The evolution of personality in patients with mild cognitive impairment.

Aims: To describe personality traits and their changes in mild cognitive impairment (MCI) and control subjects. Methods: Sixty-three MCI and 90 control subjects were asked to describe their current personality traits by the Structured Interview for the Five-Factor Model (SIFFM). For each subject, a close relative retrospectively assessed these descriptions both as to the previous and current personality traits, using the Revised NEO Personality Inventory, Form R (NEO-PI-R). Results: Self-assessed MCI subjects reported significantly lower scores in the openness dimension than control subjects [F(1, 150) = 9.84, p = 0.002, ηp(2) = 0.06]. In current observer ratings, MCI subjects had higher scores on neuroticism [F(1, 137) = 7.55, p = 0.007, ηp(2) = 0.05] and lower ones on extraversion [F(1, 137) = 6.40, p = 0.013, ηp(2) = 0.04], openness [F(1, 137) = 9.93, p = 0.002, ηp(2) = 0.07], agreeableness [F(1, 137) = 10.18, p = 0.002, ηp(2) = 0.07] and conscientiousness [F(1, 137) = 25.96, p < 0.001, ηp(2) = 0.16]. Previous personality traits discriminated the groups as previous openness [odds ratio (OR) = 0.97, 95% confidence interval (CI) = 0.95-0.99, p = 0.014] and conscientiousness (OR = 0.96, 95% CI 0.94-0.98, p = 0.001) were negatively related to MCI group membership. In MCI subjects, conscientiousness [F(1, 137) = 19.20, p < 0.001, ηp(2) = 0.12] and extraversion [F(1, 137) = 22.27, p < 0.001, ηp(2) = 0.14] decreased between previous and current evaluations and neuroticism increased [F(1, 137) = 22.23, p < 0.001, ηp(2) = 0.14], whereas no significant change was found in control subjects. Conclusions: MCI subjects undergo significant personality changes. Thus, personality assessment may aid the early detection of dementia. © 2013 S. Karger AG, Basel.

Updated Swiss guidelines for the treatment and follow-up of cutaneous melanoma.

Melanoma is the most common lethal cutaneous neoplasm. In order to harmonize treatment and follow-up of melanoma patients, guidelines for the management of melanoma in Switzerland have been inaugurated in 2001. These have been approved by all Swiss medical societies involved in the care of melanoma patients. New data necessitated changes concerning the safety margins (reduction to maximally 2 cm) and modifications of the recommendations of follow-up.

Propranolol as an adjunct therapy for hyperthyroid tremor.

We evaluated the use of propranolol as an adjunct to carbimazole in the treatment of hyperthyroid tremor and tachycardia in a double-blind, cross-over and placebo-controlled study. Seven patients were given carbimazole plus either placebo or propranolol (40 mg) for 1 month and then switched to the alternative adjunct treatment for a further month. All patients showed significant improvements (p < 0.001) of heart rate and tremor amplitude after 1 or 2 months from baseline. One month after the baseline, the mean improvements of heart rate were 23% for the carbimazole + placebo group and 38% for carbimazole + propranolol group. Tremor also improved during the 1st month of the study by 31% in the carbimazole + placebo group versus 59% in the carbimazole + propranolol group. Whereas further improvements were observed in both variables in those receiving propranolol as the second adjunct treatment, this was not the case in those who received placebo during the same period. These findings confirm that the beta-blocker propranolol is a useful adjunct in the early treatment of both the tremor and tachycardia of hyperthyroidism.

Characterization of NALP2 and NALP3 IL-1β processing inflammasomes

Résumé II y a cinq ans, la découverte d'un nouveau domaine, le PYD domaine, lié aux domaines de la mort, a permis la description de la nouvelle famille des NALP protéines. L'analyse structurelle de cette famille de protéines révéla la présence de deux autres domaines, impliqués dans l'oligomerisation, NACHT, et la détection des ligands, Leucine rich repeats ou LRR. Cette architecture protéique est homologue à celle qui est décrite pour les NODs, les Tol1 récepteurs et tes protéines de résistance chez les plantes. Cette homologie suggère une possible implication des NALPs dans la régulation de l'immunité innée. Premièrement, nous avons décrit les composants minimaux qui permettent à l'inflammasomeNALP3 d'activer la caspase pro-inflammatoire, caspase-1. En comparaison à NALP1, NALP3 ne contient pas de FIIND domaine, ni de CARD domaine en C-terminus et n'interagit pas avec caspase-5. Nous avons découvert une protéine très homologue au C-terminus de NALP1, Cardinal, qui se lie au NACHT domaine de NALP2 et NALP3 par l'intermédiaire de son FIIND domaine. Cardinal possède la capacité d'interagir avec caspase-l, mais seul ASC semble être nécessaire à la maturation de la prointerleukine-1β suite à la stimulation de NALP3. Deuxièmement, notre étude s'est concentrée sur la nature du stimulus capable d'induire la formation et l'activation de l'inflammasome-NALP3. Nous avons démontré que l'ajout de muramyl dipeptide (MDP), produit à partir de la digestion enzymatique de peptidoglycaris bactériens, induit à la fois l'expression de la proIL-1β par la voie NOD2 et sa maturation en IL-1β active par la voie NALP3. Bien que le MDP active l'inflammasome-NALP3, il est incapable d'induire la sécrétion de l'IL-1β mature dans la lignée cellulaire THP1, comparé aux monocytes primaires humains. Cette différence pourrait être liée à l'absence, dans les THP1, de la protéine Filamin, qui est proposée d'interagir avec Cardinal. L'implication de NALP3 dans la maturation de l'IL-lb est confirmée suite à la découverte de mutations sur le gène CIAS1/NALP3/cryopyrin associées à trois maladies auto-inflammatoires : le syndrome de Muckle-Wells (MWS), l'urticaire familial au froid (FCU) et le syndrome CINCA/NOMID. Une élévation constitutive de la maturation et de la sécrétion de la proIL-1β en absence de stimulation MDP est détectée dans les macrophages des patients Muckle-Wells. En conclusion, nos études ont démontré que l'inflammasome-NALP3 doit être finement régulé pour éviter une activité incontrôlée qui représente la base moléculaire des symptômes associés aux syndromes auto-inflammatoires liés à NALP3. Summary Five years ago, the description of the NALP family originated from the discovery of a new death-domain fold family, the PYD domain. NALP contains aprotein-protein interaction domain (PYD), an oligomerization domain (NACHT) and a ligand-sensing domain, leucine rich repeats or LRR. This protein architecture shares similarity with receptors involved in immunity, such as NODS, Toll receptors (TLRs) and related plant resistance proteins, and points to an important role of NALPs in defense mechanisms. We first described the minimal complex involved in the pro-inflammatory Interleukin-1beta (IL-1β) cytokine maturation, called the inflammasome, which contains NALP3. In contrast to NALP1, NALP3, like other members of the NALP family, is devoid of C-terminal FIIND and CARD domains and does not interact with the pro-inflammatory caspase-5. Interestingly, a homolog of the C-terminal portion of NALP1 was found in the human genome and was named Cardinal. We found that NALP2 and NALP3 interact with the CARD-containing proteins Cardinal. Cardinal is able to bind to caspase-1 but is not required for IL-1β maturation through NALP3 activation, as demonstrated for the adaptor ASC. Secondly, our study focused on the stimuli involved in the activation of the NALP3 inflammasome. MDP was shown to induce the expression of proIL1β through NOD2 and then the maturation into active IL-1β by activation of the NALP3 inflammasome. However, in the monocytic THP1 cell line, secretion of IL-1β upon MDP stimulation seems to be independent of the inflammasome activation compared to human primary monocytes. This difference might be linked to a Cardinal-interacting protein, filamin. Until now, the role of Cardinal and filamin is still unknown and remains to be elucidated. Finally, mutations in the NALP3/cryopyrin/CIAS1 gene are associated with three autoinflammatory diseases: Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and CINCA. Constitutive, elevated IL-1β maturation and secretion, even in the absence of MDP stimulation, was observed in macrophages from Muckle-Wells patients and confirmed a key role for the NALP3 inflammasome in innate immunity In conclusion, our studies describes the formation of the NALP3 inflammasome and suggests that this complex has to be tightly regulated to avoid an increased deregulated inflammasome activity that is the molecular basis for the symptoms associated with NALP3-dependent autoinflammatory disorders.

The role of Notch signaling during hematopoietic lineage commitment.

Over the last few years a vast amount of progress has been made in identifying mechanisms controlling lineage commitment and plasticity of hematopoietic precursors to different lymphoid or myeloid lineages. This has been due largely to the ability to identify and isolate rare cell populations in order to investigate their developmental potential, together with the development of inducible and/or tissue specific targeting technology. One family of proteins that has been postulated to be involved in hematopoietic stem cell maintenance as well as in multiple commitment processes during T cell development is the Notch receptors and their ligands. In this review we will summarize recent findings and controversies regarding the role of Notch signaling in the myeloid and lymphoid systems.

Floating arterial thrombus related stroke treated by intravenous thrombolysis.

BACKGROUND: The effects of intravenous thrombolysis on floating thrombi in cervical and intracranial arteries of acute ischemic stroke patients are unknown. Similarly, the best prevention methods of early recurrences remain controversial. This study aimed to describe the clinical and radiological outcome of thrombolyzed strokes with floating thrombi. METHODS: We retrospectively analyzed all thrombolyzed stroke patients in our institution between 2003 and 2010 with floating thrombi on acute CT-angiography before the intravenous thrombolysis. The floating thrombus was diagnosed if an elongated thrombus of at least 5 mm length, completely surrounded by contrast on supra-aortic neck or intracerebral arteries, was present on CT-angiography. Demographics, vascular risk factors, and comorbidities were recorded and stroke etiology was determined after a standardized workup. Repeat arterial imaging was performed by CTA at 24 h or before if clinical worsening was noted and then by Doppler and MRA during the first week and at four months. RESULTS: Of 409 thrombolyzed stroke patients undergoing acute CT Angiography, seven (1.7%) had a floating thrombus; of these seven, six had it in the anterior circulation. Demographics, risk factors and stroke severity of these patients were comparable to the other thrombolyzed patients. After intravenous thrombolysis, the floating thrombi resolved completely at 24 h in four of the patients, whereas one had an early recurrent stroke and one developed progressive worsening. One patient developed early occlusion of the carotid artery with floating thrombus and subsequently a TIA. The two patients with a stable floating thrombus had no clinical recurrences. In the literature, only one of four reported cases were found to have a thrombolysis-related early recurrence. CONCLUSIONS: Long-term outcome seemed similar in thrombolyzed patients with floating thrombus, despite a possible increase of very early recurrence. It remains to be established whether acute mechanical thrombectomy could be a safer and more effective treatment to prevent early recurrence. However, intravenous thrombolysis should not be withheld in eligible stroke patients.

La réhabilitation psychosociale a l'aube du XXIème siècle. I: Principes, population cible et pathologie en cause

The relatively recent development of the psychosocial rehabilitation has its origins mainly in the progress of modern psychopharmacology, the assertion of the rights of the patients and the result of the studies showing that the evolution of persons suffering from severe and persistent mental illnesses can prove to be positive in many cases. In spite of the heterogeneity of the experiences and of the theoretical references, the core principles of the psychosocial rehabilitation imposed themselves. These principles can be classified according to three levels, that of relational ethics, that of the method of intervention and that of the institutional device. A recent study showed that 2.4@1000 of the general adult population of the Canton of Vaud live in sociotherapeutic and rehabilitation accommodations. In this sample, there is a important percentage of relatively young persons (55.3% are under 40). In institutional accommodation there is a majority of patients suffering from major personality disorders and addiction (40.6%), followed by psychotic disorders (37.2%), persistent mood disorders (12.3%), neurotic disorders (6.6%) and psycho-organic disorders (3.3%). In home based rehabilitation, the ratio of patients with psychotic disorders is more important (53.1%). This difference would indicate that people with schizophrenia would have a better social outcome than personality disorders with addiction

Perampanel: a significant liver enzyme inducer in some patients?

Perampanel is one of the latest released antiepileptic drugs (AEDs). Early studies suggest no significant liver enzyme induction from this compound. We report on two patients with medically resistant epilepsy, who had perampanel added to their usual regimen. Both experienced a worsening of their epilepsy and presented in convulsive status epilepticus; concurrent antiepileptic drug levels (phenytoin, phenobarbital, rufinamide) were significantly decreased (<50%) in comparison with levels prior to perampanel introduction. Intravenous load and significant increase of maintenance dosages were needed to restore therapeutic drug levels. In one patient, further increase of perampanel resulted in a new drop of phenytoin level. This suggests that perampanel could, in some subjects, induce liver enzymes and interact with concomitant AEDs; monitoring levels of concomitant compounds could be useful.

The role of mycorrhizas in more sustainable oil palm cultivation

Oil palm is a significant and developing crop in many developing countries. The introduction of oil palm puts pressure on natural resources because it is often planted in cleared-cut land that previously supported other crops or was forested. This has led to environmental concerns which require attention. Hence it is important that new plantations are managed in a sustainable way to reduce the impact of oil palm cultivation on ecosystems whilst maximising yield and productivity to farmers. The application of arbuscular mycorrhizal fungi (AMF) technology is one option that can benefit both agronomic plant health and ecosystems. AMF have the potential to increase conventional agricultural productivity and are crucial for the sustainable functioning of agricultural ecosystems. This paper provides an insight into how AMF application might benefit oil palm cultivation through more sustainable management and the practical use of AMF for oil palm plantations.

Seeing the Wood through the Trees: The Current State of Higher Systematics in the Strepsirhini.

Strepsirhines comprise 10 living or recently extinct families, ≥50% of extant primate families. Their phylogenetic relationships have been intensively studied, but common topologies have only recently emerged; e.g. all recent reconstructions link the Lepilemuridae and Cheirogaleidae. The position of the indriids, however, remains uncertain, and molecular studies have placed them as the sister to every clade except Daubentonia, the preferred sister group of morphologists. The node subtending Afro-Asian lorisids has been similarly elusive. We probed these phylogenetic inconsistencies using a test data set including 20 strepsirhine taxa and 2 outgroups represented by 3,543 mtDNA base pairs, and 43 selected morphological characters, subjecting the data to maximum parsimony, maximum likelihood and Bayesian inference analyses, and reconstructing topology and node ages jointly from the molecular data using relaxed molecular clock analyses. Our permutations yielded compatible but not identical evolutionary histories, and currently popular techniques seem unable to deal adequately with morphological data. We investigated the influence of morphological characters on tree topologies, and examined the effect of taxon sampling in two experiments: (1) we removed the molecular data only for 5 endangered Malagasy taxa to simulate 'extinction leaving a fossil record'; (2) we removed both the sequence and morphological data for these taxa. Topologies were affected more by the inclusion of morphological data only, indicating that palaeontological studies that involve inserting a partial morphological data set into a combined data matrix of extant species should be interpreted with caution. The gap of approximately 10 million years between the daubentoniid divergence and those of the other Malagasy families deserves more study. The apparently contemporaneous divergence of African and non-daubentoniid Malagasy families 40-30 million years ago may be related to regional plume-induced uplift followed by a global period of cooling and drying. © 2013 S. Karger AG, Basel.

Changes in ubiquitin immunoreactivity in developing rat brain: a putative role for ubiquitin and ubiquitin conjugates in dendrite outgrowth and differentiation.

The role of ubiquitin in development of the mammalian brain has been studied using a monoclonal antibody, RHUb1, specific for ubiquitin. Immunodevelopment of western blots of homogenate samples of the cerebral cortex, hippocampus and cerebellum prepared from animals of known postnatal age show marked developmental changes in conjugate level. Striking decreases in the level of a prominent conjugate of molecular weight 22,000, which is identified as ubiquitinated histone, are observed during the first postnatal week in the cerebral cortex and hippocampus, but not the cerebellum. A marked overall developmental decrease in the level of high-molecular-weight (> 40,000) ubiquitin conjugates which occurs predominantly during the third, but also the fourth, postnatal week is observed in all three regions. Immunocytochemical data obtained with the RHUb1 antibody show intense staining of neuronal perikarya, nuclei and dendrites in early postnatal cerebral cortex and hippocampus. Staining of pyramidal cell perikarya and dendrites is particularly prominent. The intensity of dendritic staining, particularly for the cerebral cortex, shows a striking decrease after postnatal day 14 and only faint dendritic staining is observed in the adult. In early postnatal cerebellum, immunoreactivity is predominantly nuclear, though some staining of the proximal regions of Purkinje cell dendrites is observed between postnatal days 4 and 19. As with the cerebral cortex and hippocampus, most of the ubiquitin reactivity is lost in adult animals. The loss of dendritic staining, particularly in the cerebral cortex, correlates with the decrease in the level of high-molecular-weight ubiquitin conjugates observed on the western blots. Immunodevelopment of western blots of a range of subcellular fractions prepared from developing rat forebrain shows that the developmental decrease in the level of high-molecular-weight ubiquitin conjugates is not uniform for all fractions. The decrease in conjugate level is most marked for the cell-soluble, mitochondrial and detergent-insoluble cytoskeletal fractions. Taken overall, the data suggest a role for ubiquitin in dendrite outgrowth and arborization, loss of dendritic ubiquitin immunoreactivity correlating with completion of these processes.

Laparoscopic and open colorectal surgery in everyday practice : retrospective study

Résumé Introduction: La plupart des études disponibles sur la chirurgie colorectale par laparoscopie concernent des patients hautement sélectionnés. Le but de cette étude est d'analyser les résultats à court et à long terme de l'ensemble des patients traités dans un service de chirurgie générale. Méthodes: Il s'agit d'une analyse rétrospective d'un registre prospectif interne au service, dans lequel tous les patients consécutifs opérés pour la première fois du colon et du rectum entre mars 1993 et décembre 1997 ont été enregistrés. Les informations concernant le suivi ont été collectées par questionnaire. Résultats: Un total de 187 patients ont été opérés par laparoscopie et 215 patients par chirurgie ouverte durant la période d'étude. Les informations concernant le suivi ont pu être collectées dans 95% des cas avec une évolution de 1-107 mois (médiane 59 mois), respectivement de 1-104 mois (médiane 53 mois). Une conversion fut nécessaire dans 28 cas (15%) mais ceux-ci restent inclus dans le groupe laparoscopie pour l'analyse par intention de traitement. Dans le groupe laparoscopie, les opérations ont duré plus longtemps (205 vs 150 min, p<0.001) mais l'hospitalisation a été plus courte (8 vs 13 jours, p<0.001). La reprise du transit a été plus rapide après laparoscopie, mais uniquement après intervention sur le colon gauche (3 vs 4 jours, p<0.01). Cependant, la sélection préopératoire (nombre plus élevé d'urgences et de patients avec un risque anesthésiologique élevé dans le groupe de la chirurgie ouverte) a été favorable à la laparoscopie. Le taux de complications (global ainsi que pour chaque complication chirurgicale) a été similaire dans les deux groupes, avec un taux global de 20% environ. Conclusions: Malgré une sélection favorable des cas, uniquement très peu d'avantages à la laparoscopie sur la chirurgie ouverte ont pu être observés. Abstract Background: Most studies available on laparoscopic colorectal surgery focus on highly selected patient groups. The aim of the present study was to review short- and long-term outcome of everyday patients treated in a general surgery department. Methods: Retrospective review was carried out of a prospective database of all consecutive patients having undergone primary laparoscopic (LAP) or open colorectal surgery between March 1993 and December 1997. Follow-up data were completed via questionnaire. Results: A total of 187 patients underwent LAP resection and 215 patients underwent open surgery. Follow up was complete in 95% with a median of 59 months (range, 1-107 months) and 53 months (range, 1-104 months), respectively. There were 28 conversions (15%) in the LAP group and these remained in the LAP group in an intention-to-treat analysis. The LAP operations lasted significantly longer for all types of resections (205 vs 150 min, P<0.001) and hospital stay was shorter (8 vs 13 days, P<0.001). Recovery of intestinal function was faster in the LAP group, but only after left-sided procedures (3 vs 4days, P<0.01). However, preoperative patient selection (more emergency operations and patients with higher American Society of Anesthesiologists (ASA) score in the open group) had a major influence on these elements and favours the LAP group. Surprisingly, the overall surgical complication rate (including long-term complications such as wound hernia) was 20% in both groups with rates of individual complications also being comparable in both groups. Conclusion: Despite a patient selection favourable to the laparoscopy group, only little advantage in postoperative outcome could be shown for the minimally invasive over the open approach in the everyday patient.