Fluoxetine exerts anti-inflammatory effects on human epidermal keratinocytes and suppresses their endothelin release.

Fluoxetine is a safe antidepressant with remarkable anti-inflammatory actions; therefore, we aimed to investigate its effects on immortalized (HaCaT) as well as primary human epidermal keratinocytes in a polyinosinic-polycytidylic acid (p(I:C))-induced inflammatory model. We found that a non-cytotoxic concentration (MTT-assay, CyQUANT-assay) of fluoxetine significantly suppressed p(I:C)-induced expression and release of several pro-inflammatory cytokines (Q-PCR, cytokine array, ELISA), and it decreased the release of the itch mediator endothelins (ELISA). These effects were not mediated by the inhibition of the NF-κB or p38 MAPK pathways (western blot), or by the suppression of the p(I:C)-induced elevation of mitochondrial ROS production (MitoSOX Red labeling). Instead, unbiased activity profiling revealed that they were most likely mediated via the inhibition of the phosphoinositide 3-kinase (PI3K) pathway. Importantly, the PI3K-inhibitor GDC0941 fully mimicked the effects of fluoxetine (Q-PCR, ELISA). Although fluoxetine was able to occupy the binding site of GDC0941 (in silico molecular docking), and exerted direct inhibitory effect on PI3K (cell-free PI3K activity assay), it exhibited much lower potency and efficacy as compared to GDC0941. Finally, RNA-Seq analysis revealed that fluoxetine deeply influenced the transcriptional alterations induced by p(I:C)-treatment, and exerted an overall anti-inflammatory activity. Collectively, our findings demonstrate that fluoxetine exerts potent anti-inflammatory effects, and suppresses the release of the endogenous itch mediator endothelins in human keratinocytes, most likely via interfering with the PI3K pathway. Thus, clinical studies are encouraged to explore whether the currently reported beneficial effects translate in vivo following its topical administration in inflammatory and pruritic dermatoses.

Nurses' Perceptions of Caring at Work: Mixed-Methods Study, Quantitative Report.

OBJECTIVES: Study objectives were to explore nurses' perceptions of self-care, co-worker, and leader caring within healthcare work environments and assess reliability of 3 Watson Caritas Scores. BACKGROUND: Assessing caring in an organization where Watson's Theory of Human Caring guides nursing practice offers insight into the professional practice environment. METHOD: This study reports quantitative data from mixed-methods descriptive, cross-sectional survey of 1307 RNs at a large healthcare system. RESULTS: Mean scores were self = 5.46, co-worker = 5.39, and leader score = 5.53, and median scores were >5.6 (range, 1-7). All scales had a positive and significant correlation to likelihood to recommend the organization, with the largest being feeling cared for by leaders. Internal reliability of the 3 scales was ≥0.9. CONCLUSION: Nurse perceptions of caring may influence the organization's reputation. Assessing the perception of caring among nursing staff after the introduction and enculturation of this framework is needed. Results support psychometric value for 3 Watson Caritas Scores.

Biochar and vegetation effects on discharge water quality from organic-substrate green roofs.

Green roofs have been increasingly used to improve stormwater management, but poor vegetation performance on roof systems, varying with vegetation type, can degrade discharge quality. Biochar has been suggested as an effective substrate additive for green roofs to improve plant performance and discharge quality. However, research on the effects of biochar and vegetation on discharge quality in the long term is lacking and the underlying mechanisms involved are unclear. We examined the effects of biochar amendment and vegetation on discharge quality on organic-substrate green roofs with pre-grown sedum mats and direct-seeded native plants for three years and investigated the key factors influencing discharge quality. Sedum mats reduced the leaching of nutrients and particulate matter by 6-64% relative to native plants, largely due to the higher initial vegetation cover of the former. Biochar addition to sedum mat green roofs resulted in the best integrated water quality due to enhanced plant cover and sorption effects. Structural equation modeling revealed that nutrient leaching was primarily influenced by rainfall depth, time, vegetation cover, and substrate pH. Although biochar-amended sedum mats showed better discharge quality from organic-substrate green roofs, additional ecosystem services may be provided by native plants, suggesting future research to optimize plant composition and cover and biochar properties for sustainable green roofs.

Stakeholder perceptions of a total market approach to family planning in Nicaragua / Percepciones de grupos interesados sobre la aplicación de un enfoque de mercado total a la planificación familiar en Nicaragua

OBJECTIVE: To assess private-sector stakeholders' and donors' perceptions of a total market approach (TMA) to family planning in Nicaragua in the context of decreased funding; to build evidence for potential strategies and mechanisms for TMA implementation (including public-private partnerships (PPPs)); and to identify information gaps and future priorities for related research and advocacy. METHODS: A descriptive exploratory study was conducted in various locations in Nicaragua from March to April 2010. A total of 24 key private-sector stakeholders and donors were interviewed and their responses analyzed using two questionnaires and a stakeholder analysis tool (PolicyMakerTM software). RESULTS: All survey participants supported a TMA, and public-private collaboration, in family planning in Nicaragua. Based on the survey responses, opportunities for further developing PPPs for family planning include building on and expanding existing governmental frameworks, such as Nicaragua's current coordination mechanism for contraceptive security. Obstacles include the lack of ongoing government engagement with the commercial (for-profit) sector and confusion about regulations for its involvement in family planning. Strategies for strengthening existing PPPs include establishing a coordination mechanism specifically for the commercial sector and collecting and disseminating evidence supporting public-private collaboration in family planning. CONCLUSIONS: There was no formal or absolute opposition to a TMA or PPPs in family planning in Nicaragua among a group of diverse nongovernmental stakeholders and donors. This type of study can help identify strategies to mobilize existing and potential advocates in achieving articulated policy goals, including diversification of funding sources for family planning to achieve contraceptive security.

OBJETIVO: Evaluar las percepciones de los grupos interesados y de los donantes del sector privado sobre la aplicación de un enfoque de mercado total a la planificación familiar en Nicaragua en el contexto de una reducción del financiamiento; establecer datos científicos que avalen posibles estrategias y mecanismos para ejecutar este tipo de enfoque (lo que incluye alianzas entre los sectores público y privado); y determinar las brechas de información y las prioridades futuras en la investigación y la promoción de este enfoque. MÉTODOS: Entre marzo y abril del 2010 se llevó a cabo un estudio exploratorio descriptivo en varios lugares de Nicaragua. Se entrevistaron 24 personas de varios grupos interesados y de donantes clave del sector privado y se analizaron sus respuestas mediante dos cuestionarios y una herramienta de análisis específica (programa informático PolicyMakerTM). RESULTADOS: Todos los encuestados respaldaron la aplicación de un enfoque de mercado total y la colaboración entre los sectores público y privado respecto de la planificación familiar en Nicaragua. Según las respuestas obtenidas en la encuesta, las oportunidades para desarrollar alianzas adicionales entre los dos sectores respecto de la planificación familiar incluyen mejorar y ampliar los marcos gubernamentales existentes, como el actual mecanismo de coordinación de Nicaragua para la seguridad anticonceptiva. Los obstáculos son la falta de colaboración actual del gobierno con el sector comercial (con fines de lucro) y la confusión acerca de la reglamentación para participar en la planificación familiar. Las estrategias para fortalecer las alianzas existentes entre los sectores público y privado comprenden el establecimiento de un mecanismo de coordinación específico para el sector comercial, y la recolección y difusión de datos que avalen la colaboración entre los dos sectores respecto de la planificación familiar. CONCLUSIONES: En la evaluación de varios grupos interesados y de donantes del sector no gubernamental no se encontró ninguna oposición formal o absoluta a un enfoque de mercado total o a la conformación de alianzas entre los sectores público y privado respecto de la planificación familiar en Nicaragua. Este tipo de estudio puede ayudar a identificar estrategias que motiven a los promotores de la causa actuales y potenciales a alcanzar las metas políticas enunciadas, lo que incluye la diversificación de las fuentes de financiamiento para la planificación familiar a fin de alcanzar la seguridad anticonceptiva.

Formative research to shape HPV vaccine introduction strategies in Peru / Investigación formativa relacionada con el diseño de estrategias para introducir la vacuna contra el VPH en Perú

OBJECTIVE: To understand the sociocultural environment, health systems' capacities, and policy processes related to cervical cancer and HPV vaccines in order to inform HPV vaccine introduction. MATERIAL AND METHODS: Mixed-method formative research using qualitative and quantitative data collection techniques. Participants included girls, parents, community leaders, health and education officials, and policymakers. RESULTS: Respondents, including policymakers, generally supported HPV vaccine introduction, due partly to appreciation for the benefits of vaccination and the desire to prevent cancer. Community-level concerns regarding safety and quality of services will need to be addressed. The immunization system in Peru is strong and has capacity for including the HPV vaccine. CONCLUSION: Formative research provides key insights to help shape an effective program for HPV vaccine introduction.

OBJETIVO: Comprender el contexto sociocultural, las capacidades del sistema de salud y las condiciones políticas vinculadas al cáncer cervical y a la vacuna contra el VPH para diseñar una estrategia apropiada de introducción de la vacuna contra el VPH. MATERIAL Y MÉTODOS: Investigación formativa usando técnicas cualitativas y cuantitativas. Los participantes incluyeron niños, padres, líderes, funcionarios del sector salud y educación, y diseñadores de políticas. RESULTADOS: Generalmente se apoya la introducción de la vacuna contra el VPH, dado que se aprecian los beneficios de la vacunación y se desea prevenir el cáncer. En la comunidad se encontraron preocupaciones sobre seguridad, confianza y calidad de atención. El sistema de inmunizaciones en el Perú es eficiente y tiene la capacidad para incluir la vacuna contra el VPH. CONCLUSIONES: La investigación formativa permite comprender elementos clave que ayudan a diseñar un programa efectivo para la introducción de la vacuna contra el VPH.