Interaction of phenol-formaldehyde condensates with isoprene rubber

The study is concerned with the interaction between p-tertiary butyl phenol-formaldehyde condensates and isoprene rubber under conditions resembling those used in industrial vulcanization processes, and involves investigations of reaction rates, mechanisms of reactions and structures produced. The work is an extension of an earlier study (A. Fitch, Thesis for Ph.D. (C.N.A.A.), 1978). 'Model' phenol-formaldehyde condensates (2-methylol 4- tert.butyl 6-methyl phenol and the ether derived from it by thermal condensation) are shown to interact with isoprene rubber (cis-l,4-polyisoprene) to form adducts containing chroman structures. The ether reacts somewhat more quickly and more efficiently than the methylol compound. 'Lewis acid' catalysts will greatly accelerate the reaction, but cause concurrent structural isomerization of the isoprene rubber, to an extent depending on the nature of the catalyst. In separate experiments involving only rubber and catalyst, it is found that, of the three catalysts examined, tin(II) chloride dihydrate causes extensive isomerization, tin(II) chloride (anhydrous) causes little isomerization and zinc(II) chloride (anhydrous) causes negligible isomerization, under the appropriate reaction conditions. The structural changes are evaluated, and involve cis-trans interconversions double-bond shifts, cyclization and crosslinking. Using zinc(II) chloride as catalyst, a study is made of the effectiveness of five different polyfunctional phenol- formaldehyde condensates as vulcanizing agents for isoprene rubber. The condensates consist of 2,6-dimethylol 4-tert. butyl phenol and four of its derivatives containing different molar proportions of methylol, dibenzyl ether and diaryl methane groups. One of the derivatives is a commercially-available vulcanizing agent. Measurements of rubber-combined phenolic material and of crosslink concentrations are made at different times of reaction, and results show that the condensates containing high proportions of dibenzyl ether links are the most efficient vulcanizing agents. Efficiency may be further improved by the addition of a formaldehyde donor to suppress side-reactions. The results indicate that, in all cases, combination with the rubber occurs through chroman linkages and the crosslinks contain at least two phenolic nuclei joined by dimethylene ether or methylene links

Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk population: The ESCARVAL-RISK study.

The potential impact of targeting different components of an adverse lipid profile in populations with multiple cardiovascular risk factors is not completely clear. This study aims to assess the association between different components of the standard lipid profile with all-cause mortality and hospitalization due to cardiovascular events in a high-risk population. This prospective registry included high risk adults over 30 years old free of cardiovascular disease (2008-2012). Diagnosis of hypertension, dyslipidemia or diabetes mellitus was inclusion criterion. Lipid biomarkers were evaluated. Primary endpoints were all-cause mortality and hospital admission due to coronary heart disease or stroke. We estimated adjusted rate ratios (aRR), absolute risk differences and population attributable risk associated with adverse lipid profiles. 51,462 subjects were included with a mean age of 62.6 years (47.6% men). During an average follow-up of 3.2 years, 919 deaths, 1666 hospitalizations for coronary heart disease and 1510 hospitalizations for stroke were recorded. The parameters that showed an increased rate for total mortality, coronary heart disease and stroke hospitalization were, respectively, low HDL-Cholesterol: aRR 1.25, 1.29 and 1.23; high Total/HDL-Cholesterol: aRR 1.22, 1.38 and 1.25; and high Triglycerides/HDL-Cholesterol: aRR 1.21, 1.30, 1.09. The parameters that showed highest population attributable risk (%) were, respectively, low HDL-Cholesterol: 7.70, 11.42, 8.40; high Total/HDL-Cholesterol: 6.55, 12.47, 8.73; and high Triglycerides/HDL-Cholesterol: 8.94, 15.09, 6.92. In a population with cardiovascular risk factors, HDL-cholesterol, Total/HDL-cholesterol and triglycerides/HDL-cholesterol ratios were associated with a higher population attributable risk for cardiovascular disease compared to other common biomarkers.S

Measuring health-related quality of life in men with osteoporosis or osteoporotic fracture

<p>Abstract</p> <p>Background</p> <p>Osteoporosis is a serious health problem that worsens the quality of life and the survival rate of individuals with this disease on account the osteoporotic fractures. Studies have long focused on women, and its presence in men has been underestimated. While many studies conducted in different countries mainly assess health-related quality of life and identify fracture risks factors in women, few data are available on a Spanish male population.</p> <p>Methods/Design</p> <p>Observational study.</p> <p>Study population</p> <p>Men ≥ 40 years of age with/without diagnosed osteoporosis and with/without osteoporotic fracture included by their family doctor.</p> <p>Measurements</p> <p>The relationship between customary clinical risk factors for osteoporotic fracture and health-related quality of life in a Spanish male population. A telephone questionnaire on health-related quality of life is made.</p> <p>Statistical analysis</p> <p>The association between qualitative variables will be assessed by the Chi-square test. The distribution of quantitative variables by Student's t-test. If the conditions for using this test are not met, the non-parametric Mann-Whitney's U test will be used.</p> <p>The validation of the results obtained by the FRAX™ tool will be performed by way of the Hosmer-Lemeshow test and by calculating the area under the Receiver Operating Characteristic (ROC) curve (AUC). All tests will be performed with a confidence intervals set at 95%.</p> <p>Discussion</p> <p>The applicability and usefulness of Health-related quality of life (HRQOL) studies are well documented in many countries. These studies allow implementing cost-effective measures in cases of a given disease and reducing the costly consequences derived therefrom. This study attempts to provide objective data on how quality of life is affected by the clinical aspects involved in osteoporosis in a Spanish male population and can be useful as well in cost utility analyses conducted by health authorities.</p> <p>The sample selected is not based on a high fracture risk group. Rather, it is composed of men in the general population, and accordingly comparisons should not lead to erroneous interpretations.</p> <p>A possible bias correction will be ensured by checking reported fractures against healthcare reports and X-rays, or by consulting health care centers as applicable.</p

La enseñanza del metabolismo: retos y oportunidades

En el marco del Proyecto de Innovación Educativa de la Universidad de Málaga PIE15-163, cuya descripción y resultados incluimos, decidimos que esta era una excelente oportunidad para reflexionar acerca de la enseñanza del metabolismo y de poner por escrito dichas reflexiones en un libro. Quisimos y pudimos contar con la colaboración de buena parte de los compañeros del Departamento de Biología Molecular y Bioquímica que apoyaron con su firma el proyecto PIE15-163 y extendimos nuestra invitaciones a otros compañeros de dentro y fuera de la Universidad de Málaga. Del Departamento de Biología Molecular y Bioquímica de la Universidad de Málaga hemos recibido aportaciones de los catedráticos Victoriano Valpuesta Fernández, Ana Rodríguez Quesada y Antonio Heredia Bayona, los profesores titulares María Josefa Pérez Rodríguez, José Luis Urdiales Ruiz e Ignacio Fajardo Paredes y la investigadora postdoctoral y profesora sustituta interina Beatriz Martínez Poveda. De otros departamentos de la Universidad de Málaga hemos contado con las aportaciones de la catedrática del Departamento de Especialidades Quirúrgicas, Bioquímica e Inmunología Pilar Morata Losa, del catedrático del Departamento de Lenguajes y Ciencias de la Computación José Francisco Aldana Montes y los componentes de su grupo de investigación Khaos Ismael Navas Delgado, María Jesús García Godoy, Esteban López Camacho y Maciej Rybinski, del catedrático Ángel Blanco López, del Área de Conocimiento de Didáctica de las Ciencias Experimentales y del Doctor en Ciencias Químicas y actual doctorando del Programa de Doctorado "Educación y Comunicación Social" Ángel Luis García Ponce. De fuera de la Universidad de Málaga, hemos contado con las aportaciones del catedrático de la Universidad de La Laguna Néstor V. Torres Darias, de la catedrática de la Universitat de les Illes Balears Pilar Roca Salom y de sus compañeros los profesores Jorge Sastre Serra y Jordi Oliver, de los catedráticos de la Universidad de Granada Rafael Salto González y María Dolores Girón González y su colaborador el Dr. José Dámaso Vílchez Rienda, del profesor titular de la Universidad de Alcalá Ángel Herráez, del investigador postdoctoral de la Universidad de Erlangen (Alemania) Guido Santos y del investigador postdoctoral de la empresa Brain Dynamics Carlos Rodríguez Caso.Hemos estructurado los contenidos del libro en diversas secciones. La primera presenta el Proyecto en cuyo marco se ha gestado la iniciativa que ha conducido a la edición del presente libro. La segunda sección la hemos titulado "¿Qué metabolismo?" e incluye diversas aportaciones personales que reflexionan acerca de qué metabolismo debe conocer un graduado en Bioquímica, en Biología, en Química, en Farmacia o en Medicina, así como una aportación acerca de qué bioquímica estructural y enzimología son útiles y necesarias para un estudiante que vaya a afrontar el estudio del metabolismo. La tercera sección, "Bases conceptuales", analiza las aportaciones del aprendizaje colaborativo, el contrato de aprendizaje y el aprendizaje basado en la resolución de casos prácticos a la mejora del proceso enseñanza-aprendizaje dentro del campo de la Bioquímica y Biología Molecular, más concretamente en el estudio del metabolismo. La cuarta sección se titula "Herramientas", es la más extensa e incluye las diversas aportaciones centradas en propuestas concretas de aplicación relevantes y útiles para la mejora de la docencia-aprendizaje del metabolismo. Sigue una sección dedicada a presentar de forma resumida los "Resultados" del proyecto PIE15-163. El libro concluye con una "coda final" en la que se reflexiona acerca del aprendizaje de la Química a la luz de la investigación didáctica.Patrocinado por el Proyecto de Innovación Educativa de la Universidad de Málaga PIE15-16

Customized Treatment in Non-Small-Cell Lung Cancer Based on EGFR Mutations and BRCA1 mRNA Expression

BACKGROUND: Median survival is 10 months and 2-year survival is 20% in metastatic non-small-cell lung cancer (NSCLC) treated with platinum-based chemotherapy. A small fraction of non-squamous cell lung cancers harbor EGFR mutations, with improved outcome to gefitinib and erlotinib. Experimental evidence suggests that BRCA1 overexpression enhances sensitivity to docetaxel and resistance to cisplatin. RAP80 and Abraxas are interacting proteins that form complexes with BRCA1 and could modulate the effect of BRCA1. In order to further examine the effect of EGFR mutations and BRCA1 mRNA levels on outcome in advanced NSCLC, we performed a prospective non-randomized phase II clinical trial, testing the hypothesis that customized therapy would confer improved outcome over non-customized therapy. In an exploratory analysis, we also examined the effect of RAP80 and Abraxas mRNA levels. METHODOLOGY/PRINCIPAL FINDINGS: We treated 123 metastatic non-squamous cell lung carcinoma patients using a customized approach. RNA and DNA were isolated from microdissected specimens from paraffin-embedded tumor tissue. Patients with EGFR mutations received erlotinib, and those without EGFR mutations received chemotherapy with or without cisplatin based on their BRCA1 mRNA levels: low, cisplatin plus gemcitabine; intermediate, cisplatin plus docetaxel; high, docetaxel alone. An exploratory analysis examined RAP80 and Abraxas expression. Median survival exceeded 28 months for 12 patients with EGFR mutations, and was 11 months for 38 patients with low BRCA1, 9 months for 40 patients with intermediate BRCA1, and 11 months for 33 patients with high BRCA1. Two-year survival was 73.3%, 41.2%, 15.6% and 0%, respectively. Median survival was influenced by RAP80 expression in the three BRCA1 groups. For example, for patients with both low BRCA1 and low RAP80, median survival exceeded 26 months. RAP80 was a significant factor for survival in patients treated according to BRCA1 levels (hazard ratio, 1.3 [95% CI, 1-1.7]; P = 0.05). CONCLUSIONS/SIGNIFICANCE: Chemotherapy customized according to BRCA1 expression levels is associated with excellent median and 2-year survival for some subsets of NSCLC patients , and RAP80 could play a crucial modulating effect on this model of customized chemotherapy. TRIAL REGISTRATION: (ClinicalTrials.gov) NCT00883480

Prediction of absolute risk of fragility fracture at 10 years in a Spanish population: validation of the WHO FRAX ™ tool in Spain

<p>Abstract</p> <p>Background</p> <p>Age-related bone loss is asymptomatic, and the morbidity of osteoporosis is secondary to the fractures that occur. Common sites of fracture include the spine, hip, forearm and proximal humerus. Fractures at the hip incur the greatest morbidity and mortality and give rise to the highest direct costs for health services. Their incidence increases exponentially with age.</p> <p>Independently changes in population demography, the age - and sex- specific incidence of osteoporotic fractures appears to be increasing in developing and developed countries. This could mean more than double the expected burden of osteoporotic fractures in the next 50 years.</p> <p>Methods/Design</p> <p>To assess the predictive power of the WHO FRAX™ tool to identify the subjects with the highest absolute risk of fragility fracture at 10 years in a Spanish population, a predictive validation study of the tool will be carried out. For this purpose, the participants recruited by 1999 will be assessed. These were referred to scan-DXA Department from primary healthcare centres, non hospital and hospital consultations. Study population: Patients attended in the national health services integrated into a FRIDEX cohort with at least one Dual-energy X-ray absorptiometry (DXA) measurement and one extensive questionnaire related to fracture risk factors. Measurements: At baseline bone mineral density measurement using DXA, clinical fracture risk factors questionnaire, dietary calcium intake assessment, history of previous fractures, and related drugs. Follow up by telephone interview to know fragility fractures in the 10 years with verification in electronic medical records and also to know the number of falls in the last year. The absolute risk of fracture will be estimated using the FRAX™ tool from the official web site.</p> <p>Discussion</p> <p>Since more than 10 years ago numerous publications have recognised the importance of other risk factors for new osteoporotic fractures in addition to low BMD. The extension of a method for calculating the risk (probability) of fractures using the FRAX™ tool is foreseeable in Spain and this would justify a study such as this to allow the necessary adjustments in calibration of the parameters included in the logarithmic formula constituted by FRAX™.</p

Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk population: the ESCARVAL-RISK study

The potential impact of targeting different components of an adverse lipid profile in populations with multiple cardiovascular risk factors is not completely clear. This study aims to assess the association between different components of the standard lipid profile with all cause mortality and hospitalization due to cardiovascular events in a high-risk population. Methods This prospective registry included high risk adults over 30 years old free of cardiovascular disease (2008±2012). Diagnosis of hypertension, dyslipidemia or diabetes mellitus was inclusion criterion. Lipid biomarkers were evaluated. Primary endpoints were all-cause mortality and hospital admission due to coronary heart disease or stroke. We estimated adjusted rate ratios (aRR), absolute risk differences and population attributable risk associated with adverse lipid profiles. Results 51,462 subjects were included with a mean age of 62.6 years (47.6% men). During an average follow-up of 3.2 years, 919 deaths, 1666 hospitalizations for coronary heart disease and 1510 hospitalizations for stroke were recorded. The parameters that showed an increased rate for total mortality, coronary heart disease and stroke hospitalization were, respectively, low HDL-Cholesterol: aRR 1.25, 1.29 and 1.23; high Total/HDL-Cholesterol: aRR 1.22, 1.38 and 1.25; and high Triglycerides/HDL-Cholesterol: aRR 1.21, 1.30, 1.09. The parameters that showed highest population attributable risk (%) were, respectively, low HDL-Cholesterol: 7.70, 11.42, 8.40; high Total/HDL-Cholesterol: 6.55, 12.47, 8.73; and high Triglycerides/ HDL-Cholesterol: 8.94, 15.09, 6.92. Conclusions In a population with cardiovascular risk factors, HDL-cholesterol, Total/HDL-cholesterol and triglycerides/HDL-cholesterol ratios were associated with a higher population attributable risk for cardiovascular disease compared to other common biomarkers

BRCA1: A Novel Prognostic Factor in Resected Non-Small-Cell Lung Cancer

BACKGROUND: Although early-stage non-small-cell lung cancer (NSCLC) is considered a potentially curable disease following complete resection, patients have a wide spectrum of survival according to stage (IB, II, IIIA). Within each stage, gene expression profiles can identify patients with a higher risk of recurrence. We hypothesized that altered mRNA expression in nine genes could help to predict disease outcome: excision repair cross-complementing 1 (ERCC1), myeloid zinc finger 1 (MZF1) and Twist1 (which regulate N-cadherin expression), ribonucleotide reductase subunit M1 (RRM1), thioredoxin-1 (TRX1), tyrosyl-DNA phosphodiesterase (Tdp1), nuclear factor of activated T cells (NFAT), BRCA1, and the human homolog of yeast budding uninhibited by benzimidazole (BubR1). METHODOLOGY AND PRINCIPAL FINDINGS: We performed real-time quantitative polymerase chain reaction (RT-QPCR) in frozen lung cancer tissue specimens from 126 chemonaive NSCLC patients who had undergone surgical resection and evaluated the association between gene expression levels and survival. For validation, we used paraffin-embedded specimens from 58 other NSCLC patients. A strong inter-gene correlation was observed between expression levels of all genes except NFAT. A Cox proportional hazards model indicated that along with disease stage, BRCA1 mRNA expression significantly correlated with overall survival (hazard ratio [HR], 1.98 [95% confidence interval (CI), 1.11-6]; P = 0.02). In the independent cohort of 58 patients, BRCA1 mRNA expression also significantly correlated with survival (HR, 2.4 [95%CI, 1.01-5.92]; P = 0.04). CONCLUSIONS: Overexpression of BRCA1 mRNA was strongly associated with poor survival in NSCLC patients, and the validation of this finding in an independent data set further strengthened this association. Since BRCA1 mRNA expression has previously been linked to differential sensitivity to cisplatin and antimicrotubule drugs, BRCA1 mRNA expression may provide additional information for customizing adjuvant antimicrotubule-based chemotherapy, especially in stage IB, where the role of adjuvant chemotherapy has not been clearly demonstrated

Correction: Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk population: The ESCARVAL-RISK study.

The potential impact of targeting different components of an adverse lipid profile in populations with multiple cardiovascular risk factors is not completely clear. This study aims to assess the association between different components of the standard lipid profile with all-cause mortality and hospitalization due to cardiovascular events in a high-risk populatio

Trends in the epidemiology of catheter-related bloodstream infections; towards a paradigm shift, Spain, 2007 to 2019

Altres ajuts: Departament de Salut. Generalitat de Catalunya ("Pla estratègic de recerca i innovació en salut (PERIS) 2019-2021"); Ministerio de Asuntos Económicos y Transformación Digital; Red Española de Investigación en Patología Infecciosa (REIPI).Background: Catheter-related bloodstream infections (CRBSI) are frequent healthcare-associated infections and an important cause of death. Aim: To analyse changes in CRBSI epidemiology observed by the Infection Control Catalan Programme (VINCat). Methods: A cohort study including all hospital-acquired CRBSI episodes diagnosed at 55 hospitals (2007-2019) in Catalonia, Spain, was prospectively conducted. CRBSI incidence rates were adjusted per 1,000patientdays. To assess the CRBSI rate trend per year, negative binomial models were used, with the number of events as the dependent variable, and the year as the main independent variable. From each model, the annual rate of CRBSI diagnosed per 1,000patientdays and the incidence rate ratio (IRR) with its 95% confidence intervals (CI) were reported. Results: During the study, 9,290 CRBSI episodes were diagnosed (mean annual incidence rate:0.20episodes/1,000patientdays). Patients' median age was 64.1years; 36.6% (3,403/9,290) were female. In total, 73.7% (n=6,845) of CRBSI occurred in non-intensive care unit (ICU) wards, 62.7% (n=5,822) were related to central venous catheter (CVC), 24.1% (n=2,236) to peripheral venous catheters (PVC) and 13.3% (n=1,232) to peripherally-inserted central venous catheters (PICVC). Incidence rate fell over the study period (IRR:0.94;95%CI:0.93-0.96), especially in the ICU (IRR:0.88;95%CI:0.87-0.89). As a whole, while episodes of CVC CRBSI fell significantly (IRR:0.88;95%CI:0.87-0.91), peripherally-inserted catheter CRBSI (PVC and PICVC) rose, especially in medical wards (IRR PICVC:1.08;95%CI:1.05-1.11; IRR PVC: 1.03; 95% 1.00-1.05). Conclusions: Over the study, CRBSIs associated with CVC and diagnosed in ICUs decreased while episodes in conventional wards involving peripherally-inserted catheters increased. Hospitals should implement preventive measures in conventional wards