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Cardiac surgeries under cardiopulmonary bypass (CPB) are complex procedures with high incidence of complications, morbidity and mortality. The inhaled nitric oxide (iNO) has been frequently used as an important composite of perioperative management during cardiac surgery under CPB. We conducted a meta-analysis of published randomized clinical trials (RCTs) to assess the effects of iNO on reducing postoperative complications, including the duration of postoperative mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay, mortality, hemodynamic improvement (the composite right ventricular failure, low cardiac output syndrome, pulmonary arterial pressure, and vasoactive inotropic score) and myocardial injury biomarker (postoperative troponin I levels). Subgroup analyses were performed to assess the effect of modification and interaction. These included iNO dosage, the timing and duration of iNO therapy, different populations (children and adults), and comparators (other vasodilators and placebo or standard care). A comprehensive search for iNO and cardiac surgery was performed on online databases. Twenty-seven studies were included after removing the duplicates and irrelevant articles. The results suggested that iNO could reduce the duration of mechanical ventilation, but had no significance in the ICU stay, hospital stay, and mortality. This may be attributed to the small sample size of the most included studies and heterogeneity in timing, dosage and duration of iNO administration. Well-designed, large-scale, multicenter clinical trials are needed to further explore the effect of iNO in improving postoperative prognosis in cardiovascular surgical patients.
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Procedimientos Quirúrgicos Cardíacos , Puente Cardiopulmonar , Óxido Nítrico , Humanos , Óxido Nítrico/administración & dosificación , Puente Cardiopulmonar/efectos adversos , Administración por Inhalación , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Complicaciones Posoperatorias/prevención & control , Tiempo de Internación , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Platelet count is associated with cardiovascular risk and mortality in several cardiovascular diseases, but the association of the nadir platelet counts post-septal myectomy with the cardiovascular complication risk in hypertrophic obstructive cardiomyopathy patients remains unclear. METHODS: This retrospective cohort study reviewed all adult patients who underwent septal myectomy at a single tertiary referral center over a 5-year period. Postoperative nadir platelet count was defined as the lowest platelet count in the first 4 postoperative days or until hospital discharge. The composite outcome included cardiovascular death, myocardial infarction, heart failure, malignant arrhythmia, cardiac tamponade, and major bleeding events within 30 days postoperatively. Univariable and multivariable logistic regression and restricted cubic spline models were used to assess the association between postoperative nadir platelet count and the 30-day postoperative cardiovascular complication risk. RESULTS: Among the 113 enrolled patients, 23 (20.4%) developed cardiovascular events within 30 days postoperatively. The incidence of postoperative cardiovascular complications was significantly higher in patients with a nadir platelet count ≤ 99 × 109/L than in those with a nadir platelet count > 99 × 109/L (33.3% vs. 7.1%, crude risk ratio: 4.67, 95% confidence interval: 1.69-12.85, P < 0.001). Multivariable logistic regression revealed that postoperative nadir platelet count was negatively associated with 30-day postoperative cardiovascular complications (adjusted odds ratio: 0.97; 95% confidence interval: 0.95-0.99; P = 0.005) and the association was linear (Pnonlinearity = 0.058) after full adjustment. The association between nadir platelet count and cardiovascular complications within 30 days post-surgery was consistent in all predefined subgroups (Pinteraction > 0.05). CONCLUSION: The postoperative nadir platelet count was significantly associated with the 30-day post-myectomy risk of cardiovascular complications in hypertrophic obstructive cardiomyopathy patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT04275544).
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Cardiomiopatía Hipertrófica , Tabiques Cardíacos , Adulto , Humanos , Recuento de Plaquetas , Resultado del Tratamiento , Estudios Retrospectivos , Tabiques Cardíacos/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Cardiomiopatía Hipertrófica/cirugía , Progresión de la EnfermedadRESUMEN
Quenched Co-based ribbon strips are widely used in the fields of magnetic amplifier, magnetic head material, magnetic shield, electric reactor, inductance core, sensor core, anti-theft system label, and so on. In this study, Co-based composite CoFeNiSiB ribbon strips with a micron width were fabricated by micro-electro-mechanical systems (MEMS) technology. The carbon and FeCoGa nanofilms were deposited for surface modification. The effect of carbon and FeCoGa nanofilm coatings on the crystal structure, surface morphology, magnetic properties, and magnetoimpedance (MI) effect of composite ribbon strips were systematically investigated. The results show that the surface roughness and coercivity of the composite ribbon strips are minimum at a thickness of the carbon coating of 60 nm. The maximum value of MI effect is 41% at 2 MHz, which is approximately 2.4 times greater than plain ribbon and 1.6 times greater than FeCoGa-coated composite ribbon strip. The addition of a carbon layer provides a conductive path for high frequency currents, which effectively reduces the characteristic frequency of the composite ribbon strip. The FeCoGa coating is able to close the flux path and reduce the coercivity, which, in turn, increases the transverse permeability and improves the MI effect. The findings indicate that a successful combination of carbon layer and magnetostrictive FeCoGa nanofilm layer can improve the MI effect and magnetic field sensitivity of the ribbon strips, demonstrating the potential of the composite strips for local and micro area field sensing applications.
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The IGF1R signaling is important in the malignant progression of cancer. However, overexpression of IGF1R has not been properly assessed in HCC. Here, we revealed that GSTZ1-1, the enzyme in phenylalanine/tyrosine catabolism, is downregulated in HCC, and its expression was negatively correlated with IGF1R. Mechanistically, GSTZ1-1 deficiency led to succinylacetone accumulation, alkylation modification of KEAP1, and NRF2 activation, thus promoting IGF1R transcription by recruiting SP1 to its promoter. Moreover, inhibition of IGF1R or NRF2 significantly inhibited tumor-promoting effects of GSTZ1 knockout in vivo. These findings establish succinylacetone as an oncometabolite, and GSTZ1-1 as an important tumor suppressor by inhibiting NRF2/IGF1R axis in HCC. Targeting NRF2 or IGF1R may be a promising treatment approach for this subset HCC.
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Carcinoma Hepatocelular/patología , Dietilnitrosamina/efectos adversos , Regulación hacia Abajo , Glutatión Transferasa/genética , Heptanoatos/metabolismo , Neoplasias Hepáticas/patología , Animales , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Células Hep G2 , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Neoplasias Experimentales , Pronóstico , Receptor IGF Tipo 1/metabolismo , Transducción de Señal , Análisis de SupervivenciaRESUMEN
Acute lung injury (ALI) accompanied with systemic inflammatory response is an important complication after cardiopulmonary bypass (CPB). Pyroptosis, which is induced by the secretion of inflammatory factors, has been implicated in ALI. However, recent studies have suggested that bone marrow mesenchymal stem cell-derived exosomes (BMMSC-Exo) can ameliorate ALI, but the mechanism is poorly understood. Therefore, we aim to examine the effects of BMMSC-Exo in CPB-induced ALI, and its underlying mechanism. CPB rat models (male Sprague-Dawley rats) were administered BMMSC-Exo intravenously before induction of ALI. Lung tissue, bronchoalveolar lavage fluid (BALF), and alveolar macrophage (AM) were collected after the treatments for further analysis, and rat AM NR8383 cells were used for in vitro study. HE staining was performed to detect macrophage infiltration. Western blot was used to detect related proteins expression. And ELISA assay was performed to investigate secretion of inflammatory factors. These results showed that BMMSC-Exo treatment ameliorated macrophage infiltration and oxidative stress, and downregulated expression of pyroptosis-related proteins, including NLRP3, cleaved caspase-1, and GSDMD-N, in the lung tissue and AM, as well as decreased the secretion of IL-18 and IL-1ß in BALF. Moreover, BMMSC-Exo activated YAP/ß-catenin signaling pathway. Overall, these findings of this study indicated that BMMSC-Exo suppressed CPB-induced pyroptosis in ALI by activating YAP/ß-catenin axis, which could be a novel strategy for lung protection during CPB.
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Lesión Pulmonar Aguda , Exosomas , Células Madre Mesenquimatosas , Ratas , Masculino , Animales , Puente Cardiopulmonar/efectos adversos , Ratas Sprague-Dawley , Regulación hacia Abajo , Piroptosis , Exosomas/metabolismo , beta Catenina/metabolismo , Lesión Pulmonar Aguda/metabolismo , Pulmón/metabolismo , Células Madre Mesenquimatosas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismoRESUMEN
BACKGROUND: Although loop diuretics (LDs) have been widely used in clinical practice, their effect on mortality when administered to patients experiencing cardiac surgery-associated acute kidney injury (CS-AKI) remains unknown. The study aimed to investigate the effectiveness of LD use in patients with CS-AKI. METHODS: Patients who underwent cardiac surgery with AKI were identified from the Medical Information Mart for Intensive Care III. Postoperative LD use in intensive care units (ICUs) was exposure. There were 2 primary outcome measures, the in-hospital mortality and ICU mortality; both were treated as time-to-event data and were analyzed via multivariable Cox proportional hazard models. Inverse probability weighting (IPW) was used to minimize bias. RESULTS: The study enrolled a total of 5478 patients, with a median age of 67 years, among which 2205 (40.3%) were women. The crude in-hospital and ICU mortality rates were significantly lower in the LD use group (525 of 4150 [12.7%] vs 434 of 1328 [32.7%], P < .001; 402 of 4150 [9.69%] vs 333 of 1328 [25.1%], P < .001). Adjusted hazard ratios suggested significant reductions in both in-hospital (hazard ratio [HR], 0.428; 95% confidence interval [CI], 0.374-0.489) and ICU mortality (HR, 0.278; 95% CI, 0.238-0.327). The IPW data showed a similar reduction, in-hospital mortality (HR, 0.434; 95% CI, 0.376-0.502) and ICU mortality (HR, 0.296; 95% CI, 0.251-0.349). Such association may act differently for patients with different fluid balance (P value for interaction < .001). CONCLUSIONS: LD use is associated with lower hospital and ICU mortality in CS-AKI patients in general. Patients under different conditions showed diverse responses toward such treatment indicating that personalized management is needed.
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BACKGROUND: The association between tissue oxygenation with postoperative acute kidney injury (AKI) in adult patients undergoing multiple valve surgery has not been specifically studied. METHODS: In this prospective exploratory cohort study, 99 patients were enrolled. The left forehead, the left forearm, the left upper thigh, and the left renal region tissue oxygen saturation using near-infrared spectroscopy were monitored. The association between each threshold and AKI was assessed. The relative and absolute thresholds were < 70%, < 75%, < 80%, < 85%, < 90%, < 95%, and < 100% baseline, and baseline-standard deviation (SD), -1.5 SD, -2 SD, -2.5 SD, and -3 SD. Multivariate logistic regression analysis was adopted to explore the association. RESULTS: AKI occurred in 53 (54%) patients. The absolute value-based SrrO2 thresholds associated with AKI were baseline-3 SD (odds ratio [OR], 4.629; 95% confidence interval [CI], 1.238-17.314; P = 0.023) and baseline-2.5 SD (OR, 2.842; 95% CI, 1.025-7.881; P = 0.045) after adjusting for the potential confounders, those are renal region tissue oxygen saturation of 55% and 60%, but not statistically significant after correcting for multiple testing (corrected P = 0.114 and 0.179, respectively). CONCLUSION: The SrrO2 desaturation, defined as < baseline - 2.5 SD or < baseline - 3 SD, may be associated with AKI. The thresholds need to be verified in future large-scale studies. TRIAL REGISTRATIONS: The study was registered at ClinicalTrials.gov, first trial registration: 26/10/2017, identifier: NCT03323203.
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Lesión Renal Aguda , Saturación de Oxígeno , Humanos , Adulto , Estudios de Cohortes , Estudios Prospectivos , Lesión Renal Aguda/etiología , RiñónRESUMEN
BACKGROUND: Volatile (inhaled) anesthetic agents have cardioprotective effects, which might improve clinical outcomes in patients undergoing coronary-artery bypass grafting (CABG). METHODS: We conducted a pragmatic, multicenter, single-blind, controlled trial at 36 centers in 13 countries. Patients scheduled to undergo elective CABG were randomly assigned to an intraoperative anesthetic regimen that included a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or to total intravenous anesthesia. The primary outcome was death from any cause at 1 year. RESULTS: A total of 5400 patients were randomly assigned: 2709 to the volatile anesthetics group and 2691 to the total intravenous anesthesia group. On-pump CABG was performed in 64% of patients, with a mean duration of cardiopulmonary bypass of 79 minutes. The two groups were similar with respect to demographic and clinical characteristics at baseline, the duration of cardiopulmonary bypass, and the number of grafts. At the time of the second interim analysis, the data and safety monitoring board advised that the trial should be stopped for futility. No significant difference between the groups with respect to deaths from any cause was seen at 1 year (2.8% in the volatile anesthetics group and 3.0% in the total intravenous anesthesia group; relative risk, 0.94; 95% confidence interval [CI], 0.69 to 1.29; P = 0.71), with data available for 5353 patients (99.1%), or at 30 days (1.4% and 1.3%, respectively; relative risk, 1.11; 95% CI, 0.70 to 1.76), with data available for 5398 patients (99.9%). There were no significant differences between the groups in any of the secondary outcomes or in the incidence of prespecified adverse events, including myocardial infarction. CONCLUSIONS: Among patients undergoing elective CABG, anesthesia with a volatile agent did not result in significantly fewer deaths at 1 year than total intravenous anesthesia. (Funded by the Italian Ministry of Health; MYRIAD ClinicalTrials.gov number, NCT02105610.).
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Anestesia Intravenosa , Anestésicos Generales/farmacología , Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria/cirugía , Administración por Inhalación , Anciano , Anestesia General , Anestésicos Intravenosos , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/fisiopatología , Procedimientos Quirúrgicos Electivos , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mortalidad , Método Simple Ciego , Volumen SistólicoRESUMEN
OBJECTIVE: To investigate the effect of volatile anesthetics on the rates of postoperative myocardial infarction (MI) and cardiac death after coronary artery bypass graft (CABG). DESIGN: A post hoc analysis of a randomized trial. SETTING: Cardiac surgical operating rooms. PARTICIPANTS: Patients undergoing elective, isolated CABG. INTERVENTIONS: Patients were randomized to receive a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or total intravenous anesthesia (TIVA). The primary outcome was hemodynamically relevant MI (MI requiring high-dose inotropic support or prolonged intensive care unit stay) occurring within 48 hours from surgery. The secondary outcome was 1-year death due to cardiac causes. MEASUREMENTS AND MAIN RESULTS: A total of 5,400 patients were enrolled between April 2014 and September 2017 (2,709 patients randomized to the volatile anesthetics group and 2,691 to TIVA). The mean age was 62 ± 8.4 years, and the median baseline ejection fraction was 57% (50-67), without differences between the 2 groups. Patients in the volatile group had a lower incidence of MI with hemodynamic complications both in the per-protocol (14 of 2,530 [0.6%] v 27 of 2,501 [1.1%] in the TIVA group; p = 0.038) and as-treated analyses (16 of 2,708 [0.6%] v 29 of 2,617 [1.1%] in the TIVA group; p = 0.039), but not in the intention-to-treat analysis (17 of 2,663 [0.6%] v 28 of 2,667 [1.0%] in the TIVA group; p = 0.10). Overall, deaths due to cardiac causes were lower in the volatile group (23 of 2,685 [0.9%] v 40 of 2,668 [1.5%] than in the TIVA group; p = 0.03). CONCLUSIONS: An anesthetic regimen, including volatile agents, may be associated with a lower rate of postoperative MI with hemodynamic complication in patients undergoing CABG. Furthermore, it may reduce long-term cardiac mortality.
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Anestésicos por Inhalación , Infarto del Miocardio , Propofol , Anciano , Anestésicos Intravenosos , Puente de Arteria Coronaria/métodos , Humanos , Persona de Mediana Edad , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/epidemiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , SevofluranoRESUMEN
BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with a high risk of postoperative acute kidney injury (AKI). Due to limitations of current diagnostic strategies, we sought to determine whether free hemoglobin (fHb) ratio (ie, levels of fHb at the end of CPB divided by baseline fHb) could predict AKI after on-pump cardiac surgery. METHODS: This is a secondary analysis of a randomized controlled trial comparing the effect of nitric oxide (intervention) versus nitrogen (control) on AKI after cardiac surgery (NCT01802619). A total of 110 adult patients in the control arm were included. First, we determined whether fHb ratio was associated with AKI via multivariable analysis. Second, we verified whether fHb ratio could predict AKI and incorporation of fHb ratio could improve predictive performance at an early stage, compared with prediction using urinary biomarkers alone. We conducted restricted cubic spline in logistic regression for model development. We determined the predictive performance, including area under the receiver-operating-characteristics curve (AUC) and calibration (calibration plot and accuracy, ie, number of correct predictions divided by total number of predictions). We also used AUC test, likelihood ratio test, and net reclassification index (NRI) to compare the predictive performance between competing models (ie, fHb ratio versus neutrophil gelatinase-associated lipocalin [NGAL], N-acetyl-ß-d-glucosaminidase [NAG], and kidney injury molecule-1 [KIM-1], respectively, and incorporation of fHb ratio with NGAL, NAG, and KIM-1 versus urinary biomarkers alone), if applicable. RESULTS: Data stratified by median fHb ratio showed that subjects with an fHb ratio >2.23 presented higher incidence of AKI (80.0% vs 49.1%; P = .001), more need of renal replacement therapy (10.9% vs 0%; P = .036), and higher in-hospital mortality (10.9% vs 0%; P = .036) than subjects with an fHb ratio ≤2.23. fHb ratio was associated with AKI after adjustment for preestablished factors. fHb ratio outperformed urinary biomarkers with the highest AUC of 0.704 (95% confidence interval [CI], 0.592-0.804) and accuracy of 0.714 (95% CI, 0.579-0.804). Incorporation of fHb ratio achieved better discrimination (AUC test, P = .012), calibration (likelihood ratio test, P < .001; accuracy, 0.740 [95% CI, 0.617-0.832] vs 0.632 [95% CI, 0.477-0.748]), and significant prediction increment (NRI, 0.638; 95% CI, 0.269-1.008; P < .001) at an early stage, compared with prediction using urinary biomarkers alone. CONCLUSIONS: Results from this exploratory, hypothesis-generating retrospective, observational study shows that fHb ratio at the end of CPB might be used as a novel, widely applicable biomarker for AKI. The use of fHb ratio might help for an early detection of AKI, compared with prediction based only on urinary biomarkers.
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Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Puente Cardiopulmonar/efectos adversos , Hemoglobinas/metabolismo , Lesión Renal Aguda/diagnóstico , Adulto , Biomarcadores/sangre , Procedimientos Quirúrgicos Cardíacos/tendencias , Puente Cardiopulmonar/tendencias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico/administración & dosificación , Nitrógeno/administración & dosificación , Estudios RetrospectivosRESUMEN
PURPOSE OF REVIEW: Over the last decades, clinical studies have suggested that transfusion of red blood cells (RBCs) might negatively impact patient outcomes. Even though large randomized clinical trials did not show differences in mortality when transfusing fresh versus standard-issue RBC units, data imply that RBCs at the very end of storage could elicit negative effects. RECENT FINDINGS: Certain alterations of RBCs during cold storage -- such as an increase of potassium and lactate in the storage solution -- have been discovered a century ago. In recent years, proteomic and metabolomic studies have shed more light into pathophysiological changes of RBCs during storage and have helped to specify the definition of old blood. These advancements are now utilized to increase the quality of stored RBCs and devise therapeutic strategies (e.g. nitric oxide, haptoglobin, or reduction of the iron load) when transfusing old blood. SUMMARY: Further research to improve the quality of RBC units and to study populations potentially at risk is warranted. Until the question whether transfusion of old blood is detrimental for specific patient populations has been answered, a deliberate use of RBC transfusion should be implemented.
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Conservación de la Sangre/estadística & datos numéricos , Transfusión de Eritrocitos/efectos adversos , Eritrocitos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de TiempoRESUMEN
Corneal wounds usually heal quickly; but diabetic patients have more fragile corneas and experience delayed and painful healing. In the present study, we compared the healing capacity of corneal epithelial cells (CECs) between normal and diabetic conditions and the potential mechanisms. Primary murine CEC derived from wild-type and diabetic (db/db) mice, as well as primary human CEC were prepared. Human CEC were exposed to high glucose (30 mM) to mimic diabetic conditions. Cell migration and proliferation were assessed using Scratch test and MTT assays, respectively. Reactive oxygen species (ROS) production in the cells was measured using dichlorofluorescein reagent. Western blot was used to evaluate the expression levels of Akt. Transepithelial electrical resistance (TEER) and zonula occludens-1 (ZO-1) expression were used to determine tight junction integrity. We found that the diabetic CEC displayed significantly slower cell proliferation and migration compared with the normal CEC from both mice and humans. Furthermore, ROS production was markedly increased in CEC grown under diabetic conditions. Treatment with an antioxidant N-acetyl cysteine (NAC, 100 µM) significantly decreased ROS production and increased wound healing in diabetic CEC. Barrier function was significantly reduced in both diabetic mouse and human CEC, while NAC treatment mitigated these effects. We further showed that Akt signaling was impaired in diabetic CEC, which was partially improved by NAC treatment. These results show that diabetic conditions lead to delayed wound-healing capacity of CEC and impaired tight junction formation in both mice and human. Increased ROS production and inhibited Akt signaling may contribute to this outcome, implicating these as potential targets for treating corneal wounds in diabetic patients.
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Movimiento Celular/fisiología , Diabetes Mellitus Experimental/fisiopatología , Células Epiteliales/metabolismo , Transducción de Señal/fisiología , Uniones Estrechas/metabolismo , Cicatrización de Heridas/fisiología , Animales , Proliferación Celular/fisiología , Células Cultivadas , Córnea/citología , Humanos , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
RATIONALE: No medical intervention has been identified that decreases acute kidney injury and improves renal outcome at 1 year after cardiac surgery. OBJECTIVES: To determine whether administration of nitric oxide reduces the incidence of postoperative acute kidney injury and improves long-term kidney outcomes after multiple cardiac valve replacement requiring prolonged cardiopulmonary bypass. METHODS: Two hundred and forty-four patients undergoing elective, multiple valve replacement surgery, mostly due to rheumatic fever, were randomized to receive either nitric oxide (treatment) or nitrogen (control). Nitric oxide and nitrogen were administered via the gas exchanger during cardiopulmonary bypass and by inhalation for 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: The primary outcome was as follows: oxidation of ferrous plasma oxyhemoglobin to ferric methemoglobin was associated with reduced postoperative acute kidney injury from 64% (control group) to 50% (nitric oxide group) (relative risk [RR], 0.78; 95% confidence interval [CI], 0.62-0.97; P = 0.014). Secondary outcomes were as follows: at 90 days, transition to stage 3 chronic kidney disease was reduced from 33% in the control group to 21% in the treatment group (RR, 0.64; 95% CI, 0.41-0.99; P = 0.024) and at 1 year, from 31% to 18% (RR, 0.59; 95% CI, 0.36-0.96; P = 0.017). Nitric oxide treatment reduced the overall major adverse kidney events at 30 days (RR, 0.40; 95% CI, 0.18-0.92; P = 0.016), 90 days (RR, 0.40; 95% CI, 0.17-0.92; P = 0.015), and 1 year (RR, 0.47; 95% CI, 0.20-1.10; P = 0.041). CONCLUSIONS: In patients undergoing multiple valve replacement and prolonged cardiopulmonary bypass, administration of nitric oxide decreased the incidence of acute kidney injury, transition to stage 3 chronic kidney disease, and major adverse kidney events at 30 days, 90 days, and 1 year. Clinical trial registered with ClinicalTrials.gov (NCT01802619).
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Lesión Renal Aguda/prevención & control , Puente Cardiopulmonar/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Óxido Nítrico/farmacología , Complicaciones Posoperatorias/prevención & control , Insuficiencia Renal Crónica/prevención & control , Femenino , Depuradores de Radicales Libres/farmacología , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
The authors describe an integrated microfluidic chip for immunodetection of the prostate specific antigen (PSA) by using giant magnetoimpedance (GMI) sensor. This chip contains an immunoreaction platform and a biomarker detection system. The immunoreaction platform contains an incubation chamber and a reactive chamber to implement immunological reaction in microfluidics. The system can detect PSA rapidly with ultra-high sensitivity. Both are fabricated by MEMS technology. Immunomagnetic beads (If PSA binds to its antibody (that is labeled with immunomagnetic beads; IMBs) it will be trapped on the surface of self-assembled film. Trapped IMBs generate a stray magnetic field under the magnetization of the external applied magnetic field and can be detected by the GMI sensor. The chip can detect PSA with a detection limit as low as 0.1 ng â mL-1 and works in the 0.1 ng â mL-1 to 20 ng â mL-1 concentration range. Compared to established GMI biosensors, the magnetic microfluidic chip reduces assay time, and lends itself to fast detection. It also avoids complex handling steps, enhances reaction efficiency and decreases experimental errors. Graphical abstract An integrated magnetic microfluidic chip which contains immunoreaction platform and biomarker detection system was designed and microfabricated by micro-electromechanical systems (MEMS) technology to detect prostate specific antigen (PSA) rapidly, and has promise in Point-of-care (PoC) diagnostic applications.
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Inmunoensayo/instrumentación , Separación Inmunomagnética/instrumentación , Dispositivos Laboratorio en un Chip , Técnicas Analíticas Microfluídicas/instrumentación , Antígeno Prostático Específico/análisis , Animales , Anticuerpos/inmunología , Biomarcadores/análisis , Diseño de Equipo , Humanos , Inmunoensayo/métodos , Separación Inmunomagnética/métodos , Límite de Detección , Ratones , Técnicas Analíticas Microfluídicas/métodos , Antígeno Prostático Específico/inmunologíaRESUMEN
In this paper, the performance of orthogonal fluxgate sensors with meander-shaped cores is studied in fundamental mode. The meander-shaped cores are made by micro-patterning technology based on a Co-based amorphous ribbon. The main advantage of this structure is that the linear operating range of the sensor can be adjusted simply by changing the number of strips, without affecting the excitation mechanism. Experiments show that a linear range of 560 µT is obtained by a meander-shaped core sensor with 12 strips. The changes in the number of strips can also increase sensitivity and reduce noise of the sensor. We can achieve a sensitivity of 600 V/T and a noise level of 0.64 nT/âHz at 1 Hz for a meander-shaped core sensor with eight strips. Compared with the performance of the sensors built using a single strip core having the same equivalent cross-sectional area, the use of meander-shaped core can provide a higher sensitivity and linearity, and a lower noise level. We also compare the performance of an eight-strip meander-shaped core orthogonal fluxgate operated in the fundamental and second-harmonic modes. Similar sensitivity for the two modes can be obtained by adjusting the excitation current. In this case, we find that the noise of sensor operating in fundamental mode is about five times lower than that of the sensor operating in second-harmonic mode. This can be interpreted as the suppression of Barkhausen noise by unipolar bias in the fundamental mode.
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Cardiac biomarkers (CBs) are substances that appear in the blood when the heart is damaged or stressed. Measurements of the level of CBs can be used in course of diagnostics or monitoring the state of the health of group risk persons. A multi-region bio-analytical system (MRBAS) based on magnetoimpedance (MI) changes was proposed for ultrasensitive simultaneous detection of CBs myoglobin (Mb) and C-reactive protein (CRP). The microfluidic device was designed and developed using standard microfabrication techniques for their usage in different regions, which were pre-modified with specific antibody for specified detection. Mb and CRP antigens labels attached to commercial Dynabeads with selected concentrations were trapped in different detection regions. The MI response of the triple sensitive element was carefully evaluated in initial state and in the presence of biomarkers. The results showed that the MI-based bio-sensing system had high selectivity and sensitivity for detection of CBs. Compared with the control region, ultrasensitive detections of CRP and Mb were accomplished with the detection limits of 1.0 pg/mL and 0.1 pg/mL, respectively. The linear detection range contained low concentration detection area and high concentration detection area, which were 1 pg/mLâ»10 ng/mL, 10â»100 ng/mL for CRP, and 0.1 pg/mLâ»1 ng/mL, 1 n/mLâ»80 ng/mL for Mb. The measurement technique presented here provides a new methodology for multi-target biomolecules rapid testing.
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Biomarcadores/química , Técnicas Biosensibles , Proteína C-Reactiva/aislamiento & purificación , Mioglobina/aislamiento & purificación , Proteína C-Reactiva/química , Impedancia Eléctrica , Humanos , Dispositivos Laboratorio en un Chip , Límite de Detección , Nanopartículas de Magnetita/química , Mioglobina/química , Troponina I/química , Troponina I/aislamiento & purificaciónRESUMEN
The chirality of photons plays a fundamental role in light-matter interactions. However, a limiting factor in photonic integrated circuits is the lack of a miniaturized component, which can distinguish the chirality in a low cost and integrated manner. Herein we numerically demonstrate a chirality-distinguishing beamsplitter that can address this challenge. It consists of an integrated polarization rotator and a linear polarization beamsplitter, which together can fulfill the task of distinguishing and splitting left- and right-handed quasi-circularly polarized modes on a chip with an ultra-broadband operation range from 1.45 µm to 1.65 µm. Owning to the reciprocity, the device can emit photons with selectable spin angular momentum depending on the chosen feeding waveguide. The device is compatible with complementary metal-oxide semiconductor technology and it may open up new avenues in the fields of on-chip nano-photonics, bio-photonics and quantum information science.
RESUMEN
This paper presents a contactless detection method for detecting prostate specific antigen with a giant magnetoresistance sensor. In contactless detection case, the prostate specific antigen sample preparation was separated from the sensor that prevented the sensor from being immersed in chemical solvents, and made the sensor implementing in immediately reuse without wash. Experimental results showed that applied an external magnetic field in a range of 50 Oe to 90 Oe, Dynabeads with a concentration as low as 0.1 µg/mL can be detected by this system and could give an approximate quantitation to the logarithmic of Dynabeads concentration. Sandwich immunoassay was employed for preparing PSA samples. The PSA capture was implemented on a gold film modified with a self-assembled monolayer and using biotinylated secondary antibody against PSA and streptavidinylated Dynabeads. With DC magnetic field in the range of 50 to 90 Oe, PSA can be detected with a detection limit as low as 0.1 ng/mL. Samples spiked with different concentrations of PSA can be distinguished clearly. Due to the contactless detection method, the detection system exhibited advantages such as convenient manipulation, reusable, inexpensive, small weight. So, this detection method was a promising candidate in biomarker detection, especially in point of care detection.
Asunto(s)
Técnicas Biosensibles , Magnetismo/instrumentación , Antígeno Prostático Específico/análisis , Anticuerpos/química , Biomarcadores/análisis , Humanos , Inmunoensayo , Límite de Detección , Masculino , MicrotecnologíaRESUMEN
The disturbing effect of the stray magnetic fields of Fe-based amorphous ribbons on the giant magnetoimpedance (GMI) sensor has been investigated systematically in this paper. Two simple methods were used for examining the disturbing effect of the stray magnetic fields of ribbons on the GMI sensor. In order to study the influence of the stray magnetic fields on the GMI effect, the square-shaped amorphous ribbons were tested in front, at the back, on the left and on the top of a meander-line GMI sensor made up of soft ferromagnetic films, respectively. Experimental results show that the presence of ribbons in front or at the back of GMI sensor shifts the GMI curve to a lower external magnetic field. On the contrary, the presence of ribbons on the left or on the top of the GMI sensor shifts the GMI curve to a higher external magnetic field, which is related to the coupling effect of the external magnetic field and the stray magnetic fields. The influence of the area and angle of ribbons on GMI was also studied in this work. The GMI sensor exhibits high linearity for detection of the stray magnetic fields, which has made it feasible to construct a sensitive magnetometer for detecting the typical stray magnetic fields of general soft ferromagnetic materials.
RESUMEN
A giant magnetoimpedance (GMI)-based biosensor was developed for detection of Escherichia coli (E. coli) O157: H7. The GMI sensor involving the sensing elements of Cr/Cu/NiFe/Cu/NiFe was fabricated by Micro Electro-Mechanical system (MEMS) technology, including thick photoresist lithography and electroplating. A separate Au film substrate as immunoplatform was used to capture E. coli O157:H7. The monoclonal mouse anti-E. coli antibody was immobilized on Au film substrate surface with a self-assembled layer. The different concentration E. coli O157:H7 (100, 300 and 500 cfu/ml) were combined with Dynabeads-antibody conjugates (DAC) respectively. DAC were prepared by conjugating streptavidin-coupled Dynabeads with biotin-labeled polyclonal mouse anti-E. coli antibodies. The classical sandwich assay was used for detection of E. coli O157:H7 targeted with Dynabeads by using antibody-antigen pair combination of biotin-streptavidin. The fundamental principle for detection of E. coli O157:H7 based on GMI sensor was that Dynabeads were employed as magnetic labels of E. coli O157:H7, and E. coli O157:H7 can be monitored by detecting the fringe field of Dynabeads using magnetic sensing elements. We observed that the GMI ratio were significantly improved due to the presence of E. coli O157:H7 combined with Dynabeads. The GMI ratio increased as the E. coli O157:H7 concentration increased. A lower detectable concentration of 100 cfu/ml was achieved in present work. The GMI-based biosensor provides a new method to rapid and sensitive detection E. coli O157:H7, which has a large potential for bio-application.