Involvement of PPAR nuclear receptors in tissue injury and wound repair.

Tissue damage resulting from chemical, mechanical, and biological injury, or from interrupted blood flow and reperfusion, is often life threatening. The subsequent tissue response involves an intricate series of events including inflammation, oxidative stress, immune cell recruitment, and cell survival, proliferation, migration, and differentiation. In addition, fibrotic repair characterized by myofibroblast transdifferentiation and the deposition of ECM proteins is activated. Failure to initiate, maintain, or stop this repair program has dramatic consequences, such as cell death and associated tissue necrosis or carcinogenesis. In this sense, inflammation and oxidative stress, which are beneficial defense processes, can become harmful if they do not resolve in time. This repair program is largely based on rapid and specific changes in gene expression controlled by transcription factors that sense injury. PPARs are such factors and are activated by lipid mediators produced after wounding. Here we highlight advances in our understanding of PPAR action during tissue repair and discuss the potential for these nuclear receptors as therapeutic targets for tissue injury.

Data Envelopment Analysis (DEA) : un guide pédagogique à l'intention des décideurs dans le secteur public

Ce guide présente la méthode Data Envelopment Analysis (DEA), une méthode d'évaluation de la performance . Il est destiné aux responsables d'organisations publiques qui ne sont pas familiers avec les notions d'optimisation mathématique, autrement dit de recherche opérationnelle. L'utilisation des mathématiques est par conséquent réduite au minimum. Ce guide est fortement orienté vers la pratique. Il permet aux décideurs de réaliser leurs propres analyses d'efficience et d'interpréter facilement les résultats obtenus. La méthode DEA est un outil d'analyse et d'aide à la décision dans les domaines suivants : - en calculant un score d'efficience, elle indique si une organisation dispose d'une marge d'amélioration ; - en fixant des valeurs-cibles, elle indique de combien les inputs doivent être réduits et les outputs augmentés pour qu'une organisation devienne efficiente ; - en identifiant le type de rendements d'échelle, elle indique si une organisation doit augmenter ou au contraire réduire sa taille pour minimiser son coût moyen de production ; - en identifiant les pairs de référence, elle désigne quelles organisations disposent des best practice à analyser.

A guide for the management of dual diagnosis for prisons.

Dual diagnosis, the co-extistence of mental health and substance misuse problems, has a higher prevalence in prisons than in the general community. This document provides good practice guidance to commissioners and practitioners on for the management of dual diagnosis within a prison setting.This resource was contributed by The National Documentation Centre on Drug Use.

A guide to working in partnership: employability provision for drug users.

The aim of this guide is to identify the key principles of partnership working and to provide case study examples of how partnership works in practice in employability provision for drug users. Developing and sustaining new and valuable relationships with the world beyond drugs is a key factor in sustainable recovery for drug users. This includes the worlds of employment, training and education. Research suggests that employment can aid the process of recovery. A qualitative study of drug users in Scotland highlighted the importance of employment and other activities to fill the ‘void’ left by drug useThis resource was contributed by The National Documentation Centre on Drug Use.

A brief cognitive behavioural intervention for regular amphetamine users. A treatment guide.

A brief intervention using motivational and cognitive behavioural approaches to help change drug use. Also offer alternative brief interventions for clients not suited to the current approach. This manual is divided into five sections: Section 1. Context Key points from the National Drug Strategy Monograph No 51. Models of Intervention and Care for Psychostimulant Users are included to present the evidence supporting this type of intervention for regular amphetamine users.  A flow-chart to place the intervention in a treatment context. Section 2. Brief background to the study and summary of results of evaluation A brief description of how the study was developed, undertaken and evaluated. A brief description of the evaluation outcome data (detailed results will be published separately). Section 3. The intervention The CBT intervention is presented in a clear and easy to use format for practitioners. Section 4. Suggested alternative brief interventions for those not suitable for the current intervention This section provides an overview of recommendations for alternative interventions for psychostimulant users who are unsuitable for the CBT intervention (e.g. those who are not considering change, experimental users etc). Section 5. Other available resources This section lists a range of other resources that are currently available for practitioners working with psychostimulant users. This treatment guide has not been designed to stand alone. Rather, practitioners are encouraged to: 1. Acquaint themselves with the current research and clinical literature. The recently completed monograph Models of Intervention and Care for Psychostimulant Users is an excellent resource for current evidence supporting practice in this area. 2. Undertake training in CBT and motivational enhancement techniques if unfamiliar with these approaches. 3. Obtain ongoing clinical supervision.This resource was contributed by The National Documentation Centre on Drug Use.

Your guide to Understanding Alzheimer's Disease and other dementias

��The purpose of this booklet is to give you general information about Alzheimer's Disease and other dementias, and to highlight their early signs and symptoms.It offers a number of tools that can be helpful in establishing whether you or someone you care for is experiencing memory problems, and there is a diary at the back of this book to help track and record various changes that you or the person you love maybe experiencing.This booklet also contains details of what steps to take next if you are concerned about someone, how a diagnosis is made, what to do if you or someone close is diagnosed with Alzheimer's Disease, and outlines the various treatments that are available.Understanding Alzheimer's Disease also focuses on the importance of the role of the carer, explains carer stress, and offers some useful suggestions for reducing the stress that can build up when caring for someone full-time.It is hoped this booklet will give you answers to the more frequently asked questions and therefore give you a better understanding of Alzheimer's Disease and dementia.��

Molecular risk assessment of BIG 1-98 participants by expression profiling using RNA from archival tissue.

Background: The purpose of the work reported here is to test reliable molecular profiles using routinely processed formalin-fixed paraffin-embedded (FFPE) tissues from participants of the clinical trial BIG 1-98 with a median follow-up of 60 months. Methods: RNA from fresh frozen (FF) and FFPE tumor samples of 82 patients were used for quality control, and independent FFPE tissues of 342 postmenopausal participants of BIG 1-98 with ER-positive cancer were analyzed by measuring prospectively selected genes and computing scores representing the functions of the estrogen receptor (eight genes, ER_8), the progesterone receptor (five genes, PGR_5), Her2 (two genes, HER2_2), and proliferation (ten genes, PRO_10) by quantitative reverse transcription PCR (qRT-PCR) on TaqMan Low Density Arrays. Molecular scores were computed for each category and ER_8, PGR_5, HER2_2, and PRO_10 scores were combined into a RISK_25 score. Results: Pearson correlation coefficients between FF- and FFPE-derived scores were at least 0.94 and high concordance was observed between molecular scores and immunohistochemical data. The HER2_2, PGR_ 5, PRO_10 and RISK_25 scores were significant predictors of disease free-survival (DFS) in univariate Cox proportional hazard regression. PRO_10 and RISK_25 scores predicted DFS in patients with histological grade II breast cancer and in lymph node positive disease. The PRO_10 and PGR_ 5 scores were independent predictors of DFS in multivariate Cox regression models incorporating clinical risk indicators; PRO_10 outperformed Ki-67 labeling index in multivariate Cox proportional hazard analyses. Conclusions: Scores representing the endocrine responsiveness and proliferation status of breast cancers were developed from gene expression analyses based on RNA derived from FFPE tissues. The validation of the molecular scores with tumor samples of participants of the BIG 1-98 trial demonstrates that such scores can serve as independent prognostic factors to estimate disease free survival (DFS) in postmenopausal patients with estrogen receptor positive breast cancer.

Gastric bypass in morbid obese patients is associated with reduction in adipose tissue inflammation via N-oleoylethanolamide (OEA)-mediated pathways.

Paradoxically, morbid obesity was suggested to protect from cardiovascular co-morbidities as compared to overweight/obese patients. We hypothesise that this paradox could be inferred to modulation of the "endocannabinoid" system on systemic and subcutaneous adipose tissue (SAT) inflammation. We designed a translational project including clinical and in vitro studies at Geneva University Hospital. Morbid obese subjects (n=11) were submitted to gastric bypass surgery (GBS) and followed up for one year (post-GBS). Insulin resistance and circulating and SAT levels of endocannabinoids, adipocytokines and CC chemokines were assessed pre- and post-GBS and compared to a control group of normal and overweight subjects (CTL) (n=20). In vitro cultures with 3T3-L1 adipocytes were used to validate findings from clinical results. Morbid obese subjects had baseline lower insulin sensitivity and higher hs-CRP, leptin, CCL5 and anandamide (AEA) levels as compared to CTL. GBS induced a massive weight and fat mass loss, improved insulin sensitivity and lipid profile, decreased C-reactive protein, leptin, and CCL2 levels. In SAT, increased expression of resistin, CCL2, CCL5 and tumour necrosis factor and reduced MGLL were shown in morbid obese patients pre-GBS when compared to CTL. GBS increased all endocannabinoids and reduced adipocytokines and CC chemokines. In morbid obese SAT, inverse correlations independent of body mass index were shown between palmitoylethanolamide (PEA) and N-oleoylethanolamide (OEA) levels and inflammatory molecules. In vitro, OEA inhibited CCL2 secretion from adipocytes via ERK1/2 activation. In conclusion, GBS was associated with relevant clinical, metabolic and inflammatory improvements, increasing endocannabinoid levels in SAT. OEA directly reduced CCL2 secretion via ERK1/2 activation in adipocytes.

Cognitive Impairment and Dementia: A Practical Guide to Daily Living for Family Caregivers

The Dementia Services Information and Development Centre based at St. James’s Hospital, Dublin recently launched a new booklet for family caregivers of people with dementia. The booklet has been written to provide practical information to family care-givers of people living at home with a cognitive impairment or a dementia and to help them better cope with the day-to-day choices and dilemmas they may confront. To download the booklet please follow this link: Cognitive Impairment and Dementia: A Practical Guide to Daily Living for Family Caregivers

The last taboo: A guide to dementia, sexuality, intimacy and sexual behaviour in care homes ILC-UK

The International Longevity Centre - UK��launched a new paper (Wednesday, 6th July 2011). The last taboo: A guide to dementia, sexuality, intimacy and sexual behaviour in care homes, provides care home workers and managers with information and practical advice on this complex, controversial and sensitive issue.The need for affection, intimacy and relationships for people with dementia in care homes has too often been ignored and side-lined in policy and practice. The onset of old age or a cognitive impairment does not erase the need for affection, intimacy and/or relationships. While the issues involved can be complex, controversial and sensitive and may challenge our own beliefs and value system, it is essential that we understand more about them to foster a more person-centred approach to dementia care. Care home residents with dementia often have complex care needs and trying to understand and respond to the more intimate and sexual aspects of a resident’s personality can be challenging.Aimed at care home workers and managers, the guide not only provides essential information on this aspect of dementia care but offers practical advice to support current work-based practices. Set out in an accessible and easy-to-read format, this guide includes case studies, questions, suggestions and a self assessment quiz to promote easy learning. It also provides a possible pathway for care home managers to develop a guiding policy on sexual expression in dementia.The guide for care staff is summarised in 10 key points:1. Some residents with dementia will have sexual or sensual needs.2. Affection and intimacy contribute to overall health and wellbeing for residents.3. Some residents with dementia will have the capacity to make decisions about their needs.4. If an individual in care is not competent to decide, the home has a duty of care towards the individual to ensure they are protected from harm.5. There are no hard and fast rules. Assess each situation on an individual basis6. Remember not everyone with dementia is heterosexual.7. Inappropriate sexual behaviour is not particularly common in dementia.8. Confront your own attitudes and behaviour towards older people and sex generally.9. Communicate – look at how you can improve communication with your colleagues, managers, residents and carers on this subject10. Look after yourself and remember your own needs as a care professional��The full paper is available: The Last Taboo

Future dementia care in Ireland: A guide

A new guide on dementia�� in Ireland was launched June 19 by Minister of State at the Department of Health Kathleen Lynch. The guide was developed to disseminate to the public, and in lay man's terms, the key findings contained in a report entitled 'Creating Excellence in Dementia Care: A Research Review to inform Ireland's National Dementia Strategy.' The new guide is a joint collaboration between�� the Living with Dementia programme, Trinity College Dublin, and the Irish Centre for Social Gerontology (ICSG), NUI Galway. The research work was funded by The Atlantic Philanthropies and supported by the Department of Health.Access the guide here: http://livingwithdementia.tcd.ie/assets/pdf/Future_Dementia_Care_in_Irel...

Fluid flow regulates stromal cell organization and CCL21 expression in a tissue-engineered lymph node microenvironment.

In the paracortex of the lymph node (LN), T zone fibroblastic reticular cells (TRCs) orchestrate an immune response by guiding lymphocyte migration both physically, by creating three-dimensional (3D) cell networks, and chemically, by secreting the chemokines CCL19 and CCL21 that direct interactions between CCR7-expressing cells, including mature dendritic cells and naive T cells. TRCs also enwrap matrix-based conduits that transport fluid from the subcapsular sinus to high endothelial venules, and fluid flow through the draining LN rapidly increases upon tissue injury or inflammation. To determine whether fluid flow affects TRC organization or function within a 3D network, we regenerated the 3D LN T zone stromal network by culturing murine TRC clones within a macroporous polyurethane scaffold containing type I collagen and Matrigel and applying slow interstitial flow (1-23 microm/min). We show that the 3D environment and slow interstitial flow are important regulators of TRC morphology, organization, and CCL21 secretion. Without flow, CCL21 expression could not be detected. Furthermore, when flow through the LN was blocked in mice in vivo, CCL21 gene expression was down-regulated within 2 h. These results highlight the importance of lymph flow as a homeostatic regulator of constitutive TRC activity and introduce the concept that increased lymph flow may act as an early inflammatory cue to enhance CCL21 expression by TRCs, thereby ensuring efficient immune cell trafficking, lymph sampling, and immune response induction.

'A healthy city is an active city: A PA planning guide' (2008)

This planning guide provides a range of ideas, information and tools for developing a comprehensive plan for creating a healthy, active city by enhancing physical activity in the urban environment. By developing, improving and supporting opportunities in the built and social environments, city leaders and their partners can enable all citizens to be physically active in day-to-day life.

The balance between the production of tumor necrosis factor-alpha and interleukin-10 determines tissue injury and lethality during intestinal ischemia and reperfusion

A major goal in the treatment of acute ischemia of a vascular territory is to restore blood flow to normal values, i.e. to "reperfuse" the ischemic vascular bed. However, reperfusion of ischemic tissues is associated with local and systemic leukocyte activation and trafficking, endothelial barrier dysfunction in postcapillary venules, enhanced production of inflammatory mediators and great lethality. This phenomenon has been referred to as "reperfusion injury" and several studies demonstrated that injury is dependent on neutrophil recruitment. Furthermore, ischemia and reperfusion injury is associated with the coordinated activation of a series of cytokines and adhesion molecules. Among the mediators of the inflammatory cascade released, TNF-alpha appears to play an essential role for the reperfusion-associated injury. On the other hand, the release of IL-10 modulates pro-inflammatory cytokine production and reperfusion-associated tissue injury. IL-1beta, PAF and bradykinin are mediators involved in ischemia and reperfusion injury by regulating the balance between TNF-alpha and IL-10 production. Strategies that enhance IL-10 and/or prevent TNF-alpha concentration may be useful as therapeutic adjuvants in the treatment of the tissue injury that follows ischemia and reperfusion.