Inhibition of Notch Pathway Enhances Photoreceptor Commitment From Cultured Retinal Stem Cells

Purpose: Consequently to the principle that photoreceptors have to be at a very precise development stage to be successfully transplanted (MacLaren 2006), we are trying to mimic this development stage in vitro using retinal stem cells. The latter one isolated from the newborn mouse retina, derived from the radial glia population, which were previously isolated and characterized in our laboratory. We developed a protocol to commit these cells to the photoreceptor fate, but even if the percentage of cells expressing photoreceptor markers is high (30%), the differentiation process is incomplete so far (Merhi-Soussi 2006). Methods: In order to ameliorate photoreceptor differentiation, we hypothesized that the Notch pathway may interfere with this process by either promoting glia commitment, or maintaining an undifferentiated state. We are thus using a gamma-secretase inhibitor (DAPT), which inhibits Notch receptor cleavage and thus Notch activation. DAPT was used either during the whole differentiation stimulation, or only during a restricted period in two various retinal stem cell lines (RSC AA and RSC MP1). Results: RT-PCR performed during cell proliferation, showed the same positive expression in both cell lines for the following genes: Math3, Six3, Hes1, NeuroD, Pax6 and Notch1. Additionally, Mash1, Hes5, Prox1, Crx and Otx2 were detected in both cell lines but with a stronger expression in RSC MP1. Opposite results were obtained for Chx10. Nrl, Peripherin/RDS, GFAP and Math5 were detected neither in RSC AA, nor in RSC MP1. The constant presence of DAPT i) leads to a 233% (RSC AA) or 900% (RSC MP1) increase in peripherin/RDS-positive (photoreceptor marker) cells, compared to controls (no DAPT, n=3, P<0.02) along with a 68% (RSC AA) or 80% (RSC MP1) decrease in GFAP- positive cells (n=3, P<0.04), ii) modifies the ratio between uni-/bi- (23%) and multi- (77%) polar peripherin/RDS-positive cells to 45% and 55%, respectively, for both cell lines and iii) reduces by 50% the total cell number during the whole differentiation process for both cell lines. Conclusions: We are now exploring whether this reduction in total cell number is due to inhibition of cell proliferation or to cell death and whether photoreceptor differentiation is promoted instead of glial induction. We also want to confirm the results obtained with DAPT with RSCs isolated from Notch1-loxP mice. Such protocol may help to better mimic photoreceptor development, but this needs to be confirmed by genomic and proteomic profile analyses.

Brain functional abnormality in schizo-affective disorder: an fMRI study.

Background.Schizo-affective disorder has not been studied to any significant extent using functional imaging. The aim of this study was to examine patterns of brain activation and deactivation in patients meeting strict diagnostic criteria for the disorder. METHOD: Thirty-two patients meeting research diagnostic criteria (RDC) for schizo-affective disorder (16 schizomanic and 16 schizodepressive) and 32 matched healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: Controls showed activation in a network of frontal and other areas and also deactivation in the medial frontal cortex, the precuneus and the parietal cortex. Schizo-affective patients activated significantly less in prefrontal, parietal and temporal regions than the controls, and also showed failure of deactivation in the medial frontal cortex. When task performance was controlled for, the reduced activation in the dorsolateral prefrontal cortex (DLPFC) and the failure of deactivation of the medial frontal cortex remained significant. CONCLUSIONS: Schizo-affective disorder shows a similar pattern of reduced frontal activation to schizophrenia. The disorder is also characterized by failure of deactivation suggestive of default mode network dysfunction.

Brain functional abnormality in schizo-affective disorder: an fMRI study.

Background.Schizo-affective disorder has not been studied to any significant extent using functional imaging. The aim of this study was to examine patterns of brain activation and deactivation in patients meeting strict diagnostic criteria for the disorder. METHOD: Thirty-two patients meeting research diagnostic criteria (RDC) for schizo-affective disorder (16 schizomanic and 16 schizodepressive) and 32 matched healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: Controls showed activation in a network of frontal and other areas and also deactivation in the medial frontal cortex, the precuneus and the parietal cortex. Schizo-affective patients activated significantly less in prefrontal, parietal and temporal regions than the controls, and also showed failure of deactivation in the medial frontal cortex. When task performance was controlled for, the reduced activation in the dorsolateral prefrontal cortex (DLPFC) and the failure of deactivation of the medial frontal cortex remained significant. CONCLUSIONS: Schizo-affective disorder shows a similar pattern of reduced frontal activation to schizophrenia. The disorder is also characterized by failure of deactivation suggestive of default mode network dysfunction.

Brain functional abnormality in schizo-affective disorder: an fMRI study.

Background.Schizo-affective disorder has not been studied to any significant extent using functional imaging. The aim of this study was to examine patterns of brain activation and deactivation in patients meeting strict diagnostic criteria for the disorder. METHOD: Thirty-two patients meeting research diagnostic criteria (RDC) for schizo-affective disorder (16 schizomanic and 16 schizodepressive) and 32 matched healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: Controls showed activation in a network of frontal and other areas and also deactivation in the medial frontal cortex, the precuneus and the parietal cortex. Schizo-affective patients activated significantly less in prefrontal, parietal and temporal regions than the controls, and also showed failure of deactivation in the medial frontal cortex. When task performance was controlled for, the reduced activation in the dorsolateral prefrontal cortex (DLPFC) and the failure of deactivation of the medial frontal cortex remained significant. CONCLUSIONS: Schizo-affective disorder shows a similar pattern of reduced frontal activation to schizophrenia. The disorder is also characterized by failure of deactivation suggestive of default mode network dysfunction.

Involuntary treatment of alcohol-dependent patients: a study of 17 consecutive cases of civil commitment.

AIM: To investigate the baseline and follow-up characteristics of a group of alcohol-dependent patients being treated under civil commitment. METHODS: This study involved a cross-sectional comparative analysis of baseline characteristics and a follow-up survey of a group of committed alcoholic patients. The study was undertaken in the Alcohol Unit of a 1,000-bed general and university hospital. The study included 17 consecutive cases of civil commitment (representing 15 patients, of whom 2 were committed twice) and a comparative group of 34 randomly selected age- and sex-matched patients. Baseline characteristics of the cases (at the time of commitment) and of patients from the comparative group were collected from medical records, including sociodemographic data, medical condition, patterns of drinking and number and dates of previous treatments for alcohol-related problems. A structured follow-up interview of the cases provided information on their medical condition, social status, patterns of alcohol use, type and duration of residential treatment as well as their perceptions of commitment. RESULTS: During a 4-year period, our Unit referred 23 cases of alcohol-dependent patients (out of 367) to the Guardianship Authority, requesting civil commitment. On 17 occasions, patients were committed to residential treatment, including 2 patients who underwent commitment on two separate occasions, thus representing a total of 15 different patients. In comparison with age- and sex-matched patients seen at the Unit, the cases were characterized by multiple medical, social and psychological alcohol-related impairments. At the time of follow-up, 14 out of 15 patients were alive, among whom 10 agreed to be interviewed. Eight of these reported complete abstinence, whereas 9 considered their alcohol problem as less severe than before. The average duration of commitment was 29 weeks. The majority of patients retrospectively considered the measure as having been justified and useful. The patients' satisfaction with the decision to commit was higher among women than among men. Health-related quality of life at the time of follow-up, as assessed by the MOS 36-Item Short Form Health Survey questionnaire, was good on average and better than that usually reported by other cohorts of alcoholics undergoing treatment. CONCLUSIONS: The usefulness of residential civil commitment of certain severely impaired alcohol-dependent patients is underscored. This study suggests that civil commitment not only may save the lives of endangered patients but could also be a health-promoting measure that may sometimes allow for recovery from dependence. Unexpectedly, this measure was retrospectively well accepted by many patients, who considered the commitment decision as having been justified and useful.

Des "psychoses affectives" aux "caractéristiques psychotiques" : les symptômes psychotiques selon le DSM, discutés à la lumière d'une série de 16 cas de dépression psychotique = From "affective psychoses" to "psychotic features": DSM's psychoticsymptoms discussed in the light of a series of 16 cases of psychoticdepression.

Objectifs. - Le DSM-5 donne une définition du symptôme psychotique indépendante de tout concept depsychose. Chez les patients dépressifs, la présence d'hallucination ou d'idée délirante, quelle que soit leurforme clinique, conduit en principe à diagnostiquer une dépression psychotique et à prescrire des neurolep-tiques. Les symptômes psychotiques sont subdivisés par le DSM en « congruents » ou « non congruents » àl'humeur. Nous discutons de la pertinence d'une catégorie de symptômes psychotiques « atypiques », peuévocateurs d'une psychose au sens classique du terme. Méthode. - Discussion de la définition opérationnelle des symptômes psychotiques du DSM, étude d'unesérie de 16 patients chez qui un diagnostic de dépression psychotique a été posé. Résultats. - Sur les 16 patients, deux seulement présentaient des symptômes psychotiques classiques, évo-cateurs d'une psychose. Chez les autres, le diagnostic reposait sur la présence de symptômes très atypiques,comme des hallucinations visuelles par exemple.

Specificities of defense mechanisms in bipolar affective disorder: relations with symptoms and therapeutic alliance.

Defense mechanisms as a central notion of psychoanalysis have inspired various levels of interest in research in psychotherapy and psychopathology. Defense specificities have only recently been investigated systematically with regard to several clinical diagnoses, such as affective and personality disorders. For the present study, 30 inpatients diagnosed with Bipolar Affective Disorder I (BD) were interviewed. An observer-rater method, the Defense Mechanisms Rating Scales (DMRS), applied to session-transcripts, of assessment of defenses was used. A matched, nonclinical control group was introduced. Defense specificities in BD encompass a set of 5 immature defenses, of which omnipotence is linked with symptom level. The level of the therapeutic alliance is predicted by mature defenses. These results are discussed with regard to the psychological vulnerability of BD, and treatment implications for psychodynamic psychotherapy with such challenging patients are evoked.

Commentary on "The Cognitive-Emotional Brain: From Interactions to Integration" by Luiz Pessoa - "On theory integration: Toward developing affective components within cognitive architectures"

In The Cognitive-Emotional Brain, Pessoa (2013) suggests that cognition and emotion should not be considered separately. We agree with this and argue that cognitive architectures can provide steady ground for this kind of theory integration and for investigating interactions among underlying cognitive processes. We briefly explore how affective components can be implemented and how neuroimaging measures can help validate models and influence theory development.

Brain functional abnormality in schizo-affective disorder: an fMRI study.

Background.Schizo-affective disorder has not been studied to any significant extent using functional imaging. The aim of this study was to examine patterns of brain activation and deactivation in patients meeting strict diagnostic criteria for the disorder. METHOD: Thirty-two patients meeting research diagnostic criteria (RDC) for schizo-affective disorder (16 schizomanic and 16 schizodepressive) and 32 matched healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: Controls showed activation in a network of frontal and other areas and also deactivation in the medial frontal cortex, the precuneus and the parietal cortex. Schizo-affective patients activated significantly less in prefrontal, parietal and temporal regions than the controls, and also showed failure of deactivation in the medial frontal cortex. When task performance was controlled for, the reduced activation in the dorsolateral prefrontal cortex (DLPFC) and the failure of deactivation of the medial frontal cortex remained significant. CONCLUSIONS: Schizo-affective disorder shows a similar pattern of reduced frontal activation to schizophrenia. The disorder is also characterized by failure of deactivation suggestive of default mode network dysfunction.

Identification-commitment inventory (ICI-Model): confirmatory factor analysis and construct validity

The aim of this study is to confirm the factorial structure of the Identification-Commitment Inventory (ICI) developed within the frame of the Human System Audit (HSA) (Quijano et al. in Revist Psicol Soc Apl 10(2):27-61, 2000; Pap Psicól Revist Col Of Psicó 29:92-106, 2008). Commitment and identification are understood by the HSA at an individual level as part of the quality of human processes and resources in an organization; and therefore as antecedents of important organizational outcomes, such as personnel turnover intentions, organizational citizenship behavior, etc. (Meyer et al. in J Org Behav 27:665-683, 2006). The theoretical integrative model which underlies ICI Quijano et al. (2000) was tested in a sample (N = 625) of workers in a Spanish public hospital. Confirmatory factor analysis through structural equation modeling was performed. Elliptical least square solution was chosen as estimator procedure on account of non-normal distribution of the variables. The results confirm the goodness of fit of an integrative model, which underlies the relation between Commitment and Identification, although each one is operatively different.

Personality effects and sex differences on the international affective picture system (IAPS) : a Spanish and Swiss study

The present study analyses the relationship between Anxiety and Impulsivity personality factors and emotions, by controlling for country and sex effects in a sample of Spanish and Swiss university students. Emotions were assessed through the International Affective Picture System (IAPS) of pictures (valence/arousal) using the Self-Assessment Manikin (SAM) procedure. The mixed valence/arousal groups' pictures were formed according to Tok, Koyuncu, Dural and Catikkas procedure (2010). Results showed that females scored significantly higher in Anxiety factor and men in Impulsivity factor in both countries. The effect of sex was highly significant for Anxiety (ŋ2: 0.12), but there was no significant effect of the country. Also, females obtained higher scores in the four valence/arousal pictures groups. The sex effect was particularly robust for negative valence-high arousal (ŋ2: 0.13). Impulsivity correlated with high ratings of positive valence-high arousal while Anxiety correlated with high ratings of negative valence-high arousal and with high ratings of negative valence-low arousal in both sexes, although scores were higher for females. Structural Equation Modelling confirmed these relationships. Nevertheless, Anxiety and Impulsivity explained only a small amount of the accounted variance of the self-reported valence and arousal of the pictures.

Nuorten esimiesten ja asiantuntijoiden organisaatioon sitoutuminen, case: Kesko Oyj

Tutkimuksen tavoitteena on selvittää miten nuoret esimiehet ja asiantuntijat ovat sitoutuneita organisaatioon. Lisäksi pyritään nostamaan esille tekijöitä, joita voidaan pitää sitoutumisen kannalta tärkeimpinä sekä hahmottamaan keinoja, joilla sitoutumiseen liittyviä tekijöitä voisi kehittää entisestään. Työn teoriaosassa keskitytään organisaatioon sitoutumiseen käsitteenä, esitellään erilaisia sitoutumismalleja, tarkastellaan sitoutumisen seurauksia sekä käydään läpi sitoutumiseen vaikuttavia tekijöitä. Työ on kvalitatiivinen eli laadullinen tutkimus. Tutkimuksen empiiriseen osioon aineisto kerättiin haastattelujen avulla Keskon nuorilta esimiehiltä ja asiantuntijoilta. Tutkimustulokset osoittavat, että haastatellut työntekijät ovat pääasiassa affektiivisesti eli tunnepitoisesti sitoutuneita organisaatioon. Sitoutumisen kannalta tärkeimpiä tekijöitä ovat itse työ jonka parissa työskennellään, organisaation tarjoamat koulutusmandollisuudet, työilmapiiri, esimiestoiminta sekä urakehitysmandollisuudet. Tulosten mukaan organisaatiossa nimenomaan halutaan työskennellä eikä sitä koeta niinkään pakkona tai velvollisuutena.