Dynamic Changes in Brain Mesenchymal Perivascular Cells Associate with Multiple Sclerosis Disease Duration, Active Inflammation, and Demyelination

Vascular changes, including blood brain barrier destabilization, are common pathological features in multiple sclerosis (MS) lesions. Blood vessels within adult organs are reported to harbor mesenchymal stromal cells (MSCs) with phenotypical and functional characteristics similar to pericytes. We performed an immunohistochemical study of MSCs/pericytes in brain tissue from MS and healthy persons. Post-mortem brain tissue from patients with early progressive MS (EPMS), late stage progressive MS (LPMS), and healthy persons were analyzed for the MSC and pericyte markers CD146, platelet-derived growth factor receptor beta (PDGFRβ), CD73, CD271, alpha-smooth muscle actin, and Ki67. The MS samples included active, chronic active, chronic inactive lesions, and normal-appearing white matter. MSC and pericyte marker localization were detected in association with blood vessels, including subendothelial CD146+PDGFRβ+Ki67+ cells and CD73+CD271+PDGFRβ+Ki67– cells within the adventitia and perivascular areas. Both immunostained cell subpopulations were termed mesenchymal perivascular cells (MPCs). Quantitative analyses of immunostainings showed active lesions containing increased regions of CD146+PDGFRβ+Ki67+ and CD73+CD271+PDGFRβ+Ki67– MPC subpopulations compared to inactive lesions. Chronic lesions presented with decreased levels of CD146+PDGFRβ+Ki67+ MPC cells compared to control tissue. Furthermore, LPMS lesions displayed increased numbers of blood vessels harboring greatly enlarged CD73+CD271+ adventitial and perivascular areas compared to control and EPMS tissue. In conclusion, we demonstrate the presence of MPC subgroups in control human brain vasculature, and their phenotypic changes in MS brain, which correlated with inflammation, demyelination and MS disease duration. Our findings demonstrate that brain-derived MPCs respond to pathologic mechanisms involved in MS disease progression and suggest that vessel-targeted therapeutics may benefit patients with progressive MS

Systematic care for caregivers of people with dementia in the ambulatory mental health service: designing a multicentre, cluster, randomized, controlled trial

Contains fulltext : 81435.pdf (publisher's version ) (Open Access)BACKGROUND: Care for people with dementia and their informal caregivers is a challenging aim in healthcare. There is an urgent need for cost-effective support programs that prevent informal caregivers of people with dementia from becoming overburdened, which might result in a delay or decrease of patient institutionalization. For this reason, we have developed the Systematic Care Program for Dementia (SCPD). The SCPD consists of an assessment of caregiver's sense of competence and suggestions on how to deal with competence deficiencies. The efficiency of the SCPD will be evaluated in our study. METHODS AND DESIGN: In our ongoing, cluster, randomized, single-blind, controlled trial, the participants in six mental health services in four regions of the Netherlands have been randomized per service. Professionals of the ambulatory mental health services (psychologists and social psychiatric nurses) have been randomly allocated to either the intervention group or the control group. The study population consists of community-dwelling people with dementia and their informal caregivers (patient-caregiver dyads) coming into the health service. The dyads have been clustered to the professionals. The primary outcome measure is the patient's admission to a nursing home or home for the elderly at 12 months of follow-up. This measure is the most important variable for estimating cost differences between the intervention group and the control group. The secondary outcome measure is the quality of the patient's and caregiver's lives. DISCUSSION: A novelty in the SCPD is the pro-active and systematic approach. The focus on the caregiver's sense of competence is relevant to economical healthcare, since this sense of competence is an important determinant of delay of institutionalization of people with dementia. The SCPD might be able to facilitate this with a relatively small cost investment for caregivers' support, which could result in a major decrease in costs in the management of dementia. Implementation on a national level will be started if the SCPD proves to be efficient. TRIAL REGISTRATION: NCT00147693

The effects of fixed and removable orthodontic retainers: a systematic review.

OBJECTIVE: In the view of the widespread acceptance of indefinite retention, it is important to determine the effects of fixed and removable orthodontic retainers on periodontal health, survival and failure rates of retainers, cost-effectiveness, and impact of orthodontic retainers on patient-reported outcomes. METHODS: A comprehensive literature search was undertaken based on a defined electronic and gray literature search strategy ( PROSPERO: CRD42015029169). The following databases were searched (up to October 2015); MEDLINE via OVID, PubMed, the Cochrane Central Register of Controlled Trials, LILACS, BBO, ClinicalTrials.gov, the National Research Register, and ProQuest Dissertation and Thesis database. Randomized and non-randomized controlled clinical trials, prospective cohort studies, and case series (minimum sample size of 20) with minimum follow-up periods of 6 months reporting periodontal health, survival and failure rates of retainers, cost-effectiveness, and impact of orthodontic retainers on patient-reported outcomes were identified. The Cochrane Collaboration's Risk of Bias tool and Newcastle-Ottawa Scale were used to assess the quality of included trials. RESULTS: Twenty-four studies were identified, 18 randomized controlled trials and 6 prospective cohort studies. Of these, only 16 were deemed to be of high quality. Meta-analysis was unfeasible due to considerable clinical heterogeneity and variations in outcome measures. The mean failure risk for mandibular stainless steel fixed retainers bonded from canine to canine was 0.29 (95 % confidence interval [CI] 0.26, 0.33) and for those bonded to canines only was 0.25 (95 % CI: 0.16, 0.33). A meta-regression suggested that failure of fixed stainless steel mandibular retainers was not directly related to the period elapsed since placement (P = 0.938). CONCLUSION: Further well-designed prospective studies are needed to elucidate the benefits and potential harms associated with orthodontic retainers