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Molecular epidemiology of circulating clinical isolates is crucial to improve prevention strategies. The Spanish Working Group on multidrug resistant tuberculosis (MDR-TB) is a network that monitors the MDR-TB isolates in Spain since 1998. The aim of this study was to present the study of the MDR-TB and extensively drug-resistant tuberculosis (XDR-TB) patterns in Spain using the different recommended genotyping methods over time by a national coordinated system. Based on the proposed genotyping methods in the European Union until 2018, the preservation of one method, MIRU-VNTR, applied to selected clustered strains permitted to maintain our study open for 20 years. The distribution of demographic, clinical and epidemiological characteristics of clustered and non-clustered cases of MDR/XDR tuberculosis with proportion differences as assessed by Pearson's chi-squared or Fisher's exact test was compared. The differences in the quantitative variables using the Student's-t test and the Mann-Whitney U test were evaluated. The results obtained showed a total of 48.4% of the cases grouped in 77 clusters. Younger age groups, having a known TB case contact (10.2% vs 4.7%) and XDR-TB (16.5% vs 1.8%) were significantly associated with clustering. The largest cluster corresponded to a Mycobacterium bovis strain mainly spread during the nineties. A total of 68.4% of the clusters detected were distributed among the different Spanish regions and six clusters involving 104 cases were grouped in 17 and 18 years. Comparison of the genotypes obtained with those European genotypes included in The European Surveillance System (TESSy) showed that 87 cases had become part of 20 European clusters. The continuity of MDR strain genotyping in time has offered a widespread picture of the situation that allows better management of this public health problem. It also shows the advantage of maintaining one genotyping method over time, which allowed the comparison between ancient, present and future samples. The molecular methods applied in this work were supported by the Carlos III Health Institute in the context of two consecutive Grants FIS15/0317 and 18/0336 and JC was awarded a scholarship by the Government of Aragon / European Social Fund, “Building Europe from Aragon”. Sí

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 × 10-4(false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteractionvalues > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.

Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p

Objetivo: Determinar si existen concentraciones de compuestos lipofílicos de origen orgánico en muestras de aceite de silicona extraídas de ojos humanos y comprobar si existe alguna relación con el tiempo de permanencia intraocular del aceite. Métodos: Por cromatografía líquida de alta resolución (HPLC) se han determinado las concentraciones de ácido retinoico, retinol, retinal, colesterol y alfa -tocoferol en 23 muestras de aceite de silicona de 1.000 cs, extraνdas de pacientes con desprendimientos complejos de retina con tiempos de permanencia intraocular variables (3 a 50 meses). Resultados: Se han encontrado concentraciones de todos los compuestos, sobre todo de colesterol, y en menor medida de alfa -tocoferol. Se ha observado una correlaciσn inversa de la edad y las concentraciones de alfa cido retinoico (p=0,023). Y una correlaciσn directa entre el tiempo de permanencia intraocular del aceite y los niveles de colesterol (p=0,0008) que se mantiene hasta los 20 meses. Conclusiones: Se confirma que el aceite de silicona no es una sustancia tan inerte ya que es capaz de disolver compuestos lipídicos procedentes de tejidos intraoculares. Existe una elevación linear de los niveles de colesterol que podría utilizarse como orientación para decidir cuándo extraer el aceite de silicona, aunque hacen falta estudios con series más grandes. Objective: To verify the existence of organic lipophylic compounds in silicone oil extracted from human eyes following its use for previous retinal detachment, and to determine the intraocular permanence time of these substances in the oil. Methods: Concentrations of retinoic acid, retinol, retinal, cholesterol and alpha -tocopherol were detected by HPLC in 23 samples of silicone oil extracted from patients with complicated retinal detachments. The time interval between the time of injection of the silicone oil and the subsequent assessment varied from 3 to 50 months (the permanence time). Results: All tested compounds were found in the samples, but these were most commonly cholesterol and less frequently alpha -tocopherol. There was an inverse relationship between retinoic acid concentration and age (p=0.023), and a direct relationship between cholesterol concentration and permanence time (p=0.0008) at least up to 20 months. Conclusions: These findings confirm that silicone oil is not an inert substance but is capable of extracting lipophylic compounds from the intraocular tissues. There is a clear linear elevation of cholesterol levels with increased intraocular permanence time. This finding could be used to further establish a safe permanence time for intraocular silicone oil used in ophthalmologic surgery. More studies with larger samples are warranted to evaluate this further.

Objetivo: Determinar si existen concentraciones de compuestos lipofílicos de origen orgánico en muestras de aceite de silicona extraídas de ojos humanos y comprobar si existe alguna relación con el tiempo de permanencia intraocular del aceite. Métodos: Por cromatografía líquida de alta resolución (HPLC) se han determinado las concentraciones de ácido retinoico, retinol, retinal, colesterol y alfa -tocoferol en 23 muestras de aceite de silicona de 1.000 cs, extraνdas de pacientes con desprendimientos complejos de retina con tiempos de permanencia intraocular variables (3 a 50 meses). Resultados: Se han encontrado concentraciones de todos los compuestos, sobre todo de colesterol, y en menor medida de alfa -tocoferol. Se ha observado una correlaciσn inversa de la edad y las concentraciones de alfa cido retinoico (p=0,023). Y una correlaciσn directa entre el tiempo de permanencia intraocular del aceite y los niveles de colesterol (p=0,0008) que se mantiene hasta los 20 meses. Conclusiones: Se confirma que el aceite de silicona no es una sustancia tan inerte ya que es capaz de disolver compuestos lipídicos procedentes de tejidos intraoculares. Existe una elevación linear de los niveles de colesterol que podría utilizarse como orientación para decidir cuándo extraer el aceite de silicona, aunque hacen falta estudios con series más grandes.

The BRCA2 mutations are implicated in a high percentage of hereditary breast cancer cases. We report a novel mutation in a Spanish breast cancer family. We analyzed DNA samples of the proband and of the living first and second degree relatives. Exon 11 of BRCA2 gene were screened by the protein truncation test and direct sequencing. We identified a novel mutation, 6857 delAA, in three affected women, diagnosed of breast cancer at 29, 51 and 45 years of age, respectively, and in a healthy male. The BRCA2 mutation seems to be implicated in the development of early-onset breast cancer cases in this family. Identification of this novel mutation adds to the information on BRCA2 gene in hereditary breast cancer in Spanish population.