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1.
JSES Int ; 8(2): 282-286, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38464451

RESUMO

Background: To compare the complications and efficacy of pain relief of the interscalene anesthetic block using either a single-injection (SI) vs. a continuous, indwelling catheter (CIC) for arthroscopic rotator cuff repair surgery. Methods: Patients undergoing primary, arthroscopic rotator cuff repair without concomitant open procedure or biceps tenodesis were prospectively enrolled by 4 fellowship-trained sports medicine and shoulder surgeons. Patients received either a SI or CIC preoperatively based on surgeon preference. Patients were contacted by phone to complete a standard questionnaire on postoperative days (PODs) 1, 3, 7, 14, and 28. Patients were asked to rate the efficacy of their subjective pain relief (scale of 0-10), document issues with the catheter, describe analgesic usage, and report pharmacological and medical complications. The primary outcome was measured as complication rate. Postoperative narcotic use, patient satisfaction, and visual analog scale pain scores were measured as secondary outcomes. Results: Seventy patients were enrolled, 33 CIC patients (13 male, 20 female, mean age 61 ± 8 years) and 37 SI patients (20 male, 17 female, mean age 59 ± 10 years). There were significantly more injection/insertion site complications in the CIC group (48%) vs. the SI group (11%, P = .001). The incidence of motor weakness was higher in the CIC group on POD 1 (P = .034), but not at any subsequent time points. On POD 1, CIC patients had a clinically significantly lower pain score compared to SI (3.2 vs. 5.4; P = .020). Similar scores were observed at subsequent time points until POD 28, when CIC again had a lower pain score (0.8 vs. 2.7; P = .005). However, this did not reach clinical significance. All patients in both groups rated a satisfaction of 9 or 10 (scale 0-10) with the anesthesia provided by their nerve block. Conclusion: CIC interscalene nerve blocks had an increased risk for injection site complications and minor complications in the immediate postoperative period when using the CIC for arthroscopic rotator cuff repair without any concomitant open procedures. CIC blocks demonstrated clinically significant superior pain relief on POD 1 but were equal to SI blocks at every time point thereafter. Superior pain relief of CIC at POD 28 was not clinically significant. CIC catheters do not appear to markedly decrease the use of postoperative narcotics. Despite this trend in complication rates and pain scores, all patients in both groups were satisfied with their nerve block.

2.
World Neurosurg ; 181: e192-e202, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37777175

RESUMO

BACKGROUND: The impact of Medicaid status on survival outcomes of patients with spinal primary malignant bone tumors (sPMBT) has not been investigated. METHODS: Using the SEER-Medicaid database, adults diagnosed between 2006 and 2013 with sPMBT including chordoma, osteosarcoma, chondrosarcoma, Ewing sarcoma, or malignant giant cell tumor (GCT) were studied. Five-year survival analysis was performed using the Kaplan-Meier method. Adjusted survival analysis was performed using Cox proportional-hazards regression controlling for age, sex, marital status, cancer stage, poverty level, vertebral versus sacral location, geography, rurality, tumor diameter, tumor grade, tumor histology, and therapy. RESULTS: A total of 572 patients with sPMBT (Medicaid: 59, non-Medicaid: 513) were identified. Medicaid patients were more likely to be younger (P < 0.001), Black (P < 0.001), live in high poverty neighborhoods (P = 0.006), have distant metastases at diagnosis (P < 0.001), and less likely to receive surgery (P = 0.006). The 5-year survival rate was 65.7% (chondrosarcoma: 70.0%, chordoma: 91.5%, Ewing sarcoma: 44.6%, GCT: 90.0%, osteosarcoma: 34.2%). Medicaid patients had significantly worse 5-year survival than non-Medicaid patients (52.0% vs. 67.2%, P = 0.02). Minority individuals on Medicaid were associated with an increased risk of cancer-specific mortality compared with White non-Medicaid patients (adjusted hazard ratio [aHR] = 2.51, [95% CI 1.18-5.35], P = 0.017). Among Medicaid patients, those who received surgery had significantly better survival than those who did not (64.5% vs. 30.6%, P = 0.001). For all patients, not receiving surgery (aHR = 1.90 [1.23-2.95], P = 0.004) and tumor diameter >50 mm (aHR=1.89 [1.10-3.25], P = 0.023) were associated with an increased risk of mortality. CONCLUSIONS: Medicaid patients may be less likely to receive surgery and suffer from poorer survival. These disparities may be especially prominent among minorities.


Assuntos
Neoplasias Ósseas , Condrossarcoma , Cordoma , Osteossarcoma , Sarcoma de Ewing , Neoplasias da Coluna Vertebral , Adulto , Estados Unidos/epidemiologia , Humanos , Sarcoma de Ewing/cirurgia , Medicaid , Cordoma/cirurgia , Neoplasias da Coluna Vertebral/patologia , Programa de SEER , Osteossarcoma/patologia , Condrossarcoma/cirurgia , Neoplasias Ósseas/patologia , Medição de Risco
3.
Ophthalmic Epidemiol ; : 1-7, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37964586

RESUMO

PURPOSE: The survival outcomes of patients with primary uveal melanomas based on Medicaid status have not been previously discussed in the literature. METHODS: The Surveillance, Epidemiology, and End Results Medicaid database were utilized to identify patients with primary uveal melanomas diagnosed between 2006 and 2013. The Kaplan-Meier method was utilized to construct 5-year survival curves in adult, non-elderly patients. Log-rank testing was used to determine differences in survival rates, and multivariate Cox proportional hazards modeling was utilized to perform adjusted survival analysis. RESULTS: A total of 1,765 patients were included (Medicaid: 81, non-Medicaid: 1684). A total of 1683 (95.4%) were White. The average age was 51.75 years (SD = 9.5 years). Medicaid patients were more likely to be unmarried, live in a high poverty neighborhood, and live in a rural area (all p < .001). We observed no significant difference in 5-year survival rates between those enrolled in Medicaid (86.6%, 95% CI: 79.1%1-94.7%) and those not enrolled in Medicaid (85.5, 95% CI: 83.8%-87.2%) (p = .80). After controlling for socioeconomic and clinical factors, Medicaid enrollment was not associated with an increased risk of mortality compared to non-Medicaid enrollment. Age (aHR: 1.04, 95% CI: 1.02-1.06, p < .001) and tumor size >10 mm (aHR: 3.04, 95% CI: 1.49-6.21, p = .002) were associated with an increased risk of mortality. CONCLUSION: Medicaid enrollment was not associated with worse cancer-specific 5-year survival. Further research needs to be elicited to better understand the role of Medicaid enrollment in patients with primary uveal melanoma.

4.
Ann Biomed Eng ; 51(8): 1738-1746, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36966247

RESUMO

Single ventricle physiology (SVP) is used to describe any congenital heart lesion that is unable to support independent pulmonary and systemic circulations. Current treatment strategies rely on a series of palliation surgeries that culminate in the Fontan physiology, which relies on the single functioning ventricle to provide systemic circulation while passively routing venous return through the pulmonary circulation. Despite significant reductions in early mortality, the presence of atrioventricular valve (AVV) regurgitation is a key predictor of heart failure in these patients. We sought to evaluate the biomechanical changes associated with the AVV in SVP physiologies. Left and right ventricles were sutured onto patient-derived 3D-printed mounts and mounted into an ex vivo systemic heart simulator capable of reproducing Norwood, Glenn, Fontan and Late Fontan physiologies. We found that the tricuspid anterior leaflet experienced elevated maximum force, average force, and maximum yank compared to the posterior and septal leaflets. Between physiologies, maximum yank was greatest in the Norwood physiology relative to the Glenn, Fontan, and Late Fontan physiologies. These contrasting trends suggest that long- and short-term mechanics of AVV failure in single ventricle differ and that AVV interventions should account for asymmetries in force profiles between leaflets and physiologies.


Assuntos
Técnica de Fontan , Cardiopatias Congênitas , Humanos , Resultado do Tratamento , Estudos Retrospectivos , Valvas Cardíacas , Ventrículos do Coração
5.
Ann Thorac Surg ; 116(6): 1241-1248, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-35835207

RESUMO

BACKGROUND: Infants account for a significant proportion of pediatric heart transplantation but also suffer from a high waitlist mortality. Donor oversizing by weight-based criteria is common practice in transplantation and is prevalent in this group. We sought to analyze the impact of oversizing on outcomes in infants. METHODS: Infant heart transplantations reported to the United Network for Organ Sharing from January 1994 to September 2019 were retrospectively analyzed. 2384 heart transplantation recipients were divided into quintiles (Q1-Q5) on the basis of donor-to-recipient weight ratio (DRWR). Multivariate Cox regression was used to estimate the effect of DRWR. The primary end point was graft survival at 1 year. RESULTS: The median DRWR for each quintile was 0.90 (0.37-1.04), 1.17 (1.04-1.29), 1.43 (1.29-1.57), 1.74 (1.58-1.97), and 2.28 (1.97-5.00). Pairwise comparisons showed improved survival for Q3 and Q4 over each of the bottom 2 quintiles and the top quintile. Regression analyses found that Q3 and Q4 were protective against graft failure compared with the bottom 2 quintiles. There was no difference in hazard among the top 3 quintiles. Significant covariates included primary diagnosis, ischemia time, serum bilirubin level, transplantation year, mechanical ventilation at transplantation, and extracorporeal membrane oxygenation at transplantation. Sex, female-to-male transplantation, and mechanical circulatory support at transplantation were not significant in univariate analyses. CONCLUSIONS: Modest oversizing by DRWR (1.29-1.97) is associated with increased survival and lower risk in infant heart transplantation. Additional investigation is needed to establish best practices for size matching in this population.


Assuntos
Transplante de Coração , Doadores de Tecidos , Humanos , Criança , Lactente , Masculino , Feminino , Estudos Retrospectivos , Análise de Regressão , Sistema de Registros , Sobrevivência de Enxerto
6.
Eur J Surg Oncol ; 49(4): 794-801, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36503726

RESUMO

BACKGROUND: Previous studies have demonstrated disparities in survival surrounding hepatocellular carcinoma (HCC) across a variety of socio-demographic factors; however, the relationship between Medicaid-status and HCC survival is poorly understood. METHODS: We constructed 5-year, disease-specific survival curves using the Kaplan-Meier method and performed an adjusted survival analysis using multivariate Cox-proportional hazard regression. RESULTS: We analyzed 17,059 non-elderly patients (12,194 non-Medicaid, 4875 Medicaid) diagnosed between 2006 and 2013 and found that Medicaid status was not associated with higher risk of diseases-specific death compared to other insurance types (p = .232, aHR 1.02, 95% CI: 0.983-1.07) after for controlling for a variety of co-variates (ie. marital status, urbanicity, etc.). We found no difference in the risk of death between patients enrolled in Medicaid for more than three years versus those enrolled for less than three years. In all models, rurality and unmarried status were also associated with an increased risk of death (aHR 1.11, 95% CI: 1.03-1.18, p = .002 and aHR 1.18, 95% CI: 1.13-1.23, p < .001, respectively). DISCUSSION: Those enrolled in Medicaid prior to HCC diagnosis may not be associated with a higher risk of disease-specific death compared to non-Medicaid enrolled patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Medicaid , Análise de Sobrevida , Medição de Risco , Disparidades em Assistência à Saúde
7.
Clin Ophthalmol ; 16: 3457-3479, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36267681

RESUMO

Purpose: Motorcycle-related injuries involving the eye and orbit are not well characterized, with a paucity of prospective studies focusing specifically on motorcycle-associated eye injuries nor literature reviews having been conducted on the subject. To better understand the injury types and descriptive characteristics of patients experiencing motorcycle-associated eye injuries, we sought to conduct a narrative review. Methods: The research team utilized the following databases: PubMed, EMBASE, and Web of Science to query for English articles from peer-reviewed journals that provided some patient data regarding eye injury due to motorcycle or moped accidents or usage. Results: A total of 65 studies were included in our qualitative synthesis. Of these studies, 40 (61.5%) were case reports, 20 retrospective case series (30.8%), and five (7.69%) were observational prospective studies. Among the 25 retrospective and prospective studies, 12 (48.0%) of these studies primarily focused on motorcycle-associated injuries. These 65 studies described a wide variety of motorcycle-associated eye injuries, including but not limited to orbital fractures and associated sequelae, foreign bodies, vitreoretinal trauma, neuro-ophthalmic trauma, corneal injuries, open globe injuries, lacerations, and globe avulsions. Conclusion: The current state of the literature indicates that knowledge regarding the ocular manifestations of motorcycle accidents is limited to mostly case reports and few retrospective cohort studies focused specifically on motorcycle-associated eye injuries. However, it is evident that the types of motorcycle-associated eye injuries are legion and predominantly seen in adult males, potentially leading to severe injuries and loss of vision and blindness.

8.
J Heart Lung Transplant ; 41(12): 1790-1797, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36210265

RESUMO

BACKGROUND: Predicted Heart Mass (PHM) has emerged as an attractive size matching metric in adult cardiac transplantation. However, since PHM was derived from a healthy adult cohort, its generalizability to the pediatric population is unclear. We hypothesize that PHM can be extended to older adolescents, and potentially broaden the donor pool available to this group. METHODS: The United Network for Organ Sharing database was retrospectively analyzed for patients aged 13 to 18 undergoing heart transplantation. Recipients were divided into quintiles (Q1-Q5) based on donor-to-recipient predicted heart mass ratios (PHMR). Primary end-point was graft survival at 5 years. RESULTS: Two thousand sixty-one adolescent heart transplant recipients between January 1994 and September 2019 were retrospectively analyzed. The median PHMR's for each quintile was 0.84 (0.59-0.92), 0.97 (0.92-1.02), 1.08 (1.02-1.14), 1.21 (1.14-1.30), and 1.44 (1.30-2.31). Kaplan-Meier survival curves demonstrated comparable survival across all quintiles of PHMR (p = 0.9). Multivariate Cox regression showed no significant difference in graft failure of the outer quintiles when compared to the middle quintile (Q1: 1.04 HR, p = 0.80; Q2: 1.02 HR, p = 0.89; Q4: 1.19 HR, p = 0.28; Q5: 1.02 HR, p = 0.89). Significant covariates included transplant year (HR: 0.95, p < 0.0001), serum bilirubin (HR: 1.04, p = 0.0004), ECMO at transplantation (HR: 2.85, p < 0.0001), and underlying diagnosis of dilated cardiomyopathy (vs congenital heart disease, HR: 0.66, p = 0.0004). CONCLUSIONS: Matching by PHM is not associated with survival or risk in adolescent heart transplant recipients. Our results underscore the ongoing need to develop an improved size-matching method in pediatric heart transplantation.


Assuntos
Transplante de Coração , Obtenção de Tecidos e Órgãos , Adulto , Adolescente , Criança , Humanos , Estudos Retrospectivos , Transplante de Coração/métodos , Doadores de Tecidos , Sobrevivência de Enxerto
9.
Eur J Cardiothorac Surg ; 62(1)2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35325098

RESUMO

OBJECTIVES: Visceral pleural invasion (VPI) guidelines, for tumours ≤4 cm are ambiguous. Non-small-cell lung cancers (NSCLCs) 3 to ≤4 cm are assigned the T2a designation. Similarly, any tumours with VPI, smaller than 3 cm, are upstaged and also assigned the same T2a designation. We hypothesized that adjuvant chemotherapy would significantly improve 5-year survival for NSCLC ≤4 cm with VPI. METHODS: The National Cancer Database was queried from 2010 to 2016 for cases of NSCLC with clinical stage I disease, ≤4 cm, who subsequently underwent surgical resection. These stage I NSCLCs were stratified according to clinical tumour sizes (0 to ≤1, 1 to ≤2, 2 to ≤3 and 3 to ≤4 cm). This cohort was then divided into groups with and without VPI and further split based on the administration of adjuvant chemotherapy. Kaplan-Meier analysis was used to calculate 5-year overall survival (OS) for patients categorized by tumour size, VPI status, and receipt of adjuvant chemotherapy. Multivariable Cox regression adjusting for tumour size and VPI status was used to determine associations between use of adjuvant chemotherapy and OS. RESULTS: A total of 61 454 patients with NSCLC and clinical tumour sizes <4 cm were identified and grouped based on size along with VPI and adjuvant chemotherapy. The 5-year OS for combined tumour sizes without VPI was higher than for patients with VPI (66.2% vs 59.5%, P < 0.001). The OS for tumour size (0 to ≤1, 1 to ≤2, 2 to ≤3 and 3 to ≤4 cm) was lower for patients with VPI regardless of size (all P ≤ 0.010). When all tumour sizes were combined, patients with VPI who received adjuvant chemotherapy had an improved 5-year OS compared to patients without adjuvant chemotherapy (65.5% vs 58.8%, P < 0.001). When cohorts were created by tumour size, only VPI tumours 3 to ≤4 cm had a statistically significant increase in 5-year OS for patients receiving adjuvant chemotherapy (68.8% vs 49.9%, P < 0.001). On multivariable Cox regression for OS, adjuvant chemotherapy was associated with significantly longer 5-year OS in tumour size 3 to ≤4 (hazard ratio = 0.62, 95% confidence interval 0.46-0.83, P = 0.001). CONCLUSIONS: VPI remains a poor prognostic factor in clinically node-negative, T2a or less, NSCLC patients. Guidelines recommend considering chemotherapy for high-risk T2aN0, margin-negative patients-including those patients with VPI. Based on the analysis, adjuvant chemotherapy should be considered specifically for 3 to ≤4 cm with VPI due to an observed 5-year OS advantage.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
10.
World J Pediatr Congenit Heart Surg ; 13(2): 166-174, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35238706

RESUMO

BACKGROUND: Neo-aortic pulmonary autografts often experience root dilation and valve regurgitation over time. This study seeks to understand the biomechanical differences between aortic and neo-aortic pulmonary roots using a heart simulator. METHODS: Porcine aortic, neo-aortic pulmonary, and pulmonary roots (n = 6) were mounted in a heart simulator (parameters: 100 mm Hg, 37 °C, 70 cycles per minute, 5.0 L/min cardiac output). Echocardiography was used to study root distensibility (percentage change in luminal diameter between systole and diastole) and valve function. Leaflet motion was tracked with high-speed videography. After 30 min in the simulator, leaflet thickness (via cryosectioning), and multiaxial modulus (via lenticular hydrostatic deformation testing) were obtained. RESULTS: There were no significant differences between aortic and neo-aortic pulmonary leaflet motion, including mean opening velocity (218 vs 248 mm/s, P = .27) or mean closing velocity (116 vs 157 mm/s, P = .12). Distensibility was similar between aortic (8.5%, 1.56 mm) and neo-aortic pulmonary (7.8%, 1.12 mm) roots (P = .59). Compared to virgin controls, native pulmonic roots exposed to systemic pressure for 30 min had reduced leaflet thickness (630 vs 385 µm, P = .049) and a reduced Young's modulus (3,125 vs 1,089 kPa, P = .077). In contrast, the aortic roots exposed to pressure displayed no significant difference in aortic leaflet thickness (1,317 vs 1,256 µm, P = .27) or modulus (5,931 vs 3,631 kPa, P = .56). CONCLUSIONS: Neo-aortic pulmonary roots demonstrated equivalence in valve function and distensibility but did experience changes in biomechanical properties and morphology. These changes may contribute to long-term complications associated with the Ross procedure.


Assuntos
Insuficiência da Valva Aórtica , Doenças das Valvas Cardíacas , Valva Pulmonar , Animais , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/cirurgia , Autoenxertos , Doenças das Valvas Cardíacas/cirurgia , Humanos , Valva Pulmonar/transplante , Suínos , Transplante Autólogo/efeitos adversos
11.
J Pediatr Surg ; 51(5): 753-61, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26932252

RESUMO

BACKGROUND: In extrahepatic biliary atresia (EHBA) obstruction of the biliary tree causes severe cholestasis leading to cirrhosis and death if left untreated in a timely manner. Infants with cholestasis may undergo many tests before EHBA diagnosis is reached. The role and place of preoperative liver biopsy in the diagnostic paradigm for EHBA have not been established. METHODS: We conducted a systematic review of MEDLINE, Embase, and CENTRAL to obtain all publications describing the sensitivity/specificity/accuracy/positive predictive value (PPV)/negative predictive value (NPV) of preoperative liver biopsy in infants with cholestasis. Screening, data extraction, and quality assessment were done in duplicate. Extracted data are described narratively and analyzed using forest plots and receiver operating characteristic curves. RESULTS: A total of 22 articles were included. Overall, the pooled accuracy of preoperative liver biopsy was 91.7%, with a sensitivity of 91.2%, specificity of 93.0% (n=1231), PPV of 91.2%, NPV of 92.5% (n=1182), and accuracy of 91.6% (n=1106). In patients who were 60days or less at time of presentation or diagnosis, the pooled sensitivity, specificity, PPV, NPV, and accuracy were 96.4%, 96.3%, 95.8%, 96.3%, and 94.9%, respectively. CONCLUSION: Quantitative analysis demonstrated preoperative biopsy to be both highly specific and sensitive in diagnosing EHBA preoperatively. It is a highly reliable test that offers a means of arriving at an early definitive diagnosis of EHBA.


Assuntos
Atresia Biliar/diagnóstico , Atresia Biliar/patologia , Fígado/patologia , Cuidados Pré-Operatórios , Atresia Biliar/cirurgia , Biópsia , Humanos , Lactente , Recém-Nascido , Sensibilidade e Especificidade
12.
Clin Exp Ophthalmol ; 44(1): 33-42, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26241518

RESUMO

BACKGROUND: Matrix metalloproteinases (MMPs) are reported to contribute to the mechanism of argon laser trabeculoplasty, but it is unknown whether they are also secreted after selective laser trabeculoplasty (SLT). The aim of this study was to investigate whether human primary trabecular meshwork (HTM) cells secrete MMP-3 after stimulation by SLT. The relationship between SLT and the two principal forms of cell death, apoptosis and necrosis, was also examined. METHODS: Non-pigmented primary HTM cells were challenged with melanin granules to artificially introduce pigmentation. Isolated non-pigmented HTM cells and 1:1 co-cultures of pigmented and non-pigmented cells were treated with 0.5-1.5 mJ SLT. Cellular metabolic activity (CMA) was quantified using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and necrosis were measured using a cell death ELISA and a lactate dehydrogenase assay, respectively. MMP-3 secretion was measured by ELISA. RESULTS: Co-cultures exhibited a dose-dependent decline in CMA and a dose-dependent increase in necrosis 4 and 24 h after SLT. Non-pigmented cells did not undergo necrosis and displayed a trend towards increased CMA. Apoptosis was reduced in non-pigmented cells but elevated in co-cultures. Increased MMP-3 secretion was observed from co-cultures but not isolated non-pigmented cells. CONCLUSIONS: Pigmentation is necessary for both post-SLT cell death and MMP-3 secretion. SLT appears to have a hormetic effect on non-pigmented HTM cells.


Assuntos
Terapia a Laser , Metaloproteinase 3 da Matriz/metabolismo , Malha Trabecular/enzimologia , Malha Trabecular/cirurgia , Trabeculectomia , Apoptose , Células Cultivadas , Técnicas de Cocultura , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Humanos , L-Lactato Desidrogenase/metabolismo , Lasers de Estado Sólido/uso terapêutico , Melaninas/farmacologia , Necrose , Sais de Tetrazólio , Tiazóis , Malha Trabecular/patologia
14.
Proc Natl Acad Sci U S A ; 110(10): 4021-6, 2013 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-23431191

RESUMO

Pretreatments such as dilute acid at elevated temperature are effective for the hydrolysis of pentose polymers in hemicellulose and also increase the access of enzymes to cellulose fibers. However, the fermentation of resulting syrups is hindered by minor reaction products such as furfural from pentose dehydration. To mitigate this problem, four genetic traits have been identified that increase furfural tolerance in ethanol-producing Escherichia coli LY180 (strain W derivative): increased expression of fucO, ucpA, or pntAB and deletion of yqhD. Plasmids and integrated strains were used to characterize epistatic interactions among traits and to identify the most effective combinations. Furfural resistance traits were subsequently integrated into the chromosome of LY180 to construct strain XW129 (LY180 ΔyqhD ackA::PyadC'fucO-ucpA) for ethanol. This same combination of traits was also constructed in succinate biocatalysts (Escherichia coli strain C derivatives) and found to increase furfural tolerance. Strains engineered for resistance to furfural were also more resistant to the mixture of inhibitors in hemicellulose hydrolysates, confirming the importance of furfural as an inhibitory component. With resistant biocatalysts, product yields (ethanol and succinate) from hemicellulose syrups were equal to control fermentations in laboratory media without inhibitors. The combination of genetic traits identified for the production of ethanol (strain W derivative) and succinate (strain C derivative) may prove useful for other renewable chemicals from lignocellulosic sugars.


Assuntos
Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Furaldeído/farmacologia , Lignina/metabolismo , Sequência de Bases , DNA Bacteriano/genética , Epistasia Genética , Escherichia coli/genética , Etanol/metabolismo , Fermentação , Genes Bacterianos , Engenharia Metabólica/métodos , Modelos Biológicos , Dados de Sequência Molecular , Polissacarídeos/metabolismo , Ácido Succínico/metabolismo , Regulação para Cima
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