Investigation of Neuropeptide Y as a metabolic marker and its effects on adipose vasculature and brainstem astrocytes

Subsets of morbidly obese patients do not appear to exhibit the expected comorbidities, as well as the fact that heightened sympathetic nervous system (SNS) activity has been known to affect metabolism. In this study, Neuropeptide Y (NPY), an SNS co-transmitter is explored as a possible biomarker for unhealthy obesity. The aims of the study were to identify a normoinsulinemic/insulin sensitive morbidly obese Caucasian patient cohort, compare differences in NPY levels in the circulation and adipose tissue between the normoinsulinemic and hyperinsulinemic subjects. I explored the hypothesis that elevated circulating peripheral NPY causes metabolic abnormalities by mediating changes in the normal function of brain stem regulatory mechanisms via inflammation of astrocytes as shown in an in vitro model of primary cell line of human fetal brain stem astrocyte cell line. Blood and abdominal adipose tissue samples were obtained from consenting, morbidly obese patients awaiting bariatric surgery for recruitment in the study. Adipokines and NPY were measured as well as gene and protein expression by real-time PCR and histology. Effect of NPY was determined on a human brainstem astrocytic primary cell-line using immunohistochemistry, real time PCR, cytokine ELISA, intracellular secondary messengers via ELISA and fluorescence microscopy. Secreted lactate levels were measured by calorimetric assays. Differences were found between metabolically healthy obese (MHO) and pathologically obese (PO)/diabetic groups in certain adipokines and insulin sensitivity, which were maintained after surgical weight loss. Differences in adipocyte cell size were visible between the two groups both in subcutaneous and omental adipose tissue depots but inflammatory cell infiltration was not different. Brain stem astrocytes expressed NPY receptors and IL-6 secretion from the astrocytes increased when exposed to a combination of NPY and noradrenaline, reflected by changes in intracellular cAMP. Cytokine array showed increases in various inflammatory cytokines under the same treatment. IL-6 treatment increased astrocyte lactate levels. In astrocytes there was greater level of adrenergic signalling and secretion of IL-6 and lactate by the cells, which could mean different metabolic balance of astrocytes and long-term effects on astrocyte chemosensing function. These findings suggest differences in susceptibility to obesity associated pathologies linked to a synergistic modulation between the intracellular signalling pathways of astrocytes, being regulated at least partially by components of the CNS and having a direct effect on the cells. Perhaps these would pave the way for targeted treatment modalities. In vivo studies in an analogous animal model would further clarify the connection between elevated peripheral NPY and its central effects on the brainstem astrocytes in mediating metabolic disease

Enhancing big data application design with the DICE framework

The focus of the DICE project is to define a quality-driven framework for developing Big data applications. DICE offers an Eclipse-based development environment, centered around a novel UML profile, to prototype, deploy, monitor, and test Big data applications. The DICE framework has been designed to natively support popular open-source solutions. The framework offers a set of 15 open source tools, which have been validated against industrial case studies in the news and media, port operations, and e-government domains

Community Engagement through Interactive Field-Based Activities

This qualitative case study consisted of social justice interactive field-based experiential learning activities designed to understand community partnerships between a university and local public school. The research question was: How can interactive field-based activities build closer community ties? The theoretical foundation incorporated Ken Zeichner’s “hybrid spaces” with the premise of field-based interactive experiences. The findings indicated the need for further activities that create partnerships between teacher education programs and neighboring public schools

Three-dimensional structure of human serum albumin

The binding locations to human serum albumin (HSA) of several drug molecules were determined at low resolution using crystallographic methods. The principal binding sites are located within subdomains IIA and IIIA. Preliminary studies suggest that an approach to increasing the in vivo efficacy of drugs which are rendered less effective or ineffective by virtue of their interaction with HSA, would be the use of competitive displacement in drug therapies and/or the development of a general inhibitor to the site within subdomain IIIA. These findings also suggest that the facilitated transfer of various ligands across organ/circulatory interfaces such as liver, kidney, and brain may be associated with binding to the IIIA subdomain

Is depression a real risk factor for acute myocardial infarction mortality? A retrospective cohort study

Background: Depression has been associated with a higher risk of cardiovascular events and a higher mortality in patients with one or more comorbidities. This study investigated whether continuative use of antidepressants (ADs), considered as a proxy of a state of depression, prior to acute myocardial infarction (AMI) is associated with a higher mortality afterwards. The outcome to assess was mortality by AD use. Methods: A retrospective cohort study was conducted in the Veneto Region on hospital discharge records with a primary diagnosis of AMI in 2002-2015. Subsequent deaths were ascertained from mortality records. Drug purchases were used to identify AD users. A descriptive analysis was conducted on patients' demographics and clinical data. Survival after discharge was assessed with a Kaplan-Meier survival analysis and Cox's multiple regression model. Results: Among 3985 hospital discharge records considered, 349 (8.8%) patients were classified as AD users'. The mean AMI-related hospitalization rate was 164.8/100,000 population/year, and declined significantly from 204.9 in 2002 to 130.0 in 2015, but only for AD users (-40.4%). The mean overall follow-up was 4.64.1years. Overall, 523 patients (13.1%) died within 30days of their AMI. The remainder survived a mean 5.3 +/- 4.0years. After adjusting for potential confounders, use of antidepressants was independently associated with mortality (adj OR=1.75, 95% CI: 1.40-2.19). Conclusions: Our findings show that AD users hospitalized for AMI have a worse prognosis in terms of mortality. The use of routinely-available records can prove an efficient way to monitor trends in the state of health of specific subpopulations, enabling the early identification of AMI survivors with a history of antidepressant use

LIMIX: genetic analysis of multiple traits

Multi-trait mixed models have emerged as a promising approach for joint analyses of multiple traits. In principle, the mixed model framework is remarkably general. However, current methods implement only a very specific range of tasks to optimize the necessary computations. Here, we present a multi-trait modeling framework that is versatile and fast: LIMIX enables to exibly adapt mixed models for a broad range of applications with different observed and hidden covariates, and variable study designs. To highlight the novel modeling aspects of LIMIX we performed three vastly different genetic studies: joint GWAS of correlated blood lipid phenotypes, joint analysis of the expression levels of the multiple transcript-isoforms of a gene, and pathway-based modeling of molecular traits across environments. In these applications we show that LIMIX increases GWAS power and phenotype prediction accuracy, in particular when integrating stepwise multi-locus regression into multi-trait models, and when analyzing large numbers of traits. An open source implementation of LIMIX is freely available at: https://github.com/PMBio/limix

Linear Growth through 12 Years is Weakly but Consistently Associated with Language and Math Achievement Scores at Age 12 Years in 4 Low- or Middle-Income Countries.

BackgroundWhether linear growth through age 12 y is associated with language and math achievement at age 12 y remains unclear.ObjectiveOur objective was to investigate associations of linear growth through age 12 y with reading skill, receptive vocabulary, and mathematics performance at age 12 y in 4 low- or middle-income countries (LMICs).MethodsWe analyzed data from the Young Lives Younger Cohort study in Ethiopia (n = 1275), India (n = 1350), Peru (n = 1402), and Vietnam (n = 1594). Age 1, 5, 8, and 12 y height-for-age z scores (HAZ) were calculated. Language and math achievement at age 12 y was assessed with the use of country-specific adaptations of the Peabody Picture Vocabulary Test, the Early Grades Reading Assessment, and a mathematics test; all test scores were standardized by age within country. We used path analysis to examine associations of HAZ with achievement scores. Twelve models were examined at each age (3 tests across 4 countries).ResultsMean HAZ in each country was <-1.00 at all ages. Overall, linear growth through age 12 y was associated with 0.4-3.4% of the variance in achievement scores. HAZ at 1 y was positively and significantly associated with the test score in 11 of the 12 models. This association was significantly mediated through HAZ at 5, 8, and 12 y in 9 of the models. HAZ at 5, 8, and 12 y was positively and significantly associated with test scores in 8, 8, and 6 models, respectively. These associations were mediated through HAZ at older ages in 6 of the HAZ at 5-y models and in 6 of the HAZ at 8-y models.ConclusionChild relative linear growth between ages 1 and 12 y was weakly but consistently associated with language and math achievement at age 12 y in 4 LMICs

WooDesign ad Arte Sella

Il tema dell'arte, architettura e design vissuto attraverso le attività dell'Associazione Arte Sella nell'ambito del proprio laboratorio naturale sulle Dolomiti. Da molti anni luogo di richiamo per artisti e sperimentatori di performances e allestimenti con elementi naturali, Arte Sella pone un unico vincolo alle opere: che siano realizzate con esclusivo utilizzo di elementi naturali trovati nel Parco e pertanto oggetto di una permanenza effimera legata al susseguirsi delle stagioni. WooDesign incrocia arte, architettura e natura in un workshop finalizzato all'allestimento delle principali zone di ingresso al Parco