Environmental Exposure to Trace Elements and Heavy Metals Preceding the Clinical Onset of Inflammatory Bowel Disease.

Background: The immune dysregulation underlying inflammatory bowel disease (IBD) can start years before the diagnosis, but the role of triggering factors and environmental exposures during this period is still uncertain. Methods: This single-center case-control study included asymptomatic subjects with an incidental diagnosis of IBD during the colorectal cancer screening program. Twenty-two minerals and 17 metals were determined at diagnosis in hair samples and compared 1:2 to healthy controls. Results: Six patients with preclinical IBD (3 ulcerative colitis, 67% left-sided; 3 Crohn's disease, 100% ileal, 67% inflammatory behavior) and 13 healthy non-IBD controls were included. No relevant occupational exposures were identified. We found statistically significant higher levels of sodium, potassium, and boron among cases compared to controls; while lower levels of zinc, uranium, copper, and germanium were observed. Conclusions: A range of environmental exposures can be identified during the preclinical phase of IBD, but their relationship with the symptomatic onset and disease progression should be further explored.

Asociación entre edadismo y sexismo en estudiantes universitarios / Association between ageism and sexism in university students

Antecedentes y objetivos El edadismo es la percepción negativa de las personas por su edad. El objetivo de esta investigación fue analizar los niveles de edadismo y su asociación con el sexismo y otros factores en universitarios. Materiales y métodos Se llevó a cabo un estudio transversal a través de una encuesta online entre los estudiantes de la Universidad de Granada (España). Se recogió información sobre variables sociodemográficas y académicas y se administró el Cuestionario de estereotipos negativos hacia la vejez (CENVE), la Escala de sexismo ambivalente (ASI), el Cuestionario breve de los cinco grandes rasgos de personalidad (BFPTSQ), la Escala sobre la ansiedad por el envejecimiento (AE) y la Escala sobre el contacto con personas mayores (CPM). Se determinaron los niveles de edadismo y se exploraron asociaciones con otras variables. A continuación, se realizó un modelo de regresión logística binaria para conocer los factores asociados a su presencia. Resultados Participaron doscientos sesenta y tres (263) estudiantes. La mayoría presentaban niveles de edadismo bajos o muy bajos (83,3%). Los estudiantes más edadistas presentaban mayores niveles de sexismo hostil (OR=1,07; p<0,01) y más ansiedad por el envejecimiento (OR=1,10; p<0,05) que los estudiantes que puntuaron bajo en edadismo. Por otra parte, ser alumno de grado fue un factor protector frente a este tipo de sesgo comparado con la realización de estudios de posgrado (OR=0,31; p<0,05). Conclusión Un mayor sexismo hostil y una mayor ansiedad por el envejecimiento se relacionan con un mayor edadismo en los estudiantes de la Universidad de Granada (España). Las universidades deben brindar conocimiento a sus alumnos sobre este problema y desarrollar programas dirigidos a evitar la discriminación de las personas mayores. (AU)

Background and aims Ageism is the negative perception towards others based on age. The aim of this research was to analyze the levels of ageism and its association with sexism and other factors in university students. Materials and methods Cross-sectional study among the students of the University of Granada. The data was collected through an online survey. Information on sociodemographic and academic variables was collected together with the Negative Stereotypes Questionnaire towards Old Age (CENVE), the Ambivalent Sexism Scale (ASI), the Brief Version of the Big Five Personality Inventory (BFPTSQ), the Anxiety Scale for Aging (AE) and the Contact with the Elderly Scale (CPM). Ageism levels were determined and associations with other variables were analyzed. A logistic regression model explored ageism’ associated factors. Results Two hundred and sixty-three students participated. Most had low or very low levels of ageism (83.3%). The most ageist students showed higher hostile sexism (OR=1.07; p<.01) and higher aging anxiety (OR=1.10; p<.05) than students with high scores in ageism. Graduate students showed protector OR for ageism when compared to postgraduate students (OR=.31; p<.05). Conclusions Higher hostile sexism and aging anxiety are associated with higher ageism in students from the University of Granada. Universities must include in their study plans knowledge about this problem and develop programs aimed at avoiding discrimination in the elderly. (AU)

Asociación entre edadismo y sexismo en estudiantes universitarios / Association between ageism and sexism in university students

Antecedentes y objetivos El edadismo es la percepción negativa de las personas por su edad. El objetivo de esta investigación fue analizar los niveles de edadismo y su asociación con el sexismo y otros factores en universitarios. Materiales y métodos Se llevó a cabo un estudio transversal a través de una encuesta online entre los estudiantes de la Universidad de Granada (España). Se recogió información sobre variables sociodemográficas y académicas y se administró el Cuestionario de estereotipos negativos hacia la vejez (CENVE), la Escala de sexismo ambivalente (ASI), el Cuestionario breve de los cinco grandes rasgos de personalidad (BFPTSQ), la Escala sobre la ansiedad por el envejecimiento (AE) y la Escala sobre el contacto con personas mayores (CPM). Se determinaron los niveles de edadismo y se exploraron asociaciones con otras variables. A continuación, se realizó un modelo de regresión logística binaria para conocer los factores asociados a su presencia. Resultados Participaron doscientos sesenta y tres (263) estudiantes. La mayoría presentaban niveles de edadismo bajos o muy bajos (83,3%). Los estudiantes más edadistas presentaban mayores niveles de sexismo hostil (OR=1,07; p<0,01) y más ansiedad por el envejecimiento (OR=1,10; p<0,05) que los estudiantes que puntuaron bajo en edadismo. Por otra parte, ser alumno de grado fue un factor protector frente a este tipo de sesgo comparado con la realización de estudios de posgrado (OR=0,31; p<0,05). Conclusión Un mayor sexismo hostil y una mayor ansiedad por el envejecimiento se relacionan con un mayor edadismo en los estudiantes de la Universidad de Granada (España). Las universidades deben brindar conocimiento a sus alumnos sobre este problema y desarrollar programas dirigidos a evitar la discriminación de las personas mayores. (AU)

Background and aims Ageism is the negative perception towards others based on age. The aim of this research was to analyze the levels of ageism and its association with sexism and other factors in university students. Materials and methods Cross-sectional study among the students of the University of Granada. The data was collected through an online survey. Information on sociodemographic and academic variables was collected together with the Negative Stereotypes Questionnaire towards Old Age (CENVE), the Ambivalent Sexism Scale (ASI), the Brief Version of the Big Five Personality Inventory (BFPTSQ), the Anxiety Scale for Aging (AE) and the Contact with the Elderly Scale (CPM). Ageism levels were determined and associations with other variables were analyzed. A logistic regression model explored ageism’ associated factors. Results Two hundred and sixty-three students participated. Most had low or very low levels of ageism (83.3%). The most ageist students showed higher hostile sexism (OR=1.07; p<.01) and higher aging anxiety (OR=1.10; p<.05) than students with high scores in ageism. Graduate students showed protector OR for ageism when compared to postgraduate students (OR=.31; p<.05). Conclusions Higher hostile sexism and aging anxiety are associated with higher ageism in students from the University of Granada. Universities must include in their study plans knowledge about this problem and develop programs aimed at avoiding discrimination in the elderly. (AU)

[Association between ageism and sexism in university students]. / Asociación entre edadismo y sexismo en estudiantes universitarios.

BACKGROUND AND AIMS: Ageism is the negative perception towards others based on age. The aim of this research was to analyze the levels of ageism and its association with sexism and other factors in university students. MATERIALS AND METHODS: Cross-sectional study among the students of the University of Granada. The data was collected through an online survey. Information on sociodemographic and academic variables was collected together with the Negative Stereotypes Questionnaire towards Old Age (CENVE), the Ambivalent Sexism Scale (ASI), the Brief Version of the Big Five Personality Inventory (BFPTSQ), the Anxiety Scale for Aging (AE) and the Contact with the Elderly Scale (CPM). Ageism levels were determined and associations with other variables were analyzed. A logistic regression model explored ageism' associated factors. RESULTS: Two hundred and sixty-three students participated. Most had low or very low levels of ageism (83.3%). The most ageist students showed higher hostile sexism (OR=1.07; p<.01) and higher aging anxiety (OR=1.10; p<.05) than students with high scores in ageism. Graduate students showed protector OR for ageism when compared to postgraduate students (OR=.31; p<.05). CONCLUSIONS: Higher hostile sexism and aging anxiety are associated with higher ageism in students from the University of Granada. Universities must include in their study plans knowledge about this problem and develop programs aimed at avoiding discrimination in the elderly.

Improving dexamethasone drug loading and efficacy in treating arthritis through a lipophilic prodrug entrapped into PLGA-PEG nanoparticles.

Targeted delivery of dexamethasone to inflamed tissues using nanoparticles is much-needed to improve its efficacy while reducing side effects. To drastically improve dexamethasone loading and prevent burst release once injected intravenously, a lipophilic prodrug dexamethasone palmitate (DXP) was encapsulated into poly(DL-lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs). DXP-loaded PLGA-PEG NPs (DXP-NPs) of about 150 nm with a drug loading as high as 7.5% exhibited low hemolytic profile and cytotoxicity. DXP-NPs were able to inhibit the LPS-induced release of inflammatory cytokines in macrophages. After an intravenous injection to mice, dexamethasone (DXM) pharmacokinetic profile was also significantly improved. The concentration of DXM in the plasma of healthy mice remained high up to 18 h, much longer than the commercial soluble drug dexamethasone phosphate (DSP). Biodistribution studies showed lower DXM concentrations in the liver, kidneys, and lungs when DXP-NPs were administered as compared with the soluble drug. Histology analysis revealed an improvement in the knee structure and reduction of cell infiltration in animals treated with the encapsulated DXP compared with the soluble DSP or non-treated animals. In summary, the encapsulation of a lipidic prodrug of dexamethasone into PLGA-PEG NPs appears as a promising strategy to improve the pharmacological profile and reduce joint inflammation in a murine model of rheumatoid arthritis.

Genomic Predictions With Nonadditive Effects Improved Estimates of Additive Effects and Predictions of Total Genetic Values in Pinus sylvestris.

Genomic selection study (GS) focusing on nonadditive genetic effects of dominance and the first order of epistatic effects, in a full-sib family population of 695 Scots pine (Pinus sylvestris L.) trees, was undertaken for growth and wood quality traits, using 6,344 single nucleotide polymorphism markers (SNPs) generated by genotyping-by-sequencing (GBS). Genomic marker-based relationship matrices offer more effective modeling of nonadditive genetic effects than pedigree-based models, thus increasing the knowledge on the relevance of dominance and epistatic variation in forest tree breeding. Genomic marker-based models were compared with pedigree-based models showing a considerable dominance and epistatic variation for growth traits. Nonadditive genetic variation of epistatic nature (additive × additive) was detected for growth traits, wood density (DEN), and modulus of elasticity (MOEd) representing between 2.27 and 34.5% of the total phenotypic variance. Including dominance variance in pedigree-based Best Linear Unbiased Prediction (PBLUP) and epistatic variance in genomic-based Best Linear Unbiased Prediction (GBLUP) resulted in decreased narrow-sense heritability and increased broad-sense heritability for growth traits, DEN and MOEd. Higher genetic gains were reached with early GS based on total genetic values, than with conventional pedigree selection for a selection intensity of 1%. This study indicates that nonadditive genetic variance may have a significant role in the variation of selection traits of Scots pine, thus clonal deployment could be an attractive alternative for the species. Additionally, confidence in the role of nonadditive genetic effects in this breeding program should be pursued in the future, using GS.

Evaluation of the efficiency of genomic versus pedigree predictions for growth and wood quality traits in Scots pine.

BACKGROUND: Genomic selection (GS) or genomic prediction is a promising approach for tree breeding to obtain higher genetic gains by shortening time of progeny testing in breeding programs. As proof-of-concept for Scots pine (Pinus sylvestris L.), a genomic prediction study was conducted with 694 individuals representing 183 full-sib families that were genotyped with genotyping-by-sequencing (GBS) and phenotyped for growth and wood quality traits. 8719 SNPs were used to compare different genomic with pedigree prediction models. Additionally, four prediction efficiency methods were used to evaluate the impact of genomic breeding value estimations by assigning diverse ratios of training and validation sets, as well as several subsets of SNP markers. RESULTS: Genomic Best Linear Unbiased Prediction (GBLUP) and Bayesian Ridge Regression (BRR) combined with expectation maximization (EM) imputation algorithm showed slightly higher prediction efficiencies than Pedigree Best Linear Unbiased Prediction (PBLUP) and Bayesian LASSO, with some exceptions. A subset of approximately 6000 SNP markers, was enough to provide similar prediction efficiencies as the full set of 8719 markers. Additionally, prediction efficiencies of genomic models were enough to achieve a higher selection response, that varied between 50-143% higher than the traditional pedigree-based selection. CONCLUSIONS: Although prediction efficiencies were similar for genomic and pedigree models, the relative selection response was doubled for genomic models by assuming that earlier selections can be done at the seedling stage, reducing the progeny testing time, thus shortening the breeding cycle length roughly by 50%.

Evolution of functional class, biochemical and echocardiographic parameters and clinical outcomes after sacubitril/valsartan initiation in daily practice.

Aim: To analyze the impact of sacubitril/valsartan on functional class, surrogate parameters and clinical outcomes in clinical practice. Methods: Retrospective study of patients with heart failure and reduced ejection fraction that started treatment with sacubitril/valsartan. Results: 149 patients (70.7 ± 9.6 years) were included. At baseline, 83.9, 15.4 and 0.7% were taking sacubitril/valsartan 24/26, 49/51 and 97/103 mg, respectively. After 316.1 ± 155.9 days, these numbers moved to 38.9, 39.6, 12.8% (8.7% discontinued). Sacubitril/valsartan improved functional class (from 2.3 ± 0.6 to 1.8 ± 0.5; p < 0.001), increased ejection fraction (from 31.2 ± 7.0 to 37.3 ± 10.5%; p < 0.001) and reduced NT-proBNP (from 3884 ± 4871 to 1975.3 ± 3006.6 pg/ml; p = 0.0001). Rates of any event, cardiovascular death and heart failure hospitalization/decompensation were 13.2 events/100 patient-years. Conclusion: Sacubitril/valsartan is effective and safe in routine practice.

Analysis of phenotypic- and Estimated Breeding Values (EBV) to dissect the genetic architecture of complex traits in a Scots pine three-generation pedigree design.

In forest tree breeding, family-based Quantitative Trait Loci (QTL) studies are valuable as methods to dissect the complexity of a trait and as a source of candidate genes. In the field of conifer research, our study contributes to the evaluation of phenotypic and predicted breeding values for the identification of QTL linked to complex traits in a three-generation pedigree population in Scots pine (Pinus sylvestris L.). A total of 11 470 open pollinated F2-progeny trees established at three different locations, were measured for growth and adaptive traits. Breeding values were predicted for their 360 mothers, originating from a single cross of two grand-parents. A multilevel LASSO association analysis was conducted to detect QTL using genotypes of the mothers with the corresponding phenotypes and Estimated Breeding Values (EBV). Different levels of genotype-by-environment (G × E) effects among sites at different years, were detected for survival and height. Moderate-to-low narrow sense heritabilities and EBV accuracies were found for all traits and all sites. We identified 18 AFLPs and 12 SNPs to be associated with QTL for one or more traits. 62 QTL were significant with percentages of variance explained ranging from 1.7 to 18.9%. In those cases where the same marker was associated to a phenotypic or an ebvQTL, the ebvQTL always explained higher proportion of the variance, maybe due to the more accurate nature of Estimated Breeding Values (EBV). Two SNP-QTL showed pleiotropic effects for traits related with hardiness, seed, cone and flower production. Furthermore, we detected several QTL with significant effects across multiple ages, which could be considered as strong candidate loci for early selection. The lack of reproducibility of some QTL detected across sites may be due to environmental heterogeneity reflected by the genotype- and QTL-by-environment effects.