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OBJETIVO: Estudiar la frecuencia de consultas médicas en las poblaciones autóctona e inmigrante en España, antes y después de una medida del Gobierno del 2012 que restringió el uso de servicios sanitarios públicos a los inmigrantes indocumentados. MATERIAL Y MÉTODOS: Los datos proceden de las Encuestas Europeas de Salud en España de 2009 y 2014. Se han analizado las consultas al médico de familia y al especialista en autóctonos e inmigrantes de 18 a 64 años. Se calcularon los incrementos porcentuales en la frecuencia de personas que consultaron en 2014 respecto a 2009 y, en cada año, la razón de porcentaje (RP) de consultas en inmigrantes frente autóctonos, con intervalos de confianza del 95% (IC del 95%). RESULTADOS: La frecuencia de consultas se incrementó en 2014 respecto a 2009, a excepción de la consulta al médico de familia en mujeres autóctonas. Los incrementos más altos se produjeron en las consultas al médico especialista en inmigrantes (39,9%) y en autóctonos (21,6%), y en las consultas al médico de familia en mujeres inmigrantes. Tras ajustar por edad y variables socioeconómicas e indicadoras de necesidad de asistencia, en ambos años no se observaron diferencias significativas entre inmigrantes y autóctonos en los 2 tipos consultas. CONCLUSIONES: En España no se redujo la frecuencia de consultas médicas al médico de familia ni al especialista entre 2009 y 2014 en la población inmigrante

OBJECTIVE: To study the frequency of medical consultations in autochthonous and immigrant populations in Spain, before and after a government measure of 2012 that restricted the use of public health services to undocumented immigrants. MATERIAL AND METHODS: The data were taken from the European Health Surveys in Spain in 2009 and 2014. An analysis was made of the consultations with the family doctor and the consultations with the medical specialist in autochthonous and immigrant populations from 18 to 64 years. Percentage increases were calculated in the frequency of people who consulted in 2014 with respect to 2009, and, in each year, the percentage ratio (PR) of consultation in immigrants with respect autochthonous, with 95% confidence intervals (95% CI). RESULTS: The frequency of consultations increased in 2014 compared to 2009, with the exception of family doctor's consultation with the autochthonous women. The highest increases occurred in visits to medical specialists in immigrants (39.9%), in autochthonous (21.6%), and in visits by the family doctor to immigrant women. After adjusting for age and socioeconomic variables and indicators of need for assistance, there were no significant differences in both years between immigrants and autochthonous in the 2 types of consultations. CONCLUSIONS: The frequency of consultations to the family doctor or medical specialist did not decrease in Spain between 2009 and 2014 in the immigrant population

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OBJECTIVE: To study the frequency of medical consultations in autochthonous and immigrant populations in Spain, before and after a government measure of 2012 that restricted the use of public health services to undocumented immigrants. MATERIAL AND METHODS: The data were taken from the European Health Surveys in Spain in 2009 and 2014. An analysis was made of the consultations with the family doctor and the consultations with the medical specialist in autochthonous and immigrant populations from 18 to 64 years. Percentage increases were calculated in the frequency of people who consulted in 2014 with respect to 2009, and, in each year, the percentage ratio (PR) of consultation in immigrants with respect autochthonous, with 95% confidence intervals (95% CI). RESULTS: The frequency of consultations increased in 2014 compared to 2009, with the exception of family doctor's consultation with the autochthonous women. The highest increases occurred in visits to medical specialists in immigrants (39.9%), in autochthonous (21.6%), and in visits by the family doctor to immigrant women. After adjusting for age and socioeconomic variables and indicators of need for assistance, there were no significant differences in both years between immigrants and autochthonous in the 2types of consultations. CONCLUSIONS: The frequency of consultations to the family doctor or medical specialist did not decrease in Spain between 2009 and 2014 in the immigrant population.

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OBJECTIVE: Natural killer (NK) cells have been involved in the pathology of different inflammatory and autoimmune disorders. Inflammation is an important regulator of osteoarthritis (OA), but the molecular and cellular mechanisms regulating this process are not well defined. DESIGN: To understand the role of NK cells in OA, we have compared the phenotype (CD56 subsets and perforin and granzyme expression) and cytotoxic function of NK cells in peripheral blood and synovial fluid from patients with OA undergoing total knee arthroplasty. RESULTS: In contrast to peripheral blood lymphocytes (PBLs), the majority of NK cells from the synovial fluid were CD56brightCD16(-) cells. As expected the expression of the cytolytic mediators perforin and granzyme B in CD56brightCD16(-) cells was low and correlated with a poor cytotoxic potential against K562 sensitive target cells. Surprisingly, this low cytotoxic NK cell subset expressed high levels of granzyme A (a protease recently characterized as a key modulator of inflammation in mouse models) in synovial fluid but not in peripheral blood. The presence of the CD56(+)brightCD16(-) cells expressing granzyme A correlated with increased levels of pro-inflammatory cytokines in synovial fluid from OA patients. CONCLUSION: Our results indicate that NK cells from the synovium of patients with OA, which present an immunoregulatory non-cytotoxic phenotype, show different phenotype comparing with NK cells from peripheral blood, especially expressing granzyme A, a pro-inflammatory molecule which may contribute to the establishment of chronic articular inflammation in this type of patients.

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BACKGROUND: To show the inequalities in premature mortality according to indicators of material welfare in Navarre. METHODS: All citizens under 75 years of age living in Navarre in 2001 were monitored for seven years to determine their vital status. House size and number of household vehicles was used as the socioeconomic status indicator. The age-adjusted total mortality rate and mortality rate from cause-specific mortality were estimated by these indicators. RESULTS: The rate ratio for all causes of death in the lower categories depending on house size is 1.14 (IC 95%: 1.05-1.24) and 1.25 (IC 95%: 1.18-1.32) in women and men respectively and 1.46 (IC 95%: 1.36-1.57) and 1.97 (IC 95%: 1.89-2.05) depending on the number of vehicles. AIDS is the leading cause of death having a greater difference in mortality rates among people with lower and higher material welfare. Other causes of death with a high difference in mortality rates are digestive diseases and diabetes mellitus in women and digestive diseases and respiratory diseases in men. CONCLUSIONS: The mortality rate in the Navarre population shows an inverse gradient to material welfare,except for some cancer sites. This gradient is higher among men than among women.

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Fundamento: Mostrar las desigualdades en mortalidad prematura según indicadores de bienestar material en Navarra. Método: Todos los ciudadanos menores de 75 años residentes en Navarra en 2001 fueron seguidos durante 7 años para conocer su estado vital. El indicador de posición socioeconómica usado ha sido la superficie de la casa y el número de vehículos del hogar. Se han estimado las tasas de mortalidad general y por causa de muerte ajustadas por edad según estos indicadores. Resultados. La razón de tasas por todas las causas de muerte en las categorías inferiores es según la superficie de la vivienda de 1,14 (IC 95%: 1,05-1,24) y 1,25 (IC 95%: 1,18-1,32) en mujeres y hombres respectivamente y de 1,46 (IC 95%: 1,36-1,57) y 1,97 (IC 95%: 1,89-2,05) según el número de vehículos. El sida es la causa de muerte que presenta una mayor diferencia en las tasas de mortalidad entre las personas con menor y mayor bienestar material. Otras causas de muerte con elevada diferencia en las tasas de mortalidad son las enfermedades digestivas y la diabetes mellitus en mujeres y las enfermedades del aparato digestivo y respiratorio en hombres. Conclusiones: La tasa de mortalidad en la población navarra muestra un gradiente inverso con el bienestar material, a excepción de algunas localizaciones de cáncer. Este gradiente es mayor entre los hombres que entre las mujeres (AU)

Background: To show the inequalities in premature mortality according to indicators of material welfare in Navarre. Methods: All citizens under 75 years of age living in Navarre in 2001 were monitored for seven years to determine their vital status. House size and number of household vehicles was used as the socioeconomic status indicator. The age-adjusted total mortality rate and mortality rate from cause-specific mortality were estimated by these indicators. Results: The rate ratio for all causes of death in the lower categories depending on house size is 1.14 (IC 95%: 1.05-1.24) and 1.25 (IC 95%: 1.18-1.32) in women and men respectively and 1.46 (IC 95%: 1.36-1.57) and 1.97 (IC 95%: 1.89-2.05) depending on the number of vehicles. AIDS is the leading cause of death having a greater difference in mortality rates among people with lower and higher material welfare. Other causes of death with a high difference in mortality rates are digestive diseases and diabetes mellitus in women and digestive diseases and respiratory diseases in men. Conclusions: The mortality rate in the Navarre population shows an inverse gradient to material welfare, except for some cancer sites. This gradient is higher among men than among women (AU)

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Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), also known as Apo-2 ligand (Apo2L), is a member of the TNF cytokine superfamily. By cross-linking TRAIL-Receptor (TRAIL-R) 1 or TRAIL-R2, also known as death receptors 4 and 5 (DR4 and DR5), TRAIL has the capability to induce apoptosis in a wide variety of tumor cells while sparing vital normal cells. The discovery of this unique property among TNF superfamily members laid the foundation for testing the clinical potential of TRAIL-R-targeting therapies in the cancer clinic. To date, two of these therapeutic strategies have been tested clinically: (i) recombinant human TRAIL and (ii) antibodies directed against TRAIL-R1 or TRAIL-R2. Unfortunately, however, these TRAIL-R agonists have basically failed as most human tumors are resistant to apoptosis induction by them. It recently emerged that this is largely due to the poor agonistic activity of these agents. Consequently, novel TRAIL-R-targeting agents with increased bioactivity are currently being developed with the aim of rendering TRAIL-based therapies more active. This review summarizes these second-generation novel formulations of TRAIL and other TRAIL-R agonists, which exhibit enhanced cytotoxic capacity toward cancer cells, thereby providing the potential of being more effective when applied clinically than first-generation TRAIL-R agonists.

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Purpose. Human Apo2-Ligand/TRAIL secreted by natural killer cells and cytotoxic T lymphocytes plays an important role immunosurveillance controlling tumor growth and metastasis. Moreover, the fact that Apo2L/TRAIL is capable of inducing cell death in tumor cells but not in normal cells makes this death ligand a promising anti-tumor agent. Previous data from our group demonstrated that Apo2L/TRAIL was physiologically released as transmembrane protein inserted in lipid vesicles, called exosomes. Recently, we demonstrated that artificial lipid nanoparticles coated with bioactive Apo2L/TRAIL (LUV-TRAIL) resembling the natural exosomes, greatly improved Apo2L/TRAIL activity and were able to induce apoptosis in hematological malignancies. In this study, we have deepened in the underlying mechanism of action of LUV-TRAIL in hematologic cells. Methods/patients. Cytotoxic ability of LUV-TRAIL was assessed on Jurkat cells either over-expressing the anti-apoptotic protein Mcl1 or down-regulating the pro-apoptotic protein Bim previously generated in our laboratory. We also tested LUV-TRAIL cytotoxic ability against primary human leukemic cells from T-cell ALL patient. Results. Silencing Bim but not Mcl-1 over-expression partially protects Jurkat cells from apoptosis induced by sTRAIL. LUV-TRAIL induced caspase-8 and caspase-3 activation and killed Jurkat-Mcl1 and Jurkat-shBim more efficiently than sTRAIL independently of the mitochondrial pathway. On the other hand, LUV-TRAIL were clearly more cytotoxic against primary leukemic cells from a T-cell ALL patient than sTRAIL. Conclusion. Tethering Apo2L/TRAIL to the surface of lipid nanoparticles greatly increases its bioactivity and could be of potential use in anti-tumor therapeutics (AU)

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PURPOSE: Human Apo2-Ligand/TRAIL secreted by natural killer cells and cytotoxic T lymphocytes plays an important role immunosurveillance controlling tumor growth and metastasis. Moreover, the fact that Apo2L/TRAIL is capable of inducing cell death in tumor cells but not in normal cells makes this death ligand a promising anti-tumor agent. Previous data from our group demonstrated that Apo2L/TRAIL was physiologically released as transmembrane protein inserted in lipid vesicles, called exosomes. Recently, we demonstrated that artificial lipid nanoparticles coated with bioactive Apo2L/TRAIL (LUV-TRAIL) resembling the natural exosomes, greatly improved Apo2L/TRAIL activity and were able to induce apoptosis in hematological malignancies. In this study, we have deepened in the underlying mechanism of action of LUV-TRAIL in hematologic cells. METHODS/PATIENTS: Cytotoxic ability of LUV-TRAIL was assessed on Jurkat cells either over-expressing the anti-apoptotic protein Mcl1 or down-regulating the pro-apoptotic protein Bim previously generated in our laboratory. We also tested LUV-TRAIL cytotoxic ability against primary human leukemic cells from T-cell ALL patient. RESULTS: Silencing Bim but not Mcl-1 over-expression partially protects Jurkat cells from apoptosis induced by sTRAIL. LUV-TRAIL induced caspase-8 and caspase-3 activation and killed Jurkat-Mcl1 and Jurkat-shBim more efficiently than sTRAIL independently of the mitochondrial pathway. On the other hand, LUV-TRAIL were clearly more cytotoxic against primary leukemic cells from a T-cell ALL patient than sTRAIL. CONCLUSION: Tethering Apo2L/TRAIL to the surface of lipid nanoparticles greatly increases its bioactivity and could be of potential use in anti-tumor therapeutics.

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BACKGROUND/OBJECTIVES: To ascertain trends in the prevalence of overweight and obesity among Spanish children and adolescents according to the socioeconomic status of the family household and area of residence across the period 1987-2007. SUBJECTS/METHODS: For study purposes, data were drawn from the 1987, 1995, 1997, 2001 and 2007 Spanish National Health Surveys. Overweight and obesity were estimated on the basis of body mass index. The following indicators of socioeconomic status were used: educational level of primary household earner and per capita income of province of residence. The statistical significance of the trend in the prevalence of overweight and obesity was assessed for each category of socioeconomic status. The χ2 test for trend was used in the case of educational level and a linear regression in the case of per capita income of province of residence. RESULTS: Although the prevalence of overweight and obesity had levelled off among boys and girls aged 5 to 9 years, it nevertheless showed a significant upward trend among those aged 10 to 15 years from families whose primary household earner had a lower educational level. The prevalence of overweight among boys in this last group was 13.1% in 1987 and 31.5% in 2007. From 1997 onwards, the prevalence of overweight and obesity among boys and girls aged 10 to 15 years increased in both the richest and the remaining provinces, although the magnitude of this increase was greater in the latter. Specifically, in these provinces the prevalence increased from 18 to 28.9% over the period of study. CONCLUSIONS: The prevalence of overweight and obesity in the childhood population in Spain has stabilised, except among adolescents, whether from lower-income families or lower-income areas, among whom a rising trend is in evidence.

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Difuse proliferative lupus nephritis (DPLN) is the most common and severe form of lupus nephritis. A predominance of IFN-gamma-producing T cells in both peripheral and renal tissues of patients with DPLN has been identified which suggests an important role for cell-mediated immunity in the pathogenesis of this complication in SLE. The biological effects of IFN-gamma rely mainly on the activity of the transcription factor called signal transducer and activator of transcription (STAT)-1. To assess the IFN-gamma/STAT-1 pathway in DPLN, we examined the expression of STAT-1 in renal biopsies from 15 DPLN patients by immunohistochemical staining with an anti-STAT-1 antibody. The expression of STAT-1 in renal tissues was correlated with several clinical and laboratory findings in these DNPN patients.STAT-1 was activated in the tubular cells in all DPLN patients. Seven of 15 DPLN biopsies (46.7%) showed positive cells in glomeruli. Five of these seven DPLN biopsies (71.4%) with positive glomerular cells showed a serum creatinine >1.5 mg/mL at the time the biopsy was carried out whereas only one of eight DPLN biopsy specimens (12.5%) without positive glomerular cells, showed a serum creatinine >1.5 mg/mL (P = 0.041). Moreover, the percentage of DPLN patients with a worse renal outcome in those who showed expression of STAT-1 in glomerulari were higher in comparison to those without STAT-1 expression (P = 0.041). Our results show that STAT-1 is activated in DPLN suggesting that biological effects of IFN-gamma in renal tissues depend, at least in part, on the activation of STAT-1.

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A functional polymorphism in PTPN22, a gene encoding a phosphatase involved in T-cell signaling, has been associated with autoimmunity. We checked for the prevalence of the PTPN22 R620W polymorphism in multiplex families affected with systemic lupus erythematosus (SLE) and other autoimmune diseases. Its association with other polymorphisms in mannose binding lectin (MBL) and FcgammaRIIa (CD32A) genes was also studied. Deoxyribonucleic acid samples were obtained from 233 Spanish individuals who belonged to 21 families in which at least two members had been diagnosed with some autoimmune disease, mainly SLE. A healthy control population was also included (n= 129). Genotyping for the R620W single-nucleotide polymorphism (SNP) was performed by restriction fragment length polymorphism analysis of polymerase chain reaction products. Allele frequency for the T allele was slightly higher in the families with autoimmune disease, especially when considering the affected individuals (0.094 vs 0.062). Actually, 18.8% affected family members vs 11.6% controls had the polymorphism (P= 0.179). Nineteen percent of affected individuals had both the PTPN22 T and the CD32A R131 alleles, whereas only 8.5% unaffected relatives had both susceptibility alleles simultaneously [P= 0.031, odds ratios 2.508 (95% confidence interval 1.066-5.896)]. The tendency toward finding the T allele more frequently in members affected with some particular autoimmune disorder suggests that this SNP may confer susceptibility to autoimmunity. The fact that more affected than unaffected relatives carried both the T and the R131 alleles simultaneously leads us to think about the existence of a combinatorial effect between genes that could help define individuals prone to autoimmune diseases.

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OBJECTIVE: It has recently been reported that some autoimmune diseases seem to be associated with a functional polymorphism in PTPN22, a gene which encodes a phosphatase known to be important in T-cell signaling. The aim of our study was to check for the prevalence of the PTPN22 R620W polymorphism in patients with systemic sclerosis. METHODS: DNA samples from 54 systemic sclerosis patients and 55 healthy controls were obtained from peripheral blood and genotyping was performed by means of a restriction fragment length polymorphism analysis of PCR products (RFLP-PCR). RESULTS: Allele frequency for the T allele was slightly higher in the patients group (0.074 versus 0.055). Eight out of the 54 systemic sclerosis patients (14.8 %) were heterozygous for this single nucleotide polymorphism whereas the CT genotype was found in 6 out of the 55 controls (10.9%). Nevertheless, the difference did not reach statistical significance (p = 0.542). Neither certain antibodies linked to systemic sclerosis (anti-centromere and anti-topoisomerase I antibodies) nor any particular clinical involvement were associated with the polymorphism. CONCLUSION: This particular single nucleotide polymorphism of PTPN22 does not seem to be associated with systemic sclerosis.

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We report here a novel DRB1 allele identified during sequence-based HLA-DRB typing. This allele was detected during routine HLA typing of a patient and his family prior to bone marrow transplantation. The new allele, DRB1*0108, was found in the patient and in a brother. Molecular cloning and sequencing confirmed that the new DRB1 allele is identical to DRB1*0101 at exon 2 except for a single nucleotide substitution at codon 37 (TauCC-->TauAlphaC), changing the encoded serine to tyrosine. This position of the beta1 domain lies in the floor of the antigen-binding groove and shows the highest polymorphism among DRB1 alleles.

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BACKGROUND: This paper considers the breast cancer screening programme in the autonomous community of Navarre, Northern Spain. Women from different areas of Northern, Central and Southern Navarre are involved. METHODS: A sample of 512 women participants and 196 non-participants was taken from a total of 60,908 women between 45 and 65 years of age who received an invitation to attend the breast cancer screening programme. The participants were asked to fill in an individual structured questionnaire in their local Health Centre and the non-participants in their homes. This was done retrospectively. RESULTS: The response rate was 100% for participants and 83.9% for non-participants. This study investigates the attitude profiles of the women attending mammography mass screening, with non-attending women (matched in educational and occupational levels) as controls. Subjects were assessed on dimensions such as attitudes towards health and illness. The results support Rosenstock's 1974 model that perceived severity of breast cancer and perceived susceptibility to breast cancer are related to participation in screening. Furthermore, results demonstrated that hypochondriacal beliefs, disease phobia and feared effects of symptoms were related to decreased participation levels. CONCLUSION: This study has explored the implication of health belief attitudes and the attitudes toward illness variables with women's participation in a breast cancer screening programme. It assesses the relative contribution of these variables to levels of participation, and the results of the study indicate that belief sets and attitudes are important components of women's cancer prevention behaviours.

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BACKGROUND: The objective of this study is to evaluate the trend in the use and accessibility of health services in Spain between 1987 and 1995-1997 in groups with different socio-economic characteristics. METHODS: The data used are taken from National Health Surveys carried out on the adult population in 1987 and 1995-97 by the Ministry of Health and Consumer Affairs. The information for 1995 and 1997 has been combined due to the different sample size, in such a way that the estimates so obtained are the mean from both years. Population analysed has been people aged 24 years and older. The following have been studied: visits to the doctor, hospitalization, visits to the dentist and the gynecologist, the time taken to reach the visits to the doctor, and the waiting time in both the visits to the doctor and ordinary hospital admission. The socio-economic characteristics used are the level of education and the socio-economic group of the respondents. The measure of the association calculated between use of services and the socio-economic characteristics was the percentage ratio estimated by binomial regression. In addition, the relative index of inequality was estimated as a global measure of inequality. RESULTS: Visits to the doctor were the most frequent factor in people without academic qualifications and the lower socio-economic group in the two periods, while visits to the dentist and the gynecologist were more frequent in the higher socio-economic groups in both periods. Statistically significant differences in the frequency of hospitalization in the two periods were not found. Neither in 1987 nor 1995/1997 were statistically significant differences found between the different socio-economic groups as regards the time taken to visits to the doctor (p > 0.05), although there were in waiting time in visits to the doctor (p < 0.05). In the second period the socio-economic differences observed in the first period in waiting time for ordinary hospital admission disappeared. CONCLUSIONS: In the second half of the 1990s the same socio-economic profile was observed in the use of health services and the time spent waiting to receive them, as in the second half of the 1980s, with the exception of waiting time for ordinary hospital admission in the second period.

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In this study we analyse the trend in socio-economic differences in mortality from ischaemic heart and cerebrovascular diseases in the economically active male population aged 25-64 years in Spain and France. The data used were taken from deaths from these two causes in 1980-1982 and 1988-1990; in the case of Spain the data came from the Eight Provinces Study. Individuals were grouped into four categories - professional/managerial, clerical/sales/service workers, farmers, and manual workers - and the mortality rate ratio was estimated with reference to the professional/managerial group. For ischaemic heart disease in 1980-1982, professionals and managers aged 25-44 years had the lowest risk of mortality in Spain, and the highest risk of mortality in France; in 1988-1990 the socioeconomic differences in mortality in Spain increased, whereas the relation was inverted in France. In 1980-1982, professionals and managers aged 45-64 years had higher mortality from ischaemic heart disease than the other occupational groups in both countries; in 1988-1990 this relation was inverted, except in the case of clerical/sales/service workers in Spain. For cerebrovascular disease, manual workers experienced the highest mortality in the 25-44 year age group in 1980-1982, and the differences increased in 1988-1990 in all groups with respect to professionals and managers in both places. Professionals and managers in France and manual workers in Spain had the highest mortality between 45 and 64 years in 1980-1982; in contrast, in 1988-1990 professionals and managers had the lowest risk of mortality from this disease in both Spain and France, although in Spain the magnitude was similar to that of clerical/sales/service workers. In general terms, mortality from each disease was different in professionals and managers than in clerical/sales/service workers. Thus, the pattern of mortality and its evolution in different socio-economic groups cannot be analysed accurately when the two occupational groups are combined in a single large group of non-manual workers.

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OBJECTIVE: To assess the implication of health-oriented behavior and state of health variables estimated to influence women's participation in a breast cancer screening program. METHODS: A sample of 512 participants and 196 nonparticipants was taken from a total of 60,908 women between 45 and 65 years of age. RESULTS: There are significant differences in women's perception of their knowledge of breast cancer, estimated prognosis, and reasons for not performing self-examination. The nonparticipant group reports more health problems. CONCLUSION: The study assesses the relative contribution of these variables to participation levels, although further empirical testing of all these issues is recommended.

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