The corticotrophin-releasing factor/urocortin system regulates white fat browning in mice through paracrine mechanisms

Objectives: The corticotrophin-releasing factor (CRF)/urocortin system is expressed in the adipose tissue of mammals, but its functional role in this tissue remains unknown. Methods: Pharmacological manipulation of the activity of CRF receptors, CRF1 and CRF2, was performed in 3T3L1 white pre-adipocytes and T37i brown pre-adipocytes during in vitro differentiation. The expression of genes of the CRF/urocortin system and of markers of white and brown adipocytes was evaluated along with mitochondrial biogenesis and cellular oxygen consumption. Metabolic evaluation of corticosterone-deficient or supplemented Crhr1-null (Crhr1−/−) mice and their wild-type controls was performed along with gene expression analysis carried out in white (WAT) and brown (BAT) adipose tissues. Results: Peptides of the CRF/urocortin system and their cognate receptors were expressed in both pre-adipocyte cell lines. In vitro pharmacological studies showed an inhibition of the expression of the CRF2 pathway by the constitutive activity of the CRF1 pathway. Pharmacological activation of CRF2 and, to a lesser extent, inhibition of CRF1 signaling induced molecular and functional changes indicating transdifferentiation of white pre-adipocytes and differentiation of brown pre-adipocytes. Crhr1−/− mice showed increased expression of CRF2 and its agonist Urocortin 2 in adipocytes that was associated to brown conversion of WAT and activation of BAT. Crhr1−/− mice were resistant to diet-induced obesity and glucose intolerance. Restoring physiological circulating corticosterone levels abrogated molecular changes in adipocytes and the favorable phenotype of Crhr1−/− mice. Conclusions: Our findings suggest the importance of the CRF2 pathway in the control of adipocyte plasticity. Increased CRF2 activity in adipocytes induces browning of WAT, differentiation of BAT and is associated with a favorable metabolic phenotype in mice lacking CRF1. Circulating corticosterone represses CRF2 activity in adipocytes and may thus regulate adipocyte physiology through the modulation of the local CRF/urocortin system. Targeting CRF receptor signaling specifically in the adipose tissue may represent a novel approach to tackle obesity

Relación de la calidad de vida profesional y el burnout en médicos de atención primaria

ObjetivoConocer la relación, si es que la hay, entre la calidad de vida profesional (CVP) y burnout de facultativos de atención primaria.DiseñoEstudio transversal mediante cuestionario CVP-35 y MBI (Maslach Burnout Inventory), por correo postal.ÁmbitoTres centros urbanos y 3 zonas de atención rural. Participó un total de 131 profesionalesMedicionesDel CVP-35 se obtienen puntuaciones que van de 0 (mínimo) a 10 (máximo). El cuestionario Maslach clasifica en nivel alto, medio y bajo de cada dimensión.ResultadosContestó a la encuesta el 71,7%. La edad media era de 44 años y la media de tarjetas sanitarias, 1.339. El número de consultas/día fue de 37; en cuanto las visitas domiciliarias, realizaban una diaria. El valor medio de la CVP fue de 4,48 (intervalo de confianza [IC] del 95%, 4,08-4,88). La percepción de la demanda tuvo una puntuación de 5,9 (IC del 95%, 5,6-6,1); la motivación intrínseca del profesional se situó en 6,5 (IC del 95%, 6,2-6,7) y el apoyo de los directivos en 3,8 (IC del 95%, 3,6-4,1). En cuanto al cuestionario MBI, se observó una despersonalización alta en el 54,3%, cansancio emocional alto en un 56,2% y realización personal alta en el 9,3%. La correlación mayor fue entre las demandas en el puesto y el cansancio emocional (r=0,6; p<0,0001), la motivación intrínseca y la realización personal (r=0,46; p<0,0001) y la calidad de vida profesional frente al cansancio emocional (r=−0,4; p<0,0005).ConclusionesLa CVP y el burnout miden dimensiones diferentes pero relacionadas. Por tanto, su utilidad es diferente en función de los objetivos. Con estos instrumentos se pueden identificar elementos clave de la gestión de personas que pueden mejorar la calidad de vida profesional.ObjectiveTo know the relationship, if this exists, between the quality of professional life (CPL) and the burnout of primary health care staff.DesignTransversal study employing CVP-35 test and MBI (Maslach Burnout Inventory), both sent by postmail.Setting3 urban centers and 3 rural centers. Total: 131 professionals.MeasuresIn the CVP-35 test, scores from 0 (minimum) to 100 (maximum) are obtained. Maslach categorised each dimension into high, medium and low level.Results71.7% answered. Medium age 44 years, average of 1339 sanitary cards. The number of visits/day was 37, home visits 1 per day. The CVP average was 4.48 (95% CI, 4.08-4.88). The damage perception in the post 5.9 (95% CI, 5.6-6.1); the professional intrinsic motivation 6.5 (95% CI, 6.2-6.7), and the manager support 3.8 (95% CI, 3.6-4.1). MBI: high depersonalization 54.3%, emotional exhaustion (r=0.6; P<.0001), intrinsic motivation, and personal accomplishment (r=0.46; P<.0001) and profesional quality of life front emotional fatigue (r= −0.4; P<.0005).ConclusionsCPL and burnout measure different but related dimensions. Therefore, its utility is dependent on the objectives. Target elements, which can improve the quality of professional life, can be identified from these tools

Otimização da extração de ergosterol assistida por ultrassons a partir do cogumelo Agaricus bisporus L.

Os cogumelos são apreciados em todo o mundo, não só pelo seu valor nutricional, sabor apurado e textura, mas também pelas suas propriedades medicinais. Existem evidências científicas que demonstram os benefícios do consumo de cogumelos, que advém da sua riqueza em compostos bioativos, tais como micosteróis, e em particular, do ergosterol. Agaricus bisporus L. é o cogumelo mais consumido em todo o mundo, apresentando um elevado teor em ergosterol, cerca de 90% da sua fração de esteróis. Assim, este torna-se numa matriz muito interessante para a obtenção de ergosterol, uma molécula de elevado valor comercial. Segundo a literatura, o teor de ergosterol pode variar entre 3 e 9 mgporg de cogumelo seco. Atualmente, os métodos tradicionais tais como a maceração e a extração em Soxhlet estão a ser substituídos por metodologias emergentes, nomeadamente a extração assistida por ultrassons, visando diminuir a quantidade de solvente utilizado, o tempo de extração e, naturalmente, aumentar o rendimento da mesma. No presente trabalho, utitizou-se A. bisporus como fonte de ergosterol, tendo-se otimizado as condições mais favoráveis à sua extração utilizando a tecnologia de ultrassons variando o tipo solvente (hexano e etanol), a amplitude (50%, 75% e 100%) e o tempo (5 min, 10 min e 15 min). Além disso, e de forma a simplificar o processo, foi avaliada a pertinência da etapa de saponificação. O etanol demonstrou ser o melhor solvente, originando os rendimentos de ergosterol mais elevados (671, 5±0,5 mg/100 g de massa seca, com 75% de amplitude durante 15 min). Com hexano foi possível extrair apenas 152,2±0,2 mg/100 g, nas mesmas condições. No entanto, o extraio obtido com hexano mostrou ter uma pureza superior (11%) ao do extraio obtido com etanol (4%). No caso do extraio etanólico, o passo de saponificação aumentou consideravelmente a sua pureza, enquanto para o extraio obtido com hexano a pureza foi similar. Na verdade, o hexano apresenta maior setetividade para os compostos lipofílicos comparativamente com o etanol. Em geral, a extração assistida por ultrassons demonstrou ser uma tecnologia eficiente para maximizar o rendimento de extração em ergosterol. Outras tecnologias emergentes, tais como a extração assistida por micro-ondas, apresentam-se promissoras podendo originar também resultados promissores

Life on the ice-edge: Paleoenvironmental significance of the radiolarian species Amphimelissa setosa in the northern hemisphere

The high-latitude Northern Hemisphere is a key region in the global climate balance. Variations in sea-ice extent affect biological productivity, CO2 exchange and carbon drawdown. Marine proxies indicative of proximity of the ice-marginal zone are therefore essential to understand these processes. Amphimelissa setosa is nowadays a dominant radiolarian species in the Arctic basin and very abundant in the high-latitude North Atlantic. This species, now absent from the North Pacific, has been widely used as a qualitative proxy of modern and past environmental conditions in the high-latitude Northern Hemisphere. Using our new and published data on the distribution of A. setosa in plankton, sediment trap, surface sediment and downcore samples, we provide a quantitative ecological context for the occurrence of this species. We find that the optimal depth and season of A. setosa in the modern North Atlantic and the Chukchi Sea are 160 m and the late boreal summer/early fall (August–October), respectively. A regression model combining environmental variables (temperature, salinity, silicate and chlorophyll-a concentrations, apparent oxygen utilization, sea-ice) at that season and depth, are able to explain 43% of the distribution of this species in surface sediments. Based on these new findings, we conclude that the presence of A. setosa in surface sediments is closely related to high primary production in the proximity of the sea-ice and areas of ice rafting. The onset of this species started at ca. 1.5 Ma in the North Pacific, linked to a gradual cooling, increased silica availability and southward advance of the ice-margins since the Early Pleistocene. Amphimelissa setosa’s decline in this region was likely caused by the development of a quasi-permanent halocline, perennial sea-ice and depletion of silica during marine isotope stage 4. In the high-latitude North Atlantic, the relative abundance of A. setosa appears to be related to cooling and supply of dissolved silica from the continent during ice-rafting events. The comprehensive approach taken in this study suggest that A. setosa is a useful proxy to explore past variations in the ice-cover in the high-latitude Northern Hemisphere.Shirshov Institute of Oceanology | Ref. 0149-2019-000

Sensitization of retinoids and corticoids to epigenetic drugs in MYC-activated lung cancers by antitumor reprogramming

Components of the SWI/SNF chromatin remodeling complex, including BRG1 (also SMARCA4), are inactivated in cancer. Among other functions, SWI/SNF orchestrates the response to retinoid acid (RA) and glucocorticoids (GC) involving downregulation of MYC. The epigenetic drugs SAHA and azacytidine, as well as RA and GC, are currently being used to treat some malignancies but their therapeutic potential in lung cancer is not well established. Here we aimed to determine the possible therapeutic effects of azacytidine and SAHA (A/S) alone or in combination with GC plus RA (GC/RA) in lung cancers with either BRG1 inactivation or MYC amplification. In vitro, responses to GC/RA treatment were more effective in MYC-amplified cells. These effects were mediated by BRG1 and involved a reprogramming towards prodifferentiation gene expression signatures and downregulation of MYC. In MYC-amplified cells, administration of GC/RA enhanced the cell growth inhibitory effects of A/S which, in turn, accentuated the prodifferentiation features promoted by GC/RA. Finally, these treatments improved overall survival of mice orthotopically implanted with MYC-amplified, but not BRG1-mutant, cells and reduced tumor cell viability and proliferation. We propose that the combination of epigenetic treatments with retinoids and corticoids of MYC-driven lung tumors constitute a strategy for therapeutic intervention in this otherwise incurable disease

The genomics of visuospatial neurocognition in obsessive-compulsive disorder: A preliminary GWAS

Background: The study of Obsessive-Compulsive Disorder (OCD) genomics has primarily been tackled by Genome-wide association studies (GWAS), which have encountered troubles in identifying replicable single nucleotide polymorphisms (SNPs). Endophenotypes have emerged as a promising avenue of study in trying to elucidate the genomic bases of complex traits such as OCD.Methods: We analyzed the association of SNPs across the whole genome with the construction of visuospatial information and executive performance through four neurocognitive variables assessed by the Rey-Osterrieth Complex Figure Test (ROCFT) in a sample of 133 OCD probands. Analyses were performed at SNP- and genelevel.Results: No SNP reached genome-wide significance, although there was one SNP almost reaching significant association with copy organization (rs60360940; P = 9.98E-08). Suggestive signals were found for the four variables at both SNP- (P < 1E-05) and gene-levels (P < 1E-04). Most of the suggestive signals pointed to genes and genomic regions previously associated with neurological function and neuropsychological traits. Limitations: Our main limitations were the sample size, which was limited to identify associated signals at a genome-wide level, and the composition of the sample, more representative of rather severe OCD cases than a population-based OCD sample with a broad severity spectrum.Conclusions: Our results suggest that studying neurocognitive variables in GWAS would be more informative on the genetic basis of OCD than the classical case/control GWAS, facilitating the genetic characterization of OCD and its different clinical profiles, the development of individualized treatment approaches, and the improvement of prognosis and treatment response

Prosumer and Product Design Through Digital Tools

Currently, the growing interest of users and consumers in the participation of the creative process has led to the typical “maker culture” practices. Consequently, there is an increasing number of prosumers - users who produce what they consume - who want to be part of the design and transformation process of the products. In order to achieve it, prosumers have begun to use digital tools that greatly facilitate this task. These tools could vary depending on the number of users involved in the process and the freedom of participation that they have on the product. It has been presented a number of qualitative classification of cases involving the end user, individually or collectively, that has influenced as a prosumer in the product design process. The objective is to study the use of digital tools in the creative phase within the design process according to their different levels of participation with respect to the final product. The cases are shown in four tables according to the number of users involved in the process and their level of participation. In these tables, other important aspects related to the study of digital tools such as the type of contribution of the prosumer to the product or the design phase in which he participates will be identified. In conclusion, this work will show if there is a pattern in the use of digital tools according to the number of users involved in the process and the freedom of participation that they have and which are the reasons for their use

Financial crises and the attainment of the SDGs: an adjusted multidimensional poverty approach

This paper analyses the impact of financial crises on the Sustainable Development Goal of eradicating poverty. To do so, we develop an adjusted Multidimensional Poverty Framework (MPF) that includes 15 indicators that span across key poverty aspects related to income, basic needs, health, education and the environment. We then use an econometric model that allows us to examine the impact of financial crises on these indicators in 150 countries over the period 1980–2015. Our analysis produces new estimates on the impact of financial crises on poverty’s multiple social, economic and environmental aspects and equally important captures dynamic linkages between these aspects. Thus, we offer a better understanding of the potential impact of current debt dynamics on Multidimensional Poverty and demonstrate the need to move beyond the boundaries of SDG1, if we are to meet the target of eradicating poverty. Our results indicate that the current financial distress experienced by many low-income countries may reverse the progress that has been made hitherto in reducing poverty. We find that financial crises are associated with an approximately 10% increase of extreme poor in low-income countries. The impact is even stronger in some other poverty aspects. For instance, crises are associated with an average decrease of government spending in education by 17.72% in low-income countries. The dynamic linkages between most of the Multidimensional Poverty indicators, warn of a negative domino effect on a number of SDGs related to poverty, if there is a financial crisis shock. To pre-empt such a domino effect, the specific SDG target 17.4 on attaining long-term debt sustainability through coordinated policies plays a key role and requires urgent attention by the international community