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Utilizing an Ingestible Biosensor to Assess Real-Time Medication Adherence

Fri, 01/22/2016 - 11:03am

Medication adherence monitoring has relied largely on indirect measures of pill ingestion including patient self-report, pharmacy refills, electronically triggered pill bottles, and pill counts. Our objective is to describe an ingestible biosensor system comprising a radio-frequency identification (RFID)-tagged gelatin capsule. Once the capsule dissolves in the stomach, the RFID tag activates to transmit a unique signal to a relay device which transmits a time-stamped message to a cloud-based server that functions as a direct measure of medication adherence. We describe a constellation of mobile technologies that provide real-time direct measures of medication adherence. Optimizing connectivity, relay design, and interactivity with users are important in obtaining maximal acceptability. Potential concerns including gut retention of metallic components of the ingestible biosensor and drug dissolution within a gelatin capsule should be considered. An ingestible biosensor incorporated into a medication management system has the potential to improve medication compliance with real-time monitoring of ingestion and prompt early behavioral intervention. Integration of ingestible biosensors for multiple disease states may provide toxicologists with salient data early in the care of poisoned patients in the future. Further research on device design and interventions to improve adherence is needed and will shape the evolving world of medication adherence.

Depression and quality of life before and after breast cancer diagnosis in older women from the Women's Health Initiative

Fri, 01/22/2016 - 11:03am

PURPOSE: Distress and reduced quality of life (QOL) are common among people with cancer. No study has compared these variables after breast cancer diagnosis to pre-cancer diagnosis levels.

METHODS: Data on women with breast cancer 50 years of age or older (n = 6949) were analyzed from the Women's Health Initiative (1993-2013). Health-related QOL (physical function, mental health) was measured using Rand-36. Depressive symptoms were measured with the six-item Center for Epidemiologic Studies Depression scale. Assessments occurred before and after the cancer diagnosis. Hierarchical linear modeling compared pre-cancer QOL and depressive symptoms to levels post-diagnosis and tested whether pre-cancer physical activity, stressful life events, sleep disturbance, and pain predicted post-diagnosis outcomes.

RESULTS: Compared with pre-cancer levels, depressive symptoms increased (20.0 % increase at 0-6 months, 12.9 % increase at 6-12 months), while physical function (-3.882 points at 0-6 months, -3.545 at 6-12 months) and mental health decreased (-2.899 points at 0-6 months, -1.672 at 6-12 months) in the first year after diagnosis (all p < .01). Depressive symptoms returned to pre-cancer levels after 10 years, but QOL remained significantly lower. At more than 10 years post-diagnosis, physical function was 2.379 points lower than pre-cancer levels (p < 0.01) while mental health was 1.922 points lower (p < 0.01). All pre-cancer predictors were associated with all outcomes. Pain predicted uniquely greater decreases in physical function post-diagnosis.

CONCLUSIONS: Depressive symptoms increased and QOL decreased following breast cancer diagnosis compared with pre-cancer levels, particularly in the first year.

IMPLICATIONS FOR CANCER SURVIVORS: QOL may remain lower for years after breast cancer diagnosis, although decreases are small.

The association between latent depression subtypes and remission after treatment with citalopram: A latent class analysis with distal outcome

Fri, 01/22/2016 - 11:03am

BACKGROUND: The objectives were to characterize latent depression subtypes by symptoms, evaluate sex differences in and examine correlates of these subtypes, and examine the association between subtype and symptom remission after citalopram treatment.

METHODS: Latent class analysis was applied to baseline data from 2772 participants in the Sequenced Treatment Alternatives to Relieve Depression trial. Indicators were from the Quick Inventory of Depressive Symptomatology. Separate multinomial logistic models identified correlates of subtypes and the association between subtype and the distal outcome of remission.

RESULTS: Four latent subtypes were identified: Mild (men: 37%, women: 27%), Moderate (men: 24%, women: 21%), Severe with Increased Appetite (men: 13%, women: 22%), and Severe with Insomnia (men: 26%, women: 31%). Generalized anxiety disorder, bulimia, and social phobia were correlated with Severe with Increased Appetite and generalized anxiety disorder, post-traumatic stress disorder, and social phobia with Severe with Insomnia. Relative to those with the Mild subtype, those with Severe with Increased Appetite (odds ratiomen (OR): 0.48; 95% confidence interval (CI): 0.25-0.92; OR women: 0.59; 95% CI: 0.41-0.86) and those with Severe Depression with Insomnia (ORmen: 0.65; 95% CI: 0.41-1.02; ORwomen: 0.45; 95% CI: 0.32-0.64) were less likely to achieve remission.

LIMITATIONS: The sample size limited exploration of higher order interactions.

CONCLUSIONS: Insomnia and increased appetite distinguished latent subtypes. Sex and psychiatric comorbidities differed between the subtypes. Remission was less likely for those with the severe depression subtypes. Sleep disturbances, appetite changes, and other mental disorders may play a role in the etiology and treatment of depression.

Common use of dietary supplements for bipolar disorder: a naturalistic, self-reported study

Fri, 01/22/2016 - 11:03am

BACKGROUND: Dietary supplements are taken by about half of Americans. Knowledge of dietary supplement use is important because they may interact with prescription drugs or other supplements, cause adverse reactions including psychiatric symptoms, or contain inherently toxic ingredients or contaminants. This study explores the use of dietary supplements by patients with bipolar disorder in the US.

METHODS: Data were obtained from an ongoing, naturalistic study of patients with bipolar disorder who received pharmacological treatment as usual. The patients self-reported their daily mood, sleep, and medications taken, including all drugs prescribed for bipolar disorder or that the patient felt impacted their mood. These included other prescribed drugs, over-the-counter drugs and dietary supplements. Drugs that received premarketing approval from the FDA were not included as dietary supplements. Patient demographics and daily medication use were characterized.

RESULTS: Data were available from 348 patients in the US who returned a mean 249.5 days of data. In addition to prescribed psychiatric drugs, 101 of the 348 patients (29 %) used a dietary supplement for at least 7 days and 69 (20 %) used a supplement long term (for at least 50 % of days). Of the 101 supplement users, 72 (71.3 %) took one supplement daily. The 101 patients tried over 40 different supplements, and the long-term users took 19 different supplements. The most commonly taken supplements for both groups were fish oil, B vitamins, melatonin, and multivitamins. Patients using supplements were more likely to be white (p < 0.001), older (p = 0.009), and ill for more years (p = 0.025).

CONCLUSIONS: Many patients with bipolar disorder use dietary supplements in addition to prescribed drugs. Physicians should obtain detailed information about all dietary supplements taken by patients with bipolar disorder.

Challenges in developing primary care physicians' motivational interviewing skills

Fri, 01/22/2016 - 11:03am

INTRODUCTION: Motivational interviewing (MI) skills are relevant for primary care providers (PCPs) who are responsible for caring for patients with diseases affected by behavior. There are significant challenges associated with developing PCP's MI skills. We report on an effort to document the acquisition of MI skills by PCPs using an objective measure of MI competence, the Motivational Interviewing Treatment Integrity (MITI) coding system.

METHOD: Eleven PCPs volunteered to participate in 6 MI workshops over a period of 6 months and to submit work samples between each of these workshops to be assessed with the MITI coding system.

RESULTS: Thirteen of the expected 55 work samples were submitted before the final workshop. A revised approach was implemented in which each participant completed 2 simulated patient encounters. None of the providers reached the MITI's Beginning Proficiency threshold of MI skill.

DISCUSSION: Six MI workshops were not sufficient to help motivated PCPs achieve Beginning Proficiency as measured by the MITI. Participants failed to submit most of the work samples for feedback on their MI practice, which may have contributed to their limited acquisition of MI skills. Helping PCPs develop MI skills likely requires more than participation in a series of workshops totaling 18 h. Questions remain about the feasibility of training PCPs to be competent in MI. Approaches such as use of simulated patients, peer observation, or specific protected time for obtaining work samples may be required.

Readmission After Resections of the Colon and Rectum: Predictors of a Costly and Common Outcome

Fri, 01/22/2016 - 11:03am

BACKGROUND: Readmission rates are a measure of surgical quality and an object of clinical and regulatory scrutiny. Despite increasing efforts to improve quality and contain cost, 6% to 25% of patients are readmitted after colorectal surgery.

OBJECTIVE: The aim of this study is to define the predictors and costs of readmission following colorectal surgery.

DESIGN: This is a retrospective cohort study of patients undergoing elective and nonelective colectomy and/or proctectomy in the Healthcare Cost and Utilization Project Florida State Inpatient Database 2007 to 2011. Readmission is defined as inpatient admission within 30 days of discharge. Univariate analyses were performed of sex, age, Elixhauser score, race, insurance type, procedure, indication, readmission diagnosis, cost, and length of stay. Multivariate analysis was performed by logistic regression. Sensitivity analysis of nonemergent admissions was conducted.

SETTINGS: This study was conducted in Florida acute-care hospitals.

PATIENTS: Patients undergoing colectomy and proctectomy from 2007 to 2011 were included.

INTERVENTION(S): There were no interventions.

MAIN OUTCOME MEASURE(S): The primary outcomes measured were readmission and the cost of readmission.

RESULTS: A total of 93,913 patients underwent colectomy; 14.7% were readmitted within 30 days. From 2007 to 2011, readmission rates remained stable (14.6%-14.2%, trend p = 0.1585). After multivariate adjustment, patient factors associated with readmission included nonwhite race, age < 65, and a diagnosis code other than neoplasm or diverticular disease (p < 0.0001). Patients with Medicare or Medicaid were more likely to be readmitted than those with private insurance (p < 0.0001). Patients with longer index admissions, those with stomas, and those undergoing all procedures other than sigmoid or transverse colectomy were more likely to be readmitted (p < 0.0001). High-volume hospitals had higher rates of readmission (p < 0.0001). The most common reason for readmission was infection (32.9%). Median cost of readmission care was $7030 (intraquartile range, $4220-$13,247). Fistulas caused the most costly readmissions ($15,174; intraquartile range, $6725-$26,660).

LIMITATIONS: Administrative data and retrospective design were limitations of this study.

CONCLUSIONS: Readmissions rates after colorectal surgery remain common and costly. Nonprivate insurance, IBD, and high hospital volume are significantly associated with readmission.

Racial Differences in the Performance of Existing Risk Prediction Models for Incident Type 2 Diabetes: The CARDIA Study

Fri, 01/22/2016 - 11:03am

OBJECTIVE: In 2010, the American Diabetes Association (ADA) added hemoglobin A1c (A1C) to the guidelines for diagnosing type 2 diabetes. However, existing models for predicting diabetes risk were developed prior to the widespread adoption of A1C. Thus, it remains unknown how well existing diabetes risk prediction models predict incident diabetes defined according to the ADA 2010 guidelines. Accordingly, we examined the performance of an existing diabetes prediction model applied to a cohort of African American (AA) and white adults from the Coronary Artery Risk Development Study in Young Adults (CARDIA).

RESEARCH DESIGN AND METHODS: We evaluated the performance of the Atherosclerosis Risk in Communities (ARIC) diabetes risk prediction model among 2,456 participants in CARDIA free of diabetes at the 2005-2006 exam and followed for 5 years. We evaluated model discrimination, calibration, and integrated discrimination improvement with incident diabetes defined by ADA 2010 guidelines before and after adding baseline A1C to the prediction model.

RESULTS: In the overall cohort, re-estimating the ARIC model in the CARDIA cohort resulted in good discrimination for the prediction of 5-year diabetes risk (area under the curve [AUC] 0.841). Adding baseline A1C as a predictor improved discrimination (AUC 0.841 vs. 0.863, P = 0.03). In race-stratified analyses, model discrimination was significantly higher in whites than AA (AUC AA 0.816 vs. whites 0.902; P = 0.008).

CONCLUSIONS: Addition of A1C to the ARIC diabetes risk prediction model improved performance overall and in racial subgroups. However, for all models examined, discrimination was better in whites than AA. Additional studies are needed to further improve diabetes risk prediction among AA. long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Mindfulness and Cardiovascular Disease Risk: State of the Evidence, Plausible Mechanisms, and Theoretical Framework

Fri, 01/22/2016 - 11:03am

The purpose of this review is to provide (1) a synopsis on relations of mindfulness with cardiovascular disease (CVD) and major CVD risk factors, and (2) an initial consensus-based overview of mechanisms and theoretical framework by which mindfulness might influence CVD. Initial evidence, often of limited methodological quality, suggests possible impacts of mindfulness on CVD risk factors including physical activity, smoking, diet, obesity, blood pressure, and diabetes regulation. Plausible mechanisms include (1) improved attention control (e.g., ability to hold attention on experiences related to CVD risk, such as smoking, diet, physical activity, and medication adherence), (2) emotion regulation (e.g., improved stress response, self-efficacy, and skills to manage craving for cigarettes, palatable foods, and sedentary activities), and (3) self-awareness (e.g., self-referential processing and awareness of physical sensations due to CVD risk factors). Understanding mechanisms and theoretical framework should improve etiologic knowledge, providing customized mindfulness intervention targets that could enable greater mindfulness intervention efficacy.

Addition of B-Type Natriuretic Peptide to Existing Clinical Risk Scores Enhances Identification of Patients at Risk for Atrial Fibrillation Recurrence After Pulmonary Vein Isolation

Fri, 01/22/2016 - 11:03am

INTRODUCTION: Predicting which patients will be free from atrial fibrillation (AF) after pulmonary vein isolation (PVI) remains challenging. Clinical risk prediction scores show modest ability to identify patients at risk for AF recurrence after PVI. B-type natriuretic peptide (BNP) is associated with risk for incident and recurrent AF but is not currently included in existing AF risk scores. We sought to evaluate the incremental benefit of adding preoperative BNP to existing risk scores for predicting AF recurrence during the 6 months after PVI.

METHODS: One hundred sixty-one patients with paroxysmal or persistent AF underwent an index PVI procedure between 2010 and 2013; 77 patients (48%) had late AF recurrence after PVI ( > 3 months post-PVI) over the 6-month follow-up period.

RESULTS: A BNP greater than or equal to 100 pg/dL (P = 0.01) and AF recurrence within 3 months after PVI (P < 0.001) were associated with late AF recurrence in multivariate analyses. Addition of BNP to existing clinical risk scores significantly improved the areas under the curve for each score, with an integrated discrimination improvement of 0.08 (P = 0.001) and a net reclassification improvement of 60% (P = 0.001) for all risk scores.

CONCLUSIONS: Circulating BNP levels are independently associated with late AF recurrence after PVI. Inclusion of BNP significantly improves the discriminative ability of CHADS2, CHA2DS2-VASc, R2CHADS2, and the HATCH score in predicting clinically significant, late AF recurrence after PVI and should be incorporated in decision-making algorithms for management of AF. B-R2CHADS2 is the best score model for prediction of late AF recurrence.

Promotion of Inflammatory Arthritis by Interferon Regulatory Factor 5 in a Mouse Model

Fri, 01/22/2016 - 11:03am

OBJECTIVE: Polymorphisms in the transcription factor interferon regulatory factor 5 (IRF5) are associated with an increased risk of developing rheumatoid arthritis (RA). This study was undertaken to determine the role of IRF5 in a mouse model of arthritis development.

METHODS: K/BxN serum-transfer arthritis was induced in mice deficient in IRF5, or lacking IRF5 only in myeloid cells, and arthritis severity was evaluated. K/BxN arthritis was also induced in mice deficient in TRIF, Toll-like receptor 2 (TLR2), TLR3, TLR4, and TLR7 to determine the pathways through which IRF5 might promote arthritis. In vitro studies were performed to determine the role of IRF5 in interleukin-1 (IL-1) receptor and TLR signaling.

RESULTS: Arthritis severity was reduced in IRF5-deficient, TRIF-deficient, TLR3-deficient, and TLR7-deficient mice. The expression of multiple genes regulating neutrophil recruitment or function and bioactive IL-1beta formation was reduced in the joints during active arthritis in IRF5-deficient mice. In vitro studies showed that TLR7 and the TRIF-dependent TLR3 pathway induce proinflammatory cytokine production in disease-relevant cell types in an IRF5-dependent manner.

CONCLUSION: Our findings indicate that IRF5 contributes to disease pathogenesis in inflammatory arthritis. This is likely due at least in part to the role of IRF5 in mediating proinflammatory cytokine production downstream of TLR7 and TLR3. Since TLR7 and TLR3 are both RNA-sensing TLRs, this suggests that endogenous RNA ligands present in the inflamed joint promote arthritis development. These findings may be relevant to human RA, since RNA capable of activating TLR7 and TLR3 is present in synovial fluid and TLR7 and TLR3 are up-regulated in the joints of RA patients.

Measuring Diversity and Inclusion in Academic Medicine: The Diversity Engagement Survey

Fri, 01/22/2016 - 11:03am

PURPOSE: To produce a physician and scientific workforce that advances high-quality research and culturally competent care, academic medical centers (AMCs) must assess their capacity for diversity and inclusion and leverage opportunities for improvement. The Diversity Engagement Survey (DES) is presented as a diagnostic and benchmarking tool.

METHOD: The 22-item DES consists of eight factors that connect engagement theory to inclusion and diversity constructs. It was piloted at 1 AMC and then administered at 13 additional U.S. AMCs in 2011-2012. Face and content validity were assessed through a review panel. Cronbach alpha was used to assess internal consistency. Confirmatory factor analysis (CFA) was used to establish construct validity. Cluster analysis was conducted to establish ability of the DES to distinguish between institutions' degrees of engagement and inclusion. Criterion validity was established using observed differences in scores for demographic groups as suggested by the literature.

RESULTS: The sample included 13,694 respondents across 14 AMCs. Cronbach alphas for the engagement and inclusion factors (range: 0.68-0.85), CFA fit indices, and item correlations with latent constructs indicated an acceptable model fit and that items measured the intended concepts. Cluster analysis of DES scores distinguished institutions with higher, middle, and lower degrees of engagement and inclusion by their respondents. Consistent with the literature, black, Hispanic/Latino, female, and LGBTQ (lesbian, gay, bisexual, transgender, queer) respondents reported lower degrees of engagement than their counterparts.

CONCLUSIONS: The DES is a reliable and valid instrument for assessment, evaluation, and external benchmarking of institutional engagement and inclusion.

Integrating Neuroscience Knowledge and Neuropsychiatric Skills Into Psychiatry: The Way Forward

Fri, 01/22/2016 - 11:03am

Increasing the integration of neuroscience knowledge and neuropsychiatric skills into general psychiatric practice would facilitate expanded approaches to diagnosis, formulation, and treatment while positioning practitioners to utilize findings from emerging brain research. There is growing consensus that the field of psychiatry would benefit from more familiarity with neuroscience and neuropsychiatry. Yet there remain numerous factors impeding the integration of these domains of knowledge into general psychiatry.The authors make recommendations to move the field forward, focusing on the need for advocacy by psychiatry and medical organizations and changes in psychiatry education at all levels. For individual psychiatrists, the recommendations target obstacles to attaining expanded neuroscience and neuropsychiatry education and barriers stemming from widely held, often unspoken beliefs. For the system of psychiatric care, recommendations address the conceptual and physical separation of psychiatry from medicine, overemphasis on the Diagnostic and Statistical Manual of Mental Disorders and on psychopharmacology, and different systems in medicine and psychiatry for handling reimbursement and patient records. For psychiatry residency training, recommendations focus on expanding neuroscience/neuropsychiatry faculty and integrating neuroscience education throughout the curriculum.Psychiatry traditionally concerns itself with helping individuals construct meaningful life narratives. Brain function is one of the fundamental determinants of individuality. It is now possible for psychiatrists to integrate knowledge of neuroscience into understanding the whole person by asking, What person has this brain? How does this brain make this person unique? How does this brain make this disorder unique? What treatment will help this disorder in this person with this brain?

The Pediatric Imaging, Neurocognition, and Genetics (PING) Data Repository

Fri, 01/22/2016 - 11:03am

The main objective of the multi-site Pediatric Imaging, Neurocognition, and Genetics (PING) study was to create a large repository of standardized measurements of behavioral and imaging phenotypes accompanied by whole genome genotyping acquired from typically-developing children varying widely in age (3 to 20 years). This cross-sectional study produced sharable data from 1493 children, and these data have been described in several publications focusing on brain and cognitive development. Researchers may gain access to these data by applying for an account on the PING portal and filing a data use agreement. Here we describe the recruiting and screening of the children and give a brief overview of the assessments performed, the imaging methods applied, the genetic data produced, and the numbers of cases for whom different data types are available. We also cite sources of more detailed information about the methods and data. Finally we describe the procedures for accessing the data and for using the PING data exploration portal.

Design of shRNA and miRNA for Delivery to the CNS

Fri, 01/22/2016 - 11:03am

Neurologic diseases tend to target various areas of the central nervous system (CNS) and can therefore result in paralysis, dementia, and death. Neurodegenerative diseases distinguish themselves from other diseases by affecting nerve cells, which unlike many other cells in our body cannot regenerate when severely injured. The discovery of RNA interference (RNAi) has enabled scientist to design new therapeutic approaches based on specific gene silencing rather than the canonical gene therapy through gene augmentation. Two types of molecules can be used for viral vector-mediated gene silencing: short hairpin RNAs (shRNAs) and artificial microRNAs (miRNAs) that have the ability to enter the RNAi pathway. Although both shRNAs and miRNAs can be used to silence genes, they enter the RNAi pathway at different points. Unlike shRNAs, miRNAs require an additional cleavage step inside the nucleus before being exported to the cytoplasm. These molecules can then be incorporated into the RNA-induced silencing complex (RISC) which utilizes sequence complementarity to recognize target mRNAs and activate either translational repression, in the case of partial complementarity, or induce mRNA cleavage in the case of complete complementarity. Elevated amounts of shRNAs, which are commonly driven by strong polymerase III promoters, can cause saturation of the endogenous RNAi machinery due to competition between endogenous and artificial molecules. Switching to a DNA polymerase II promoter is an alternative to reduce shRNA production, thereby reducing toxicity. Even though the molecules are designed to target specific mRNAs there may be off-target effects due to nonspecific binding that must be accounted for during the design process. In this chapter we discuss the design and in vitro screening of shRNAs and artificial miRNAs.

Clinical epidemiology of heart failure with preserved ejection fraction (HFpEF) in comparatively young hospitalized patients

Fri, 01/22/2016 - 11:03am

BACKGROUND: While heart failure with preserved ejection fraction (HFpEF) is primarily a disease of old age, risk factors that contribute to HFpEF are not limited to older patients. The objectives of this population-based observational study were to describe the clinical epidemiology of HFpEF in younger ( < 65years) as compared with older ( > /=65years) patients hospitalized with acute decompensated heart failure.

METHODS AND RESULTS: We reviewed the medical records of residents of central Massachusetts hospitalized with HFpEF at all 11 greater Worcester (MA) medical centers during the 5 study years of 1995, 2000, 2002, 2004, and 2006. Among the 2398 patients hospitalized with confirmed HFpEF, 357 (14.9%) were < 65years old. Younger patients were more likely to be male, non-Caucasian, obese, and to have a history of diabetes and chronic kidney disease than older patients with HFpEF. Younger patients hospitalized with HFpEF were less likely to have received commonly prescribed cardiac medications, had a longer hospital stay, and experienced significantly lower post-discharge death rates than older hospitalized patients.

CONCLUSION: While HFpEF is predominantly a disease of old age, data from longitudinal studies remain needed to identify risk factors in younger individuals that may predispose them to the development of HFpEF.

The Fly Neuromuscular Junction: Structure and Function

Thu, 01/21/2016 - 3:37pm

The Drosophila larval neuromuscular junction (NMJ) has become one of the most powerful model systems to ask key neurobiological questions. This synapse is unparalleled by its accessibility, its simplicity, and the ability to manipulate genes important for synapse development and function. Its synapses have properties shared by many organisms including humans. The vast majority of genes that when mutated cause congenital disorders of the nervous system in humans, are present in the fruit fly genome, and fly models of human disorders are available. Thus, this preparation is a powerful tool to understand the normal function of these genes. This book reviews outstanding work by recognized leaders in the fields of Drosophila cellular neurogenetics including developmental neurobiology, mechanisms of synaptic function, and experience dependent changes at synapses. The book also includes step-by-step protocols to study the cellular biology of the NMJ, making it a vital resource for researchers beginning their investigations with this system, for those who are training students and postdoctoral fellows in this area, or simply as a general reference material for neuroscientists and neuroscience professors in general.

Wnts and TGF beta in synaptogenesis: old friends signalling at new places

Thu, 01/21/2016 - 3:37pm

The formation of mature synaptic connections involves the targeted transport and aggregation of synaptic vesicles, the gathering of presynaptic release sites and the clustering of postsynaptic neurotransmitter receptors and ion channels. Positional cues are required to orient the cytoskeleton in the direction of neuronal outgrowth, and also to direct the juxtaposition of synaptic protein complexes at the pre- and postsynaptic membranes. Both anterograde and retrograde factors are thought to contribute positional information during synaptic differentiation, and recent studies in vertebrates and invertebrates have begun to uncover a new role in this process for proteins that are essential for pattern formation in the early embryo.

Exosomes go with the Wnt

Thu, 01/21/2016 - 3:37pm

Exosomes, small secreted microvesicles, are implicated in intercellular communication in diverse cell types, transporting protein, lipid and nucleic acid cargo that impact the physiology of recipient cells. Besides the signaling function of exosomes they also serve as a mechanism to dispose obsolete cellular material. Particularly exciting is the involvement of exosomal communication in the nervous system, as this has important implications for brain development and function. The properties of exosomes are also beginning to entice the biomedical community since they represent potentially novel avenues for the targeted delivery of customized exosome cargo, such as miRNAs, during disease. Our findings implicating exosomes in trans-synaptic communication emerged from the serendipitous observation that at the Drosophila larval neuromuscular junction (NMJ) the release of a signaling molecule, Wnt1/Wingless (Wg) and its binding partner Evenness Interrupted (Evi)/Wntless (Wls)/Sprint (Srt), were released by motorneurons in association with vesicles, which we postulated to be exosomes. In our most recent paper using in vivo analysis at the Drosophila NMJ as well as in cultured insect cells we formally demonstrate that Evi rides in exosomes that are released to the extracellular space and identify some of the players involved in their release. In addition, a proteomic analysis of exosomes highlights novel potential function of exosomes.

Nucleus to Synapse Nesprin1 Railroad Tracks Direct Synapse Maturation through RNA Localization

Thu, 01/21/2016 - 3:37pm

An important mechanism underlying synapse development and plasticity is the localization of mRNAs that travel from the nucleus to synaptic sites. Here we demonstrate that the giant nuclear-associated Nesprin1 (dNesp1) forms striated F-actin-based filaments, which we dubbed "railroad tracks," that span from muscle nuclei to postsynaptic sites at the neuromuscular junction in Drosophila. These railroad tracks specifically wrap around immature boutons formed during development and in response to electrical activity. In the absence of dNesp1, mRNAs normally localized at postsynaptic sites are lacking and synaptic maturation is inhibited. This dNesp1 function does not depend on direct association of dNesp1 isoforms with the nuclear envelope. We also show that dNesp1 functions with an unconventional myosin, Myo1D, and that both dNesp1 and Myo1D are mutually required for their localization to immature boutons. These studies unravel a novel pathway directing the transport of mRNAs from the nucleus to postsynaptic sites during synaptic maturation.

Implementing Standardized Patients to Teach Cultural Competency to Graduate Nursing Students

Fri, 01/15/2016 - 5:07pm

Background: Although many programs emphasize knowledge enhancement on caring for patients from diverse cultural backgrounds, few integrate cultural assessments, skills, and encounters with these patients. To fill this gap, an objective structured clinical examination (OSCE) with culturally diverse standardized patients was introduced to 29 first-year graduate nursing students.

Method: The learning experience was implemented in three phases: (a) Pretest, (b) didactic introduction to culturally sensitive issues, and (c) video-recorded OSCE with two ethnically diverse, standardized patients. A posttest and final evaluation concluded the experience.

Results/Conclusions: The objective scoring of student competency from the SPs was positive, especially their assessment of patient use of alternative therapies. The students perceived that their critical thinking skills were enhanced.