240 resultados para focal adhesions
Resumo:
The ecological relevance of behavioural syndromes is little studied in cooperative breeding systems where it is assumed that the behavioural type might influence individual decisions on helping and dispersal (e.g. shy, nonaggressive and nonexplorative individuals remain philopatric and helpful, whereas bold, aggressive, explorative individuals compete for vacancies outside their group and disperse). We measured the behavioural type of 19 subordinates in the cooperatively breeding cichlid fish Neolamprologus pulcher in their natural environment by quantifying six behavioural traits up to four times ('trials') in three different contexts, by presenting them with a conspecific intruder, a predator or nothing inside a tube. We found only moderate within-context repeatability (intraclass correlation coefficients) of the focal individual's behaviour, except for attacking either the conspecific or the predator inside the tube. The focal individual's attack rate of the tube was also positively affected by its group size. Averaging traits per context removed the between-trial variation, and consequently the across-context repeatability was very high for all six traits, except for territory maintenance. Trait values depended significantly on the context, except for territory defence. Consequently, individuals could be classified into different behavioural types based on their reaction towards the tube, but surprisingly, and opposite to laboratory studies in this species, ranging propensity and territory maintenance were not included in this behavioural syndrome. We suggest that more studies are needed to compare standardized focal personality tests (e.g. exploration propensity) with actual behaviour observed in nature (e.g. ranging and dispersal).
Resumo:
Dans le domaine de la perception, l'apprentissage est contraint par la présence d'une architecture fonctionnelle constituée d'aires corticales distribuées et très spécialisées. Dans le domaine des troubles visuels d'origine cérébrale, l'apprentissage d'un patient hémi-anopsique ou agnosique sera limité par ses capacités perceptives résiduelles, mais un déficit de reconnaissance visuelle de nature apparemment perceptive, peut également être associé à une altération des représentations en mémoire à long terme. Des réseaux neuronaux distincts pour la reconnaissance - cortex temporal - et pour la localisation des sons - cortex pariétal - ont été décrits chez l'homme. L'étude de patients cérébro-lésés confirme le rôle des indices spatiaux dans un traitement auditif explicite du « where » et dans la discrimination implicite du « what ». Cette organisation, similaire à ce qui a été décrit dans la modalité visuelle, faciliterait les apprentissages perceptifs. Plus généralement, l'apprentissage implicite fonde une grande partie de nos connaissances sur le monde en nous rendant sensible, à notre insu, aux règles et régularités de notre environnement. Il serait impliqué dans le développement cognitif, la formation des réactions émotionnelles ou encore l'apprentissage par le jeune enfant de sa langue maternelle. Le caractère inconscient de cet apprentissage est confirmé par l'étude des temps de réaction sériels de patients amnésiques dans l'acquisition d'une grammaire artificielle. Son évaluation pourrait être déterminante dans la prise en charge ré-adaptative. [In the field of perception, learning is formed by a distributed functional architecture of very specialized cortical areas. For example, capacities of learning in patients with visual deficits - hemianopia or visual agnosia - from cerebral lesions are limited by perceptual abilities. Moreover a visual deficit in link with abnormal perception may be associated with an alteration of representations in long term (semantic) memory. Furthermore, perception and memory traces rely on parallel processing. This has been recently demonstrated for human audition. Activation studies in normal subjects and psychophysical investigations in patients with focal hemispheric lesions have shown that auditory information relevant to sound recognition and that relevant to sound localisation are processed in parallel, anatomically distinct cortical networks, often referred to as the "What" and "Where" processing streams. Parallel processing may appear counterintuitive from the point of view of a unified perception of the auditory world, but there are advantages, such as rapidity of processing within a single stream, its adaptability in perceptual learning or facility of multisensory interactions. More generally, implicit learning mechanisms are responsible for the non-conscious acquisition of a great part of our knowledge about the world, using our sensitivity to the rules and regularities structuring our environment. Implicit learning is involved in cognitive development, in the generation of emotional processing and in the acquisition of natural language. Preserved implicit learning abilities have been shown in amnesic patients with paradigms like serial reaction time and artificial grammar learning tasks, confirming that implicit learning mechanisms are not sustained by the cognitive processes and the brain structures that are damaged in amnesia. In a clinical perspective, the assessment of implicit learning abilities in amnesic patients could be critical for building adapted neuropsychological rehabilitation programs.]
Resumo:
Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors worldwide and its incidence has increased over the last years in most developed countries. The majority of HCCs occur in the context of liver cirrhosis. Therefore, patients with cirrhosis and those with hepatitis B virus infection should enter a surveillance program. Detection of a focal liver lesion by ultrasound should be followed by further investigations to confirm the diagnosis and to permit staging. A number of curative and palliative treatment options are available today. The choice of treatment will depend on the tumor stage, liver function and the presence of portal hypertension as well as the general condition of the patient. A multidisciplinary approach is mandatory to offer to each patient the best treatment.
Resumo:
OBJECTIVE: Targeting neuroprotectants specifically to the cells that need them is a major goal in biomedical research. Many peptidic protectants contain an active sequence linked to a carrier such as the transactivator of transcription (TAT) transduction sequence, and here we test the hypothesis that TAT-linked peptides are selectively endocytosed into neurons stressed by excitotoxicity and focal cerebral ischemia. METHODS: In vivo experiments involved intracerebroventricular injection of TAT peptides or conventional tracers (peroxidase, fluorescein isothiocyanate-dextran) in young rats exposed to occlusion of the middle cerebral artery at postnatal day 12. Cellular mechanisms of uptake were analyzed in dissociated cortical neuronal cultures. RESULTS: In both models, all tracers were taken up selectively into stressed neurons by endocytosis. In the in vivo model, this was neuron specific and limited to the ischemic area, where the neurons displayed enhanced immunolabeling for early endosomal antigen-1 and clathrin. The highly efficient uptake of TAT peptides occurred by the same selective mechanism as for conventional tracers. All tracers were targeted to the nucleus and cytoplasm of neurons that appeared viable, although ultimately destined to die. In dissociated cortical neuronal cultures, an excitotoxic dose of N-methyl-D-aspartate induced a similar endocytosis. It was 100 times more efficient with TAT peptides than with dextran, because the former bound to heparan sulfate proteoglycans at the cell surface, but it depended on dynamin and clathrin in both cases. INTERPRETATION: Excitotoxicity-induced endocytosis is the main entry route for protective TAT peptides and targets selectively the neurons that need to be protected.
Resumo:
RESUME Nous rapportons l'étude d'une famille de 49 membres sur 5 générations. Parmi 35 membres étudiés, 18 sont atteints d'Osteolyse Expansive Familiale (OEF). L'OEF est une dysplasie osseuse génétique rare, autosomique dominante, dont les altérations locales et générales du squelette ont une distribution périphérique prédominante qui devient manifeste à partir de la deuxième décennie de vie. Une résorption ostéoclastique progressive, accompagnée d'une faible activité ostéoblastique, est à l'origine d'une expansion médullaire osseuse. Cette dernière est caractérisée par une raréfaction de la moelle osseuse qui est remplacée par du tissu fibreux et de la graisse. L'amincissement de la moelle osseuse aboutit à des déformations invalidantes, sévères et douloureuses du squelette, avec tendance aux fractures spontanées. La première manifestation clinique de la maladie est une surdité de transmission très précoce résultant d'une lyse de la chaîne ossiculaire. Radiologiquement, il existe toujours une pneumatisation marquée de la mastoïde et du rocher. Les dents montrent des signes importants de résorption osseuse au niveau de la région apicale et/ou du collet, dont l'aspect est caractéristique et unique. La phosphatase alcaline sérique, l'hydroxyproline et la deoxypiridoline urinaire sont élevées à des taux variables. Le taux de calcium et d'hormone parathyroïdienne est normal. Le traitement par les diphosphonates, la calcitonine et la vitamine D est inefficace. Histologiquement, l'OEF présente des similitudes avec la maladie de Paget, mais l'âge de début, la distribution des lésions osseuses, les altérations dentaires et de l'oreille moyenne, ainsi que la progression clinique sont différents. Il en va de même pour la dysplasie fibreuse, l'ostéite fibro-kystique et l'ostéogénèse imparfaite. Le gêne responsable de la maladie se localise dans la région du chromosome 18q21-22. Récemment, des mutations du TNFRSF 11A, gêne qui codifie le RANK, ont été identifiées comme étant la cause de l'OEF. La duplication de la 18ème paire de base au niveau de l'exon 1 suggère qu'il correspond au site de l'anomalie. La technique chirurgicale et les résultats audiométriques à court et long terme de 13 interventions chez 8 patients sont présentés. ABSTRACT Objectives: Familial Expansive Osteolysis (EEO) is a rare autosomal dominant bone dys¬plasia. The disease can show general and focal skeletal alterations, the latter having a pre¬dominantly peripheral distribution. Onset occurs after the second decade of life. Patients and methods: We present the study, of 30 years, of a family consisting of 49 members covering five generations. Results: Among the 35 members studied, 18 have familial expansive osteolysis (FEO). The first clinical sign of the condition is transmission deafness at an early age. The features of the teeth has a unique and characteristic appearance. Thinning of the corti¬cal bone leads to severe, painful, disabling deformities. Serum alkaline phosphatase, and urinary hydroxyproline and deoxipyridinoline are elevated. Calcium and parathyroid hor¬mone are normal. Treatment with diphosphonates, calcitonin and vitamin D has been unsuccessful. We present the surgical technology and the results to short and long term of 13 interventions on 8 patients. Conclusion: Progressive osteoclastic reabsorption accompanied by weak osteoblastic activ¬ity results in medullary expansion characterized by rarefaction of the bone marrow, which is replaced by fibrous tissue and fat. FE0 is histologically similar to Paget disease, but the age of onset, the distribution of the bone lesions, the dental and middle ear alterations, and the clin¬ical progression are different. These features also differentiate FE0 from fibrous dysplasia, fibrocystic osteitis and imperfect osteogenesis. The gene responsible for EEO is located in the 18q21-22 chromosome region. Mutations in TNFRSF11A, the gene encoding receptor activa¬tor of nuclear factor-kappa-B (RANK), has been recently identified as the cause of FEO. A duplication of 18 base pairs in exon 1 of the TNFRSF11A gene suggests that this corresponds to the site of the anomaly and can be considered a "hot spot" for mutations.
Resumo:
BACKGROUND: A few recent studies have found indications of the effectiveness of inpatient psychotherapy for depression, usually of an extended duration. However, there is a lack of controlled studies in this area and to date no study of adequate quality on brief psychodynamic psychotherapy for depression during short inpatient stay exists. The present article describes the protocol of a study that will examine the relative efficacy, the cost-effectiveness and the cost-utility of adding an Inpatient Brief Psychodynamic Psychotherapy to pharmacotherapy and treatment-as-usual for inpatients with unipolar depression. METHODS/DESIGN: The study is a one-month randomized controlled trial with a two parallel group design and a 12-month naturalistic follow-up. A sample of 130 consecutive adult inpatients with unipolar depression and Montgomery-Asberg Depression Rating Scale score over 18 will be recruited. The study is carried out in the university hospital section for mood disorders in Lausanne, Switzerland. Patients are assessed upon admission, and at 1-, 3- and 12- month follow-ups. Inpatient therapy is a manualized brief intervention, combining the virtues of inpatient setting and of time-limited dynamic therapies (focal orientation, fixed duration, resource-oriented interventions). Treatment-as-usual represents the best level of practice for a minimal treatment condition usually proposed to inpatients. Final analyses will follow an intention-to-treat strategy. Depressive symptomatology is the primary outcome and secondary outcome includes measures of psychiatric symptomatology, psychosocial role functioning, and psychodynamic-emotional functioning. The mediating role of the therapeutic alliance is also examined. Allocation to treatment groups uses a stratified block randomization method with permuted block. To guarantee allocation concealment, randomization is done by an independent researcher. DISCUSSION: Despite the large number of studies on treatment of depression, there is a clear lack of controlled research in inpatient psychotherapy during the acute phase of a major depressive episode. Research on brief therapy is important to take into account current short lengths of stay in psychiatry. The current study has the potential to scientifically inform appropriate inpatient treatment. This study is the first to address the issue of the economic evaluation of inpatient psychotherapy. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry (ACTRN12612000909820).
Resumo:
SUMMARY: Epilepsy surgery is the most effective way to control seizures in patients with drug-resistant focal epilepsy, often leading to improvements in cognition, behaviour, and quality of life. Risks of serious adverse events and deterioration of clinical status can be minimised in carefully selected patients. Accordingly, guidelines recommend earlier and more systematic assessment of patients' eligibility for surgery than is seen at present. The effectiveness of surgical treatment depends on epilepsy type, underlying pathology, and accurate localisation of the epileptogenic brain region by various clinical, neuroimaging, and neurophysiological investigations. Substantial progress has been made in the methods of presurgical assessment, particularly in patients with normal features on MRI, but evidence is scarce for the indication and effect of most presurgical investigations, with no biomarker precisely delineating the epileptogenic zone. A priority for the development of epilepsy surgery is the generation of high-level evidence to promote the harmonisation and dissemination of best practices.
Resumo:
Cilengitide is a high-affinity cyclic pentapeptdic alphaV integrin antagonist previously reported to suppress angiogenesis by inducing anoikis of endothelial cells adhering through alphaVbeta3/alphaVbeta5 integrins. Angiogenic endothelial cells express multiple integrins, in particular those of the beta1 family, and little is known on the effect of cilengitide on endothelial cells expressing alphaVbeta3 but adhering through beta1 integrins. Through morphological, biochemical, pharmacological and functional approaches we investigated the effect of cilengitide on alphaVbeta3-expressing human umbilical vein endothelial cells (HUVEC) cultured on the beta1 ligands fibronectin and collagen I. We show that cilengitide activated cell surface alphaVbeta3, stimulated phosphorylation of FAK (Y(397) and Y(576/577)), Src (S(418)) and VE-cadherin (Y(658) and Y(731)), redistributed alphaVbeta3 at the cell periphery, caused disappearance of VE-cadherin from cellular junctions, increased the permeability of HUVEC monolayers and detached HUVEC adhering on low-density beta1 integrin ligands. Pharmacological inhibition of Src kinase activity fully prevented cilengitide-induced phosphorylation of Src, FAK and VE-cadherin, and redistribution of alphaVbeta3 and VE-cadherin and partially prevented increased permeability, but did not prevent HUVEC detachment from low-density matrices. Taken together, these observations reveal a previously unreported effect of cilengitide on endothelial cells namely its ability to elicit signaling events disrupting VE-cadherin localization at cellular contacts and to increase endothelial monolayer permeability. These effects are potentially relevant to the clinical use of cilengitide as anticancer agent.
Resumo:
Early epilepsy is known to worsen the developmental prognosis of young children with a congenital focal brain lesion, but its direct role is often very difficult to delineate from the other variables. This requires prolonged periods of follow-up with simultaneous serial electrophysiological and developmental assessments which are rarely obtained. We studied a male infant with a right prenatal infarct in the territory of the right middle cerebral artery resulting in a left spastic hemiparesis, and an epileptic disorder (infantile spasms with transient right hemihypsarrhythmia and focal seizures) from the age of 7 months until the age of 4 years. Pregnancy and delivery were normal. A dissociated delay of early language acquisition affecting mainly comprehension without any autistic features was documented. This delay was much more severe than usually expected in children with early focal lesions, and its evolution, with catch-up to normal, was correlated with the active phase of the epilepsy. We postulate that the epilepsy specifically amplified a pattern of delayed language emergence, mainly affecting lexical comprehension, reported in children with early right hemisphere damage.
Resumo:
A right heart metastasis of a small-cell lung cancer was found on the whole-body F-fluoro-deoxy-glucose positron emission tomography/computed tomography (F-FDG-PET/CT) of a 69-year-old smoker investigated for a right pulmonary mass discovered on chest radiography after a fracture of the right humerus. The PET scan showed an increased FDG uptake by the mass in the right lung and an intense, atypical focal activity of the right ventricle strongly suggestive of a neoplastic process. CT-guided lung biopsy revealed a small-cell lung cancer and myocardial biopsy confirmed the presence of a cardiac metastasis. The patient was treated with six cycles of chemotherapy followed by radiation therapy, which included the heart lesion. At follow-up PET/CT 2 months after the end of treatment, the abnormal cardiac uptake had disappeared, whereas increased FDG uptake persisted in the pulmonary residual mass.
Resumo:
Geriatric patients presenting to the ED are at high risk of mortality as well as of cognitive or functional decline. Thus, ED is an ideal spot for interventions that can improve their outcome. In this article, we summarize six recent studies, regarding the utilization of prognostic evaluation scores in geriatric patients presenting to the ED, adverse drug reactions, the significance of elevated troponin in patients who have remained on the ground after a fall, the rationale of performing head CT in patients without focal neurologic findings after a fall, the ideal treatment of a proximal femoral fracture and the excessive use of urinary catheters in the ED.
Resumo:
Connectivity among demes in a metapopulation depends on both the landscape's and the focal organism's properties (including its mobility and cognitive abilities). Using individual-based simulations, we contrast the consequences of three different cognitive strategies on several measures of metapopulation connectivity. Model animals search suitable habitat patches while dispersing through a model landscape made of cells varying in size, shape, attractiveness and friction. In the blind strategy, the next cell is chosen randomly among the adjacent ones. In the near-sighted strategy, the choice depends on the relative attractiveness of these adjacent cells. In the far-sighted strategy, animals may additionally target suitable patches that appear within their perceptual range. Simulations show that the blind strategy provides the best overall connectivity, and results in balanced dispersal. The near-sighted strategy traps animals into corridors that reduce the number of potential targets, thereby fragmenting metapopulations in several local clusters of demes, and inducing sink-source dynamics. This sort of local trapping is somewhat prevented in the far-sighted strategy. The colonization success of strategies depends highly on initial energy reserves: blind does best when energy is high, near-sighted wins at intermediate levels, and far-sighted outcompetes its rivals at low energy reserves. We also expect strong effects in terms of metapopulation genetics: the blind strategy generates a migrant-pool mode of dispersal that should erase local structures. By contrast, near- and far-sighted strategies generate a propagule-pool mode of dispersal and source-sink behavior that should boost structures (high genetic variance among- and low variance within local clusters of demes), particularly if metapopulation dynamics is also affected by extinction-colonization processes. Our results thus point to important effects of the cognitive ability of dispersers on the connectivity, dynamics and genetics of metapopulations.
Resumo:
PURPOSE: Colonoscopy is reported to be a safe procedure that is routinely performed for the diagnosis and treatment of colorectal diseases. Splenic rupture is considered to be a rare complication with high mortality and morbidity that requires immediate diagnosis and management. Nonoperative management (NOM), surgical treatment (ST), and, more recently, proximal splenic artery embolization (PSAE) have been proposed as treatment options. The goal of this study was to assess whether PSAE is safe even in high-grade ruptures. METHODS: We report two rare cases of post colonoscopy splenic rupture. A systematic review of the literature from 2002 to 2010 (first reported case of PSAE) was performed and the three types of treatment compared. RESULTS: All patients reviewed (77 of 77) presented with intraperitoneal hemorrhage due to isolated splenic trauma. Splenic rupture was high-grade in most patients when grading was possible. Six of 77 patients (7.8Â %) were treated with PSAE, including the 2 cases reported herein. Fifty-seven patients (74Â %) underwent ST. NOM was attempted first in 25 patients with a high failure rate (11 of 25 [44Â %]) and requiring a salvage procedure, such as PSAE or ST. Previous surgery (31 of 59 patients), adhesions (10 of 13), diagnostic colonoscopies (49 of 71), previous biopsies or polypectomies (31 of 57) and female sex (56 of 77) were identified as risk factors. In contrast, splenomegaly (0 of 77 patients), medications that increase the risk of bleeding (13 of 30) and difficult colonoscopies (16 of 51) were not identified as risk factors. PSAE was safe and effective even in elderly patients with comorbidities and those taking medications that increase the risk of bleeding, and the length of the hospital stay was similar to that after ST. CONCLUSION: We propose a treatment algorithm based on clinical and radiological criteria. Because of the high failure rate after NOM, PSAE should be the treatment of choice to manage grade I through IV splenic ruptures after colonoscopy in hemodynamically stabilized patients.
Resumo:
Schizophrenia is postulated to be the prototypical dysconnection disorder, in which hallucinations are the core symptom. Due to high heterogeneity in methodology across studies and the clinical phenotype, it remains unclear whether the structural brain dysconnection is global or focal and if clinical symptoms result from this dysconnection. In the present work, we attempt to clarify this issue by studying a population considered as a homogeneous genetic sub-type of schizophrenia, namely the 22q11.2 deletion syndrome (22q11.2DS). Cerebral MRIs were acquired for 46 patients and 48 age and gender matched controls (aged 6-26, respectively mean age = 15.20 ± 4.53 and 15.28 ± 4.35 years old). Using the Connectome mapper pipeline (connectomics.org) that combines structural and diffusion MRI, we created a whole brain network for each individual. Graph theory was used to quantify the global and local properties of the brain network organization for each participant. A global degree loss of 6% was found in patients' networks along with an increased Characteristic Path Length. After identifying and comparing hubs, a significant loss of degree in patients' hubs was found in 58% of the hubs. Based on Allen's brain network model for hallucinations, we explored the association between local efficiency and symptom severity. Negative correlations were found in the Broca's area (p < 0.004), the Wernicke area (p < 0.023) and a positive correlation was found in the dorsolateral prefrontal cortex (DLPFC) (p < 0.014). In line with the dysconnection findings in schizophrenia, our results provide preliminary evidence for a targeted alteration in the brain network hubs' organization in individuals with a genetic risk for schizophrenia. The study of specific disorganization in language, speech and thought regulation networks sharing similar network properties may help to understand their role in the hallucination mechanism.
Resumo:
Pyogenic liver abscess is a severe condition and a therapeutic challenge. Treatment failure may be due to an unrecognized ingested foreign body that migrated from the gastrointestinal tract. There has recently been a marked increase in the number of reported cases of this condition, but initial misdiagnosis as cryptogenic liver abscess still occurs in the majority of cases. We conducted the current study to characterize this entity and provide a diagnostic strategy applicable worldwide. To this end, data were collected from our case and from a systematic review that identified 59 well-described cases. Another systematic review identified series of cryptogenic-and Asian Klebsiella-liver abscess; these data were pooled and compared with the data from the cases of migrated foreign body liver abscess. The review points out the low diagnostic accuracy of history taking, modern imaging, and even surgical exploration. A fistula found through imaging procedures or endoscopy warrants surgical exploration. Findings suggestive of foreign body migration are symptoms of gastrointestinal perforation, computed tomography demonstration of a thickened gastrointestinal wall in continuity with the abscess, and adhesions seen during surgery. Treatment failure, left lobe location, unique location (that is, only 1 abscess location within the liver), and absence of underlying conditions also point to the diagnosis, as shown by comparison with the cryptogenic liver abscess series. This study demonstrates that migrated foreign body liver abscess is a specific entity, increasingly reported. It usually is not cured when unrecognized, and diagnosis is mainly delayed. This study provides what we consider the best available evidence for timely diagnosis with worldwide applicability. Increased awareness is required to treat this underestimated condition effectively, and further studies are needed.