Association study of genetic variants of pro-inflammatory chemokine and cytokine genes in systemic lupus erythematosus

BACKGROUND. Several lines of evidence suggest that chemokines and cytokines play an important role in the inflammatory development and progression of systemic lupus erythematosus. The aim of this study was to evaluate the relevance of functional genetic variations of RANTES, IL-8, IL-1alpha, and MCP-1 for systemic lupus erythematosus. METHODS. The study was conducted on 500 SLE patients and 481 ethnically matched healthy controls. Genotyping of polymorphisms in the RANTES, IL-8, IL-1alpha, and MCP-1 genes were performed using a real-time polymerase chain reaction (PCR) system with pre-developed TaqMan allelic discrimination assay. RESULTS. No significant differences between SLE patients and healthy controls were observed when comparing genotype, allele or haplotype frequencies of the RANTES, IL-8, IL-1alpha, and MCP-1 polymorphisms. In addition, no evidence for association with clinical sub-features of SLE was found. CONCLUSION. These results suggest that the tested functional variation of RANTES, IL-8, IL-1alpha, and MCP-1 genes do not confer a relevant role in the susceptibility or severity of SLE in the Spanish population.

Efectos del consumo de aceites termo-oxidados sobre la peroxidación lipídica en animales de laboratorio.

INTRODUCTION The quality of fats and oils used for frying is as important as the quality of the final product since during the frying process oxidization by-products are formed and become part of the diet, being potentially harmful for the consumers' health. OBJECTIVE To determine the effects of thermo-oxidised fats and oils on the oxidization of plasma lipoproteins inexperimental rats. METHODS Determination by means of spectrophotometric techniques of those substances reacting with thiobarbituric acid and total cholesterol (enzymatic method) in the sera of 40 Wistar rats that consumed crude thermooxidised oils and fats with different levels of malonil aldehyde(MDA) for 30 days. RESULTS The group of rats receiving a diet with thermooxidised oils and fats experienced significant increases in MDA plasma levels throughout the study period, lipid peroxidation being higher with increasing MDA content (p < 0.05) regardless the type of fat compound consumed. However, those rats receiving crude oils and fats kept plasma levels of lipidic peroxides without significant changes throughout the experimental period (p > 0.05). By contrast, cholesterol levels increased towards the end of the experimental period in both the rats consuming crude fats and those consuming thermo-oxidised fats (p < 0.05). CONCLUSIONS Consumption of oils and fats submitted to repeat thermal heating has an influence on plasma lipidic peroxidation, which becomes higher with increasing number of heating processes applied, so that it would advisable not to abuse of reheating the oils used for frying foods.

Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans.

Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.

Enfermedad pulmonar obstructiva crónica: proceso asistencial integrado. 2ª ed

En noviembre de 2015, se ha publicado la 3ª edición de este proceso (http://hdl.handle.net/10668/2125). Existe una guía de información para pacientes "Conozca cómo vivir mejor con la EPOC" basada en la 2ª edición de este Proceso.

Conozca cómo vivir mejor con la EPOC: Respuestas sencillas a las preguntas más frecuentes sobre la enfermedad pulmonar obstructiva crónica (EPOC)

La guía se apoya en los contenidos del Enfermedad Pulmonar Obstructiva Crónica: Proceso Asistencial Integrado. http://hdl.handle.net/123456789/219

Ankle-brachial index in HIV infection

Prognosis for patients with the human immunodeficiency virus (HIV) has improved with the introduction of highly active antiretroviral therapy (HAART). Evidence over recent years suggests that the incidence of cardiovascular disease is increasing in HIV patients. The ankle-brachial index (ABI) is a cheap and easy test that has been validated in the general population. Abnormal ABI values are associated with increased cardiovascular mortality. To date, six series of ABI values in persons with HIV have been published, but none was a prospective study. No agreement exists concerning the risk factors for an abnormal ABI, though its prevalence is clearly higher in these patients than in the general population. Whether this higher prevalence of an abnormal ABI is associated with a higher incidence of vascular events remains to be determined.

A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p≤5×10−7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10−8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2×10−8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5×10−8; rs1229984-ADH1B, p = 7×10−9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

El final de la vida en la infancia y la adolescencia: aspectos éticos y jurídicos en la atención sanitaria

Coordinadores: María J. Escudero Carretero, Pablo Simón Lorda

Use of the internet as a source of health information by Spanish adolescents

The Internet is a fundamental part of the daily life of adolescents, they consider it as a safe and confidential source of information on health matters. The aims is to describe the experience of Spanish adolescents searching for health information on the Internet. Methods A cross-sectional study of 811 school-age adolescents in Granada was carried out. An adapted and piloted questionnaire was used which was controlled by trained personnel. Sociodemographic and health variables were included together with those concerning the conditions governing access to and use of information and communication technologies (ICT). Results 811 adolescents were surveyed (99.38% response rate), mean age was 17 years old. Of these, 88% used the Internet; 57.5% used it on a daily or weekly basis and 38.7% used it occasionally. Nearly half the sample group (55.7%) stated that they used the Internet to search for health-related information. The main problems reported in the search for e-health were the ignorance of good web pages (54.8%) and the lack of confidence or search skills (23.2%). Conclusions In conclusion, it seems plausible to claim that websites designed and managed by health services should have a predominant position among interventions specifically addressed to young people.

Air pollution exposure during pregnancy and reduced birth size: a prospective birth cohort study in Valencia, Spain

Background Maternal exposure to air pollution has been related to fetal growth in a number of recent scientific studies. The objective of this study was to assess the association between exposure to air pollution during pregnancy and anthropometric measures at birth in a cohort in Valencia, Spain. Methods Seven hundred and eighty-five pregnant women and their singleton newborns participated in the study. Exposure to ambient nitrogen dioxide (NO2) was estimated by means of land use regression. NO2 spatial estimations were adjusted to correspond to relevant pregnancy periods (whole pregnancy and trimesters) for each woman. Outcome variables were birth weight, length, and head circumference (HC), along with being small for gestational age (SGA). The association between exposure to residential outdoor NO2 and outcomes was assessed controlling for potential confounders and examining the shape of the relationship using generalized additive models (GAM). Results For continuous anthropometric measures, GAM indicated a change in slope at NO2 concentrations of around 40 μg/m3. NO2 exposure >40 μg/m3 during the first trimester was associated with a change in birth length of -0.27 cm (95% CI: -0.51 to -0.03) and with a change in birth weight of -40.3 grams (-96.3 to 15.6); the same exposure throughout the whole pregnancy was associated with a change in birth HC of -0.17 cm (-0.34 to -0.003). The shape of the relation was seen to be roughly linear for the risk of being SGA. A 10 μg/m3 increase in NO2 during the second trimester was associated with being SGA-weight, odds ratio (OR): 1.37 (1.01-1.85). For SGA-length the estimate for the same comparison was OR: 1.42 (0.89-2.25). Conclusions Prenatal exposure to traffic-related air pollution may reduce fetal growth. Findings from this study provide further evidence of the need for developing strategies to reduce air pollution in order to prevent risks to fetal health and development.

Effectiveness of a nurse-led case management home care model in Primary Health Care. A quasi-experimental, controlled, multi-centre study

Background Demand for home care services has increased considerably, along with the growing complexity of cases and variability among resources and providers. Designing services that guarantee co-ordination and integration for providers and levels of care is of paramount importance. The aim of this study is to determine the effectiveness of a new case-management based, home care delivery model which has been implemented in Andalusia (Spain). Methods Quasi-experimental, controlled, non-randomised, multi-centre study on the population receiving home care services comparing the outcomes of the new model, which included nurse-led case management, versus the conventional one. Primary endpoints: functional status, satisfaction and use of healthcare resources. Secondary endpoints: recruitment and caregiver burden, mortality, institutionalisation, quality of life and family function. Analyses were performed at base-line, and at two, six and twelve months. A bivariate analysis was conducted with the Student's t-test, Mann-Whitney's U, and the chi squared test. Kaplan-Meier and log-rank tests were performed to compare survival and institutionalisation. A multivariate analysis was performed to pinpoint factors that impact on improvement of functional ability. Results Base-line differences in functional capacity – significantly lower in the intervention group (RR: 1.52 95%CI: 1.05–2.21; p = 0.0016) – disappeared at six months (RR: 1.31 95%CI: 0.87–1.98; p = 0.178). At six months, caregiver burden showed a slight reduction in the intervention group, whereas it increased notably in the control group (base-line Zarit Test: 57.06 95%CI: 54.77–59.34 vs. 60.50 95%CI: 53.63–67.37; p = 0.264), (Zarit Test at six months: 53.79 95%CI: 49.67–57.92 vs. 66.26 95%CI: 60.66–71.86 p = 0.002). Patients in the intervention group received more physiotherapy (7.92 CI95%: 5.22–10.62 vs. 3.24 95%CI: 1.37–5.310; p = 0.0001) and, on average, required fewer home care visits (9.40 95%CI: 7.89–10.92 vs.11.30 95%CI: 9.10–14.54). No differences were found in terms of frequency of visits to A&E or hospital re-admissions. Furthermore, patients in the control group perceived higher levels of satisfaction (16.88; 95%CI: 16.32–17.43; range: 0–21, vs. 14.65 95%CI: 13.61–15.68; p = 0,001). Conclusion A home care service model that includes nurse-led case management streamlines access to healthcare services and resources, while impacting positively on patients' functional ability and caregiver burden, with increased levels of satisfaction.

Increased neurotransmitter release at the neuromuscular junction in a mouse model of polyglutamine disease.

In Huntington's disease (HD), the expansion of polyglutamine (polyQ) repeats at the N terminus of the ubiquitous protein huntingtin (htt) leads to neurodegeneration in specific brain areas. Neurons degenerating in HD develop synaptic dysfunctions. However, it is unknown whether mutant htt impacts synaptic function in general. To investigate that, we have focused on the nerve terminals of motor neurons that typically do not degenerate in HD. Here, we have studied synaptic transmission at the neuromuscular junction of transgenic mice expressing a mutant form of htt (R6/1 mice). We have found that the size and frequency of miniature endplate potentials are similar in R6/1 and control mice. In contrast, the amplitude of evoked endplate potentials in R6/1 mice is increased compared to controls. Consistent with a presynaptic increase of release probability, synaptic depression under high-frequency stimulation is higher in R6/1 mice. In addition, no changes were detected in the size and dynamics of the recycling synaptic vesicle pool. Moreover, we have found increased amounts of the synaptic vesicle proteins synaptobrevin 1,2/VAMP 1,2 and cysteine string protein-α, and the SNARE protein SNAP-25, concomitant with normal levels of other synaptic vesicle markers. Our results reveal that the transgenic expression of a mutant form of htt leads to an unexpected gain of synaptic function. That phenotype is likely not secondary to neurodegeneration and might be due to a primary deregulation in synaptic protein levels. Our findings could be relevant to understand synaptic toxic effects of proteins with abnormal polyQ repeats.

Apoyo social a drogodependientes en programa de mantenimiento con metadona en una prisión

Goal: To learn more about the social support available to patients participating in a prison methadone maintenance program (PMM). Methodology: Descriptive, with controls. Setting: A penitentiary in Albolote (Granada) Population Sample: The total prison population was 1,579; 364 patients were included in the PMM; 35 were female and 329 were male. 60 patients, 7 women and 53 men, were used as cases. 30 non-drug dependent prisoners, 3 women and 27 men, were the control group. They had no antecedents of problems with drug addiction. Interventions: Interviews with cases and controls to learn about their addictive antecedents, family structure, socio-economic level, and a hetero-applied MOS questionnaire was completed. Percentages of each social support variable were obtained and compared using the chi-squared technique. Results: The overall support received is low in 38 cases (74.5%) and in 9 controls (30%): p = 0.0001. OR 0.1466, confidence interval at 95% (0.0538-0.3989). Support received is normal in 13 cases (25%) and 21 controls (70%): p = 0.0007. OR 0.69, confidence interval at 95% (0.44-0.93). All of the variables were statistically significant for non-drug addicts, except for emotional support, which was the same for both groups. Conclusion: The perception of inmates participating in the methadone maintenance program was that they received less social support than the non-drug dependent inmates.