992 research outputs found

    The Efficacy of Mindfulness-Based Cognitive Therapy as a Public Mental Health Intervention for Adults with Mild to Moderate Depressive Symptomatology: A Randomized Controlled Trial

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    Objective Although there has been growing evidence for the efficacy of mindfulness-based cognitive therapy (MBCT) for different clinical populations, its effectiveness as a public mental health intervention has not been studied. The present study evaluates a community-based MBCT intervention for adults with mild to moderate depressive symptomatology in a large multi-site, pragmatic randomized controlled trial. Method The participants with mild to moderate depressive symptomatology were recruited from the general population and randomized to the MBCT intervention (n = 76) or to a waiting list control group (n = 75). Participants completed measures before and after the intervention. Participants in the experimental condition also completed these measures at a 3-month follow-up. Results In the experimental condition significant reductions in depression, anxiety, and experiential avoidance, and improvements in mindfulness and emotional- and psychological mental health were found, compared to the waiting list (effect sizes Cohen's d = 0.31–0.56). These effects were sustained at the 3-month follow-up. The likelihood of a clinically significant change in depressive symptoms was significantly higher for the MBCT group [odds ratio (OR) 3.026, p<0.01 at post-treatment; NNT = 5.10]. Discussion MBCT as a public mental health intervention for adults with mild to moderate depressive symptoms seems effective and applicable in a natural setting

    Interobserver variation in CD30 immunohistochemistry interpretation; consequences for patient selection for targeted treatment

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    AimsCD30 immunohistochemistry (IHC) in malignant lymphoma is used for selection of patients in clinical trials using brentuximab vedotin, an antibody drug-conjugate targeting the CD30 molecule. For reliable implementation in daily practice and meaningful selection of patients for clinical trials, information on technical variation and interobserver reproducibility of CD30 immunohistochemistry (IHC) staining is required. Methods and resultsWe conducted a three-round reproducibility assessment of CD30 scoring for categorised frequency and intensity, including a technical validation, a live polling' pre- and post-instruction scoring round and a web-based round including individual scoring with additional IHC information to mimic daily diagnostic practice. Agreement in all three scoring rounds was poor to fair ( = 0.12-0.35 for CD30-positive tumour cell percentage and = 0.16-0.41 for staining intensity), even when allowing for one category of freedom in percentage of tumour cell positivity ( = 0.30-0.61). The first round with CD30 staining performed in five independent laboratories showed objective differences in staining intensity. In the second round, approximately half the pathologists changed their opinion on CD30 frequency after a discussion on potential pitfalls, highlighting hesitancy in decision-making. Using fictional cut-off points for percentage of tumour cell positivity, agreement was still suboptimal ( = 0.35-0.60). ConclusionsLack of agreement in cases with heterogeneous expression is shown to influence patient eligibility for treatment with brentuximab vedotin, both in clinical practice and within the context of clinical trials, and limits the potential predictive value of the relative frequency of CD30-positive neoplastic cells for clinical response

    Residual C-peptide secretion and hypoglycemia awareness in people with type 1 diabetes

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    INTRODUCTION: This study aimed to assess the association between fasting serum C-peptide levels and the presence of impaired awareness of hypoglycemia (IAH) in people with type 1 diabetes. RESEARCH DESIGN AND METHODS: We performed a cross-sectional study among 509 individuals with type 1 diabetes (diabetes duration 5-65 years). Extensive clinical data and fasting serum C-peptide concentrations were collected and related to the presence or absence of IAH, which was evaluated using the validated Dutch version of the Clarke questionnaire. A multivariable logistic regression model was constructed to investigate the association of C-peptide and other clinical variables with IAH. RESULTS: In 129 (25%) individuals, residual C-peptide secretion was detected, while 75 (15%) individuals reported IAH. The median (IQR) C-peptide concentration among all participants was 0.0 (0.0-3.9) pmol/L. The prevalence of severe hypoglycemia was lower in people with demonstrable C-peptide versus those with absent C-peptide (30% vs 41%, p=0.025). Individuals with IAH were older, had longer diabetes duration, more frequently had macrovascular and microvascular complications, and more often used antihypertensive drugs, antiplatelet agents and cholesterol-lowering medication. There was a strong association between IAH and having a severe hypoglycemia in the preceding year. In multivariable regression analysis, residual C-peptide, either continuously or dichotomous, was associated with lower prevalence of IAH (p=0.040-0.042), while age at diabetes onset (p=0.001), presence of microvascular complications (p=0.003) and body mass index (BMI) (p=0.003) were also independently associated with the presence of IAH. CONCLUSIONS: Higher BMI, the presence of microvascular complications and higher age at diabetes onset were independent risk factors for IAH in people with type 1 diabetes, while residual C-peptide secretion was associated with lower risk of this complication

    Genetic and biological characterisation of an avian-like H1N2 swine influenza virus generated by reassortment of circulating avian-like H1N1 and H3N2 subtypes in Denmark

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    BACKGROUND: The influenza A virus subtypes H1N1, H1N2 and H3N2 are the most prevalent subtypes in swine. In 2003, a reassorted H1N2 swine influenza virus (SIV) subtype appeared and became prevalent in Denmark. In the present study, the reassortant H1N2 subtype was characterised genetically and the infection dynamics compared to an “avian-like” H1N1 virus by an experimental infection study. METHODS: Sequence analyses were performed of the H1N2 virus. Two groups of pigs were inoculated with the reassortant H1N2 virus and an “avian-like” H1N1 virus, respectively, followed by inoculation with the opposite subtype four weeks later. Measurements of HI antibodies and acute phase proteins were performed. Nasal virus excretion and virus load in lungs were determined by real-time RT-PCR. RESULTS: The phylogenetic analysis revealed that the reassorted H1N2 virus contained a European “avian-like” H1-gene and a European “swine-like” N2-gene, thus being genetically distinct from most H1N2 viruses circulating in Europe, but similar to viruses reported in 2009/2010 in Sweden and Italy. Sequence analyses of the internal genes revealed that the reassortment probably arose between circulating Danish “avian-like” H1N1 and H3N2 SIVs. Infected pigs developed cross-reactive antibodies, and increased levels of acute phase proteins after inoculations. Pigs inoculated with H1N2 exhibited nasal virus excretion for seven days, peaking day 1 after inoculation two days earlier than H1N1 infected pigs and at a six times higher level. The difference, however, was not statistically significant. Pigs euthanized on day 4 after inoculation, had a high virus load in all lung lobes. After the second inoculation, the nasal virus excretion was minimal. There were no clinical sign except elevated body temperature under the experimental conditions. CONCLUSIONS: The “avian-like” H1N2 subtype, which has been established in the Danish pig population at least since 2003, is a reassortant between circulating swine “avian-like” H1N1 and H3N2. The Danish H1N2 has an “avian-like” H1 and differs from most other reported H1N2 viruses in Europe and North America/Asia, which have H1-genes of human or “classical-swine” origin, respectively. The variant seems, however, also to be circulating in countries like Sweden and Italy. The infection dynamics of the reassorted “avian-like” H1N2 is similar to the older “avian-like” H1N1 subtype

    Effects of high glucose and TGF-β1 on the expression of collagen IV and vascular endothelial growth factor in mouse podocytes

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    Effects of high glucose and TGF-β1 on the expression of collagen IV and vascular endothelial growth factor in mouse podocytes.BackgroundThe podocyte takes center stage in the pathogenesis of glomerular basement membrane (GBM) thickening and proteinuria in diabetic glomerulopathy. In part, GBM thickening may occur when the podocyte synthesizes increased amounts of collagen IV. Proteinuria may develop if the podocyte secretes excessive amounts of vascular endothelial growth factor (VEGF), which may increase the glomerular permeability to macromolecules. The augmented production of collagen IV and VEGF may be caused by metabolic mediators of diabetes such as hyperglycemia and transforming growth factor-β (TGF-β).MethodsThe effects of high glucose and exogenous TGF-β1 were examined on a mouse podocyte cell line that retains its differentiated phenotype. The gene expression and protein production of certain alpha chains of collagen IV, the major isoforms of VEGF, and components of the TGF-β system were assayed. An inhibitor of TGF-β signaling was used to determine whether some of the high glucose effects might be mediated by the TGF-β system.ResultsCompared with normal glucose (5.5 mmol/L), high glucose (HG, 25 mmol/L) for 14 days stimulated [3H]-proline incorporation, a measure of collagen production, by 1.8-fold, and exogenous TGF-β1 (2 ng/mL) for 24 hours stimulated proline incorporation by 2.4-fold. Northern analysis showed that exposure to HG for 14 days increased the mRNA level of α1(IV) collagen by 51% and α5(IV) by 90%, whereas treatment with TGF-β1 (2 ng/mL) for 24 hours decreased the mRNA level of α1(IV) by 36% and α5(IV) by 40%. Consistent with these effects on mRNA expression, Western blotting showed that HG increased α1(IV) protein by 44% and α5(IV) by 28%, while TGF-β1 decreased α1(IV) protein by 29% and α5(IV) by 7%. In contrast to their opposing actions on α1 and α5(IV), both HG and exogenous TGF-β1 increased α3(IV) collagen and VEGF, with TGF-β1 having the greater effect. An inhibitor of the TGF-β type I receptor (ALK5) was able to prevent the stimulation of α3(IV) and VEGF proteins by HG. Unlike in other renal cell types, HG did not increase TGF-β1 mRNA or protein in the podocyte, but HG did induce the expression of the ligand-binding TGF-β type II receptor (TβRII). Because HG had up-regulated TβRII after two weeks, the addition of physiological-dose TGF-β1 (0.010 ng/mL) for 24 hours stimulated the production of α3(IV) and VEGF proteins to a greater extent in high than in normal glucose. Up-regulation of TβRII in the podocyte was corroborated by immunohistochemistry of the kidney cortex in the db/db mouse, a model of type 2 diabetes.ConclusionsHigh glucose and exogenous TGF-β1 exert disparate effects on the expression of α1 and α5(IV) collagen. However, high glucose and TGF-β1 coordinately induce the production of α3(IV) collagen and VEGF in the podocyte. The HG-induced increases in α3(IV) collagen and VEGF proteins are mediated by the TGF-β system. By increasing the expression of TβRII, high glucose may augment the response of the podocyte to ambient levels of TGF-β1

    Surveillance sanitaire des cocoteraies adultes en Afrique de l'Ouest. I. Contrôles ordinaires

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    La plupart des ravageurs connus dans les cocoteraies d'Afrique de l'Ouest passent le plus souvent inaperçus, bien qu'ils soient toujours présents. Dans certaines conditions, difficiles à définir, il y a pullulation d'un ou de plusieurs d'entre eux et, en conséquence, des dégâts importants peuvent alors se produire. Des contrôles sanitaires fréquents sont nécessaires pour la conduite de la méthode de lutte intégrée, généralement adoptée à présent en défense des cultures, ce qui suppose une bonne connaissance des ravageurs, de leur biologie et de leurs ennemis naturels. Comme pour le palmier à huile, il y a deux types de contrôles phytosanitaires : - les contrôles ordinaires, décrits dans ces " Conseils ", qui permettent de suivre l'ensemble des populations de ravageurs, d'insectes auxiliaires, et de détecter toute anomalie susceptible de se traduire par des dégâts préjudiciables ; - les contrôles spéciaux, spécifiques d'un ravageur donné, qui feront l'objet d'une autre page de Pratique agricole (1 ), et sont réalisés sur un échantillon d'observation plus important. Ils permettent de suivre plus précisément l'évolution de ce ravageur, l'intensité et l'étendue des dégâts qu'il provoque. Toutefois, la décision d'intervention par traitement ne peut être prise à bon escient qu'après examen attentif des résultats d'un ou de plusieurs contrôles spéciaux réalisés après détection de l'attaque par un contrôle ordinaire. La présente " Page de pratique agricole " traite de la conduite des contrôles phytosanitaires en cocoteraie de plus de quatre ans, entrée en production. La surveillance des jeunes cocoteraies, beaucoup plus vulnérables, fera également l'objet d'autres " Conseils ". (Résumé d'auteur
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