TRAIL/TRAIL Receptor System and Susceptibility to Multiple Sclerosis

The TNF-related apoptosis inducing ligand (TRAIL)/TRAIL receptor system participates in crucial steps in immune cell activation or differentiation. It is able to inhibit proliferation and activation of T cells and to induce apoptosis of neurons and oligodendrocytes, and seems to be implicated in autoimmune diseases. Thus, TRAIL and TRAIL receptor genes are potential candidates for involvement in susceptibility to multiple sclerosis (MS). To test whether single-nucleotide polymorphisms (SNPs) in the human genes encoding TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 are associated with MS susceptibility, we performed a candidate gene case-control study in the Spanish population. 59 SNPs in the TRAIL and TRAIL receptor genes were analysed in 628 MS patients and 660 controls, and validated in an additional cohort of 295 MS patients and 233 controls. Despite none of the SNPs withstood the highly conservative Bonferroni correction, three SNPs showing uncorrected p values<0.05 were successfully replicated: rs4894559 in TRAIL gene, p = 9.8×10(-4), OR = 1.34; rs4872077, in TRAILR-1 gene, p = 0.005, OR = 1.72; and rs1001793 in TRAILR-2 gene, p = 0.012, OR = 0.84. The combination of the alleles G/T/A in these SNPs appears to be associated with a reduced risk of developing MS (p = 2.12×10(-5), OR = 0.59). These results suggest that genes of the TRAIL/TRAIL receptor system exerts a genetic influence on MS.

Testing of Diagnostic Methods for Detection of Influenza Virusfor Optimal Performance in the Context of an Influenza Surveillance Network

Influenza surveillance networks must detect early the viruses that will cause the forthcoming annual epidemics and isolate the strains for further characterization. We obtained the highest sensitivity (95.4%) with a diagnostic tool that combined a shell-vial assay and reverse transcription-PCR on cell culture supernatants at 48 h, and indeed, recovered the strain

Meat consumption and mortality - results from the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND Recently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS Included in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality. RESULTS As of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and 'other causes of death'. The consumption of poultry was not related to all-cause mortality. CONCLUSIONS The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.

In vitro methods for diagnosing nonimmediate hypersensitivity reactions to drugs.

Nonimmediate drug hypersensitivity reactions (DHRs) are difficult to manage in daily clinical practice, mainly owing to their heterogeneous clinical manifestations and the lack of selective biological markers. In vitro methods are necessaryto establish a diagnosis, especially given the low sensitivity of skin tests and the inherent risks of drug provocation testing. In vitro evaluation of nonimmediate DHRs must include approaches that can be applied during the different phases of the reaction. During the acute phase, monitoring markers in both skin and peripheral blood helps to discriminate between immediate and nonimmediate DHRs with cutaneous responses and to distinguish between reactions that, although they present similar clinical symptoms, are produced by different immunological mechanisms and therefore have a different treatment and prognosis. During the resolution phase, in vitro testing is used to detect the response of T cells to drug stimulation; however, this approach has certain limitations, such as the lack of validated studies assessing sensitivity. Moreover, in vitro tests indicate an immune response that is not always related to a DHR. In this review, members of the Immunology and Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC) provide an overview of the most widely used in vitro tests for evaluating nonimmediate DHRs.

Performing masculinity, influencing health: a qualitative mixed-methods study of young Spanish men

Background: The literature shows how gender mandates contribute to differences in exposure and vulnerability to certain health risk factors. This paper presents the results of a study developed in the south of Spain, where research aimed at understanding men from a gender perspective is still limited. Objective: The aim of this paper is to explore the lay perceptions and meanings ascribed to the idea of masculinity, identifying ways in which gender displays are related to health. Design: The study is based on a mixed-methods data collection strategy typical of qualitative research. We performed a qualitative content analysis focused on manifest and latent content. Results: Our analysis showed that the relationship between masculinity and health was mainly defined with regard to behavioural explanations with an evident performative meaning. With regard to issues such as driving, the use of recreational drugs, aggressive behaviour, sexuality, and body image, important connections were established between manhood acts and health outcomes. Different ways of understanding and performing the male identity also emerged from the results. The findings revealed the implications of these aspects in the processes of change in the identity codes of men and women. Conclusions: The study provides insights into how the category ‘man’ is highly dependent on collective practices and performative acts. Consideration of how males perform manhood acts might be required in guidance on the development of programmes and policies aimed at addressing gender inequalities in health in a particular local context.

Impact of obesity-related genes in Spanish population

Background: The objective was to investigate the association between BMI and single nucleotide polymorphisms previously identified of obesity-related genes in two Spanish populations. Forty SNPs in 23 obesity-related genes were evaluated in a rural population characterized by a high prevalence of obesity (869 subjects, mean age 46 yr, 62% women, 36% obese) and in an urban population (1425 subjects, mean age 54 yr, 50% women, 19% obese). Genotyping was assessed by using SNPlex and PLINK for the association analysis. Results: Polymorphisms of the FTO were significantly associated with BMI, in the rural population (beta 0.87, p-value <0.001). None of the other SNPs showed significant association after Bonferroni correction in the two populations or in the pooled analysis. A weighted genetic risk score (wGRS) was constructed using the risk alleles of the Tag-SNPs with a positive Beta parameter in both populations. From the first to the fifth quintile of the score, the BMI increased 0.45 kg/m2 in Hortega and 2.0 kg/m2 in Pizarra. Overall, the obesity predictive value was low (less than 1%). Conclusion: The risk associated with polymorphisms is low and the overall effect on BMI or obesity prediction is minimal. A weighted genetic risk score based on genes mainly acting through central nervous system mechanisms was associated with BMI but it yields minimal clinical prediction for the obesity risk in the general population.

Nuestra experiencia clínica en los rescates de PTR con el sistema Legión

We carried out a descriptive, retrospective study with a sample side of 121 patients with Legión® prosthesis replacement in our Vírgen del Rocío hospital area, in the city of Seville, from May of 2008 until March of 2011. This study included epidemiological data as well as technical information about the process performed, including post-operative pain, mobility and functional results using a functional assessment scale and series of radiological studies. Average follow-up was 19 months, with a mean age of 71 years and 87% women. We obtained an average of 20.41º for articular balance obtained, correction of prior deformities by restoring the tibia-femoral axis to the anatomic e balance articular angle; we resolved bone loss prior to replacement and carried out an adequate balance of the inter-lineal joint. 66% of the patients continued with no post-operative pain, with the other 33% reporting slight to moderate pain. With regards to pain at the point of the stem, we have found no significant relationship with the incidence angle of the stem on the cortical or with the type of cement. We observed a 74% rate of intervention without complications, with complications being rupture of the patellar tendon in one patient, one case of peri-prosthesis fracture, two iatrogenic avulsion fractures of the anterior tibial tuberosity and seven infections (4 were diagnosed previously).

Evaluation of the IL2/IL21, IL2RA and IL2RB genetic variants influence on the endogenous non-anterior uveitis genetic predisposition.

BACKGROUND Recently, different genetic variants located within the IL2/IL21 genetic region as well as within both IL2RA and IL2RB loci have been associated to multiple autoimmune disorders. We aimed to investigate for the first time the potential influence of the IL2/IL21, IL2RA and IL2RB most associated polymorphisms with autoimmunity on the endogenous non-anterior uveitis genetic predisposition. METHODS A total of 196 patients with endogenous non-anterior uveitis and 760 healthy controls, all of them from Caucasian population, were included in the current study. The IL2/IL21 (rs2069762, rs6822844 and rs907715), IL2RA (2104286, rs11594656 and rs12722495) and IL2RB (rs743777) genetic variants were genotyped using TaqMan® allelic discrimination assays. RESULTS A statistically significant difference was found for the rs6822844 (IL2/IL21 region) minor allele frequency in the group of uveitis patients compared with controls (P(-value)=0.02, OR=0.64 CI 95%=0.43-0.94) although the significance was lost after multiple testing correction. Furthermore, no evidence of association with uveitis was detected for the analyzed genetic variants of the IL2RA or IL2RB loci. CONCLUSION Our results indicate that analyzed IL2/IL21, IL2RA and IL2RB polymorphisms do not seem to play a significant role on the non-anterior uveitis genetic predisposition although further studies are needed in order to clear up the influence of these loci on the non-anterior uveitis susceptibility.

Iron metabolism, inflammation and anemia in critically ill patients. A cross-sectional study.

INTRODUCTION For critically patients, enteral immunonutrition results in notable reductions in infections and in length of stay in hospital, but not on mortality, raising the question as to whether this relate to the heterogeneous nature of critically ill patients or to the absence of the altered absorption of specific nutrients within the immunonutrient mix (e.g. iron). Immune-associated functional iron deficiency (FID) is not only one of the many causes or anaemia in the critically ill, but also a cause of inappropriate immune response, leading to a longer duration of episodes of systemic inflammatory response syndrome and poor outcome. OBJECTIVE This prospective cross-sectional study was undertaken to assess the prevalence of FID in critically ill patients during their stay in intensive care (ICU) in order to find the more appropriate population of patients that can benefit from iron therapy. METHOD Full blood cell counts, including reticulocytes (RETIC), serum iron (SI), transferring levels (TRF) and saturation (satTRF), serum TFR receptor (sTfR), ferritin (FRT) and C-reactive protein (CRP) were measured in venous blood samples from 131 random patients admitted to the ICU for at least 24 h (Length of ICU stay, LIS; min: 1 day; max: 38 days). RESULTS Anaemia (Hb < 12 g/dL) was present in 76% of the patients (Hb < 10 g/dL in 33%), hypoferremia (SI < 45 microg/dl) in 69%; satTRF < 20% in 53%; FRT < 100 ng/mL in 23%; sTfR > 2.3 mg/dL in 13%; and CRP > 0.5 mg/dL in 88%. Statistically significant correlations (r of Pearson; *p < 0.05, **p < 0.01) were obtained for serum CRP levels and WBC**, Hb*, TRF**, satTRF*, and FRT**. There was also a strong correlation between TRF and FRT (-0.650**), but not between FRT and satTRF or SI. LIS correlated with Hb*, CRP**, TRF*, satTRF* and FRT**. CONCLUSIONS A large proportion of critically ill patients admitted to the ICU presented the typical functional iron deficiency (FID) of acute inflammation-related anaemia (AIRA). This FID correlates with the inflammatory status and the length of stay at the ICU. However, 21% of the ICU patients with AIRA had an associated real iron deficiency (satTRF < 20; FRT < 100 and sTfR > 2.3). Since oral supplementation of iron seems to be ineffective, all these patients might benefit of iv iron therapy for correction of real or functional iron deficiency, which in turn might help to ameliorate their inflammatory status.

Evaluation of quality improvement for cesarean sections caesarean section programmes through mixed methods.

BACKGROUND The rate of avoidable caesarean sections (CS) could be reduced through multifaceted strategies focusing on the involvement of health professionals and compliance with clinical practice guidelines (CPGs). Quality improvements for CS (QICS) programmes (QICS) based on this approach, have been implemented in Canada and Spain. OBJECTIVES Their objectives are as follows: 1) Toto identify clusters in each setting with similar results in terms of cost-consequences, 2) Toto investigate whether demographic, clinical or context characteristics can distinguish these clusters, and 3) Toto explore the implementation of QICS in the 2 regions, in order to identify factors that have been facilitators in changing practices and reducing the use of obstetric intervention, as well as the challenges faced by hospitals in implementing the recommendations. METHODS Descriptive study with a quantitative and qualitative approach. 1) Cluster analysis at patient level with data from 16 hospitals in Quebec (Canada) (n = 105,348) and 15 hospitals in Andalusia (Spain) (n = 64,760). The outcome measures are CS and costs. For the cost, we will consider the intervention, delivery and complications in mother and baby, from the hospital perspective. Cluster analysis will be used to identify participants with similar patterns of CS and costs based, and t tests will be used to evaluate if the clusters differed in terms of characteristics: Hospital level (academic status of hospital, level of care, supply and demand factors), patient level (mother age, parity, gestational age, previous CS, previous pathology, presentation of the baby, baby birth weight). 2) Analysis of in-depth interviews with obstetricians and midwives in hospitals where the QICS were implemented, to explore the differences in delivery-related practices, and the importance of the different constructs for positive or negative adherence to CPGs. Dimensions: political/management level, hospital level, health professionals, mothers and their birth partner. DISCUSSION This work sets out a new approach for programme evaluation, using different techniques to make it possible to take into account the specific context where the programmes were implemented.

Correcting non cephalic presentation with moxibustion: study protocol for a multi-centre randomised controlled trial in general practice.

BACKGROUND Non cephalic presentation in childbirth involves various risks to both the mother and the foetus. The incidence in Spain is 3.8% of all full-term pregnancies. The most common technique used to end the gestation in cases of non cephalic presentation is that of caesarian section, and although it provokes a lower rate of morbi-mortality than does vaginal delivery in such situations, there remains the possibility of traumatic injury to the foetal head and neck, while maternal morbidity is also increased. The application of heat (moxibustion) to an acupuncture point, in order to correct non cephalic presentation, has been practised in China since ancient times, but as yet there is insufficient evidence of its real effectiveness. METHODS/DESIGN The experimental design consists of a multi-centre randomised controlled trial with three parallel arms, used to compare real moxibustion, sham moxibustion and the natural course of events, among pregnant women with a non cephalic presentation and a gestational duration of 33-35 weeks (estimated by echography). The participants in the trial will be blinded to both interventions. The results obtained will be analyzed by professionals, blinded with respect to the allocation to the different types of intervention. In addition, we intend to carry out a economic analysis. DISCUSSION This trial will contribute to the development of evidence concerning moxibustion in the correction of non cephalic presentations. The primary outcome variable is the proportion of cephalic presentations at term. As secondary outcomes, we will evaluate the proportion of cephalic presentations at week 38 of gestation, determined by echography, together with the safety of the technique, the specificity of moxibustion and the control of the blinding process. This study has been funded by the Health Ministry of the Andalusian Regional Government. TRIAL REGISTRATION Current Controlled Trials ISRCTN10634508.

Endometriosis: alternative methods of medical treatment.

Endometriosis is an inflammatory estrogen-dependent disease defined by the presence of endometrial glands and stroma at extrauterine sites. The main purpose of endometriosis management is alleviating pain associated to the disease. This can be achieved surgically or medically, although in most women a combination of both treatments is required. Long-term medical treatment is usually needed in most women. Unfortunately, in most cases, pain symptoms recur between 6 months and 12 months once treatment is stopped. The authors conducted a literature search for English original articles, related to new medical treatments of endometriosis in humans, including articles published in PubMed, Medline, and the Cochrane Library. Keywords included "endometriosis" matched with "medical treatment", "new treatment", "GnRH antagonists", "Aromatase inhibitors", "selective progesterone receptor modulators", "anti-TNF α", and "anti-angiogenic factors". Hormonal treatments currently available are effective in the relief of pain associated to endometriosis. Among new hormonal drugs, association to aromatase inhibitors could be effective in the treatment of women who do not respond to conventional therapies. GnRH antagonists are expected to be as effective as GnRH agonists, but with easier administration (oral). There is a need to find effective treatments that do not block the ovarian function. For this purpose, antiangiogenic factors could be important components of endometriosis therapy in the future. Upcoming researches and controlled clinical trials should focus on these drugs.