Interaction of GABA and Excitatory Amino Acids in the Basolateral Amygdala: Role in Cardiovascular Regulation

Activation of the amygdala in rats produces cardiovascular changes that include increases in heart rate and arterial pressure as well as behavioral changes characteristic of emotional arousal. The objective of the present study was to examine the interaction of GABA and excitatory amino acid (EAA) receptors in the basolateral amygdala (BLA) in regulating cardiovascular function. Microinjection of the GABAA receptor antagonist bicuculline methiodide (BMI) or the E A A receptor agonists NMDA or AMPA into the same region of the BLA of conscious rats produced dose-related increases in heart rate and arterial pressure. Injection of the nonselective EAA receptor antagonist kynurenic acid into the BLA prevented or reversed the cardiovascular changes caused by local injection of BMI or the noncompetitive GABA antagonist picrotoxin. Conversely, local pretreatment with the glutamate reuptake inhibitorl-trans-pyrrolidine-2,4-dicarboxylic acid enhanced the effects of intra-amygdalar injection of BMI. The cardiovascular effects of BMI were also attenuated by injection of either the NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) or the AMPA receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX). When these two EAA receptor antagonists were combined, their ability to suppress BMI-induced tachycardic and pressor responses was additive. These findings indicate that the cardiovascular effects caused by blockade of GABAergic inhibition in the BLA of the rat are dependent on activation of local NMDA and AMPA receptors

Counselors as Advocates: Effects of a Pilot Project Designed to Develop Advocacy Knowledge and Confidence in Trainees

While there has been increased attention to advocacy within counseling and counseling psychology, it has been noted that trainees generally feel unprepared to engage in advocacy and do not participant e in this type of work to a large extent, even with increased age or professional experience). The qualitative study summarizes the findings of a project within a graduate multicultural counseling course designed to increase trainee knowledge and confidence related to advocacy. This project required students (N = 19) to complete individual advocacy projects in the community, with opportunities for self-reflection and evaluation of their progress throughout the semester. Student reflection responses about the effects of this project were analyzed using methods from Grounded Theory by a collaborative research team. This process resulted in a core category of responses that included expanded definitions of advocacy, increased self-confidence regarding advocacy work, obstacles encountered, and reactions to the course assignment. Implications and future directions are discussed

A direct comparison of the consequences of plant genotypic and species diversity on communities and ecosystem function

Biodiversity loss is proceeding at an unprecedented rate, yet we lack a thorough understanding of the consequences of losing diversity at different scales. While species diversity is known to impact community and ecosystem processes, genotypic diversity is assumed to have relatively smaller effects. Nonetheless, a few recent studies suggest that genotypic diversity may have quantitatively similar ecological consequences compared to species diversity. Here we show that increasing either genotypic diversity of common evening primrose (Oenothera biennis) or species diversity of old?field plant species resulted in nearly equivalent increases (?17%) in aboveground primary production. The predominant mechanism explaining this effect, niche complementarity, was similar for each type of diversity. Arthropod species richness also increased with both types of plant diversity, but the mechanisms leading to this effect differed: abundance?driven accumulation of arthropod species was important in plant genotypic polycultures, whereas resource specialization was important in plant species polycultures. Thus, similar increases in primary productivity differentially impacted higher trophic levels in response to each type of plant diversity. These results highlight important ecological similarities and differences between genotypic and species diversity and suggest that genotypic diversity may play a larger role in community and ecosystem processes than previously realized.The NSF (DEB- 0950231 to A. A. Agrawal and IGERT small grant in Biogeochemistry and Environmental Biocomplexity to S. H. McArt, S. C. Cook-Patton, and A. L. Parachnowitsch) and USDA-NRI (2006-35302-17431 to J. S. Thaler) supported this wor

Correlation of esophageal pressure-flow analysis findings with bolus transit patterns on videofluoroscopy

This is a pre-copyedited, author-produced version of an article accepted for publication in Diseases of the Esophagus following peer review. The version of record Omari TI, Szczesniak MM, Maclean J, Myers JC, Rommel N, Cock C and Cook IJ. Correlation of esophageal pressure-flow analysis findings with bolus transit patterns on videofluoroscopy. Dis Esophagus. 2016 Feb-Mar;29(2):166-73. and is available online at: http://dx.doi.org/10.1111/dote.12300 Copyright © 2017 The International Society for Diseases of the EsophagusPressure-flow analysis quantifies the interactions between bolus transport and pressure generation. We undertook a pilot study to assess the interrelationships between pressure-flow metrics and fluoroscopically determined bolus clearance and bolus transport across the esophagogastric junction (EGJ). We hypothesized that findings of abnormal pressure-flow metrics would correlate with impaired bolus clearance and reduced flow across the EGJ. Videofluoroscopic images, impedance, and pressure were recorded simultaneously in nine patients with dysphagia (62–82 years, seven male) tested with liquid barium boluses. A 3.6 mm diameter solid-state catheter with 25 × 1 cm pressure/12 × 2 cm impedance was utilized. Swallowed bolus clearance was assessed using a validated 7-point radiological bolus transport scale. The cumulative period of bolus flow across the EGJ was also fluoroscopically measured (EGJ flow time). Pressure only parameters included the length of breaks in the 20 mmHg iso-contour and the 4 second integrated EGJ relaxation pressure (IRP4s). Pressure-flow metrics were calculated for the distal esophagus, these were: time from nadir impedance to peak pressure (TNadImp to PeakP) to quantify bolus flow timing; pressure flow index (PFI) to integrate bolus pressurization and flow timing; and impedance ratio (IR) to assess bolus clearance. When compared with controls, patients had longer peristaltic breaks, higher IRs, and higher residual EGJ relaxation pressures (break length of 8 [2, 13] vs. 2 [0, 2] cm, P = 0.027; IR 0.5 ± 0.1 vs. 0.3 ± 0.0, P = 0.019; IRP4s 11 ± 2 vs. 6 ± 1 mmHg, P = 0.070). There was a significant positive correlation between higher bolus transport scores and longer peristaltic breaks (Spearman correlation r = 0.895, P < 0.001) and with higher IRs (r = 0.661, P < 0.05). Diminished EGJ flow times correlated with a shorter TNadImp to PeakP (r = −0.733, P < 0.05) and a higher IR (r = −0.750, P < 0.05). Longer peristaltic breaks and higher IR correlate with failed bolus clearance on videofluoroscopy. The metric TNadImp to PeakP appears to be a marker of the period of time over which the bolus flows across the EGJ

Guidance of sentinel lymph node biopsy decisions in patients with T1-T2 melanoma using gene expression profiling.

AIM: Can gene expression profiling be used to identify patients with T1-T2 melanoma at low risk for sentinel lymph node (SLN) positivity? PATIENTS & METHODS: Bioinformatics modeling determined a population in which a 31-gene expression profile test predicted \u3c5% SLN positivity. Multicenter, prospectively-tested (n = 1421) and retrospective (n = 690) cohorts were used for validation and outcomes, respectively. RESULTS: Patients 55-64 years and ≥65 years with a class 1A (low-risk) profile had SLN positivity rates of 4.9% and 1.6%. Class 2B (high-risk) patients had SLN positivity rates of 30.8% and 11.9%. Melanoma-specific survival was 99.3% for patients ≥55 years with class 1A, T1-T2 tumors and 55.0% for class 2B, SLN-positive, T1-T2 tumors. CONCLUSION: The 31-gene expression profile test identifies patients who could potentially avoid SLN biopsy

Culture of equine fibroblast-like synoviocytes on synthetic tissue scaffolds towards meniscal tissue engineering: a preliminary cell-seeding study

Introduction. Tissue engineering is a new methodology for addressing meniscal injury or loss. Synovium may be an ideal source of cells for in vitro meniscal fibrocartilage formation, however, favorable in vitro culture conditions for synovium must be established in order to achieve this goal. The objective of this study was to determine cellularity, cell distribution, and extracellular matrix (ECM) formation of equine fibroblast-like synoviocytes (FLS) cultured on synthetic scaffolds, for potential application in synovium-based meniscal tissue engineering. Scaffolds included open-cell poly-L-lactic acid (OPLA) sponges and polyglycolic acid (PGA) scaffolds cultured in static and dynamic culture conditions, and PGA scaffolds coated in poly-L-lactic (PLLA) in dynamic culture conditions.Materials and Methods. Equine FLS were seeded on OPLA and PGA scaffolds, and cultured in a static environment or in a rotating bioreactor for 12 days. Equine FLS were also seeded on PGA scaffolds coated in 2% or 4% PLLA and cultured in a rotating bioreactor for 14 and 21 days. Three scaffolds from each group were fixed, sectioned and stained with Masson’s Trichrome, Safranin-O, and Hematoxylin and Eosin, and cell numbers and distribution were analyzed using computer image analysis. Three PGA and OPLA scaffolds from each culture condition were also analyzed for extracellular matrix (ECM) production via dimethylmethylene blue (sulfated glycosaminoglycan) assay and hydroxyproline (collagen) assay. PLLA coated PGA scaffolds were analyzed using double stranded DNA quantification as areflection of cellularity and confocal laser microscopy in a fluorescent cell viability assay.Results. The highest cellularity occurred in PGA constructs cultured in a rotating bioreactor, which also had a mean sulfated glycosaminoglycan content of 22.3 µg per scaffold. PGA constructs cultured in static conditions had the lowest cellularity. Cells had difficulty adhering to OPLA and the PLLA coating of PGA scaffolds; cellularity was inversely proportional to the concentration of PLLA used. PLLA coating did not prevent dissolution of the PGA scaffolds. All cell scaffold types and culture conditions produced non-uniform cellular distribution.Discussion/Conclusion. FLS-seeding of PGA scaffolds cultured in a rotating bioreactor resulted in the most optimal cell and matrix characteristics seen in this study. Cells grew only in the pores of the OPLA sponge, and could not adhere to the PLLA coating of PGA scaffold, due to the hydrophobic property of PLA. While PGA culture in a bioreactor produced measureable GAG, no culture technique produced visible collagen. For this reason, and due to the dissolution of PGA scaffolds, the culture conditions and scaffolds described here are not recommended for inducing fibrochondrogenesis in equine FLS for meniscal tissue engineering

First Results from the Mojave Volatiles Prospector (MVP) Field Campaign, a Lunar Polar Rover Mission Analog

The Mojave Volatiles Prospector (MVP) project is a science-driven field program with the goal to produce critical knowledge for conducting robotic exploration of the Moon. MVP will feed science, payload, and operational lessons learned to the development of a real-time, short-duration lunar polar volatiles prospecting mission. MVP achieves these goals through a simulated lunar rover mission to investigate the composition and distribution of surface and subsurface volatiles in a natural and a priori unknown environment within the Mojave Desert, improving our understanding of how to find, characterize, and access volatiles on the Moon. The MVP field site is the Mojave Desert, selected for its low, naturally occurring water abundance. The Mojave typically has on the order of 2-6% water, making it a suitable lunar analog for this field test. MVP uses the Near Infrared and Visible Spectrometer Subsystem (NIRVSS), Neutron Spectrometer Subsystem (NSS), and a downward facing GroundCam camera on the KREX-2 rover to investigate the relationship between the distribution of volatiles and soil crust variation. Through this investigation, we mature robotic in situ instruments and concepts of instrument operations, improve ground software tools for real time science, and carry out publishable research on the water cycle and its connection to geomorphology and mineralogy in desert environments. A lunar polar rover mission is unlike prior space missions and requires a new concept of operations. The rover must navigate 3-5 km of terrain and examine multiple sites in in just ~6 days. Operational decisions must be made in real time, requiring constant situational awareness, data analysis and rapid turnaround decision support tools. This presentation will focus on the first science results and operational architecture findings from the MVP field deployment relevant to a lunar polar rover mission

Screening for Major Depressive Disorder in Children and Adolescents: A Systematic Review for the U.S. Preventive Services Task Force

BACKGROUND: Major depressive disorder (MDD) is common among children and adolescents and is associated with functional impairment and suicide. PURPOSE: To update the 2009 U.S. Preventive Services Task Force (USPSTF) systematic review on screening for and treatment of MDD in children and adolescents in primary care settings. DATA SOURCES: Several electronic searches (May 2007 to February 2015) and searches of reference lists of published literature. STUDY SELECTION: Trials and recent systematic reviews of treatment, test-retest studies of screening, and trials and large cohort studies for harms. DATA EXTRACTION: Data were abstracted by 1 investigator and checked by another; 2 investigators independently assessed study quality. DATA SYNTHESIS: Limited evidence from 5 studies showed that such tools as the Beck Depression Inventory and Patient Health Questionnaire for Adolescents had reasonable accuracy for identifying MDD among adolescents in primary care settings. Six trials evaluated treatment. Several individual fair- and good-quality studies of fluoxetine, combined fluoxetine and cognitive behavioral therapy, escitalopram, and collaborative care demonstrated benefits of treatment among adolescents, with no associated harms. LIMITATION: The review included only English-language studies, narrow inclusion criteria focused only on MDD, high thresholds for quality, potential publication bias, limited data on harms, and sparse evidence on long-term outcomes of screening and treatment among children younger than 12 years. CONCLUSION: No evidence was found of a direct link between screening children and adolescents for MDD in primary care or similar settings and depression or other health-related outcomes. Evidence showed that some screening tools are accurate and some treatments are beneficial among adolescents (but not younger children), with no evidence of associated harms. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality

Myocardial ischemia in the absence of epicardial coronary artery disease in Friedreich's ataxia

We present the first in vivo detection of microvascular abnormality in a patient with Friedreich's ataxia (FA) without epicardial coronary artery disease using cardiac magnetic resonance (CMR). The patient had exertional chest pain and dyspnea prompting referral for cardiac evaluation. These symptoms were reproduced during intravenous adenosine infusion, and simultaneous first-pass perfusion imaging showed a significant subendocardial defect; both symptoms and perfusion deficit were absent at rest. Epicardial coronaries were free of disease by invasive angiography; together, these findings support the notion of impaired myocardial perfusion reserve in FA