Matrix alkalinization: a novel mitochondrial signal for sustained pancreatic beta-cell activation.

Nutrient secretagogues activate mitochondria of the pancreatic beta-cell through the provision of substrate, hyperpolarisation of the inner mitochondrial membrane and mitochondrial calcium rises. We report that mitochondrial matrix pH, a parameter not previously studied in the beta-cell, also exerts an important control function in mitochondrial metabolism. During nutrient stimulation matrix pH alkalinises, monitored by the mitochondrial targeted fluorescent pH-sensitive protein mtAlpHi or (31)P-NMR inorganic phosphate chemical shifts following saturation transfer. Compared with other cell types, the resting mitochondrial pH was surprisingly low, rising from pH 7.25 to 7.7 during nutrient stimulation of rat beta-cells. As cytosolic alkalinisation to the nutrient was of much smaller amplitude, the matrix alkalinisation was accompanied by a pronounced increase of the DeltapH across the inner mitochondrial membrane. Furthermore, matrix alkalinisation closely correlates with the cytosolic ATP net increase, which is also associated with elevated ATP synthesis rates in mitochondria. Preventing DeltapH increases in permeabilised cells abrogated substrate-driven ATP synthesis. We propose that the mitochondrial pH and DeltapH are key determinants of mitochondrial energy metabolism and metabolite transport important for cell activation.

[Level of evidence for case management in Alzheimer's disease: a literature review]. / Niveau de preuve de la gestion de cas dans la maladie d'Alzheimer : revue de littérature.

Alzheimer's disease or related diseases patients are particularly vulnerable to fragmentation of the French system of care and support. The government has decided to implement a national plan from which two key steps are the implementation of integration and case management. We report results of a review of the literature on both the definition of these concepts and their impacts as reported in randomized controlled studies. Important differences are noticeable between studies concerning the spectrum of integration (acute and long-term care, social and health sectors, institutional and liberal sectors and financing mode notably). Case-management has multiple sense, and it must be paid attention to intensity and context of the intervention. According to available evidence, case management is likely to improve, for the person with Alzheimer's, quality of care, quality of life and quality of life of caregivers at least. Conditions for a program to be successful are adequate targeting of the target population, sufficient level of integration and adequate intensity of case management. The programs most successful and most intensive relate an effect on prevention of loss of autonomy, even death, and no extra cost. The effects on hospitalization or entry into the institution are currently hypothetical and should be further studied.

Cerebral amyloid angiopathy with co-localization of prion protein and beta-amyloid in an 85-year-old patient with sporadic Creutzfeldt-Jakob disease.

We report on an 85-year-old woman with hypertensive cerebral arteriolosclerosis who presented with rapidly progressive encephalopathy leading to death within 4 months. Magnetic resonance imaging showed mild cortical atrophy consistent with her age and diffuse leukoaraiosis. Her CSF 14-3-3 protein was positive. Neuropathology showed severe spongiform change and gliosis in the grey matter and immunohistochemistry revealed diffuse prion protein deposition in a predominant synaptic pattern. She had no family history of neurological disorder and genotyping did not show any prion protein gene mutation, in keeping with a diagnosis of sporadic Creutzfeldt-Jakob disease. There was also diffuse amyloid angiopathy involving the cortical and leptomeningeal arterioles of the cerebral hemispheres and cerebellum and the capillaries of the grey matter. The amyloid angiopathy expressed beta-amyloid but also prion protein and double immunostaining confirmed co-localization of both proteins in many vessel walls. Alzheimer's type pathology was restricted to a few diffuse beta-amyloid plaques in the entorhinal cortex and rare tangles in the hippocampus. Deposition of prion protein in cerebral vessels has been reported in a single case of stop codon 145 mutation of the PRNP gene. Co-localization of beta-amyloid and prion protein in the same amyloid plaque has been described in elderly patients with Creutzfeldt-Jakob or Gerstmann-Sträussler-Scheinker diseases but only exceptionally in cerebral amyloid angiopathy. In this patient, hypertensive cerebrovascular disease may have contributed to the failure to eliminate both proteins from the brain.

[The French Society of Geriatrics and Gerontology position paper on the concept of integration. Part two]. / Prise de position de la Société française de gériatrie et gérontologie sur le concept d'intégration : texte intégral Deuxième partie.

The concept of integrated services delivery, although dating from the 1990s, has only recently appeared in French public health policy. To clarify the concept and its adaptation to the reality of the French systems of healthcare and social services, the French Society of Geriatrics and Gerontology established an interdisciplinary working group. This article reports that group's findings according to three axes: the definition of integration, the objectives of this organizational approach and the means needed to achieve them. Analysis of the literature indicated that integration is a process that aims to overcome the fragmentation of services for vulnerable people. This process requires a multilevel approach, particularly concerning how to modify public policies and financing systems. Notably, all relevant levels need to develop shared processes, tools, resources, finance, interventions and returns on the latter. Indeed, this sharing is the ultimate proof of evolution towards integration. In the second part of the position paper, its authors have developed arguments that could lead professionals and non-professional caregivers to adopt integrated care as an answer to their aspirations. Policy-maker perspectives and politicians are also analyzed. Bearing in mind that integrated care necessarily will always involve a human component which may find expression during individual case-management; relations between integration and case managements are clarified. Finally, lessons learned from national and international experiments are examined. Results suggest that integrated care must to be accompanied by a local pilot. Results of recent experiments have shown that it is possible to initiate a dynamic towards integrated care in France and hence join the international movement towards adapting our healthcare systems to new challenges.

The French Society of Geriatrics and Gerontology position paper on the concept of integration.

INTRODUCTION: The concept of integration, although dating from the 1990s, has only recently appeared in French public health policy. It must be linked with 'coordination', which is the base of most French public policies applied to geriatrics since the 1960s. Herein, we report the French Society of Geriatrics and Gerontology working group's findings according to three axes: definition of integration, objectives of this organisational approach and the means needed to achieve them. DISCUSSION: Integration is a process that aims to overcome the fragmentation of services for vulnerable people. This process requires a multilevel approach, particularly concerning how to modify public policies and financing systems. Notably, all relevant levels need to develop shared processes, tools, resources, financing, interventions and action-reports on the latter. Integration must be accompanied by a local dedicated professional (the 'pilot'). Results of recent experiments showed that it is possible to implement integrative dynamics in France.

[The French Society of Geriatrics and Gerontology position paper on the concept of integration, Part One]. / Prise de position de la Société française de gériatrie et gérontologie sur le concept d'intégration : texte intégral Première partie.

The concept of integrated services delivery, although dating from the 1990s, has only recently appeared in the French public health policy. To clarify the concept and its adaptation to the reality of the French systems of healthcare and social services, the French Society of Geriatrics and Gerontology established an interdisciplinary working group. This article reports the group's findings according to three axes: the definition of integration, the objectives of this organizational approach and the means needed to achieve them. Analysis of the literature indicated that integration is a process that aims to overcome the fragmentation of services for vulnerable people. This process requires a multilevel approach, particularly concerning how to modify public policies and financing systems. Notably, all relevant levels need to develop shared processes, tools, resources, finance, interventions and feed-back on the latter. Indeed, this sharing is the ultimate proof of evolution towards integration. In this first part of the position paper, its authors analyzed integrated care definitions used in international literature in view of designing the most important components of integrated care. The examination of this concept must be articulated with the idea of "coordination" which has been the cornerstone of the majority of public policies applied to the field of geriatrics and gerontology since the 1960s in France. The components of integrated care highlight that it is an ambitious process leading to real systemic modification. The authors also have proposed to open up a dialogue between citizens' aspirations and integrated care objectives with the aim to verify that the latter respond to the needs as expressed by the targeted group.