Mice lacking DIO3 exhibit sex-specific alterations in circadian patterns of corticosterone and gene expression in metabolic tissues.

Disruption of circadian rhythms is associated with neurological, endocrine and metabolic pathologies. We have recently shown that mice lacking functional type 3 deiodinase (DIO3), the enzyme that clears thyroid hormones, exhibit a phase shift in locomotor activity, suggesting altered circadian rhythm. To better understand the physiological and molecular basis of this phenotype, we used Dio3+/+ and Dio3-/- mice of both sexes at different zeitgeber times (ZTs) and analyzed corticosterone and thyroxine (T4) levels, hypothalamic, hepatic, and adipose tissue expression of clock genes, as well as genes involved in the thyroid hormone action or physiology of liver and adipose tissues. Wild type mice exhibited sexually dimorphic circadian patterns of genes controlling thyroid hormone action, including Dio3. Dio3-/- mice exhibited altered hypothalamic expression of several clock genes at ZT12, but did not disrupt the overall circadian profile. Expression of clock genes in peripheral tissues was not disrupted by Dio3 deficiency. However, Dio3 loss in liver and adipose tissues disrupted circadian profiles of genes that determine tissue thyroid hormone action and physiology. We also observed circadian-specific changes in serum T4 and corticosterone as a result of DIO3 deficiency. The circadian alterations manifested sexual dimorphism. Most notable, the time curve of serum corticosterone was flattened in Dio3-/- females. We conclude that Dio3 exhibits circadian variations, influencing the circadian rhythmicity of thyroid hormone action and physiology in liver and adipose tissues in a sex-specific manner. Circadian disruptions in tissue physiology may then contribute to the metabolic phenotypes of DIO3-deficient mice.

Epigenetic developmental programming and intergenerational effects of thyroid hormones.

Mounting evidence is showing that altered signaling through the nuclear hormone receptor superfamily can cause abnormal, long-term epigenetic changes which translate into pathological modifications and susceptibility to disease. These effects seem to be more prominent if the exposure occurs early in life, when transcriptomic profiles are rapidly changing. At this time, the coordination of the complex coordinated processes of cell proliferation and differentiation that characterize mammalian development. Such exposures may also alter the epigenetic information of the germ line, potentially leading to developmental changes and abnormal outcomes in subsequent generations. Thyroid hormone (TH) signaling is mediated by specific nuclear receptors, which have the ability to markedly change chromatin structure and gene transcription, and can also regulate other determinants of epigenetic marks. TH exhibits pleiotropic effects in mammals, and during development, its action is regulated in a highly dynamic manner to suit the rapidly evolving needs of multiple tissues. Their molecular mechanisms of action, timely developmental regulation and broad biological effects place THs in a central position to play a role in the developmental epigenetic programming of adult pathophysiology and, through effects on the germ line, in inter- and trans-generational epigenetic phenomena. These areas of epigenetic research are in their infancy, and studies regarding THs are limited. In the context of their characteristics as epigenetic modifiers and their finely tuned developmental action, here we review some of the observations underscoring the role that altered TH action may play in the developmental programming of adult traits and in the phenotypes of subsequent generations via germ line transmission of altered epigenetic information. Considering the relatively high prevalence of thyroid disease and the ability of some environmental chemicals to disrupt TH action, the epigenetic effects of abnormal levels of TH action may be important contributors to the non-genetic etiology of human disease.

Developmental thyroid hormone action on pro-opiomelanocortin-expressing cells programs hypothalamic BMPR1A depletion and brown fat activation.

Thyroid hormone excess secondary to global type 3 deiodinase (DIO3) deficiency leads to increased locomotor activity and reduced adiposity, but also to concurrent alterations in parameters of the leptin-melanocortin system that would predict obesity. To distinguish the underlying contributions to the energy balance phenotype of DIO3 deficiency, we generated mice with thyroid hormone excess targeted to pro-opiomelanocortin (POMC)-expressing cells via cell-specific DIO3 inactivation. These mice exhibit a male-specific phenotype of reduced hypothalamic Pomc expression, hyperphagia, and increased activity in brown adipose tissue, with adiposity and serum levels of leptin and thyroid hormones remained normal. These male mice also manifest a marked and widespread hypothalamic reduction in the expression of bone morphogenetic receptor 1a (BMPR1A), which has been shown to cause similar phenotypes when inactivated in POMC-expressing cells. Our results indicate that developmental overexposure to thyroid hormone in POMC-expressing cells programs energy balance mechanisms in a sexually dimorphic manner by suppressing adult hypothalamic BMPR1A expression.

DIO3 protects against thyrotoxicosis-derived cranio-encephalic and cardiac congenital abnormalities.

Maternal hyperthyroidism is associated with an increased incidence of congenital abnormalities at birth, but it is not clear which of these defects arise from a transient developmental excess of thyroid hormone and which depend on pregnancy stage, antithyroid drug choice, or unwanted subsequent fetal hypothyroidism. To address this issue, we studied a mouse model of comprehensive developmental thyrotoxicosis secondary to a lack of type 3 deiodinase (DIO3). Dio3-/- mice exhibited reduced neonatal viability on most genetic backgrounds and perinatal lethality on a C57BL/6 background. Dio3-/- mice exhibited severe growth retardation during the neonatal period and cartilage loss. Mice surviving after birth manifested brain and cranial dysmorphisms, severe hydrocephalus, choanal atresia, and cleft palate. These abnormalities were noticeable in C57BL/6J Dio3-/- mice at fetal stages, in addition to a thyrotoxic heart with septal defects and thin ventricular walls. Our findings stress the protecting role of DIO3 during development and support the hypothesis that human congenital abnormalities associated with hyperthyroidism during pregnancy are caused by transient thyrotoxicosis before clinical intervention. Our results also suggest thyroid hormone involvement in the etiology of idiopathic pathologies including cleft palate, choanal atresia, Chiari malformations, Kaschin-Beck disease, and Temple and other cranio-encephalic and heart syndromes.

Thyroid Hormone Deiodinases: Dynamic Switches in Developmental Transitions.

Thyroid hormones exert pleiotropic, essential actions in mammalian, including human, development. These actions depend on provision of thyroid hormones in the circulation but also to a remarkable extent on deiodinase enzymes in target tissues that amplify or deplete the local concentration of the primary active form of the hormone T3 (3,5,3'-triiodothyronine), the high affinity ligand for thyroid hormone receptors. Genetic analyses in mice have revealed key roles for activating (DIO2) and inactivating (DIO3) deiodinases in cell differentiation fates and tissue maturation, ultimately promoting neonatal viability, growth, fertility, brain development, and behavior, as well as metabolic, endocrine, and sensory functions. An emerging paradigm is how the opposing activities of DIO2 and DIO3 are coordinated, providing a dynamic switch that controls the developmental timing of a tissue response, often during neonatal and maturational transitions. A second paradigm is how cell to cell communication within a tissue determines the response to T3. Deiodinases in specific cell types, often strategically located near to blood vessels that convey thyroid hormones into the tissue, can regulate neighboring cell types, suggesting a paracrine-like layer of control of T3 action. We discuss deiodinases as switches for developmental transitions and their potential to influence tissue dysfunction in human thyroid disorders.

Body size and weight change over adulthood and risk of breast cancer by menopausal and hormone receptor status: a pooled analysis of 20 prospective cohort studies.

Associations between anthropometric factors and breast cancer (BC) risk have varied inconsistently by estrogen and/or progesterone receptor (ER/PR) status. Associations between prediagnostic anthropometric factors and risk of premenopausal and postmenopausal BC overall and ER/PR status subtypes were investigated in a pooled analysis of 20 prospective cohorts, including 36,297 BC cases among 1,061,915 women, using multivariable Cox regression analyses, controlling for reproductive factors, diet and other risk factors. We estimated dose-response relationships and tested for nonlinear associations using restricted cubic splines. Height showed positive, linear associations for premenopausal and postmenopausal BC risk (6-7% RR increase per 5 cm increment), with stronger associations for receptor-positive subtypes. Body mass index (BMI) at cohort baseline was strongly inversely associated with premenopausal BC risk, and strongly positively-and nonlinearly-associated with postmenopausal BC (especially among women who never used hormone replacement therapy). This was primarily observed for receptor-positive subtypes. Early adult BMI (at 18-20 years) showed inverse, linear associations for premenopausal and postmenopausal BC risk (21% and 11% RR decrease per 5 kg/m2, respectively) with stronger associations for receptor-negative subtypes. Adult weight gain since 18-20 years was positively associated with postmenopausal BC risk, stronger for receptor-positive subtypes, and among women who were leaner in early adulthood. Women heavier in early adulthood generally had reduced premenopausal BC risk, independent of later weight gain. Positive associations between height, baseline (adult) BMI, adult weight gain and postmenopausal BC risk were substantially stronger for hormone receptor-positive versus negative subtypes. Premenopausal BC risk was positively associated with height, but inversely with baseline BMI and weight gain (mostly in receptor-positive subtypes). Inverse associations with early adult BMI seemed stronger in receptor-negative subtypes of premenopausal and postmenopausal BC.

Thyroid hormone influences brain gene expression programs and behaviors in later generations by altering germ line epigenetic information.

Genetic factors do not fully account for the relatively high heritability of neurodevelopmental conditions, suggesting that non-genetic heritable factors contribute to their etiology. To evaluate the potential contribution of aberrant thyroid hormone status to the epigenetic inheritance of neurological phenotypes, we examined genetically normal F2 generation descendants of mice that were developmentally overexposed to thyroid hormone due to a Dio3 mutation. Hypothalamic gene expression profiling in postnatal day 15 F2 descendants on the paternal lineage of ancestral male and female T3-overexposed mice revealed, respectively, 1089 and 1549 differentially expressed genes. A large number of them, 675 genes, were common to both sets, suggesting comparable epigenetic effects of thyroid hormone on both the male and female ancestral germ lines. Oligodendrocyte- and neuron-specific genes were strongly overrepresented among genes showing, respectively, increased and decreased expression. Altered gene expression extended to other brain regions and was associated in adulthood with decreased anxiety-like behavior, increased marble burying and reduced physical activity. The sperm of T3-overexposed male ancestors revealed significant hypomethylation of CpG islands associated with the promoters of genes involved in the early development of the central nervous system. Some of them were candidates for neurodevelopmental disorders in humans including Nrg3, Nrxn1, Gabrb3, Gabra5, Apba2, Grik3, Reln, Nsd1, Pcdh8, En1, and Elavl2. Thus, developmental levels of thyroid hormone influence the epigenetic information of the germ line, disproportionately affecting genes with critical roles in early brain development, and leading in future generations to disease-relevant alterations in postnatal brain gene expression and adult behavior.

Spermatogonial Type 3 Deiodinase Regulates Thyroid Hormone Target Genes in Developing Testicular Somatic Cells.

Premature overexposure to thyroid hormone causes profound effects on testis growth, spermatogenesis, and male fertility. We used genetic mouse models of type 3 deiodinase (DIO3) deficiency to determine the genetic programs affected by premature thyroid hormone action and to define the role of DIO3 in regulating thyroid hormone economy in testicular cells. Gene expression profiling in the neonatal testis of DIO3-deficient mice identified 5699 differentially expressed genes. Upregulated and downregulated genes were, respectively, involved according to DAVID analysis with cell differentiation and proliferation. They included anti-Müllerian hormone and genes involved in the formation of the blood-testis barrier, which are specific to Sertoli cells (SCs). They also included steroidogenic genes, which are specific to Leydig cells. Comparison with published data sets of genes enriched in SCs and spermatogonia, and responsive to retinoic acid (RA), identified a subset of genes that were regulated similarly by RA and thyroid hormone. This subset of genes showed an expression bias, as they were downregulated when enriched in spermatogonia and upregulated when enriched in SCs. Furthermore, using a genetic approach, we found that DIO3 is not expressed in SCs, but spermatogonia-specific inactivation of DIO3 led to impaired testis growth, reduced SC number, decreased cell proliferation and, especially during neonatal development, altered gene expression specific to somatic cells. These findings indicate that spermatogonial DIO3 protects testicular cells from untimely thyroid hormone signaling and demonstrate a mechanism of cross-talk between somatic and germ cells in the neonatal testis that involves the regulation of thyroid hormone availability and action.

Adult onset of type 3 deiodinase deficiency in mice alters brain gene expression and increases locomotor activity.

Constitutive loss of the type 3 deiodinase (DIO3) causes abnormally increased levels of thyroid hormone action in the developing and adult brain, leading to an array of behavioral abnormalities. To determine to what extent those phenotypes derive from a lack of DIO3 in the adult brain, versus developmental consequences, we created a mouse model of conditional DIO3 inactivation. Mice carrying "floxed" Dio3 alleles and a tamoxifen-inducible cre transgene were injected with tamoxifen at two months of age. Compared to oil-injected controls, the brain tissue of these mice showed a 75-80% decrease in DIO3 activity and 85-95% Dio3 mRNA was expressed from recombinant alleles. Mice with adult DIO3 deficiency did not show significant differences in growth, serum thyroid hormone parameters or behaviors related to anxiety and depression. However, female mice exhibited elevated locomotor activity and increased marble-burying behavior. They also manifested relatively modest alterations in the expression of T3-dependent genes and genes related to hyperactivity in a sex- and region-specific manner. Upon thyroid hormone treatment, the expression response of T3-regulated genes was generally more pronounced in DIO3-deficient female mice than in female controls, while the opposite effect of altered genotype was noticed in males. The extent of the molecular and behavioral phenotypes of adult-onset DIO3 deficiency suggests that a substantial proportion of the neurological abnormalities caused by constitutive DIO3 deficiency has a developmental origin. However, our results show that DIO3 in the adult brain also influences behavior and sensitivity to thyroid hormone action in a sexually dimorphic fashion.

A Framework for Leveraging "Big Data" to Advance Epidemiology and Improve Quality: Design of the VA Colonoscopy Collaborative.

OBJECTIVE: To describe a framework for leveraging big data for research and quality improvement purposes and demonstrate implementation of the framework for design of the Department of Veterans Affairs (VA) Colonoscopy Collaborative. METHODS: We propose that research utilizing large-scale electronic health records (EHRs) can be approached in a 4 step framework: 1) Identify data sources required to answer research question; 2) Determine whether variables are available as structured or free-text data; 3) Utilize a rigorous approach to refine variables and assess data quality; 4) Create the analytic dataset and perform analyses. We describe implementation of the framework as part of the VA Colonoscopy Collaborative, which aims to leverage big data to 1) prospectively measure and report colonoscopy quality and 2) develop and validate a risk prediction model for colorectal cancer (CRC) and high-risk polyps. RESULTS: Examples of implementation of the 4 step framework are provided. To date, we have identified 2,337,171 Veterans who have undergone colonoscopy between 1999 and 2014. Median age was 62 years, and 4.6 percent (n = 106,860) were female. We estimated that 2.6 percent (n = 60,517) had CRC diagnosed at baseline. An additional 1 percent (n = 24,483) had a new ICD-9 code-based diagnosis of CRC on follow up. CONCLUSION: We hope our framework may contribute to the dialogue on best practices to ensure high quality epidemiologic and quality improvement work. As a result of implementation of the framework, the VA Colonoscopy Collaborative holds great promise for 1) quantifying and providing novel understandings of colonoscopy outcomes, and 2) building a robust approach for nationwide VA colonoscopy quality reporting.

Burnout y engagement en estudiantes universitarios de enfermería / Burnout and engagement among university nursing students

Los universitarios se encuentran sometidos a cargas académicas prolongadas que ocuparan la mayor parte de su tiempo. La capacidad para hacer frente a estas situaciones de estrés durante su formación, dependerá ente otras cosas, de la disposición personal para afrontar las demandas académicas. Objetivo: Describir el nivel de burnout (agotamiento, cinismo y eficacia académica) y el compromiso académico a través de la variable engagement (absorción, dedicación y vigor), además de analizar las asociaciones, relaciones y predicciones entre estas variables en estudiantes de Enfermería. Material y método. Estudio descriptivo transversal en 1009 sujetos. Instrumentos de recogida de datos: Maslach Burnout Inventory y Utrech Work Engagement en versión estudiantes. Resultados: Las dimensiones del burnout y engagement correlacionan entre sí. A mayor eficacia académica menos agotamiento y cinismo y mayor puntuación en todas las dimensiones del engagement académico. El vigor y la dedicación predicen puntuaciones más altas en eficacia académica. Las mujeres se perciben con puntuaciones más bajas en cinismo y más altas en eficacia académica, absorción y dedicación. Conclusiones: Los alumnos muestran más burnout cuando manifiestan altas puntuaciones de agotamiento y cinismo y bajas en eficacia académica, además valores altos en las tres dimensiones del engagement indican alto compromiso con sus estudios. La relación entre estas variables pone de manifiesto la diferencia entre hombres y mujeres y la influencia positiva del engagement en la eficacia académica del estudiante. El fomento de engagement puede ser una oportunidad para superar las tareas académicas y para enfrentarse al mundo laboral con mayor probabilidad de éxito

University students are tasked with a protracted academic workload that occupies the greater part of their time. Their ability to cope with the stress this entails during their degree course will partly depend on their personal response to these academic demands. Objective: to describe nursing students’ level of burnout (exhaustion, cynicism and academic efficacy) and academic engagement through the variable engagement (absorption, dedication and vigour), and to analyse associations, relations and predictions between these variables. Materials and method: cross-sectional descriptive study with 1009 subjects. Data collection instruments: student versions of the Maslach Burnout Inventory and the Utrecht Work Engagement Scale. Results: the dimensions of burnout and engagement correlated with each other. The higher the score for academic efficacy, the lower the scores for exhaustion and cynicism and the higher the score in all dimensions of academic engagement. Vigour and dedication predicted higher scores for academic efficacy. Females' self-perceptions indicated lower scores for cynicism and higher scores for academic efficacy, absorption and dedication. Conclusions: students evidenced more burnout when they obtained high scores for exhaustion and cynicism and low scores for academic efficacy. In addition, high scores for the three dimensions of engagement indicated high commitment to their studies. The relationship between these variables indicates a difference between males and females and a positive influence of engagement on students' academic efficacy. Promoting engagement could help students to deal with academic tasks and enter the labour market with a greater probability of success

Type 3 Deiodinase Role on Central Thyroid Hormone Action Affects the Leptin-Melanocortin System and Circadian Activity.

The role of thyroid hormones (THs) in the central regulation of energy balance is increasingly appreciated. Mice lacking the type 3 deiodinase (DIO3), which inactivates TH, have decreased circulating TH levels relative to control mice as a result of defects in the hypothalamic-pituitary-thyroid axis. However, we have shown that the TH status of the adult Dio3-/- brain is opposite that of the serum, exhibiting enhanced levels of TH action. Because the brain, particularly the hypothalamus, harbors important circuitries that regulate metabolism, we aimed to examine the energy balance phenotype of Dio3-/- mice and determine whether it is associated with hypothalamic abnormalities. Here we show that Dio3-/- mice of both sexes exhibit decreased adiposity, reduced brown and white adipocyte size, and enhanced fat loss in response to triiodothyronine (T3) treatment. They also exhibit increased TH action in the hypothalamus, with abnormal expression and T3 sensitivity of genes integral to the leptin-melanocortin system, including Agrp, Npy, Pomc, and Mc4r. The normal to elevated serum levels of leptin, and elevated and repressed expression of Agrp and Pomc, respectively, suggest a profile of leptin resistance. Interestingly, Dio3-/- mice also display elevated locomotor activity and increased energy expenditure. This occurs in association with expanded nighttime activity periods, suggesting a disrupted circadian rhythm. We conclude that DIO3-mediated regulation of TH action in the central nervous system influences multiple critical determinants of energy balance. Those influences may partially compensate each other, with the result likely contributing to the decreased adiposity observed in Dio3-/- mice.

Decreased anxiety- and depression-like behaviors and hyperactivity in a type 3 deiodinase-deficient mouse showing brain thyrotoxicosis and peripheral hypothyroidism.

Hypo- and hyperthyroid states, as well as functional abnormalities in the hypothalamic-pituitary-thyroid axis have been associated with psychiatric conditions like anxiety and depression. However, the nature of this relationship is poorly understood since it is difficult to ascertain the thyroid status of the brain in humans. Data from animal models indicate that the brain exhibits efficient homeostatic mechanisms that maintain local levels of the active thyroid hormone, triiodothyronine (T3) within a narrow range. To better understand the consequences of peripheral and central thyroid status for mood-related behaviors, we used a mouse model of type 3 deiodinase (DIO3) deficiency (Dio3 -/- mouse). This enzyme inactivates thyroid hormone and is highly expressed in the adult central nervous system. Adult Dio3 -/- mice exhibit elevated levels of T3-dependent gene expression in the brain, despite peripheral hypothyroidism as indicated by low circulating levels of thyroxine and T3. Dio3 -/- mice of both sexes exhibit hyperactivity and significantly decreased anxiety-like behavior, as measured by longer time spent in the open arms of the elevated plus maze and in the light area of the light/dark box. During the tail suspension, they stayed immobile for a significantly shorter time than their wild-type littermates, suggesting decreased depression-like behavior. These results indicate that increased thyroid hormone in the brain, not necessarily in peripheral tissues, correlates with hyperactivity and with decreases in anxiety and depression-like behaviors. Our results also underscore the importance of DIO3 as a determinant of behavior by locally regulating the brain levels of thyroid hormone.

MCT8 Deficiency in Male Mice Mitigates the Phenotypic Abnormalities Associated With the Absence of a Functional Type 3 Deiodinase.

Mice deficient in the type 3 deiodinase (D3KO mice) manifest impaired clearance of thyroid hormone (TH), leading to elevated levels of TH action during development. This alteration causes reduced neonatal viability, growth retardation, and central hypothyroidism. Here we examined how these phenotypes are affected by a deficiency in the monocarboxylate transporter 8 (MCT8), which is a major contributor to the transport of the active thyroid hormone, T3, into the cell. MCT8 deficiency eliminated the neonatal lethality of type 3 deiodinase (D3)-deficient mice and significantly ameliorated their growth retardation. Double-mutant newborn mice exhibited similar peripheral thyrotoxicosis and increased brain expression of T3-dependent genes as mice with D3 deficiency only. Later in neonatal life and adulthood, double-mutant mice manifested central and peripheral TH status similar to mice with single MCT8 deficiency, with low serum T4, elevated serum TSH and T3, and decreased T3-dependent gene expression in the hypothalamus. In double-mutant adult mice, both thyroid gland size and the hypothyroidism-induced rise in TSH were greater than those in mice with single D3 deficiency but less than those in mice with MCT8 deficiency alone. Our results demonstrate that the marked phenotypic abnormalities observed in the D3-deficient mouse, including perinatal mortality, growth retardation, and central hypothyroidism in adult animals, require expression of MCT8, confirming the interdependent relationship between the TH transport into cells and the deiodination processes.

The Type 3 Deiodinase Is a Critical Determinant of Appropriate Thyroid Hormone Action in the Developing Testis.

Timely and appropriate levels of thyroid hormone (TH) signaling are necessary to ensure normal developmental outcomes in many tissues. Studies using pharmacological models of altered TH status have revealed an influence of these hormones on testis development and size, but little is known about the role of endogenous determinants of TH action in the developing male gonads. Using a genetic approach, we demonstrate that the type 3 deiodinase (D3), which inactivates TH and protects developing tissues from undue TH action, is a key factor. D3 is highly expressed in the developing testis, and D3-deficient (D3KO) mice exhibit thyrotoxicosis and cell proliferation arrest in the neonatal testis, resulting in an approximately 75% reduction in testis size. This is accompanied by larger seminiferous tubules, impaired spermatogenesis, and a hormonal profile indicative of primary hypogonadism. A deficiency in the TH receptor-α fully normalizes testis size and adult testis gene expression in D3KO mice, indicating that the effects of D3 deficiency are mediated through this type of receptor. Similarly, genetic deficiencies in the D2 or in the monocarboxylate transporter 8 partially rescue the abnormalities in testis size and gonadal axis gene expression featured in the D3KO mice. Our study highlights the testis as an important tissue in which determinants of TH action coordinately converge to ensure normal development and identifies D3 as a critical factor in testis development and in testicular protection from thyrotoxicosis.

[Psychological distress in health sciences college students and its relationship with academic engagement]. / Malestar psicológico en estudiantes universitarios de ciencias de la salud y su relació con engagement academic.

OBJECTIVE: To determine the prevalence of psychological distress and its relationship with academic engagement (absorption, dedication and vigor), sex and degree among students from four public universities. METHOD: A non-experimental,comparative correlational, quantitative investigation without intervention. STUDY POPULATION: 1840 nursing and physical therapy students. The data collection tool used was a questionnaire. RESULTS: A 32.2% prevalence of psychological distress was found in the subjects; a correlation between vigor and psychological distress was found for all of the subjects and also for women. High absorption and dedication scores and low psychological distress scores predicted higher vigor scores. CONCLUSION: The risk of psychological distress is high, especially for women. Women seem to have a higher level of psychological distress than men. Vigor, energy and mental resilience positively influence psychological distress and can be a vehicle for better results during the learning and studying process.

Genomic imprinting variations in the mouse type 3 deiodinase gene between tissues and brain regions.

The Dio3 gene, which encodes for the type 3 deiodinase (D3), controls thyroid hormone (TH) availability. The lack of D3 in mice results in tissue overexposure to TH and a broad neuroendocrine phenotype. Dio3 is an imprinted gene, preferentially expressed from the paternally inherited allele in the mouse fetus. However, heterozygous mice with paternal inheritance of the inactivating Dio3 mutation exhibit an attenuated phenotype when compared with that of Dio3 null mice. To investigate this milder phenotype, the allelic expression of Dio3 was evaluated in different mouse tissues. Preferential allelic expression of Dio3 from the paternal allele was observed in fetal tissues and neonatal brain regions, whereas the biallelic Dio3 expression occurred in the developing eye, testes, and cerebellum and in the postnatal brain neocortex, which expresses a larger Dio3 mRNA transcript. The newborn hypothalamus manifests the highest degree of Dio3 expression from the paternal allele, compared with other brain regions, and preferential allelic expression of Dio3 in the brain relaxed in late neonatal life. A methylation analysis of two regulatory regions of the Dio3 imprinted domain revealed modest but significant differences between tissues, but these did not consistently correlate with the observed patterns of Dio3 allelic expression. Deletion of the Dio3 gene and promoter did not result in significant changes in the tissue-specific patterns of Dio3 allelic expression. These results suggest the existence of unidentified epigenetic determinants of tissue-specific Dio3 imprinting. The resulting variation in the Dio3 allelic expression between tissues likely explains the phenotypic variation that results from paternal Dio3 haploinsufficiency.

Inteligencia emocional y vínculo laboral en trabajadores del Centro San Camilo / Emotional intelligence and engagement in San Camilo Centre workers

Las organizaciones están comprometidas desde hace tiempo con la promoción de la salud y del bienestar de los trabajadores. Con este referente se realizó el presente estudio; el objetivo fue describir y analizar las asociaciones que existen entre las variables inteligencia emocional y engagement. La población fueron 150 trabajadores del Centro San Camilo. Los instrumentos de evaluación utilizados son la escala de Inteligencia Emocional (EIE-33), la escala de Inteligencia Emocional (EIE-25), el Trait Meta-Mood Scale (TMMS-24) y cuestionario de Utrecht Work Engagement Scale (UWES). Es un estudio descriptivo correlacional. En los trabajadores del Centro San Camilo existe asociación entre la inteligencia emocional y el engagement. Así la inteligencia emocional, entendida como la capacidad para adquirir habilidades o competencias para la adaptación de las demandas profesionales, potencia un estado mental positivo relacionado con el trabajo y ello repercute en la calidad asistencial y en la salud de la población atendida (AU)

For some time organizations are committed with health promotion and workers welfare. Under this concern this study has been conducted; the aim was to describe and analyse the existing associations between emotional intelligence and engagement variables. The population were 150 workers from San Camilo Centre. The assessment instruments used were the scale of Emotional Intelligence (EIE-33), the scale of Emotional Intelligence (EIE-25), the Trait Meta-Mood Scale (TMMS-25) and the questionnaire of Utrecht Work Engagement Scale (UWES). It is a descriptive correlational study. In San Camilo Centre workers there is association between emotional intelligence and engagement. Emotional intelligence, understood as the capacity to acquire skills or competencies for the adaptation to professional demands thus enhances a positive mental state work-related and this affects the quality of care and the assisted population health (AU)

Type 3 deiodinase deficiency causes spatial and temporal alterations in brain T3 signaling that are dissociated from serum thyroid hormone levels.

The type 3 deiodinase (D3) is an enzyme that inactivates thyroid hormones (TH) and is highly expressed during development and in the central nervous system. D3-deficient (D3KO) mice develop markedly elevated serum T(3) level in the perinatal period. In adulthood, circulating T(4) and T(3) levels are reduced due to functional deficits in the thyroid axis and peripheral tissues (i.e. liver) show evidence of decreased TH action. Given the importance of TH for brain development, we aimed to assess TH action in the brain of D3KO mice at different developmental stages and determine to what extent it correlates with serum TH parameters. We used a transgenic mouse model (FINDT3) that expresses the reporter gene ß-galactosidase (ß-gal) in the central nervous system as a readout of local TH availability. Together with experiments determining expression levels of TH-regulated genes, our results show that after a state of thyrotoxicosis in early development, most regions of the D3KO brain show evidence of decreased TH action at weaning age. However, later in adulthood and in old age, the brain again manifests a thyrotoxic state, despite reduced serum TH levels. These region-specific changes in brain TH status during the life span of the animal provide novel insight into the important role of the D3 in the developing and adult brain. Our results suggest that, even if serum concentrations of TH are normal or low, impaired D3 activity may result in excessive TH action in multiple brain regions, with potential consequences of altered neural function that may be of clinical relevance to neurological and neuroendocrine disorders.

Sensores de glucosa con información en tiempo real. GUARDIAN RT™/PARADIGM RT™ / Glucose Sensors which provide real time information. GUARDIAN RT™/PARADIGM RT™

Este trabajo amplía el póster que fue presentado al Encuentro Internacional de Educadores en Diabetes en Cádiz, 24-25 de mayo de 2007. En él se explica un programa específico estructurado para la colocación y retirada del sistema de monitorización de glucosa en tiempo real Guardian RT'99 así como para el adiestramiento de cara a utilizar la información en tiempo real por el paciente y retrospectivamente por el equipo de la Unidad de Diabetes(AU)

This report amplifies the poster which was presented at the International Meeting of Diabetes Educators which took place in Cadiz on May 24-25 in 2007. In this report, the authors explain a specific program structured to insert and remove a glucose monitoring real time system called Guardian RT'99, plus the authors provide an explanation how to properly use the real time information which this monitoring system provides to patients and to the Diabetes Ward medical team respectively(AU)