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1.
Support Care Cancer ; 25(11): 3495-3504, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28612159

RESUMO

PURPOSE: The aims of this study were to identify the work ability (WA) of breast cancer (BC) survivors during the course of their illness, and the relationships between personal-, disease-, and work-related factors, and their WA. METHODS: This is a cross-sectional survey study. One hundred fifty-one participants with the response rate of 88.9% were recruited from the community in 2014 and 2015. RESULTS: BC survivors' WA was at its highest before diagnosis, and then dropped to the lowest during treatment. Although their current WA had improved, it has not bounced back to that before diagnosis. The resignation rate was 35.8%. Factors positively associated with current WA included (a) age and year of diagnosis, (b) physical and psychological health and (c) WA before diagnosis or during treatment, working years, work control and mastery. However, compliance with appropriate healthy eating habits and believing in personal health controlled by chance were negatively associated with current WA. Furthermore, the participants would more likely to have higher current WA if they (a) were more optimistic with good stress management; (b) currently were not receiving treatment or other illnesses; (c) perceived less effects of their health problems, physical workloads or their cancer diagnoses on their work and (d) perceived continue to work in the next 2 years, with good ability to handle physical and mental work. CONCLUSIONS: This study confirmed that most BC survivors continued to work after their diagnoses. The factors affecting their WA were multifactorial. It is important to enhance their positive thinking.


Assuntos
Neoplasias da Mama/reabilitação , Retorno ao Trabalho/psicologia , Sobreviventes/psicologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , Carga de Trabalho , Adulto Jovem
2.
Drugs ; 76(5): 567-88, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26863149

RESUMO

Eravacycline is an investigational, synthetic fluorocycline antibacterial agent that is structurally similar to tigecycline with two modifications to the D-ring of its tetracycline core: a fluorine atom replaces the dimethylamine moiety at C-7 and a pyrrolidinoacetamido group replaces the 2-tertiary-butyl glycylamido at C-9. Like other tetracyclines, eravacycline inhibits bacterial protein synthesis through binding to the 30S ribosomal subunit. Eravacycline demonstrates broad-spectrum antimicrobial activity against Gram-positive, Gram-negative, and anaerobic bacteria with the exception of Pseudomonas aeruginosa. Eravacycline is two- to fourfold more potent than tigecycline versus Gram-positive cocci and two- to eightfold more potent than tigecycline versus Gram-negative bacilli. Intravenous eravacycline demonstrates linear pharmacokinetics that have been described by a four-compartment model. Oral bioavailability of eravacycline is estimated at 28 % (range 26-32 %) and a single oral dose of 200 mg achieves a maximum plasma concentration (C max) and area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) of 0.23 ± 0.04 mg/L and 3.34 ± 1.11 mg·h/L, respectively. A population pharmacokinetic study of intravenous (IV) eravacycline demonstrated a mean steady-state volume of distribution (V ss) of 320 L or 4.2 L/kg, a mean terminal elimination half-life (t ½) of 48 h, and a mean total clearance (CL) of 13.5 L/h. In a neutropenic murine thigh infection model, the pharmacodynamic parameter that demonstrated the best correlation with antibacterial response was the ratio of area under the plasma concentration-time curve over 24 h to the minimum inhibitory concentration (AUC0-24h/MIC). Several animal model studies including mouse systemic infection, thigh infection, lung infection, and pyelonephritis models have been published and demonstrated the in vivo efficacy of eravacycline. A phase II clinical trial evaluating the efficacy and safety of eravacycline in the treatment of community-acquired complicated intra-abdominal infection (cIAI) has been published as well, and phase III clinical trials in cIAI and complicated urinary tract infection (cUTI) have been completed. The eravacycline phase III program, known as IGNITE (Investigating Gram-Negative Infections Treated with Eravacycline), investigated its safety and efficacy in cIAI (IGNITE 1) and cUTI (IGNITE 2). Eravacycline met the primary endpoint in IGNITE 1, while data analysis for IGNITE 2 is currently ongoing. Common adverse events reported in phase I-III studies included gastrointestinal effects such as nausea and vomiting. Eravacycline is a promising intravenous and oral fluorocycline that may offer an alternative treatment option for patients with serious infections, particularly those caused by multidrug-resistant Gram-negative pathogens.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Tetraciclinas/farmacologia , Animais , Antibacterianos/farmacocinética , Disponibilidade Biológica , Ensaios Clínicos como Assunto , Meia-Vida , Humanos , Testes de Sensibilidade Microbiana/métodos , Minociclina/análogos & derivados , Minociclina/farmacocinética , Minociclina/farmacologia , Tetraciclinas/farmacocinética , Tigeciclina
3.
Science ; 337(6100): 1353-6, 2012 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-22984072

RESUMO

The dimorphic switch from a single-cell budding yeast to a filamentous form enables Saccharomyces cerevisiae to forage for nutrients and the opportunistic pathogen Candida albicans to invade human tissues and evade the immune system. We constructed a genome-wide set of targeted deletion alleles and introduced them into a filamentous S. cerevisiae strain, Σ1278b. We identified genes involved in morphologically distinct forms of filamentation: haploid invasive growth, biofilm formation, and diploid pseudohyphal growth. Unique genes appear to underlie each program, but we also found core genes with general roles in filamentous growth, including MFG1 (YDL233w), whose product binds two morphogenetic transcription factors, Flo8 and Mss11, and functions as a critical transcriptional regulator of filamentous growth in both S. cerevisiae and C. albicans.


Assuntos
Candida albicans/crescimento & desenvolvimento , Candida albicans/genética , Regulação Fúngica da Expressão Gênica , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/genética , Alelos , Biofilmes/crescimento & desenvolvimento , Candida albicans/citologia , Análise Mutacional de DNA , Deleção de Genes , Hifas/genética , Hifas/crescimento & desenvolvimento , Proteínas Nucleares/genética , Saccharomyces cerevisiae/citologia , Proteínas de Saccharomyces cerevisiae/genética , Transativadores/genética , Fatores de Transcrição/genética , Transcrição Gênica
4.
Science ; 328(5977): 469, 2010 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-20413493

RESUMO

We generated a high-resolution whole-genome sequence and individually deleted 5100 genes in Sigma1278b, a Saccharomyces cerevisiae strain closely related to reference strain S288c. Similar to the variation between human individuals, Sigma1278b and S288c average 3.2 single-nucleotide polymorphisms per kilobase. A genome-wide comparison of deletion mutant phenotypes identified a subset of genes that were conditionally essential by strain, including 44 essential genes unique to Sigma1278b and 13 unique to S288c. Genetic analysis indicates the conditional phenotype was most often governed by complex genetic interactions, depending on multiple background-specific modifiers. Our comprehensive analysis suggests that the presence of a complex set of modifiers will often underlie the phenotypic differences between individuals.


Assuntos
Regulação Fúngica da Expressão Gênica , Genes Essenciais , Genes Fúngicos , Saccharomyces cerevisiae/genética , Cruzamentos Genéticos , Deleção de Genes , Redes Reguladoras de Genes , Variação Genética , Genoma Fúngico , Genótipo , Mutação , Fenótipo , Análise de Sequência de DNA
5.
Brain Lang ; 89(1): 108-14, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15010242

RESUMO

Many studies have found that patients with Alzheimer's disease (AD) perform significantly worse than normal controls on verbal fluency tasks. Moreover, some studies have found that AD patients' deficits compared to controls are more severe for semantic fluency (e.g., vegetables) than for letter fluency (e.g. words that begin with F). These studies, however, have not taken category size into account. A comparison of AD patients and age-matched controls on three semantic and three letter categories revealed that both the size and type of a category significantly predicted AD patients' deficits on verbal fluency tasks. These results suggest that the verbal fluency of AD patients will be most attenuated on large semantic categories.


Assuntos
Doença de Alzheimer/diagnóstico , Semântica , Medida da Produção da Fala , Idoso , Doença de Alzheimer/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tempo de Reação , Valores de Referência
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