Systemic Effects Induced by Hyperoxia in a Preclinical Model of Intra-abdominal Sepsis

Supplemental oxygen is a supportive treatment in patients with sepsis to balance tissue oxygen delivery and demand in the tissues. However, hyperoxia may induce some pathological effects. We sought to assess organ damage associated with hyperoxia and its correlation with the production of reactive oxygen species (ROS) in a preclinical model of intra-abdominal sepsis. For this purpose, sepsis was induced in male, Sprague-Dawley rats by cecal ligation and puncture (CLP). We randomly assigned experimental animals to three groups: control (healthy animals), septic (CLP), and sham-septic (surgical intervention without CLP). At 18 h after CLP, septic (n = 39), sham-septic (n = 16), and healthy (n = 24) animals were placed within a sealed Plexiglas cage and randomly distributed into four groups for continuous treatment with 21%, 40%, 60%, or 100% oxygen for 24 h. At the end of the experimental period, we evaluated serum levels of cytokines, organ damage biomarkers, histological examination of brain and lung tissue, and ROS production in each surviving animal. We found that high oxygen concentrations increased IL-6 and biomarkers of organ damage levels in septic animals, although no relevant histopathological lung or brain damage was observed. Healthy rats had an increase in IL-6 and aspartate aminotransferase at high oxygen concentration. IL-6 levels, but not ROS levels, are correlated with markers of organ damage. In our study, the use of high oxygen concentrations in a clinically relevant model of intra-abdominal sepsis was associated with enhanced inflammation and organ damage. These findings were unrelated to ROS release into circulation. Hyperoxia could exacerbate sepsis-induced inflammation, and it could be by itself detrimental. Our study highlights the need of developing safer thresholds for oxygen therapy

Reconocimiento de la tradici?n constructiva y la cultura habitacional de la comunidad ind?gena Mesa de Cucuana Aceituno en Ortega Tolima

348 p. Recurso Electr?nicoEste proyecto de grado busca reconocer la tradici?n constructiva y la cultura habitacional de la comunidad ind?gena Mesa de Cucuana Aceituno, en el Municipio de Ortega, Departamento del Tolima; para preservar las din?micas socio-espaciales de la poblaci?n del cabildo, que a trav?s de los a?os han venido desapareciendo a ra?z de diferentes factores. Con la finalidad de ofrecerles a los habitantes de la comunidad ind?gena una alternativa de vivienda acorde a sus modos de vida y din?micas espaciales tradicionales; y as? ayudar a subsanar el d?ficit tanto cualitativo como cuantitativo presente actualmente en la comunidad, se plantea el reconocimiento de la habitabilidad mediante la investigaci?n meticulosa para desarrollar una propuesta coherente con lo descrito anteriormente. De esta manera, el trabajo se desarrolla en tres etapas: Reconocimiento de las t?cnicas tradicionales, procesos y materialidad en la construcci?n de viviendas propias del territorio ind?gena de Mesa de Cucuana Aceituno. Seguidamente, el estudio y an?lisis de los modos de vida, costumbres y tradiciones de la habitabilidad de la poblaci?n con respecto a sus viviendas y el entorno donde se encuentran emplazadas. Finalmente, a partir de todo el reconocimiento desarrollado, plantear el dise?o arquitect?nico y urban?stico de una propuesta de agrupaci?n de viviendas junto con tres modelos de vivienda ind?gena acordes con sus costumbres y tradiciones, respetando su cultura habitacional y las condiciones de su entorno; por ?ltimo, proyectar un esquema b?sico del dise?o de un equipamiento social y sede del Cabildo Mesa de Cucuana Aceituno, como espacio complementario a la vivienda.This degree seeks to recognize the traditional construction and residential culture of the indigenous community Mesa of Cucuana Aceituno, in the municipality of Ortega, Department of Tolima; to preserve the socio-spatial dynamics of the population of the Town Hall, that through the years have been disappearing as a result of various factors. With the purpose of offer you to the inhabitants of the community indigenous an alternative of housing according to their modes of life and dynamic space traditional; and thus help to remedy the deficit both qualitative as quantitative present currently in the community. In this way, the work develops in three stages: recognition of traditional techniques, processes and material in the construction of houses of the indigenous territory of Mesa of Cucuana Aceituno. Then, the study and analysis of the ways of life, customs and traditions of the habitability of the population with regard to their homes and the environment where they are placed. Finally, through the design architectural and urban project three models of housing indigenous chords with their customs and traditions, a proposed of grouping of housing, respecting its culture housing and the conditions of its environment, and, finally, a scheme basic of the design of an equipment social and headquarters of the Cabildo Mesa of Cucuana Aceituno, as space complementary to it housing. Key words: Indigenous housing, liveability, constructive traditio

Fast evaluation of the adsorption energy of organic molecules on metals via graph neural networks

Modeling in heterogeneous catalysis requires the extensive evaluation of the energy of molecules adsorbed on surfaces. This is done via density functional theory but for large organic molecules it requires enormous computational time, compromising the viability of the approach. Here we present GAME-Net, a graph neural network to quickly evaluate the adsorption energy. GAME-Net is trained on a well-balanced chemically diverse dataset with C1–4 molecules with functional groups including N, O, S and C6–10 aromatic rings. The model yields a mean absolute error of 0.18 eV on the test set and is 6 orders of magnitude faster than density functional theory. Applied to biomass and plastics (up to 30 heteroatoms), adsorption energies are predicted with a mean absolute error of 0.016 eV per atom. The framework represents a tool for the fast screening of catalytic materials, particularly for systems that cannot be simulated by traditional methods

Mercado de formaci?n y disponibilidad de profesionales de ciencias de la salud en el Per?

Objectives. To describe the availability and demand of professional training programs for eight health science professions in Peru. Study the profiles of the physicians, nurses and midwives that these programs train and their competencies to work at the primary health care level. Materials and methods. Cross-sectional study using data on the volume of applicants, students and graduates of these eight professional training programs during the period 2007 - 2011. In addition, the curricula of professional training programs for physicians, nurses and midwives from public and private universities were analyzed, along with competency profiles developed by Professional Colleges and the Ministry of Health. Results. Admission rates in public and private universities vary by program: 4% and 28% respectively for medical schools, and 18% and 90% for nursing. Graduation rates were estimated at approximately 43% and 53% of students entering medicine and nursing training programs respectively. Contrasting the profiles of recently graduated professionals in medicine, nursing and midwifery, with the skills required by the Ministry of Health for professionals working in primary care the first level of care, indicate that these recently graduated professionals are not necessarily or specifically trained to work in primary care. Conclusions. Demand for professional training in health sciences exists and its supply is met predominantly by private universities. Competency profiles developed by the MOH for the basic professional health team in primary care shows a clear disconnect regarding the current supply of trained professionals.Objetivos. Describir el mercado de formaci?n y la disponibilidad de profesionales de ocho carreras de ciencias de la salud en Per?. Adem?s, examinar los perfiles de los m?dicos, enfermeros y obstetras que se forman y sus competencias para trabajar en el primer nivel de atenci?n. Materiales y m?todos. Estudio transversal utilizando datos de volumen de postulantes, ingresantes y graduados de ocho profesiones durante el periodo de 2007?2011. Tambi?n se analizaron los planes de estudio de programas de formaci?n de m?dicos, enfermeros y obstetras de universidades p?blicas y privadas, y los perfiles de competencias elaborados por los colegios profesionales y el Ministerio de Salud (MINSA). Resultados. Las tasas de ingreso en universidades p?blicas y privadas var?an seg?n la carrera: 4 y 28% respectivamente para Medicina Humana, y 18 y 90% para Enfermer?a. Adem?s, se estima que se grad?an aproximadamente 43 y 53% de los estudiantes que ingresan a Medicina y Enfermer?a, respectivamente. El an?lisis del perfil de los profesionales recientemente graduados en Medicina, Enfermer?a y Obstetricia, al ser contrastados con el perfil de competencias priorizadas para los profesionales que laboran en el primer nivel de atenci?n elaborado por el MINSA, indican que no est?n necesariamente ni espec?ficamente formados para trabajar en este nivel de atenci?n. Conclusiones. Existe demanda de formaci?n para profesionales de ciencias de la salud y predomina la oferta por parte de universidades privadas. Los perfiles de competencias desarrollados por el MINSA muestran un claro divorcio con respecto a la oferta actual de profesionales formados

Value of Serum NEUROG1 Methylation for the Detection of Advanced Adenomas and Colorectal Cancer

Aberrant DNA methylation detected in liquid biopsies is a promising approach for colorectal cancer (CRC) detection, including premalignant advanced adenomas (AA). We evaluated the diagnostic capability of serum NEUROG1 methylation for the detection of AA and CRC. A CpG island in NEUROG1 promoter was assessed by bisulfite pyrosequencing in a case-control cohort to select optimal CpGs. Selected sites were evaluated through a nested methylation-specific qPCR custom assay in a screening cohort of 504 asymptomatic family-risk individuals. Individuals with no colorectal findings and benign pathologies showed low serum NEUROG1 methylation, similar to non-advanced adenomas. Contrarily, individuals bearing AA or CRC (advanced neoplasia-AN), exhibited increased NEUROG1 methylation. Using >1.3518% as NEUROG1 cut-off (90.60% specificity), 33.33% of AN and 32.08% of AA were identified, detecting 50% CRC cases. Nonetheless, the combination of NEUROG1 with fecal immunochemical test (FIT), together with age and gender through a multivariate logistic regression resulted in an AUC = 0.810 for AN, and 0.796 for AA, detecting all cancer cases and 35-47% AA (specificity 98-95%). The combination of NEUROG1 methylation with FIT, age and gender demonstrated a convenient performance for the detection of CRC and AA, providing a valuable tool for CRC screening programs in asymptomatic individuals

Oncogenic driver mutations predict outcome in a cohort of head and neck squamous cell carcinoma (HNSCC) patients within a clinical trial

234 diagnostic formalin-fixed paraffin-embedded (FFPE) blocks from homogeneously treated patients with locally advanced head and neck squamous cell carcinoma (HNSCC) within a multicentre phase III clinical trial were characterised. The mutational spectrum was examined by next generation sequencing in the 26 most frequent oncogenic drivers in cancer and correlated with treatment response and survival. Human papillomavirus (HPV) status was measured by p16INK4a immunohistochemistry in oropharyngeal tumours. Clinicopathological features and response to treatment were measured and compared with the sequencing results. The results indicated TP53 as the most mutated gene in locally advanced HNSCC. HPV-positive oropharyngeal tumours were less mutated than HPV-negative tumours in TP53 (p < 0.01). Mutational and HPV status influences patient survival, being mutated or HPV-negative tumours associated with poor overall survival (p < 0.05). No association was found between mutations and clinicopathological features. This study confirmed and expanded previously published genomic characterization data in HNSCC. Survival analysis showed that non-mutated HNSCC tumours associated with better prognosis and lack of mutations can be identified as an important biomarker in HNSCC. Frequent alterations in PI3K pathway in HPV-positive HNSCC could define a promising pathway for pharmacological intervention in this group of tumours

Increased urinary markers of kidney damage in the institutionalized frail elderly due to recurrent urinary tract infections.

Objective: To characterize the impact on kidney injury of recurrent urinary tract infections (RUTI) in the frail elderly. Methods: Prospective observational study in 200 frail elderly subjects for 1 year. Groups: GA (n = 100): subjects without RUTI, GB (n = 100): subjects with RUTI. Variables: age, concomitant diseases, glomerular filtration rate (GFR), urine neutrophil gelatinase-associated lipocalin (NGAL) at the beginning (NGAL-1) and end (NGAL-2) of the study, urine N-acetyl glucosaminidase (NAG) at the beginning (NAG-1) and the end (NAG-2) of the study, urine transforming growth factor-beta 1 (TGFbeta-1). Descriptive statistics, Mann-Whitney test, Chi-squared test, Fisher's exact test, and multivariate analysis were used. Results: Mean age was 84.33 (65-99) years old, with no difference between GA and GB. Mean NGAL-1 was 1.29 ng/ml (0.04-8). There was lower in GA than in GB. Mean NGAL-2 was 1.41 ng/ml (0.02-9.22). NGAL-2 was lower in GA than in GB. Mean NAG-1 was 0.38 UU.II/ml (0.01-2.63. NAG-1 in GA was lower than in GB. Mean NAG-2 was 0.44 UU.II/ml (0-3.41). NAG-2 was lower in GA compared with GB. Mean TGFbeta-1 was 23.43 pg/ml (0.02-103.76). TGFbeta-1 was lower in GA than GB. There were no differences in the presence of secondary diagnoses between GA and GB. NAG-2 and NGAL-1 were the most determining factors of renal function; in GA it was NGAL-2, followed by NAG-1; in GB it was NGAL-1, followed by NAG-2. Conclusion: Frail elderly with RUTI have higher urinary levels of renal injury markers, specifically NGAL, NAG, and TGFbeta-1, chronically in periods between urinary tract infection (UTI). Urinary markers of renal injury, specifically NGAL, NAG, and TGFbeta-1, identify early deterioration of renal function, compared with serum creatinine, or albuminuria, in frail elderly with recurrent urinary infections

Ethnic and Gender Wage Gaps in Ecuador

Returns to labor for workers with similar endowments of productive characteristics in Ecuador are influenced by two characteristics that, arguably, should play no role on the determination of wages: gender and ethnicity. This paper analyzes wage gaps due to both characteristics in Ecuador for the period 2003-2007, applying a matching comparisons technique developed in Ñopo (2008). The results indicate ethnic wage gaps that are notably higher than gender wage gaps. Furthermore, ethnic wage gaps are higher among males than among females. Differences in human capital characteristics, however, explain almost one-half of the ethnic wage gaps but only a small fraction of the gender wage gaps. Both gender and ethnic wage gaps are more pronounced at the lower extremes of the earnings distribution

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1