The Use of Coronary Imaging for Predicting Future Cardiovascular Events.

Background: Despite advancements in coronary artery disease (CAD) treatment with drug-eluting stent, its morbidity and mortality remain high. In context, intravascular imaging-guided percutaneous coronary intervention (PCI) is increasingly recommended for better clinical outcomes in patient with CAD. Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), as one of the intravascular imaging methods, is effective in detecting lipid-rich plaques, which is crucial for identifying high-risk or vulnerable plaques employing near-infrared light. High lipid core burden, as identified by NIRS-IVUS, correlates with an increased risk of adverse cardiac events and shows varying degrees of efficacy in plaque management and event prevention. Summary: This article addresses about how NIRS-IVUS can be used to predict event of CAD. The study highlights the crucial role of NIRS-IVUS in predicting future cardiovascular events. Findings indicate that the presence of high lipid core burden is related to increased risks of periprocedural myocardial infarction and reduced coronary flow during PCI. The study also outlines the predictive value of NIRS-IVUS in non-culprit lesions, where plaques with high lipid core burden significantly increase the occurrence of major adverse cardiac events as demonstrated in the PROSPECT II trial. In terms of therapeutic strategies, the study reviews the effectiveness of high-intensity lipid-lowering strategies in stabilizing vulnerable plaques, as evidenced in trials such as the YELLOW and PACMAN AMI trials. Key Messages: NIRS-IVUS emerges as a valuable diagnostic tool in treating CAD. It effectively identifies vulnerable plaques and aids in predicting and preventing future adverse cardiac events. However, to enhance its practicality and promote widespread adoption in clinical settings, further long-term outcome research of NIRS-IVUS-guided PCI is necessary. These efforts can potentially make NIRS-IVUS a more accessible and indispensable tool in cardiovascular disease management.

Prognostic Value of Poststenting Fractional Flow Reserve After Imaging-Guided Optimal Stenting.

BACKGROUND: Prognostic value of poststenting fractional flow reserve (FFR) remains uncertain in patients undergoing an imaging-guided optimal stenting strategy. OBJECTIVES: The authors evaluated the prognostic value of poststenting FFR according to the intracoronary imaging-guided lesion preparation, stent sizing, and postdilation (iPSP) strategy to optimize stent outcomes. METHODS: Poststenting FFR assessment was performed in 1,108 lesions in 1,005 patients from the IRIS-FFR registry. The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization at 5 years. RESULTS: At the index procedure, 326 lesions (29.4%) were treated using all 3 parts of the iPSP strategy. In the overall population, poststenting FFR was significantly associated with the risk of TVF at 5 years (per 0.01 increase of FFR, adjusted HR [aHR]: 0.94; 95% CI: 0.90-0.98; P = 0.004). Significant interaction was detected between poststenting FFR and the iPSP strategy on the risk of TVF at 5 years (P = 0.045 for interaction). In the iPSP group, poststenting FFR was not associated with the risk of TVF at 5 years (per 0.01 increase of FFR, aHR: 1.00; 95% CI: 0.96-1.05; P = 0.95), whereas a significant association between poststenting FFR and TVF at 5 years was observed in the no iPSP group (per 0.01 increase of FFR, aHR: 0.94; 95% CI: 0.90-0.99; P = 0.009). CONCLUSIONS: Poststenting FFR showed a significant association with cardiac events. However, its prognostic value appeared to be limited after the application of an imaging-guided optimal stenting strategy.

Flexible low-profile external ventricular drain catheter for real-time brain monitoring.

External ventricular drainage is one of the most common neurosurgical procedures in the world for acute hydrocephalus, which must be performed carefully by a neurosurgeon. Although various neuromonitoring external ventricular drain (EVD) catheters have been utilized, they still suffer from rigidity and bulkiness to mitigate post-EVD placement trauma. Here, we introduce a flexible and low-profile smart EVD catheter using a class of technologies with sensitive electrical materials, seamless integration, and flexible mechanics, which serves as a highly soft and minimally invasive device to monitor electrical brain signals. This device reliably captures biopotentials in real time while exhibiting remarkable flexibility and reliability. The seamless integration of its sensory system promises a minimally invasive EVD placement on brain tissue. This work validates the device's distinct characteristics and performances through in vitro experiments and computational analysis. Collectively, this device's exceptional patient- and user-friendly attributes highlight its potential as one of the most practical EVD catheters.

Microfluidic Detection and Analysis of Microplastics Using Surface Nanodroplets.

Detection of microplastics from water is crucial for various reasons, such as food safety monitoring, monitoring of the fate and transport of microplastics, and development of preventive measures for their occurrence. Currently, microplastics are detected by isolating them using filtration, separation by centrifugation, or membrane filtration, subsequently followed by analysis using well-established analytical methods, such as Raman spectroscopy. However, due to their variability in shape, color, size, and density, isolation using the conventional methods mentioned above is cumbersome and time-consuming. In this work, we show a surface-nanodroplet-decorated microfluidic device for isolation and analysis of small microplastics (diameter of 10 µm) from water. Surface nanodroplets are able to capture nearby microplastics as water flows through the microfluidic device. Using a model microplastic solution, we show that microplastics of various sizes and types can be captured and visualized by using optical and fluorescence microscopy. More importantly, as the surface nanodroplets are pinned on the microfluidic channel, the captured microplastics can also be analyzed using a Raman spectroscope, which enables both physical (i.e., size and shape) and chemical (i.e., type) characterization of microplastics at a single-particle level. The technique shown here can be used as a simple, fast, and economical detection method for small microplastics.

Optimal Minimal Stent Area and Impact of Stent Underexpansion in Left Main Up-Front 2-Stent Strategy.

BACKGROUND: We previously reported the use of minimal stent area to predict angiographic in-stent restenosis after drug-eluting stent implantation for unprotected left main (LM) disease. We aimed to evaluate the optimal minimal stent area criteria for up-front LM 2-stenting based on long-term clinical outcomes. METHODS: We identified 292 consecutive patients with LM bifurcation stenosis who were treated using the crush technique. The final minimal stent area was measured in the ostial left anterior descending artery (LAD), ostial left circumflex artery (LCX), and distal LM. The primary outcome was 5-year major adverse cardiac events, including all-cause death, myocardial infarction, and target lesion revascularization. RESULTS: The minimal stent area cutoff values that best predicted the 5-year major adverse cardiac events were 11.8 mm2 for distal LM (area under the curve, 0.57; P=0.15), 8.3 mm2 for LAD ostium (area under the curve, 0.62; P=0.02), and 5.7 mm2 for LCX ostium (area under the curve, 0.64; P=0.01). Using these criteria, the risk of 5-year major adverse cardiac events was significantly associated with stent underexpansion in the LAD ostium (hazard ratio, 3.14; [95% CI, 1.23-8.06]; P=0.02) and LCX ostium (hazard ratio, 2.60 [95% CI, 1.11-6.07]; P=0.03) but not in the distal LM (hazard ratio, 0.81 [95% CI, 0.34-1.91]; P=0.63). Patients with stent underexpansion in both ostial LAD and LCX had a significantly higher rate of 5-year major adverse cardiac events than those with no or 1 underexpanded stent of either ostium (P<0.01). CONCLUSIONS: Stent underexpansion in the LAD and LCX ostium was significantly associated with long-term outcomes in patients who underwent up-front 2-stenting for LM bifurcation stenosis.

Overcoming the Interfacial Photocatalytic Degradation of Nonfullerene Acceptor-Based Organic Photovoltaics by Introducing a UV-A-Insensitive Titanium Suboxide Layer.

Although recent dramatic advances in power conversion efficiencies (PCEs) have resulted in values over 19%, the poor photostability of organic photovoltaics (OPVs) has been a serious bottleneck to their commercialization. The photocatalytic effect, which is caused by incident ultraviolet-A (UV-A, 320-400 nm) light in the most commonly used zinc oxide (ZnOX) electron transport layer (ETL), significantly deteriorates the photostability of OPVs. In this work, we develop a new and facile method to enhance the photostability of nonfullerene acceptor-based OPVs by introducing UV-A-insensitive titanium suboxide (TiOX) ETL. Through an in-depth analysis of mass information at the interface between the ETL and photoactive layer, we confirm that the UV-A-insensitive TiOX suppresses the photocatalytic effect. The resulting device employing the TiOX ETL shows excellent photostability, obtaining 80% of the initial PCE for up to 200 h under 1 sun illumination, which is 10 times longer than that of the conventional ZnOX system (19 h).

Three-Year Cardiovascular Outcomes of Telmisartan in Patients with Hypertension: An Electronic Health Record-Based Cohort Study.

BACKGROUND: Telmisartan exhibits superior efficacy in controlling 24-hour blood pressure (BP) compared with other angiotensin receptor blockers (ARBs). However, data on its cardiovascular effects in patients with hypertension are limited. This study aimed to evaluate the cardiovascular outcomes in patients taking telmisartan compared to those taking other ARBs. METHODS: This multicenter retrospective study used data from the Korea University Medical Center database, built from electronic health records. A total of 19,247 patients taking two or more antihypertensive medications were identified. Patients prescribed telmisartan (telmisartan users) were compared with those prescribed an ARB other than telmisartan (other ARB users). The primary outcome was major adverse cardiac events (MACE), a composite of cardiovascular death, myocardial infarction, stroke, and hospitalizations due to heart failure. The adjusted outcomes were compared using 1:1 propensity score (PS) matching. RESULTS: Overall, 3,437 (17.9%) patients were telmisartan users. These patients were more likely to be younger and male and less likely to have a history of chronic kidney disease, dialysis, or heart failure. In the PS-matched cohort, BP control was similar in both groups; however, telmisartan users exhibited significantly lower visit-to-visit BP variability. The adjusted 3-year MACE rate was similar between telmisartan users (4.6%) and other ARB users (4.7%, log-rank p = 0.75), with comparable safety profiles. CONCLUSIONS: In real-world practice, telmisartan showed cardiovascular outcomes similar to those of other ARBs in patients with hypertension taking two or more antihypertensive drugs.

Uropathogenic distribution and antibiotic resistance patterns according to multidrug-resistant bacteria colonization status in patients with stroke.

Urinary tract infections (UTI) are common in patients with stroke. The colonization of multidrug-resistant organisms (MDR) has recently become a global issue, and infection with MDR is associated with a poorer prognosis. This study aimed to investigate the uropathogenic distribution in stroke patients according to MDR colonization and investigate the infection risk and antibiotic resistance of each uropathogen to help determine initial antibiotic treatment. This study is a retrospective study conducted on patients who underwent inpatient treatment for stroke at Kosin University Gospel Hospital in 2019 to 2021. The participants were classified into Group VRE if vancomycin-resistant Enterococcus (VRE) colonization was confirmed, Group CRE if carbapenem-resistant Enterobacteriaceae (CRE) colonization was confirmed, and Group Negative if no MDR colonization was confirmed. Urine culture was performed if symptomatic UTI was suspected. Uropathogenic distribution, antibiotic resistance patterns were assessed by one-way analysis of variance, independent t-test, and Pearson chi-square test. And the infection risk factors for each uropathogen were assessed by multinomial logistic regression analysis. Six hundred thirty-three participants were enrolled. The mean age of all participants was 69.77 ±â€…14.91, with 305 males and 328 females, including 344 hemorrhagic strokes and 289 ischemic strokes. No growth in urine culture was the most common finding (n = 281), followed by Escherichia coli (E.coli) (n = 141), and Enterococcus spp. (n = 80). Group Negative had significantly more cases of no growth in urine culture than Group VRE (Odds ratio [OR], 11.698; 95% confidence interval [CI], 3.566-38.375; P < .001) and than Group CRE (OR, 11.381; 95% CI, 2.665-48.611; P < .001). Group VRE had significantly more E.coli (OR, 2.905; 95% CI, 1.505-5.618; P = .001), and more Enterococcus (OR, 4.550; 95% CI, 2.253-9.187; P < .001) than Group Negative. There was no statistical difference in antibiotic resistance according to MDR colonization in E coli, but for Enterococcus spp., Group VRE and CRE showed significantly more resistance to numerous antibiotics than Group Negative. MDR colonization increases the risk of UTI and is associated with greater antibiotic resistance. For appropriate administration of antibiotics in UTI, continuous monitoring of the latest trends in uropathogenic distribution is required, and clinicians should pay more attention to the use of initial empirical antibiotics in patients with MDR colonization.

High platelet reactivity strongly predicts early stent thrombosis in patients with drug-eluting stent implantation.

Stent thrombosis (ST) is a fatal complication after percutaneous coronary intervention (PCI). The association between P2Y12 reaction unit (PRU) level and stent thrombosis occurrence remains unclear. Based on the multicenter, observational PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) registry of patients with drug-eluting stents (DES) implantation, a total of 11,714 patients with PRU values were analyzed. We sought to identify the predictors of early stent thrombosis (EST) and compared the primary outcome, a composite of cardiac death, myocardial infarction, and revascularization, between EST and non-EST groups. EST, defined as definite ST within 1 month after index PCI, occurred in 51 patients. PRU values were significantly higher in the EST group (263.5 ± 70.8 vs. 217.5 ± 78.7, p < 0.001). In multivariable analysis, PRU ≥ 252 (OR, 5.10; 95% CI 1.58-16.46; p = 0.006) and aspirin reaction unit ≥ 414 (OR 4.85; 95% CI 1.07-21.97; p = 0.040) were independent predictors of EST. The cumulative incidence of primary composite outcome at one year was significantly higher in the EST group (38.2% vs. 3.9%, Log-rank p < 0.001). In patients treated with clopidogrel after successful DES implantation, EST was associated with higher platelet reactivities, and a greater risk of cardiovascular events.Trial Registration: clinicaltrials.gov Identifier: NCT04734028.

Cardiovascular outcomes according to on-treatment systolic blood pressure in older hypertensive patients: a multicenter cohort using a common data model.

OBJECTIVE: In the growing population of older patients with hypertension, limited evidence supports an association between lowering systolic blood pressure (SBP) and decreased adverse events. We aimed to investigate cardiovascular outcomes according to on-treatment SBP in older hypertensive patients. METHODS: This multicenter, retrospective study used data from the Korea University Medical Center database built on electronic health records from 2017 to 2022. Patients initiated on at least two antihypertensive drugs in combination were followed for three years. The patients were grouped by average on-treatment SBP in 10-mmHg increments from <110 to 160 mmHg or more. The primary outcome was a composite of all-cause death, myocardial infarction, stroke, and hospitalization due to heart failure. RESULTS: A total of 6427 patients aged ≥75 years (mean age, 80 years) were identified. The incidence of the primary outcome was lowest in individuals with an SBP of 120-129 mmHg (14.0%, P  < 0.001), and the adjusted hazard ratio for the primary outcome showed a J-shaped relationship with on-treatment SBP. Achieving an SBP of 120-129 mmHg showed acceptable safety profiles, including electrolyte imbalance, acute kidney injury, new-onset atrial fibrillation, and new-onset dementia or Alzheimer's disease when compared to the group with SBP of 130-139 mmHg. CONCLUSIONS: An average on-treatment SBP of less than 130 mmHg was associated with improved outcomes in older hypertensive patients without raising safety concerns. These findings support the target SBP of 130 mmHg in older patients, if tolerated.

Machine learning models to predict the warfarin discharge dosage using clinical information of inpatients from South Korea.

As warfarin has a narrow therapeutic window and obvious response variability among individuals, it is difficult to rapidly determine personalized warfarin dosage. Adverse drug events(ADE) resulting from warfarin overdose can be critical, so that typically physicians adjust the warfarin dosage through the INR monitoring twice a week when starting warfarin. Our study aimed to develop machine learning (ML) models that predicts the discharge dosage of warfarin as the initial warfarin dosage using clinical data derived from electronic medical records within 2 days of hospitalization. During this retrospective study, adult patients who were prescribed warfarin at Asan Medical Center (AMC) between January 1, 2018, and October 31, 2020, were recruited as a model development cohort (n = 3168). Additionally, we created an external validation dataset (n = 891) from a Medical Information Mart for Intensive Care III (MIMIC-III). Variables for a model prediction were selected based on the clinical rationale that turned out to be associated with warfarin dosage, such as bleeding. The discharge dosage of warfarin was used the study outcome, because we assumed that patients achieved target INR at discharge. In this study, four ML models that predicted the warfarin discharge dosage were developed. We evaluated the model performance using the mean absolute error (MAE) and prediction accuracy. Finally, we compared the accuracy of the predictions of our models and the predictions of physicians for 40 data point to verify a clinical relevance of the models. The MAEs obtained using the internal validation set were as follows: XGBoost, 0.9; artificial neural network, 0.9; random forest, 1.0; linear regression, 1.0; and physicians, 1.3. As a result, our models had better prediction accuracy than the physicians, who have difficulty determining the warfarin discharge dosage using clinical information obtained within 2 days of hospitalization. We not only conducted the internal validation but also external validation. In conclusion, our ML model could help physicians predict the warfarin discharge dosage as the initial warfarin dosage from Korean population. However, conducting a successfully external validation in a further work is required for the application of the models.

Exaptation of I4760M mutation in ryanodine receptor of Spodoptera exigua (Lepidoptera: Noctuidae): Lessons from museum and field samples.

Since 2007, diamide insecticides have been widely used in Korea to control various types of lepidopteran pests including Spodoptera exigua. For nearly a decade, diamide resistance in field populations of S. exigua across 18 localities has been monitored using bioassays. Despite their short history of use, resistance to diamide insecticides has emerged. Based on the LC50 values, some field populations showed a higher level of resistance to chlorantraniliprole, a diamide insecticide, compared to that of the susceptible strain, although regional and temporal variations were observed. To investigate resistance at a molecular level, we examined three mutations (Y4701C, I4790M, and G4946E) in the ryanodine receptor (RyR), which is the primary mechanism underlying diamide insecticide resistance. DNA sequencing showed that only the I4790M mutation was found in most field populations. As resistance levels varied significantly despite the uniform presence of the I4790M mutation, we considered the presence of another resistance factor. Further, the I4790M mutation was also found in S. exigua specimens collected prior to the commercialization of diamide insecticides in Korea as well as in other countries, such as the USA. This finding led us to hypothesize that the I4790M mutation were predisposed in field populations owing to selection factors other than diamide use. For further clarification, we conducted whole-genome sequencing of S. exigua (449.83 Mb) and re-sequencing of 18 individual whole genomes. However, no additional non-synonymous mutations were detected in the RyR-coding region. Therefore, we concluded that the high level of diamide insecticide resistance in Korean S. exigua is not caused by mutations at the target site, RyR, but is attributed to other factors that need to be investigated in future studies.

Age- and Sex-Specific Disparities in Outcomes After Ticagrelor Versus Clopidogrel in East Asian Patients.

It is unknown whether there are age- and gender-related differences in the safety and efficacy of potent P2Y12 inhibitors in East Asian populations with a different bleeding or ischemic propensity. Using data from the TICAKOREA (Ticagrelor Versus Clopidogrel in Asian/Korean Patients with ACS Intended for Invasive Management) trial comparing ticagrelor versus clopidogrel for 800 Korean patients with acute coronary syndrome, the safety and efficacy outcomes were compared according to age (<75 vs ≥75 years) and gender (men vs women). The primary bleeding end point was clinically significant bleeding, and the primary ischemic end point was a major adverse cardiovascular event (MACE) at 12 months. The incidences of clinically significant bleeding were significantly higher after ticagrelor than after clopidogrel in patients aged <75 years (adjusted hazard ratio [HR] 2.56, 95% confidence interval [CI] 1.40 to 4.67) but not in patients aged ≥75 years (adjusted HR 1.1, 95% CI 0.40 to 3.38). The incidences of MACEs were significantly higher after ticagrelor than after clopidogrel in patients aged ≥75 years (adjusted HR 6.14, 95% CI 1.40 to 26.90) but not in patients aged <75 years (adjusted HR 0.93, 95% CI 0.50 to 1.73). The incidences of clinically significant bleeding were significantly higher after ticagrelor than after clopidogrel in men (adjusted HR 2.69, 95% CI 1.38 to 5.24) but not in women (adjusted HR 1.49, 95% CI 0.64 to 3.46). The adjusted risks of MACEs after ticagrelor or clopidogrel were not significantly different between men and women. In conclusion, there were substantial age- and gender-related differences in bleeding and ischemic outcomes after ticagrelor or clopidogrel in Korean patients with acute coronary syndrome. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique identifier: NCT02094963.

Valor pronóstico a 10 años de la angiografía coronaria por TAC en pacientes asintomáticos con diabetes tipo 2 / Ten-year prognostic value of coronary CT angiography in asymptomatic patients with type 2 diabetes

Introducción y objetivos: La escala UKPDS (acrónimo inglés de «Estudio Prospectivo de Diabetes del Reino Unido») tiene un valor limitado para la predicción de eventos de enfermedad arterial coronaria (EAC). El estudio pretende investigar el valor añadido de la angiografía coronaria por tomografía computarizada (ACTC) sobre la escala de riesgo UKPDS para la predicción a 10 años de eventos cardiacos adversos en pacientes asintomáticos con diabetes tipo 2. Métodos: Se evaluó a 589 pacientes diabéticos asintomáticos sin historia de EAC a quienes se les realizó una ACTC. El objetivo principal estaba compuesto por muerte cardiaca, infarto de miocardio no mortal, angina inestable que requiere hospitalización y revascularización. Se estimó la habilidad de discriminación y reclasificación para modelos de predicción que incluían combinaciones de la categoría UKPDS, gravedad de estenosis y puntuación de calcio arterial coronario por ACTC. Resultados: La incidencia del objetivo primario fue del 12,4%. A lo largo de 10 años de seguimiento, los pacientes sin placa ateroesclerótica por ACTC tendieron a tener un bajo ratio de eventos coronarios en tanto que aquellos con EAC obstructiva tuvieron una mayor ratio de eventos, independientemente de la categoría de riesgo de la escala UKPDS. EL modelo que solo incluyó la categoría UKPDS tuvo un índice C de Harrell de 0,658; añadiendo el grado de estenosis coronaria al modelo se incrementó significativamente el índice C en 0,066 (p=0,004), en tanto que la adición del CSC incrementó el índice C en solo 0,039 (p=0,056). Globalmente, la información de la ACTC añadida a la categoría de riesgo UKPDS mejoró el ratio de reclasificación para la predicción del objetivo primario. Conclusiones: En pacientes asintomáticos con diabetes tipo 2, la información de la ACTC para EAC...(AU)

Introduction and objectives: The United Kingdom Prospective Diabetes Study (UKPDS) risk score has limited value for predicting coronary artery disease (CAD) events. We investigated the additive value of coronary computed tomography angiography (CCTA) on top of the UKPDS risk score in predicting 10-year adverse cardiac events in asymptomatic patients with type 2 diabetes. Methods: We evaluated 589 asymptomatic diabetic patients without a history of CAD who underwent CCTA. The primary outcome was a composite of cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, and revascularization. We estimated the discrimination and reclassification ability for the prediction models, which included combinations of the UKPDS category, severity of stenosis, and coronary artery calcium score by CCTA. Results: The incidence of the primary outcome was 12.4%. During 10 years of follow-up, patients without plaque by CCTA tended to have a low CAD event rate, while those with obstructive CAD tended to have a high event rate, irrespective of the baseline UKPDS risk category. The model that included only the UKPDS category had a Harrell's c-index of 0.658; adding the degree of stenosis to the model significantly increased the c-index by 0.066 (P=.004), while adding coronary artery calcium score increased the c-index by only 0.039 (P=.056). Overall, CCTA information in addition to the UKPDS risk category improved the reclassification rate for predicting the primary outcome. Conclusions: In asymptomatic patients with type 2 diabetes, CCTA information for CAD provided significant incremental discriminatory power beyond the UKPDS risk score category for predicting 10-year adverse coronary events.(AU)

The Activation of the LIMK/Cofilin Signaling Pathway via Extracellular Matrix-Integrin Interactions Is Critical for the Generation of Mature and Vascularized Cardiac Organoids.

The generation of mature and vascularized human pluripotent stem cell-derived cardiac organoids (hPSC-COs) is necessary to ensure the validity of drug screening and disease modeling. This study investigates the effects of cellular aggregate (CA) stemness and self-organization on the generation of mature and vascularized hPSC-COs and elucidates the mechanisms underlying cardiac organoid (CO) maturation and vascularization. COs derived from 2-day-old CAs with high stemness (H-COs) and COs derived from 5-day-old CAs with low stemness (L-COs) were generated in a self-organized microenvironment via Wnt signaling induction. This study finds that H-COs exhibit ventricular, structural, metabolic, and functional cardiomyocyte maturation and vessel networks consisting of endothelial cells, smooth muscle cells, pericytes, and basement membranes compared to L-COs. Transcriptional profiling shows the upregulation of genes associated with cardiac maturation and vessel formation in H-COs compared with the genes in L-COs. Through experiments with LIMK inhibitors, the activation of ROCK-LIMK-pCofilin via ECM-integrin interactions leads to cardiomyocyte maturation and vessel formation in H-COs. Furthermore, the LIMK/Cofilin signaling pathway induces TGFß/NODAL and PDGF pathway activation for the maturation and vascularization of H-COs. The study demonstrates for the first time that LIMK/Cofilin axis activation plays an important role in the generation of mature and vascularized COs.

Photopically Transparent Organic Solar Cells with Tungsten Oxide-Based Multilayer Electrodes.

The tailoring of the average photopic transmittance (APT) of transparent organic solar cells (T-OSCs) has been the greatest challenge in building-integrated photovoltaic applications for future smart solar windows to regulate indoor brightness, maintain a human circadian rhythm, and positively impact human emotions by allowing the observation of the external environment. However, a notorious trade-off exists between the APT and power conversion efficiency (PCE) of T-OSCs, mainly due to the absence of highly conductive and transparent top electrodes, which are a key building block determining the PCE and APT. Herein, we demonstrate a new tungsten oxide (WO3)-based multilayer as a highly conductive and transparent top electrode that provides an excellent APT while maintaining a high PCE in T-OSCs. With the assistance of optical simulation based on a transfer matrix method to calculate the optimum thicknesses of the multilayer electrodes, we achieve the best-performing T-OSC with a PCE of 7.0% and a full device APT of 46.7%, resulting in a high light utilization efficiency of 3.27%, which is superior to that of T-OSCs based on the same photoactive system. Furthermore, superior thermal stability at 85 °C in an N2 atmosphere is observed in WO3-based T-OSCs, maintaining 98% of the initial PCE after about 231 h. Our findings provide new insights into the development of T-OSCs with high efficiency and transparency.

Safety and cardiovascular effectiveness of olmesartan in combination therapy for advanced hypertension: an electronic health record-based cohort study.

OBJECTIVE: Compared with placebo, olmesartan has been linked to numerical imbalances in cardiovascular mortality. There is a paucity of contemporary real-world evidence on this agent for different study populations. This study investigated the clinical outcomes of olmesartan and other antihypertensives in patients with advanced hypertension. METHODS: This multicenter retrospective study used data from the Korea University Medical Center database, built from electronic health records. Patients prescribed at least two antihypertensive medications as a combined therapy were followed-up for 3 years. The primary outcome was a composite of all-cause mortality, myocardial infarction (MI), stroke, and hospitalization for heart failure. Adjusted outcomes were compared using propensity score (PS) matching. RESULTS: Among 24 806 patients, 4050 (16.3%) were olmesartan users between January 2017 and December 2018. The average patient age was 64 years, 45% were women, and 41% had diabetes. Olmesartan users were younger and less likely to have diabetes mellitus or chronic kidney disease. In PS-matched cohort, the 3-year cumulative incidences of the primary outcome were similar between the two groups ( P  = 0.91). The cumulative incidence of MI at 3 years was 1.4% in olmesartan users (4.8 per 1000 person-years) and 1.5% in active comparators (5.2 per 1000 person-years; P  = 0.74). Olmesartan also showed similar safety profiles, including acute kidney injury and newly started dialysis. CONCLUSIONS: In real-world practice, olmesartan use in combination therapy resulted in similar cardiovascular outcomes when compared with those of active comparators, and our findings did not show any conclusive evidence that olmesartan is harmful in patients with hypertension.

Inference of selection pressures that drive insecticide resistance in Anopheles and Culex mosquitoes in Korea.

Pyrethroids are primarily used for mosquito control in Korea. However, high frequencies of mutations conferring resistance to not only pyrethroids but also to other insecticides have been found in mosquito populations. This study aimed to examine the hypothesis that insecticides used outside of public health may play a role in selection. Briefly, the resistance mutation frequencies to three insecticide groups (pyrethroids, organophosphates, and cyclodienes) were estimated in two representative groups of mosquito species (Anopheles Hyrcanus Group and Culex pipiens complex). The relationship between these frequencies and the land-use status of the collection sites was investigated through multiple regression analysis. In the Anopheles Hyrcanus Group, the frequencies of both ace1 (organophosphate resistance) and rdl (cyclodiene resistance) mutations were positively correlated with 'proximity to golf course', possibly be due to the insecticides used for turf maintenance. They also showed positive correlations with field area and rice paddy area, respectively, suggesting the role of agricultural insecticides in the selection of these resistance traits. For the Cx. pipiens complex, the kdr (pyrethroid resistance), ace1, and rdl mutations were positively correlated with the residential area, field, and rice paddy, respectively. Therefore, pyrethroids used for public health could serve as a direct source of resistance selection pressure against kdr, whereas non-public health insecticides may pose primary selection pressure against the ace1 and rdl traits. The current findings suggest that the insecticides used in agriculture and the golf industry play a significant role in mosquito selection, despite variations in the extent of indirect selection pressure according to the mosquito groups and insecticide classes.

Characterization of the common bed bug's eggshell and egg glue proteins.

An insect egg is one of the most vulnerable stages of insect life, and the evolutionary success of a species depends on the eggshell protecting the embryo and the egg glue securing the attachment. The common bed bug (Cimex lectularius), notorious for its painful and itchy bites, infests human dwellings to feed on blood. They are easier to find these days as they adapt to develop resistance against commonly used insecticides. In this study, we identify and characterize the eggshell protein and the probable egg glue protein (i.e. keratin associated protein 5-10 like protein) of the bed bug by using mass spectrometry and bioinformatics analysis. Furthermore, by using transcription profiling and in vivo RNA interference, we show evidences that the keratin associated protein 5-10 like protein functions as the glue protein. Finally, structural characterizations on the two proteins are performed using recombinant proteins. Amino acid sequences of various insect eggshell and egg glue proteins support their independent evolution among different insect groups. Hence, inhibiting the function of these proteins related to the earliest stage of life can achieve species-specific population control. In this respect, our results would be a starting point in developing new ways to control bed bug population.

Exploring the potential role of defensins in differential vector competence of body and head lice for Bartonella quintana.

BACKGROUND: The body and head lice of humans are conspecific, but only the body louse functions as a vector to transmit bacterial pathogens such as Bartonella quintana. Both louse subspecies have only two antimicrobial peptides, defensin 1 and defensin 2. Consequently, any differences in the molecular and functional properties of these two louse subspecies may be responsible for the differential vector competence between them. METHODS: To elucidate the molecular basis of vector competence, we compared differences in the structural properties and transcription factor/microRNA binding sites of the two defensins in body and head lice. Antimicrobial activity spectra were also investigated using recombinant louse defensins expressed via baculovirus. RESULTS: The full-length amino acid sequences of defensin 1 were identical in both subspecies, whereas the two amino acid residues in defensin 2 were different between the two subspecies. Recombinant louse defensins showed antimicrobial activities only against the representative Gram-positive Staphylococcus aureus but not against either Gram-negative Escherichia coli or the yeast Candida albicans. However, they did show considerable activity against B. quintana, with body louse defensin 2 being significantly less potent than head louse defensin 2. Regulatory sequence analysis revealed that the gene units of both defensin 1 and defensin 2 in body lice possess decreased numbers of transcription factor-binding sites but increased numbers of microRNA binding sites, suggesting relatively lower transcription activities of body louse defensins. CONCLUSIONS: The significantly lower antibacterial activities of defensin 2 along with the reduced probability of defensin expression in body lice likely contribute to the relaxed immune response to B. quintana proliferation and viability, resulting in higher vector competence of body lice compared to head lice.