Adaptive Immune Response to Mycobacterium abscessus Complex (MABSC) in Cystic Fibrosis and the Implications of Cross-Reactivity.

Background: We aimed to characterise the adaptive immune response to Mycobacterium abscessus complex (MABSC) and its cross-reactivity with Mycobacterium avium complex (MAC) and Mycobacterium bovis (Bacille Calmette-Guérin, BCG) in cystic fibrosis (CF) patients and non-CF controls in terms of lymphocyte proliferation and immunophenotyping, cytokine production and anti-MABSC IgG plasma levels. Methods: In this cross-sectional analysis, peripheral blood mononuclear cells (PBMC) from CF patients with MABSC (CF/MABSC, n=12), MAC infection history (CF/MAC, n=5), no NTM history (CF/NTM-, n=15), BCG-vaccinated (C/BCG+, n=9) and non-vaccinated controls (C/BCG-, n=8) were cultured for four days under stimulation with an in-house MABSC lysate and we used flow cytometry to assess lymphocyte proliferation (given by lymphoblast formation) and immunophenotypes. Cytokine production was assessed after overnight whole blood stimulation with the same lysate, and anti-MABSC IgG levels were measured in plasma from non-stimulated blood. Results: All CF/MABSC patients had increased CD3+ and CD19+ lymphoblast formation upon PBMC stimulation with MABSC lysate. There was a higher rate of CD3+ than CD19+ lymphoblasts, predominance of CD4+ over CD8+ lymphoblasts, IFN-γ, TNF-α and IL-2 production, low production of the Th17-associated IL-17, and discrete or no production of Th2/B cell-associated cytokines soluble CD40 ligand (CD40L), IL-4 and IL-5, indicating a Th1-dominated phenotype and infection restricted to the lungs. A similar pattern was seen in C/BCG+ controls, and CF/MAC patients, pointing to cross-reactivity. MABSC-IgG levels were higher in CF/MABSC patients than in both control groups, but not CF/NTM- patients, most of whom also had CD3+ and/or CD19+ lymphoblast formation upon PBMC stimulation, indicating previous exposure, subclinical or latent infection with MABSC or other NTM. Conclusion: The anti-MABSC immune response is Th1-skewed and underlines the cross-reactivity in the anti-mycobacterial immune response. The results, together with published clinical observations, indicate that BCG vaccination may cross-react against NTM in CF patients, and this should be investigated. Due to cross-reactivity, it would also be interesting to investigate whether a combination of MABSC-induced cytokine production by blood cells and anti-MABSC IgG measurement can be useful for identifying latent or subclinical infection both with MABSC and other NTM in CF patients.

Mechanisms of humoral immune response against Pseudomonas aeruginosa biofilm infection in cystic fibrosis.

P. aeruginosa chronic lung infection is the major cause of morbidity and mortality in patients with cystic fibrosis (CF), and is characterized by a biofilm mode of growth, increased levels of specific IgG antibodies and immune complex formation. However, despite being designed to combat this infection, such elevated humoral response is not associated with clinical improvement, pointing to a lack of anti-pseudomonas effectiveness. The mode of action of specific antibodies, as well as their structural features, and even the background involving B-cell production, stimulation and differentiation into antibody-producing cells in the CF airways are poorly understood. Thus, the aim of this review is to discuss studies that have addressed the intrinsic features of the humoral immune response and provide new insights regarding its insufficiency in the CF context.

Draft Genome Sequence of Hymenobacter sp. Strain AT01-02, Isolated from a Surface Soil Sample in the Atacama Desert, Chile.

Here, we report the 5.09-Mb draft genome sequence of Hymenobacter sp. strain AT01-02, which was isolated from a surface soil sample in the Atacama Desert, Chile. The isolate is extremely resistant to UV-C radiation and is able to accumulate high intracellular levels of Mn/Fe.

Diffusion of efficacious interventions for children and adolescents with mental health problems.

BACKGROUND: Child and adolescent mental health problems are prevalent and require adequate interventions. Despite several evidence-based interventions for these problems described in the literature, few studies addressed strategies to diffuse efficacious interventions for child mental disorders especially in developing countries. METHODS: An extensive but not systematic review of the literature was performed aiming to identify evidence-based interventions for children and adolescents with mental disorders, professionals to target in disseminating these interventions, and the available strategies to diffuse information. RESULTS: Substantial evidence-based information is available to guide preventive, psychosocial and psychopharmacological interventions. The effectiveness of treatments in real-world settings and the cost-effectiveness of interventions are rarely tested. Professionals at different levels (teachers, school counselors, social workers, general practitioners, pediatricians, child psychologists and psychiatrists) should be targeted in diffusing efficacious interventions for child mental health problems worldwide. Telepsychiatry and the internet seem to be the most promising strategies to diffuse knowledge with lower costs. CONCLUSIONS: Medical and allied professionals must incorporate child and adolescent mental health issues in their under- and postgraduate curricula, and be better prepared to critically evaluate available information. Professionals need to disseminate evidence-based programs to guide parents and teachers in developing countries to deal with child and adolescent difficulties. Countries need to explore internet solutions for dissemination of medical information.

Implementation of evidence-based practices for children in four countries: a project of the World Psychiatric Association.

OBJECTIVE: The present study examined implementation issues in adopting cognitive-behavioral therapies in routine clinical settings in four countries reflecting diverse cultures, languages, settings, and traditions. METHOD: A Director's Systems Survey was administered prior to program implementation and one year later. Therapist ratings on attitudes about evidence-based practices and satisfaction were also gathered. RESULTS: All sites reported successful adoption of the program, although significant variations existed in fiscal support, family involvement, prior experience with cognitive-behavioral therapies, and plans for sustainability. Therapists' ratings indicated overall satisfaction with the implementation of the project. Findings from the Director's Systems Survey pointed to five factors facilitating implementation: 1) early adoption and guidance by innovative leaders (i.e., the Directors); 2) attention to the "fit" between the intervention model and local practices; 3) attention to front-end implementation processes (e.g., cultural adaptation, translation, training, fiscal issues); 4) attention to back-end processes early in the project (e.g., sustainability); and 5) establishing strong relationships with multiple stakeholders within the program setting. CONCLUSIONS: The implementation issues here mirror those identified in other studies of evidence-based practices uptake. Some of the obstacles to implementation of evidence-based practices may be generic, whereas issues such as the impact of political/economic instability, availability of translated materials, constitute unique stressors that differentially affect implementation efforts within specific countries.

Development of adaptable and flexible treatment manuals for externalizing and internalizing disorders in children and adolescents.

In this paper we describe the process used to develop treatment manuals for internalizing and externalizing disorders in children and adolescents. These manuals were developed to offer health care providers and others working in child mental health a flexible intervention that could be adapted to different countries and localities based on: 1) the amount of health care and school resources that are available; 2) the nature and severity of the types of problems children have; and 3) the preferences and cultural factors that are important within these communities. We also discuss the experiences and cultural issues faced by sites in Egypt, Lebanon, Israel, and Brazil who volunteered to implement the manualized treatment programs. The feedback received from these sites indicates that the manuals can be implemented to help children with internalizing and externalizing problems.

Training of evidence-based assessment and intervention approaches in cross-cultural contexts: challenges and solutions.

Dissemination of evidence-based assessment and intervention approaches for child and adolescent with behavioral and/or emotional problems is now a priority in the field worldwide. However, developing staff competence in evidence-based assessment and intervention approaches in different countries is complicated by some environmental and economic constraints. In this paper a distance training/supervision model is discussed. We describe seven specific challenges encountered and solutions used for overcoming the obstacles in order to implement evidence-based assessment and intervention approaches in different sites in Brazil, Egypt, Israel, and Lebanon.

An examination of cross-cultural systems implementing evidence-based assessment and intervention approaches.

Implementation of evidence-based assessment and intervention approaches for youth with behavioral and/or emotional problems is rising to recognition worldwide. Feasibility research is critical to examine what characteristics of systems allow for success or barriers to the implementation of evidence-based practices into real-world settings, especially when working cross-culturally. This paper briefly reviews the experience of 4 international sites to understand how the overall structure and specific site variables directed the implementation of the World Health Organization and the World Psychiatry Association project. Discussion includes a thematic summary of the successes and challenges experienced by the sites, and future directions of feasibility studies.

Implementation of evidence-based practices for children in four countries: a project of the World Psychiatric Association / Implementação de práticas baseadas em evidências para o tratamento de crianças em quatro países: um projeto da Associação Mundial de Psiquiatria

OBJETIVE: The present study examined implementation issues in adopting cognitive-behavioral therapies in routine clinical settings in four countries reflecting diverse cultures, languages, settings, and traditions. METHOD: A Director's Systems Survey was administered prior to program implementation and one year later. Therapist ratings on attitudes about evidence-based practices and satisfaction were also gathered. RESULTS: All sites reported successful adoption of the program, although significant variations existed in fiscal support, family involvement, prior experience with cognitive-behavioral therapies, and plans for sustainability. Therapists' ratings indicated overall satisfaction with the implementation of the project. Findings from the Director's Systems Survey pointed to five factors facilitating implementation: 1) early adoption and guidance by innovative leaders (i.e., the Directors); 2) attention to the "fit" between the intervention model and local practices; 3) attention to front-end implementation processes (e.g., cultural adaptation, translation, training, fiscal issues); 4) attention to back-end processes early in the project (e.g., sustainability); and 5) establishing strong relationships with multiple stakeholders within the program setting. CONCLUSIONS: The implementation issues here mirror those identified in other studies of evidence-based practices uptake. Some of the obstacles to implementation of evidence-based practices may be generic, whereas issues such as the impact of political/economic instability, availability of translated materials, constitute unique stressors that differentially affect implementation efforts within specific countries.

OBJETIVO: Este estudo visa a examinar problemas na implementação de técnicas psicoterápicas cognitivo-comportamentais em ambientes clínicos de atendimento primário em quatro países que refletem diversas culturas, línguas, ambientes e tradições. MÉTODO: Uma pesquisa foi aplicada aos diretores de Sistemas Clínicos antes da implementação do programa e um ano após. Também foram coletados dados sobre como os terapeutas avaliavam as ações relativas à prática baseada em evidências e qual seu grau de satisfação com essa prática. RESULTADOS: Todos os locais de implementação relataram a adoção bem sucedida do programa, ainda que com significativas variações no apoio fiscal, envolvimento familiar, experiência prévia com terapias cognitivo-comportamentais e planos de sustentação em longo prazo. As avaliações dos terapeutas indicaram uma satisfação generalizada com a implementação do projeto. Achados da pesquisa com os diretores dos Sistemas Clínicos apontaram cinco fatores que facilitaram a implementação: 1) rápida adoção e orientação por líderes inovadores (i.e., os diretores); 2) atenção à adequação entre o modelo de intervenção e as práticas locais; 3) atenção desde o início à relação entre os processos de implementação e os usuários finais (e.g., adaptação cultural, tradução, treinamento, problemas fiscais); 4) atenção precoce aos processos de retaguarda do projeto (e.g., sustentação); e 5) estabelecimento de relações estreitas com múltiplos financiadores da instalação do programa. CONCLUSÕES: Os problemas de implementação encontrados neste estudo se assemelham aos identificados em outros estudos sobre a aquisição de práticas baseadas em evidência. Alguns dos obstáculos para a implementação de práticas baseadas em evidência podem ser generalizados, ao passo que problemas como o impacto da instabilidade político-econômica e disponibilidade de materiais traduzidos constituem estressores peculiares que afetam de forma diferenciada os esforços de implementação em cada país.

Development of adaptable and flexible treatment manuals for externalizing and internalizing disorders in children and adolescents / Desenvolvimento de manuais adaptáveis e flexíveis para transtornos de externalização e internalização em crianças e adolescentes

In this paper we describe the process used to develop treatment manuals for internalizing and externalizing disorders in children and adolescents. These manuals were developed to offer health care providers and others working in child mental health a flexible intervention that could be adapted to different countries and localities based on: 1) the amount of health care and school resources that are available; 2) the nature and severity of the types of problems children have; and 3) the preferences and cultural factors that are important within these communities. We also discuss the experiences and cultural issues faced by sites in Egypt, Lebanon, Israel, and Brazil who volunteered to implement the manualized treatment programs. The feedback received from these sites indicates that the manuals can be implemented to help children with internalizing and externalizing problems.

Neste artigo, descrevemos o processo utilizado para elaborar manuais de tratamento para transtornos de externalização e intrnalização em crianças e adolescentes. Esses manuais foram elaborados para oferecer uma intervenção flexível para provedores de atenção à saúde e demais profissionais que trabalham com a saúde mental da criança, podendo ser adaptados a diferentes países e localidades, com base: 1) no nível de atenção médica e de recursos educacionais disponíveis; 2) na natureza e na gravidade dos tipos de problemas que as crianças apresentam; e 3) nas preferências e fatores culturais que são importantes nessas comunidades. Discutimos, também, as experiências e os problemas culturais enfrentados pelas localidades no Egito, Líbano, Israel e Brasil que foram voluntárias em implementar os programas de tratamento especificados nos manuais. O retorno recebido dessas localidades indica que os manuais podem ser implementados para auxiliar as crianças com problemas de externalização e internalização.

Training of evidence-based assessment and intervention approaches in cross-cultural contexts: challenges and solutions / Treinamento de estratégias de intervenção e avaliação baseadas em evidências em contextos transculturais: desafios e soluções

Dissemination of evidence-based assessment and intervention approaches for child and adolescent with behavioral and/or emotional problems is now a priority in the field worldwide. However, developing staff competence in evidence-based assessment and intervention approaches in different countries is complicated by some environmental and economic constraints. In this paper a distance training/supervision model is discussed. We describe seven specific challenges encountered and solutions used for overcoming the obstacles in order to implement evidence-based assessment and intervention approaches in different sites in Brazil, Egypt, Israel, and Lebanon.

A disseminação de estratégias de intervenção e avaliação baseadas em evidências para crianças e adolescentes com problemas comportamentais e/ou emocionais é hoje uma prioridade mundial. No entanto, o desenvolvimento de equipes capacitadas para implementação de estratégias de intervenção e avaliação baseadas em evidências nos diferentes países é limitado por restrições ambientais e econômicas. Neste artigo, discute-se um modelo de treinamento/supervisão à distância. Em seguida, são descritos sete desafios específicos encontrados e as soluções utilizadas para superar os obstáculos para implementação de estratégias de intervenção e avaliação baseadas em evidências em diferentes localidades no Brasil, Egito, Israel e Líbano.

An examination of cross-cultural systems implementing evidence-based assessment and intervention approaches / Exame dos sistemas transculturais que implementam estratégias de intervenção e avaliação baseadas em evidências

Implementation of evidence-based assessment and intervention approaches for youth with behavioral and/or emotional problems is rising to recognition worldwide. Feasibility research is critical to examine what characteristics of systems allow for success or barriers to the implementation of evidence-based practices into real-world settings, especially when working cross-culturally. This paper briefly reviews the experience of 4 international sites to understand how the overall structure and specific site variables directed the implementation of the World Health Organization and the World Psychiatry Association project. Discussion includes a thematic summary of the successes and challenges experienced by the sites, and future directions of feasibility studies.

A implementação de estratégias de intervenção e avaliação baseadas em evidências para jovens com problemas comportamentais e/ou emocionais está assumindo reconhecimento internacional. Estudos de praticabilidade são críticos para examinar quais características dos sistemas permitem êxito ou se constituem em barreiras para a implementação de práticas baseadas em evidências em instituições do mundo real, especialmente quando trabalhando de forma transcultural. Este estudo revisa brevemente a experiência de quatro localidades internacionais para compreender como a estrutura geral e as variáveis específicas da localidade orientaram a implementação do projeto da Organização Mundial de Saúde e da Associação Mundial de Psiquiatria. A discussão inclui um resumo temático dos êxitos e desafios vivenciados pelas localidades e os caminhos futuros de estudos de praticabilidade.