Consejería de Salud y Consumo

Environmental carcinogens contained in air pollution, such as polycyclic aromatic hydrocarbons, aromatic amines or N-nitroso compounds, predominantly form DNA adducts but can also generate interstrand cross-links and reactive oxygen species. If unrepaired, such lesions increase the risk of somatic mutations and cancer. Our study investigated the relationships between 22 polymorphisms (and their haplotypes) in 16 DNA repair genes belonging to different repair pathways in 1094 controls and 567 cancer cases (bladder cancer, 131; lung cancer, 134; oral-pharyngeal cancer, 41; laryngeal cancer, 47; leukaemia, 179; death from emphysema and chronic obstructive pulmonary disease, 84). The design was a case-control study nested within a prospective investigation. Among the many comparisons, few polymorphisms were associated with the diseases at the univariate analysis: XRCC1-399 Gln/Gln variant homozygotes [odds ratios (OR) = 2.20, 95% confidence intervals (CI) = 1.16-4.17] and XRCC3-241 Met/Met homozygotes (OR = 0.51, 95% CI = 0.27-0.96) and leukaemia. The recessive model in the stepwise multivariate analysis revealed a possible protective effect of XRCC1-399Gln/Gln in lung cancer (OR = 0.22, 95% CI = 0.05-0.98), and confirmed an opposite effect (OR = 2.47, 95% CI = 1.02-6.02) in the leukaemia group. Our results also suggest that the XPD/ERCC1-GAT haplotype may modulate leukaemia (OR = 1.28, 95% CI = 1.02-1.61), bladder cancer (OR = 1.38, 95% CI = 1.06-1.79) and possibly other cancer risks. Further investigations of the combined effects of polymorphisms within these DNA repair genes, smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process.

INTRODUCTION: Although frailty is common among community-dwelling older adults, its prevalence in Europe and how this varies between countries is unclear. METHODS: A systematic review and meta-analysis of literature on frailty prevalence in 22 European countries involved in the Joint Action ADVANTAGE was conducted. RESULTS: Sixty-two papers, representing 68 unique datasets were included. Meta-analysis showed an overall estimated frailty prevalence of 18% (95% confidence interval, CI, 15-21%). The prevalence in community (n = 53) vs non-community based studies (n = 15) was 12% (95% CI 10-15%) and 45% (95% CI 27-63%), respectively. Pooled prevalence in community studies adopting a physical phenotype was 12% (95% CI 10-14%, n = 45) vs 16% (95% CI 7-29%, n = 8) for all other definitions. Sub-analysis of a subgroup of studies assessed as high-quality (n = 47) gave a pooled estimate of 17% (95% CI 13-21%). CONCLUSIONS: The considerable and significant heterogeneity found warrants the development of common methodological approaches to provide accurate and comparable frailty prevalence estimates at population-level.

OBJECTIVES: To describe the epidemiological and clinical characteristics of an outbreak of occupational silicosis and the associated working conditions. METHODS: Cases were defined as men working in the stone cutting, shaping, and finishing industry in the province of Cádiz, diagnosed with silicosis between July 2009 and May 2012, and were identified and diagnosed by the department of pulmonology of the University Hospital of Puerto Real (Cádiz). A census of workplaces using quartz conglomerates was carried out to determine total numbers of potentially exposed workers. A patient telephone survey on occupational exposures and a review of medical records for all participants were conducted. RESULTS: Silicosis was diagnosed in 46 men with a median age of 33 years and a median of 11 years working in the manufacturing of countertops. Of these cases, 91.3% were diagnosed with simple chronic silicosis, with an abnormal high-resolution computerized tomography (HRCT) scan. One patient died during the study period. Employer non-compliance in prevention and control measures was frequently reported, as were environmental and individual protection failures. CONCLUSIONS: The use of new construction materials such as quartz conglomerates has increased silicosis incidence due to intensive occupational exposures, in the context of high demand fuelled by the housing boom. This widespread exposure poses a risk if appropriate preventive measures are not undertaken.

The asymptotic response of donor stars in interacting binary systems to very rapid mass loss is characterized by adiabatic expansion throughout their interiors. In this limit, energy generation and heat flow through the stellar interior can be neglected. We model this response by constructing model sequences, beginning with a donor star filling its Roche lobe at an arbitrary point in its evolution, holding its specific entropy and composition profiles fixed as mass is removed from the surface. The stellar interior remains in hydrostatic equilibrium. Luminosity profiles in these adiabatic models of mass-losing stars can be reconstructed from the specific entropy profiles and their gradients. These approximations are validated by comparison with time-dependent binary mass transfer calculations. We describe how adiabatic mass loss sequences can be used to quantify threshold conditions for dynamical time scale mass transfer, and to establish the range of post-common envelope binaries that are allowed energetically.

Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with <4 BMs/day on SSAs (or ≥1 symptom or ≥4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE). The primary safety and efficacy endpoints were incidence of treatment-emergent adverse events (TEAEs) and percent change from baseline in 24-h u5-HIAA at week 12. Patients ( N = 76) were randomly assigned (1:1:1) to receive placebo or telotristat ethyl 250 mg or 500 mg 3 times per day (tid); 67 continued receiving telotristat ethyl 500 mg tid during the OLE. Through week 12, TEAEs were generally mild to moderate in severity; 5 (placebo), 1 (telotristat ethyl 250 mg) and 3 (telotristat ethyl 500 mg) patients experienced serious events, and the rate of TEAEs in the OLE was comparable. At week 12, significant reductions in u5-HIAA from baseline were observed, with Hodges–Lehmann estimators of median treatment differences from placebo of −54.0% (95% confidence limits, −85.0%, −25.1%, P < 0.001) and −89.7% (95% confidence limits, −113.1%, −63.9%, P < 0.001) for telotristat ethyl 250 mg and 500 mg. These results support the safety and efficacy of telotristat ethyl when added to SSAs in patients with CS diarrhea (ClinicalTrials.gov identifier: Nbib2063659).

Objetivo. Conocer la sobrecarga sentida por los cuidadores y las repercusiones que este rol representa sobre su calidad de vida, su salud en las esferas fsica, psquica y social y su necesidad de utilizacin de los recursos sanitarios (frecuentacin). Diseo. Estudio observacional y analtico de casos y controles Emplazamiento. Centro de salud de caractersticas urbanas. Participantes. El grupo de estudio fue formado por 156 cuidadores principales y el grupo control por 156 personas adscritas al centro de salud que no realizaban funciones de cuidador principal, emparejadas por edad, sexo y nmero de patologas crnicas padecidas

Staphylococcal food poisoning, one of the most common food-borne diseases, results from ingestion of one or more staphylococcal enterotoxins (SEs) produced by Staphylococcus aureus in foods. In the present study, 64 S. aureus isolates recovered from foods and food handlers, associated or not associated with food-poisoning outbreaks in Spain, were investigated. They were assigned to 31 strains by spa typing, multilocus sequence typing (MLST), exotoxin gene content, and antimicrobial resistance. The strains belonged to 10 clonal complexes (CCs): CC5 (29.0%), CC30 (25.8%), CC45 (16.1%), CC8, CC15 (two strains each), CC1, CC22, CC25, CC59, and CC121 (one strain each). They contained hemolysin genes (90.3%); lukED (77.4%); exfoliatin genes eta, etd (6.5% each), and etb (3.2%); tst (25.8%); and the following enterotoxin or enterotoxin-like genes or clusters: sea (38.7%), seb (12.9%), sec (16.1%), sed-selj with or without ser (22.9%), selk-selq (6.5%), seh, sell, selp (9.7% each), egc1 (32.3%), and egc2 (48.4%). The number of se and sel genes ranged from zero to 12. All isolates carrying tst, and most isolates with genes encoding classical enterotoxins (SEA, SEB, SEC, and SED), expressed the corresponding toxin(s). Two CC5 isolates from hamburgers (spa type t002, sequence type 5 [ST5]; spa type t2173, ST5) were methicillin resistant and harbored staphylococcal cassette chromosome mec (SCCmec) IVd. Six (19.4%) were mupirocin resistant, and one (spa type t120, ST15) from a food handler carried mupA (MIC, 1,250 μg/ml). Resistance to ampicillin (blaZ) (61.3%), erythromycin (ermA-ermC or ermC) (25.8%), clindamycin (msrA-msrB or msrB) (16.1%), tetracycline (tetK) (3.2%), and amikacin-gentamicin-kanamycin-tobramycin (aphA with aacA plus aphD or aadD) (6.5%) was also observed. The presence of S. aureus strains with an important repertoire of virulence and resistance determinants in the food chain represents a potential health hazard for consumers and merits further observation.

The Spanish Guideline on the Management of Asthma, better known by its acronym in Spanish GEMA, has been available for more than 20 years. Twenty-one scientific societies or related groups both from Spain and internationally have participated in the preparation and development of the updated edition of GEMA, which in fact has been currently positioned as the reference guide on asthma in the Spanish language worldwide. Its objective is to prevent and improve the clinical situation of people with asthma by increasing the knowledge of healthcare professionals involved in their care. Its purpose is to convert scientific evidence into simple and easy-to-follow practical recommendations. Therefore, it is not a monograph that brings together all the scientific knowledge about the disease, but rather a brief document with the essentials, designed to be applied quickly in routine clinical practice. The guidelines are necessarily multidisciplinary, developed to be useful and an indispensable tool for physicians of different specialties, as well as nurses and pharmacists. Probably the most outstanding aspects of the guide are the recommendations to: establish the diagnosis of asthma using a sequential algorithm based on objective diagnostic tests; the follow-up of patients, preferably based on the strategy of achieving and maintaining control of the disease; treatment according to the level of severity of asthma, using six steps from least to greatest need of pharmaceutical drugs, and the treatment algorithm for the indication of biologics in patients with severe uncontrolled asthma based on phenotypes. And now, in addition to that, there is a novelty for easy use and follow-up through a computer application based on the chatbot-type conversational artificial intelligence (ia-GEMA). La Guía Española para el Manejo del Asma, mejor conocida por su acrónimo en español, GEMA, está a nuestra disposición desde hace más de veinte años. Veintiuna sociedades científicas o grupos relacionados, tanto de España como de otros países, han participado en la preparación y desarrollo de la edición actualizada de GEMA que, de hecho, se ha posicionado en la actualidad a nivel mundial como la guía de referencia sobre asma en lengua española. Su objetivo es prevenir y mejorar la situación clínica de las personas con asma, aumentando el conocimiento de los profesionales sanitarios involucrados en su cuidado. Su propósito es convertir la evidencia científica en recomendaciones prácticas sencillas y fáciles de seguir. Por lo tanto, no se trata de una monografía que reúna todo el conocimiento científico sobre la enfermedad, sino más bien de un documento conciso con lo esencial, diseñado para ser aplicado rápidamente en la práctica clínica de rutina. Las recomendaciones son necesariamente multidisciplinares, están desarrolladas para ser útiles y una herramienta indispensable para médicos de diferentes especialidades, así como para profesionales de enfermería y farmacia. Seguramente, los aspectos más destacados de la guía son las recomendaciones para: establecer el diagnóstico del asma utilizando un algoritmo secuencial basado en pruebas diagnósticas objetivas; el seguimiento de los pacientes, preferentemente basado en la estrategia de lograr y mantener el control de la enfermedad; el tratamiento según el nivel de gravedad del asma utilizando seis escalones, desde la menor hasta la mayor necesidad de medicamentos, y el algoritmo de tratamiento basado en fenotipos para la indicación de biológicos en pacientes con asma grave no controlada. A esto se suma ahora una novedad para su fácil uso y seguimiento a través de una aplicación informática basada en la inteligencia artificial conversacional de tipo chatbot (ia-GEMA).

Antihypertensive drug adherence (ADA) is a mainstay in blood pressure control. Education through mobile phone short message system (SMS) text messaging could improve ADA. The authors conducted a randomized study involving 314 patients with hypertension with <6 months of antihypertensive treatment from the Preventive Health Program of 12 different primary care centers in Santiago, Chile. Patients were randomly assigned to receive or not receive SMS related to ADA and healthy lifestyle. Adherence was assessed by the self-reported four-item scale Morisky-Green-Levine questionnaire at baseline and after 6 months of follow-up, with four of four positive questions classified as good adherence. Group comparison for adherence was performed by means of a logistic regression model, adjusting by baseline adherence, age older than 60 years, and sex. A total of 163 patients were randomized to receive and 151 to not receive SMS. After 6 months of follow-up, ADA in the non-SMS group decreased from 59.3% to 51.4% (P=.1). By contrast, adherence increased from 49% to 62.3% (P=.01) in the SMS group. Text messaging intervention improved ADA (risk ratio, 1.3; 95% confidence interval, 1.0-1.6 [P<.05]). At 6-month follow-up, text messaging resulted in an increase in reporting ADA in this hypertensive Latino population. This approach could become an effective tool to overcome poor medication adherence in the community.

MicroRNAs (miRNAs) have been shown to be important in early development and maintenance of human embryonic stem cells (hESCs). The miRNA miR-302-367 is specifically expressed in hESCs, and its expression decays on differentiation. We previously identified the structure of the gene coding for the human miR-302-367 cluster and characterized its promoter. The promoter activity was functionally validated in hESCs, opening up new avenues to further investigate how these miRNA molecules fit in the complex molecular network conferring "stemness" properties to hESCs. The physiological roles of specific miRNA-mRNA interactions remain largely unknown. Here, we investigated putative miR-302-367 mRNA targets in hESCs, potentially relevant for ESC biology. We found that the Nodal inhibitors Lefty1 and Lefty2 are post-transcriptionally targeted by miR-302s in hESCs. Functional analyses indicate that miR-302s negatively modulate the level of lefties, and become upstream regulators of the TGFβ/Nodal pathway, functioning via Smad-2/3 signaling. Overexpression of the miR-302-367 cluster in hESCs causes a delay in early hESC differentiation, as measured by enhanced levels of ESC-specific transcription factors, coupled to a faster teratoma formation in mice transplanted with miR-302-367-expressing hESCs and a concomitant impairment of germ layer specification, displaying robust decreased levels of early mesodermal, endodermal, and ectodermal specific markers. These findings suggest that Lefty is negatively modulated by miR-302s in hESCs, which plays an important role in maintaining the balance between pluripotency and germ layer specification.

Levels of plasma DNA concentrations in cancer patients have been shown to be higher than the plasma DNA concentrations found in healthy subjects. The value of plasma DNA levels for development of neoplastic or pulmonary disease was evaluated in a large prospective study. Plasma samples (n = 1,184) were analyzed from 776 controls, 359 cases of cancer (lung, bladder, oral cavity, pharynx, larynx, leukemia) and 49 deaths from chronic obstructive pulmonary disease (COPD), including never smokers and ex-smokers, from 9 countries across Europe. The amount of plasma DNA was variable across the European Prospective Investigation into Cancer and Nutrition (EPIC) centers. High DNA concentrations in some centers might be due to the type of population recruited and/or the treatment of the samples. An elevated and statistically significant odds ratio (OR) was found for COPD deaths (OR = 2.53; 95% CI = 1.06-6.02), while nonsignificant increased ORs were present for oral cancers, cancers of the pharynx and larynx and leukemia. When the analyses were stratified by time since recruitment (below or above 36 months), the increased ORs were limited to the more recent period of recruitment, i.e., a time elapsed between blood drawing and disease onset lower than 36 months. This was particularly true for COPD deaths (OR = 12.7; 95% CI = 1.57-103) and leukemia (OR = 2.37; 95% CI = 1.20-4.67).

Cases of West Nile neuroinvasive disease (WNND) in Spain increased in summer 2020. Here we report on this increase and the local, regional and national public health measures taken in response. We analysed data from regional surveillance networks and the National Epidemiological Surveillance Network, both for human and animal West Nile virus (WNV) infection. During the 2020 season, a total of 77 human cases of WNV infection (median age 65 years; 60% males) were detected in the south-west of Spain; 72 (94%) of these cases developed WNND, presenting as meningoencephalitis, seven of which were fatal. In the previous two decades, only six human cases of WNND were detected in Spain. Reduced activities for vector control this season, together with other factors, might have contributed to the massive increase. Public health measures including vector control, campaigns to raise awareness among physicians and the general population, and interventions to ensure the safety of donations of blood products, organs, cells and tissues were effective to reduce transmission. Going forward, maintenance of vector control activities and an update of the vector-borne diseases response plan in Spain is needed.

In last decades, nursing has undergone an accelerated process of changing identity, for which has contributed to the social recognition, a more autonomous professional intervention and the process of knowledge construction that the confirmes it through the research in the context of other sciences.\nThis whole process has impressed not only changes in care practice, in teaching and research. The generalization of doctoral programs and post-doctoral has been an asset to building a body of knowledge that accelerated the process of finding professional, social, cultural, political and academic recognition.\nThe construction of knowledge must be closely linked to processes of dissemination and diffusion, either through international research networks or through publications internationally. Publications either in paper form and electronic platform, organized, and disseminated by dozens of databases allow easy access, low cost and possibility of wide dissemination of research results, contribute to the exchange of knowledge globally and in real time, and avoid the deepening of inequalities related to unequal access to cultural goods.\nHowever there are still difficulties to join the scientific community to the expansion of digital publications, due to entrenched cultural practices, inadequate information and lack of benchmarks, as well as lack of incentive to publish digital media for lack of scientific acceptance. Yet today's digital publications have a scope, spread, impact and dynamism editorial incomparably larger than a printed journal. We now face a major change with regard to the growing impact of electronic dissemination although there is still resistance to the use of digital databases of open access in areas such as Anthropology, History, Literature and Linguistics.\nThe REUOL, with almost four years of existence, being made into a magazine web platform, has been an important landmark in the academic world, contributing to wide dissemination of research. Its editorial board, the quality and quantity of items, a consistent policy on the criteria for publication, coupled with open and free access, which gives more visibility and transparency to what is produced, reinforcing its role of serving society by promoting dissemination of scientific knowledge.\nThe articles published in this number may review the high quality that REUOL has in the academic and scientific word. I invite everyone to a critical reading of them.

El fomento de la salud y bienestar con enfoque biopsicosocial es una preocupación de los gobiernos, cuyas búsquedas se soportan en la formación de profesionales de las Ciencias Sociales y Biomédicas con la intención de conservar la articulación entre el contexto social y el proceso salud-enfermedad para identificar las oportunidades de intervención interdisciplinaria que tienden a la prevención de la enfermedad y la promoción de la salud. Los temas tratados en este libro pueden servir como fundamento teórico para estudiantes y docentes de pregrado y posgrado que tienen interés en profundizar y potenciar sus contenidos con la búsqueda de respuestas a los nuevos retos que se generan por los cambios políticos, económicos, demográficos y epidemiológicos en diferentes entornos.

COVID-19 is a major worldwide health problem because of acute respiratory distress syndrome, and mortality. Several lines of evidence have suggested a relationship between the vitamin D endocrine system and severity of COVID-19. We present a survival study on a retrospective cohort of 15,968 patients, comprising all COVID-19 patients hospitalized in Andalusia between January and November 2020. Based on a central registry of electronic health records (the Andalusian Population Health Database, BPS), prescription of vitamin D or its metabolites within 15-30 days before hospitalization were recorded. The effect of prescription of vitamin D (metabolites) for other indication previous to the hospitalization was studied with respect to patient survival. Kaplan-Meier survival curves and hazard ratios support an association between prescription of these metabolites and patient survival. Such association was stronger for calcifediol (Hazard Ratio, HR = 0.67, with 95% confidence interval, CI, of [0.50-0.91]) than for cholecalciferol (HR = 0.75, with 95% CI of [0.61-0.91]), when prescribed 15 days prior hospitalization. Although the relation is maintained, there is a general decrease of this effect when a longer period of 30 days prior hospitalization is considered (calcifediol HR = 0.73, with 95% CI [0.57-0.95] and cholecalciferol HR = 0.88, with 95% CI [0.75, 1.03]), suggesting that association was stronger when the prescription was closer to the hospitalization.

OBJECTIVE: To evaluate the safety and efficacy of sibutramine 15 mg by mouth once per day in obese patients over a period of 6 months. RESEARCH METHODS AND PROCEDURES: A monocenter, double-blind, placebo controlled, parallel, prospective clinical trial was carried out. Sixty-nine male and female obese patients (body mass index [BMI] > 30 kg/m2) aged 16 to 65 years entered the trial. RESULTS: 22 of 35 patients in the sibutramine group and 9 of 34 patients in the placebo group completed the trial. The high dropout rate in the sibutramine group was due to adverse events in 3 cases, lack of efficacy (as judged by patients) in 7, loss to follow-up in 2, and an orthopedic device being worn in 1; in the placebo group the dropouts were ascribed to lack of efficacy (as judged by patients) in 17 cases and to loss to follow-up in 8 cases. Using the method of last observation carried forward, the weight loss in the sibutramine group was 10.27 kg (95% confidence intervals [95% CI] 7.66; 13.07) and 1.26 kg (95% CI 0.3; 2.23) in the placebo group. The BMI loss was 4.17 kg/m2 (95% CI 3.11; 5.22) in the sibutramine group and 0.53 kg/m2 (95% CI 0.13; 0.92) in the placebo group. The waist circumference reduction was 12.51 cm (95% CI 9.25; 15.77) in the sibutramine group and 3.26 cm (95% CI 1.38; 5.14) in the control group (p<0.05 by paired Student's t test for all the intragroup comparisons). Twenty-three sibutramine patients had 34 adverse events, the most frequent adverse events in the sibutramine group were upper respiratory tract infections (n = 6) and constipation (n = 6); 16 placebo patients had 21 adverse events. Three sibutramine patients withdrew their informed consent when they had adverse events. DISCUSSION: The results show that sibutramine induces significant loss of body weight and waist circumference. Cardiovascular function was not significantly affected by sibutramine. Sibutramine was well tolerated by most of the patients.

INTRODUCTION: Cognitive impairment, a clinical entity causing complete or partial intellectual dysfunction, is a major public health concern that poses a challenge for health and social services. The purpose of this study is to estimate the prevalence of this disorder in people aged 65 and older visiting the primary care physician in 5 health sentinel networks. METHOD: A sample of patients visiting their primary care doctor on 4 randomly selected days completed the Mini-Cog screening test. Diagnosis of cognitive impairment was confirmed with the Mini-Mental State Examination and the Alzheimer's Questionnaire. We estimated raw and adjusted rates using demographic and social variables. RESULTS: We included 4,624 patients from 5 autonomous communities and representing a population of 1,723,216 inhabitants. The adjusted prevalence rate was 18.5% (95% CI 17.3-19.7], with differences between sentinel networks. Women showed higher adjusted rates than men: 18.5 vs. 14.3%. The highest prevalence rate was observed in people aged 85 and older (45.3%); prevalence rates vary depending on education level and marital status. CONCLUSIONS: Cognitive impairment is a frequent reason for consultations in primary care. Its prevalence is higher in women and increases exponentially with age. A number of sensitive, validated tools have been proven useful in screening for and confirming cognitive impairment. Using these tools in primary care settings enables early treatment of these patients.

Blindness due to corneal diseases is a common pathology affecting up to 23 million individuals worldwide. The tissue-engineered anterior human cornea, which is currently being tested in a Phase I/II clinical trial to treat severe corneal trophic ulcers with preliminary good feasibility and safety results. This bioartificial cornea is based on a nanostructured fibrin-agarose biomaterial containing human allogeneic stromal keratocytes and cornea epithelial cells, mimicking the human native anterior cornea in terms of optical, mechanical, and biological behavior. This product is manufactured as a clinical-grade tissue engineering product, fulfilling European requirements and regulations. The clinical translation process included several phases: an initial in vitro and in vivo preclinical research plan, including preclinical advice from the Spanish Medicines Agency followed by additional preclinical development, the adaptation of the biofabrication protocols to a good manufacturing practice manufacturing process, including all quality controls required, and the design of an advanced therapy clinical trial. The experimental development and successful translation of advanced therapy medicinal products for clinical application has to overcome many obstacles, especially when undertaken by academia or SMEs. We expect that our experience and research strategy may help future researchers to efficiently transfer their preclinical results into the clinical settings.

Metabolizing enzymes, which often display genetic polymorphisms, are involved in the activation of compounds present in tobacco smoke that may be relevant to gastric carcinogenesis. We report the results of a study looking at the association between risk of gastric adenocarcinoma and polymorphisms in genes CYP1A1, CYP1A2, EPHX1, and GSTT1. A nested case-control study was carried out within the European Prospective Investigation into Cancer and Nutrition, developed in 10 European countries. The study includes 243 newly diagnosed cases of histologically confirmed gastric adenocarcinoma and 946 controls matched by center, age, sex, and date of blood collection. Genotypes were determined in nuclear DNA from WBCs. We found an increased risk of gastric cancer for homozygotes for C (histidine) variant in Y113H of EPHX1 (odds ratio, 1.91; 95% confidence interval, 1.19-3.07) compared with subjects with TC/TT. There was also a significant increased risk for smokers carrying at least one variant allele A in Ex7+129C>A (m4) of CYP1A1 and never smokers with null GSTT1 and allele A in the locus -3859G>A of CYP1A2. Most of these genes are involved in the activation and detoxification of polycyclic aromatic hydrocarbons, suggesting a potential role of these compounds in gastric carcinogenesis.

OBJECTIVES: To broaden knowledge of the molecular bases and genetics of multidrug resistance in clinical isolates of Salmonella enterica serotype 4,5,12:i:- belonging to the Spanish clone. METHODS: The relatedness of the isolates was determined by phage typing and XbaI-PFGE. Resistance genes, integrons and transposable elements were identified by PCR amplification and sequencing. Plasmids were characterized by alkaline lysis, S1-PFGE, conjugation, replicon typing and Southern blot hybridization. RESULTS: The isolates were closely related and resistant to five to seven antimicrobials (ampicillin, chloramphenicol, gentamicin, streptomycin/spectinomycin, sulphonamides, trimethoprim and tetracycline, arranged in different combinations). Most of the responsible genes were provided by a conventional class 1 integron with the dfrA12-orfF-aadA2 variable region, an atypical class 1 integron containing sul3 next to the estX-psp-aadA2-cmlA1-aadA1 variable region and a truncated Tn1721 transposon carrying tet(A). A defective Tn21 with the mer operon and ISVsa3 associated with sul2 were also detected. All resistance genes and mobile genetic elements were located on large, non-conjugative and highly variable plasmids carrying one (A/C) or two (A/C and N) replicons, as well as virulence genes of pSLT. CONCLUSIONS: IncA/C plasmids are responsible for multidrug resistance in an increasing number of relevant human and animal bacterial pathogens, and hence are regarded as an important threat to public health. Those found in the Spanish clone of Salmonella 4,5,12:i:- constitute a relevant example of short-term evolution, and could have been involved in the successful adaptation of this pathogen.