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BACKGROUND: We compared dissociative seizure specific cognitive behavior therapy (DS-CBT) plus standardized medical care (SMC) to SMC alone in a randomized controlled trial. DS-CBT resulted in better outcomes on several secondary trial outcome measures at the 12-month follow-up point. The purpose of this paper is to evaluate putative treatment mechanisms. METHODS: We carried out a secondary mediation analysis of the CODES trial. 368 participants were recruited from the National Health Service in secondary / tertiary care in England, Scotland, and Wales. Sixteen mediation hypotheses corresponding to combinations of important trial outcomes and putative mediators were assessed. Twelve-month trial outcomes considered were final-month seizure frequency, Work and Social Adjustment Scale (WSAS), and the SF-12v2, a quality-of-life measure providing physical (PCS) and mental component summary (MCS) scores. Mediators chosen for analysis at six months (broadly corresponding to completion of DS-CBT) included: (a) beliefs about emotions, (b) a measure of avoidance behavior, (c) anxiety and (d) depression. RESULTS: All putative mediator variables except beliefs about emotions were found to be improved by DS-CBT. We found evidence for DS-CBT effect mediation for the outcome variables dissociative seizures (DS), WSAS and SF-12v2 MCS scores by improvements in target variables avoidance behavior, anxiety, and depression. The only variable to mediate the DS-CBT effect on the SF-12v2 PCS score was avoidance behavior. CONCLUSIONS: Our findings largely confirmed the logic model underlying the development of CBT for patients with DS. Interventions could be additionally developed to specifically address beliefs about emotions to assess whether it improves outcomes.
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Terapia Cognitivo-Comportamental , Análise de Mediação , Convulsões , Humanos , Terapia Cognitivo-Comportamental/métodos , Masculino , Feminino , Adulto , Convulsões/terapia , Pessoa de Meia-Idade , Transtornos Dissociativos/terapia , Qualidade de Vida , Resultado do Tratamento , Ansiedade/terapia , Avaliação de Resultados em Cuidados de Saúde , Depressão/terapia , EscóciaRESUMO
BACKGROUND: Since the recent conflicts in Iraq and Afghanistan, the short-term focus of military healthcare research has been on the consequences of deployment for mental health and on those wounded or injured in combat. Now that these conflicts have ended for the UK Armed Forces, it is important to consider the longer term physical and mental health consequences, and just as importantly, the links between these. The aims of this study were to determine the most common physical conditions requiring a hospital admission in UK military personnel and whether they were more common in personnel with a mental health condition, smokers, and/or those misusing alcohol compared to those without. METHODS: Data linkage of a prospective UK military cohort study to electronic admitted patient care records for England, Wales and Scotland. Nine thousand nine hundred ninety military personnel completed phase 2 of a military cohort study (56% response rate, data collected from 2007 to 2009), with analyses restricted to 86% of whom provided consent for linkage to healthcare records (n = 8602). Ninety percent were male and the mean age at phase 2 was 36 years. The outcome was physical non communicable diseases (NCDs) requiring a hospital admission which occurred after phase 2 of the cohort when the mental health, smoking and alcohol use exposure variables had been assessed until the end of March 2014. RESULTS: The most common NCDs requiring a hospital admission were gastrointestinal disorders 5.62% (95% Confidence Intervals (CI) 5.04, 6.19) and joint disorders 5.60% (95% CI 5.02, 6.18). Number of NCDs requiring a hospital admission was significantly higher in those with a common mental disorder (Hazard ratio (HR) 1.40 (95% CI 1.16-1.68), post-traumatic stress disorder (HR 1.78 (95% CI 1.32-2.40)) and in current smokers (HR 1.35 (95% CI 1.12-1.64) compared to those without the disorder, and non-smokers, respectively. CONCLUSIONS: Military personnel with a mental health problem are more likely to have an inpatient hospital admission for NCDs compared to those without, evidencing the clear links between physical and mental health in this population.
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Transtornos Mentais , Militares , Doenças não Transmissíveis , Transtornos de Estresse Pós-Traumáticos , Campanha Afegã de 2001- , Afeganistão , Estudos de Coortes , Inglaterra , Feminino , Hospitais , Humanos , Armazenamento e Recuperação da Informação , Iraque , Guerra do Iraque 2003-2011 , Masculino , Transtornos Mentais/epidemiologia , Saúde Mental , Doenças não Transmissíveis/epidemiologia , Estudos Prospectivos , Escócia , Reino Unido/epidemiologia , País de GalesRESUMO
BACKGROUND: Cognitive remediation (CR) is a psychological therapy, which improves cognitive and social functioning in people with schizophrenia. It is now being implemented within routine clinical services and mechanisms of change are being explored. We designed a new generation computerised CR programme, CIRCuiTS (Computerised Interactive Remediation of Cognition - a Training for Schizophrenia), to enhance strategic and metacognitive processing, with an integrated focus on the transfer of cognitive skills to daily living. This large trial tested its feasibility to be delivered in therapist-led and independent sessions, and its efficacy for improved cognitive and social functioning. METHODS: A two arm single blind randomised superiority trial comparing CIRCuiTS plus treatment-as-usual (TAU) with TAU alone in 93 people with a diagnosis of schizophrenia. Cognitive, social functioning and symptom outcomes were assessed at pre- and post-therapy and 3 months later. RESULTS: 85% adhered to CIRCuiTS, completing a median of 28 sessions. There were significant improvements in visual memory at post-treatment (p = 0.009) and follow-up (p = 0.001), and a trend for improvements in executive function at post-treatment (p = 0.056) in favour of the CIRCuiTS group. Community function was also differentially and significantly improved in the CIRCuiTS group at post-treatment (p = 0.003) but not follow-up, and was specifically predicted by improved executive functions. CONCLUSIONS: CIRCuiTS was beneficial for improving memory and social functioning. Improved executive functioning emerges as a consistent predictor of functional gains and should be considered an important CR target to achieve functional change. A larger-scale effectiveness trial of CIRCuiTS is now indicated.
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BACKGROUND: There is limited evidence for effective interventions in the treatment of post-traumatic stress symptoms within individuals diagnosed with schizophrenia. Clinicians have concerns about using exposure treatments with this patient group. The current trial was designed to evaluate a 16-session cognitive restructuring programme, without direct exposure, for the treatment of post-traumatic stress symptoms specifically within individuals diagnosed with schizophrenia. METHOD: A multicentre randomized controlled single-blinded trial with assessments at 0 months, 6 months (post-treatment) and 12 months (follow-up) was conducted. A total of 61 participants diagnosed with schizophrenia and exhibiting post-traumatic stress symptoms were recruited. Those randomized to treatment were offered up to 16 sessions of cognitive-behaviour therapy (CBT, including psychoeducation, breathing training and cognitive restructuring) over a 6-month period, with the control group offered routine clinical services. The main outcome was blind rating of post-traumatic stress symptoms using the Clinician Administered PTSD Scale for Schizophrenia. Secondary outcomes were psychotic symptoms as measured by the Positive and Negative Symptom Scale and the Psychotic Symptom Rating Scale. RESULTS: Both the treatment and control groups experienced a significant decrease in post-traumatic stress symptoms over time but there was no effect of the addition of CBT on either the primary or secondary outcomes. CONCLUSIONS: The current trial did not demonstrate any effect in favour of CBT. Cognitive restructuring programmes may require further adaptation to promote emotional processing of traumatic memories within people diagnosed with a psychotic disorder.
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Terapia Cognitivo-Comportamental/métodos , Avaliação de Resultados em Cuidados de Saúde , Esquizofrenia/terapia , Transtornos de Estresse Pós-Traumáticos/terapia , Adulto , Comorbidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/epidemiologia , Método Simples-Cego , Transtornos de Estresse Pós-Traumáticos/epidemiologiaRESUMO
BACKGROUND: Against a backdrop of increasing research, clinical and taxonomic attention in non-suicidal self-injury (NSSI), evidence suggests a link between NSSI and eating disorders (ED). The frequency estimates of NSSI in ED vary widely. Little is known about the sources of this variation, and no meta-analysis has quantified the association between ED and NSSI. METHOD: Using random-effects meta-analyses, meta-regression analyses, and 1816-6466 unique participants with various ED, we estimated the weighted average percentage of individuals with ED, those with anorexia nervosa (AN) and those with bulimia nervosa (BN) who are reported to have a lifetime history of NSSI across studies. We further examined predictors of NSSI in ED. RESULTS: The weighted average percentage of patients with a lifetime history of NSSI was 27.3% [95% confidence interval (CI) 23.8-31.0%] for ED, 21.8% (95% CI 18.5-25.6%) for AN, and 32.7% (95% CI 26.9-39.1%) for BN. The difference between BN and AN was statistically significant [odds ratio (OR) 1.77, 95% CI 1.14-2.77, p = 0.013]. The odds of NSSI increased by 24% for every 10% increase in the percentage of participants with histories of suicide attempts (OR 1.24, 95% CI 1.04-1.48, p = 0.020) and decreased by 26% for every 10% increase in the percentage of participants with histories of substance abuse (OR 0.74, 95% CI 0.58-0.95, p = 0.023). CONCLUSIONS: In the specific context of ED, NSSI is highly prevalent and correlates positively with attempted suicide, urging for NSSI-focused treatments. A novel finding is that NSSI is potentially antagonized by substance abuse.
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Comorbidade , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Comportamento Autodestrutivo/epidemiologia , Tentativa de Suicídio/estatística & dados numéricos , PrevalênciaRESUMO
BACKGROUND: Depression and anxiety in Parkinson's disease are common and frequently co-morbid, with significant impact on health outcome. Nevertheless, management is complex and often suboptimal. The existence of clinical subtypes would support stratified approaches in both research and treatment. METHOD: Five hundred and thirteen patients with Parkinson's disease were assessed annually for up to 4 years. Latent transition analysis (LTA) was used to identify classes that may conform to clinically meaningful subgroups, transitions between those classes over time, and baseline clinical and demographic features that predict common trajectories. RESULTS: In total, 64.1% of the sample remained in the study at year 4. LTA identified four classes, a 'Psychologically healthy' class (approximately 50%), and three classes associated with psychological distress: one with moderate anxiety alone (approximately 20%), and two with moderate levels of depression plus moderate or severe anxiety. Class membership tended to be stable across years, with only about 15% of individuals transitioning between the healthy class and one of the distress classes. Stable distress was predicted by higher baseline depression and psychiatric history and younger age of onset of Parkinson's disease. Those with younger age of onset were also more likely to become distressed over the course of the study. CONCLUSIONS: Psychopathology was characterized by relatively stable anxiety or anxious-depression over the 4-year period. Anxiety, with or without depression, appears to be the prominent psychopathological phenotype in Parkinson's disease suggesting a pressing need to understanding its mechanisms and improve management.
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Ansiedade/epidemiologia , Depressão/epidemiologia , Doença de Parkinson/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Reino Unido/epidemiologiaRESUMO
PURPOSE: The increasing use of amyloid PET in Alzheimer's disease research and clinical trials has motivated efforts to standardize methodology. We compared retention of the (11)C radiotracer Pittsburgh Compound B (PiB) and that of two (18)F amyloid radiotracers (florbetapir and flutemetamol) using two study populations. We also examined the feasibility of converting between tracer-specific measures, using PiB as the common link between the two (18)F tracers. METHODS: One group of 40 subjects underwent PiB and flutemetamol imaging sessions and a separate group of 32 subjects underwent PiB and florbetapir imaging sessions. We compared cortical and white matter retention for each (18)F tracer relative to that of PiB, as well as retention in several reference regions and image analysis methods. Correlations between tracer pairs were used to convert tracer-specific threshold values for amyloid positivity between tracers. RESULTS: Cortical retention for each pair of tracers was strongly correlated regardless of reference region (PiB-flutemetamol, ρ = 0.84-0.99; PiB-florbetapir, ρ = 0.83-0.97) and analysis method (ρ = 0.90-0.99). Compared to PiB, flutemetamol had higher white matter retention, while florbetapir had lower cortical retention. Two previously established independent thresholds for amyloid positivity were highly consistent when values were converted between tracer pairs. CONCLUSION: Despite differing white and grey matter retention characteristics, cortical retention for each (18)F tracer was highly correlated with that of PiB, enabling conversion of thresholds across tracer measurement scales with a high level of internal consistency. Standardization of analysis methods and measurement scales may facilitate the comparison of amyloid PET data obtained using different tracers.
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Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Amiloide/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Idoso , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Substância Branca/diagnóstico por imagem , Substância Branca/metabolismoRESUMO
BACKGROUND: Reduced P300 event-related potential (ERP) amplitude and latency prolongation have been reported in patients with schizophrenia compared to healthy controls. However, the influence of antipsychotics (and dopamine) on ERP measures are poorly understood and medication confounding remains a possibility. METHOD: We explored ERP differences between 36 drug-naive patients with schizophrenia and 138 healthy controls and examined whether P300 performance was related to dopamine transporter (DAT) availability, both without the confounding effects of medication. We also conducted a random effects meta-analysis of the available literature, synthesizing the results of three comparable published articles and our local study. RESULTS: No overall significant difference was found in mean P300 ERP between patients and controls in latency or in amplitude. There was a significant gender effect, with females showing greater P300 amplitude than males. A difference between patients and controls in P300 latency was evident with ageing, with latency increasing faster in patients. No effect of DAT availability on P300 latency or amplitude was detected. The meta-analysis computed the latency pooled standardized effect size (PSES; Cohen's d) of -0.13 and the amplitude PSES (Cohen's d) of 0.48, with patients showing a significant reduction in amplitude. CONCLUSIONS: Our findings suggest the P300 ERP is not altered in the early stages of schizophrenia before medication is introduced, and the DAT availability does not influence the P300 ERP amplitude or latency. P300 ERP amplitude reduction could be an indicator of the progression of illness and chronicity.
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Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Potenciais Evocados P300/fisiologia , Esquizofrenia/metabolismo , Esquizofrenia/fisiopatologia , Adolescente , Adulto , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Tomografia Computadorizada de Emissão de Fóton Único , Adulto JovemRESUMO
BACKGROUND: Prior studies of Alzheimer's disease (AD) biomarker disclosure have answered important questions about individuals' safety after learning and comprehending their amyloid PET results; however, these studies have typically employed highly structured disclosure protocols and focused on the psychological impact of disclosure (e.g., anxiety, depression, and suicidality) in homogeneous populations. More work is needed to develop flexible disclosure protocols and study outcomes in ethnoculturally representative samples. METHODS: The Alzheimer's Disease Neuroimaging Initiative (ADNI) is formally incorporating amyloid PET disclosure into the newest protocol (ADNI-4). Participants across the cognitive spectrum who wish to know their amyloid PET results may learn them. The pragmatic disclosure process spans four timepoints: (1) a pre-disclosure visit, (2) the PET scan and its read, (3) a disclosure visit, and (4) a post-disclosure check-in. This process applies to all participants, with slight modifications to account for their cognitive status. In designing this process, special emphasis was placed on utilizing investigator discretion. Participant measures include perceived risk of dementia, purpose in life, and disclosure satisfaction. Investigator assessment of the disclosure visit (e.g., challenges encountered, topics discussed, etc.) is also included. RESULTS: Data collection is ongoing. Results will allow for more robust characterization of the impact of learning amyloid PET results on individuals and describe the perspectives of investigators. CONCLUSION: The pragmatic design of the disclosure process in ADNI-4 coupled with the novel participant and investigator data will inform future disclosure practices. This is especially important as disclosure of biomarker results expands in research and care.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico por imagem , Revelação , Tomografia por Emissão de Pósitrons , Neuroimagem/métodos , Amiloide , BiomarcadoresRESUMO
OBJECTIVE: To examine the prevalence, incidence and risk factors associated with visual hallucinations (VHs) amongst people suffering from Parkinson's disease (PD). METHODS: We recruited 513 patients with PD from movement disorder and PD clinics within three sites in the UK. Patients were interviewed using a series of standardised clinical rating scales at baseline, 12, 24 and 36 months. Data relating to VHs were collected using the North-East Visual Hallucinations Interview. Prevalence rates for VHs at each assessment were recorded. Associations were determined using multiple regression analysis. RESULTS: Cross-sectional prevalence rates for VHs at baseline, 12, 24 and 36 months indicated VHs in approximately 50% of patients. A cumulative frequency of 82.7% of cases at the end of the study period exhibited VHs. The incidence rate for VHs was 457 cases per 1000 population. Longer disease duration, greater impairment in activities of daily living and higher rates of anxiety were most commonly associated with VHs. No factors predictive of VHs could be ascertained. CONCLUSIONS: When examined longitudinally, VHs affect more patients than is commonly assumed in cross-sectional prevalence studies. Clinicians should routinely screen for VHs throughout the disease course. Disease duration, impairment in activities of daily living and anxiety presented as co-morbidities associated with VHs in PD, and therefore those presenting with VHs should be screened for anxiety disorder and vice versa.
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Alucinações/epidemiologia , Doença de Parkinson/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Alucinações/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Análise de Regressão , Fatores de Risco , Reino Unido/epidemiologiaRESUMO
OBJECTIVE: We explored moderators of cognitive behavioural therapy (CBT) treatment effects and predictors of outcome at 12-month follow-up in the CODES Trial (N = 368) comparing CBT plus standardised medical care (SMC) vs SMC-alone for dissociative seizures (DS). METHODS: We undertook moderator analyses of baseline characteristics to determine who had benefited from being offered CBT 12 months post-randomisation. Outcomes included: monthly DS frequency, psychosocial functioning (Work and Social Adjustment Scale - WSAS), and health-related quality of life (Mental Component Summary (MCS) and Physical Component Summary (PCS) SF-12v2 scores). When moderating effects were absent, we tested whether baseline variables predicted change irrespective of treatment allocation. RESULTS: Moderator analyses revealed greater benefits (p < 0.05) of CBT on DS frequency for participants with more (≥22) symptoms (Modified PHQ-15) or ≥ 1 current (M.I.N.I.-confirmed) comorbid psychiatric diagnosis at baseline. The effect of CBT on PCS scores was moderated by gender; women did better than men in the CBT + SMC group. Predictors of improved outcome included: not receiving disability benefits, lower anxiety and/or depression scores (PCS, MCS, WSAS); shorter duration, younger age at DS onset, employment, fewer symptoms and higher educational qualification (PCS, WSAS); stronger belief in the diagnosis and in CBT as a "logical" treatment (MCS). Some variables that clinically might be expected to moderate/predict outcome (e.g., maladaptive personality traits, confidence in treatment) were not shown to be relevant. CONCLUSION: Patient complexity interacted with treatment. CBT was more likely to reduce DS frequency in those with greater comorbidity. Other patient characteristics predicted outcome regardless of the received intervention.
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Terapia Cognitivo-Comportamental , Transtorno Conversivo , Adulto , Feminino , Humanos , Masculino , Qualidade de Vida , Convulsões/psicologia , Resultado do TratamentoRESUMO
Primary culture of mammary epithelial cells (MEC) was exposed to ethyl-acetate, chloroform and hexane extracts of Pistacia lentiscus (lentisk). The hexane extract contained mainly ethyl gallate whereas the chloroform extract contained mainly ethyl-gallate with smaller amount of gallic acid, and the ethyl-acetate extract contained mainly rutin, gallic acid and myricetin. Ethyl acetate extract increased secretion of protein and fat and improved mitochondrial activity. The enhancing effect on protein production was attributed to myricetin, one of the polyphenols in the ethyl-acetate extract whereas gallic acid did not affect protein production or secretion. Interestingly, exposure to the isolated polyphenols did not improve mitochondrial productivity and activity as effectively as exposure to the complete plant extract. The results indicated that polyphenols improve production of milk constituents by MEC, through different modes of action for different polyphenols suggesting an additive or even synergistic effect on production traits of mammary cells.
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BACKGROUND: Parkinson's disease (PD) brings with it a range of stresses and challenges with which a patient must cope. The type of coping strategies employed can impact upon well-being, although findings from coping studies in PD remain inconsistent. The variety of coping scales used without validation in PD has been cited as a possible cause of this inconsistency. The present study sought to examine the validity of the coping inventory for stressful situations (CISS) in a sample of patients with PD. METHODS: Five hundred and twenty-five patients with PD were recruited as part of a longitudinal investigation of mood states in PD. Four hundred and seventy-one participants completed the CISS. Confirmatory factor analysis was used to explore the structural validity of the scale. Internal reliability, test-retest reliability, convergent validity and discriminant validity were assessed using Cronbach's alpha, intraclass correlations and Pearson's correlations. RESULTS: Both three and four factor solutions were examined. The four factor model was found to provide a better fit of the data than the three factor model. The internal reliability, discriminant validity, convergent validity, and test-retest reliability of the CISS scales were shown to be good. Use of emotion-focused coping was associated with greater depression and anxiety whilst, task-oriented coping was associated with better psychological well-being. CONCLUSION: The results provide support for the validity and reliability of the CISS as a measure of coping in patients with PD. Further research into the relationship between coping and well-being is warranted. The identification of helpful and unhelpful coping strategies may guide the development of evidence-based therapies to improve well-being in patients with PD.
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Adaptação Psicológica , Doença de Parkinson/psicologia , Estresse Psicológico , Idoso , Idoso de 80 Anos ou mais , Análise Fatorial , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes Psicológicos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Estresse Psicológico/psicologiaRESUMO
OBJECTIVE: To evaluate cognitive behaviour therapy for psychosis (CBTp) delivered by non-expert therapists, using CBT relevant measures. METHOD: Participants (N = 74) were randomised into immediate therapy or waiting list control groups. The therapy group was offered 6 months of therapy and followed up 3 months later. The waiting list group received therapy after waiting 9 months (becoming the delayed therapy group). RESULTS: Depression improved in the combined therapy group at both the end of therapy and follow-up. Other significant effects were found in only one of the two therapy groups (positive symptoms; cognitive flexibility; uncontrollability of thoughts) or one of the two time points (end of therapy: general symptoms, anxiety, suicidal ideation, social functioning, resistance to voices; follow-up: power beliefs about voices, negative symptoms). There was no difference in costs between the groups. CONCLUSION: The only robust improvement was in depression. Nevertheless, there were further encouraging but modest improvements in both emotional and cognitive variables, in addition to psychotic symptoms.
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Terapia Cognitivo-Comportamental , Depressão/terapia , Transtornos Psicóticos/terapia , Adolescente , Adulto , Idoso , Antipsicóticos/uso terapêutico , Ansiedade , Terapia Cognitivo-Comportamental/métodos , Terapia Cognitivo-Comportamental/organização & administração , Serviços Comunitários de Saúde Mental/organização & administração , Grupos Controle , Depressão/etiologia , Humanos , Pessoa de Meia-Idade , Relações Profissional-Paciente , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/complicações , Transtornos Psicóticos/fisiopatologia , Ajustamento Social , Ideação Suicida , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
We assessed the potential of phenolic compounds from Pistacia lentiscus (lentisk) to enhance production of milk constituents in bovine mammary epithelial cells (MEC). MEC were exposed to 0 (control), 1 or 10 ppm of polyphenols from lentisk ethanolic extract (PLEE) for 24 h. PLEE were absorbed by the MEC plasma membrane, but also penetrated the cell to accumulate in and around the nucleus. PLEE increased triglyceride content in the cell and its secretion to the medium, and significantly increased intracellular lipid droplet diameter. Compared to control, PLEE increased dose-dependently the lactose synthesis, secretion of whey proteins, and contents of casein. To evaluate mitochondrial activity under pro-oxidant load, MEC were preincubated with PLEE and exposed for 2 h to H2O2. Exposure to H2O2 increased the proportion of cells with impaired mitochondrial membrane potential twofold in controls, but not in PLEE-pre-treated cells. Accordingly, proton leakage was markedly decreased by PLEE, and coupling efficiency between the respiratory chain and ATP production was significantly enhanced. Thus, lentisk polyphenols divert energy to production of milk fat, protein and lactose, with less energy directed to cellular damage control; alternatively, PLEE enables MEC to maintain energy and oxidative status under extreme metabolic rate required for milk production and secretion, and reduces the limitation on energy required to support production.
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Células Epiteliais/efeitos dos fármacos , Glândulas Mamárias Animais/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Pistacia/química , Extratos Vegetais/farmacologia , Animais , Bovinos , Células Cultivadas , Células Epiteliais/metabolismo , Feminino , Glicolipídeos/metabolismo , Glicoproteínas/metabolismo , Lactose/metabolismo , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/metabolismo , Consumo de Oxigênio/efeitos dos fármacosRESUMO
Macrophages are key contributors to vascularization, but the mechanisms behind their actions are not understood. Here, we show that diverse macrophage phenotypes have distinct effects on endothelial cell behavior, with resulting effects on vascularization of engineered tissues. In Transwell coculture, proinflammatory M1 macrophages caused endothelial cells to up-regulate genes associated with sprouting angiogenesis, whereas prohealing (M2a), proremodeling (M2c), and anti-inflammatory (M2f) macrophages promoted up-regulation of genes associated with pericyte cell differentiation. In 3D tissue-engineered human blood vessel networks in vitro, short-term exposure (1 day) to M1 macrophages increased vessel formation, while long-term exposure (3 days) caused regression. When human tissue-engineered blood vessel networks were implanted into athymic mice, macrophages expressing markers of both M1 and M2 phenotypes wrapped around and bridged adjacent vessels and formed vessel-like structures themselves. Last, depletion of host macrophages inhibited remodeling of engineered vessels, infiltration of host vessels, and anastomosis with host vessels.
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Células Endoteliais , Engenharia Tecidual , Animais , Diferenciação Celular , Macrófagos , Camundongos , FenótipoRESUMO
In a previous study, we showed that access to willow fodder decreased somatic cell counts (SCC) in the milk of local Mamber goats grazing in brushland at the end of lactation. To test whether the consumption of willow affects the cells of the immune system, Alpine crossbred dairy goats grazing in the same environment were either offered free access to freshly cut willow fodder (W, n = 24) or not (C, n = 24) for 2 weeks. The willow fodder contained 7.5 g/kg DM of salicin. The other major secondary compounds were catechin, myricitrin, hyperin and chlorogenic acid (2.2, 2.6, 1.0 and 0.75 g/kg DM, respectively). Udder health status was determined before the experiment, and each of the two groups included five (W) or six (C) goats defined as infected, as established by microbial cfu in milk, and 19 (W) or 18 (C) non-infected goats. Goats ingested, on average, 600 g of DM from willow (25% of food intake), resulting in minor changes in dietary quality compared to the controls, as established by faecal near-IR spectrometry. Throughout the 2 weeks of experiment, differences between groups in dietary CP contents were minor and affected neither by infection nor by access to willow; the dietary percentage of neutral detergent fibre (NDF) decreased in C and increased in W; dietary acid detergent fibre (ADF) increased; and the dietary tannin contents decreased for both treatments. However, milking performance and milk quality attributes in both W and C goats were similar. Initial SCC and milk neutrophil (cluster of differentiation (CD)18+ and porcine granulocyte (PG)68) cell counts were higher in infected than in non-infected goats; counts decreased significantly in W but not in C uninfected goats. The percentage of CD8+ T-cells increased in all C goats, while in the W group, a significant increase was found only for infected goats. The consumption of willow mitigated an increase in CD8+ in blood and triggered an increase in CD8+ in milk, suggesting an immune-regulatory effect independent of udder status. To our knowledge, this is the first report of a direct nutraceutical effect of fodder ingestion on the immune status of goats.
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Leite , Salix , Ração Animal , Animais , Feminino , Cabras , Lactação , SuínosRESUMO
BACKGROUND: There are multiple models of mental illness that inform professional and lay understanding. Few studies have formally investigated psychiatrists' attitudes. We aimed to measure how a group of trainee psychiatrists understand familiar mental illnesses in terms of propositions drawn from different models. METHOD: We used a questionnaire study of a sample of trainees from South London and Maudsley National Health Service (NHS) Foundation Trust designed to assess attitudes across eight models of mental illness (e.g. biological, psychodynamic) and four psychiatric disorders. Methods for analysing repeated measures and a principal components analysis (PCA) were used. RESULTS: No one model was endorsed by all respondents. Model endorsement varied with disorder. Attitudes to schizophrenia were expressed with the greatest conviction across models. Overall, the 'biological' model was the most strongly endorsed. The first three components of the PCA (interpreted as dimensions around which psychiatrists, as a group, understand mental illness) accounted for 56% of the variance. Each main component was classified in terms of its distinctive combination of statements from different models: PC1 33% biological versus non-biological; PC2 12% 'eclectic' (combining biological, behavioural, cognitive and spiritual models); and PC3 10% psychodynamic versus sociological. CONCLUSIONS: Trainee psychiatrists are most committed to the biological model for schizophrenia, but in general are not exclusively committed to any one model. As a group, they organize their attitudes towards mental illness in terms of a biological/non-biological contrast, an 'eclectic' view and a psychodynamic/sociological contrast. Better understanding of how professional group membership influences attitudes may facilitate better multidisciplinary working.
Assuntos
Atitude do Pessoal de Saúde , Transtornos Mentais/psicologia , Médicos/psicologia , Psiquiatria , Adulto , Fatores Etários , Feminino , Humanos , Internato e Residência , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Projetos Piloto , Análise de Componente Principal , Psicologia do Esquizofrênico , Inquéritos e Questionários , Reino UnidoRESUMO
BACKGROUND: There is good evidence that psychotic symptoms segregate into symptom dimensions. However, it is still unclear how these dimensions are associated with risk indicators and other clinical variables, and whether they have advantages over categorical diagnosis in clinical practice. We investigated symptom dimensions in a first-onset psychosis sample and examined their associations with risk indicators and clinical variables. We then examined the relationship of categorical diagnoses to the same variables. METHOD: We recruited 536 patients as part of a population-based, incidence study of psychosis. Psychopathology was assessed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). A principal axis factor analysis was performed on symptom scores. The relationship of dimension scores with risk indicators and with clinical variables was then examined employing regression analyses. Finally, regression models were compared to assess the contribution of dimensions versus diagnosis in explaining these variables. RESULTS: Factor analysis gave rise to a five-factor solution of manic, reality distortion, negative, depressive and disorganization symptom dimensions. The scores of identified dimensions were differentially associated with specific variables. The manic dimension had the highest number of significant associations; strong correlations were observed with shorter duration of untreated psychosis, acute mode of onset and compulsory admission. Adding dimensional scores to diagnostic categories significantly increased the amount of variability explained in predicting these variables; the reverse was also true but to a lesser extent. CONCLUSIONS: Categorical and dimensional representations of psychosis are complementary. Using both appears to be a promising strategy in conceptualising psychotic illnesses.
Assuntos
Classificação Internacional de Doenças , Transtornos Psicóticos/classificação , Adolescente , Adulto , Comorbidade , Estudos Transversais , Manual Diagnóstico e Estatístico de Transtornos Mentais , Análise Fatorial , Feminino , Humanos , Incidência , Inteligência , Masculino , Abuso de Maconha/epidemiologia , Abuso de Maconha/psicologia , Pessoa de Meia-Idade , Admissão do Paciente , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Psicometria , Psicopatologia , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/psicologia , Fatores de Risco , Comportamento Social , Adulto JovemRESUMO
A human intestinal intraepithelial lymphocyte (IEL) T cell line was established from jejunum to characterize the structure and function of the alpha beta T cell antigen receptors (TCRs) expressed by this population. Single-sided polymerase chain reaction (PCR) amplification cloning and quantitative PCR amplification of the TCR chains from the cell line and from fresh IELs demonstrated that IELs were oligoclonal. The IEL T cell line exhibited CD1-specific cytotoxicity and a dominant IEL T cell clone was CD1c-specific. Thus, human jejunal intraepithelial lymphocytes are oligoclonal and recognize members of the CD1 gene family.