X-ray crystallographic and theoretical studies of an anticonvulsant enaminone:methyl 4-(4'-bromophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate

Objective: The aims of this study were to establish the structure of the potent anticonvulsant enaminone methyl 4-(4′-bromophenyl)amino-6-methyl-2- oxocyclohex-3-en-1-oate (E139), and to determine the energetically preferred conformation of the molecule, which is responsible for the biological activity. Materials and Methods: The structure of the molecule was determined by X-ray crystallography. Theoretical ab initio calculations with different basis sets were used to compare the energies of the different enantiomers and to other structurally related compounds. Results: The X-ray crystal structure revealed two independent molecules of E139, both with absolute configuration C11(S), C12(R), and their inverse. Ab initio calculations with the 6-31G, 3-21G and STO-3G basis sets confirmed that the C11(S), C12(R) enantiomer with both substituents equatorial had the lowest energy. Compared to relevant crystal structures, the geometry of the theoretical structures shows a longer C-N and shorter C=O distance with more cyclohexene ring puckering in the isolated molecule. Conclusion: Based on a pharmacophoric model it is suggested that the enaminone system HN-C=C-C=O and the 4-bromophenyl group in E139 are necessary to confer anticonvulsant property that could lead to the design of new and improved anticonvulsant agents. Copyright © 2003 S. Karger AG, Basel.

Sensor and software use for the glycaemic management of insulin-treated type 1 and type 2 diabetes patients

Lowering glucose levels, while avoiding hypoglycaemia, can be challenging in insulin-treated patients with diabetes. We evaluated the role of ambulatory glucose profile in optimising glycaemic control in this population. Insulin-treated patients with type 1 and type 2 diabetes were recruited into a prospective, multicentre, 100-day study and randomised to control (n = 28) or intervention (n = 59) groups. The intervention group used ambulatory glucose profile, generated by continuous glucose monitoring, to assess daily glucose levels, whereas the controls relied on capillary glucose testing. Patients were reviewed at days 30 and 45 by the health care professional to adjust insulin therapy. Comparing first and last 2 weeks of the study, ambulatory glucose profile-monitored type 2 diabetes patients (n = 28) showed increased time in euglycaemia (mean ± standard deviation) by 1.4 ± 3.5 h/day (p = 0.0427) associated with reduction in HbA1c from 77 ± 15 to 67 ± 13 mmol/mol (p = 0.0002) without increased hypoglycaemia. Type 1 diabetes patients (n = 25) showed reduction in hypoglycaemia from 1.4 ± 1.7 to 0.8 ± 0.8 h/day (p = 0.0472) associated with a marginal HbA1c decrease from 75 ± 10 to 72 ± 8 mmol/mol (p = 0.0508). Largely similar findings were observed comparing intervention and control groups at end of study. In conclusion, ambulatory glucose profile helps glycaemic management in insulin-treated diabetes patients by increasing time spent in euglycaemia and decreasing HbA1c in type 2 diabetes patients, while reducing hypoglycaemia in type 1 diabetes patients.

Annotated record of the detailed examination of Mn deposits from DSDP Site 160, Leg 16 (Cores 16-160-1, 16-160-2 and 16-160-3)

DSDP 160 forms part of a series of sites in the eastern equatorial Pacific on the west flank of the East Pacific Rise. Earlier legs of the Deep Sea Drilling Project, in particular Legs 5 and 9, have reported sediments rich in oxides of iron and perhaps other transition metals just above basement in the eastern Pacific. These occurrences roughly define a broad zone on the west flank of the rise. Site DSDP 160 lies on this trend and were selected by the Pacific Site Selection Panel to test the extent of such deposits.

Geological reference standards (JLK-1,JSD-1, JSD-2, JSD-3,JMS-1, JMS-2) measured by Itrax-XRF core scanner in different exposure times

X-ray fluorescence (XRF) core-scanning is a fast and nondestructive technique to assess elemental variations of unprocessed sediments. However, although the exposure time of XRF-scanning directly affects the scanning counts and total measurement time, only a few studies have considered the influence of exposure time during the scan. How to select an optimal exposure time to achieve reliable results and reduce the total measurement time is an important issue. To address this question, six geological reference materials from the Geological Survey of Japan (JLK-1, JMS-1, JMS-2, JSD-1, JSD-2, and JSD-3) were scanned by the Itrax-XRF core scanner using the Mo- and the Cr-tube with different exposure times to allow a comparison of scanning counts with absolute concentrations. The regression lines and correlation coefficients of elements that are generally used in paleoenvironmental studies were examined for the different exposure times and X-ray tubes. The results show that for those elements with relatively high concentrations or high detectability, the correlation coefficients are higher than 0.90 for all exposure times. In contrast, for the low detectability or low concentration elements, the correlation coefficients are relatively low, and improve little with increased exposure time. Therefore, we suggest that the influence of different exposure times is insignificant for the accuracy of the measurements. Thus, caution must be taken when interpreting the results of elements with low detectability, even when the exposure times are long and scanning counts are reasonably high.

Vulnerabilidade ao Stress e Autoestima em Professores do 1.º, 2.º E 3.º Ciclo

Introdução: O stress condiciona o comportamento e desenvolvimento pessoal, podendo ter consequências preocupantes ao nível individual e organizacional. Os professores são uma classe reconhecida como estando sujeita a elevados níveis de stress, fator que prejudica a qualidade do ensino em geral. Objetivos: Avaliar a vulnerabilidade ao stress; identificar os principais fatores de stress e avaliar a correlação entre autoestima e stress, em professores do 1.º, 2.º e 3.º ciclos do ensino básico. Metodologia: Estudo correlacional, com uma amostra constituída por 60 professores do 1.º, 2.º e 3.º ciclos de escolaridade, de escolas do concelho de Leiria. Para a análise das variáveis em estudo foram aplicados: um questionário sociodemográfico; a Rosenberg Self-Esteem Scale (RSES); o Questionário de stress nos professores: ensino básico e secundário (QSPEBS) e a Escala de vulnerabilidade ao stress (23 QVS). Resultados: O estudo revela que 65% dos professores percecionam a profissão como stressante e que 30% são vulneráveis ao stress. O principal fator de stress identificado foi comportamentos inadequados/indisciplina dos alunos. Verificou-se uma correlação negativa entre a autoestima e a vulnerabilidade ao stress dos professores. Conclusão: Conclui-se que, quanto mais elevada é a auto-estima, menor é a vulnerabilidade dos professores ao stress e que, apesar de não se registarem níveis significativos de vulnerabilidade ao stress na população docente, a maioria dos professores perceciona a sua atividade profissional como geradora de elevados níveis de stress, sendo os comportamentos inadequados/indisciplina dos alunos o fator que mais contribui para o stress nos docentes. / Introduction: Stress affects behavior and personal development, and may have severe consequences either at the individual or organizational level. Teachers are identified as a class exposed to high levels of stress, factor that affects the quality of education in general. Objectives: To assess stress vulnerability; identify key stressors and assess the correlation between self-esteem and stress in primary and secondary school teachers. Methodology: A sociodemographic questionnaire and three self-report measures were administered to a sample of 60 primary and secondary teachers from Leiria district: the Rosenberg Self-Esteem Scale (RSES); a teachers stress questionnaire for primary, secondary and high school (QSPEBS) and a scale to access stress vulnerability (23 QVS). Results: The study reveals that 65% of teachers perceive the profession as stressful and that 30% are vulnerable to stress. The main stressor identified is inappropriate/disruptive behavior of students. There is a negative correlation between self-esteem and vulnerability to stress of teachers. Conclusion: We conclude that a higher self-esteem leads to less stress vulnerability in teachers and that, despite the non-significant level of vulnerability determined in this study, most teachers perceive their activity as stressful, being inappropriate/disruptive behavior of students the factor that most contributes for that.

Diseño de un modelo para promover emprendimiento en estudiantes de secundaria en grados 10° y 11° de estratos 1,2 y 3 en Colombia

páginas: 150

Síntesis, caracterización y estudio de compuestos de coordinación con el ligando N,N¿dimetil-N-N-bis(2-hidroxi-3-metoxi-5-metilbencil) etilendiamina (H2L)

257 p.

Aportación de la bioimpedancia espectroscópica en el estado nutricional y de hidratación del paciente en hemodiálisis: impacto en la morbi-mortalidad

Aportación de la bioimpedancia espectroscópica en la valoración del estado de nutrición e hidratación del paciente en hemodiálisis. Impacto en la morbimortalidad. Los pacientes con enfermedad renal crónica tienen una mortalidad muy superior a la población general, siendo la principal causa la cardiovascular (Foley et al. 2005; Locatelli et al. 2004). Como consecuencia del gran impacto que tienen el estado nutricional ( Pifer et al. 2002; Gracia Iguacel et al. 2013) y la sobrehidratación (Kalantar Zadeh et al. 2009; Wizemann et al. 2009; Agarwal et al. 2010; Chazot et al. 2012) en la mortalidad, en los ultimos años se han desarrollado distintos métodos de análisis de la composición corporal, entre los cuales se encuentra la Bioimpedancia Espectroscópica (BIS). Esta herramienta permite cuantificar los diversos compartimentos del cuerpo (fundamentalmente masa magra, masa grasa y agua corporal) proporcionando al clínico información útil para la toma de decisiones, fundamentalmente en lo que respecta a la sobrecarga de volumen, aspecto fundamental en el manejo del paciente en hemodiálisis (López Gómez et al. 2011). La justificación de esta investigación se basa en existen pocos estudios longitudinales que analicen la evolución en el tiempo de marcadores nutricionales bioquímicos clásicos así como parámetros de bioimpedancia y su asociación con la morbimortalidad; no existiendo aún consenso sobre si los distintos marcadores pronósticos son mas predictivos con medidas basales o con medidas de seguimiento en el tiempo, por lo que nuestro trabajo puede contribuir a clarificar este aspecto. Además, existe un desconocimiento sobre el estado inflamatorio, la prevalencia de DPE y de sobrehidratación en la población en hemodiálisis de nuestro entorno por lo que consideramos importante analizarla para saber dónde estamos y en qué podemos mejorar. Objetivos: 1.- Impacto de la composición corporal así como de marcadores nutricionales bioquímicos e inflamatorios seguidos en el tiempo, sobre la morbimortalidad (evento compuesto muerte-hospitalización). 2.- Prevalencia del Síndrome de Desgaste Proteico Energético en función de distintas herramientas utilizadas para su valoración (criterios ISRNM, score MIS, y bioimpedancia).3.-Correlación entre los parámetros de bioimpedancia y parámetros bioquímicos nutricionales e inflamatorios. 4.- Análisis de la evolución en el tiempo de los parámetros bioquímicos, antropométricos y de bioimpedancia en el global de la muestra y en distintos grupos atendiendo al sexo, presencia de diabetes y grado de inflamación.. Diseño: Estudio observacional prospectivo de 15 meses de duración (Octubre/2013-Dic/2014) en pacientes prevalentes en hemodiálisis. Se ha realizado un corte transversal con los datos del primer mes de inclusión del paciente en el estudio (basal), a partir del cual se ha iniciado el seguimiento en el tiempo cada 2 meses. La mediana de seguimiento del estudio ha sido de 12 meses (RI 10-13 m). Pacientes y métodos: el nº de pacientes incluidos en el estudio fue de 169. Se incluyeron los pacientes estables, con mas de 3 meses en HD, excluyendose pacientes con ingreso reciente, proceso infeccioso o inflamatorio en 3 meses previos, neoplasia activa, marcapasos unipolar o con umbral de sensibilidad desconocido. Todos los pacientes firmaron el consentimiento informado. La prevalencia de DPE se analizó en el momento inicial y final del estudio. Para el análisis de la morbimortalidad se consideraron todos los ingresos de causa no programada, así como los éxitus por cualquier causa. Las funciones de supervivencia se calcularon mediante el análisis de Kaplan-Meier Para la identificación de las variables predictoras independientes del evento compuesto (muerte y / u hospitalización) se realizó un modelo de Cox univariante con las variables analíticas ( basal, media, mediana, máximo y mínimo) y demográficas y un modelo de Cox ajustado por edad,sexo e IMC con los parámetros de bioimpedancia . Las variables que dieron significativas en estos modelos (P < 0,05) se introdujeron en un modelo de Cox multivariante. Resultados. La prevalencia de DPE según criterios del ISRNM fue del 9.3 % en el momento basal, y del 4,3% en el momento de finalización del estudio. La prevalencia de sobrehidratación medida como AvROH fue del 20,1%. Durante el periodo de seguimiento se produjeron cambios significativos fundamentalmente en el índice de tejido graso (ITG) y en la sobrehidratación en los meses de verano (AvROH y TAFO). El 26% de la población de estudio tuvo al menos un ingreso hospitalario. 21 pacientes fallecieron durante el seguimiento (12,4% de la población). La principal causa de ingreso y éxitus fue la cardiovascular; consituyendo el 35% de los ingresos y el 57% de los éxitus. Los parámetros que presentaron asociación con el evento compuesto fueron: TAFO mínimo (HR 1.319: IC 95% 1.029-1.691; p= 0.029), PCR mediana (HR 1.032; IC 95% 1.014-1.050; p=0.001), albúmina máxima (HR 0.286; IC95% 0.085-0.966), colesterol total (HR 1.011; IC 95% 1.003-1.019; p=0.007) y nivel de 25 OH vit D (HR 0.947; IC 95% 0.915-0.981); p= 0.002). Conclusiones: El principal resultado de nuestro trabajo fue que la sobrehidratación, (medida como TAFO) se asoció de forma independiente con la morbimortalidad, y que las medidas seguidas en el tiempo (TAFO mínimo) tuvieron un mayor poder predictivo que las medidas basales. Adicionalmente; el estado nutricional e inflamatorio, medido mediante parámetros individuales, supuso un mayor impacto en la morbimortalidad que parámetros agrupados, como el score MIS o el síndrome DPE según criterios ISRNM. En nuestro estudio hemos encontrado importantes diferencias en la prevalencia de DPE en función de la herramienta utilizada (criterios ISRNM, MIS y parámetros de bioimpedancia). Finalmente, la periodicidad de la medición de las diferentes variables a lo largo del seguimiento nos ha permitido apreciar los cambios estacionales en los parámetros de bioimpedancia, los cuales se han acompañado de cambios en sentido inverso de algunos de los parámetros bioquímicos nutricionales.

Grip strength and functional recovery after hip fracture: An observational study in elderly population

Muscle strength is a common issue in fragility syndrome and sarcopenia, both of them involved in the pathogenesis of falls and fractures. The objective is to study the relationship between hand grip strength and functional recovery after hip fracture surgery. This prospective observational study included patients aged 65. years and older who were admitted to hospital for hip fracture surgery during a 12 month period. Functional status (Barthel Index), mental status (Cruz Roja Index), hand grip strength, 25/OH-Vitamin D plasmatic levels were evaluated at admission. Follow-up was performed 3. months after discharge to assess functional status and survival. Correlations between hand grip strength and the rest of variables were evaluated. Univariate and multivariate analyses were further applied. Mean age of subjects was 85.1. ±. 0.63 years. Out of 127 subjects, 103 were women and 24 were men. Hand grip strength was obtained in 85 patients (76.5%) and, values were between 3.3 and 24.8. kg and 81 patients (95.2%) had values below cut-point of sarcopenia considering European Working Group of Sarcopenia criteria. Hand grip strength at admission shows significant association to Barthel index at three months and functional recovery. It is also associated with age (P <. 0.001) (r = 0.81), sex (P = 0.001), cognitive status by Cruz Roja Index (P <. 0.001) and functional status measured at admission by Barthel Index (P <. 0.01) (r = -0.22). Multivariate analysis confirmed that variables were independently associated to grip strength. Hand grip strength measured at admission in Orthogeriatric Unit after hip fracture is directly related to functional recovery in elderly patients.

A Rapid And Simple Capillary Electrophoresis Method For Indirect Determination Of The Biocide 2,2-dibromo-3-nitrilo-propionamide (dbnpa) In Cooling Waters.

A capillary zone electrophoresis (CE) method was developed for the determination of the biocide 2,2-dibromo-3-nitrilo-propionamide (DBNPA) in water used in cooling systems. The biocide is indirectly determined by CE measurement of the concentration of bromide ions produced by the reaction between the DBNPA and bisulfite. The relationship between the bromide peak areas and the DBNPA concentrations showed a good linearity and a coefficient of determination (R(2)) of 0.9997 in the evaluated concentration range of 0-75 μmol L(-1). The detection and quantification limits for DBNPA were 0.23 and 0.75 μmol L(-1), respectively. The proposed CE method was successfully applied for the analysis of samples of tap water and cooling water spiked with DBNPA. The intra-day and inter-day (intermediary) precisions were lower than 2.8 and 6.2%, respectively. The DBNPA concentrations measured by the CE method were compared to the values obtained by a spectrophotometric method and were found to agree well.

New Interaction Partners For Nek4.1 And Nek4.2 Isoforms: From The Dna Damage Response To Rna Splicing.

Neks are serine-threonine kinases that are similar to NIMA, a protein found in Aspergillus nidulans which is essential for cell division. In humans there are eleven Neks which are involved in different biological functions besides the cell cycle control. Nek4 is one of the largest members of the Nek family and has been related to the primary cilia formation and in DNA damage response. However, its substrates and interaction partners are still unknown. In an attempt to better understand the role of Nek4, we performed an interactomics study to find new biological processes in which Nek4 is involved. We also described a novel Nek4 isoform which lacks a region of 46 amino acids derived from an insertion of an Alu sequence and showed the interactomics profile of these two Nek4 proteins. Isoform 1 and isoform 2 of Nek4 were expressed in human cells and after an immunoprecipitation followed by mass spectrometry, 474 interacting proteins were identified for isoform 1 and 149 for isoform 2 of Nek4. About 68% of isoform 2 potential interactors (102 proteins) are common between the two Nek4 isoforms. Our results reinforce Nek4 involvement in the DNA damage response, cilia maintenance and microtubule stabilization, and raise the possibility of new functional contexts, including apoptosis signaling, stress response, translation, protein quality control and, most intriguingly, RNA splicing. We show for the first time an unexpected difference between both Nek4 isoforms in RNA splicing control. Among the interacting partners, we found important proteins such as ANT3, Whirlin, PCNA, 14-3-3ε, SRSF1, SRSF2, SRPK1 and hNRNPs proteins. This study provides new insights into Nek4 functions, identifying new interaction partners and further suggests an interesting difference between isoform 1 and isoform 2 of this kinase. Nek4 isoform 1 may have similar roles compared to other Neks and these roles are not all preserved in isoform 2. Besides, in some processes, both isoforms showed opposite effects, indicating a possible fine controlled regulation.

Educação fisica escolar : proposta para formação de lideres comunitarios para alunos de 2ª e 3ª series do ensino medio

Universidade Estadual de Campinas . Faculdade de Educação Física

Socioeconomic Differences in Preferences and Willingness-to-Pay for Insulin Delivery Systems in Type 1 and Type 2 Diabetes

Background: An evaluation of patients' preferences is necessary to understand the demand for different insulin delivery systems. The aim of this study was to investigate the association between socioeconomic status (SES) and patients' preferences and willingness to pay (WTP) for various attributes of insulin administration for diabetes management. Methods: We conducted a discrete choice experiment (DCE) to determine patients' preferences and their WTP for hypothetical insulin treatments. Both self-reported annual household income and education completed were used to explore differences in treatment preferences and WTP for different attributes of treatment across different levels of SES. Results: The DCE questionnaire was successfully completed by 274 patients. Overall, glucose control was the most valued attribute by all socioeconomic groups, while route of insulin delivery was not as important. Patients with higher incomes were willing to pay significantly more for better glucose control and to avoid adverse events compared to lower income groups. In addition, they were willing to pay more for an oral short-acting insulin ($Can 71.65 [95% confidence interval, $40.68, $102.62]) compared to the low income group ($Can 9.85 [95% confidence interval, 14.86, 34.56; P < 0.01]). Conversely, there were no differences in preferences when the sample was stratified by level of education. Conclusions: This study revealed that preferences and WTP for insulin therapy are influenced by income but not by level of education. Specifically, the higher the income, the greater desire for an oral insulin delivery system, whereas an inhaled route becomes less important for patients.