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BACKGROUND: Poor transition planning contributes to discontinuity of care at the child-adult mental health service boundary (SB), adversely affecting mental health outcomes in young people (YP). The aim of the study was to determine whether managed transition (MT) improves mental health outcomes of YP reaching the child/adolescent mental health service (CAMHS) boundary compared with usual care (UC). METHODS: A two-arm cluster-randomised trial (ISRCTN83240263 and NCT03013595) with clusters allocated 1:2 between MT and UC. Recruitment took place in 40 CAMHS (eight European countries) between October 2015 and December 2016. Eligible participants were CAMHS service users who were receiving treatment or had a diagnosed mental disorder, had an IQ ⩾ 70 and were within 1 year of reaching the SB. MT was a multi-component intervention that included CAMHS training, systematic identification of YP approaching SB, a structured assessment (Transition Readiness and Appropriateness Measure) and sharing of information between CAMHS and adult mental health services. The primary outcome was HoNOSCA (Health of the Nation Outcome Scale for Children and Adolescents) score 15-months post-entry to the trial. RESULTS: The mean difference in HoNOSCA scores between the MT and UC arms at 15 months was -1.11 points (95% confidence interval -2.07 to -0.14, p = 0.03). The cost of delivering the intervention was relatively modest (17-65 per service user). CONCLUSIONS: MT led to improved mental health of YP after the SB but the magnitude of the effect was small. The intervention can be implemented at low cost and form part of planned and purposeful transitional care.
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Servicios de Salud Mental , Trastornos Psicóticos , Adolescente , Humanos , Adulto , Salud Mental , Europa (Continente) , Evaluación de Resultado en la Atención de SaludRESUMEN
BACKGROUND: Social skills interventions are commonly deployed for adolescents with autism spectrum disorder (ASD). Because effective and appropriate social skills are determined by cultural factors that differ throughout the world, the effectiveness of these interventions relies on a good cultural fit. Therefore, the ACCEPT study examines the effectiveness of the Dutch Program for the Education and Enrichment of Relational Skills (PEERS®) social skills intervention. METHODS/DESIGN: This study is a two-arm parallel group randomized controlled trial (RCT) in which adolescents are randomly assigned (after baseline assessment) to one of two group interventions (PEERS® vs. active control condition). In total, 150 adolescents are to be included, with multi-informant involvement of their parents and teachers. The ACCEPT study uses an active control condition (puberty psychoeducation group training, focussing on social-emotional development) and explores possible moderators and mediators in improving social skills. The primary outcome measure is the Contextual Assessment of Social Skills (CASS). The CASS assesses social skills performance in a face to face social interaction with an unfamiliar, typically developing peer, making this a valuable instrument to assess the social conversational skills targeted in PEERS®. In addition, to obtain a complete picture of social skills, self-, parent- and teacher-reported social skills are assessed using the Social Skills improvement System (SSiS-RS) and Social Responsiveness Scale (SRS-2). Secondary outcome measures (i.e. explorative mediators) include social knowledge, social cognition, social anxiety, social contacts and feelings of parenting competency of caregivers. Moreover, demographic and diagnostic measures are assessed as potential moderators of treatment effectiveness. Assessments of adolescents, parents, and teachers take place at baseline (week 0), intermediate (week 7), post intervention (week 14), and at follow-up (week 28). CONCLUSION: This is the first RCT on the effectiveness of the PEERS® parent-assisted curriculum which includes an active control condition. The outcome of social skills is assessed using observational assessments and multi-informant questionnaires. Additionally, factors related to social learning are assessed at several time points, which will enable us to explore potential mediators and moderators of treatment effect. TRAIL REGISTRATION: Dutch trail register NTR6255 (NL6117). Registered February 8th, 2017 - retrospectively registered.
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Trastorno del Espectro Autista/terapia , Relaciones Interpersonales , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Habilidades Sociales , Adolescente , Femenino , Humanos , Masculino , Países Bajos , Grupo Paritario , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Mental health disorders in the child and adolescent population are a pressing public health concern. Despite the high prevalence of psychopathology in this vulnerable population, the transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) has many obstacles such as deficiencies in planning, organisational readiness and policy gaps. All these factors contribute to an inadequate and suboptimal transition process. A suite of measures is required that would allow young people to be assessed in a structured and standardised way to determine the on-going need for care and to improve communication across clinicians at CAMHS and AMHS. This will have the potential to reduce the overall health economic burden and could also improve the quality of life for patients travelling across the transition boundary. The MILESTONE (Managing the Link and Strengthening Transition from Child to Adult Mental Health Care) project aims to address the significant socioeconomic and societal challenge related to the transition process. This protocol paper describes the development of two MILESTONE transition-related measures: The Transition Readiness and Appropriateness Measure (TRAM), designed to be a decision-making aide for clinicians, and the Transition Related Outcome Measure (TROM), for examining the outcome of transition. METHODS: The TRAM and TROM have been developed and were validated following the US FDA Guidance for Patient-reported Outcome Measures which follows an incremental stepwise framework. The study gathers information from service users, parents, families and mental health care professionals who have experience working with young people undergoing the transition process from eight European countries. DISCUSSION: There is an urgent need for comprehensive measures that can assess transition across the CAMHS/AMHS boundary. This study protocol describes the process of development of two new transition measures: the TRAM and TROM. The TRAM has the potential to nurture better transitions as the findings can be summarised and provided to clinicians as a clinician-decision making support tool for identifying cases who need to transition and the TROM can be used to examine the outcomes of the transition process. TRIAL REGISTRATION: MILESTONE study registration: ISRCTN83240263 Registered 23-July-2015 - ClinicalTrials.gov NCT03013595 Registered 6 January 2017.
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Servicios de Salud del Adolescente , Trastornos Mentales/terapia , Servicios de Salud Mental , Transición a la Atención de Adultos , Adolescente , Adulto , Niño , Estudios de Cohortes , Europa (Continente) , Humanos , Salud Mental , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Reproducibilidad de los ResultadosRESUMEN
Following publication of the original article [1], the authors reported they wanted to reinstate a co-author, who previously declined his authorship due to a misinterpretation of authorship limitations per research center.
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BACKGROUND: Transition from distinct Child and Adolescent Mental Health (CAMHS) to Adult Mental Health Services (AMHS) is beset with multitude of problems affecting continuity of care for young people with mental health needs. Transition-related discontinuity of care is a major health, socioeconomic and societal challenge globally. The overall aim of the Managing the Link and Strengthening Transition from Child to Adult Mental Health Care in Europe (MILESTONE) project (2014-19) is to improve transition from CAMHS to AMHS in diverse healthcare settings across Europe. MILESTONE focuses on current service provision in Europe, new transition-related measures, long term outcomes of young people leaving CAMHS, improving transitional care through 'managed transition', ethics of transitioning and the training of health care professionals. METHODS: Data will be collected via systematic literature reviews, pan-European surveys, and focus groups with service providers, users and carers, and members of youth advocacy and mental health advocacy groups. A prospective cohort study will be conducted with a nested cluster randomised controlled trial in eight European Union (EU) countries (Belgium, Croatia, France, Germany, Ireland, Italy, Netherlands, UK) involving over 1000 CAMHS users, their carers, and clinicians. DISCUSSION: Improving transitional care can facilitate not only recovery but also mental health promotion and mental illness prevention for young people. MILESTONE will provide evidence of the organisational structures and processes influencing transition at the service interface across differing healthcare models in Europe and longitudinal outcomes for young people leaving CAMHS, solutions for improving transitional care in a cost-effective manner, training modules for clinicians, and commissioning and policy guidelines for service providers and policy makers. TRIAL REGISTRATION: "MILESTONE study" registration: ISRCTN ISRCTN83240263 Registered 23 July 2015; ClinicalTrials.gov NCT03013595 Registered 6 January 2017.
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Servicios de Salud del Adolescente , Servicios de Salud Mental , Salud Mental , Transferencia de Pacientes/métodos , Adolescente , Servicios de Salud del Adolescente/economía , Servicios de Salud del Adolescente/tendencias , Adulto , Niño , Estudios de Cohortes , Análisis Costo-Beneficio/métodos , Análisis Costo-Beneficio/tendencias , Europa (Continente)/epidemiología , Femenino , Personal de Salud/economía , Personal de Salud/tendencias , Humanos , Masculino , Salud Mental/economía , Salud Mental/tendencias , Servicios de Salud Mental/economía , Servicios de Salud Mental/tendencias , Estudios Multicéntricos como Asunto/economía , Estudios Multicéntricos como Asunto/métodos , Transferencia de Pacientes/economía , Transferencia de Pacientes/tendencias , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto/economía , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Encuestas y Cuestionarios , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: Psychopathology manifests itself primarily in late adolescence and continues into adulthood. Continuity of care is essential during this phase of life. The current care service distinguishes between child/adolescent (CAMHS) and adult mental health services (AMHS). The separation of services can interfere with the continuity of care.
AIM: To map professionals' experiences of and views on the transition and associated problems that young people can experience as they are transferred from CAMHS to AMHS.
METHOD: We distributed an online questionnaire among professionals providing mental health care to young people (aged 15-25) with psychiatric problems.
RESULTS: The questionnaire was completed by 518 professionals. Decisions relating to transition were generally based on the professional's own deliberations. The preparation consisted mainly of discussing changes with the adolescent and his or her parents. The majority of transition-related problems were experienced in CAMHS, particularly with regard to collaboration with AMHS. Respondents were of the opinion that the developmental age ought to be the determining factor in the decision-making process with regard to transition and they considered it important that developmentally appropriate services should be available in order to bridge the gap.
CONCLUSION: Professionals in CAMHS and AMHS are encountering problems in preparing the transitional phase and in organising the required structural collaboration between the two separate services. The problems relate mainly to coordination, communication and rules and regulations. Professionals are keen to improve the situation and want to see greater flexibility. In their view, there should be a wider range of specialised facilities for young people, enabling them to benefit from transitional psychiatry.
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Servicios de Salud del Adolescente/organización & administración , Trastornos Mentales/terapia , Servicios de Salud Mental/organización & administración , Psiquiatría/organización & administración , Transición a la Atención de Adultos , Adolescente , Adulto , Conducta Cooperativa , Femenino , Humanos , Masculino , Países Bajos , Padres/psicología , Adulto JovenRESUMEN
Recent findings showing significant correlations between phospholipase A2 (PLA2) activity and structural changes in schizophrenic brains contribute to the membrane hypothesis of schizophrenia, which was hampered because a clean functional link between elevated PLA2 activity and brain structure was missing (Neuroimage, 2010; 52: 1314-1327). We measured membrane fluidity parameters and found that brain membranes isolated from the prefrontal cortex of schizophrenic patients showed significantly increased flexibility of fatty acid chains. Our findings support a possible link between elevated PLA2 activity in cortical areas of schizophrenic patients and subsequent alterations of the biophysical parameters of neuronal membranes leading to structural changes in these areas.
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Fluidez de la Membrana , Neuronas/química , Corteza Prefrontal/química , Esquizofrenia/metabolismo , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuronas/metabolismo , Corteza Prefrontal/metabolismoRESUMEN
OBJECTIVE: Neurofeedback has been proposed as an effective alternative for pharmacological treatment in children with attention-deficit/hyperactivity disorder (ADHD), with potentially long-term and delayed benefits. However, the specificity of such long-term behavioral improvements remains inconclusive and therefore additional research into the neurophysiological effects of neurofeedback is needed. We compared long-term effects of theta/beta neurofeedback (NFB) to methylphenidate (MPH) and physical activity (PA, semi-active control intervention) on electroencephalogram (EEG) power spectra. Based on the vigilance stabilization model, we hypothesized further reductions in theta and alpha power in the NFB compared to the control groups. METHOD: EEG power spectra (theta, alpha and beta) during resting and task conditions were recorded at pre-, post-intervention and 6-months follow-up in 67 children, aged 7-13 (NFB: n = 24, MPH: n = 23, or PA: n = 20). RESULTS: Analyses revealed no power spectra differences at follow-up between MPH and NFB (range p = .165-.905) and PA and NFB (range p = .172-.822). CONCLUSIONS: No evidence was found for the specificity of theta/beta NFB at follow-up. SIGNIFICANCE: This was the first study into long-term neurophysiological effects of theta/beta NFB. Future studies are encouraged to explore both specific and non-specific mechanisms of NFB. CLINICAL TRIALS REGISTRATION: Train Your Brain? Exercise and neurofeedback intervention for ADHD, https://clinicaltrials.gov/show/NCT01363544, Ref. No. NCT01363544.
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Trastorno por Déficit de Atención con Hiperactividad/terapia , Ritmo beta/fisiología , Corteza Cerebral/fisiopatología , Neurorretroalimentación/métodos , Ritmo Teta/fisiología , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Niño , Electroencefalografía , Femenino , Humanos , MasculinoRESUMEN
INTRODUCTION: The aim of this study is to investigate the nanocrystallization of steels caused by the transformation from the austenitic to the martensitic phase induced by a severe plastic deformation (SPD) treatment. In this framework, we applied an air blast shot peening treatment, which is a simple protocol widely used for industrial purposes. METHODS: AISI 286 and AISI 316 specimens were peened for different times and polished using diamond pastes in order to remove corrugations higher than 1 mum. The characterization of the steel surfaces was performed by atomic force microscopy (AFM) operating in contact mode. Additional EDXD measurements were performed to confirm the phase transition. RESULTS AND DISCUSSION: An AFM-based characterization at nanometric level of the steel surfaces is provided. When the peening exceeds a threshold time that, as expected, depends on the steel composition, a uniform nanostructuration is detected. It is well known that such rearrangement is associated to the growth of a martensitic phase. To date, AFM has been employed in this field only for few applications and to solve specific problems. On the other hand, our results demonstrate that this is a useful technique for the characterization of hardened surfaces, especially when non-destructive sample preparation treatments are required. Moreover, we show that AFM can be a useful tool also for in situ industrial diagnostics of metallic parts.
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Mammary cancer and pyometra are important health hazards associated with ovary conservation in pet dogs. Early ovariohysterectomy may reduce the incidence of these two diseases, but an estimate of the extent to which the development of mammary cancer or pyometra adversely influences overall longevity is missing. As a first step toward addressing this knowledge gap, the results of a historical cohort study of Rottweilers that lived in North America are reported. Questionnaires completed by owners and veterinarians were used to obtain lifetime health and medical information on 242 female Rottweilers, including years of lifetime ovary exposure, age at death, and cause of death. To determine the extent to which longevity was shortened in females that developed these ovary-associated diseases, age-anchored life expectancy-defined as the median number of remaining years until death for females alive at specified ages during the life course-and years of life lost, a measure of premature mortality, were estimated. Mammary carcinoma was diagnosed in 19 (7.9%) females; median age at diagnosis was 8.5 years; case fatality was 37%. Pyometra was diagnosed in 16 (6.6%) females; median age at diagnosis was 5.4 years; case fatality was 7%. Median lifetime ovary exposure for the study population was 4.3 years. Although risk for developing both diseases increased with longer ovary exposure, longer ovary exposure (≥4.3 years) was also associated with an overall longevity advantage-a 33% decrease in mortality, living 17 months longer than females with shorter ovary exposure (P=0.002). Analysis of age-anchored life expectancy showed that at no time points during the life course was the current or future diagnosis of mammary carcinoma or pyometra associated with shortened survival compared to females who never developed these conditions. This lack of longevity disadvantage is an expected result for diseases with late-onset, moderate (<50%) case fatality (mammary carcinoma) or low (<10%) case fatality (pyometra). These findings fail to support the notion that a strategy, such as elective ovariohysterectomy, implemented to reduce the incidence of mammary carcinoma and pyometra will beneficially impact overall longevity. It follows that future efforts to find and implement effective longevity-promoting interventions should look beyond reducing the incidence of a particular disease to considering trade-offs.
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Neoplasias de la Mama/veterinaria , Enfermedades de los Perros/fisiopatología , Enfermedades de los Perros/cirugía , Esperanza de Vida , Ovariectomía/veterinaria , Piómetra/veterinaria , Animales , Neoplasias de la Mama/fisiopatología , Neoplasias de la Mama/cirugía , Perros , Femenino , Promoción de la Salud/métodos , Histerectomía/veterinaria , Longevidad/fisiología , Ovario/fisiopatología , Piómetra/fisiopatología , Piómetra/cirugíaRESUMEN
OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) has been associated with widespread brain abnormalities in white and grey matter, affecting not only local, but global functional networks as well. In this study, we explored these functional networks using source-reconstructed electroencephalography in ADHD and typically developing (TD) children. We expected evidence for maturational delay, with underlying abnormalities in the default mode network. METHODS: Electroencephalograms were recorded in ADHD (n=42) and TD (n=43) during rest, and functional connectivity (phase lag index) and graph (minimum spanning tree) parameters were derived. Dependent variables were global and local network metrics in theta, alpha and beta bands. RESULTS: We found evidence for a more centralized functional network in ADHD compared to TD children, with decreased diameter in the alpha band (ηp2=0.06) and increased leaf fraction (ηp2=0.11 and 0.08) in the alpha and beta bands, with underlying abnormalities in hub regions of the brain, including default mode network. CONCLUSIONS: The finding of a more centralized network is in line with maturational delay models of ADHD and should be replicated in longitudinal designs. SIGNIFICANCE: This study contributes to the literature by combining high temporal and spatial resolution to construct EEG network topology, and associates maturational-delay and default-mode interference hypotheses of ADHD.
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Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Encéfalo/fisiopatología , Sustancia Gris/fisiopatología , Red Nerviosa/fisiopatología , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Niño , Electroencefalografía , Femenino , Sustancia Gris/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/diagnóstico por imagenRESUMEN
OBJECTIVE: Children with ADHD have difficulties attending to task-relevant events, which has been consistently associated with reductions in the amplitude of the P3b event-related potential (ERP) component. However, the underlying neural networks involved in this P3b reduction remain elusive. Therefore, this study explored source localization of P3b alterations in children with ADHD, aiming at a more detailed account of attentional difficulties. METHODS: Dense array ERPs were obtained for 36 children with ADHD and 49 typically developing children (TD) using an auditory oddball task. The P3b component (310-410 ms) was individually localized with the LAURA distributed linear inverse solution method and compared between groups. RESULTS: The ADHD group showed reduced P3b amplitudes in response to targets compared to the TD group. Differences were located primarily in frontopolar (cinguloopercular network, BA10) and temporoparietal regions (ventral attention network, BA39 and 19) in the left hemisphere. Reductions in P3b amplitudes were related to more inattention and hyperactivity/impulsivity problems in the ADHD group. CONCLUSIONS: The results show alterations in both top-down and bottom-up attention-related brain areas, which may underlie P3b amplitude reductions in children with ADHD. SIGNIFICANCE: This study provides novel data on both temporal and spatial aspects of dysfunctional attention processes in ADHD.
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Estimulación Acústica/métodos , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Corteza Cerebral/fisiopatología , Electroencefalografía/métodos , Potenciales Relacionados con Evento P300/fisiología , Desempeño Psicomotor/fisiología , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Niño , Femenino , Humanos , Masculino , Tiempo de Reacción/fisiologíaRESUMEN
The goal of this study was to explore relations between teacher characteristics (i.e., competence and wellbeing); social classroom relationships (i.e., teacher-child and peer interactions); and children's social, emotional, and behavioral classroom adjustment. These relations were explored at both the individual and classroom levels among 414 children with emotional and behavioral disorders placed in special education. Two models were specified. In the first model, children's classroom adjustment was regressed on social relationships and teacher characteristics. In the second model, reversed links were examined by regressing teacher characteristics on social relationships and children's adjustment. Results of model 1 showed that, at the individual level, better social and emotional adjustment of children was predicted by higher levels of teacher-child closeness and better behavioral adjustment was predicted by both positive teacher-child and peer interactions. At the classroom level, positive social relationships were predicted by higher levels of teacher competence, which in turn were associated with lower classroom levels of social problems. Higher levels of teacher wellbeing were directly associated with classroom adaptive and maladaptive child outcomes. Results of model 2 showed that, at the individual and classroom levels, only the emotional and behavioral problems of children predicted social classroom relationships. At the classroom level, teacher competence was best predicted by positive teacher-child relationships and teacher wellbeing was best predicted by classroom levels of prosocial behavior. We discuss the importance of positive teacher-child and peer interactions for children placed in special education and suggest ways of improving classroom processes by targeting teacher competence.
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Conducta Infantil/psicología , Ajuste Emocional , Docentes , Relaciones Interpersonales , Ajuste Social , Conducta Social , Adolescente , Niño , Preescolar , Educación Especial , Emociones , Femenino , Humanos , Masculino , Instituciones Académicas , Medio SocialRESUMEN
In mainstream education, positive relationships with teachers and peers have been found to positively influence children's behavioral development. However, high levels of classroom behavior problems may hinder the formation of such positive relationships. Therefore, findings from mainstream education cannot be generalized to special education. The present study investigated the developmental links between disobedience and positive as well as negative relationships with teachers and peers among boys in restrictive special educational settings. At three assessment waves across one school year, teacher-reports of teacher-child closeness and conflict, and peer-reports of peer acceptance, rejection and disobedience were collected among 340 boys (mean age = 10.1 years, SD = 1.58, range = 5-13) with psychiatric disorders receiving special education. Autoregressive cross-lagged models were fitted to explore the nature of these developmental links. The impact of boys' age was examined using multiple group analyses. Findings supported the importance of teacher-child conflict, but not closeness, and positive and negative peer relationships for the development of boys' disobedience, with a stronger effect of negative than positive relationships. However, teacher-child and peer relationships were not longitudinally related and the effect of boys' age was minimal. This study extends prior research by suggesting that, despite differences in educational setting and severity of behavior problems between children in mainstream and special education, reducing negative classroom interactional patterns is most important in preventing the development of problematic classroom behavior in boys with severe social-emotional and behavioral difficulties.
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Trastornos de la Conducta Infantil/psicología , Educación Especial , Relaciones Interpersonales , Trastornos Mentales/psicología , Conducta Social , Adolescente , Niño , Preescolar , Conflicto Psicológico , Docentes , Humanos , Masculino , Grupo ParitarioRESUMEN
Phospholipase A2 (PLA2) is a key-enzyme in the metabolism of membrane phospholipids. In cholinergic neurons PLA2 controls the physico-chemical properties of neuronal membranes as well as the breakdown of phosphatidylcholine to produce choline for acetylcholine synthesis. Moreover PLA2 influences the processing and secretion of the amyloid precursor protein, which gives rise to the beta-amyloid peptide, the major component of the amyloid plaque in Alzheimer's disease (AD). In the present study PLA2 activity was investigated in post-mortem brains from 23 patients with AD and 20 nondemented elderly controls. In AD brains PLA2 activity was significantly decreased in the parietal and to a lesser degree in the frontal cortex. Lower PLA2 activity correlated significantly with an earlier onset of the disease, higher counts of neurofibrillary tangles and senile plaques and an earlier age at death, indicating a relationship between abnormally low PLA2 activity and a more severe form of the illness. The present results provide new evidence for a disordered phospholipid metabolism in AD brains and suggest that reduced PLA2 activity may contribute to the cholinergic deficit and to the production of amyloidogenic peptides in the disease.
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Enfermedad de Alzheimer/enzimología , Encéfalo/enzimología , Fosfolipasas A/metabolismo , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Fosfolipasas A2RESUMEN
The intracellular enzyme phospholipase A2 (PLA2) plays an essential role in the breakdown of membrane phospholipids, which regulate the physicochemical properties of the cell membrane. In the brain PLA2 has been reported to influence receptor function and signal transduction. Regarding dopaminergic neurons, data from animals experiments and from binding studies suggest that PLA2 activation reduces dopaminergic neurotransmission. In the present study we investigated intracellular PLA2 in platelets from 31 DSM-III-R paranoid schizophrenic patients (15 neuroleptic-naive) compared to 31 healthy individuals and to 31 non-schizophrenic psychiatric controls, both matched to the schizophrenics by age and sex. Platelet PLA2 activity was significantly increased in schizophrenics as compared to healthy and to psychiatric controls. Neuroleptic treatment reduced significantly the enzyme activity. Our findings in platelets suggest an accelerated breakdown of membrane phospholipids in schizophrenia. An accelerated phospholipid breakdown has also been reported in the frontal cortex from schizophrenic patients. Further studies should clarify whether increased PLA2 in the brain, as observed in platelets, could contribute to a frontal dysfunction in schizophrenia.
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Plaquetas/enzimología , Fosfolipasas A/metabolismo , Esquizofrenia/sangre , Adulto , Membrana Celular/enzimología , Femenino , Humanos , Técnicas In Vitro , Masculino , Fosfolipasas A2RESUMEN
beta-amyloid peptide (A beta) and several A beta-fragments decrease the fluidity of human cortex membranes in a concentration dependent fashion. The effect of A beta on membrane fluidity increases with peptide length, is most pronounced for A beta 1-43 and can be seen at concentrations as low as 100 nmol/l. While the fragment A beta 25-35 is active, scrambled peptide (A beta 35-25) when investigated under similar conditions shows no effects on membrane fluidity. The effect of A beta peptides on fluidity of the phospholipid bilayer is more pronounced in the hydrocarbon core (labeled with the fluorescence probe 1,6-diphenylhexa-1,3,5-triene) than in the region of the hydrophilic heads (labeled with the fluorescence probe 1-[4'-(trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene). It is suggested that the effect of A beta on neuronal membranes is probably a major initial mechanism in a cascade of events finally leading to neurotoxicity and cell death in Alzheimer's disease.
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Péptidos beta-Amiloides/farmacología , Encéfalo/fisiología , Fluidez de la Membrana/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Enfermedad de Alzheimer/fisiopatología , Apolipoproteínas E/farmacología , Membrana Celular/fisiología , Difenilhexatrieno/análogos & derivados , Difenilhexatrieno/metabolismo , Femenino , Polarización de Fluorescencia , Colorantes Fluorescentes , Humanos , Membrana Dobles de Lípidos/metabolismo , Masculino , Fosfolípidos/metabolismoRESUMEN
There is compelling evidence that depression constitutes an independent risk factor for cardiovascular morbidity and mortality. As exaggerated platelet reactivity is associated with an increased risk of intra-arterial thrombus formation, we studied platelet aggregability in patients with major depression both before and after 5 weeks of anti-depressant therapy as well as in healthy control subjects. Twenty-two depressed patients and 24 healthy control subjects participated in the study. Washed and rediluted platelets were stimulated with the agonists collagen and thrombin in three concentration steps. Depression was associated with a higher aggregability after stimulation with thrombin in the intermediate concentration and with collagen at the low concentration, with ceiling effects for the other concentrations. After 5 weeks of anti-depressant therapy, aggregability was somewhat less exaggerated, although this effect did not reach statistical significance. We thus conclude that major depression is associated with increased platelet aggregability, which seems to persist even under a marked improvement in depressive symptomatology. This effect may contribute to the increased cardiovascular morbidity in depressed patients.
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Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/sangre , Agregación Plaquetaria , Adulto , Biomarcadores , Enfermedades Cardiovasculares/etiología , Estudios de Casos y Controles , Estudios Transversales , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria/efectos de los fármacos , RiesgoRESUMEN
Starvation of four Escherichia coli clinical strains in seawater and drinking water for nine days revealed that various changes of hydrolytic enzymes were induced. Several gelatinolytic and caseinolytic activities differing in mol mass were detected both in seawater and drinking water starved cells by substrate gel electrophoresis. The major activities of gelatinase migrated with mol masses of approximately 170 kDa and approximately 45 kDa. On the contrary, hyaluronolytic activities were detected only in cells cultured in Mueller Hinton broth with average mol masses of 36 kDa and 45 kDa. Acid and alkaline phosphohydrolytic activities were detected by native electrophoresis. Both activities were decreased in number of bands in E. coli cells starved either in seawater or drinking water.
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Escherichia coli/enzimología , Gelatinasas/metabolismo , Hialuronoglucosaminidasa/metabolismo , Metaloendopeptidasas/metabolismo , Monoéster Fosfórico Hidrolasas/metabolismo , Electroforesis en Gel de Poliacrilamida , Agua de Mar , Abastecimiento de AguaRESUMEN
OBJECTIVE: While an association between androgens and different types of aggression has been well documented in male offenders, the influence of androgens on externalizing behavior in adolescents at risk for antisocial behavior has not been investigated so far. METHODS: Plasma levels of the main androgen metabolites testosterone (T) and 5a-dihydrotestosterone (DHT) were measured in N = 119 14-year-olds (51 boys, 68 girls) from a prospective longitudinal study of children at risk. The Achenbach Child Behavior Checklist (CBCL) and the Youth Self Report Form (YSR) were used to assess externalizing behavior at age 14. RESULTS: The CBCL revealed significant positive correlations between DHT levels and the subscales "externalizing problems" and the problem scales "aggressive behavior" and "delinquent behavior" in male adolescents. Only the YSR subscale "delinquent behavior" exhibited a marginally significant association with DHT. Neither scale showed any significant correlations between androgen levels and externalizing behavior in female adolescents. CONCLUSIONS: Earlier findings of androgen effects on aggressive and antisocial behavior in male offenders were confirmed for male adolescents from a general population sample. The results stress the importance of the androgen metabolite DHT.