In pancreatic ductal adenocarcinoma blood concentrations of some organochlorine compounds and coffee intake are independently associated with KRAS mutations

8 pages, 4 pages.-- PMID: 19797353 [PubMed].-- Printed version published Nov 2009.While KRAS activation is a fundamental initiating event in the aetiopathogenesis of pancreatic ductal adenocarcinoma (PDA), environmental factors influencing the occurrence and persistence of KRAS mutations remain largely unknown. The objective was to test the hypothesis that in PDA there are aetiopathogenic relationships among concentrations of some organochlorine compounds (OCs) and the mutational status of the KRAS oncogene, as well as among the latter and coffee intake. Incident cases of PDA were interviewed and had blood drawn at hospital admission (N = 103). OCs were measured by high-resolution gas chromatography with electron capture detection. Cases whose tumours harboured a KRAS mutation had higher concentrations of p,p′-dichlorodiphenyltrichloroethane (DDT), p,p′-dichlorodiphenyldichloroethene (DDE) and polychlorinated biphenyls (PCBs) 138, 153 and 180 than cases with wild-type KRAS, but differences were statistically significant only for p,p′-DDT and PCBs 138 and 153. The association between coffee intake and KRAS mutations remained significant (P-trend < 0.015) when most OCs where accounted for. When p,p′-DDT, PCB 153, coffee and alcohol intake were included in the same model, all were associated with KRAS (P = 0.042, 0.007, 0.016 and 0.025, respectively). p,p′-DDT, p,p′-DDE and PCB 138 were significantly associated with the two most prevalent KRAS mutations (Val and Asp). OCs and coffee may have independent roles in the aetiopathogenesis of PDA through modulation of KRAS activation, acquisition or persistence, plausibly through non-genotoxic or epigenetic mechanisms. Given that KRAS mutations are the most frequent abnormality of oncogenes in human cancers, and the lifelong accumulation of OCs in humans, refutation or replication of the findings is required before any implications are assessed.Government of Catalonia (2009 SGR 1350); ‘Red temática de investigación cooperativa de centros en Cáncer’ (C03/10); ‘Red temática de investigación cooperativa de centros en Epidemiología y salud pública’ (C03/09); CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III, Madrid, Government of Spain.Peer reviewe

Metodología para la Evaluación de la Integridad Estructural de Cilindros de Gas Natural Comprimido “GNC”

The design of a vessel for natural compress gas in transporting vehicles, must consider the different operative conditions during its useful life. This must be considered to assess security conditions. For the standardization of a new vessel, the design process must include, beside the guidelines own of this stage, the necessary analysis techniques to evaluate the defects for considering the residual life during the periodic inspections. An evaluation procedure, for design and periodic inspection stages, with detailed scopes and requirements in each operative time of the equipment, are presented. Advanced analysis techniques, as Finite Elements Method and Fracture Mechanics, among others, are used. Based in this work, a proposal for the inclusion of these evaluation techniques in the corresponding standards is made.El diseño de un recipiente destinado al almacenamiento de Gas Natural Comprimido, para vehículos de transporte, debe considerar las distintas situaciones operativas que se presentan a lo largo del servicio, con el objeto de garantizar las condiciones de seguridad que el mismo requiere. El diseño debería incluir, además de las pautas que son propias en esta etapa, para su homologación, como recipiente nuevo, las técnicas de análisis necesarias que contemplen la evaluación de defectos con determinación de la vida residual, en las revisiones periódicas durante el servicio. En este trabajo se presenta un procedimiento de evaluación aplicable a la etapa de diseño y a la revisión periódica, en donde se detallan los alcances y requerimientos de cada etapa, utilizando técnicas avanzadas de análisis, alternativas a través de la aplicación del Método de Elementos Finitos, la Mecánica de Fractura, y la Emisión Acústica, entre otras. Basándose en los resultados de estos trabajos se realiza una propuesta para la inclusión de éstas técnicas de evaluación en las correspondientes normas de aplicación

Perinatal and childhood factors and risk of breast cancer subtypes in adulthood

BACKGROUND: Accumulated exposure to hormones and growth factors during early life may influence the future risk of breast cancer (BC). This study examines the influence of childhood-related, socio-demographic and anthropometric variables on BC risk, overall and by specific pathologic subtypes. METHODS: This is a case-control study where 1539 histologically-confirmed BC cases (23-85 years) and 1621 population controls, frequency matched by age, were recruited in 10 Spanish provinces. Perinatal and childhood-related characteristics were directly surveyed by trained staff. The association with BC risk, globally and according to menopausal status and pathologic subtypes, was evaluated using logistic and multinomial regression models, adjusting for tumor specific risk factors. RESULTS: Birth characteristics were not related with BC risk. However, women with high socioeconomic level at birth presented a decreased BC risk (OR=0.45; 95% CI=0.29-0.70), while those whose mothers were aged over 39 years at their birth showed an almost significant excess risk of hormone receptor positive tumors (HR+) (OR=1.35; 95% CI=0.99-1.84). Women who were taller than their girl mates before puberty showed increased postmenopausal BC risk (OR=1.26; 95% CI=1.03-1.54) and increased HR+ BC risk (OR=1.26; 95% CI=1.04-1.52). Regarding prepubertal weight, while those women who were thinner than average showed higher postmenopausal BC risk (OR=1.46; 95% CI=1.20-1.78), associated with HR+ tumors (OR=1.34; 95% CI=1.12-1.61) and with triple negative tumors (OR=1.56; 95% CI=1.03-2.35), those who were heavier than average presented lower premenopausal BC risk (OR=0.64; 95% CI=0.46-0.90) and lower risk of epidermal growth factor receptor positive tumors (OR=0.61; 95% CI=0.40-0.93). CONCLUSION: These data reflect the importance of hormones and growth factors in the early stages of life, when the mammary gland is in development and therefore more vulnerable to proliferative stimuli

Intermittent Hypoxia Is Associated With High Hypoxia Inducible Factor-1α but Not High Vascular Endothelial Growth Factor Cell Expression in Tumors of Cutaneous Melanoma Patients

Epidemiological associations linking between obstructive sleep apnea and poorer solid malignant tumor outcomes have recently emerged. Putative pathways proposed to explain that these associations have included enhanced hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) cell expression in the tumor and altered immune functions via intermittent hypoxia (IH). Here, we examined relationships between HIF-1α and VEGF expression and nocturnal IH in cutaneous melanoma (CM) tumor samples. Prospectively recruited patients with CM tumor samples were included and underwent overnight polygraphy. General clinical features, apnea-hypopnea index (AHI), desaturation index (DI4%), and CM characteristics were recorded. Histochemical assessments of VEGF and HIF-1α were performed, and the percentage of positive cells (0, 75%) was blindly tabulated for VEGF expression, and as 0, 0-5.9, 6.0-10.0, >10.0% for HIF-1α expression, respectively. Cases with HIF-1α expression >6% (high expression) were compared with those 75% of cells was compared with those with <75%. 376 patients were included. High expression of VEGF and HIF-1α were seen in 88.8 and 4.2% of samples, respectively. High expression of VEGF was only associated with increasing age. However, high expression of HIF-1α was significantly associated with age, Breslow index, AHI, and DI4%. Logistic regression showed that DI4% [OR 1.03 (95% CI: 1.01-1.06)] and Breslow index [OR 1.28 (95% CI: 1.18-1.46)], but not AHI, remained independently associated with the presence of high HIF-1α expression. Thus, IH emerges as an independent risk factor for higher HIF-1α expression in CM tumors and is inferentially linked to worse clinical CM prognostic indicators.IA is supported by SEPAR (086/2014 and 595/2017). MM-G is supported by the Instituto de Salud Carlos III (PI16/01772) and cofinanced by the European Development Regional Find “A way to achieve Europe” (ERDF) and SEPAR (211/2012). ER-F is the recipient of a postdoctoral fellowship from “Fundación Científica de la Asociación Española Contra el Cáncer” and supported by FMM-2013/0075 of “Fundación Mutua Madrileña.” JR-P is supported by FIS 2014/1737 from the Spanish Ministry of Health. RF is supported in part by the Spanish Ministry of Economy and Competitiveness—Instituto de Salud Carlos III (FIS-PI14/00004); DG is supported by National Institutes of Health grant 1R01HL130984 and by the Herbert T. Abelson Chair in Pediatrics

International Consensus Document on Obstructive Sleep Apnea

El objetivo principal de este documento internacional de consenso sobre apnea obstructiva del sueno es proporcionar unas directrices que permitan a los profesionales sanitarios tomar las mejores decisiones en la asistencia de los pacientes adultos con esta enfermedad según un resumen crítico de la literatura más actualizada. El grupo de trabajo de expertos se ha constituido principalmente por 17 sociedades científicas y 56 especialistas con amplia representación geográfica (con la participación de 4 sociedades internacionales), además de un metodólogo experto y un documentalista del Centro Cochrane Iberoamer icano. El documento consta de un manuscrito principal, con las novedades más relevantes del DIC, y una serie de manuscritos online que recogen las búsquedas bibliográficas sistemáticas de cada uno de los apartados del DIC. Este documento no cubre la edad pediátrica ni el manejo del paciente en ventilación mecánica crónica no invasiva (que se publicarán en sendos documentos de consenso aparte)

Plasma concentrations of persistent organic pollutants and pancreatic cancer risk

dyab115Findings and limitations of previous studies on persistent organic pollutants (POPs) and pancreatic cancer risk support conducting further research in prospective cohorts.We conducted a prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Participants were 513 pancreatic cancer cases and 1020 matched controls. Concentrations of 22 POPs were measured in plasma collected at baseline.Some associations were observed at higher concentrations of p, p’-DDT, trans-nonachlor, β-hexachlorocyclohexane and the sum of six organochlorine pesticides and of 16 POPs. The odds ratio (OR) for the upper quartile of trans-nonachlor was 1.55 (95\.06-2.26; P for trend = 0.025). Associations were stronger in the groups predefined as most valid (participants having fasted \gt;6 h, with microscopic diagnostic confirmation, normal weight, and never smokers), and as most relevant (follow-up ≥10 years). Among participants having fasted \gt;6 h, the ORs were relevant for 10 of 11 exposures. Higher ORs were also observed among cases with microscopic confirmation than in cases with a clinical diagnosis, and among normal-weight participants than in the rest of participants. Among participants with a follow-up ≥10 years, estimates were higher than in participants with a shorter follow-up (for trans-nonachlor: OR = 2.14, 1.01 to 4.53, P for trend = 0.035). Overall, trans-nonachlor, three PCBs and the two sums of POPs were the exposures most clearly associated with pancreatic cancer risk.Individually or in combination, most of the 22 POPs analysed did not or only moderately increased the risk of pancreatic cancer.Peer reviewe

Antimicrobial Defined Daily Dose in Neonatal Population: Validation in the Clinical Practice

Paediatric Antimicrobial Defined Daily Dose Study Group KiDDDs.Currently, there is no validated method for estimating antimicrobial consumption in the neonatal population, as it exists for adults using Defined Daily Doses (DDD). In neonatology, although there are different methods, each one with advantages and disadvantages, there is no unified criterion for use. The aim of this study is to validate the neonatal DDD designed as a new standardised form of antimicrobial consumption over this population.M.M.-T. received financial support from the Subprograma Río Hortega, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spain (CM21/00115). The project has been carried out without financial funding but is supported by the Spanish Society of Hospital Pharmacy (SEFH), the Working Group on Pharmaceutical Care in Infectious Diseases of the SEFH (Afinf) and Spanish working group on paediatric pharmacy of the SEFH (gefp).Peer reviewe

Intermittent hypoxia is associated with high hypoxia inducible factor-1α but not high vascular endothelial growth factor cell expression in tumors of cutaneous melanoma patients

Epidemiological associations linking between obstructive sleep apnea and poorer solid malignant tumor outcomes have recently emerged. Putative pathways proposed to explain that these associations have included enhanced hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) cell expression in the tumor and altered immune functions via intermittent hypoxia (IH). Here, we examined relationships between HIF-1α and VEGF expression and nocturnal IH in cutaneous melanoma (CM) tumor samples. Prospectively recruited patients with CM tumor samples were included and underwent overnight polygraphy. General clinical features, apnea-hypopnea index (AHI), desaturation index (DI4%), and CM characteristics were recorded. Histochemical assessments of VEGF and HIF-1α were performed, and the percentage of positive cells (0, 75%) was blindly tabulated for VEGF expression, and as 0, 0-5.9, 6.0-10.0, >10.0% for HIF-1α expression, respectively. Cases with HIF-1α expression >6% (high expression) were compared with those 75% of cells was compared with those with <75%. 376 patients were included. High expression of VEGF and HIF-1α were seen in 88.8 and 4.2% of samples, respectively. High expression of VEGF was only associated with increasing age. However, high expression of HIF-1α was significantly associated with age, Breslow index, AHI, and DI4%. Logistic regression showed that DI4% [OR 1.03 (95% CI: 1.01-1.06)] and Breslow index [OR 1.28 (95% CI: 1.18-1.46)], but not AHI, remained independently associated with the presence of high HIF-1α expression. Thus, IH emerges as an independent risk factor for higher HIF-1α expression in CM tumors and is inferentially linked to worse clinical CM prognostic indicators