Insulin-like growth factor-I and C-reactive protein during pregnancy and maternal risk of non-epithelial ovarian cancer: a nested case-control study.

BACKGROUND: Insulin-like growth factor-I (IGF-I) and C-reactive protein (CRP) may be positively associated with the risk of epithelial ovarian cancer (EOC) but no previous studies have investigated their associations with non-epithelial ovarian cancers (NEOC). METHODS: A case-control study was nested within the Finnish Maternity Cohort. Case subjects were 58 women diagnosed with sex cord-stromal tumors (SCST) and 30 with germ cell tumors (GCT) after recruitment. Control subjects (144 for SCST and 74 for GCT) were matched for age, parity, and date of blood donation of the index case. RESULTS: Doubling of IGF-I concentration was not related to maternal risk of either SCST (OR 0.97, 95% CI 0.58-1.62) or GCT (OR 1.13, 95% CI 0.51-2.51). Similarly, doubling of CRP concentrations was not related to maternal risk of either SCST (OR 1.10, 95% CI 0.85-1.43) or GCT (OR 0.93, 95% CI 0.68-1.28). CONCLUSIONS: Pre-diagnostic IGF-I and CRP concentrations during the first trimester of pregnancy were not associated with increased risk of NEOC in the mother. Risk factors for NEOC may differ from those of EOC.

Efectividad de una estrategia de intervención preventiva, basada en entrevistas telefónicas estructuradas, en una población laboral con riesgo cardiovascular moderado/alto.

OBJECTIVE This study assesses the effectiveness of a structured telephone survey on cardiovascular prevention, in modifying lifestyle, on cardiovascular risk parameters, percentage of smoking cessation and overall cardiovascular risk (CVR). DESIGN Quasi-experimental study of preventive intervention. SETTING Ibermutuamur (Spanish Accident and Health Insurance Company). Centres established throughout Spain. PARTICIPANTS A total of 4,792 workers with moderate/high cardiovascular risk who had agreed to be contacted by phone. Subjects with a previous diagnosis of cardiovascular disease and those receiving treatment for hypertension, hypercholesterolemia or diabetes were excluded. INTERVENTION A final total of 3,085 workers were contacted and were followed up by telephone surveys on the first, fourth and eighth month after the initial check up (CU) in order to emphasise cardiovascular health advice (Group A); we failed to contact 1,707 workers, who only attended the baseline and one year CUs (Group B). PRINCIPAL OUTCOMES: CUs included medical records and physical examination, with two blood pressure measurements, Body Mass Index (BMI), and biochemical parameters. Cardiovascular risk was stratified following the European cardiovascular SCORE. Individuals with a relative risk higher than 4 were also considered as high-risk. All workers were informed about their cardiovascular risk profile (CVRF) and healthy cardiovascular lifestyle measures. They were also given a letter for their General Practitioner (GP) to inform them on the worker's cardiovascular risk level. RESULTS A total of 71.5% of the workers were over 45 years, 95.0% males, 76.6% manual workers ("Blue Collar") and 69.7% smokers. Both groups showed improvement in lipid parameters, blood pressure, smoking cessation and overall cardiovascular risk in the second CU. There were significant differences in favour of Group A as regards blood pressure, lipids (except HDL cholesterol), BMI, glycaemia, smoking cessation (A: 23.5%/B: 19.44%, P=0.001) and CVR stratum improvement (A: 46.6%/B: 37.7%, P=0.0001). The large majority (85%) of workers read preventive recommendations; 33% knew their risk level and 73% knew their CVRF. 52.9% gave the letter to the GP, which led them to start therapies on diet (47%), hypertension (19.5%), dyslipidaemia (16.7%), diabetes (4.4%) and smoking (2.9%) and no changes were made in 36.5% of cases. CONCLUSIONS The results of this study suggests that cardiovascular prevention strategy based on structured telephone surveys on high/moderate CVR subjects to promote lifestyle changes could be effective at reducing CVR. A clinical trial is required for confirmation. Sending information on CVRF following routine medial CUs and Primary Care involvement, could contribute to the positive changes observed.

Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease.

The aetiology of autoimmune hepatitis (AIH) is uncertain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs. AIH usually develops in individuals with a genetic background mainly consisting of some risk alleles of the major histocompatibility complex (HLA). Many drugs have been linked to AIH phenotypes, which sometimes persist after drug discontinuation, suggesting that they awaken latent autoimmunity. At least three clinical scenarios have been proposed that refers to drug- induced autoimmune liver disease (DIAILD): AIH with drug-induced liver injury (DILI); drug induced-AIH (DI-AIH); and immune mediated DILI (IM-DILI). In addition, there are instances showing mixed features of DI-AIH and IM-DILI, as well as DILI cases with positive autoantibodies. Histologically distinguishing DILI from AIH remains a challenge. Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however, a detailed standardised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diagnosis between both entities. Growing information on the relationship of drugs and AIH is being available, being drugs like statins and biologic agents more frequently involved in cases of DIAILD. In addition, there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepatotoxicity. Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of disease.

The oral cancer epidemic in central and eastern Europe.

To monitor recent trends in oral and pharyngeal cancer mortality in 38 European countries, we analyzed data provided by the World Health Organization over the period 1975-2004. Joinpoint analysis was used to identify significant changes in trends. In the European Union (EU), male mortality rates rose by 2.1% per year between 1975 and 1984, by 1.0% between 1984 and 1993, and declined by 1.3% between 1993 and 2004, to reach an overall age-standardized rate of 6.1/100,000 in 2000-2004. Mortality rates were much lower in women, and the rate in the EU rose by 0.9% per year up to 2000, and levelled off to 1.1/100,000 in 2000-2004. In France and Italy - which had the highest rates in the past - male rates have steadily declined during the last two decades (annual percent change, APC=-4.8% in 1998-2004 in France, and -2.6% in 1986-2003 in Italy). Persisting rises were, however, observed in several central and eastern European countries, with exceedingly high rates in Hungary (21.1/100,000; APC=6.9% in 1975-1993 and 1.4% in 1993-2004) and Slovakia (16.9/100,000; APC=0.14% in 1992-2004). In middle aged (35 to 64) men, oral and pharyngeal cancer mortality rates in Hungary (55.2/100,000) and Slovakia (40.8/100,000) were comparable to lung cancer rates in several major European countries. The highest rates for women were in Hungary (3.3/100,000; APC=4.7% in 1975-2004) and Denmark (1.6/100,000; APC=1.3% in 1975-2001). Oral and pharyngeal cancer mortality essentially reflects the different patterns in tobacco smoking and alcohol drinking, including drinking patterns and type of alcohol in central Europe. (c) 2009 UICC.

Prótesis unicompartimental lateral de rodilla. Indicaciones, técnica y resultados a mediocorto plazo

Objectives: In patients with lateral osteoarthritis of the knee, use of external unicompartmental knee arthroplasty it is a well known surgical alternative, used by the minor trauma involved, short hospital stay and rapid recovery. The purpose of this study is to show the clinical outcomes to short-medium term of patients undergoing this procedure. Methods: we describe the technique used and the peculiarities of the prosthesis (A Mobile-bearing lateral unicompartmental knee replacement, Oxford Domed ®). This is an observational retrospective longitudinal study, of 15 arthroplasties performed in 13 women and 2 men, between 2010 and 2013, with a mean age of 60’7 years, with a diagnosis of lateral osteoarthritis of the knee, without involvement of the medial or patellofemoral compartment and cruciate ligaments functionally intact, with a mean follow up of 25 months. All patients complete the Oxford Knee Score and Visual Analog Scale (VAS) during the study. Results: The results are favorable, with an improvement of 6.60 points on the EVA, 3.73 for 1 in the postoperatory funcionality, the OKS very satisfactory with an average of 38 points over 50 and without any postoperative function surgical revision. Anserine tendinitis was observed in 20% of cases. Conclusions: The benefits of this surgery against their alternatives are assessed, and their potential drawbacks. External unicompartmental knee arthroplasty is an effective alternative in cases of knee osteoarthritis of the lateral compartment with no other associated injuries.

ACTG-HIV symptoms changes in patients switched to RPV/FTC/TDF due to previous intolerance to CART. Interim analysis of the PRO-STR study.

INTRODUCTION Tolerability and convenience are crucial aspects for the long-term success of combined antiretroviral therapy (cART). The aim of this study was to investigate the impact in routine clinical practice of switching to the single tablet regimen (STR) RPV/FTC/TDF in patients with intolerance to previous cART, in terms of patients' well-being, assessed by several validated measures. METHODS Prospective, multicenter study. Adult HIV-infected patients with viral load under 1.000 copies/mL while receiving a stable ART for at least the last three months and switched to RPV/FTC/TDF due to intolerance of previous regimen, were included. Analyses were performed by ITT. Presence/magnitude of symptoms (ACTG-HIV Symptom Index), quality of life (EQ-5D, EUROQoL & MOS-HIV), adherence (SMAQ), preference of treatment and perceived ease of medication (ESTAR) through 48 weeks were performed. RESULTS Interim analysis of 125 patients with 16 weeks of follow up was performed. 100 (80%) were male, mean age 46 years. Mean CD4 at baseline was 629.5±307.29 and 123 (98.4%) had viral load <50 copies/mL; 15% were HCV co-infected. Ninety two (73.6%) patients switched from a NNRTI (84.8% from EFV/FTC/TDF) and 33 (26.4%) from a PI/r. The most frequent reasons for switching were psychiatric disorders (51.2%), CNS adverse events (40.8%), gastrointestinal (19.2%) and metabolic disorders (19.2%). At the time of this analysis (week 16), four patients (3.2%) discontinued treatment: one due to adverse events, two virologic failures and one with no data. A total of 104 patients (83.2%) were virologically suppressed (<50 copies/mL). The average degree of discomfort in the ACTG-HIV Symptom Index significantly decreased from baseline (21±15.55) to week 4 (10.89±12.36) & week 16 (10.81±12.62), p<0.001. In all the patients, quality of life tools showed a significant benefit in well-being of the patients (Table 1). Adherence to therapy significantly and progressively increased (SMAQ) from baseline (54.4%) to week 4 (68%), p<0.001 and to week 16 (72.0%), p<0.001. CONCLUSIONS Switching to RPV/FTC/TDF from another ARV regimen due to toxicity, significantly improved the quality of life of HIV-infected patients, both in mental and physical components, and improved adherence to therapy while maintaining a good immune and virological response.

Plasma Elaidic Acid Level as Biomarker of Industrial Trans Fatty Acids and Risk of Weight Change: Report from the EPIC Study.

BACKGROUND Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow-up, age, energy, alcohol, smoking status, physical activity, and region. RESULTS In women, doubling elaidic acid was associated with a decreased risk of weight loss (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.55-0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5-year follow-up (OR = 1.23, 95% CI = 0.97-1.56, p = 0.082) (p-trend<.0001). In men, a trend was observed for doubling elaidic acid level and risk of weight loss (OR = 0.82, 95% CI = 0.66-1.01, p = 0.062) while no significant association was found with risk of weight gain during the 5-year follow-up (OR = 1.08, 95% CI = 0.88-1.33, p = 0.454). No association was found for saturated and cis-monounsaturated fatty acids. CONCLUSIONS These data suggest that a high intake of industrial trans fatty acids may decrease the risk of weight loss, particularly in women. Prevention of obesity should consider limiting the consumption of highly processed foods, the main source of industrially-produced trans fatty acids.

El proyecto EMECAM: Estudio Multicéntrico Español sobre la Relación entre la Contaminación Atmosférica y la Mortalidad. Antecedentes, participantes, objetivos y métodología.

In recent years, a growing number of studies suggests that increases in air pollution levels may have short-term impact on human health, even at pollution levels similar to or lower than those which have been considered to be safe to date. The different methodological approaches and the varying analysis techniques employed have made it difficult to make a direct comparison among all of the findings, preventing any clear conclusions from being drawn. This has led to multicenter projects such as the APHEA (Short-Term Impact of Air Pollution on Health. A European Approach) within a European Scope. The EMECAM Project falls within the context of the aforesaid multicenter studies and has a wide-ranging projection nationwide within Spain. Fourteen (14) cities throughout Spain were included in this Project (Barcelona, Metropolitan Area of Bilbao, Cartagena, Castellón, Gijón, Huelva, Madrid, Pamplona, Seville, Oviedo, Valencia, Vigo, Vitoria and Saragossa) representing different sociodemographic, climate and environmental situations, adding up to a total of nearly nine million inhabitants. The objective of the EMECAM project is that to asses the short-term impact of air pollution throughout all of the participating cities on the mortality for all causes, on the population and on individuals over age 70, for respiratory and cardiovascular design causes. For this purpose, with an ecological, the time series data analyzed taking the daily deaths, pollutants, temperature data and other factors taken from records kept by public institutions. The period of time throughout which this study was conducted, although not exactly the same for all of the cities involved, runs in all cases from 1990 to 1996. The degree of relationship measured by means of an autoregressive Poisson regression. In the future, the results of each city will be combined by means of a meta-analysis.

Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort.

BACKGROUND Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers. METHODS To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort. RESULTS A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis. CONCLUSION Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer.

Regression of cardiac growth in kidney transplant recipients using anti-m-TOR drugs plus RAS blockers: a controlled longitudinal study.

BACKGROUND Left ventricular hypertrophy (LVH) is common in kidney transplant (KT) recipients. LVH is associated with a worse outcome, though m-TOR therapy may help to revert this complication. We therefore conducted a longitudinal study to assess morphological and functional echocardiographic changes after conversion from CNI to m-TOR inhibitor drugs in nondiabetic KT patients who had previously received RAS blockers during the follow-up. METHODS We undertook a 1-year nonrandomized controlled study in 30 non-diabetic KT patients who were converted from calcineurin inhibitor (CNI) to m-TOR therapy. A control group received immunosuppressive therapy based on CNIs. Two echocardiograms were done during the follow-up. RESULTS Nineteen patients were switched to SRL and 11 to EVL. The m-TOR group showed a significant reduction in LVMi after 1 year (from 62 ± 22 to 55 ± 20 g/m2.7; P=0.003, paired t-test). A higher proportion of patients showing LVMi reduction was observed in the m-TOR group (53.3 versus 29.3%, P=0.048) at the study end. In addition, only 56% of the m-TOR patients had LVH at the study end compared to 77% of the control group (P=0.047). A significant change from baseline in deceleration time in early diastole was observed in the m-TOR group compared with the control group (P=0.019). CONCLUSIONS Switching from CNI to m-TOR therapy in non-diabetic KT patients may regress LVH, independently of blood pressure changes and follow-up time. This suggests a direct non-hemodynamic effect of m-TOR drugs on cardiac mass.

Rheumatoid arthritis response to treatment across IgG1 allotype - anti-TNF incompatibility: a case-only study.

INTRODUCTION We have hypothesized that incompatibility between the G1m genotype of the patient and the G1m1 and G1m17 allotypes carried by infliximab (INX) and adalimumab (ADM) could decrease the efficacy of these anti-tumor necrosis factor (anti-TNF) antibodies in the treatment of rheumatoid arthritis (RA). METHODS The G1m genotypes were analyzed in three collections of patients with RA totaling 1037 subjects. The first, used for discovery, comprised 215 Spanish patients. The second and third were successively used for replication. They included 429 British and Greek patients and 393 Spanish and British patients, respectively. Two outcomes were considered: change in the Disease Activity Score in 28 joint (ΔDAS28) and the European League Against Rheumatism (EULAR) response criteria. RESULTS An association between less response to INX and incompatibility of the G1m1,17 allotype was found in the discovery collection at 6 months of treatment (P = 0.03). This association was confirmed in the replications (P = 0.02 and 0.08, respectively) leading to a global association (P = 0.001) that involved a mean difference in ΔDAS28 of 0.4 units between compatible and incompatible patients (2.3 ± 1.5 in compatible patients vs. 1.9 ± 1.5 in incompatible patients) and an increase in responders and decrease in non-responders according to the EULAR criteria (P = 0.03). A similar association was suggested for patients treated with ADM in the discovery collection, but it was not supported by replication. CONCLUSIONS Our results suggest that G1m1,17 allotypes are associated with response to INX and could aid improved therapeutic targeting in RA.

Producció i anàlisi estructural d’aliatges magnètics amb memòria de forma

L’objectiu d’aquest projecte és la producció d’aliatges tipus Heusler per estudiar lesestructures corresponents i portar a terme un estudi experimental per poder analitzarla influència de la composició en la transformació martensítica del material, en concret s’avalua la influència de la concentració de Snen presència del Co. Per assolir aquest objectiu es produeixen i es caracteritzen tresaliatges Heusler no estequiomètrics amb composició Mn50Ni45-XSnXCo5 on x pren elvalor de 5, 7’5 i 10. Els aliatges estudiats són. • Mn50Ni40Sn5Co5• Mn50Ni37,5Sn7,5Co5• Mn50Ni35Sn10Co5

The evolution of universities' relations with the business sector in Brazil: What national publications between 1980 and 2012 reveal

ABSTRACT This paper addresses the changes in university-industry relations in Brazil regarding innovation activities. It is based on a survey of articles published in major national journals or presented at the most relevant Brazilian and regional conferences, between 1980 and 2012. The year 1980 was chosen due to the creation of the Technological Innovation Offices (NITs), which was the first government initiative to encourage knowledge transfer from universities to companies; the second was the Innovation Act of 2004. Our assumption was that after the Act the number of academic papers on this subject would increase, bringing new ideas and propositions of models to enhance this relationship. The methodology employed a qualitative, exploratory approach, using bibliographical research and a bibliometric analysis of 247 papers. Literature review of international studies shows the discussion of problems and suggestions for improvements, while in Brazil there is still a debate on whether this collaboration should occur, and if this is a legitimate role for the university. Despite the numerical growth, the content analysis showed few papers on new configurations and procedures for partnership management. We conclude that university-industry relations are not a regular and totally accepted process in Brazilian public universities, which reflect an ideological bias against cooperation with firms.