The Possible Role of Epigenetics in Gestational Diabetes: Cause, Consequence, or Both

Gestational diabetes mellitus (GDM) is defined as the glucose intolerance that is not present or recognized prior to pregnancy. Several risk factors of GDM depend on environmental factors that are thought to regulate the genome through epigenetic mechanisms. Thus, epigenetic regulation could be involved in the development of GDM. In addition, the adverse intrauterine environment in patients with GDM could also have a negative impact on the establishment of the epigenomes of the offspring

Superconducting properties of the attractive Hubbard model

A self-consistent set of equations for the one-electron self-energy in the ladder approximation is derived for the attractive Hubbard model in the superconducting state. The equations provide an extension of a T-matrix formalism recently used to study the effect of electron correlations on normal-state properties. An approximation to the set of equations is solved numerically in the intermediate coupling regime, and the one-particle spectral functions are found to have four peaks. This feature is traced back to a peak in the self-energy, which is related to the formation of real-space bound states. For comparison we extend the moment approach to the superconducting state and discuss the crossover from the weak (BCS) to the intermediate coupling regime from the perspective of single-particle spectral densities.Comment: RevTeX format, 8 figures. Accepted for publication in Z.Phys.

Genetic and Non-genetic Predictors of LINE-1 Methylation in Leukocyte DNA.

Background: Altered DNA methylation has been associated with various diseases. Objective: We evaluated the association between levels of methylation in leukocyte DNA at long interspersed nuclear element 1 (LINE-1) and genetic and non-genetic characteristics of 892 control participants from the Spanish Bladder Cancer/EPICURO study. Methods: We determined LINE-1 methylation levels by pyrosequencing. Individual data included demographics, smoking status, nutrient intake, toenail concentrations of 12 trace elements, xenobiotic metabolism gene variants, and 515 polymorphisms among 24 genes in the one-carbon metabolism pathway. To assess the association between LINE-1 methylation levels (percentage of methylated cytosines) and potential determinants, we estimated beta coefficients (βs) by robust linear regression. Results: Women had lower levels of LINE-1 methylation than men (β = –0.7, p = 0.02). Persons who smoked blond tobacco showed lower methylation than nonsmokers (β = –0.7, p = 0.03). Arsenic toenail concentration was inversely associated with LINE-1 methylation (β = –3.6, p = 0.003). By contrast, iron (β = 0.002, p = 0.009) and nickel (β = 0.02, p = 0.004) were positively associated with LINE-1 methylation. Single nucleotide polymorphisms (SNPs) in DNMT3A (rs7581217-per allele, β = 0.3, p = 0.002), TCN2 (rs9606756-GG, β = 1.9, p = 0.008; rs4820887-AA, β = 4.0, p = 4.8 × 10–7; rs9621049-TT, β = 4.2, p = 4.7 × 10–9), AS3MT (rs7085104-GG, β = 0.7, p = 0.001), SLC19A1 (rs914238, TC vs. TT: β = 0.5 and CC vs. TT: β = –0.3, global p = 0.0007) and MTHFS (rs1380642, CT vs. CC: β = 0.3 and TT vs. CC; β = –0.8, global p = 0.05) were associated with LINE-1 methylation. Conclusions: We identified several characteristics, environmental factors, and common genetic variants that predicted DNA methylation among study participants.This work was partially supported by the Association for International Cancer Research (AICR; grant 09-0780, and a doctoral scholarship awarded to S.M.T.); Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, MINECO, Spain (grants 00/0745, PI051436, PI061614, PI09-02102, and G03/174); Red Temática de Investigación Cooperativa en Cáncer (grant RD06/0020-RTICC); the U.S. National Institutes of Health (grant RO1-CA089715); a postdoctoral fellowship awarded to A.F.S.A. from the Fundación Científica de la AECC; Fundació Marató TV3; and The Johns Hopkins University Vredenburg Scholarship awarded to A.L.C

Tuberculosis en la Comunidad de Madrid. incidencia en personas extranjeras y españolas durante el período 1996-2004.

Fundamento: La inmigración desde países de alta prevalencia de tuberculosis hacia otros más desarrollados afecta a la evolución global de la tuberculosis en los últimos años. El objetivo de este estudio fue describir la influencia de los casos de tuberculosis en personas extranjeras sobre la incidencia de la enfermedad en la Comunidad de Madrid en el período 1996 a 2004. Métodos: Los datos procedían del Registro Regional de Casos de Tuberculosis, y del padrón de 1996 y los padrones continuos de 1998 a 2004. Se estimó la incidencia de tuberculosis según país de origen desde 1996 a 2004, por sexo y grupos de edad. Se calcularon c2 para tendencia lineal, razones de incidencia y proporción de casos en personas extranjeras. Resultados: La incidencia de tuberculosis pasó de 34,3 casos por 105 habitantes en 1996 a 16,9 casos por 105 habitantes en 2004. Para los nacidos en España cambió de 33,2 casos por 105 habitantes en 1996 a 12,7 casos por 105 habitantes en 2004, y para los extranjeros de 50,5 casos por 105 habitantes en 1996 a 42,9 casos por 105 habitantes en 2004. La razón de la incidencia entre extranjeros y españoles fue superior a 1 en todos los años, con valor máximo en 2003, en el que se detectaron 4,2 casos en extranjeros por cada caso en españoles (IC 95% 3,7-4,7). El porcentaje de casos extranjeros pasó del 5,2% en 1996 al 35,1% en 2004. Conclusiones: La incidencia de tuberculosis en extranjeros fue mayor que entre los españoles y no disminuyó significativamente en el período 1996-2004, lo que está contribuyendo a que la tuberculosis se haya estabilizado. Esta situación y las características de esta población han de ser tenidas en cuenta en los esfuerzos para el control de esta enfermedad

Clinical and molecular parameters associated to pneumonitis development in non-small-cell lung cancer patients receiving chemoimmunotherapy from NADIM trial

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Bristol-Myers Squibb (BMS); Grupo Español de Cáncer de Pulmón (GECP); European Social Fund (ESF) i Comunidad de Madrid (PEJD-2019-PRE/BMD-17006, PEJ16/MED/AI-1972, PEJD-2018-PRE/SAL-8641).Background Pneumonitis (Pn) is one of the main immune-related adverse effects, having a special importance in lung cancer, since they share affected tissue. Despite its clinical relevance, Pn development remains an unpredictable treatment adverse effect, whose mechanisms are mainly unknown, being even more obscure when it is associated to chemoimmunotherapy. Methods In order to identify parameters associated to treatment related Pn, we analyzed clinical variables and molecular parameters from 46 patients with potentially resectable stage IIIA non-small-cell lung cancer treated with neoadjuvant chemoimmunotherapy included in the NADIM clinical trial (NCT03081689). Pn was defined as clinical or radiographic evidence of lung inflammation without alternative diagnoses, from treatment initiation to 180 days. Results Among 46 patients, 12 developed Pn (26.1%). Sex, age, smoking status, packs-year, histological subtype, clinical or pathological response, progression-free survival, overall survival and number of nivolumab cycles, were not associated to Pn development. Regarding molecular parameters at diagnosis, Pn development was not associated to programmed death ligand 1, TPS, T cell receptor repertoire parameters, or tumor mutational burden. However, patients who developed Pn had statistically significant lower blood median levels of platelet to monocyte ratio (p=0.012) and teratocarcinoma-derived growth factor 1 (p=0.013; area under the curve (AUC) 0.801), but higher median percentages of natural killers (NKs) (p=0.019; AUC 0.786), monocytes (p=0.017; AUC 0.791), MSP (p=0.006; AUC 0.838), PARN (p=0.017; AUC 0.790), and E-Cadherin (p=0.022; AUC 0.788). In addition, the immune scenario of Pn after neoadjuvant treatment involves: high levels of neutrophils and NK cells, but low levels of B and T cells in peripheral blood; increased clonality of intratumoral T cells; and elevated plasma levels of several growth factors (EGF, HGF, VEGF, ANG-1, PDGF, NGF, and NT4) and inflammatory cytokines (MIF, CCL16, neutrophil gelatinase-associated lipocalin, BMP-4, and u-PAR). Conclusions Although statistically underpowered, our results shed light on the possible mechanisms behind Pn development, involving innate and adaptative immunity, and open the possibility to predict patients at high risk. If confirmed, this may allow the personalization of both, the surveillance strategy and the therapeutic approaches to manage Pn in patients receiving chemoimmunotherapy