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Both inhalation injury and acute respiratory distress syndrome (ARDS) are risk factors that predict mortality in severely burned patients. Extracorporeal life support (ECLS) is widely used to rescue these patients; however, its efficacy and safety in this critical population have not been well defined. We report our experience of using ECLS for the treatment of severely burned patients with concurrent inhalation injury and ARDS.This was a retrospective analysis of 14 patients collected from a single medical burn center from 2012 to 2019. All patients suffered from major burns with inhalation injury and ARDS, and were treated with ECLS.The median total body surface area of deep dermal or full thickness burns was 94.5%, ranging 47.7-99.0 %. The median revised Baux score was 122.0, ranging 90.0-155.0. All patients developed ARDS with a median partial pressure of arterial oxygen to a fraction of inspired oxygen ratio of 61.5, ranging 49.0-99.0. Indications for ECLS included sustained hypoxemia and unstable hemodynamics. The median interval for initiating ECLS was 2.5 days, ranging 1.0-156.0 days. The median duration of ECLS was 2.9 days, ranging 0.3-16.7 days. The overall survival to discharge was 42.8%. Causes of death included sepsis and multiple organ failure. ECLS-related complications included cannulation bleeding, catheter-related infection, and hemolysis. The incidence of risk factors reported in literature were higher in non-survivors, including Baux120, albumin3.0 g/dL, and lactate8 mmol/L.For severely burned patients with concurrent inhalation injury and ARDS, ECLS could be a salvage treatment to improve sustained hypoxemia. However, the efficacy of hemodynamic support was limited. Identifying definite ECLS indications and rigorous patient selection would contribute to better clinical outcomes.

ScCO2-decellularized artery graft having tremendous application in vascular regenerative medicine.It with physiological-like responses, including high potential of biocompatibility and long-term patency, lower risk of aneurysm after xenotransplantation.

Multivalent ions modify the properties of the solid/liquid interfaces, and in some cases, they can even invert the polarity of surface charge, having large consequences for separation processes based on charge. The so-called charge inversion is observed as a switch from negative surface charge in monovalent salts, e.g., KCl, to effective positive surface charge in multivalent salts that is possible through a strong accumulation and correlation of the multivalent ions at the surface. It is not known yet, however, whether the density of the positive charge induced by charge inversion depends on the pore opening diameter, especially in extreme nanoconfinement. Here, we probe how the effective surface charge induced by charge inversion is influenced by the pore opening diameter using a series of nanopores with an opening between 4 and 25 nm placed in contact with trivalent chromium ions in tris(ethylenediamine)chromium(III) sulfate at different concentrations. Our results suggest that the effective positive charge density can indeed be modified by nanoconfinement to the extent that is dependent on the pore diameter, salt concentration, and applied voltage. In addition, the correlated ions can increase the transmembrane current in nanopores with an opening diameter down to 10 nm and cause a significant blockage of the current for narrower pores. The results provide guidelines to control ionic transport at the nanoscale with multivalent ions and demonstrate that in the same experimental conditions, differently sized pores in the same porous material can feature different surface charge density and possibly ion selectivity.

Ultrathin nanopore sensors allow single-molecule and polymer measurements at sub-microsecond time resolution enabled by high current signals (∼10-30 nA). We demonstrate for the first time the experimental probing of the ultrafast translocation and folded dynamics of double-stranded DNA (dsDNA) through a nanopore at 10 MHz bandwidth with acquisition of data points per 25 ns (150 MB/s). By introducing a rigorous algorithm, we are able to accurately identify each current level present within translocation events and elucidate the dynamic folded and unfolded behaviors. The remarkable sensitivity of this system reveals distortions of short-lived folded states at a lower bandwidth. This work revisits probing of dsDNA as a model polymer and develops broadly applicable methods. The combined improvements in sensor signals, instrumentation, and large data analysis methods uncover biomolecular dynamics at unprecedentedly small time scales.

Although extracorporeal life support (ECLS) can provide emergency systemic perfusion for acute fulminant myocarditis (AFM), the mortality rate remains extremely high, especially in those undergoing extracorporeal cardiopulmonary resuscitation (ECPR). Temporary ventricular assist device (VAD) can provide a more physiological blood flow direction and better subsequent organ perfusion than ECLS. We investigated temporary VAD efficacy in ECPR-revived AFM patients.During January 2012-May 2019, we retrospectively recruited 22 AFM patients with hemodynamic collapse and ECPR; 11 underwent ECLS only and 11 underwent additional VAD support after ECLS. Systemic perfusion was compared via laboratory biochemistry at post-ECPR days 2 (D2) and 4 (D4). Consciousness and cardiac function were assessed through the Glasgow Coma Scale (GCS) and echocardiography, respectively. All major complications and causes of mortality were recorded; 30-day survival was analyzed and risk factors were predicted.The VAD group had significantly better hemodynamic improvement; more inotropes being tapered at D2 and D4; better data representative of systemic perfusion, including albumin, pH, bicarbonate, and lactate levels at D4; and better 30-day survival (72.7% vs. 27.2%, p = 0.033). The causes of mortality included central failure, multiple organ failure, and bacteremia with sepsis. The risk factors included lethal dysrhythmia before ECLS, GCS5 at D2, and elevated cardiac enzymes at D4.For AFM patients, temporary VAD could provide better systemic perfusion and organ preservation than ECLS. VAD had better survival, including improved recovery and successful transplantation. Hence, temporary VAD should be considered if ECLS cannot revive the sustained cardiogenic shock.

In this paper, we introduce a new variant of domination called the outer-paired domination. For a graph [Formula: see text], an outer-paired dominating set [Formula: see text] is a dominating set of [Formula: see text] such that the induced subgraph of [Formula: see text] contains a perfect matching. The outer-paired domination number of a graph [Formula: see text] is the cardinality of a minimum outer-paired dominating set of [Formula: see text]. We show that finding the outer-paired domination number of a graph [Formula: see text] is NP-hard on bipartite graphs, chordal graphs, and planar graphs. We also propose a linear-time algorithm for solving the outer-paired domination problem on trees.

The switching of "ON" and "OFF" states of an ionic diode is investigated by considering a conical nanopore partially functionalized two polyelectrolyte (PE) layers via layer-by-layer deposition. Through observing the inversion of its rectification behavior, we demonstrate the function of the PE bilayers in ionic transport regulation. The ionic diode exhibits an ultrahigh ion rectification at a low level of pH. In an aqueous NaCl solution at pH 2, for example, the ratio of the current at "ON" state and that at "OFF" state can be about 800 and 200 for 1 and 100 mM, respectively. This remarkable gating behavior can be explained by the anion-pump-induced ion accumulation in the neutral region as well as the depletion zone at the interface. Our results further demonstrate the possibility of achieving an ultrahigh rectification in an ionic diode having a unipolar-like configuration.

We fabricate on-chip solid-state nanofluidic-2D nanopore systems that can limit the range of motion for DNA in the sensing region of a nanopore. We do so by creating devices containing one or more silicon nitride pores and silicon nitride pillars supporting a 2D pore that orient DNA within a nanopore device to a restricted geometry, yet allow the free motion of ions to maintain a high signal-to-noise ratio. We discuss two concepts with two and three independent electrical connections and corresponding nanopore chip device architectures to achieve this goal in practice. Here, we describe device fabrication and transmission electron microscope (TEM) images, and provide simulated translocations based on the finite element analysis in 3D to demonstrate its merit. In both methods, there is a main 2D nanopore which we refer to as a "sensing" nanopore (monolayer MoS2 in this paper). A secondary layer is either an array of guiding pores sharing the same electrode pair as the sensing pore (Method 1) or a single, independently contacted, guiding pore (Method 2). These pores are constructed parallel to the "sensing" pore and serve as "guiding" elements to stretch and feed DNA into the atomically thin sensing pore. We discuss the practical implementation of these concepts with nanofluidic and Si-based technology, including detailed fabrication steps and challenges involved for DNA applications in solution.

Background: Some research indicated that hypothyroidism has huge adverse effects for the metabolic, cardiovascular, respiratory, and immune systems. However, there is no confirmed conclusion for the effect of cardiovascular surgery. This cohort study aims to investigate the prognosis of hypothyroidism patient at the age under 65-year-old after coronary artery bypass grafting (CABG) surgery. Method: From the National Health Insurance Research Database of Taiwan, 1586 patients with hypothyroidism who underwent elective CABG surgery were selected, along with 6334 patients who underwent surgery in a ratio of 1:4 sex-, age- and index year-matched controls, who were out of hypothyroidism. We used Cox proportional hazard analysis to compare the rate of 30-day, 5-year mortality, post-operative atrial fibrillation, respiratory complication during an average of 10-year follow-up. Result: Post-CABG patients had more hospital days, which was associated with hypothyroidism, male, DM and higher CCI_R (p < 0.001). Post-CABG patients had more inpatient respiratory complications, which was associated with hypothyroidism (p = 0.041), DM and CCI_R (p < 0.001, p = 0.046), and there was no difference in 1-year respiratory complication, tracheostomy in the same hospital course and within 1 year, repeated PCI, Af, CVVH, cerebral infarction, 30-day and 5-year mortality rate. Conclusions: Hypothyroidism correlates to post-CABG ventilator-related complications and pneumonia, and prolonged hospital days, but no effect on 30-day, 5-year mortality, post-operative atrial fibrillation and cerebral infarction rate. Thyroid function survey might include routinely preoperative survey for CABG outcome prognosis.

Cardiovascular complications are leading causes of morbidity and mortality in patients with chronic kidney disease (CKD). CKD significantly affects cardiac calcium (Ca2+) regulation, but the underlying mechanisms are not clear. The present study investigated the modulation of Ca2+ homeostasis in CKD mice. Echocardiography revealed impaired fractional shortening (FS) and stroke volume (SV) in CKD mice. Electrocardiography showed that CKD mice exhibited longer QT interval, corrected QT (QTc) prolongation, faster spontaneous activities, shorter action potential duration (APD) and increased ventricle arrhythmogenesis, and ranolazine (10 µmol/L) blocked these effects. Conventional microelectrodes and the Fluo‐3 fluorometric ratio techniques indicated that CKD ventricular cardiomyocytes exhibited higher Ca2+ decay time, Ca2+ sparks, and Ca2+ leakage but lower [Ca2+]i transients and sarcoplasmic reticulum Ca2+ contents. The CaMKII inhibitor KN93 and ranolazine (RAN; late sodium current inhibitor) reversed the deterioration in Ca2+ handling. Western blots revealed that CKD ventricles exhibited higher phosphorylated RyR2 and CaMKII and reduced phosphorylated SERCA2 and SERCA2 and the ratio of PLB‐Thr17 to PLB. In conclusions, the modulation of CaMKII, PLB and late Na+ current in CKD significantly altered cardiac Ca2+ regulation and electrophysiological characteristics. These findings may apply on future clinical therapies.

Objective Aortic aneurysms (AAs) and intracranial aneurysms (IAs) share several clinical risk factors, a genetic predisposition, and molecular signaling pathways. Nonetheless, associations between IAs and AAs remain to be thoroughly validated in large-scale studies. In addition, no effective medical therapies exist for unruptured IAs or AAs. Methods Data for this nationwide, population-based, retrospective, cohort study described herein were obtained from the National Health Insurance Research Database in Taiwan. The study outcomes assessed were (1) the cumulative incidence of IAs, which was compared between AA and patients without an AA and (2) the cumulative incidence of IAs in patients with AAs during the 13-year follow-up period, which was further compared among those who underwent open surgical repair (OSR), endovascular aneurysm repair or nonsurgical treatment (NST). Results Our analyses included 20,280 patients with an AA and 20,280 propensity score-matched patients without an AA. Compared with the patients without an AA, patients with AA exhibited a significantly increased risk of an IA diagnosis (adjusted hazard ratio [HR], 3.395; P Conclusions We demonstrated an association between IAs and AAs, even after adjusting for several comorbidities. We also found that OSR was associated with fewer recognized IAs than NST.

Background: Atypical antipsychotics increase the risk of atrial arrhythmias and sudden cardiac death. This study investigated whether ziprasidone, a second-generation antipsychotic, affected intracellular Ca2+ and Na+ regulation and oxidative stress, providing proarrhythmogenic substrates in atriums. Methods: Electromechanical analyses of rabbit atrial tissues were conducted. Intracellular Ca2+ monitoring using Fluo-3, the patch-clamp method for ionic current recordings, and a fluorescence study for the detection of reactive oxygen species and intracellular Na+ levels were conducted in enzymatically dissociated atrial myocytes. Results: Ziprasidone-treated atriums showed sustained triggered activities after rapid pacing, which were inhibited by KN-93 and ranolazine. A reduced peak L-type Ca2+ channel current and enhanced late Na+ current were observed in ziprasidone-treated atrial myocytes, together with an increased cytosolic Na+ level. KN-93 suppressed the enhanced late Na+ current in ziprasidone-treated atrial myocytes. Atrial myocytes treated with ziprasidone showed reduced Ca2+ transient amplitudes and sarcoplasmic reticulum (SR) Ca2+ stores, and increased SR Ca2+ leakage. Cytosolic and mitochondrial reactive oxygen species production was increased in atrial myocytes treated with ziprasidone. TNF-α and NLRP3 were upregulated in ziprasidone-treated myocytes, and the level of phosphorylated calcium/calmodulin-dependent protein kinase II protein was increased. Conclusions: Our results suggest that ziprasidone increases the occurrence of atrial triggered activity and causes intracellular Ca2+ and Na+ dysregulation, which may result from enhanced oxidative stress and activation of the TNF-α/NLRP3 inflammasome pathway in ziprasidone-treated myocytes.

Background: Lipotoxicity causes endoplasmic reticulum (ER) stress, leading to cell apoptosis. Sirtuin 1 (Sirt1) regulates gene transcription and cellular metabolism. In this study, we investigated the role of Sirt1 in palmitate-induced ER stress. Methods: Both H9c2 myoblasts and heart-specific Sirt1 knockout mice fed a palmitate-enriched high-fat diet were used. Results: The high-fat diet induced C/EBP homologous protein (CHOP) and activating transcription factor 4 (ATF4) expression in both Sirt1 knockout mice and controls. The Sirt1 knockout mice showed higher CHOP and ATF4 expression compared to those in the control. Palmitic acid (PA) induced ATF4 and CHOP expression in H9c2 cells. PA-treated H9c2 cells showed decreased cytosolic NAD+/NADH alongside reduced Sirt1′s activity. The H9c2 cells showed increased ATF4 and CHOP expression when transfected with plasmid encoding dominant negative mutant Sirt1. Sirt1 activator SRT1720 did not affect CHOP and ATF4 expression. Although SRT1720 enhanced the nuclear translocation of ATF4, the extent of the binding of ATF4 to the CHOP promoter did not increase in PA treated-H9c2 cells. Conclusion: PA-induced ER stress is mediated through the upregulation of ATF4 and CHOP. Cytosolic NAD+ concentration is diminished by PA-induced ER stress, leading to decreased Sirt1 activity. The Sirt1 activator SRT1720 promotes the nuclear translocation of ATF4 in PA-treated H9c2 cells.

Enabled by proteins, we present an all-electrical method for rapid detection of small pharmaceuticals (ibuprofen and sulfamethoxazole [SMZ]) in aqueous media using silicon nitride pores. Specifically, we use carrier proteins, bovine serum albumin (BSA), and take advantage of their interactions with two small drug molecules to form BSA-drug complexes which can be detected by nm-diameter pores, thereby confirming the presence of small pharmaceuticals. We demonstrate detection of ibuprofen and SMZ at concentrations down to 100 nM (∼21 μg/L) and 48.5 nM (12 μg/L), respectively. We observe changes in electrical signal characteristics (reflected in event durations, rates, current magnitudes, and estimated particle diameters) of BSA-drug complexes compared to BSA-only, and differences between these two small pharmaceuticals, possibly paving a path toward developing selective sensors by identifying "electrical fingerprints" of these molecules in the future. These distinct electrical signals are likely a combined result of diffusion, electrophoretic and electroosmotic effects, interactions between the pore and particles, which depend on pore diameters, pH, and the resulting surface charges. The use of single-molecule-counting nanopores allows sensing of small pharmaceuticals, studies of protein conformational changes, and may aid in efforts to evaluate the impact of small drug molecules on aquatic and human life.

Background: Categorization of hospital emergency capability (CHEC) is a policy implemented worldwide to regionalize critical emergent care. The CHEC policy mainly uses time-based indicators as emergency care quality measurements.Objectives: We aimed to explore the CHEC policy spotlight effect on critical time-sensitive diseases with and without the influence of time-based surveillance indicators and guidelines. Research Design: We conducted a nationwide retrospective cohort study between 2005–2011. Regarding critical time-sensitive diseases, our study targeted acute ischemic stroke (AIS), ST-segment elevation myocardial infarction (STEMI), septic shock, and major trauma. We selected diagnosis and treatment guideline adherence as process quality measures and defined medical utilization, upward transfer rate, and short-term mortality rate as outcome indicators. Subjects: The Taiwan National Health Insurance 2005 Longitudinal Health Insurance Database contains one million random cases, including medical records and hospital information. Results: During this 7-year study AIS, STEMI, septic shock, and major trauma, respectively. AIS and STEMI cohorts had significantly higher rates of guideline adherence and better process quality than those of septic shock and major trauma cohorts. Furthermore, AIS and STEMI cohorts had a significant increase in diagnosis costs. Conclusion: The CHEC policy spotlight effect exists in critical time-sensitive diseases with time-based quality indicators. Importantly, disease entities without these indicators may experience decreases in diagnosis and treatment guideline adherence, indirectly jeopardizing their outcomes.

Background: Nitroglycerin facilitates microcirculation and oxygen delivery through vasodilation. The purpose of this study was to clarify the effects of nitroglycerin-induced vasodilation and potential hypotension on tissue perfusion under cerebral oximetry monitoring during rewarming in cardiopulmonary bypass. Methods: Elective cardiac surgical patients were randomly assigned to either a nitroglycerin group (n = 32) with an intravenous infusion of 1–5 mcg/kg/min or a control group (n = 31) with 0–0.1 mcg/kg/min infusion, since the initiation of rewarming. Perioperative arterial blood gas data were collected in addition to hemodynamic variables, cerebral oximetry values, urine output, and postoperative outcomes. Results: Nearly one-fifth (6/32) of patients in the nitroglycerin group experienced transient (≤5 min) profound hypotension (mean arterial blood pressure ≤40 mmHg) after the initiation of infusion. There were no significant differences between groups in terms of perioperative levels of cerebral oximetry, cardiac index, plasma glucose, lactate, bicarbonate, base excess, or post-bypass activated coagulation time. In the nitroglycerin group, urine output was nonsignificantly higher during cardiopulmonary bypass (p = 0.099) and within 8 h after surgery (p = 0.157). Perioperative transfused blood products, postoperative inotropic doses, extubation time, and intensive care unit stay were comparable for the two groups. Conclusions: Initiation of intravenous nitroglycerin infusion (at 1–5 mcg/kg/min) during rewarming in hypothermic cardiopulmonary bypass resulted in transient profound hypotension in one-fifth of patients and did not improve perioperative cerebral oxygenation, tissue perfusion, and coagulation in cardiac surgery.

Background and aims Atherosclerosis preferentially develops in arterial branches and curvatures where vascular endothelium is exposed to disturbed flow. In this study, the effects of disturbed flow on the regulation of vascular endothelial phosphoproteins and their contribution to therapeutic application in atherogenesis were elucidated. Methods Porcine models, large-scale phosphoproteomics, transgenic mice, and clinical specimens were used to discover novel site-specific phosphorylation alterations induced by disturbed flow in endothelial cells (ECs). Results A large-scale phosphoproteomics analysis of native endothelium from disturbed (athero-susceptible) vs. pulsatile flow (athero-resistant) regions of porcine aortas led to the identification of a novel atherosclerosis-related phosphoprotein vinculin (VCL) with disturbed flow-induced phosphorylation at serine 721 (VCLS721p). The induction of VCLS721p was mediated by G-protein-coupled receptor kinase 2 (GRK2)S29p and resulted in an inactive form of VCL with a closed conformation, leading to the VE-cadherin/catenin complex disruption to enhance endothelial permeability and atherogenesis. The generation of novel apolipoprotein E-deficient (ApoE−/−) mice overexpressing S721-non-phosphorylatable VCL mutant in ECs confirmed the critical role of VCLS721p in promoting atherosclerosis. The administration of a GRK2 inhibitor to ApoE−/− mice suppressed plaque formation by inhibiting endothelial VCLS721p. Studies on clinical specimens from patients with coronary artery disease (CAD) revealed that endothelial VCLS721p is a critical clinicopathological biomarker for atherosclerosis progression and that serum VCLS721p level is a promising biomarker for CAD diagnosis. Conclusions The findings of this study indicate that endothelial VCLS721p is a valuable hemodynamic-based target for clinical assessment and treatment of vascular disorders resulting from atherosclerosis.

BackgroundAim of this study was to evaluate the prognostic of tumor volume reduction rate (TVRR) status post induction chemotherapy (IC) in LA-HNSCC.MethodsPatients with newly diagnosed LA-HNSCC from year 2007 to 2016 at a single center were included in this retrospective study. All patients had received IC as TPF (taxotere, platinum, fluorouracil) followed by daily definitive intensity-modulated radiotherapy (IMRT) for 70 Gy in 35 fractions concurrent with or without cisplatin-based chemotherapy. Tumor volume reduction rate of the primary tumor (TVRR-T) and lymph node (TVRR-N) was measured and calculated by contrast-enhanced CT images at diagnosis, and one month after final IC cycle, and analyzed though a univariate and multivariate Cox regression model.ResultsNinety patients of the primary cancer sites at hypopharynx (31/90, 34.4%), oropharynx (29/90, 32.2%), oral cavity (19/90, 21.1%) and larynx (11/90, 12.2%) were included in this study, with a median follow-up time interval of 3.9 years. In univariate Cox regression analysis, the TVRR-T as the only variable showed a significant difference for disease-free survival (DFS) (hazard ratio [HR] 0.77, 95% confidence interval (CI) 0.63 to 0.96; P = 0.02), aside from cancer site, RECIST, age and IC dose. In multivariate Cox regression analysis, The TVRR-T was also an independently significant prognostic factor for DFS (HR 0.77, 95% CI 0.62 to 0.97; P = 0.02). At a cutoff value using TVRR-T of 50% in Kaplan-Meier survival analysis, the DFS was significant higher with TVRR-T ≥ 50% group (log-rank test, p = 0.024), and also a trend of improved OS. (log-rank test, p = 0.069).ConclusionsTVRR-T was related to improved DFS and trend of improved OS. Other factors including patient’s age at diagnosis, the primary cancer site, and RECIST, were not significantly related to DFS.

Resistive pulse sensing using solid-state nanopores provides a unique platform for detecting the structure and concentration of molecules of different types of analytes in an electrolyte solution. The capture of an entity into a nanopore is subject not only to the electrostatic force but also the effect of electroosmotic flow originating from the charged nanopore surface. In this study, we theoretically analyze spherical particle electrophoretic behavior near the entrance of a charged nanopore. By investigating the effects of pore size, particle-pore distance, and salt concentration on particle velocity, we summarize dominant mechanisms governing particle behavior for a range of conditions. In the literature, the Helmholtz-Smoluchowski equation is often adopted to evaluate particle translocation by considering the zeta potential difference between the particle and nanopore surfaces. We point out that, due to the difference of the electric field inside and outside the nanopore and the influence from the existence of the particle itself, the zeta potential of the particle, however, needs to be at least 30% higher than that of the nanopore to allow the particle to enter into the nanopore when its velocity is close to zero. Accordingly, we summarize the effective salt concentrations that enable successful particle capture and detection for different pore sizes, offering direct guidance for nanopore applications.

Background: Lipotoxicity causes endoplasmic reticulum (ER) stress, leading to cell apoptosis. Sirtuin 1 (Sirt1) regulates gene transcription and cellular metabolism. In this study, we investigated the role of Sirt1 in palmitate-induced ER stress. Methods: H9c2 myoblasts and heart-specific Sirt1 knockout mice fed a palmitate-enriched high-fat diet were used. Results: The high-fat diet induced C/EBP homologous protein (CHOP) and activating transcription factor 4 (ATF4) expression in both Sirt1 knockout mice and controls. Sirt1 knockout mice showed higher CHOP and ATF4 expression compared to those in control. Palmitic acid (PA) induced ATF4 and CHOP expression in H9c2 cells. PA-treated H9c2 cells showed decreased cytosolic NAD+/NADH alongside reduced Sirt1’s activity. H9c2 cells showed increased ATF4 and CHOP expression when transfected with plasmid encoding dominant negative mutant Sirt1. Sirt1 activator SRT1720 did not affect CHOP and ATF4 expression. Although SRT1720 enhanced nuclear translocation of ATF4, the extent of the binding of ATF4 to the CHOP promoter did not increase further in PA treated-H9c2 cells.Conclusion: PA-induced ER stress is mediated through upregulation of ATF4 and CHOP. Cytosolic NAD+ concentration is diminished by PA-induced ER stress, leading to decreased Sirt1 activity. The Sirt1 activator SRT1720 promotes nuclear translocation of ATF4 in PA-treated H9c2 cells.

This retrospective cohort study aimed to evaluate the association between acetylcholinesterase inhibitors (AChEI) usage and the risk of lung cancer. Data from 116,106 new users of AChEI and 348,318, at a ratio of 1:3, matched by age, sex, and index-year, between 2000 and 2015 controls were obtained from the Taiwan Longitudinal Health Insurance Database in this cohort study. The Cox regression model was used to compare the risk of lung cancer. The adjusted hazard ratio (aHR) of lung cancer for AChEI users was 1.198 (95% confidence interval [CI] = 0.765–1.774, p = 0.167). However, the adjusted HR for patients aged ≥ 65 was adjusted to HR: 1.498 (95% CI = 1.124–1.798, p

Background: Both inhalation injury and acute respiratory distress syndrome (ARDS) are risk factors that predict mortality in severely burned patients. Extracorporeal life support (ECLS) is widely used to rescue these patients; however, its efficacy and safety in this critical population have not been well defined. We report our experience of using ECLS for treatment of severely burned patients with concurrent inhalation injury and ARDS. Methods: This is a retrospective analysis of 14 patients, including 10 males and four females, collected from a single medical burn center from 2012 to 2019. The mean age was 38.6±12.3 (range, 19-59) years. All suffered from major burns with inhalation injury. The average total body surface area of deep dermal or full thickness (DD/FT) burns was 81.6±20.0% (range, 47–99%). The average revised Baux score was 137.3 ± 22.6 (range, 107 – 172). All had developed ARDS with mean PaO2/FiO2 of 67.8±17.3. Indications for ECLS included sustained hypoxemia and unstable hemodynamics. The mean interval for initiating ECLS was 20.3 ± 40.8 days (range, 1-156 days). Results: The mean duration of ECLS was 5.0±5.6 days (range, 0.3-16.7 days). The overall survival to discharge was 42.8%. Causes of death included sepsis (n=4) and multiple organ failure (n=4). The ECLS-related complications included cannulation bleeding, catheter-related infection, and hemolysis. The predicted risk factors of mortality before ECLS included lactate>8 mmol/L and Baux score>120. Conclusions: For severely burned patients with concurrent inhalation injury and ARDS, ECLS could be a salvage treatment to improve sustained hypoxemia. However, the efficacy of hemodynamic support seemed limited. Definite ECLS indications and rigorous patient selection would contribute to better clinical outcomes.

Phosphodiesterase inhibitors can be used to enhance second messenger signaling to regulate intracellular CaMice with cardiac-specific Sirt1 knockout (Sirt1Sirt1Our results suggest that ITI-214 improves intracellular Ca

Surface charge plays a very important role in biological processes including ionic and molecular transport across a cell membrane. Placement of charges and charge patterns on walls of polymer and solid-state nanopores allowed preparation of ion-selective systems as well as ionic diodes and transistors to be applied in building biological sensors and ionic circuits. In this article, we show that the surface charge of a 10 nm diameter silicon nitride nanopore placed in contact with a salt gradient is not a constant value, but rather it depends on applied voltage and magnitude of the salt gradient. We found that even when a nanopore was in contact with solutions of pH equivalent to the isoelectric point of the pore surface, the pore walls became charged with voltage-dependent charge density. Implications of the charge gating for detection of proteins passing through a nanopore were considered, as well. Experiments performed with single 30 nm long silicon nitride nanopores were described by continuum modeling, which took into account the surface reactions on the nanopore walls and local modulation of the solution pH in the pore and at the pore entrances. The results revealed that manipulation of surface charge can occur without changing pH of the background electrolyte, which is especially important for applications where maintaining pH at a constant and physiological level is necessary. The system presented also offers a possibility to modulate polarity and magnitude of surface charges in a two-electrode setup, which previously was accomplished in more complex multielectrode systems.

Ni-only and Ni-CeO2 particles decorated on Al2O3 support material were prepared for an effective catalytic reductive amination of polypropylene glycol (PPG) to polyetheramines (PEA). Incipient wetness impregnation was employed for the preparation of catalysts followed by complementary material characterization (powder XRD, SEM, HRTEM, XPS, H2-TPR and NH3-TPD). High selectivity to PEA (~ 100%) was achieved. The catalytic activity obtained was proportional to Ni and Ce loadings (CCe), when CCe ≤ 15%. Hybridization with CeO2 inhibited formation of nickel nitride and enhanced activity (by 15.3%) and operation stability of Ni catalyst (by 20×). The present work has demonstrated a facile route to fabricate Ni-CeO2 hybrid catalysts on alumina support material and provided mechanistic understanding of the synergistic effect occurred for the heterogeneous catalytic reductive amination.

Chemically functionalized bioinspired nanopores are widely adopted to control the ionic transport for various purposes. A detailed understanding of the underlying mechanisms is not only desirable but also necessary for device design and experimental data interpretation. Here, the conductance and the ion selectivity of a conical nanopore surface modified by a polyelectrolyte (PE) layer are studied through adjusting the pH, the bulk salt concentration, and the level of the applied potential bias. Possible mechanisms are proposed and discussed in detail. We show that the conductance is sensitive to the variation in the solution pH. The ion selectivity of the nanopore is influenced significantly by both the solution pH and the level of the applied potential bias. In particular, a cation-selective nanopore might become anion-selective through raising the applied potential bias. The ion transport behavior can be tuned easily by adjusting the level of pH, salt concentration, and applied potential bias, thereby providing useful information for the design of nanopore-based sensing devices.

Extending previous electrokinetic analyses based on a Newtonian fluid to power-law fluids, we investigate the behaviors of the ion current rectification (ICR) and the ion selectivity S of a conical nanopore having a pH-regulated surface. The bulk salt concentration Cbulk, the solution pH, and the power-law index n are examined in detail for their influences on these behaviors. We show that the ICR ratio for the case where pH is lower than the isoelectric point (IEP) of the nanopore surface is different both quantitatively and qualitatively from that for the case where pH > IEP. The relative magnitude of the ICR ratio as n varies depends largely on the level of Cbulk. In contrast, S (pH IEP), where | S | decreases with increasing Cbulk and/or decreasing n. In addition, S is very sensitive to n, for example, a decrease of n from 1.0 (Newtonian fluid) to 0.9 (pseudoplastic fluid) can yield a 245% increase in S at Cbulk = 100 mM. Implying that the performance of ion separation can be improved by tuning the fluid viscosity. Mechanisms are proposed for explaining the observed behaviors in the ICR ratio.

Dementia and aortic aneurysms share clinical risk factors and molecular signaling pathways. However, the association between dementia and aortic aneurysms has not been examined. The potential effects of open surgical repair (OSR) of aortic aneurysms on future dementia events are unknown.We conducted this nationwide population-based, retrospective cohort study using the Taiwanese National Health Insurance Research Database (NHIRD). The cumulative incidence of dementia over a 13-yearfollow-up period was compared among 1)aortic aneurysms and non-aortic aneurysm patients and 2)aortic aneurysm patients who underwent OSR, endovascular aneurysm repair (EVAR) or nonsurgical treatment (NST).This study enrolled 19,921 aortic aneurysms patients and 19,921 matched controls. The aortic aneurysm cohort exhibited a significantly increased incidence of dementia compared with the controls (adjusted hazard ratio (HR)=3.559, p0.001). Furthermore, 5409 aortic aneurysm patients were treated with surgical intervention, whereas 5409 matched aortic aneurysm patients were not. Aortic aneurysm patients who underwent OSR had a significantly lower incidence of dementia than those who underwent NST (adjusted HR=0.638, 95% confidence interval (CI)=0.411-0.764, p0.001). Patients who underwent EVAR did not have a lower incidence of dementia than those who underwent NST.OSR was associated with a reduced incidence of dementia in patients with aortic aneurysms compared to NST.

The potential applications of biomimetic artificial nanopores in versatile fields capture much attention in the past few decades. Although it is known that applying simultaneously an electric poten...

Bioinspired, artificial functional nanochannels for intelligent molecular and ionic transport control have versatile potential applications in nanofluidics, energy conversion, and controlled drug release. To simulate the gating and rectification functions of biological ion channels, we model the electrokinetic ion transport phenomenon in an asymmetric double-gated nanochannel having a pH-regulated, zwitterionic surface. Taking account of the effect of electroosmotic flow (EOF), the conductance of the nanochannel and its ion current rectification (ICR) behavior are investigated and the associated mechanisms interpreted. In particular, the influences of the solution pH, the bulk salt concentration, and the base opening radius and the surface curvature of the nanochannel on these behaviors are examined. We show that through adjusting the base opening radius and the surface curvature of a nanochannel, its ICR behavior can be tuned effectively. In addition to proposing underlying mechanisms for the phenomena observed, the results gathered in this study also provide necessary information for designing relevant devices.

The power generated from the Gibbs free energy of mixing through reverse electrodialysis (RED) is a promising renewable energy of great potential. In this study the performance of a nanochannel having a pH-regulated surface in RED is examined, focusing on the influence of the bulk salt concentration, the distribution of H + , and the nanochannel size and its shape. Taking account of the effect of osmotic flow, we consider three types of nanochannel: bullet-shaped, conical, and trumpet-shaped nanochannels. Because the smaller the nanochannel space the more significant the degree of electric double layer overlapping the trumpet-shaped nanochannel has the best ion selectivity. As the ratio of (nanochannel length/curvature radius) varies the maximum power generated from a bullet-shaped nanochannel has a local maximum. This can be explained by the associated diffusion potential and the electric current passing through it. The results gathered provide desirable and necessary information for designing RED devices. In particular, the maximum power generation can be achieved by choosing appropriately the shape and the size of a nanochannel, and the bulk concentration ratio.

Background: The extracorporeal life support (ECLS) and temporary bilateral ventricular assist device (t-BiVAD) are commonly applied in patients with cardiogenic shock. Prolonged cardiopulmonary resuscitation (CPR) has poor prognosis. Herein, we report our findings on a combined ECLS and t-BiVAD approach to salvage cardiogenic-shock patients with CPR for more than one hour. Methods: Fifty-nine patients with prolonged CPR and rescued by ECLS and subsequent t-BiVAD were retrospectively collected between January 2015 and December 2019. Primary diagnoses included ischemic, dilated cardiomyopathy, acute myocardial infarction, post-cardiotomy syndrome, and fulminant myocarditis. The mean LVEF was 16.9% ± 6.56% before t-BiVAD. The median ECLS-to-VAD interval is 26 h. Results: A total of 26 patients (44%) survived to weaning, including 13 (22%) bridged to recovery, and 13 (22%) bridged to transplantation. Survivors to discharge demonstrated better systemic perfusion and hemodynamics than non-survivors. The CentriMag-related complications included bleeding (n = 22, 37.2%), thromboembolism (n = 5, 8.4%), and infection (n = 4, 6.7%). The risk factors of mortality included Glasgow Coma Scale (Motor + Eye) ≤ 5, and lactate ≥ 8 mmol/L at POD-1, persistent ventricular rhythm or asystole, and total bilirubin ≥ 6 mg/dL at POD-3. Mortality factors included septic shock (n = 11, 18.6%), central failure (n = 10, 16.9%), and multiple organ failure (n = 12, 20.3%). Conclusions: Combined ECLS and t-BiVAD could be a salvage treatment for patients with severe cardiogenic shock, especially for those already having prolonged CPR. This combination can correct organ malperfusion and allow sufficient time to bridge patients to recovery and heart transplantation, especially in Asia, where donation rates are low, as well as intracorporeal VAD or total artificial heart being seldom available.

This article aims to analyze the impact of Taiwan’s 2008 opening policy to Chinese tourists and the effects of cross-strait relations on both Chinese and non-Chinese inbound tourists into Taiwan, with controls in place for other factors. Using annual country-level panel data over the 2000–2016 period, along with the application of the generalized method of moments approach and several static panel data models, the empirical results suggest that while Taiwan’s opening policy to Chinese tourists has had an enhancement effect, there has been no crowding-out effect on either Chinese or non-Chinese inbound tourists into Taiwan. In addition, the cross-strait relations are found to have a negative effect on non-Chinese inbound tourists, but a positive effect on Chinese inbound tourists visiting Taiwan. We conclude that, compared to non-Chinese inbound tourists into Taiwan, the Chinese inbound tourists into Taiwan is both economically and politically oriented.

Taking account of the influence of electroosmotic flow, the behavior of the ion current rectification of a charged conical nanochannel is studied theoretically focusing on the effect of ionic valence. A continuum-based model comprising coupled Poisson-Nernst-Planck (PNP) equations for the ionic mass transport and Navier-Stokes equations for the hydrodynamic field is adopted. We show that if the bulk salt concentration is fixed, the behavior of the current-voltage curve depends highly on the ionic valence, which arises from the difference in ionic strength and ion diffusivity. As the bulk salt concentration varies, the rectification factor shows a local maximum, and the bulk salt concentration at which it occurs depends upon the salt valence: the higher the valence the lower that concentration. However, regardless of the salt valence, the ionic strength at which that local maximum occurs is essentially the same, implying that the thickness of electric double layer is the key factor. Due to the difference in ionic diffusivity, the magnitude of the rectification factor depends upon the type of salt. For example, the rectification factor of KCl is larger than that of KNO3. The qualitative behavior of the ion current rectification of a positively charged conical nanochannel is similar to that of a negatively charged nanochannel.

Background Transcatheter aortic valve implantation has been an established treatment in patients with symptomatic severe aortic stenosis. However, the postoperative antiplatelet regimen after transcatheter aortic valve implantation was not established certainly. The aim of this meta-analysis is to compare the safety and efficacy of single- (SAPT) and dual-antiplatelet therapies (DAPT) in patients undergoing transcatheter aortic valve implantation. Methods Eligible randomized controlled trials and cohort studies published before February 2021 were retrieved from PubMed, Embase, and the Cochrane Library. We calculated odds ratios with 95% confidence intervals. Results Nine articles, involving 19,277 patients, met the selection criteria. In the short-term outcome, compared with SAPT, DAPT was associated with a significantly higher rate of bleeding (odds ratios, 95% confidence intervals: 3.00, 1.67–5.38) and showed no significant differences in thrombotic events (odds ratios, 95% confidence intervals: 1.25, 0.74–2.11) and all-cause mortality (odds ratios, 95% confidence intervals: 0.84; 0.42–1.69). In the long-term outcome, DAPT was associated with a significantly higher bleeding rate (odds ratios, 95% confidence intervals: 1.85, 1.24–2.78) and showed no differences in thrombotic events (odds ratios, 95% confidence intervals: 1.13, 0.86–1.48) and all-cause mortality (odds ratios, 95% confidence intervals: 1.12, 0.95–1.32). Our trial sequential analysis confirmed DAPT didn’t confer any benefit for reducing all-cause mortality and thrombotic events, and carried a higher risk of bleeding than SAPT. Conclusions SAPT should be a sufficient antiplatelet strategy in post- transcatheter aortic valve implantation patients without indications for oral anticoagulation medication, especially in the long-term follow-up period.

Additional file 6: Table 2. Segmented autoregressive integrated moving average model analysis of the percentage of emergency department visits according to Charlson comorbidity index groups.

Supervisory and Data Acquisition (SCADA) systems control and monitor modern power networks. As attacks targeting SCADA systems are increasing, significant research is conducted to defend SCADA networks including variations of anomaly detection. Due to the sensitivity of real data, many defence mechanisms have been tested only in small testbeds or emulated traffic that were designed with assumptions on how SCADA systems behave. This work provides a timing characterization of IEC-104 spontaneous traffic and compares the results from emulated traffic and real traffic to verify if the network characteristics appearing in testbeds and emulated traffic coincide with real traffic. Among three verified characteristics, two of them appear in the real dataset but in a less regular way, and one does not appear in the collected real data. The insights from these observations are discussed in terms of presumed differences between emulated and real traffic and how those differences are generated.

Additional file 7: Table 3. Segmented autoregressive integrated moving average model analysis of the appropriate ED visit rate by the Charlson Comorbidity Index group.