Creation of an Open-Access, Mutation-Defined Fibroblast Resource for Neurological Disease Research

Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community

An academic and regional nurse research collaborative: Implications for nursing research.

INTRODUCTION: A diverse group of nurses and research Network Coordinators formed a collaboration to advance nursing research within Johns Hopkins Clinical Research Network, a partnership of academic and community hospitals in the mid-Atlantic region. The purpose of the Nurse Research Collaborative (NRC) is to provide mentoring, mutual growth, and assist the health care organizations to fulfill nursing research requirements. BACKGROUND: We created a multiinstitutional nursing research organization with diversity of member participants and health care facilities. The NRC structure allowed nonacademic facilities to engage in a variety of nursing research projects. This allows for increases in study sample sizes of diverse populations to support and expand nursing research. The NRC is modeled after a physician clinical research network with an aligned mission, vision, goals, and strategic priorities across member organizations. MAIN IDEAS: To strengthen multiinstitutional nursing research capability, the NRC developed an infrastructure of leadership, regular meetings, and formal educational presentations. The NRC completed three research studies, facilitating the Institutional Review Board application process, reviewing documents and contracts, providing individual institutional support, and coordinating site leader functions. CONCLUSION: A research collaboration of nurses, across multiple hospitals provides efficiencies and expertise not otherwise available in every organization

A Qualitative Study of Midlevel Nurse Managers\u27 Perspectives of Scholarly Inquiry.

OBJECTIVE: This study explored the key characteristics and needs of midlevel nurse managers (MLNMs) who support and engage clinical nurses (CNs) in scholarly inquiry. BACKGROUND: Healthcare organizations expect CNs to participate in scholarly inquiry, incorporating evidence-based interventions to improve outcomes and safety. How the MLNM supports and engages CNs in scholarly inquiry remains unclear. METHODS: Twelve semistructured interviews of MLNMs occurred at several facilities in the mid-Atlantic region utilizing the institutional review board-acknowledged protocol. Theme interpretation utilized inductive analysis. RESULTS: Four recurrent themes emerged from the interviews related to the value of scholarly inquiry: 1) securing organizational resources to promote scholarly inquiry; 2) knowledge and experience in scholarly inquiry; 3) actions supporting scholarly inquiry; and 4) the value of scholarly inquiry within the organization. CONCLUSIONS: Senior nursing leadership and healthcare organizations must recognize the value and provide the infrastructure to support scholarly inquiry. Infrastructure includes education, dedicated time, access to expertise, and resources

Creation of an open-access, mutation-defined fibroblast resource for neurological disease research.

Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community

A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease

OBJECTIVE: To evaluate the efficacy and safety of a selective serotonin reuptake inhibitor (SSRI) and a serotonin and norepinephrine reuptake inhibitor (SNRI) in the treatment of depression in Parkinson disease (PD). METHODS: A total of 115 subjects with PD were enrolled at 20 sites. Subjects were randomized to receive an SSRI (paroxetine; n = 42), an SNRI (venlafaxine extended release [XR]; n = 34), or placebo (n = 39). Subjects met DSM-IV criteria for a depressive disorder, or operationally defined subsyndromal depression, and scored >12 on the first 17 items of the Hamilton Rating Scale for Depression (HAM-D). Subjects were followed for 12 weeks (6-week dosage adjustment, 6-week maintenance). Maximum daily dosages were 40 mg for paroxetine and 225 mg for venlafaxine XR. The primary outcome measure was change in the HAM-D score from baseline to week 12. RESULTS: Treatment effects (relative to placebo), expressed as mean 12-week reductions in HAM-D score, were 6.2 points (97.5% confidence interval [CI] 2.2 to 10.3, p = 0.0007) in the paroxetine group and 4.2 points (97.5% CI 0.1 to 8.4, p = 0.02) in the venlafaxine XR group. No treatment effects were seen on motor function. CONCLUSIONS: Both paroxetine and venlafaxine XR significantly improved depression in subjects with PD. Both medications were generally safe and well tolerated and did not worsen motor function. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that paroxetine and venlafaxine XR are effective in treating depression in patients with PD

Population doubling levels of fibroblast cell lines.

<p>Population doubling levels were calculated for each of the cell lines available in the NINDS repository at the time of cryopreservation. Individual points of the graph correspond to the PDL of individual fibroblast lines, the horizontal line represents the mean PDL for each disease category. PDLs ranged between 2–8 with a mean PDL of ∼5 for both control and disease cell lines. A full list of PDLs for individual cell lines in provided in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043099#pone.0043099.s001" target="_blank">Table S1</a>.</p

Fibroblast morphology and marker expression remain consistent during prolonged culture.

<p>Fibroblast lines were immunostained with antibodies FSP1 and TE7 at multiple consecutive passages (A). Passage numbers are indicated above the panels. Morphology, FSP1 and TE7 staining did not change during five consecutive subculturings (n = 6, representative images from line NM34737, carrying the PSEN1 M146I mutation are shown). FSP1 levels were also detected by western blotting of fibroblast cell lysates (B). FSP1 was detected as a single band at 12 kDa in all fibroblast lines examined (top panel, n = 6). β-actin was used as a loading control (bottom panel). No variation in FSP1 levels was observed between passages or between cell lines.</p

Fibroblast cultures express the mesenchymal markers FSP1 and TE7.

<p>Cells generated from skin punch biopsies were verified as fibroblasts by morphological assessment (A) and positive staining with antibodies to fibroblast-specific protein 1 (FSP1) and fibroblast-specific clone TE7 (B, 63×). All fibroblasts examined (n = 6) demonstrated positive staining with both antibodies.</p

Fibroblast lines generated in this study.

<p>Disease, gene, mutation and mode of inheritance for fibroblast cell lines. The current status of each line (available, submitted but not yet in catalogue) is indicated. Where the status is left blank, this indicates fibroblast lines have been generated but are awaiting submission to the NINDS repository. All variants are heterozygous unless otherwise stated. References indicate where families have been described in the literature. D = autosomal dominant, R = autosomal recessive.</p