A spatial risk approach towards integrated marine spatial planning: A case study on European hake nursery areas in the North Alboran Sea.

Europe's Blue Growth strategy promotes the intensification of human activities at sea and increases the environmental risk such as the decline of the provision of key ecosystem services and potential conflicts among human activities. The fishing sector, in the Alboran Sea, is economically and culturally one of the most important and relies on overexploited target species such as European hake (Merlucius merlucius). Here we identified and quantified the impact of human pressures on the capacity of marine habitats to support the provision of food as an important ecosystem service. We modelled the spatial distribution of nursery areas of European hake in the Alboran Sea, using General Additive Models (GAM) and overlaid those with European Nature Information System (EUNIS) habitats. A sensitivity analysis of hake nursery areas to cumulative human impacts identified the Bay of Malaga as the most sensitive area with trawling frequencies up to 60 times higher than the habitats recovery time. Further, we identified an increased conflict potential among human activities such as trawling and extraction with the presence of Marine Protected Areas (MPAs), which provide MPAs a high vulnerability similar to that found in unprotected areas. Future scenarios considering the increase of renewable energy and alternative food production show conflicts between aquaculture and MPAs as well as offshore wind farms and offshore shipping. Hence, our results show strong arguments for an integrated spatial management approach, including benthic trawling. We also suggest restricting trawling activities inside MPAs to safeguard the habitats capacity to support ecosystem services. Our spatially explicit assessment framework is transparent and transferable to other Mediterranean regions. Thus, it can function as a model on how to incorporate cumulative effect assessments in marine spatial planning processes.

Methylation profile of triple-negative breast carcinomas.

Breast cancer is a group of clinically, histopathologically and molecularly heterogeneous diseases, with different outcomes and responses to treatment. Triple-negative (TN) breast cancers are defined as tumors that lack the expression of estrogen receptor, progesterone receptor and epidermal growth factor receptor 2. This subgroup accounts for 15% of all types of breast cancer and its prevalence is higher among young African, African-American and Latino women. The hypermethylation of CpG islands (CpGI) is a common epigenetic alteration for suppressing gene expression in breast cancer and has been shown to be a key factor in breast carcinogenesis. In this study we analyzed the hypermethylation of 110 CpGI within 69 cancer-related genes in TN tumors. For the methylation analysis, we used the methyl-specific multiplex-ligation probe amplification assay. We found that the number of methylated CpGI is similar between TN and non-TN tumors, but the methylated genes between the groups are different. The methylation profile of TN tumors is defined by the methylation of five genes (that is, CDKN2B, CD44, MGMT, RB and p73) plus the non-methylation of 11 genes (that is, GSTP1, PMS2, MSH2, MLH1, MSH3, MSH6, DLC1, CACNA1A, CACNA1G, TWIST1 and ID4). We conclude that TN tumors have a specific methylation profile. Our findings give new information for better understanding tumor etiology and encourage future studies on potential drug targets for triple-negative breast tumors, which now lack a specific treatment.

Situación epidemiológica de la tuberculosis en el mundo y en España / No disponible

La tuberculosis (TB) es una causa importante de enfermedad y muerte en todo el mundo, especialmente en Asia y África. El número de casos nuevos está bajando en todas las regiones de la OMS excepto en la europea, en la que se mantiene. En esta región, la tasa media de notificación en 2006 fue de 48 casos por 100.000 habitantes (422.830 casos), con gran variabilidad entre los países. En España, los datos de la Red Nacional de Vigilancia Epidemiológica muestran una tendencia decreciente en las tasas hasta 18 casos por 100.000 en 2007. Las tasas son más altas en varones y adultos jóvenes y la proporción de casos en extranjeros está aumentando. El Plan Nacional para la prevención y el control de TB en España fue aprobado en 2007 y está siendo desarrollado. Desde 2008, el Centro Europeo para el Control de Enfermedades (ECDC) y OMS/EURO, coordinan la vigilancia de la TB en Europa (AU)

Tuberculosis (TB) is a major cause of illness and death worldwide, especially in Asia and Africa. The number of new cases per capita is falling in all WHO regions except the European Region, in which is stable. In this Region, The overall notification rate averaged 48 cases per 100,000 (422,830 cases) in 2006, with large variability between countries. In Spain, the TB data from the National Surveillance Network show a slow decreasing trend in the national rates (18 cases per 100,000 in 2007, provisional data). The rates are higher in males and in young adults and the proportion of cases in foreigners is increasing. The National Plan for the Prevention and Control of TB in Spain was released in 2007 and is being developed. The ECDC (The European Centre for Disease Prevention and Control) and WHO/EURO, are jointly coordinating the TB surveillance in Europe from January 2008 onwards (AU)

Seroprevalence of HIV and HTLV in a representative sample of the Spanish population.

HIV and HTLV seroprevalence was determined by means of unlinked anonymous testing of 2144 sera, originally obtained from primary care patients by representative sampling of the Spanish population aged 15-39 years in 1996. HIV-1 seroprevalence was 4.3 per 1000 population in the 15-39 years age group [95% confidence interval (CI), 1.5-10.7] and 5.6 per 1000 (95% CI, 1.8-15.3) in the 20-39 years age group. Seroprevalence proved higher in males and urban residents. No antibodies to HIV-2 and HTLV-I were detected in any of the sera studied. However, presence of antibodies to HTLV-II was confirmed in one serum sample, while HTLV seroreactivity, though detected in another, could not be typed. The two HTLV-positive results equated to a seroprevalence of 1.9 per 1000 in the 20-39 years age group (95% CI, 0.3-8.6). HIV-I seroprevalence was consistent with previous estimates yielded by back-calculation. The level of HTLV seroprevalence found suggests endemicity.

The Spanish multidrug resistant tuberculosis network.

The network to monitor the spread of multidrug resistance tuberculosis (MDR-TB) in Spain based on genomic typing and set up in January 1998 benefits from the participation of about 90% of the laboratories of the national health system. Of the 94 MDR-TB pa

c-erbB-2 (HER-2/neu) protein and drug resistance in breast cancer patients treated with induction chemotherapy.

Expression of c-erbB-2 protein has been associated with poor prognosis and poor response to chemotherapy in breast cancer patients. In the present prospective study, we have analyzed whether c-erbB-2, p53 and P170 proteins may be determinants of tumor resistance in locally advanced breast cancer patients treated with induction chemotherapy. Biopsies (n = 60) were examined by immuno-histochemistry; in 62% of cases core or incisional biopsies were taken before drug administration, allowing comparison in paired biopsies of the cytological and molecular changes induced by treatment Sixty percent of the patients received relatively high doses of FAC or FEC (5-fluorouracil, doxorubicin or epirubicin and cyclophosphamide), and 40% received relatively high doses of doxorubicin or epirubicin alone. No significant changes were observed in the molecular markers studied following chemotherapy; in the few biopsies where changes appeared, the changes did not exhibit any significant or similar trend. For 30 of the patients who received FAC/FEC treatment, follow-up reached a median of 34 months. In these cases, neither the clinical (reduction in tumor size) nor the histological (evaluated after neoadjuvant chemotherapy) responses showed statistically significant differences between the patients who developed distant metastases and the disease-free patients. c-erbB-2 was over-expressed in 50% of patients who developed distant metastases vs. 7% of the disease-free patients. Disease free survival (DFS) curves between c-erbB-2-positive and c-erbB-2-negative patients were statistically significant. No correlation between p53 or P170 expression with DFS was found. Our results suggest that c-erbB-2 protein expression is associated with development of distant metastases in breast cancer patients treated with relatively high doses of anthracyclines in induction chemotherapy.

Heat shock protein expression and drug resistance in breast cancer patients treated with induction chemotherapy.

Heat shock proteins (Hsps) are induced in vitro by several cytotoxic drugs; in human breast cancer cells these proteins appear to be involved in anti-cancer drug resistance. The present report was designed to analyze whether chemotherapy affects in vivo the expression of Hsp27, Hsp70, Hsc70 and Hsp90 in breast cancer patients treated with induction chemotherapy and whether these proteins may be determinants of tumor resistance to drug administration. We have analyzed 35 biopsies from breast cancer patients treated with induction chemotherapy. Expression of the Hsps in the tumors was compared with (i) histological and clinical responses to chemotherapy, (ii) tumor cell proliferation measured by proliferating cell nuclear antigen (PCNA) immunostaining and nucleolar organizer regions (AgNORs) staining and (iii) the expression of estrogen and progesterone receptors. We also compared disease-free survival (DFS) and overall survival (OS) with the expression of the Hsps studied. After chemotherapy, nuclear Hsp27 and Hsp70 expression was increased and Hsp70 and Hsc70 cytoplasmic expression was decreased. A high nuclear proportion of Hsp70 in tumor cells (>10%) correlated significantly with drug resistance. We also observed that patients whose tumors expressed nuclear or a high cytoplasmic proportion (>66%) of Hsp27 had shorter DFS. The combination of Hsp27 and Hsp70 levels showed a strong correlation with DFS. Neither the cellular proliferation nor the levels of steroid receptors showed any significant difference before or after drug administration or during follow-up of patients. Our results suggest that Hsp27 and Hsp70 are involved in drug resistance in breast cancer patients treated with combination chemotherapies.

Integration of estrogen and progesterone receptors with pathological and molecular prognostic factors in breast cancer patients.

In this study we have examined biopsies from women with localized primary breast cancer to investigate the prognostic performance of estrogen receptors (ER) and progesterone receptors (PR) for estimating the metastatic probability of the patients, and to explore whether discrimination gets better by combining clinicopathological and other molecular parameters into a score. This prospective study involved 205 patients with a median follow-up of 5 y. Among the evaluated clinicopathological data were: patient's age; tumor size; axillary lymph node involvement; and tumor grade. The most representative tumor samples were derived to a single laboratory for immunohistochemical evaluation of the following molecular markers: ER, PR, proliferating cell nuclear antigen (PCNA), p53 protein product, erbB-2 (HER-2/neu) oncoprotein, and P170 glycoprotein (mdrl gen product). Distant metastases (study endpoint) appeared in 19.5% (40/205) of the patients, most of these patients presented a mixture of poor, regular and good prognostic factors. Disease-free survival analysis procedures (Kaplan-Meier method) identified tumor size, axillary lymph node involvement, tumor grade, receptor status, PCNA, p53, erbB-2 and P170 as useful prognostic factors. Proportional hazard regression analysis (Cox) identified in order of importance erbB-2, tumor size, receptors status, tumor grade and PCNA as useful prognostic factors. To facilitate the evaluation of the prognostic factors, a practical and simple score system was derived. A high pathological score identified 65% of the patients that developed distant metastases, while a high molecular score was obtained in 57% of patients with metastatic disease. There was a significant improvement in the diagnosis of probability of being with distant metastases when the pathological score was combined with the molecular score, 82% of the patients with distant metastases showed an elevated combined score. Validation of this scoring system will need further larger studies (validation set as opposed to the training set used in the present study). Due to the complexity of events in cancer, the evaluation of a combination of prognostic factors should be of value to clinicians to make a more objective estimate of the prognosis of individual breast cancer patients.

Heat shock proteins and cell proliferation in human breast cancer biopsy samples.

Human breast cancers may overexpress certain heat shock protein (hsp) family members, proteins which are involved with cell proliferation and differentiation as well as with disease prognosis and drug resistance. Here, we have studied the relationship between the expression of two hsps (hsp27 and hsp70) and the proliferative activity of tumor cells in 40 biopsies from breast cancer patients. Twenty of these tumors were selected for a detailed colocalization study. Immunocytochemistry was done using specific antibodies against hsp27 and hsp70. Cell proliferation was studied analyzing the expression of proliferating cell nuclear antigen (PCNA) (late G1, S, and G2 phases of the cell cycle) and the number of silver-staining nucleolar organizer regions (AgNORs) (G1 phase). The colocalization study revealed a statistically significant inverse correlation between hsp27 expression and cell proliferation in 16/19 (84%) of the cases evaluated by PCNA immunostaining, and in 11/16 (69%) of the cases evaluated by AgNORs. In contrast, a statistically significant positive correlation between hsp70 expression and elevated cell proliferation was seen in almost 85% of the cases evaluated by PCNA staining, and in almost 50% of the cases evaluated by AgNORs. Moreover, in 22% (9/40) of the breast cancer samples examined, hsp70 was clearly associated with the mitotic spindle. A Western blot analysis revealed that hsp70 was coprecipitated with taxol-polymerized tubulin. The association of hsp70 with the mitotic spindle was not clearly noted in lung carcinoma samples (N = 20) or in normal cells displaying elevated mitotic activity. These studies thus demonstrate that in a significant percentage of clinical breast cancers hsp27 overexpression is inversely correlated with cell proliferation, while hsp70 is clearly associated with the mitotic spindle and cell proliferation. These results add evidence to the concept that in human breast cancers hsp27 may be involved in cell growth arrest and increased differentiation while, in contrast, hsp70 may be involved in cell proliferation; further studies will be necessary to elucidate these possible cause-and-effect relationships.

Interregional foodborne salmonellosis outbreak due to powdered infant formula contaminated with lactose-fermenting Salmonella virchow.

Spain's Salmonella surveillance system backed by regionally-based epidemiologists around the country made it possible to detect and halt the spread of a foodborne salmonellosis outbreak due to powdered infant formula contaminated with a lactose-fermenting strain of Salmonella virchow. Forty-eight cases involving children, mostly under 7 months old, were detected in 14 out of Spain's 17 Regions. The outbreak started in January and ended in June 1994. All cases were microbiologically confirmed. The implicated strain had a 3.6 kb plasmid, was susceptible to all antimicrobials tested except nitrofurantoin and was phagetype 4a. Isolates from 8 of 24 Brand "A" milk samples tested had the same characteristics as case isolates. All affected/suspect batches of Brand "A" milk were destroyed and the product withdrawn from sale, which led to the end of the outbreak. This incident underscores the importance of maintaining surveillance systems able to detect and prevent foodborne outbreaks and alert to the possibility of isolating unusual lactose-fermenting Salmonella serotypes in especially sensitive food products.

Estrogen receptors, progesterone receptors, and cell proliferation in human breast cancer.

The breast is a target organ for estrogens and progesterone. These hormones control several functions of the normal and abnormal mammary epithelium including cell proliferation. Most of the actions of estrogens and progesterone are mediated via specific steroid receptors, and one would expect that proliferating cells should contain estrogen receptors (ER) and/or progesterone receptors (PR). However, the correlation between receptor expression and cell proliferation is still controversial. In the present study we have examined 29 human breast cancer samples; in 17 of them we evaluated the simultaneous ER and PR localization with that of proliferating cell nuclear antigen (PCNA) and silver-stained nucleolar organizer regions (AgNORs) in a cell-by-cell study. We found that in almost 50% of the tumor biopsies examined, the cells expressing ER were significantly associated with elevated cell proliferation. In another group (38%) there were not significant differences between ER expression and cell proliferation. In only one of the samples (6%) the cells expressing ER showed lower cell proliferation. The study also revealed that in 44% of the tumors the PR expressing cells were associated with elevated cell proliferation. In a second group the PR expression was not significantly associated with cell proliferation (33% of the cases). Finally, in 22% of the samples the cells carrying PR showed lower cell proliferation. We also detected lower ER immunoreactivity in 30% of the breast cancer biopsies with one of the monoclonal antibodies against ER (antibody 1D5 directed against the A/B domain). This group of tumors was PR-negative (or very weakly positive) and had high proliferation. The presence of tumors with 'abnormal' ER proteins and displaying ER/PR significantly associated with elevated cell proliferation could have implications in human breast cancer treatment.

Sociodemographic predictors and temporal trends of extrapulmonary tuberculosis as an AIDS-defining disease in Spain.

OBJECTIVE: To identify the factors associated with the presentation of extrapulmonary tuberculosis (EPTB) in AIDS diagnosis and to analyse its temporal trend. DESIGN: Analysis of AIDS surveillance data. METHODS: The study was based on AIDS cases diagnosed in Spain between 1988 and 1993, and reported up to September 1994. The proportion of patients presenting with EPTB at AIDS diagnosis was analysed by sociodemographic characteristics and year of diagnosis. RESULTS: Of the 22,445 AIDS cases diagnosed in Spain from 1988 to 1993, 6526 patients (29.1%; 95% confidence interval, 28.5-29.7) presented with EPTB at diagnosis, making it the most frequent AIDS-defining disease. The highest proportions of EPTB reported at AIDS diagnosis were observed for injecting drug users (IDU; 35.4%) and the heterosexual transmission category (23.5%). The proportion of EPTB was lower in women [relative risk (RR), 0.85; P < 0.001], and higher in 15-29-year-olds (34.2%) and patients with a prison record (44.3 versus 25.4%; RR, 1.75; P < 0.001). AIDS patients resident in provinces with high respiratory TB mortality rates among the general population exhibited a higher proportion of EPTB (RR, 1.45; P < 0.001). The effect of any one variable was maintained by controlling for all others. The proportion of patients with EPTB at AIDS diagnosis revealed a downward trend from 1988 to 1993 (P = 0.007), which was observed in IDU and heterosexuals but not in homosexual/bisexual men (P = 0.421). CONCLUSIONS: Factors such as injecting drug use, prison record or residence in high TB-endemic areas are associated with a greater frequency of EPTB at AIDS diagnosis. These factors must be considered for specific prophylaxis to be efficiently applied.

Ecocardiografía Doppler en la fibrosis endomiocardica / Echo-Doppler studies of endomyocardial fibrosis

Doce pacientes con fibrosis endomiócardica, con comprobación angiográfica y/o histológica, fueron estudiados mediante ecocardiografía Doppler con el propósito de describir las características ecocardiográficas e identificar los sitios de afección. La edad promedio de los pacientes fue de 41 años (límites de 16 a 59 años); 2 hombres y 10 mujeres. Tres paciente (25 por ciento) tuvieron afección aislada del ventrículo derecho; 1 paciente (8 por ciento), del ventrículo izquierdo y, en 8 pacientes (66 por ciento), el compromiso fue biventricular. Los hallazgos ecocardiográficos Doppler fueron: dilatación de la aurícula derecha (91 por ciento), dilatación del tracto de salida del ventrículo derecho (83 por ciento), movimiento septal paradójico (83 por ciento), dilatación de la aurícula izquierda (33 por ciento), prolapso valvular mitral y tricuspídeo (50 por ciento), derrame pericárdico (41 por ciento), insuficiencia mitral (75 por ciento), insuficiencia tricuspídea (100 por ciento), obliteración de ápex (50 por ciento) y patrón de llenado tipo restrictivo (50 por ciento). La ecocardiografía Doppler es un método útil en el diagnóstico de la fibrosis endomiocárdica, los hallazgos de ventrículos normales o pequeños con obliteración del ápex, que contrasta con aurículas muy dilatadas, de insuficiencia mitral y/o tricuspídea con un patrón de llenado de tipo restrictivo son característicos de esta enfermead. En nuestro medio, la localización aislada o predominante del ventrículo derecho fue la más frecuente: respresentó el 83 por ciento de los casos.

Corticotropin-releasing hormone, luteinizing hormone-releasing hormone, growth hormone-releasing hormone, and somatostatin-like immunoreactivities in biopsies from breast cancer patients.

The presence of immunoreactive adrenocorticotropin-releasing hormone (CRH), luteinizing hormone-releasing hormone (LHRH), growth hormone-releasing hormone (GHRH), and somatostatin has been investigated by immunohistochemistry in forty biopsies from breast cancer patients. All of these hypothalamic hormones were found in about 30% of the samples, seen in the cytoplasm or in the nuclei of the tumor cells. Positive immunostaining for the hypothalamic hormones was present in colloid, lobular, and infiltrating ductal carcinomas. There was not a clear relationship between occurrence of staining for the hypothalamic hormones and the histologic grade of tumors or the clinical stage of the disease. Immunoreactive LHRH was more frequently found in breast tumors with estrogen and progesterone receptors. On the other hand, preneoplastic breast lesions expressed mainly somatostatin, while immunoreactivity was absent in normal mammary tissue.

Poliomyelitis in Spain, 1982-1984: virologic and epidemiologic studies.

The authors present a detailed study of poliomyelitis in Spain for the years 1982, 1983, and 1984. The 50 cases reported have been epidemiologically classified following World Health Organization guidelines. Virus was isolated from 43 of these cases. Intratypic characterization was done using specifically absorbed antisera classifying the strains as non-Sabin-like and Sabin-like. The neutralizing antibodies in whole and fractionated sera were also determined. The largest number of paralytic poliomyelitis cases, 28, was found in children in the first year of life. Thirty of the cases were unvaccinated children. Poliomyelitis was not detected in adults during the period described. Wild strains isolated were type I and III, primarily from Gypsies. There was a significant incidence of vaccine-associated cases in recipients, as well as in contacts during 1982 and 1983. The cases were located in the Mediterranean and Southern zone. In 1984, total and vaccine-associated cases dropped dramatically.