand was severely impaired in all monkeys; this was followed by progressive functional recovery. Remarkably, anti-Nogo-A antibody-treated monkeys recovered faster and significantly better than control antibody-treated monkeys, considering both the score for vertical and horizontal slots (Mann-Whitney test: P = 0.05 and 0.035, respectively) and the contact time (P = 0.008 and 0.005, respectively). Detailed analysis of the lesions excluded the possibility that this conclusion may have been caused by differences in lesion properties between the two groups of monkeys.