Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70

Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-gamma-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-gamma expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-gamma production, but also the protective function of iNKT cells in arthritis

La adhesión de las enfermeras al Método Canguro: subvención para la administración del cuidado de enfermería

;;OBJETIVO:;; construir um modelo teórico explicativo acerca da adesão das enfermeiras ao Método Canguru na Unidade de Terapia Intensiva Neonatal, a partir dos significados e interações para a gerência do cuidado.;;;;MÉTODO:;; pesquisa qualitativa, guiada pelo referencial da Grounded Theory. Foram entrevistadas oito enfermeiras de uma Unidade de Terapia Intensiva Neonatal da cidade do Rio de Janeiro. A análise comparativa dos dados percorreu as etapas de codificação aberta, axial e seletiva, sendo construído um modelo teórico do tipo condicional-causal.;;;;RESULTADOS:;; emergiram quatro categorias principais que compuseram o paradigma de análise: Vestindo a camisa do Método Canguru; Trabalhando com a complexidade do Método Canguru; Encontrando (des)motivação para aplicar o Método Canguru; e Deparando-se com os desafios para a adesão e aplicação do Método Canguru.;;;;CONCLUSÕES:;; o fenômeno central revelou que cada enfermeira e profissional da equipe possui um papel de multiplicador de valores e práticas que podem ou não ser construtivas, influenciando potencialmente na (des)continuidade do Método Canguru na Unidade de Terapia Intensiva Neonatal. Os achados podem ser utilizados para o delineamento de estratégias gerenciais que ultrapassem os cursos e treinamentos e garantam o fortalecimento do modelo assistencial.;;;;OBJECTIVE:;; construct an explanatory theoretical model about nurses' adherence to the Kangaroo Care Method at the Neonatal Intensive Care Unit, based on the meanings and interactions for care management.;;;;METHOD:;; qualitative research, based on the reference framework of the Grounded Theory. Eight nurses were interviewed at a Neonatal Intensive Care Unit in the city of Rio de Janeiro. The comparative analysis of the data comprised the phases of open, axial and selective coding. A theoretical conditional-causal model was constructed.;;;;RESULTS:;; four main categories emerged that composed the analytic paradigm: Giving one's best to the Kangaroo Method; Working with the complexity of the Kangaroo Method; Finding (de)motivation to apply the Kangaroo Method; and Facing the challenges for the adherence to and application of the Kangaroo Method.;;;;CONCLUSIONS:;; the central phenomenon revealed that each nurse and team professional has a role of multiplying values and practices that may or may not be constructive, potentially influencing the (dis)continuity of the Kangaroo Method at the Neonatal Intensive Care Unit. The findings can be used to outline management strategies that go beyond the courses and training and guarantee the strengthening of the care model.;;;;OBJETIVO:;; construir un modelo teórico explicativo acerca de la adhesión de las enfermeras al Método Canguro en la Unidad de Terapia Intensiva Neonatal, a partir de los significados e interacciones para la administración del cuidado.;;;;MÉTODO:;; investigación cualitativa, guiada por el referencial de la Grounded Theory. Fueron entrevistadas ocho enfermeras de una Unidad de Terapia Intensiva Neonatal de la ciudad de Rio de Janeiro. El análisis comparativo de los datos recorrió las etapas de codificación abierta, axial y selectiva, siendo construido un modelo teórico del tipo condicional-causal.;;;;RESULTADOS:;; surgieron cuatro categorías principales que compusieron los paradigmas del análisis: Vistiendo la camisa del Método Canguro; Trabajando con la complejidad del Método Canguro; Encontrando (des)motivación para aplicar el Método Canguro; y Encontrando los desafíos para la adhesión y aplicación del Método Canguro.;;;;CONCLUSIONES:;; el fenómeno central reveló que cada enfermera y profesional del equipo posee un papel de multiplicador de valores y prácticas que pueden o no ser constructivas, influenciando potencialmente en la (des)continuidad del Método Canguro en la Unidad de Terapia Intensiva Neonatal. Los hallazgos pueden ser utilizados para el delineamiento de estrategias de administración que sobrepasen los cursos y entrenamientos y garanticen el fortalecimiento del modelo asistencial.;

A Review of Pharmacologic Treatment for Compulsive Buying Disorder

At present, no treatment recommendations can be made for compulsive buying disorder. Recent studies have found evidence for the efficacy of psychotherapeutic options, but less is known regarding the best pharmacologic treatment. The purpose of this review is to present and analyze the available published evidence on the pharmacological treatment of compulsive buying disorder. To achieve this, we conducted a review of studies focusing on the pharmacological treatment of compulsive buying by searching the PubMed/MEDLINE database. Selection criteria were applied, and 21 studies were identified. Pharmacological classes reported included antidepressants, mood stabilizers, opioid antagonists, second-generation antipsychotics, and N-methyl-D-aspartate receptor antagonists. We found only placebo-controlled trials for fluvoxamine; none showed effectiveness against placebo. Three open-label trials reported clinical improvement with citalopram; one was followed by a double-blind discontinuation. Escitalopram was effective in an open-label trial but did not show efficacy in the double-blind phase. Memantine was identified as effective in a pilot open-label study. Fluoxetine, bupropion, nortriptyline, clomipramine, topiramate and naltrexone were only reported to be effective in clinical cases. According to the available literature, there is no evidence to propose a specific pharmacologic agent for compulsive buying disorder. Future research is required for a better understanding of both pathogenesis and treatment of this disorder.info:eu-repo/semantics/publishedVersio

A realist synthesis of randomised control trials involving use of community health workers for delivering child health interventions in low and middle income countries

<p>Abstract</p> <p>Background</p> <p>A key constraint to saturating coverage of interventions for reducing the burden of childhood illnesses in Low and Middle Income Countries (LMIC) is the lack of human resources. Community health workers (CHW) are potentially important actors in bridging this gap. Evidence exists on effectiveness of CHW in management of some childhood illnesses (IMCI). However, we need to know how and when this comes to be. We examine evidence from randomized control trials (RCT) on CHW interventions in IMCI in LMIC from a realist perspective with the aim to see if they can yield insight into the working of the interventions, when examined from a different perspective.</p> <p>Methods</p> <p>The realist approach involves educing the mechanisms through which an intervention produced an outcome in a particular context. 'Mechanisms' are reactions, triggered by the interaction of the intervention and a certain context, which lead to change. These are often only implicit and are actually hypothesized by the reviewer. This review is limited to unravelling these from the RCTs; it is thus a hypothesis generating exercise.</p> <p>Results</p> <p>Interventions to improve CHW performance included 'Skills based training of CHW', 'Supervision and referral support from public health services', 'Positioning of CHW in the community'. When interventions were applied in context of CHW programs embedded in local health services, with beneficiaries who valued services and had unmet needs, the interventions worked if following mechanisms were triggered: anticipation of being valued by the community; perception of improvement in social status; sense of relatedness with beneficiaries and public services; increase in self esteem; sense of self efficacy and enactive mastery of tasks; sense of credibility, legitimacy and assurance that there was a system for back-up support. Studies also showed that if context differed, even with similar interventions, negative mechanisms could be triggered, compromising CHW performance.</p> <p>Conclusion</p> <p>The aim of this review was to explore if RCTs could yield insight into the working of the interventions, when examined from a different, a realist perspective. We found that RCTs did yield some insight, but the hypotheses generated were very general and not well refined. These hypotheses need to be tested and refined in further studies.</p