Involvement of Protein Kinase C and Protein Kinase A in the Enhancement of L-type Calcium Current by GABA\u3csub\u3eB\u3c/sub\u3e Receptor Activation in Neonatal Hippocampus

In the early neonatal period activation of GABAB receptors attenuates calcium current through N-type calcium channels while enhancing current through L-type calcium channels in rat hippocampal neurons. The attenuation of N-type calcium current has been previously demonstrated to occur through direct interactions of the βγ subunits of Gi/o G-proteins, but the signal transduction pathway for the enhancement of L-type calcium channels in mammalian neurons remains unknown. In the present study, calcium currents were elicited in acute cultures from postnatal day 6–8 rat hippocampi in the presence of various modulators of protein kinase A (PKA) and protein kinase C (PKC) pathways. Overnight treatment with an inhibitor of Gi/o (pertussis toxin, 200 ng/ml) abolished the attenuation of calcium current by the GABAB agonist, baclofen (10 μM) with no effect on the enhancement of calcium current. These data indicate that while the attenuation of N-type calcium current is mediated by the Gi/o subtype of G-protein, the enhancement of L-type calcium current requires activation of a different G-protein. The enhancement of the sustained component of calcium current by baclofen was blocked by PKC inhibitors, GF-109203X (500 nM), chelerythrine chloride (5 μM), and PKC fragment 19–36 (2 μM) and mimicked by the PKC activator phorbol-12-myristate-13-acetate (1 μM). The enhancement of the sustained component of calcium current was blocked by PKA inhibitors H-89 (1 μM) and PKA fragment 6–22 (500 nM) but not Rp-cAMPS (30 μM) and it was not mimicked by the PKA activator, 8-Br-cAMP (500 μM–1 mM). The data suggest that activation of PKC alone is sufficient to enhance L-type calcium current but that PKA may also be involved in the GABAB receptor mediated effect

Modulation of L-type Calcium Current by GABA-B Receptor Activation in the Neonatal Rat Hippocampus

During the early postnatal period, the inhibitory neurotransmitter γ-aminobutyric acid (GABA) facilitates current through voltage-dependent L-type calcium channels by activating metabotropic GABAB receptors in the rat hippocampus. In the present study, the effects of the GABAB receptor agonist baclofen on L-type currents were tested using whole-cell voltage clamp recording on neurons isolated from the superior region of hippocampi obtained from pups of various ages to determine the exact time course of L-type current facilitation. The facilitation of L-type current by GABAB receptors is more prominent during the second week of development. One developmental process that L-type current may be involved in is changes in the expression of the K+Cl- co-transporter (KCC2) and N+K+2Cl- co-transporter (NKCC1), which are necessary in the maturation of the GABAergic system. To investigate whether calcium influx through L-type channels and GABAB receptor activation affects the expression of chloride transporters during the early neonatal period, hippocampal cultures isolated from day 0 pups were treated with a GABAB agonist or an L-type channel antagonist for one week. Steady state KCC2 and NKCC1 levels were determined by Western blot analysis. Blockade of L-type channels drastically reduced KCC2 expression but not NKCC1 expression, suggesting that the upregulation of KCC2 in the first postnatal week is dependent on calcium influx through L-type channels. The involvement of protein kinase C (PKC) and A (PKA) in the signaling pathway of L-type current modulation by GABAB receptors was also investigated using electrophysiological experiments. The facilitatory response of baclofen was blocked in the presence of PKC inhibitors, but not PKA inhibitors. Direct activation of PKC using a phorbol ester mimicked the facilitation of L-type current seen with baclofen, whereas facilitation was not seen with direct activation of PKA with a cAMP analogue. Together, these experiments have demonstrated that the facilitation of L-type current by GABAB receptor activation is maximal during the second postnatal week in development and is mediated by PKC. In addition, calcium influx through L-type channels also contributes to the maturation of the GABAergic system

Best Practice for Providing Social Care and Support to People Living with Concurrent Sight Loss and Dementia: Professional Perspectives

Purpose-Approximately 100,000 people in the UK aged 75 and over have concurrent dementia and sight loss, but current understanding of their experiences, needs and preferences is limited. The purpose of this paper is to report on a research project that explored the provision of social care and support for older people with both conditions. Design/methodology/approach-The project was a collaboration between the universities of York, Worcester, Bournemouth and Cambridge, supported by the Thomas Pocklington Trust and the Housing and Dementia Research Consortium. Data for this paper were drawn from focus groups held in 2013 involving 47 professionals across the dementia, sight loss and housing sectors. Findings-Thematic analysis identified five main barriers to providing high-quality, cost-effective social care and support: time constraints; financial limitations; insufficient professional knowledge; a lack of joint working; and inconsistency of services. The requirements of dementia and sight loss often conflict, which can limit the usefulness of equipment, aids and adaptations. Support and information needs to address individual needs and preferences. Research limitations/implications-Unless professionals consider dementia and sight loss together, they are unlikely to think about the impact of both conditions and the potential of their own services to provide effective support for individuals and their informal carers. Failing to consider both conditions together can also limit the availability and accessibility of social care and support services. This paper is based on input from a small sample of self-selecting professionals across three geographical regions of England. More research is needed in this area. Practical implications-There are growing numbers of people living with concurrent dementia and sight loss, many of whom wish to remain living in their own homes. There is limited awareness of the experiences and needs of this group and limited provision of appropriate services aids/adaptations. A range of measures should be implemented in order to support independence and well-being for people living with both conditions and their family carers. These include increased awareness, improved assessment, more training and greater joint working. Social implications-People living with dementia or sight loss are at high risk of social isolation, increasingly so for those with both conditions. Services that take an inclusive approach to both conditions can provide crucial opportunities for social interaction. Extra care housing has the potential to provide a supportive, community-based environment that can help residents to maintain social contact. Originality/value-This paper adds much-needed evidence to the limited existing literature, and reflects the views of diverse professionals across housing, health and social car

Influence of charge on filtration across renal basement membrane films in vitro

AbstractInfluence of charge on filtration across renal basement membrane films in vitro. The filtration of differently charged species of myoglobin and dextran across films of isolated basement membrane in vitro showed that the filtration behavior of both polymers was influenced by charge. Rejection increased with increasing negative charge. Titration of the isolated basement membrane revealed an isoionic point of pH 5.5 and an isoelectric point of pH 5.7. The net negative charge at pH 7.4 was 0.15 mEq/g protein; this charge was attributed to carboxylate anion. Glycosaminoglycan sulphate did not contribute significantly to the net charge. Filtration of narrow range dextran fractions across films of basement membrane at the isoelectric point markedly reduced differences in filtration due to charge confirming that the differences in behavior found at pH 7.4 were due to charge interactions between the solutes and the membranes. Physical characterization of the charged and uncharged dextran fractions revealed no substantial differences in size or shape for the differently charged species.Influence de la charge sur la filtration à travers des films de membrane basale rénale in vitro. La filtration d'espèces différemment chargées de myoglobine et de dextran à travers des films de membrane basale isolée in vitro a montré que le comportement de filtration des deux polymères était influencé par la charge. Le rejet s'élevait lorsque la charge négative augmentait. La titration de la membrane basale isolée a révélé un point isoionique de pH 5,5 et un point isoélectrique de pH 5,7. La charge négative nette à pH 7,4 était de 0,15 mEq/g protéines; cette charge a été attribuée à l'anion carboxylate. Le sulfate de glycosaminoglycan ne contribuait pas significativement à la charge nette. La filtration de fractions d'étendues étroites de dextran à travers des films de membrane basale au point isoélectrique réduisait de façon marquée les différences de filtration dûes à la charge, confirmant que ses différences de comportement trouvées à pH 7,4 étaient dûes à des interactions de charge entre les solutes et les membranes. La caratérisation physique des fractions de dextran chargées ou non n'a pas révélé de différence substantielle dans la taille ou la forme des espèces de charges différentes

How Do Learning Communities Affect First-Year Latino Students?

Do learning communities with pedagogies of active learning, collaborative learning, and integration of course material affect the learning, achievement, and persistence of first-year Latino university students? The data for this project was obtained from a survey of 1,330 first-year students in the First-Year Learning Community Program at Texas A&M University-Corpus Christi in fall 2005. Using survey data combined with student background characteristics and multivariate analyses, the findings reveal that learning communities had a positive effect on all students’ first semester GPA, and that learning community practices, especially collaborative learning, benefit Latino students. The study also proposes a technique for estimating the impact of learning communities on Latino students

Criando Coerência a partir de Mensagens Políticas Complexas: Perceção dos Educadores de Educação Especial e Políticas de Accountability baseadas em Standards

Federal special education and accountability policies requires that educators individualize instruction for students with disabilities, while simultaneously ensuring that the vast majority of these students meet age-based grade-level standards and assessment targets. In this paper, we examine this dynamic interplay between policies through analysis of policy documents and interviews that reveal how a sample of educators grapple with their simultaneous implementation. We found that educators made sense of some facets of the policies as complementary and others as contradictory. NCLB and IDEA offered consistent and specific guidelines defining “highly qualified” teachers and educators reported a clear and accurate understanding of these policy demands. On an issue where there was no specific guidance from NCLB–the placement of special education students–educators interpreted the law as promoting the inclusion of more students in general education courses, often to an extent that contradicted the guidance offered by IDEA. With respect to fundamental issues of teaching and learning, NCLB and IDEA represent contradictory theories of action and educators perceived conflict and expressed concerns about unintended consequences for students. Based on our empirical findings, we conclude with a set of theoretical propositions regarding how the alignment of policy messages influences educators’ interpretation of policies, which in turn may have implications for how they enact policies.  Las políticas nacionales para la educación especial y la rendición de cuentas (accountability) requiere que los educadores individualicen la instrucción para los estudiantes con discapacidades, garantizando al mismo tiempo que la mayoría de estos estudiantes puedan alcanzar los estándares basados en su edad, nivel de educación y los objetivos de la evaluación. En este artículo se discute la interacción dinámica entre las políticas a través del análisis de documentos de política y entrevistas que revelan cómo una muestra de educadores se encarga de su ejecución simultánea. Se encontró que algunos educadores interpretan estas facetas como complementarias de las políticas y otras como de índole contradictoria. Las directivas de NCLB (Ley No Child Left Behind) e IDEA (Individuals with Disabilities Education Act - Ley para los Individuos con Discapacidades) proporcionan directrices para la definición consistente y específica de que es un docente "altamente calificado" y los educadores y reportaron una comprensión clara y precisa de estas demandas políticas. En una materia para la cual no había una orientación específica de NCLB - la ubicación de los estudiantes de educación especial - educadores han interpretado la ley como promoviendo la inclusión de todos los estudiantes en los cursos de educación general, a menudo de una manera que contradice las orientaciones dadas por IDEA. Para las cuestiones fundamentales de la enseñanza y el aprendizaje, NCLB e IDEA representan teorías contradictorias de acción y educadores perciben el conflicto y expresan sus preocupaciones acerca de las consecuencias no deseadas para los estudiantes. En base a los resultados empíricos, se concluye con un conjunto de proposiciones teóricas acerca de cómo alinear los mensajes políticos que influyen en la interpretación de la política por los educadores, que a su vez pueden tener implicaciones en cómo se implementan las políticas.Políticas nacionais de educação especial e de accountability requerem que os educadores individualizem o ensino para alunos com deficiências, assegurando, simultaneamente, que a maioria desses alunos atinge os standards baseados na idade e nível de ensino e as metas da avaliação. Neste artigo, analisámos esta interação dinâmica entre políticas através da análise de documentos políticos e entrevistas que revelam como uma amostra de educadores lida com a sua simultânea implementação. Descobrimos que os educadores interpretaram algumas facetas das políticas como complementares e outras como contraditórias. NCLB (No Child Left Behind Act – Ato Nenhuma criança deixada para trás) e IDEA (Individuals with Disabilities Education Act – Ato para a Educação de Indivíduos com Deficiências) fornecem orientações consistentes e específicas para a definição de professores “altamente qualificados” e os educadores relataram um entendimento claro e preciso dessas demandas políticas. Num assunto para o qual não havia nenhuma orientação específica a partir do NCLB – a colocação dos alunos de educação especial – os educadores interpretaram a lei como promovendo a inclusão de mais alunos em cursos de educação geral, de uma forma que frequentemente contradiz a orientação fornecida pelo IDEA. Relativamente a questões fundamentais de ensino e aprendizagem, NCLB e IDEA representam teorias de ação contraditórias e os educadores percebem o conflito e expressam preocupações sobre as consequências não intencionais para os alunos. Com base nos nossos resultados empíricos, concluímos com um conjunto de proposições teóricas a respeito do modo como o alinhamento de mensagens políticas influencia a interpretação das políticas pelos educadores, que por sua vez pode ter implicações na forma como eles adotam as políticas

Practice of Namaste Care for People Living with Dementia in the UK

Originating in the US, Namaste Care aims to improve quality of life for people with advanced dementia. However, recognition in the UK is sparse. This article reports on research that aims to create consistent understanding of the purpose, application and effect of Namaste Care. Using an online survey, telephone interviews and discussion group with UK practitioners we explored Namaste Care practice, its components and implementation challenges. Findings show that Namaste Care has potential to improve quality of life in advanced dementia and is held in high regard by practitioners. However, understanding is inconsistent and practical implementation highly varied

Dementia Carers Count: Evaluation of the Dementia Carer's Support Courses

Dementia Carer's Support Courses: Impact Repor

The Admiral Nurse Competency Framework: Encouraging Engagement and Putting it into Practice

BACKGROUND: Admiral Nurses undertake complex work with families living with dementia. Dementia UK commissioned The Association for Dementia Studies to refresh the Admiral Nurse Competency Framework and enable Admiral Nurses to articulate and critically reflect on their own practice progression. The Admiral Nurses were involved throughout the process to refresh the framework to ensure it was evidence based. METHOD: To encourage engagement with the framework, The Association for Dementia Studies worked with the Admiral Nurses during a roll-out phase. An exercise was developed to initiate critical reflective discussion. Critiquing a colleague's practice is a skill, provoking defensiveness if not facilitated thoughtfully. RESULTS: An exercise combining art cards with case study analysis worked well, promoting critical reflective dialogue between Admiral Nurses as peers. Engagement and feedback were positive, and the neutrality of the exercise provided a safe environment with the flexibility to allow in-depth and meaningful discussions. CONCLUSION: This technique could benefit work-based learning, facilitating creative critical reflection within practice