Atlas interactivo de mortalidad de Andalucía (AIMA)

Until now, mortality atlases have been static. Most of them describe the geographical distribution of mortality using count data aggregated over time and standardized mortality rates. However, this methodology has several limitations. Count data aggregated over time produce a bias in the estimation of death rates. Moreover, this practice difficult the study of temporal changes in geographical distribution of mortality. On the other hand, using standardized mortality hamper to check differences in mortality among groups. The Interactive Mortality Atlas in Andalusia (AIMA) is an alternative to conventional static atlases. It is a dynamic Geographical Information System that allows visualizing in web-site more than 12.000 maps and 338.00 graphics related to the spatio-temporal distribution of the main death causes in Andalusia by age and sex groups from 1981. The objective of this paper is to describe the methods used for AIMA development, to show technical specifications and to present their interactivity. The system is available from the link products in www.demap.es. AIMA is the first interactive GIS that have been developed in Spain with these characteristics. Spatio-temporal Hierarchical Bayesian Models were used for statistical data analysis. The results were integrated into web-site using a PHP environment and a dynamic cartography in Flash. Thematic maps in AIMA demonstrate that the geographical distribution of mortality is dynamic, with differences among year, age and sex groups. The information nowadays provided by AIMA and the future updating will contribute to reflect on the past, the present and the future of population health in Andalusia.

Three-year multicenter surveillance of community-acquired Listeria monocytogenes meningitis in adults

BACKGROUND. Listeria monocytogenes is the third most frequent cause of bacterial meningitis. The aim of this study is to know the incidence and risk factors associated with development of acute community-acquired Lm meningitis in adult patients and to evaluate the clinical features, management, and outcome in this prospective case series. METHODS. A descriptive, prospective, and multicentric study carried out in 9 hospitals in the Spanish Network for Research in Infectious Diseases (REIPI) over a 39-month period. All adults patients admitted to the participating hospitals with the diagnosis of acute community-acquired bacterial meningitis (Ac-ABM) were included in this study. All these cases were diagnosed on the basis of a compatible clinical picture and a positive cerebrospinal fluid (CSF) culture or blood culture. The patients were followed up until death or discharge from hospital. RESULTS. Two hundred and seventy-eight patients with Ac-ABM were included. Forty-six episodes of Lm meningitis were identified in 46 adult patients. In the multivariate analysis only age (OR 1.026; 95% CI 1.00-1.05; p = 0.042), immunosuppression (OR 2.520; 95% CI 1.05-6.00; p = 0.037), and CSF/blood glucose ratio (OR 39.42; 95% CI 4.01-387.50; p = 0.002) were independently associated with a Lm meningitis. The classic triad of fever, neck stiffness and altered mental status was present in 21 (49%) patients, 32% had focal neurological findings at presentation, 12% presented cerebellum dysfunction, and 9% had seizures. Twenty-nine (68%) patients were immunocompromised. Empirical antimicrobial therapy was intravenous ampicillin for 34 (79%) of 43 patients, in 11 (32%) of them associated to aminoglycosides. Definitive ampicillin plus gentamicin therapy was significantly associated with unfavourable outcome (67% vs 28%; p = 0.024) and a higher mortality (67% vs 32%; p = 0.040).The mortality rate was 28% (12 of 43 patients) and 5 of 31 (16.1%) surviving patients developed adverse clinical outcome. CONCLUSIONS Elderly or immunocompromised patients, and a higher CSF/blood glucose ratio in patients with Ac-ABM must alert clinicians about Lm aetiology. Furthermore, we observed a high incidence of acute community-acquired Lm meningitis in adults and the addition of aminoglycosides to treatment should be avoid in order to improve the patients' outcome. Nevertheless, despite developments in intensive care and antimicrobial therapy, this entity is still a serious disease that carries high morbidity and mortality rates.

Cefaleas : proceso asistencial integrado

Proceso asistencial integrado. Publicado en la página web de la Consejería de Salud: www.juntadeandalucia.es/salud (Consejería de Salud / Profesionales / Nuestro Compromiso por la Calidad / Procesos Asistenciales Integrados)

11.440 menús semanales para enfermos renales crónicos

Fichas combinables entre sí por días de la semana, divididas en dos bloques: Desayuno-Comida y Merienda-Cena

Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription.

DNA sequence variation has been associated with quantitative changes in molecular phenotypes such as gene expression, but its impact on chromatin states is poorly characterized. To understand the interplay between chromatin and genetic control of gene regulation, we quantified allelic variability in transcription factor binding, histone modifications, and gene expression within humans. We found abundant allelic specificity in chromatin and extensive local, short-range, and long-range allelic coordination among the studied molecular phenotypes. We observed genetic influence on most of these phenotypes, with histone modifications exhibiting strong context-dependent behavior. Our results implicate transcription factors as primary mediators of sequence-specific regulation of gene expression programs, with histone modifications frequently reflecting the primary regulatory event.

Guía de servicios de sanidad ambiental

Publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social / Ciudadanía / Nuestra Salud / Medio ambiente y Salud)

Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study.

BACKGROUND Hypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information. METHODS A subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years) was genotyped for the LPL-HindIII (rs320), S447X (rs328), D9N (rs1801177) and N291S (rs268) polymorphisms, the APOA5-S19W (rs3135506) and -1131T/C (rs662799) variants, and the APOE polymorphism (rs429358; rs7412) using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable) and the association of variant combinations with TG levels and hypertriglyceridemia (TG > or = 1.69 mmol/L), including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption. RESULTS We found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p < 0.0001). In addition, the D9N, N291S, S19W and -1131T/C variants and the APOE-epsilon4 allele were significantly associated with an independent additive TG-raising effect (p < 0.05, p < 0.01, p < 0.001, p < 0.0001 and p < 0.001, respectively). Grouping individuals according to the presence of TG-lowering or TG-raising polymorphisms showed significant differences in TG levels (p < 0.0001), with the lowest levels exhibited by carriers of two lowering variants (10.2% reduction in TG geometric mean with respect to individuals who were homozygous for the frequent alleles of all the variants), and the highest levels in carriers of raising combinations (25.1% mean TG increase). Thus, carrying two lowering variants was protective against HTG (OR = 0.62; 95% CI, 0.39-0.98; p = 0.042) and having one single raising polymorphism (OR = 1.20; 95% CI, 1.39-2.87; p < 0.001) or more (2 or 3 raising variants; OR = 2.90; 95% CI, 1.56-5.41; p < 0.001) were associated with HTG. CONCLUSION Our results showed a significant independent additive effect on TG levels of the LPL polymorphisms HindIII, S447X, D9N and N291S; the S19W and -1131T/C variants of APOA5, and the epsilon4 allele of APOE in our study population. Moreover, some of the variant combinations studied were significantly associated with the absence or the presence of hypertriglyceridemia.

Molecular characterization of 39 de novo sSMC: contribution to prognosis and genetic counselling, a prospective study.

Small supernumerary marker chromosomes (sSMCs) are structurally abnormal chromosomes that cannot be characterized by karyotype. In many prenatal cases of de novo sSMC, the outcome of pregnancy is difficult to predict because the euchromatin content is unclear. This study aimed to determine the presence or absence of euchromatin material of 39 de novo prenatally ascertained sSMC by array-comparative genomic hybridization (array-CGH) or single nucleotide polymorphism (SNP) array. Cases were prospectively ascertained from the study of 65,000 prenatal samples [0.060%; 95% confidence interval (CI), 0.042-0.082]. Array-CGH showed that 22 markers were derived from non-acrocentric markers (56.4%) and 7 from acrocentic markers (18%). The 10 additional cases remained unidentified (25.6%), but 7 of 10 could be further identified using fluorescence in situ hybridization; 69% of de novo sSMC contained euchromatin material, 95.4% of which for non-acrocentric markers. Some sSMC containing euchromatin had a normal phenotype (31% for non-acrocentric and 75% for acrocentric markers). Statistical differences between normal and abnormal phenotypes were shown for the size of the euchromatin material (more or less than 1 Mb, p = 0.0006) and number of genes (more or less than 10, p = 0.0009). This study is the largest to date and shows the utility of array-CGH or SNP array in the detection and characterization of de novo sSMC in a prenatal context.

Congenital ataxia and hemiplegic migraine with cerebral edema associated with a novel gain of function mutation in the calcium channel CACNA1A.

Mutations in the CACNA1A gene, encoding the α1 subunit of the voltage-gated calcium channel Ca(V)2.1 (P/Q-type), have been associated with three neurological phenotypes: familial and sporadic hemiplegic migraine type 1 (FHM1, SHM1), episodic ataxia type 2 (EA2), and spinocerebellar ataxia type 6 (SCA6). We report a child with congenital ataxia, abnormal eye movements and developmental delay who presented severe attacks of hemiplegic migraine triggered by minor head traumas and associated with hemispheric swelling and seizures. Progressive cerebellar atrophy was also observed. Remission of the attacks was obtained with acetazolamide. A de novo 3 bp deletion was found in heterozygosity causing loss of a phenylalanine residue at position 1502, in one of the critical transmembrane domains of the protein contributing to the inner part of the pore. We characterized the electrophysiology of this mutant in a Xenopus oocyte in vitro system and showed that it causes gain of function of the channel. The mutant Ca(V)2.1 activates at lower voltage threshold than the wild type. These findings provide further evidence of this molecular mechanism as causative of FHM1 and expand the phenotypic spectrum of CACNA1A mutations with a child exhibiting severe SHM1 and non-episodic ataxia of congenital onset.

The TT genotype of the STAT4 rs7574865 polymorphism is associated with high disease activity and disability in patients with early arthritis

BACKGROUND The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis. METHODOLOGY AND RESULTS We studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5' allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28) as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01-0.83], p = 0.044). Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = -0.27 [-0.56- -0.01], p = 0.042; TT genotype = -0.68 [-1.64- -0.27], p = 0.162). After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype. CONCLUSIONS Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability.

A microRNA Signature Associated with Early Recurrence in Breast Cancer.

Recurrent breast cancer occurring after the initial treatment is associated with poor outcome. A bimodal relapse pattern after surgery for primary tumor has been described with peaks of early and late recurrence occurring at about 2 and 5 years, respectively. Although several clinical and pathological features have been used to discriminate between low- and high-risk patients, the identification of molecular biomarkers with prognostic value remains an unmet need in the current management of breast cancer. Using microarray-based technology, we have performed a microRNA expression analysis in 71 primary breast tumors from patients that either remained disease-free at 5 years post-surgery (group A) or developed early (group B) or late (group C) recurrence. Unsupervised hierarchical clustering of microRNA expression data segregated tumors in two groups, mainly corresponding to patients with early recurrence and those with no recurrence. Microarray data analysis and RT-qPCR validation led to the identification of a set of 5 microRNAs (the 5-miRNA signature) differentially expressed between these two groups: miR-149, miR-10a, miR-20b, miR-30a-3p and miR-342-5p. All five microRNAs were down-regulated in tumors from patients with early recurrence. We show here that the 5-miRNA signature defines a high-risk group of patients with shorter relapse-free survival and has predictive value to discriminate non-relapsing versus early-relapsing patients (AUC = 0.993, p-value<0.05). Network analysis based on miRNA-target interactions curated by public databases suggests that down-regulation of the 5-miRNA signature in the subset of early-relapsing tumors would result in an overall increased proliferative and angiogenic capacity. In summary, we have identified a set of recurrence-related microRNAs with potential prognostic value to identify patients who will likely develop metastasis early after primary breast surgery.

La violencia contra la mujer en la pareja como factor asociado a una mala salud física y psíquica.

OBJECTIVE: To study the impact of intimate partner violence (IPV) on women's physical and psychological health. DESIGN: Cross-sectional study. SETTING:Primary care centers in 3 Andalusian provinces. PATIENTS: A total of 425 women, aged 18 to 65 years, were recruited following the same randomisation process in 6 primary care centers. MEASUREMENTS: A self-administered structured questionnaire for this study was used to gather the information. As well as sociodemographic variables, the instrument included questions about IPV, physical health indicators (chronic disease and type, lifetime surgeries, days in bed), psychological health (psychological morbidity, use of tranquilizers, antidepressants, pain killers, alcohol and recreational drugs), self-perceived health and social support. RESULTS: Of 425 women, 31.5% ever experienced any type of partner violence. Women experiencing IPV were more likely to suffer a chronic disease. IPV was significantly associated with a number of adverse health outcomes, including spending more than 7 days in bed in the last three months (ORa=2.96; CI 95%, 1.00-8.76), psychological morbidity (ORa=2.68; CI 95%, 1.60-4.49) and worse self-perceived health (ORa=1.89; CI 95%, 1.04-3.43), after controlling for potential confounding variables. CONCLUSION: This study shows that ever experiencing IPV is associated with a worse psychological and self-perceived health. Physical injuries are not the only "evidence" of the presence of IPV. Primary health care professionals are in a privileged position to help women who are abused by their partners.

Spontaneous NA+ transients in individual mitochondria of intact astrocytes.

Mitochondria in intact cells maintain low Na(+) levels despite the large electrochemical gradient favoring cation influx into the matrix. In addition, they display individual spontaneous transient depolarizations. The authors report here that individual mitochondria in living astrocytes exhibit spontaneous increases in their Na(+) concentration (Na(mit)(+) spiking), as measured using the mitochondrial probe CoroNa Red. In a field of view with approximately 30 astrocytes, up to 1,400 transients per minute were typically detected under resting conditions. Na(mit)(+) spiking was also observed in neurons, but was scarce in two nonneural cell types tested. Astrocytic Na(mit)(+) spikes averaged 12.2 +/- 0.8 s in duration and 35.5 +/- 3.2 mM in amplitude and coincided with brief mitochondrial depolarizations; they were impaired by mitochondrial depolarization and ruthenium red pointing to the involvement of a cation uniporter. Na(mit)(+) spiking activity was significantly inhibited by mitochondrial Na(+)/H(+) exchanger inhibition and sensitive to cellular pH and Na(+) concentration. Ca(2+) played a permissive role on Na(mit)(+) spiking activity. Finally, the authors present evidence suggesting that Na(mit)(+) spiking frequency was correlated with cellular ATP levels. This study shows that, under physiological conditions, individual mitochondria in living astrocytes exhibit fast Na(+) exchange across their inner membrane, which reveals a new form of highly dynamic and localized functional regulation.

Constitución Española y Constitución Europea

Breu comentari crític de la decisió del TC de 13 de desembre de 2004. Seguint el suggeriment que li havia fet el Consell d'Estat, el Govern va plantejar al TC quatre qüestions sobre la possible compatibilitat de la Constitució per a Europa amb la CE.