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Clin Genet ; 2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30417332


Telephone disclosure of cancer genetic test results is noninferior to in-person disclosure. However, how patients who prefer in-person communication of results differ from those who agree to telephone disclosure is unclear but important when considering delivery models for genetic medicine. Patients undergoing cancer genetic testing were recruited to a multicenter, randomized, noninferiority trial (NCT01736345) comparing telephone to in-person disclosure of genetic test results. We evaluated preferences for in-person disclosure, factors associated with this preference and outcomes compared to those who agreed to randomization. Among 1178 enrolled patients, 208 (18%) declined randomization, largely given a preference for in-person disclosure. These patients were more likely to be older (P = 0.007) and to have had multigene panel testing (P < 0.001). General anxiety (P = 0.007), state anxiety (P = 0.008), depression (P = 0.011), cancer-specific distress (P = 0.021) and uncertainty (P = 0.03) were higher after pretest counseling. After disclosure of results, they also had higher general anxiety (P = 0.003), depression (P = 0.002) and cancer-specific distress (P = 0.043). While telephone disclosure is a reasonable alternative to in-person disclosure in most patients, some patients have a strong preference for in-person communication. Patient age, distress and complexity of testing are important factors to consider and requests for in-person disclosure should be honored when possible.

Mol Microbiol ; 107(5): 610-622, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29266479


Lignocellulose degradation by microbes plays a central role in global carbon cycling, human gut metabolism and renewable energy technologies. While considerable effort has been put into understanding the biochemical aspects of lignocellulose degradation, much less work has been done to understand how these enzymes work in an in vivo context. Here, we report a systems level study of xylan degradation in the saprophytic bacterium Cellvibrio japonicus. Transcriptome analysis indicated seven genes that encode carbohydrate active enzymes were up-regulated during growth with xylan containing media. In-frame deletion analysis of these genes found that only gly43F is critical for utilization of xylo-oligosaccharides, xylan, and arabinoxylan. Heterologous expression of gly43F was sufficient for the utilization of xylo-oligosaccharides in Escherichia coli. Additional analysis found that the xyn11A, xyn11B, abf43L, abf43K, and abf51A gene products were critical for utilization of arabinoxylan. Furthermore, a predicted transporter (CJA_1315) was required for effective utilization of xylan substrates, and we propose this unannotated gene be called xntA (xylan transporter A). Our major findings are (i) C. japonicus employs both secreted and surface associated enzymes for xylan degradation, which differs from the strategy used for cellulose degradation, and (ii) a single cytoplasmic ß-xylosidase is essential for the utilization of xylo-oligosaccharides.

J Microbiol Methods ; 130: 136-143, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27664455


Physiological studies of recalcitrant polysaccharide degradation are challenging for several reasons, one of which is the difficulty in obtaining a reproducibly accurate real-time measurement of bacterial growth using insoluble substrates. Current methods suffer from several problems including (i) high background noise due to the insoluble material interspersed with cells, (ii) high consumable and reagent cost and (iii) significant time delay between sampling and data acquisition. A customizable substrate and cell separation device would provide an option to study bacterial growth using optical density measurements. To test this hypothesis we used 3-D printing to create biomass containment devices that allow interaction between insoluble substrates and microbial cells but do not interfere with spectrophotometer measurements. Evaluation of materials available for 3-D printing indicated that UV-cured acrylic plastic was the best material, being superior to nylon or stainless steel when examined for heat tolerance, reactivity, and ability to be sterilized. Cost analysis of the 3-D printed devices indicated they are a competitive way to quantitate bacterial growth compared to viable cell counting or protein measurements, and experimental conditions were scalable over a 100-fold range. The presence of the devices did not alter growth phenotypes when using either soluble substrates or insoluble substrates. We applied biomass containment to characterize growth of Cellvibrio japonicus on authentic lignocellulose (non-pretreated corn stover), and found physiological evidence that xylan is a significant nutritional source despite an abundance of cellulose present.

Bactérias/crescimento & desenvolvimento , Biomassa , Contaminação de Equipamentos , Impressão Tridimensional/instrumentação , Solubilidade , Bactérias/metabolismo , Metabolismo dos Carboidratos , Celulose/metabolismo , Cellvibrio/genética , Cellvibrio/crescimento & desenvolvimento , Cellvibrio/metabolismo , Desenho de Equipamento/economia , Desenho de Equipamento/instrumentação , Lignina/química , Viabilidade Microbiana , Mutação , Nylons/química , Espectrofotometria , Aço Inoxidável/química , Esterilização , Xilanos/metabolismo , Zea mays/química
Breast Cancer Res Treat ; 153(3): 659-67, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26386956


Women living in rural areas of the U.S. face disparities in screening mammography and breast cancer outcomes. We sought to evaluate utilization of mammography, awareness of screening guidelines, and attitudes towards screening among rural insured U.S. women. We conducted a cross-sectional self-administered anonymous survey among 2000 women aged 40-64 insured by the National Rural Electric Cooperative Association, a non-profit insurer for electrical utility workers in predominantly rural areas across the U.S. Outcomes included mammographic screening in the past year, screening interval, awareness of guidelines, and perceived barriers to screening. 1588 women responded to the survey (response rate 79.4 %). 74 % of respondents lived in a rural area. Among women aged 40-49, 66.5 % reported mammographic screening in the past year. 46 % received annual screening, 32 % biennial screening, and 22 % rare/no screening. Among women aged 50-64, 77.1 % reported screening in the past year. 63 % received annual screening, 25 % biennial screening, and 12 % rare/no screening. The majority of women (98 %) believed that the mammography can find breast cancer early and save lives. Less than 1 % of younger women, and only 14 % of women over age 50 identified the recommendations of the U.S. Preventative Services Screening Task Force as the current expert recommendations for screening. Screening practices tended to follow perceived guideline recommendations. When rural U.S. women over age 40 have insurance, most receive breast cancer screening. The screening guidelines of cancer advocacy groups and specialty societies appear more influential and widely recognized than those of the U.S. preventative services taskforce.

Neoplasias da Mama/epidemiologia , Detecção Precoce de Câncer , Conhecimentos, Atitudes e Prática em Saúde , Seguro Saúde , Programas de Rastreamento , Aceitação pelo Paciente de Cuidados de Saúde , Guias de Prática Clínica como Assunto , Adulto , Idoso , Estudos Transversais , Cultura , Feminino , Inquéritos Epidemiológicos , Humanos , Mamografia , Pessoa de Meia-Idade , Percepção , População Rural , Fatores Socioeconômicos , Estados Unidos/epidemiologia
Diabetologia ; 57(11): 2282-95, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25091629


AIMS/HYPOTHESIS: Targeted metabolomic and transcriptomic approaches were used to evaluate the relationship between skeletal muscle metabolite signatures, gene expression profiles and clinical outcomes in response to various exercise training interventions. We hypothesised that changes in mitochondrial metabolic intermediates would predict improvements in clinical risk factors, thereby offering novel insights into potential mechanisms. METHODS: Subjects at risk of metabolic disease were randomised to 6 months of inactivity or one of five aerobic and/or resistance training programmes (n = 112). Pre/post-intervention assessments included cardiorespiratory fitness ([Formula: see text]), serum triacylglycerols (TGs) and insulin sensitivity (SI). In this secondary analysis, muscle biopsy specimens were used for targeted mass spectrometry-based analysis of metabolic intermediates and measurement of mRNA expression of genes involved in metabolism. RESULTS: Exercise regimens with the largest energy expenditure produced robust increases in muscle concentrations of even-chain acylcarnitines (median 37-488%), which correlated positively with increased expression of genes involved in muscle uptake and oxidation of fatty acids. Along with free carnitine, the aforementioned acylcarnitine metabolites were related to improvements in [Formula: see text], TGs and SI (R = 0.20-0.31, p < 0.05). Muscle concentrations of the tricarboxylic acid cycle intermediates succinate and succinylcarnitine (R = 0.39 and 0.24, p < 0.05) emerged as the strongest correlates of SI. CONCLUSIONS/INTERPRETATION: The metabolic signatures of exercise-trained skeletal muscle reflected reprogramming of mitochondrial function and intermediary metabolism and correlated with changes in cardiometabolic fitness. Succinate metabolism and the succinate dehydrogenase complex emerged as a potential regulatory node that intersects with whole-body insulin sensitivity. This study identifies new avenues for mechanistic research aimed at understanding the health benefits of physical activity. Trial registration NCT00200993 and NCT00275145 Funding This work was supported by the National Heart, Lung, and Blood Institute (National Institutes of Health), National Institute on Aging (National Institutes of Health) and National Institute of Arthritis and Musculoskeletal and Skin Diseases (National Institutes of Health).

Exercício/fisiologia , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Adolescente , Adulto , Idoso , Aminoácidos de Cadeia Ramificada/metabolismo , Carnitina/análogos & derivados , Carnitina/metabolismo , Feminino , Humanos , Masculino , Metabolômica , Pessoa de Meia-Idade , Ácido Succínico/metabolismo , Adulto Jovem