This study investigated temporal trends in the treatment and mortality of patients with cardiogenic shock (CS) in Taiwan in relation to acute myocardial infarction (AMI) accreditation implemented in ...2009 and the unavailability of percutaneous ventricular assist devices.
Data of patients diagnosed as having CS between January 2003 and December 2017 were collected from Taiwan's National Health Insurance Research Database. Each case was followed from the date of emergency department arrival or hospital admission for the first incident associated with a CS diagnosis up to a 1-year interval. Measurements included demographics, comorbidities, treatment, mortality, and medical costs. Using an interrupted time-series (ITS) design with multi-level mixed-effects logistic regression model, we assessed the impact of AMI accreditation implementation on the mortality of patients with AMI and CS overall and stratified by the hospital levels.
In total, 64 049 patients with CS (mean age:70 years; 62% men) were identified. The incidence rate per 10
person-years increased from 17 in 2003 to 25 in 2010 and plateaued thereafter. Average inpatient costs increased from 159 125 points in 2003 to 240 993 points in 2017, indicating a 1.5-fold increase. The intra-aortic balloon pump application rate was approximately 22-25% after 2010 (p = 0.093). Overall, in-hospital, 30-day, and 1-year mortality declined from 60.3%, 63.0%, and 69.3% in 2003 to 47.9%, 50.8% and 59.8% in 2017, respectively. The decline in mortality was more apparent in patients with AMI-CS than in patients with non-AMI-CS. The ITS estimation revealed a 2% lower in-hospital mortality in patients with AMI-CS treated in district hospitals after the AMI accreditation had been implemented for 2 years.
In Taiwan, the burden of CS has consistently increased due to high patient complexity, advanced therapies, and stable incidence. Mortality declined over time, particularly in patients with AMI-CS, which may be attributable to advancements in AMI therapies and this quality-improving policy.
The tumor microenvironment (TME) governs all aspects of cancer progression and in vitro 3D cell culture platforms are increasingly developed to emulate the interactions between components of the ...stromal tissues and cancer cells. However, conventional cell culture platforms are inadequate in recapitulating the TME, which has complex compositions and dynamically changing matrix mechanics. In this study, we developed a dynamic gelatin-hyaluronic acid hybrid hydrogel system through integrating modular thiol-norbornene photopolymerization and enzyme-triggered on-demand matrix stiffening. In particular, gelatin was dually modified with norbornene and 4-hydroxyphenylacetic acid to render this bioactive protein photo-crosslinkable (through thiol-norbornene gelation) and responsive to tyrosinase-triggered on-demand stiffening (through HPA dimerization). In addition to the modified gelatin that provides basic cell adhesive motifs and protease cleavable sequences, hyaluronic acid (HA), an essential tumor matrix, was modularly and covalently incorporated into the cell-laden gel network. We systematically characterized macromer modification, gel crosslinking, as well as enzyme-triggered stiffening and degradation. We also evaluated the influence of matrix composition and dynamic stiffening on pancreatic ductal adenocarcinoma (PDAC) cell fate in 3D. We found that either HA-containing matrix or a dynamically stiffened microenvironment inhibited PDAC cell growth. Interestingly, these two factors synergistically induced cell phenotypic changes that resembled cell migration and/or invasion in 3D. Additional mRNA expression array analyses revealed changes unique to the presence of HA, to a stiffened microenvironment, or to the combination of both. Finally, we presented immunostaining and mRNA expression data to demonstrate that these irregular PDAC cell phenotypes were a result of matrix-induced epithelial-mesenchymal transition (EMT).
According to the locus coeruleus–norepinephrine (LC–NE) theory, activity of the LC, the major releaser of NE in the brain, regulates inhibitory control. As there is reciprocal communication between ...circulating epinephrine and the LC, plasma epinephrine is used as the index of LC–NE activity. The aim of this crossover randomized controlled trial is to expand on previous findings by investigating the effects of free‐weight, multiple‐joint, and structural barbell resistance exercises. Previous studies have had some methodological limitations, such as failure to report the process of randomization, absence of resistance exercise familiarization before the maximal strength testing, and lack of protocol publication. To address these issues, this study incorporates resistance exercise familiarization, transparent reporting of randomization, and submission as a registered report. The results suggest that a single session of resistance exercise (barbell squat, press, and deadlift) with an intensity of 65%–78% 1RM for five repetitions (70%–90% relative intensity) and three sets with 3‐min rest intervals improved Stroop congruent reaction time (RT) only (t(27) = −2.663, mean reduction = −15 ms, p = .013, 95% CI −26, −3). No significant enhancements were observed in Stroop incongruent RT, inhibitory control as indexed by Stroop effect, or inhibitory control as indexed by the RT difference between the Stroop task and the simple reaction task. Moreover, the alterations in plasma epinephrine levels did not significantly associate with changes in any measure of cognitive performance.
By addressing previous methodological limitations and employing a registered report format, this study provides more reliable findings on the effects of acute resistance exercise on cognitive performance. We found that, although acute resistance exercise enhances a certain cognitive outcome measured by the Stroop task, the improvement does not appear to be associated with changes in plasma epinephrine.
Major depressive disorder (MDD) has become a leading contributor to the global burden of disease; however, there are currently no reliable biological markers or physiological measurements for ...efficiently and effectively dissecting the heterogeneity of MDD. Here we propose a novel method based on scalp electroencephalography (EEG) signals and a robust spectral-spatial EEG feature extractor called kernel eigen-filter-bank common spatial pattern (KEFB-CSP). The KEFB-CSP first filters the multi-channel raw EEG signals into a set of frequency sub-bands covering the range from theta to gamma bands, then spatially transforms the EEG signals of each sub-band from the original sensor space to a new space where the new signals (i.e., CSPs) are optimal for the classification between MDD and healthy controls, and finally applies the kernel principal component analysis (kernel PCA) to transform the vector containing the CSPs from all frequency sub-bands to a lower-dimensional feature vector called KEFB-CSP. Twelve patients with MDD and twelve healthy controls participated in this study, and from each participant we collected 54 resting-state EEGs of 6 s length (5 min and 24 s in total). Our results show that the proposed KEFB-CSP outperforms other EEG features including the powers of EEG frequency bands, and fractal dimension, which had been widely applied in previous EEG-based depression detection studies. The results also reveal that the 8 electrodes from the temporal areas gave higher accuracies than other scalp areas. The KEFB-CSP was able to achieve an average EEG classification accuracy of 81.23% in single-trial analysis when only the 8-electrode EEGs of the temporal area and a support vector machine (SVM) classifier were used. We also designed a voting-based leave-one-participant-out procedure to test the participant-independent individual classification accuracy. The voting-based results show that the mean classification accuracy of about 80% can be achieved by the KEFP-CSP feature and the SVM classifier with only several trials, and this level of accuracy seems to become stable as more trials (i.e., <7 trials) are used. These findings therefore suggest that the proposed method has a great potential for developing an efficient (required only a few 6-s EEG signals from the 8 electrodes over the temporal) and effective (~80% classification accuracy) EEG-based brain-computer interface (BCI) system which may, in the future, help psychiatrists provide individualized and effective treatments for MDD patients.
The anticancer efficacy of TNF‐related apoptosis‐inducing ligand (TRAIL)‐based therapy is limited because of systemic toxicity, poor bioavailability, and development of TRAIL resistance. We developed ...a tumor‐targeted LCPP (lipid/calcium/phosphate/protamine) nanoparticle (NP) to deliver TRAIL plasmid DNA (pDNA) into hepatocellular carcinoma (HCC) cells in a mouse model of HCC. TRAIL pDNA was encapsulated in a pH stimuli‐responsive calcium phosphate (CaP) core, and protamine was added to facilitate nuclear delivery of pDNA. In addition, intracellular release of Ca2+ from the CaP core overcame TRAIL resistance by calcium influx‐dependent DR5 up‐regulation. TRAIL expression also attenuated fibrosis in liver tissues surrounding HCCs by reverting activated hepatic stellate cells (HSCs) to a quiescent state or by directly inducing apoptosis in activated HSCs. Conclusion: TRAIL pDNA delivered by HCC‐targeted LCPP NPs in combination with conventional sorafenib treatment attenuated HCC progression as well as liver fibrosis. Overall, our study presents an effective TRAIL‐based cancer therapy that could be developed for clinical applications. (Hepatology 2018;67:899–913)
Previous studies showed that ZAPL (PARP-13.1) exerts its antiviral activity via its N-terminal zinc fingers that bind the mRNAs of some viruses, leading to mRNA degradation. Here we identify a ...different antiviral activity of ZAPL that is directed against influenza A virus. This ZAPL antiviral activity involves its C-terminal PARP domain, which binds the viral PB2 and PA polymerase proteins, leading to their proteasomal degradation. After the PB2 and PA proteins are poly(ADP-ribosylated), they are associated with the region of ZAPL that includes both the PARP domain and the adjacent WWE domain that is known to bind poly(ADP-ribose) chains. These ZAPL-associated PB2 and PA proteins are then ubiquitinated, followed by proteasomal degradation. This antiviral activity is counteracted by the viral PB1 polymerase protein, which binds close to the PARP domain and causes PB2 and PA to dissociate from ZAPL and escape degradation, explaining why ZAPL only moderately inhibits influenza A virus replication. Hence influenza A virus has partially won the battle against this newly identified ZAPL antiviral activity. Eliminating PB1 binding to ZAPL would be expected to substantially increase the inhibition of influenza A virus replication, so that the PB1 interface with ZAPL is a potential target for antiviral development.
•Systematic analysis of a megacity water management model and economic benefit-costs.•Flood mitigation solutions by optimal combination of multiple LID devices.•Upstream and highland areas are ...suitable for buffer and retaining LIDs, respectively.•Green roof and bioretention cell show best B/C values for all rainfall RPs in Taipei.•LID combinations are effective in reducing peak flow and delaying peak time.
This study establishes an innovative systematic optimization model for megacity flood mitigation by combining multiple Low Impact Development (LID) devices, taking into consideration a Benefit-Cost (B/C) Analysis. The contributions provided by this study include: (1) analysis of flooding consequences on a developing megacity; (2) development of a technical approach enabling an automatic and effective optimization process, linking with an embedded Storm Water Management Model (SWMM); and (3) proposal of adaptive solutions using a combined layout design scheme. Our investigation sets the Benefit/Cost ratio as the objective function to deal with flooding in all return periods (RPs). The decision variables correspond to the allocated areas and quantity of LID devices, including porous pavements, bioretention cells, infiltration trenches, rain barrels, vegetable swales, green roofs, and tree boxes. Under such layout, the flooding loss was simulated with SWMM, and the optimal solution was solved by employing a Simulated Annealing (SA) algorithm. Min-Sheng Community in Taipei is chosen as a study area for demonstrating the applicability of the developed model. Results show that the B/C ratio of identified optimal design can reach 1.448, with green roofs and bioretention cells as main devices, and rain barrels and porous pavements as secondary supplies. Regarding rainfalls in all RPs, the peak flows and delay of peak times at Fu-Yuan Pumping Station can decrease significantly in the range of 5.75–29.80% and 12.50–20%, respectively; and 9.52%–23.49% and 12.50%–37.5% at the subcatchments. The efficiency of flood detention is higher for low RPs than high RPs, while the time-delay ability is smaller.
Objective
To investigate natural‐ and unnatural‐cause mortality at different follow‐up time points in Taiwanese patients with anorexia nervosa (AN) and bulimia nervosa (BN).
Method
In this ...longitudinal cohort study, 330,393 patients, including 2143 patients with AN, 13,590 with BN, and 20 times as many respective non‐AN and non‐BN patients, were followed up for 16 years. We performed conditional Cox regression survival analysis to examine the risk of mortality in the AN and BN groups relative to the comparison group.
Results
A total of 1242 patients died, including 101 and 343 patients with AN and BN, respectively. Mortality rates for AN and BN were 5.42 and 2.90 deaths per 1000 person‐years, respectively. Compared with the non‐AN group, the AN group had a significantly higher risk of both natural‐ and unnatural‐cause mortality, and the BN group had a significantly higher risk of unnatural‐cause mortality. Suicide was the most common cause of death, and suicide risk was significantly higher in both the AN and BN groups. All‐cause mortality risk was the highest at the beginning of follow‐up and markedly declined in the AN group. In the BN group, all‐cause mortality risk was lower but stable at follow‐up. The risk of unnatural‐cause mortality remained high throughout the follow‐up period for both the groups.
Conclusions
Early detection and treatment for associated physical problems in patients with AN are crucial. Regular monitoring for unnatural‐cause mortality events (mainly suicide) in AN and BN over time is also crucial.
Public Significance
AN had a significantly higher risk of both natural‐ and unnatural‐cause mortality and BN had a significantly higher risk of death from unnatural causes. All‐cause mortality risk was highest at the beginning of follow‐up in AN, but unnatural‐cause mortality risk remained high throughout the follow‐up period for both groups. Our findings imply that early detection and treatment in AN and regular monitoring for unnatural‐cause mortality events in AN and BN are crucial.
A self-tuning proportional-integral (PI) controller in which the controller gains are adapted using the particle swarm optimization (PSO) technique is proposed for a static synchronous compensator ...(STATCOM). An efficient formula for the estimation of system load impedance using real-time measurements is derived. Based on the estimated system load, a PSO algorithm, which takes the best particle gains, the best global gains, and previous change of gains into account, is employed to reach the desired controller gains. To demonstrate the effectiveness of the proposed PSO self-tuning PI controller for a STATCOM, experimental results for a system under different loading conditions are presented. Results from the self-tuning PI controller are compared with those from the fixed-gain PI controllers.
Objective
To investigate the incidence and risk of renal‐related complications in a nationwide cohort of Taiwanese patients with anorexia nervosa (AN).
Method
This longitudinal cohort study analyzed ...the data of 43,951 individuals—comprising 2091 patients with AN and their controls matched (1:20) using propensity scores according to sex, age, degree of urbanization of residence, socioeconomic status, and year of diagnosis—from a population‐based health insurance database; the study lasted 16 years. We used Kaplan–Meier curves to estimate the cumulative incidence of renal events. We also performed Cox proportional regression and constructed a risk model with death as a competing event (both adjusted for basic characteristics, renal diseases, and psychiatric comorbidities) to examine the risk of dialysis and renal outcomes in the AN group relative to the control group.
Results
In total, 204 and 10 patients with AN had renal‐related outcomes and end‐stage renal disease (ESRD), respectively. The cumulative incidence rates of all renal outcomes and ESRD in the AN group were 10.72% and .64%, respectively, at 10‐year follow‐up. Compared with the control group, the AN group had a significantly higher risk of acute dialysis (adjusted hazard ratio 2.10 95% confidence interval 1.19–3.68), hypokalemia, hypovolemia, nephritis, acute renal failure, and chronic renal failure. The AN group did not have a significantly higher risk of ESRD.
Discussion
The elevated risks of acute dialysis and some renal outcomes in AN highlight the importance of monitoring electrolyte imbalance and renal malfunctioning.
Public Significance
Malnutrition and purging behaviors may cause renal complications in patients with AN. In this longitudinal cohort study, we found that the 10‐year cumulative incidence of all renal outcomes in AN was 10.72%, and that patients with AN had a two‐fold higher risk of overall renal outcomes compared with those without AN. Our findings imply that weight restoration and ceasing purging behaviors are crucial for recovery from AN.
PDF
