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1.
Cancer Causes Control ; 29(7): 619-630, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29761303

RESUMO

There have been few published studies on differences between Blacks and Whites in the estimated effects of alcohol and tobacco use on the incidence of head and neck cancer (HNC) in the United States. Previous studies have been limited by small numbers of Blacks. Using pooled data from 13 US case-control studies of oral, pharyngeal, and laryngeal cancers in the International Head and Neck Cancer Epidemiology Consortium, this study comprised a large number of Black HNC cases (n = 975). Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for several tobacco and alcohol consumption characteristics. Blacks were found to have consistently stronger associations than Whites for the majority of tobacco consumption variables. For example, compared to never smokers, Blacks who smoked cigarettes for > 30 years had an OR 4.53 (95% CI 3.22-6.39), which was larger than that observed in Whites (OR 3.01, 95% CI 2.73-3.33; pinteraction < 0.0001). The ORs for alcohol use were also larger among Blacks compared to Whites. Exclusion of oropharyngeal cases attenuated the racial differences in tobacco use associations but not alcohol use associations. These findings suggest modest racial differences exist in the association of HNC risk with tobacco and alcohol consumption.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Grupos Raciais/estatística & dados numéricos , Uso de Tabaco/epidemiologia , Estudos de Casos e Controles , Humanos , Fatores de Risco , Estados Unidos/epidemiologia
2.
Int J Gynaecol Obstet ; 145(3): 293-299, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30929251

RESUMO

OBJECTIVE: To assess the effect of length of hospital stay on postoperative outcomes after minimally invasive hysterectomy. METHODS: A retrospective cohort analysis was conducted of women who underwent minimally invasive hysterectomy (vaginal or laparoscopic) for benign conditions between January 1, 2014 and December 31, 2016, using the American College of Surgeons National Surgical Quality Improvement Program database. Patient information and 30-day outcomes were compared using multivariable logistic regression after adjusting for patient demographics and medical and procedure variables. RESULTS: The analysis included 31 347 patients. Women discharged the day after surgery were more likely to be African-American, older, have prior abdominal surgery, and a higher ASA classification. Prevalence of organ space infection and readmissions were lower in the same day discharge group. No differences between same- and next-day discharge were found for surgical site infection or urinary tract infection (adjusted odds ratios (aORs) 0.83 (95% [CI] 0.65-1.07; P=0.156) and 0.85 (95% CI 0.68-1.06; P=0.151), respectively). Same-day hospital discharge was associated with a reduced chance of readmission (aOR=0.68, 95% CI 0.54-0.87; P=0.002). CONCLUSION: Same-day hospital discharge after minimally invasive hysterectomy lowered the risk of readmission and did not increase the risk of postoperative complications.


Assuntos
Histerectomia/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Adulto , Feminino , Humanos , Histerectomia/métodos , Laparoscopia/métodos , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , Melhoria de Qualidade , Estudos Retrospectivos
3.
Mol Cell Biol ; 37(12)2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28320873

RESUMO

Tubulointerstitial fibrosis (TIF) is recognized as a final phenotypic manifestation in the transition from chronic kidney disease (CKD) to end-stage renal disease (ESRD). Here we show that conditional inactivation of Sav1 in the mouse renal epithelium resulted in upregulated expression of profibrotic genes and TIF. Loss of Sav1 induced Stat3 activation and a senescence-associated secretory phenotype (SASP) that coincided with the development of tubulointerstitial fibrosis. Treatment of mice with the YAP inhibitor verteporfin (VP) inhibited activation of genes associated with senescence, SASPs, and activation of Stat3 as well as impeded the development of fibrosis. Collectively, our studies offer novel insights into molecular events that are linked to fibrosis development from Sav1 loss and implicate VP as a potential pharmacological inhibitor to treat patients at risk for developing CKD and TIF.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Senescência Celular , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Fator de Transcrição STAT3/metabolismo , Injúria Renal Aguda/genética , Injúria Renal Aguda/patologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Ácidos Aristolóquicos , Senescência Celular/efeitos dos fármacos , Senescência Celular/genética , Colágeno/metabolismo , Fibrose , Deleção de Genes , Regulação da Expressão Gênica/efeitos dos fármacos , Nefropatias/genética , Nefropatias/patologia , Túbulos Renais/efeitos dos fármacos , Camundongos Knockout , Fenótipo , Fosfoproteínas/metabolismo , Porfirinas/farmacologia , Verteporfina , Proteínas de Sinalização YAP
4.
J Vis Exp ; (115)2016 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-27768027

RESUMO

In this demonstration, spheroids formed from the ß-TC6 insulinoma cell line were cultured as a model of manufacturing a mammalian islet cell product to demonstrate how regulating nutrient levels can improve cell yields. In previous studies, bioreactors facilitated increased culture volumes over static cultures, but no increase in cell yields were observed. Limitations in key nutrients such as glucose, which were consumed between batch feedings, can lead to limitations in cell expansion. Large fluctuations in glucose levels were observed, despite the increase in glucose concentrations in the media. The use of continuous feeding systems eliminated fluctuations in glucose levels, and improved cell growth rates when compared with batch fed static and SSB culture methods. Additional increases in growth rates were observed by adjusting the feed rate based on calculated nutrient consumption, which allowed the maintenance of physiological glucose over three weeks in culture. This method can also be adapted for other cell types.


Assuntos
Técnicas de Cultura de Células , Animais , Reatores Biológicos , Linhagem Celular , Meios de Cultura , Glucose , Ácido Láctico , Mamíferos
5.
PLoS One ; 8(10): e76611, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24204645

RESUMO

Cellular therapies are emerging as a standard approach for the treatment of several diseases. However, realizing the promise of cellular therapies across the full range of treatable disorders will require large-scale, controlled, reproducible culture methods. Bioreactor systems offer the scale-up and monitoring needed, but standard stirred bioreactor cultures do not allow for the real-time regulation of key nutrients in the medium. In this study, ß-TC6 insulinoma cells were aggregated and cultured for 3 weeks as a model of manufacturing a mammalian cell product. Cell expansion rates and medium nutrient levels were compared in static, stirred suspension bioreactors (SSB), and continuously fed (CF) SSB. While SSB cultures facilitated increased culture volumes, no increase in cell yields were observed, partly due to limitations in key nutrients, which were consumed by the cultures between feedings, such as glucose. Even when glucose levels were increased to prevent depletion between feedings, dramatic fluctuations in glucose levels were observed. Continuous feeding eliminated fluctuations and improved cell expansion when compared with both static and SSB culture methods. Further improvements in growth rates were observed after adjusting the feed rate based on calculated nutrient depletion, which maintained physiological glucose levels for the duration of the expansion. Adjusting the feed rate in a continuous medium replacement system can maintain the consistent nutrient levels required for the large-scale application of many cell products. Continuously fed bioreactor systems combined with nutrient regulation can be used to improve the yield and reproducibility of mammalian cells for biological products and cellular therapies and will facilitate the translation of cell culture from the research lab to clinical applications.


Assuntos
Técnicas de Cultura Celular por Lotes , Reatores Biológicos , Meios de Cultura/química , Esferoides Celulares , Animais , Técnicas de Cultura Celular por Lotes/instrumentação , Técnicas de Cultura Celular por Lotes/métodos , Linhagem Celular , Proliferação de Células , Terapia Baseada em Transplante de Células e Tecidos/métodos , Glucose/química , Glucose/metabolismo , Humanos , Esferoides Celulares/metabolismo , Fatores de Tempo
6.
Regen Med ; 7(5): 685-95, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22954439

RESUMO

Numerous advances have been made in pancreatic ß-cell replacement therapies for diabetes mellitus. While these therapies provide a positive impact and possible cure for the individual recipient, access is limited by availability of donor tissues. The derivation of pluripotent stem cells using efficient differentiation technologies has resulted in the generation of insulin-producing cells with characteristics similar to islet ß-cells. Experimental transplantation studies have shown that these cells are capable of reducing hyperglycemia in short-term assays. Novel methodologies that facilitate the neogenesis of ß-cells from endogenous hepatic or pancreatic tissue sources are also being investigated as a ß-cell replacement strategy. Further research is necessary to protect these transplanted or regenerated cells from diabetic autoimmune pathology.


Assuntos
Técnicas de Cultura de Células/métodos , Diabetes Mellitus/terapia , Células Secretoras de Insulina/transplante , Medicina Regenerativa , Animais , Modelos Animais de Doenças , Humanos , Células-Tronco Pluripotentes/citologia
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