Assessing the Need for Standardized Pre-Chemotherapy Education: An Outpatient Oncology Clinic Initiative

Abstract Purpose: In a diverse southern California outpatient oncology clinic, assess the need for standardized pre-chemotherapy education for newly diagnosed cancer patients to aid in the improvement of health literacy, self-management of side effects, satisfaction, and reduction of anxiety. Background: Cancer patients often feel anxious, overwhelmed, and confused by the abundance of information and medical jargon that they must digest. One southern California outpatient oncology clinic identified the need for consistent, standardized procedure in providing chemotherapy education and assessing treatment knowledge in newly-diagnosed cancer patients as evidenced by: inconsistent attendance in educational classes and or appointments, inability to articulate treatment after presentation of written material, numerous follow-up telephone calls, and uncertainty about techniques to self-manage symptoms and side effects. Evidence shows that when done appropriately, providing multiple methods of pre-chemotherapy education is effective in preventing and reducing anxiety, improvement in health literacy recall, and ability to self-mange side effects in patients receiving chemotherapy for the first time. Process: This evidence-based practice project was built on the foundation of the Ace Star Model of Knowledge Transformation framework and the gate control pain theory. An integrated literature review was piloted to examine the best methods of providing chemotherapy education in the effort to improve patient’s health literacy, self-management of treatment side effects, patient satisfaction, and the reduction of anxiety. Outcomes: The implementation of standardized procedure in methods of pre-chemotherapy education are pending. Conclusion: Standardizing the process of chemotherapy education can provide measurable improvement in quality of care, productivity, adherence to treatment, and morale for chemotherapy patients by enhancing their level of health care literacy and sills for self-management of chemotherapy-related side effects

Combining neuroprotectants in a model of retinal degeneration: no additive benefit

The central nervous system undergoing degeneration can be stabilized, and in some models can be restored to function, by neuroprotective treatments. Photobiomodulation (PBM) and dietary saffron are distinctive as neuroprotectants in that they upregulate protective mechanisms, without causing measurable tissue damage. This study reports a first attempt to combine the actions of PBM and saffron. Our working hypothesis was that the actions of PBM and saffron in protecting retinal photoreceptors, in a rat light damage model, would be additive. Results confirmed the neuroprotective potential of each used separately, but gave no evidence that their effects are additive. Detailed analysis suggests that there is actually a negative interaction between PBM and saffron when given simultaneously, with a consequent reduction of the neuroprotection. Specific testing will be required to understand the mechanisms involved and to establish whether there is clinical potential in combining neuroprotectants, to improve the quality of life of people affected by retinal pathology, such as age-related macular degeneration, the major cause of blindness and visual impairment in older adults.This work was supported by the Australian Research Council Centre of Excellence in Vision Science, by the Sir Zelman Cowen Universities Fund and the Lord Mayor’s Charitable Foundation, by Australian Travel Awards for L’Aquila Researchers (ARIA) to FDM and SR and by a Ministero dell’Istruzione, dell’Universita` e della Ricerca dedicato ai PRIN, Progetti di Ricerca di Interesse Nazionale (MIUR-PRIN) (2010-2011) research grant to SB

Institutionalized Delinquent and Maladjusted Juveniles: A Psycholegal Systems Analysis

I. Introduction II. The Criminal Justice and Mental Health Systems ... A. Angles A1 and A2 ... B. A1→B1, or A2→B2 … C. Angles B1 and B2 ... D. The Shuffle: A1→C1→A1 or A2; or A2→C2→A2 or A1; or A1→B2 or C1→B2 ... E. The Merger ... F. Prospects for Change ... G. Summary III. The Juvenile Justice System ... A. Legal Rights at Intake in the Juvenile Justice System (Angle A3 ) ... B. Legal Rights during Juvenile Incarceration (A3 to B3) ... C. Controversy over the Goal of Juvenile Justice (Angle B3) ... D. Dumping (Angle C3) and Shuffling (A3→C3→A3 or A1 or A2; or A3→A1 or A2) in the Juvenile Justice System ... E. Merger with the Criminal Justice System ... F. Summary IV. Juveniles in the Mental Health System ... A. Commitment of Juveniles to Mental Health Facilities (Angle A4) ... B. Incipient Legalization at Angle A4 ... C. Prospects for Further Legalization at Angle A4 ... D. Prospects for Treatment Rights (A4→B4) ... E. The Future of the Juvenile Mental Health System ... F. Summary V. Conclusio

Institutionalized Delinquent and Maladjusted Juveniles: A Psycholegal Systems Analysis

I. Introduction II. The Criminal Justice and Mental Health Systems ... A. Angles A1 and A2 ... B. A1→B1, or A2→B2 … C. Angles B1 and B2 ... D. The Shuffle: A1→C1→A1 or A2; or A2→C2→A2 or A1; or A1→B2 or C1→B2 ... E. The Merger ... F. Prospects for Change ... G. Summary III. The Juvenile Justice System ... A. Legal Rights at Intake in the Juvenile Justice System (Angle A3 ) ... B. Legal Rights during Juvenile Incarceration (A3 to B3) ... C. Controversy over the Goal of Juvenile Justice (Angle B3) ... D. Dumping (Angle C3) and Shuffling (A3→C3→A3 or A1 or A2; or A3→A1 or A2) in the Juvenile Justice System ... E. Merger with the Criminal Justice System ... F. Summary IV. Juveniles in the Mental Health System ... A. Commitment of Juveniles to Mental Health Facilities (Angle A4) ... B. Incipient Legalization at Angle A4 ... C. Prospects for Further Legalization at Angle A4 ... D. Prospects for Treatment Rights (A4→B4) ... E. The Future of the Juvenile Mental Health System ... F. Summary V. Conclusio

Single neuron transcriptomics identify SRSF/ SR protein B52 as a regulator of axon growth and Choline acetyltransferase splicing.

We removed single identified neurons from living Drosophila embryos to gain insight into the transcriptional control of developing neuronal networks. The microarray analysis of the transcriptome of two sibling neurons revealed seven differentially expressed transcripts between both neurons (threshold: log(2)1.4). One transcript encodes the RNA splicing factor B52. Loss of B52 increases growth of axon branches. B52 function is also required for Choline acetyltransferase (ChAT ) splicing. At the end of embryogenesis, loss of B52 function impedes splicing of ChAT, reduces acetylcholine synthesis, and extends the period of uncoordinated muscle twitches during larval hatching. ChAT regulation by SRSF proteins may be a conserved feature since changes in SRSF5 expression and increased acetylcholine levels in brains of bipolar disease patients have been reported recently

aPKC-mediated displacement and actomyosin-mediated retention polarize Miranda in <i>Drosophila</i> neuroblasts

International audienceCell fate assignment in the nervous system of vertebrates and invertebrates often hinges on the unequal distribution of molecules during progenitor cell division. We address asymmetric fate determinant localization in the developing Drosophila nervous system, specifically the control of the polarized distribution of the cell fate adapter protein Miranda. We reveal a step-wise polarization of Miranda in larval neuroblasts and find that Miranda’s dynamics and cortical association are differently regulated between interphase and mitosis. In interphase, Miranda binds to the plasma membrane. Then, before nuclear envelope breakdown, Miranda is phosphorylated by aPKC and displaced into the cytoplasm. This clearance is necessary for the subsequent establishment of asymmetric Miranda localization. After nuclear envelope breakdown, actomyosin activity is required to maintain Miranda asymmetry. Therefore, phosphorylation by aPKC and differential binding to the actomyosin network are required at distinct phases of the cell cycle to polarize fate determinant localization in neuroblasts

Pro-resolving and anti-arthritic properties of the MC1 selective agonist PL8177

BACKGROUND: Melanocortins are peptides endowed with anti-inflammatory and pro-resolving activities. Many of these effects are mediated by the Melanocortin receptor 1 (MC(1)) as reported in several experimental settings. As such, MC(1) can be a viable target for the development of new therapies that mimic endogenous pro-resolving mediators. The aim of this study was to assess the immunopharmacology of a selective MC(1) agonist (PL8177) in vitro and in a mouse model of inflammatory arthritis. METHODS: PL8177 and the natural agonist αMSH were tested for activation of mouse and human Melanocortin receptors (MC(1,3,4,5)), monitoring cAMP accumulation and ERK1/2 phosphorylation, using transiently transfected HEK293A cells. The anti-inflammatory and pro-resolving effects of PL8177 and αMSH were evaluated using mouse peritoneal Macrophages. Finally, a model of K/BxN serum transfer induced arthritis was used to determine the in vivo potential of PL8177. RESULTS: PL8177 activates mouse and human MC(1) with apparent EC(50) values of 0.01 and 1.49 nM, respectively, using the cAMP accumulation assay. Similar profiles were observed for the induction of ERK phosphorylation (EC(50): 0.05 and 1.39 nM). PL8177 displays pro-resolving activity (enhanced Macrophage efferocytosis) and counteracts the inflammatory profile of zymosan-stimulated macrophages, reducing the release of IL-1β, IL-6, TNF-α and CCL-2. In the context of joint inflammation, PL8177 (3mg/kg i.p.) reduces clinical score, paw swelling and incidence of severe disease as well as the recruitment of immune cells into the arthritic joint. CONCLUSION: These results demonstrate that the MC(1) agonism with PL8177 affords therapeutic effects in inflammatory conditions including arthritis. SIGNIFICANCE: Drugs targeting the Melanocortin system have emerged as promising therapeutics for several conditions including inflammation or obesity. Multiple candidates are under clinical development, and some have already reached approval. Here we present the characterization of a novel drug candidate, PL8177, selective for the Melanocortin 1 receptor (MC(1)), demonstrating its selectivity profile on cAMP and ERK1/2 phosphorylation signaling pathways, of relevance as selective drugs will translate into lesser off-target effect. PL8177 also demonstrated, not only anti-inflammatory activity, but pro-resolving actions due to its ability to enhance efferocytosis (i.e. the phagocytosis of apoptotic cells), endowing this molecule with therapeutic advantages compared to classical anti-inflammatory drugs. Using a mouse model of inflammatory arthritis, the compound demonstrated in vivo efficacy by reducing clinical score, paw swelling and overall disease severity. Taken together, these results present Melanocortin-based therapies, and specifically targeting MC(1) receptor, as a promising strategy to manage chronic inflammatory diseases

Control of Neural Daughter Cell Proliferation by Multi-level Notch/Su(H)/E(spl)-HLH Signaling

The Notch pathway controls proliferation during development and in adulthood, and is frequently affected in many disorders. However, the genetic sensitivity and multi-layered transcriptional properties of the Notch pathway has made its molecular decoding challenging. Here, we address the complexity of Notch signaling with respect to proliferation, using the developing Drosophila CNS as model. We find that a Notch/Su(H)/E(spl)-HLH cascade specifically controls daughter, but not progenitor proliferation. Additionally, we find that different E(spl)-HLH genes are required in different neuroblast lineages. The Notch/Su(H)/E(spl)-HLH cascade alters daughter proliferation by regulating four key cell cycle factors: Cyclin E, String/Cdc25, E2f and Dacapo (mammalian p21CIP1/p27KIP1/p57Kip2). ChIP and DamID analysis of Su(H) and E(spl)-HLH indicates direct transcriptional regulation of the cell cycle genes, and of the Notch pathway itself. These results point to a multi-level signaling model and may help shed light on the dichotomous proliferative role of Notch signaling in many other systems

Spindle positioning in the stem cell niche

Stem cells are the source of differentiated cells that constitute tissues and organs. Two fundamental characteristics of stem cells are their abilities to self‐renew stem cell identity and to produce differentiated cells, the balance of which can be achieved by asymmetric stem cell division. Many stem cells have been shown to reside in a stem cell niche, the home of stem cells that regulates the stem cell behavior. Recent studies have revealed the critical contribution of cytoskeletons in achieving asymmetric stem cell division: mitotic spindles in dividing stem cells are often oriented with respect to the stem cell niche, which is supported by concerted actions of microtubule networks and components at the cell membrane such as adherens junctions, the actin cytoskeleton, and the extracellular matrix. In this article, we review the mechanism of stem cell spindle orientation, with emphasis on its relationship with the stem cell niche, and discuss how it contributes to tissue development and homeostasis. WIREs Dev Biol 2012, 1:215–230. doi: 10.1002/wdev.16 For further resources related to this article, please visit the WIREs website .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90343/1/16_ftp.pd