Antitumor activities of ATP-competitive inhibitors of mTOR in colon cancer cells.

BACKGROUND: The mammalian target of rapamycin (mTOR) is frequently activated in colon cancers due to mutations in the phosphatidylinositol 3-kinase (PI3K) pathway. Targeting mTOR with allosteric inhibitors of mTOR such as rapamycin reduces colon cancer progression in several experimental models. Recently, a new class of mTOR inhibitors that act as ATP-competitive inhibitors of mTOR, has been developed. The effectiveness of these drugs in colon cancer cells has however not been fully characterized. METHODS: LS174T, SW480 and DLD-1 colon cancer cell lines were treated with PP242 an ATP-competitive inhibitor of mTOR, NVP-BEZ235, a dual PI3K/mTOR inhibitor or rapamycin. Tumor cell growth, proliferation and survival were assessed by MTS assay, 5-bromo-2'-deoxyuridine (BrDU) incorporation or by quantification of DNA fragmentation respectively. In vivo, the anticancer activity of mTOR inhibitors was evaluated on nude mice bearing colon cancer xenografts. RESULTS: PP242 and NVP-BEZ235 reduced the growth, proliferation and survival of LS174T and DLD-1 colon cancer cells more efficiently than rapamycin. Similarly, PP242 and NVP-BEZ235 also decreased significantly the proliferation and survival of SW480 cells which were resistant to the effects of rapamycin. In vivo, PP242 and NVP-BEZ235 reduced the growth of xenografts generated from LS174T and SW480 cells. Finally, we also observed that the efficacy of ATP-competitive inhibitors of mTOR was enhanced by U0126, a MEK inhibitor. CONCLUSIONS: Taken together, these results show that ATP-competitive inhibitors of mTOR are effective in blocking colon cancer cell growth in vitro and in vivo and thus represent a therapeutic option in colon cancer either alone or in combination with MEK inhibitors.

Annual report of the Iowa Highway Research Board Research and Development Activities FY 2006

The Highway Division of the Iowa Department of Transportation engages in research and development for two reasons: first, to find workable solutions to the many problems that require more than ordinary, routine investigation; and second, to identify and implement improved engineering and management practices. This report is submitted in compliance with Sections 310.36 and 312.3A, Code of Iowa, which direct the submission of a report of the Secondary Road Research Fund and the Street Research Fund, respectively. It is a report of the status of research and development projects, which were in progress on June 30, 2006; it is also a report on projects completed during the fiscal year beginning July 1, 2005, and ending June 30, 2006.

MEDICAL STUDENT IN THE FAMILY HEALTH STRATEGY ON THE FIRST YEARS OF COLLEGE: PERCEPTION OF GRADUATES

There is a lack of knowledge about the effective value of the experience gained by medical students who participate in the Family Health Strategy (Estratégia Saúde da Família (ESF)) during the early stages of their medical training. This teaching strategy is based on learning by experiencing the problems that exist in real life. This study proposed to understand the value of this teaching strategy from the viewpoint of the students who had participated, after their graduation. The method adopted was a qualitative study conducted through interviews with students who graduated in the years 2009, 2010 and 2011. The data analysis used the hermeneutic dialectic technique as its model. The graduates considered that this experience enabled them to understand the organization and functioning of the health service and the context of the daily life of the users. This experience facilitated the doctor patient relationship, the development of clinical reasoning and the bond with the user. However the students emphasized that a lack of maturity prevented them gaining a higher level of benefit from the experience. Therefore, although the structure of the course is permeated by advances and challenges, it was concluded that this experience contributed to the student's learning of certain essential elements of medical training.

Contributory factors for the functional independence of oldest old

OBJECTIVE To investigate the socioeconomic and clinical factors that contribute to the functional independence of the oldest old of a community. METHOD Cross-sectional quantitative study whose sample consisted of 214 elderly people registered in Basic Health Units. Data were collected through structured interviews and application of the Functional Independence Measure. We used descriptive statistics, and for association of the variables we used the Student t-test, ANOVA and Tukey's test for multiple comparisons. RESULTS The significant variables that contributed to the functional independence were remaining economically active, practicing physical and leisure activities, having a social life, eating fruits, vegetables and meat. The orientation to conduct these practices reduces the demand for care and help needed in everyday activities. CONCLUSION Maintaining independence is primordial to delay disability and presents itself as an excellent field of work for nursing.

Cytochrome P-450 activities in human and rat brain microsomes.

The role of cytochrome P450 in the metabolism of dextromethorphan, amitriptyline, midazolam, S-mephenytoin, citalopram, fluoxetine and sertraline was investigated in rat and human brain microsomes. Depending on the parameters, the limit of quantification using gas chromatography-mass spectrometry methods was between 1.6 and 20 pmol per incubation, which generally contained 1500 microg protein. Amitriptyline was shown to be demethylated to nortriptyline by both rat and human microsomes. Inhibition studies using ketoconazole, furafylline, sulfaphenazole, omeprazole and quinidine suggested that CYP3A4 is the isoform responsible for this reaction whereas CYP1A2, CYP2C9, CYP2C19 and CYP2D6 do not seem to be involved. This result was confirmed by using a monoclonal antibody against CYP3A4. Dextromethorphan was metabolized to dextrorphan in rat brain microsomes and was inhibited by quinidine and by a polyclonal antibody against CYP2D6. Only the addition of exogenous reductase allowed the measurement of this activity in human brain microsomes. Metabolites of the other substrates could not be detected, possibly due to an insufficiently sensitive method. It is concluded that cytochrome P450 activity in the brain is very low, but that psychotropic drugs could undergo a local cerebral metabolism which could have pharmacological and/or toxicological consequences.

Gentamicin Improves the Activities of Daptomycin and Vancomycin against Enterococcus faecalis In Vitro and in an Experimental Foreign-Body Infection Model.

For enterococcal implant-associated infections, the optimal treatment regimen has not been defined. We investigated the activity of daptomycin, vancomycin, and gentamicin (and their combinations) against Enterococcus faecalis in vitro and in a foreign-body infection model. Antimicrobial activity was investigated by time-kill and growth-related heat production studies (microcalorimetry) as well as with a guinea pig model using subcutaneously implanted cages. Infection was established by percutaneous injection of E. faecalis in the cage. Antibiotic treatment for 4 days was started 3 h after infection. Cages were removed 5 days after end of treatment to determine the cure rate. The MIC, the minimal bactericidal concentration (MBC) in the logarithmic phase, and the MBC in the stationary phase were 1.25, 5, and >20 μg/ml for daptomycin, 1, >64, and >64 μg/ml for vancomycin, and 16, 32, and 4 μg/ml for gentamicin, respectively. In vitro, gentamicin at subinhibitory concentrations improved the activity against E. faecalis when combined with daptomycin or vancomycin in the logarithmic and stationary phases. In the animal model, daptomycin cured 25%, vancomycin 17%, and gentamicin 50% of infected cages. In combination with gentamicin, the cure rate for daptomycin increased to 55% and that of vancomycin increased to 33%. In conclusion, daptomycin was more active than vancomycin against adherent E. faecalis, and its activity was further improved by the addition of gentamicin. Despite a short duration of infection (3 h), the cure rates did not exceed 55%, highlighting the difficulty of eradicating E. faecalis from implants already in the early stage of implant-associated infection.

Validity of the Katz Index to assess activities of daily living by informants in neuropathological studies

Abstract OBJECTIVE To analyze the evidences of construct validity of the Katz Index for the retrospective assessment of activities of daily living (ADL) by informants, to assist neuropathological studies in the elderly. METHOD A cross-sectional study analyzed the functional ability of ADL measure by the Katz Index, of 650 cases randomly selected from the Brazilian Brain Bank of the Ageing Brain Study Group (BBBABSG) database. Sample was divided in two subsamples for the analysis (N=325, each) and then stratified according to cognitive decline assessed by the Clinical Dementia Rating Scale (CDR). Factor analyses with calculations of internal consistency and invariance were performed. RESULTS Factor analysis evidenced a unidimensional instrument with optimal internal consistency, in all subgroups. Goodness of fit indices were obtained after two treatments of covariance, indicating adequacy of the scale for assessing ADL by informants. The scale is invariant to cognitive decline meaning that it can be used for subjects with or without cognitive impairment. CONCLUSION Katz Index is valid for the retrospective assessment of basic ADL by informants, with optimal reliability.

Padrão de intervenções de enfermagem realizadas em vítimas de trauma segundo o Nursing Activities Score

RESUMO Objetivo Identificar o padrão de intervenções de enfermagem realizadas em vítimas de trauma nas primeiras 24 horas de internação na Unidade de Terapia Intensiva (UTI). Método Estudo prospectivo, realizado na UTI de um hospital em São Paulo, Brasil. O instrumento Nursing Activities Score (NAS) foi utilizado para identificar as intervenções de enfermagem. Resultados A casuística foi composta por 200 pacientes, a maioria homens, com idade média de 40,7 anos, vítimas de acidentes de transporte. A média do NAS foi de 71,3% e o padrão de intervenções de enfermagem identificado incluiu as atividades de monitorização e controles; investigações laboratoriais; medicação, exceto drogas vasoativas; procedimentos de higiene; cuidados com drenos; mobilização e posicionamento; suporte e cuidado aos familiares e pacientes; tarefas administrativas e gerenciais; suporte respiratório; cuidado com vias aéreas artificiais; e tratamento para melhora da função pulmonar. Nas intervenções de monitorização e mobilização, houve a necessidade de cuidados além do normalmente requerido por pacientes de UTI. Conclusão Os resultados desta pesquisa trazem importantes contribuições para o planejamento de ações que visem a capacitação e o dimensionamento da equipe de enfermagem na unidade crítica.

Carga de trabalho de enfermagem: preditor de infecção relacionada à assistência à saúde na terapia intensiva?

RESUMO Objetivo Analisar a influência da carga de trabalho de enfermagem na ocorrência de infecção relacionada à assistência à saúde (IRAS) em pacientes na Unidade de Terapia Intensiva (UTI), segundo o tipo de tratamento. Método Estudo de coorte retrospectivo desenvolvido em nove UTI em São Paulo, Brasil, de setembro a dezembro de 2012. A carga de trabalho de enfermagem foi mensurada pelo Nursing Activities Score (NAS). Os testes T-Student, Exato de Fisher e regressões logísticas foram utilizados nas análises. Resultados A casuística foi composta por 835 pacientes (54,3±17,3 anos; 57,5% do sexo masculino), dentre os quais 12,5% adquiriram IRAS na UTI. O NAS dos pacientes admitidos para tratamento clínico foi de 71,3±10,9 e para cirúrgico, 71,6±9,2. O tempo de permanência na unidade e a gravidade foram fatores preditivos para ocorrência de IRAS em pacientes admitidos nas UTI para tratamento clínico ou cirúrgico e o sexo masculino apenas para pacientes cirúrgicos. Ao considerar as admissões independentes do tipo de tratamento, além das variáveis citadas, o índice de comorbidades também permaneceu no modelo de regressão. O NAS não foi fator preditivo de IRAS. Conclusão A carga de trabalho de enfermagem não exerceu influência na ocorrência de IRAS nos pacientes deste estudo.

Iowa College Student Aid Commission Performance Report, FY 2007

Agency Performance Report

Avaliação da carga de trabalho no pós-operatório de cirurgia cardíaca segundo o Nursing Activities Score

RESUMO Objetivo Identificar os fatores associados à carga de trabalho de enfermagem no cuidado a pacientes no pós-operatório de cirurgia cardíaca. Método Estudo de coorte prospectivo, conduzido com 187 pacientes da Unidade de Terapia Intensiva Cirúrgica (UTI) do Instituto do Coração. Os dados foram coletados nas primeiras 24 e 72 horas do paciente na UTI. A variável dependente foi a carga de trabalho calculada por meio do Nursing Activities Score (NAS) e as independentes foram de natureza demográfico-clínicas e escores de morbimortalidade. Para análise dos dados utilizou-se os testes de Wilcoxon-Mann-Whitney e de correlação de Spearman, e a regressão linear com modelo de efeitos mistos. Resultados A maioria dos pacientes era do sexo masculino (59,4%), com média de idade de 61 anos (±12,7) e 43,9% desenvolveram algum tipo de complicação no pós-operatório. Nas 24 horas, a carga de trabalho foi de 82,4% (±3,4) e foi de 58,1% (±3,4) nas 72 horas. Os fatores associados ao aumento do NAS foram: tempo de internação do paciente na UTI (p=0,036) e a presença de complicações (p<0,001). Conclusão A gravidade do paciente nas 24 horas, em oposição a inúmeros estudos, não influenciou no aumento da carga de trabalho, a qual se mostrou associada ao tempo de internação e às complicações.

Interrater reliability of Nursing Activities Score among Intensive Care Unit health professionals

ABSTRACT Objective To analyze the interrater reliability of NAS among critical care nurses and managers in an ICU. Method This was a methodological study performed in an adult, general ICU in Norway. In a random selection of patients, the NAS was scored on 101 patients by three raters: a critical care nurse, an ICU physician and a nurse manager. Interrater reliability was analyzed by agreement between groups and kappa statistics. Results The mean NAS were 88.4 (SD=16.2) and 88.7 (SD=24.5) respectively for the critical care nurses and nurse managers. A lower mean of 83.7 (SD=21.1) was found for physicians. The 18 medical interventions showed higher agreement between critical care nurses and physicians (85.6%), than between critical care nurses and nurse managers (78.7). In the five nursing activities the Kappa-coefficients were low for all activities in all compared groups. Conclusion The study indicated a satisfactory agreement of nursing workload between critical care nurses and managers.