N-Arachidonoyl Dopamine Modulates Acute Systemic Inflammation via Nonhematopoietic TRPV1.

N-Arachidonoyl dopamine (NADA) is an endogenous lipid that potently activates the transient receptor potential vanilloid 1 (TRPV1), which mediates pain and thermosensation. NADA is also an agonist of cannabinoid receptors 1 and 2. We have reported that NADA reduces the activation of cultured human endothelial cells by LPS and TNF-α. Thus far, in vivo studies using NADA have focused on its neurologic and behavioral roles. In this article, we show that NADA potently decreases in vivo systemic inflammatory responses and levels of the coagulation intermediary plasminogen activator inhibitor 1 in three mouse models of inflammation: LPS, bacterial lipopeptide, and polymicrobial intra-abdominal sepsis. We also found that the administration of NADA increases survival in endotoxemic mice. Additionally, NADA reduces blood levels of the neuropeptide calcitonin gene-related peptide but increases the neuropeptide substance P in LPS-treated mice. We demonstrate that the anti-inflammatory effects of NADA are mediated by TRPV1 expressed by nonhematopoietic cells and provide data suggesting that neuronal TRPV1 may mediate NADA's anti-inflammatory effects. These results indicate that NADA has novel TRPV1-dependent anti-inflammatory properties and suggest that the endovanilloid system might be targeted therapeutically in acute inflammation

Idaho National Engineering Laboratory Radiological Environmental Surveillance Program 1995 annual report

This report describes calendar year 1995 environmental surveillance activities of Environmental Monitoring and Water Resources of Lockheed Martin Idaho Technologies Company, performed at the following Waste Management Facilities: the Radioactive Waste Management Complex, the Waste Experimental Reduction Facility, the Mixed Waste Storage Facility, and tow surplus facilities. Results of the sampling performed by the Radiological Environmental Surveillance Program, Site Environmental Surveillance Program, and the United States Geological Survey at these facilities are included in this report. The primary purposes of monitoring are to evaluate environmental conditions, to provide and interpret data, to verify compliance with applicable regulations or standards and to ensure protection of human health and the environment. This report compares 1995 environmental surveillance data with US DOE Derived Concentration Guides and with data form previous years

Projected t-SNE for batch correction

Motivation: Low-dimensional representations of high-dimensional data are routinely employed in biomedical research to visualize, interpret and communicate results from different pipelines. In this article, we propose a novel procedure to directly estimate t-SNE embeddings that are not driven by batch effects. Without correction, interesting structure in the data can be obscured by batch effects. The proposed algorithm can therefore significantly aid visualization of high-dimensional data. Results: The proposed methods are based on linear algebra and constrained optimization, leading to efficient algorithms and fast computation in many high-dimensional settings. Results on artificial single-cell transcription profiling data show that the proposed procedure successfully removes multiple batch effects from t-SNE embeddings, while retaining fundamental information on cell types. When applied to single-cell gene expression data to investigate mouse medulloblastoma, the proposed method successfully removes batches related with mice identifiers and the date of the experiment, while preserving clusters of oligodendrocytes, astrocytes, and endothelial cells and microglia, which are expected to lie in the stroma within or adjacent to the tumours. Contact: [email protected]

Association Between Single Nucleotide Polymorphisms in the Cannabinoid Receptor Gene (CNR1) and Impulsivity in Southwest California Indians

Abstract Impulsivity is a personality trait characterized by acting suddenly in an unplanned manner in order to satisfy a desire without consideration for the consequences of such behavior. There are several psychiatric disorders that include the term impulsivity as a criterion and, therefore, it has been suggested that impulsivity may be an important phenotype that may link a number of different behavioral disorders, including substance abuse. This study's aims were to determine if a significant association could be detected between the (AAT)n triplet repeat polymorphism as well as 5 single nucleotide polymorphisms (SNPs) in or near the CNR1 receptor gene and impulsivity in Southwest California ‘Mission’ Indians (SWC). Impulsivity was assessed using a scale derived from the Maudsley personality inventory, and blood samples were collected for DNA analyses from 251 individuals recruited from local Indian reservations. The estimated heritability (h 2 ) for the impulsivity phenotype was 0.20 + 0.12 ( p < .004). Impulsivity was significantly associated with the 6-repeat allele of the triplet repeat polymorphism (AATn/A6; p < .0001), as well as four SNPs in or near the CNR1 receptor gene: rs1535255 ( p = .001), rs2023239 ( p = .004), rs1049353 ( p < .001) and rs806368 ( p < .0006). These studies provide data to suggest that the CNR1 receptor gene may be significantly associated with impulsivity in SWC Indians

Effect of octanoic acid-rich formula on plasma ghrelin levels in cachectic patients with chronic respiratory disease

<p>Abstract</p> <p>Background</p> <p>For cachectic patients with chronic respiratory disease (CRD), conventional enteral nutrition formula is an optional treatment to maintain energy balance. The molecular mechanisms by which enteral nutrition formula controls appetite and weight remain unknown. We examined whether enteral nutrition formula rich in octanoic acids would increase plasma levels of ghrelin, an appetite-stimulating hormone produced in the stomach, in cachectic patients with CRD.</p> <p>Methods</p> <p>Plasma ghrelin profiles in cachectic patients with CRD were assessed and compared with those in age- and sex-matched controls. Plasma levels of acyl-ghrelin, an active ghrelin modified by octanoic acids, and desacyl-ghrelin were measured separately. We examined changes in 24-h plasma ghrelin profiles before and after single administration of the formula. We also evaluated the effects of 2-week administration of the formula on plasma ghrelin levels and nutritional status in patients.</p> <p>Results</p> <p>The ratio of acyl-ghrelin to desacyl-ghrelin in plasma was lower in patients than in controls. Single administration of the formula did not change plasma desacyl-ghrelin levels, but induced an increase in acyl-ghrelin levels. Two-week treatment with the formula was effective in increasing weight and acyl-ghrelin, along with improving nutritional status in patients.</p> <p>Conclusion</p> <p>These results show that the formula contributes to increased weight, which may be associated with induction of acyl-ghrelin production in cachectic patients with CRD.</p

Long-term symptoms in dizzy patients examined in a university clinic

Background: The long-term course of dizziness was investigated combining medical chart and survey data. The survey was undertaken median (interquartile range (IQR)) 4.6 (4.3) years after the initial medical examination. Methods: Chart data comprised sex, age, diagnosis, symptom duration, postural sway and neck pain. Survey data comprised symptom severity assessed by the Vertigo Symptom Scale – Short Form (VSS-SF), and data regarding current state of dizziness, medication, neck pain and other chronic conditions. Results: The sample consisted of 503 patients, the mean (standard deviation (SD)) age was 50.0 (11.6) years, women being slightly overrepresented (60%). Severe problems with dizziness (VSS-SF mean (SD) 13.9, (10.8)) were indicated in the total group and in 5 of 6 diagnostic sub-groups. Vertigo/balance- and autonomic/anxiety-related symptoms were present in all groups. Current dizziness was confirmed by 73% who had significantly more severe problems than the non-dizzy (VSS-SF mean (SD): 17.2 (10.1) versus 5.0 (7.3)). Symptoms were related to vertigo/balance more than to autonomic/anxiety (test of interaction p < 0.001). Based on simple logistic regression analysis, sex, symptom duration, neck pain, sway and diagnoses predicted dizziness. Symptom duration and neck pain remained predictors in the adjusted analysis. Age, symptom duration, neck pain, sway and diagnoses predicted vertigo/balance-related dizziness in both regression analyses. Sex, neck pain and sway predicted development of autonomic/anxiety-related dizziness according to simple regression analysis, while only neck pain remained a significant predictor in the adjusted analysis. With respect to diagnosis, simple regression analysis showed significant reduced likelihood for development of dizziness in all vestibular sub-groups when compared to the non-otogenic dizziness group. With respect to vertigo/balance- and autonomic/anxiety-related symptoms, the implication of diagnostic belonging varied. No effect of diagnoses was seen in adjusted analyses. Conclusion: The majority of patients had persistent and severe problems with dizziness. The wait-and-see attitude before referral to specialist institutions may be questioned. Early, active movements seem necessary, and attention should be paid to the presence of neck pain. Diagnoses had limited prognostic value. Questionnaire-based evaluations could assist in classification and identification of type of dizziness and thereby provide a better basis for specific rehabilitation

Clarification of the Three-Body Decay of 12C (12.71 MeV)

Using β decays of a clean source of 12 N produced at the IGISOL facility, we have measured the breakup of the 12 C (12.71 MeV) state into three α particles with a segmented particle detector setup. The high quality of the data permits solving the question of the breakup mechanism of the 12.71 MeV state, a longstanding problem in few-body nuclear physics. Among existing models, a modified sequential model fits the data best, but systematic deviations indicate that a three-body description is needed

Delayed β-cell response and glucose intolerance in young women with Turner syndrome

<p>Abstract</p> <p>Background</p> <p>To investigate glucose homeostasis in detail in Turner syndrome (TS), where impaired glucose tolerance (IGT) and type 2 diabetes are frequent.</p> <p>Methods</p> <p>Cross sectional study of women with Turner syndrome (TS)(n = 13) and age and body mass index matched controls (C) (n = 13), evaluated by glucose tolerance (oral and intravenous glucose tolerance test (OGTT and IVGTT)), insulin sensitivity (hyperinsulinemic, euglycemic clamp), beta-cell function (hyperglycaemic clamp, arginine and GLP-1 stimulation) and insulin pulsatility.</p> <p>Results</p> <p>Fasting glucose and insulin levels were similar. Higher glucose responses was seen in TS during OGTT and IVGTT, persisting after correction for body weight or muscle mass, while insulin responses were similar in TS and C, despite the higher glucose level in TS, leading to an insufficient increase in insulin response during dynamic testing. Insulin sensitivity was comparable in the two groups (TS vs. control: 8.6 ± 1.8 vs. 8.9 ± 1.8 mg/kg*30 min; p = 0.6), and the insulin responses to dynamic β-cell function tests were similar. Insulin secretion patterns examined by deconvolution analysis, approximate entropy, spectral analysis and autocorrelation analysis were similar. In addition we found low IGF-I, higher levels of cortisol and norepinephrine and an increased waist-hip ratio in TS.</p> <p>Conclusions</p> <p>Young normal weight TS women show significant glucose intolerance in spite of normal insulin secretion during hyperglycaemic clamping and normal insulin sensitivity. We recommend regularly testing for diabetes in TS.</p> <p>Trial Registration</p> <p>Registered with <url>http://clinicaltrials.com</url>, ID nr: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00419107">NCT00419107</a></p

Low-lying resonance states in the Be-9 continuum

Excited states in Be-9 from 2 to 9 MeV are studied via beta delayed particle emission from Li-9. The broad overlapping particle unbound states are investigated using an extension of an experimental method developed for dealing with three-body decays of broad isolated levels. The results confirm the existence of a broad state at 5 MeV, with a width of 2 MeV. Angular correlations are used for firm spin determinations for this and other levels