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Neuromorphic circuits that can function under extreme deformations are important for various data-driven wearable and robotic applications. Herein, biphasic liquid metal particle (BMP) with unprecedented stretchability and strain-insensitivity (ΔR/R0 = 1.4@ 1200% strain) is developed to realize a stretchable neuromorphic circuit that mimics a spike-based biologic sensory system. The BMP consists of liquid metal particles (LMPs) and rigid liquid metal particles (RLMPs), which are homogeneously mixed via spontaneous solutal-Marangoni mixing flow during coating. This permits facile single step patterning directly on various substrates at room temperature. BMP is highly conductive (2.3 × 106 S/m) without any post activation steps. BMP interconnects are utilized for a sensory system, which is capable of distinguishing variations of biaxial strains with a spiking neural network, thus demonstrating their potential for various sensing and signal processing applications.
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Background: Extracorporeal membrane oxygenation (ECMO) patients have a high incidence of acute kidney injury (AKI). Extracorporeal cardiopulmonary resuscitation (ECPR) patients are more likely to develop AKI than ECMO patients because of serious injury during cardiac arrest (CA). Objectives: This study aims to assess the occurrence and outcomes of AKI in ECPR and ECMO, and to identify specific risk factors and clinical implications of AKI in ECPR. Methods: This is a retrospective observational study from a single tertiary care hospital in Gwangju, Korea. Adults (≥18 years) who received ECMO with cardiac etiology in the emergency and inpatient departments from January 2015 to December 2021 were included. The patients (n = 169) were divided into two groups, ECPR and ECMO without CA, and the occurrence of AKI was investigated. The primary outcome of the study was in-hospital mortality, and the secondary outcomes were six-month cerebral performance category (CPC) and AKI during hospitalization. Results: The incidence of AKI was significantly higher with ECPR (67.5 %) than with ECMO without CA (38.4 %). ECPR was statistically significant for Expire (adjusted OR (aOR) 2.45, 95 % CI 1.28-4.66) and Poor CPC (2.59, 1.32-5.09). AKI was also statistically significant for Expire (6.69, 3.37-13.29) and Poor CPC (5.45, 2.73-10.88). AKI was the determining factor for the outcomes of ECPR (p = 0.01). Conclusions: ECPR patients are more likely to develop AKI than ECMO without CA patients. In ECPR patients, AKI leads to poor outcomes. Therefore, clinicians should be careful not to develop AKI in ECPR patients.
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BACKGROUND: Within the trauma system, the emergency department (ED) is the hospital's first contact and is vital for allocating medical resources. However, there is generally limited information about patients that die in the ED. OBJECTIVE: The aim of this study was to develop an artificial intelligence (AI) model to predict trauma mortality and analyze pertinent mortality factors for all patients visiting the ED. METHODS: We used the Korean National Emergency Department Information System (NEDIS) data set (N=6,536,306), incorporating over 400 hospitals between 2016 and 2019. We included the International Classification of Disease 10th Revision (ICD-10) codes and chose the following input features to predict ED patient mortality: age, sex, intentionality, injury, emergent symptom, Alert/Verbal/Painful/Unresponsive (AVPU) scale, Korean Triage and Acuity Scale (KTAS), and vital signs. We compared three different feature set performances for AI input: all features (n=921), ICD-10 features (n=878), and features excluding ICD-10 codes (n=43). We devised various machine learning models with an ensemble approach via 5-fold cross-validation and compared the performance of each model with that of traditional prediction models. Lastly, we investigated explainable AI feature effects and deployed our final AI model on a public website, providing access to our mortality prediction results among patients visiting the ED. RESULTS: Our proposed AI model with the all-feature set achieved the highest area under the receiver operating characteristic curve (AUROC) of 0.9974 (adaptive boosting [AdaBoost], AdaBoost + light gradient boosting machine [LightGBM]: Ensemble), outperforming other state-of-the-art machine learning and traditional prediction models, including extreme gradient boosting (AUROC=0.9972), LightGBM (AUROC=0.9973), ICD-based injury severity scores (AUC=0.9328 for the inclusive model and AUROC=0.9567 for the exclusive model), and KTAS (AUROC=0.9405). In addition, our proposed AI model outperformed a cutting-edge AI model designed for in-hospital mortality prediction (AUROC=0.7675) for all ED visitors. From the AI model, we also discovered that age and unresponsiveness (coma) were the top two mortality predictors among patients visiting the ED, followed by oxygen saturation, multiple rib fractures (ICD-10 code S224), painful response (stupor, semicoma), and lumbar vertebra fracture (ICD-10 code S320). CONCLUSIONS: Our proposed AI model exhibits remarkable accuracy in predicting ED mortality. Including the necessity for external validation, a large nationwide data set would provide a more accurate model and minimize overfitting. We anticipate that our AI-based risk calculator tool will substantially aid health care providers, particularly regarding triage and early diagnosis for trauma patients.
Subject(s)
Artificial Intelligence , Fractures, Bone , Humans , Retrospective Studies , Republic of Korea , Emergency Service, HospitalABSTRACT
Background: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with cardiorespiratory failure. The serum albumin level is an important prognostic marker in critically ill patients. We evaluated the efficacy of using pre-ECMO serum albumin levels to predict 30-day mortality in patients with cardiogenic shock (CS) who underwent venoarterial (VA) ECMO. Methods: We reviewed the medical records of 114 adult patients who underwent VA-ECMO between March 2021 and September 2022. The patients were divided into survivors and non-survivors. Clinical data before and during ECMO were compared. Results: Patients' mean age was 67.8±13.6 years, and 36 (31.6%) were female. The proportion of survival to discharge was 48.6% (n=56). Cox regression analysis showed that the pre-ECMO albumin level independently predicted 30-day mortality (hazard ratio, 0.25; 95% confidence interval [CI], 0.11-0.59; p=0.002). The area under the receiver operating characteristic curve of albumin levels (pre-ECMO) was 0.73 (standard error [SE], 0.05; 95% CI, 0.63-0.81; p<0.001; cut-off value=3.4 g/dL). Kaplan-Meier survival analysis showed that the cumulative 30-day mortality was significantly higher in patients with a pre-ECMO albumin level ≤3.4 g/dL than in those with a level >3.4 g/dL (68.9% vs. 23.8%, p<0.001). As the adjusted amount of albumin infused increased, the possibility of 30-day mortality also increased (coefficient=0.140; SE, 0.037; p<0.001). Conclusion: Hypoalbuminemia during ECMO was associated with higher mortality, even with higher amounts of albumin replacement, in patients with CS who underwent VA-ECMO. Further studies are needed to predict the timing of albumin replacement during ECMO.
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BACKGROUND: The poor performance of conventional techniques used in cardiovascular disease patients requiring hemodialysis or arterial bypass grafting has prompted tissue engineers to search for clinically appropriate off-the-shelf vascular grafts. Most patients with cardiovascular disease lack suitable autologous tissue because of age or previous surgery. Commercially available vascular grafts with diameters of < 5 mm often fail because of thrombosis and intimal hyperplasia. RESULT: Here, we tested tubular biodegradable poly-e-caprolactone/polydioxanone (PCL/PDO) electrospun vascular grafts in a rat model of aortic interposition for up to 12 weeks. The grafts demonstrated excellent patency (100%) confirmed by Doppler Ultrasound, resisted aneurysmal dilation and intimal hyperplasia, and yielded neoarteries largely free of foreign materials. At 12 weeks, the grafts resembled native arteries with confluent endothelium, synchronous pulsation, a contractile smooth muscle layer, and co-expression of various extracellular matrix components (elastin, collagen, and glycosaminoglycan). CONCLUSIONS: The structural and functional properties comparable to native vessels observed in the neoartery indicate their potential application as an alternative for the replacement of damaged small-diameter grafts. This synthetic off-the-shelf device may be suitable for patients without autologous vessels. However, for clinical application of these grafts, long-term studies (> 1.5 years) in large animals with a vasculature similar to humans are needed.
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Hypovolemia may be underestimated due to compensatory mechanisms. In this systematic review and meta-analysis, we investigated the diagnostic accuracy of a flat inferior vena cava (IVC) on computed tomography (CT) for predicting the development of shock and mortality in trauma patients. Relevant studies were obtained by searching PubMed, EMBASE, and Cochrane databases (articles up to 16 September 2022). The number of 2-by-2 contingency tables for the index test were collected. We adopted the Bayesian bivariate random-effects meta-analysis model. Twelve studies comprising a total of 1706 patients were included. The flat IVC on CT showed 0.46 pooled sensitivity (95% credible interval [CrI] 0.32-0.63), 0.87 pooled specificity (95% CrI 0.78-0.94), and 0.78 pooled AUC (95% CrI 0.58-0.93) for the development of shock. The flat IVC for mortality showed 0.48 pooled sensitivity (95% CrI 0.21-0.94), 0.70 pooled specificity (95% CrI 0.47-0.88), and 0.60 pooled AUC (95% CrI 0.26-0.89). Regarding the development of shock, flat IVC provided acceptable accuracy with high specificity. Regarding in-hospital mortality, the flat IVC showed poor accuracy. However, these results should be interpreted with caution due to the high risk of bias and substantial heterogeneity in some included studies.
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BACKGROUND: Physical trauma-related mortality places a heavy burden on society. Estimating the mortality risk in physical trauma patients is crucial to enhance treatment efficiency and reduce this burden. The most popular and accurate model is the Injury Severity Score (ISS), which is based on the Abbreviated Injury Scale (AIS), an anatomical injury severity scoring system. However, the AIS requires specialists to code the injury scale by reviewing a patient's medical record; therefore, applying the model to every hospital is impossible. OBJECTIVE: We aimed to develop an artificial intelligence (AI) model to predict in-hospital mortality in physical trauma patients using the International Classification of Disease 10th Revision (ICD-10), triage scale, procedure codes, and other clinical features. METHODS: We used the Korean National Emergency Department Information System (NEDIS) data set (N=778,111) compiled from over 400 hospitals between 2016 and 2019. To predict in-hospital mortality, we used the following as input features: ICD-10, patient age, gender, intentionality, injury mechanism, and emergent symptom, Alert/Verbal/Painful/Unresponsive (AVPU) scale, Korean Triage and Acuity Scale (KTAS), and procedure codes. We proposed the ensemble of deep neural networks (EDNN) via 5-fold cross-validation and compared them with other state-of-the-art machine learning models, including traditional prediction models. We further investigated the effect of the features. RESULTS: Our proposed EDNN with all features provided the highest area under the receiver operating characteristic (AUROC) curve of 0.9507, outperforming other state-of-the-art models, including the following traditional prediction models: Adaptive Boosting (AdaBoost; AUROC of 0.9433), Extreme Gradient Boosting (XGBoost; AUROC of 0.9331), ICD-based ISS (AUROC of 0.8699 for an inclusive model and AUROC of 0.8224 for an exclusive model), and KTAS (AUROC of 0.1841). In addition, using all features yielded a higher AUROC than any other partial features, namely, EDNN with the features of ICD-10 only (AUROC of 0.8964) and EDNN with the features excluding ICD-10 (AUROC of 0.9383). CONCLUSIONS: Our proposed EDNN with all features outperforms other state-of-the-art models, including the traditional diagnostic code-based prediction model and triage scale.
Subject(s)
Artificial Intelligence , Humans , Hospital Mortality , Trauma Severity Indices , Injury Severity Score , Republic of Korea , Retrospective StudiesABSTRACT
Osteoporosis is a disease caused by impaired bone remodeling that is especially prevalent in elderly and postmenopausal women. Although numerous chemical agents have been developed to prevent osteoporosis, arguments remain regarding their side effects. Here, we demonstrated the effects of loganin, a single bioactive compound isolated from Cornus officinalis, on osteoblast and osteoclast differentiation in vitro and on ovariectomy (OVX)-induced osteoporosis in mice in vivo. Loganin treatment increased the differentiation of mouse preosteoblast cells into osteoblasts and suppressed osteoclast differentiation in primary monocytes by regulating the mRNA expression levels of differentiation markers. Similar results were obtained in an osteoblast-osteoclast co-culture system, which showed that loganin enhanced alkaline phosphatase (ALP) activity and reduced TRAP activity. In in vivo experiments, the oral administration of loganin prevented the OVX-induced loss of bone mineral density (BMD) and microstructure in mice and improved bone parameters. In addition, loganin significantly increased the serum OPG/RANKL ratio and promoted osteogenic activity during bone remodeling. Our findings suggest that loganin could be used as an alternative treatment to protect against osteoporosis.
Subject(s)
Osteogenesis , Osteoporosis , Female , Animals , Mice , Iridoids , Osteoblasts , Osteoporosis/drug therapyABSTRACT
Metabolic abnormalities, such as preexisting diabetes or hyperglycemia or hypoglycemia during hospitalization aggravated the severity of COVID-19. We evaluated whether diabetes history, hyperglycemia before and during extracorporeal membrane oxygenation (ECMO) support, and hypoglycemia were risk factors for mortality in patients with COVID-19. This study included data on 195 patients with COVID-19, who were aged ≥19 years and were treated with ECMO. The proportion of patients with diabetes history among nonsurvivors was higher than that among survivors. Univariate Cox regression analysis showed that in-hospital mortality after ECMO support was associated with diabetes history, renal replacement therapy (RRT), and body mass index (BMI) < 18.5 kg/m2. Glucose at admission >200 mg/dL and glucose levels before ventilator >200 mg/dL were not associated with in-hospital mortality. However, glucose levels before ECMO >200 mg/dL and minimal glucose levels during hospitalization <70 mg/dL were associated with in-hospital mortality. Multivariable Cox regression analysis showed that glucose >200 mg/dL before ECMO and minimal glucose <70 mg/dL during hospitalization remained risk factors for in-hospital mortality after adjustment for age, BMI, and RRT. In conclusion, glucose >200 mg/dL before ECMO and minimal glucose level <70 mg/dL during hospitalization were risk factors for in-hospital mortality among COVID-19 patients who underwent ECMO.
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BACKGROUND: Traumatic tracheal injury is a rare type of trauma. In this type of injury, catastrophes may occur owing to a failure to secure the patient's airway. Extracorporeal membrane oxygenation (ECMO) is rescue therapy available for the treatment of urgent cardiorespiratory distress until the patient's vital signs have stabilized. The various applications of ECMO configurations have expanded the scope for this therapy. CASE PRESENTATION: We describe the case of a 66-year-old man with tracheal rupture with thyroid cartilage fracture due to cultivator handle who was treated with veno-venous ECMO. This case reflects the role and limitations of veno-venous ECMO, in which patient survival was possible with a bi-femoral configuration while also ensuring a clear airway. CONCLUSION: We shared our experience with bi-femoral veno-venous ECMO as a therapeutic option to contribute to choosing an appropriate approach. Based on our review of the literature, the present case was an uncommon report of survival after tracheal rupture due to trauma without other complications.
Subject(s)
Extracorporeal Membrane Oxygenation , Tracheal Diseases , Aged , Femoral Artery , Humans , Male , Rupture , TracheaABSTRACT
Background and Objectives: Traumatic duodenal injury is a rare disease with limited evidence. We aimed to evaluate the risk factors for postoperative leakage and outcomes of pyloric exclusion after duodenal grade 2 and 3 injury. Materials and Methods: We reviewed a prospectively collected trauma database for the period January 2004-December 2020. Patients with grade 2 and 3 traumatic duodenal injury were included. To identify the risk factors for postoperative leakage, we used a stepwise multivariable logistic regression model and a least absolute shrinkage and selection operator (LASSO) logistic model. We constructed a receiver operator characteristic (ROC) curve to predict risk factors for postoperative leakage. Results: During the 17-year period, 179,887 trauma patients were admitted to a regional trauma center in Korea. Of these patients, 74 (0.04%) had duodenal injuries. A total of 49 consecutive patients had grade 2 and 3 traumatic duodenal injuries and underwent laparotomy. The incidence of postoperative leakage was 32.6% (16/49). Overall mortality was 18.4% (9/49). A stepwise multivariable logistic regression and LASSO logistic regression model showed that time from injury to initial operation was the sole statistically significant risk factor. The ROC curve at the optimal threshold of 15.77 h showed the following: area under ROC curve, 0.782; sensitivity, 68.8%; specificity, 87.9%; positive predictive value, 73.3%; and negative predictive value, 85.3%. There was no significant difference in outcomes between primary repair alone and pyloric exclusion. Conclusions: Time from injury to initial operation may be the sole significant risk factor for postoperative duodenal leakage. Pyloric exclusion may not be able to prevent postoperative leakage.
Subject(s)
Duodenum , Trauma Centers , Duodenum/injuries , Duodenum/surgery , Humans , Postoperative Period , Retrospective Studies , Risk FactorsABSTRACT
Objective: Post-cardiotomy extracorporeal membrane oxygenation (PC-ECMO) is a known rescue therapy for neonates and pediatric patients who failed to wean from cardiopulmonary bypass (CPB) or who deteriorate in intensive care unit (ICU) due to various reasons such as low cardiac output syndrome (LCOS), cardiac arrest and respiratory failure. We conducted a systematic review and meta-analysis to assess the survival in neonates and pediatric patients who require PC-ECMO and sought the difference in survivals by each indication for PC-ECMO. Design: Systematic review and meta-analysis. Setting: Multi-institutional analysis. Participants: Neonates and pediatric patients who requires PC- ECMO. Interventions: ECMO after open-heart surgery. Results: Twenty-six studies were included in the analysis with a total of 186,648 patients and the proportion of the population who underwent PC-ECMO was 2.5% (2,683 patients). The overall pooled proportion of survival in this population was 43.3% [95% Confidence interval (CI): 41.3-45.3%; I 2: 1%]. The survival by indications of PC-ECMO were 44.6% (95% CI: 42.6-46.6; I 2: 0%) for CPB weaning failure, 47.3% (95% CI: 39.9-54.7%; I 2: 5%) for LCOS, 37.6% (95% CI: 31.0-44.3%; I 2: 32%) for cardiac arrest and 47.7% (95% CI: 32.5-63.1%; I 2: 0%) for respiratory failure. Survival from PC-ECMO for single ventricle or biventricular physiology, was reported by 12 studies. The risk ratio (RR) was 0.74 for survival in patients with single ventricle physiology (95% CI: 0.63-0.86; I 2: 40%, P < 0.001). Eight studies reported on the survival after PC-ECMO for genetic conditions. The RR was 0.93 for survival in patients with genetic condition (95% CI: 0.52-1.65; I 2: 65%, P = 0.812). Conclusions: PC-ECMO is an effective modality to support neonates and pediatric patients in case of failed CPB weaning and deterioration in ICU. Even though ECMO seems to improve survival, mortality and morbidity remain high, especially in neonates and pediatric patients with single ventricle physiology. Most genetic conditions alone should not be considered a contraindication to ECMO support, further studies are needed to determine which genetic abnormalities are associated with favorable outcome.
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Mesenchymal stem cells (MSCs) are an attractive candidate for the treatment of inflammatory bowel disease (IBD), but their poor delivery rate to an inflamed colon is a major factor hampering the clinical potential of stem cell therapies. Moreover, there remains a formidable hurdle to overcome with regard to survival and homing in to injured sites. Here, we develop a strategy utilizing monodisperse hydrogel microcapsules with a thin intermediate oil layer prepared by a triple-emulsion drop-based microfluidic approach as an in-situ oral delivering carrier. The oral delivery of stem-cell-loaded hydrogel microcapsules (SC-HM) enhances MSC survival and retention in the hostile stomach environment due to the intermediate oil layer and low value of the overall stiffness, facilitating programmable cell release during gastrointestinal peristalsis. SC-HM is shown to induce tissue repair, reduce the colonic macrophage infiltration responsible for the secretion of the pro-inflammatory factors, and significantly mitigate the severity of IBD in a mouse model, where MSCs released by SC-HM successfully accumulate at the colonic crypt. Moreover, a metagenomics analysis reveals that SC-HM ameliorates the dysbiosis of specific bacterial genera, including Bacteroides acidifaciens, Lactobacillus (L.) gasseri, Lactobacillus reuteri, and L. intestinalis, implying optimization of the microorganism's composition and abundance. These findings demonstrate that SC-HM is a potential IBD treatment candidate.
Subject(s)
Inflammatory Bowel Diseases , Mesenchymal Stem Cells , Microbiota , Animals , Capsules , Hydrogels/pharmacology , Inflammation , Inflammatory Bowel Diseases/drug therapy , MiceABSTRACT
BACKGROUND: The effectiveness of extracorporeal membrane oxygenation (ECMO) for patients with refractory cardiogenic shock or cardiac arrest is being established, and serum lactate is well known as a biomarker of end-organ perfusion. We evaluated the efficacy of pre-ECMO lactate for predicting 6-month survival in patients with acute coronary syndrome (ACS) undergoing ECMO. METHODS: We reviewed the medical records of 148 patients who underwent veno-arterial (VA) ECMO for ACS between January 2015 and June 2020. These patients were divided into survivors and non-survivors based on 6-month survival. All clinical data before and during ECMO were compared between the 2 groups. RESULTS: Patients' mean age was 66.0±10.5 years, and 116 (78.4%) were men. The total survival rate was 45.9% (n=68). Cox regression analysis showed that the pre-ECMO lactate level was an independent predictor of 6-month mortality (hazard ratio, 1.210; 95% confidence interval [CI], 1.064-1.376; p=0.004). The area under the receiver operating characteristic curve of pre-ECMO lactate was 0.64 (95% CI, 0.56-0.72; p=0.002; cut-off value=9.8 mmol/L). Kaplan-Meier survival analysis showed that the cumulative survival rate at 6 months was significantly higher among patients with a pre-ECMO lactate level of 9.8 mmol/L or less than among those with a level exceeding 9.8 mmol/L (57.3% vs. 31.8%, p=0.0008). CONCLUSION: A pre-ECMO lactate of 9.8 mmol/L or less may predict a favorable outcome at 6 months in ACS patients undergoing VA-ECMO. Further research aiming to improve the accuracy of predictions of reversibility in patients with high pre-ECMO lactate levels is essential.
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BACKGROUND: We have designed a reinforced drug-loaded vascular graft composed of polycaprolactone (PCL) and polydioxanone (PDO) via a combination of electrospinning/3D printing approaches. To evaluate its potential for clinical application, we compared the in vivo blood compatibility and performance of PCL/PDO + 10%DY grafts doped with an antithrombotic drug (dipyridamole) with a commercial expanded polytetrafluoroethylene (e-PTFE) graft in a porcine model. METHODS: A total of 10 pigs (weight: 25-35 kg) were used in this study. We made a new 5-mm graft with PCL/PDO composite nanofiber via the electrospinning technique. We simultaneously implanted a commercially available e-PTFE graft (n = 5) and our PCL/PDO + 10%DY graft (n = 5) into the carotid arteries of the pigs. No anticoagulant/antiplatelet agent was administered during the follow-up period, and ultrasonography was performed weekly to confirm the patency of the two grafts in vivo. Four weeks later, we explanted and compared the performance of the two grafts by histological analysis and scanning electron microscopy (SEM). RESULTS: No complications, such as sweating on the graft or significant bleeding from the needle hole site, were seen in the PCL/PDO + 10%DY graft immediately after implantation. Serial ultrasonographic examination and immunohistochemical analysis demonstrated that PCL/PDO + 10%DY grafts showed normal physiological blood flow and minimal lumen reduction, and pulsed synchronously with the native artery at 4 weeks after implantation. However, all e-PTFE grafts occluded within the study period. The luminal surface of the PCL/PDO + 10%DY graft in the transitional zone was fully covered with endothelial cells as observed by SEM. CONCLUSION: The PCL/PDO + 10%DY graft was well tolerated, and no adverse tissue reaction was observed in porcine carotid models during the short-term follow-up. Colonization of the graft by host endothelial and smooth muscle cells coupled with substantial extracellular matrix production marked the regenerative capability. Thus, this material may be an ideal substitute for vascular reconstruction and bypass surgeries. Long-term observations will be necessary to determine the anti-thrombotic and remodeling potential of this device.
Subject(s)
Nanofibers , Thrombosis , Animals , Blood Vessel Prosthesis , Carotid Arteries/pathology , Carotid Arteries/surgery , Endothelial Cells , Polytetrafluoroethylene , Swine , Thrombosis/pathologyABSTRACT
In nature, individual cells are compartmentalized by a membrane that protects the cellular elements from the surrounding environment while simultaneously equipped with an antioxidant defense system to alleviate the oxidative stress resulting from light, oxygen, moisture, and temperature. However, this mechanism has not been realized in cellular mimics to effectively encapsulate and retain highly reactive antioxidants. Here, we report cell-inspired hydrogel microcapsules with an interstitial oil layer prepared by utilizing triple emulsion drops as templates to achieve enhanced retention of antioxidants. We employ ionic gelation for the hydrogel shell to prevent exposure of the encapsulated antioxidants to free radicals typically generated during photopolymerization. The interstitial oil layer in the microcapsule serves as an stimulus-responsive diffusion barrier, enabling efficient encapsulation and retention of antioxidants by providing an adequate pH microenvironment until osmotic pressure is applied to release the cargo on-demand. Moreover, addition of a lipophilic reducing agent in the oil layer induces a complementary reaction with the antioxidant, similar to the nonenzymatic antioxidant defense system in cells, leading to enhanced retention of the antioxidant activity. Furthermore, we show the complete recovery and even further enhancement in antioxidant activity by lowering the storage temperature, which decreases the oxidation rate while retaining the complementary reaction with the lipophilic reducing agent.
Subject(s)
Antioxidants/pharmacology , Biocompatible Materials/pharmacology , Capsules/pharmacology , Hydrogels/pharmacology , Mineral Oil/chemistry , Animals , Antioxidants/chemistry , Biocompatible Materials/chemistry , Caco-2 Cells , Capsules/chemistry , Humans , Hydrogels/chemistry , Hydrogen-Ion Concentration , Materials Testing , Mice , NIH 3T3 Cells , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolismABSTRACT
The aim of the study is to develop artificial intelligence (AI) algorithm based on a deep learning model to predict mortality using abbreviate injury score (AIS). The performance of the conventional anatomic injury severity score (ISS) system in predicting in-hospital mortality is still limited. AIS data of 42,933 patients registered in the Korean trauma data bank from four Korean regional trauma centers were enrolled. After excluding patients who were younger than 19 years old and those who died within six hours from arrival, we included 37,762 patients, of which 36,493 (96.6%) survived and 1269 (3.4%) deceased. To enhance the AI model performance, we reduced the AIS codes to 46 input values by organizing them according to the organ location (Region-46). The total AIS and six categories of the anatomic region in the ISS system (Region-6) were used to compare the input features. The AI models were compared with the conventional ISS and new ISS (NISS) systems. We evaluated the performance pertaining to the 12 combinations of the features and models. The highest accuracy (85.05%) corresponded to Region-46 with DNN, followed by that of Region-6 with DNN (83.62%), AIS with DNN (81.27%), ISS-16 (80.50%), NISS-16 (79.18%), NISS-25 (77.09%), and ISS-25 (70.82%). The highest AUROC (0.9084) corresponded to Region-46 with DNN, followed by that of Region-6 with DNN (0.9013), AIS with DNN (0.8819), ISS (0.8709), and NISS (0.8681). The proposed deep learning scheme with feature combination exhibited high accuracy metrics such as the balanced accuracy and AUROC than the conventional ISS and NISS systems. We expect that our trial would be a cornerstone of more complex combination model.
Subject(s)
Wounds and Injuries/mortality , Abbreviated Injury Scale , Artificial Intelligence/statistics & numerical data , Benchmarking/statistics & numerical data , Databases, Factual/statistics & numerical data , Hospital Mortality , Humans , Injury Severity Score , Trauma Centers/statistics & numerical dataABSTRACT
This preliminary study aimed to screen non-coding RNAs (ncRNAs) from plasma exosomes as a new method for cervical cancer diagnosis. Differentially expressed RNAs were initially selected from among a group of 12 healthy individuals (normal group) and a pretreatment group of 30 patients with cervical cancer (cancer group). Then, we analyzed the association between an ncRNA-mRNA network and cancer using ingenuity pathway analysis after secondary selection according to the number and correlation of mRNAs (or ncRNAs) relative to changes in the expression of primarily selected ncRNAs (or mRNAs) before and after chemoradiotherapy. The number of RNAs selected from the initial RNAs was one from 13 miRNAs, four from 42 piRNAs, four from 28 lncRNAs, nine from 18 snoRNAs, 10 from 76 snRNAs, nine from 474 tRNAs, nine from 64 yRNAs, and five from 67 mRNAs. The combination of miRNA (miR-142-3p), mRNAs (CXCL5, KIF2A, RGS18, APL6IP5, and DAPP1), and snoRNAs (SNORD17, SCARNA12, SNORA6, SNORA12, SCRNA1, SNORD97, SNORD62, and SNORD38A) clearly distinguished the normal samples from the cancer group samples. We present a method for efficiently screening eight classes of RNAs isolated from exosomes for cervical cancer diagnosis using mRNAs (or ncRNAs) altered by chemoradiotherapy.
Subject(s)
Uterine Cervical Neoplasms , Early Detection of Cancer , Female , Gene Expression Profiling , Humans , MicroRNAsABSTRACT
Kaempferol, a bioflavonoid present in fruits and vegetables, has a variety of antioxidant and anti-inflammatory capacities, but the functional role of kaempferol in oxidative skin dermal damage has yet to be well studied. In this study, we examine the role of kaempferol during the inflammation and cell death caused by 12-O-tetradecanoylphorbol-13-acetate (TPA) in normal human dermal fibroblasts (NHDF). TPA (5 µM) significantly induced cytotoxicity of NHDF, where a robust increase in the interleukin (IL)-1ß mRNA among the various pro-inflammatory cytokines. The skin fibroblastic cytotoxicity and IL-1ß expression induced by TPA were significantly ameliorated by a treatment with 100 nM of kaempferol. Kaempferol blocked the production of the intracellular reactive oxygen species (ROS) responsible for the phosphorylation of c-Jun N-terminal kinase (JNK) induced by TPA. Interestingly, we found that kaempferol inhibited the phosphorylation of nuclear factor-kappa B (NF-κB) and the inhibitor NF-κB (IκBα), which are necessary for the expression of cleaved caspase-3 and the IL-1ß secretion in TPA-treated NHDF. These results suggest that kaempferol is a functional agent that blocks the signaling cascade of the skin fibroblastic inflammatory response and cytotoxicity triggered by TPA.
Subject(s)
Dermatologic Agents/pharmacology , Fibroblasts/drug effects , Interleukin-1beta/metabolism , JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors , Kaempferols/pharmacology , Skin/drug effects , Tetradecanoylphorbol Acetate/pharmacology , Blotting, Western , Cell Line , Enzyme-Linked Immunosorbent Assay , Fibroblasts/metabolism , Humans , JNK Mitogen-Activated Protein Kinases/metabolism , Reactive Oxygen Species/metabolism , Real-Time Polymerase Chain Reaction , Skin/metabolismABSTRACT
Astaxanthin, a natural antioxidant carotenoid, is a nutrient with diverse health benefits, given that it decreases the risk of oxidative stress-related diseases. In the present study, we investigate the functional role of astaxanthin during autophagic cell death induced by the estrogenic endocrine-disrupting chemical bisphenol A (BPA) in normal human dermal fibroblasts (NHDF). BPA significantly induced apoptotic cell death and autophagy in NHDF. Autophagic cell death evoked by BPA was significantly restored upon a treatment with astaxanthin (10 µM) via the inhibition of intracellular reactive oxygen species (ROS) production. Astaxanthin inhibited the phosphorylation of extracellular signal-regulated kinases (ERK) stimulated by ROS production, but it did not influence the activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) in BPA-treated NHDF. Astaxanthin abrogated the ERK-mediated activation of nuclear factor-kappa B (NF-κB), which is responsible for the mRNA expression of LC3-II, Beclin-1, Atg12, and Atg14 during apoptotic cell death induced by BPA. These results indicate that astaxanthin is a pharmacological and nutritional agent that blocks the skin fibroblastic autophagic cell death induced by BPA in human dermal fibroblasts.