Estudi d'adipoquines com a marcadors plasmàtics de síndrome metabòlica

La síndrome metabòlica s’associa amb un risc elevat de desenvolupar diabetis tipus 2 i malaltia cardiovascular. La síndrome metabòlica es defineix com un clúster d’anormalitats metabòliques i, d’entre totes, l’obesitat abdominal constitueix el factor de risc més prevalent i crític en el desenvolupament de la síndrome metabòlica, el risc cardiovascular augmentat i la resistència a la insulina. La prevalença augmentada de l’obesitat en la població a nivell mundial ha portat el teixit adipós al primer pla dels estudis epidemiològics. Anteriorment es considerava el reservori energètic de l’organisme, actualment es parla del teixit adipós com un òrgan endocrí, metabòlicament molt actiu, implicat en diferents vies i processos metabòlics. L’etiologia de l’obesitat és complexa i multifactorial, però es fa evident en la disfuncionalitat del teixit adipós. Un teixit adipós disfuncional veu superada la seva capacitat d’emmagatzemar lípid i respon amb la hipersecreció de diferents molècules (adipoquines, citoquines i mediadors inflamatoris) a favor de la resistència a la insulina, proinflamatòries i proaterogèniques. La fatty acid-binding protein 4 (FABP4) i la retinol-binding protein 4 (RBP4) són dues adipoquines que en circulació, es desconeix la funció exacta que duen a terme. Estudis recents han suggerit la FABP4 com a marcador d’adipositat, síndrome metabòlica i diabetis tipus 2. I, RBP4, malgrat que les dades de diferents estudis en humans desperten certa controvèrsia, s’ha associat amb la resistència a la insulina i el desenvolupament de la diabetis tipus 2. En aquesta memòria es recullen els treballs en què es va estudiar el paper d’aquestes adipoquines en relació a malalties de base metabòlica amb afectació del teixit adipós com són la síndrome metabòlica, la diabetis tipus 2, la hiperlipèmia familiar combinada i la, lipodistrofia associada a tractament combinat antiretroviral de la infecció pel virus de la immunodeficiència humana (VIH).

Series enlazadas de los principales agregados nacionales de la EPA,1964-2009 (RegDat_EPA_nac_v10)

En el presente trabajo se recopilan y extienden diversas series históricas de los principales agregados nacionales de la Encuesta de Población Activa (EPA) y se construyen nuevas series anuales homogéneas de las mismas variables para el período 1964-2009 corrigiendo algunas de las rupturas que persisten en las series históricas más recientes del INE.

Self-reported social class in adolescents: validity and relationship with gradients in self-reported health

Background: Analyzing social differences in the health of adolescents is a challenge. The accuracy of adolescent's report on familial socio-economic position is unknown. The aims of the study were to examine the validity of measuring occupational social class and family level of education reported by adolescents aged 12 to 18, and the relationship between social position and self-reported health.Methods: A sample of 1453 Spanish adolescents 12 to 18 years old from urban and rural areas completed a self-administered questionnaire including the Child Health and Illness Profile-Adolescent Edition (CHIP-AE), and data on parental occupational social class (OSC) and level of education (LE). The responsible person for a sub-sample of teenagers (n = 91) were interviewed by phone. Kappa coefficients were estimated to analyze agreement between adolescents and proxy-respondents, and logistic regression models were adjusted to analyze factors associated with missing answers and disagreements. Effect size (ES) was calculated to analyze the relationship between OSC, LE and the CHIP-AE domain scores.Results: Missing answers were higher for father's (24.2%) and mother's (45.7%) occupational status than for parental education (8.4%, and 8.1% respectively), and belonging to a non-standard family was associated with more incomplete reporting of social position (OR = 4,98; 95%CI = 1,3–18,8) as was agreement between a parent and the adolescent. There were significant social class gradients, most notably for aspects of health related to resilience to threats to illness.ConclusionAdolescents can acceptably self-report on family occupation and level of education. Social class gradients are present in important aspects of health in adolescents.

Genetic evidence of heterogeneity in intrahepatic cholestasis of pregnancy

Background and aims: The aim of this study was to investigate the genetic aetiology of intrahepatic cholestasis of pregnancy (ICP) and the impact of known cholestasis genes (BSEP, FIC1, and MDR3) on the development of this disease. Patients and methods: Sixty nine Finnish ICP patients were prospectively interviewed for a family history of ICP, and clinical features were compared in patients with familial ICP (patients with a positive family history, n=11) and sporadic patients (patients with no known family history of ICP, n=58). For molecular genetic analysis, 16 individuals from two independently ascertained Finnish ICP families were genotyped for the flanking markers for BSEP, FIC1, and MDR3. Results: The pedigree structures in 16% (11/69) of patients suggested dominant inheritance. Patients with familial ICP had higher serum aminotransferase levels and a higher recurrence risk (92% v 40%). Both segregation of haplotypes and multipoint linkage analysis excluded BSEP, FIC1, and MDR3 genes in the studied pedigrees. Additionally, the MDR3 gene, previously shown to harbour mutations in ICP patients, was negative for mutations when sequenced in four affected individuals from the two families. Conclusions: These results support the hypothesis that the aetiology of ICP is heterogeneous and that ICP is due to a genetic predisposition in a proportion of patients. The results of molecular genetic analysis further suggest that the previously identified three cholestasis genes are not likely to be implicated in these Finnish ICP families with dominant inheritance.

Una aproximación a las funciones ejecutivas en el trastorno del espectro autista

Introducción: La hipótesis psicológica de la disfunción ejecutiva desempeña un papel crucial para explicar el fenotipo conductual de las personas con trastornos del espectro autista (TEA), relacionada también con otras hipótesis como el déficit en teoría de la mente o la hipótesis de la coherencia central débil. Sin embargo, ninguna de estas hipótesis son mutuamente excluyentes y los comportamientos que tienen su origen en alguna de esas tres hipótesis están también moldeados y mantenidos por otros procesos y factores. Desarrollo: Este artículo revisa la manifestación conductual y el estado de la investigación sobre las funciones ejecutivas en personas con TEA y su impacto en las habilidades de planificación, de flexibilidad mental y cognitiva, generatividad, inhibición de respuesta, habilidades mentalistas y sentido de la actividad. Conclusión: Aunque la disfunción ejecutiva ha ido ganando peso como hipótesis explicativa en las personas con TEA, persisten algunas dificultades relevantes que precisan de mayor y más detallada investigación. Por otro lado, son muy escasos los programas de intervención con eficacia demostrada que minimicen los efectos de la disfunción ejecutiva en el autismo.

CX3CR1 is a modifying gene of survival and progression in Amyotrophic Lateral Sclerosis

The objective of this study was to investigate the association of functional variants of the human CX3CR1 gene (Fractalkine receptor) with the risk of Amyotrophic Lateral Sclerosis disease (ALS), the survival and the progression rate of the disease symptoms in a Spanish ALS cohort. 187 ALS patients (142sporadic [sALS] and 45 familial) and 378 controls were recruited. We investigated CX3CR1 V249I (rs3732379) and T280M (rs3732378) genotypes and their haplotypes as predictors of survival, the progression rate of the symptoms (as measured by ALSFRS-R and FVC decline) and the risk of suffering ALS disease. The results indicated that sALS patients with CX3CR1 249I/I or 249V/I genotypes presented a shorter survival time (42.21±4.82) than patients with 249V/V genotype (67.48±7.28; diff=-25.27 months 95%CI [-42.09,-8.45]; p=0.003). The survival time was shorter in sALS patients with spinal topography and CX3CR1 249I alleles (diff -29.78 months; 95%CI [-49.42,-10.14]; p=0.003). The same effects were also observed in the spinal sALS patients with 249I-280M haplotype (diff=-27.23 months; 95%CI [-49.83,-4.64]; p=0.018). In the sALS group, the CX3CR1 249I variant was associated with a faster progression of the disease symptoms (OR= 2.32; 95IC%[1.24, 4.33]; p=0.007). There was no evidence for association of these two CX3CR1 variants with ALS disease risk. The association evidenced herein is clinically relevant and indicates that CX3CR1 could be a disease-modifying gene in sALS. The progression rate of the disease"s symptoms and the survival time is affected in patients with one or two copies of the CX3CR1 249I allele. The CX3CR1 is the most potent ALS survival genetic factor reported to date. These results reinforce the role of the immune system in ALS pathogenesis.

Analysis of meiotic recombination in 22q11.2, a region that frequently undergoes deletions and duplications

Background: The 22q11.2 deletion syndrome is the most frequent genomic disorder with an estimated frequency of 1/4000 live births. The majority of patients (90%) have the same deletion of 3 Mb (Typically Deleted Region, TDR) that results from aberrant recombination at meiosis between region specific low-copy repeats (LCRs). Methods: As a first step towards the characterization of recombination rates and breakpoints within the 22q11.2 region we have constructed a high resolution recombination breakpoint map based on pedigree analysis and a population-based historical recombination map based on LD analysis. Results: Our pedigree map allows the location of recombination breakpoints with a high resolution (potential recombination hotspots), and this approach has led to the identification of 5 breakpoint segments of 50 kb or less (8.6 kb the smallest), that coincide with historical hotspots. It has been suggested that aberrant recombination leading to deletion (and duplication) is caused by low rates of Allelic Homologous Recombination (AHR) within the affected region. However, recombination rate estimates for 22q11.2 region show that neither average recombination rates in the 22q11.2 region or within LCR22-2 (the LCR implicated in most deletions and duplications), are significantly below chromosome 22 averages. Furthermore, LCR22-2, the repeat most frequently implicated in rearrangements, is also the LCR22 with the highest levels of AHR. In addition, we find recombination events in the 22q11.2 region to cluster within families. Within this context, the same chromosome recombines twice in one family; first by AHR and in the next generation by NAHR resulting in an individual affected with the del22q11.2 syndrome. Conclusion: We show in the context of a first high resolution pedigree map of the 22q11.2 region that NAHR within LCR22 leading to duplications and deletions cannot be explained exclusively under a hypothesis of low AHR rates. In addition, we find that AHR recombination events cluster within families. If normal and aberrant recombination are mechanistically related, the fact that LCR22s undergo frequent AHR and that we find familial differences in recombination rates within the 22q11.2 region would have obvious health-related implications.

Contaminación de suelos y aguas subterráneas por vertidos industriales

En los países industrializados, la contaminación de suelos y aguas subterráneas por el vertido incontrolado de residuos industriales es uno de los problemas más preocupantes que se plantean, ya que su eliminación no es fácil ni barata de realizar, y sus efectos persisten durante muchos años. En España este problema es especialmente notorio a causa de una gestión inadecuada derivada de la descoordinación existente entre los diferentes sectores involucrados: administración, empresas, técnicos y científicos. La ausencia de instalaciones suficientes para su tratamiento, ha llevado a la práctica de vertidos en los cauces de ríos y en el subsuelo o a su almacenamiento en vertederos incontrolados...

Parkinson"s disease DJ-1 L166P alters rRNA biogenesis by exclusion of TTRAP from the nucleolus and sequestration into cytoplasmic aggregates via TRAF6

Mutations in PARK7/DJ-1 gene are associated to autosomal recessive early onset forms of Parkinson"s disease (PD). Although large gene deletions have been linked to a loss-of-function phenotype, the pathogenic mechanism of missense mutations is less clear. The L166P mutation causes misfolding of DJ-1 protein and its degradation. L166P protein may also accumulate into insoluble cytoplasmic aggregates with a mechanism facilitated by the E3 ligase TNF receptor associated factor 6 (TRAF6). Upon proteasome impairment L166P activates the JNK/p38 MAPK apoptotic pathway by its interaction with TRAF and TNF Receptor Associated Protein (TTRAP). When proteasome activity is blocked in the presence of wild-type DJ-1, TTRAP forms aggregates that are localized to the cytoplasm or associated to nucleolar cavities, where it is required for a correct rRNA biogenesis. In this study we show that in post-mortem brains of sporadic PD patients TTRAP is associated to the nucleolus and to Lewy Bodies, cytoplasmic aggregates considered the hallmark of the disease. In SH-SY5Y neuroblastoma cells, misfolded mutant DJ-1 L166P alters rRNA biogenesis inhibiting TTRAP localization to the nucleolus and enhancing its recruitment into cytoplasmic aggregates with a mechanism that depends in part on TRAF6 activity. This work suggests that TTRAP plays a role in the molecular mechanisms of both sporadic and familial PD. Furthermore, it unveils the existence of an interplay between cytoplasmic and nucleolar aggregates that impacts rRNA biogenesis and involves TRAF6

Racionalización versus racionamiento en la práctica de la nutrición clínica; cuarta lección Jesús Culebras

La situación económica actual ha dado pie al tema de esta conferencia que se desarrollará en dos grandes apartados: primero, trataremos de ideas generales sobre la racionalización versus el racionamiento en la sanidad, y, posteriormente, del racionamiento en la práctica de la nutrición clínica. Racionalizar, según la Real Academia Española de la Lengua, es organizar la producción o el trabajo de manera que aumente los ren - dimientos o reduzca los costos con el mínimo esfuerzo. Mientras que por racionamiento se entiende la acción y efecto de racionar o limitar el consumo de algo para evitar consecuencias negativas. En Europa, el porcentaje del Producto Interior Bruto destinado a Sanidad cae progresivamente mientras el coste de la Sanidad no para de aumentar. Desde el punto de vista económico, éste sería el principal motivo por el que las autoridades sanitarias parece que no tienen más alternativa que racionar. ¿Hasta qué punto el principio ético de justicia es compatible con el racionamiento? Éticamente, parece que para aceptar el racionamiento debería cumplirse no sólo una distribución justa de los recursos limitados sino también el uso racional de los mismos. Si se acepta que el recorte en prestaciones sanitarias es necesario, deberíamos responder a diversas preguntas: ¿qué es lo ético no recortar?, ¿quién decide lo que es médicamente necesario?, ¿cómo se decide? Sin respuestas coherentes a estas preguntas resulta díficil, éticamente, aceptar el racionamiento a nivel sanitario. Al tratar el racionamiento en la práctica de la nutrición clínica, debemos centrarnos en cómo el racionamiento afecta a la desnutrición, y más concretamente de la desnutrición relacionada con la enfermedad, ya que ello centra el origen de la Nutrición Clínica. Por su importancia e implicaciones se están llevando a cabo, en diversos países entre ellos en España, acciones integradas en la estrategia de la Unión Europea: “Together for health: a Strategic Approach for the EU 2008-2013” encaminadas a tomar medidas dirigidas a prevenir y tratar la desnutrición. Pero a pesar de ello, las restricciones persisten, situándonos en la necesidad imperativa de utilizar todas las herramientas a nuestro alcance para prevenir el desarrollo de la desnutrición en los pacientes en riesgo, para detectar precozmente los pacientes con desnutrición o riesgo de desarrollarla y para establecer las medidas de actuación más adecuadas.

Birth Weight, Working Memory and Epigenetic Signatures in IGF2 and Related Genes: A MZ Twin Study.

Neurodevelopmental disruptions caused by obstetric complications play a role in the etiology of several phenotypes associated with neuropsychiatric diseases and cognitive dysfunctions. Importantly, it has been noticed that epigenetic processes occurring early in life may mediate these associations. Here, DNA methylation signatures at IGF2 (insulin-like growth factor 2) and IGF2BP1-3 (IGF2-binding proteins 1-3) were examined in a sample consisting of 34 adult monozygotic (MZ) twins informative for obstetric complications and cognitive performance. Multivariate linear regression analysis of twin data was implemented to test for associations between methylation levels and both birth weight (BW) and adult working memory (WM) performance. Familial and unique environmental factors underlying these potential relationships were evaluated. A link was detected between DNA methylation levels of two CpG sites in the IGF2BP1 gene and both BW and adult WM performance. The BW-IGF2BP1 methylation association seemed due to non-shared environmental factors influencing BW, whereas the WM-IGF2BP1 methylation relationship seemed mediated by both genes and environment. Our data is in agreement with previous evidence indicating that DNA methylation status may be related to prenatal stress and later neurocognitive phenotypes. While former reports independently detected associations between DNA methylation and either BW or WM, current results suggest that these relationships are not confounded by each other.

La diversitat funcional al treball

L’accés al mercat laboral per part de les persones amb diversitat funcional no està exempt de dificultats. Encara avui persisteixen barreres que societat i empresa han de superar com són els estereotips o prejudicis cap a les persones amb capacitats diferents. Perquè les persones en risc d’exclusió social puguin augmentar les seves opcions de trobar una feina plantegem, a la primera part de l’article, un pla d’acompanyament personalitzat a la inserció laboral que permeti al candidat augmentar els seus nivells d’ocupabilitat. A la segona meitat, canviem el focus d’atenció cap a l’empresa i proposem com la presència de persones amb diversitat funcional pot generar valor dins d’una organització.

Risk factors for colorectal cancer in subjects with family history of the disease.

The relationship between lifestyle factors, past medical conditions, daily meal frequency, diet and the risk of 'familial' colorectal cancer has been analysed using data from a case-control study conducted in northern Italy. A total of 1584 colorectal cancer patients and 2879 control subjects were admitted to a network of hospitals in the Greater Milan area and the Pordenone province. The subjects included for analysis were the 112 cases and the 108 control subjects who reported a family history of colorectal cancer in first-degree relatives. Colorectal cancer cases and control subjects with family history were similarly distributed according to sex, age, marital status, years of schooling and social class. Familial colorectal cancer was associated with meal frequency, medical history of diabetes (relative risk, RR = 4.6) and cholelithiasis (RR = 5.2). Significant positive trends of increasing risk with more frequent consumption were observed for pasta (RR = 2.5, for the highest vs the lowest intake tertile), pastries (RR = 2.4), red meat (RR = 2.9), canned meat (RR = 1.9), cheese (RR = 3.5) and butter (RR = 1.9). Significant inverse associations and trends in risk were observed for consumption of poultry (RR = 0.4), tomatoes (RR = 0.2), peppers (RR = 0.3) and lettuce (RR = 0.3). Significant inverse trends in risk with increasing consumption for beta-carotene and ascorbic acid were observed (RR = 0.5 and 0.4 respectively, highest vs lowest intake tertile). These results suggest that risk factors for subjects with a family history of colorectal cancer in first-degree relatives are not appreciably different from recognized risk factors of the disease in the general population.