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PURPOSE: To investigate the safety and efficacy of percutaneous cholecystoduodenal stent (CDS) placement to prevent recurrence of acute cholecystitis in patients who were unfit for cholecystectomy. METHODS: Between April 2016 and January 2022, 46 patients [median age (range) = 81 (37-99) years; men = 15] with acute cholecystitis who were unfit for surgery underwent percutaneous cholecystostomy followed by a CDS placement in two institutions. Plastic stents of three different materials were used [polyethylene, polyurethane (PU), and polycarbonate (PCB)-based PU]. Clinical outcomes, including technical and clinical success rates and early (

Abstract Age-dependent accumulation of amyloid plaques in patients with sporadic Alzheimer’s disease (AD) is associated with reduced amyloid clearance. Older microglia have a reduced ability to phagocytose amyloid, so phagocytosis of amyloid plaques by microglia could be regulated to prevent amyloid accumulation. Furthermore, considering the aging-related disruption of cell cycle machinery in old microglia, we hypothesize that regulating their cell cycle could rejuvenate them and enhance their ability to promote more efficient amyloid clearance. First, we used gene ontology analysis of microglia from young and old mice to identify differential expression of cyclin-dependent kinase inhibitor 2A (p16ink4a), a cell cycle factor related to aging. We found that p16ink4a expression was increased in microglia near amyloid plaques in brain tissue from patients with AD and 5XFAD mice, a model of AD. In BV2 microglia, small interfering RNA (siRNA)-mediated p16ink4a downregulation transformed microglia with enhanced amyloid phagocytic capacity through regulated the cell cycle and increased cell proliferation. To regulate microglial phagocytosis by gene transduction, we used poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles, which predominantly target microglia, to deliver the siRNA and to control microglial reactivity. Nanoparticle-based delivery of p16ink4a siRNA reduced amyloid plaque formation and the number of aged microglia surrounding the plaque and reversed learning deterioration and spatial memory deficits. We propose that downregulation of p16ink4a in microglia is a promising strategy for the treatment of Alzheimer’s disease.

Abstract Background Growing evidence suggests that not only cerebrovascular disease but also Alzheimer’s disease (AD) pathological process itself cause cerebral white matter degeneration, resulting in white matter hyperintensities (WMHs). Some preclinical evidence also indicates that white matter degeneration may precede or affect the development of AD pathology. This study aimed to clarify the direction of influence between in vivo AD pathologies, particularly beta-amyloid (Aβ) and tau deposition, and WMHs through longitudinal approach. Methods Total 282 older adults including cognitively normal and cognitively impaired individuals were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE) cohort. The participants underwent comprehensive clinical and neuropsychological assessment, [11C] Pittsburgh Compound B PET for measuring Aβ deposition, [18F] AV-1451 PET for measuring tau deposition, and MRI scans with fluid-attenuated inversion recovery image for measuring WMH volume. The relationships between Aβ or tau deposition and WMH volume were examined using multiple linear regression analysis. In this analysis, baseline Aβ or tau were used as independent variables, and change of WMH volume over 2 years was used as dependent variable to examine the effect of AD pathology on increase of WMH volume. Additionally, we set baseline WMH volume as independent variable and longitudinal change of Aβ or tau deposition for 2 years as dependent variables to investigate whether WMH volume could precede AD pathologies. Results Baseline Aβ deposition, but not tau deposition, had significant positive association with longitudinal change of WMH volume over 2 years. Baseline WMH volume was not related with any of longitudinal change of Aβ or tau deposition for 2 years. We also found a significant interaction effect between baseline Aβ deposition and sex on longitudinal change of WMH volume. Subsequent subgroup analyses showed that high baseline Aβ deposition was associated with increase of WMH volume over 2 years in female, but not in male. Conclusions Our findings suggest that Aβ deposition accelerates cerebral WMHs, particularly in female, whereas white matter degeneration appears not influence on longitudinal Aβ increase. The results also did not support any direction of influence between tau deposition and WMHs.

Abstract This study synthesized a highly efficient KOH-treated sunflower stem activated carbon (KOH-SSAC) using a two-step pyrolysis process and chemical activation using KOH. The resulting material exhibited exceptional properties, such as a high specific surface area (452 m2/g) and excellent adsorption capacities for phenol (333.03 mg/g) and bisphenol A (BPA) (365.81 mg/g). The adsorption process was spontaneous and exothermic, benefiting from the synergistic effects of hydrogen bonding, electrostatic attraction, and stacking interactions. Comparative analysis also showed that KOH-SSAC performed approximately twice as well as sunflower stem biochar (SSB), indicating its potential for water treatment and pollutant removal applications. The study suggests the exploration of optimization strategies to further enhance the efficiency of KOH-SSAC in large-scale scenarios. These findings contribute to the development of improved materials for efficient water treatment and pollution control.

Abstract Elastic waves involving mechanical particle motions of solid media can couple volumetric and shear deformations, making their manipulation more difficult than electromagnetic waves. Thereby, circularly polarized waves in the elastic regime have been little explored, unlike their counterparts in the electromagnetic regime, where their practical usage has been evidenced in various applications. Here, we explore generating perfect circular polarization of elastic waves in an isotropic solid medium. We devise a novel strategy for converting a linearly polarized wave into a circularly polarized wave by employing an anisotropic medium, which induces a so-far-unexplored coupled resonance phenomenon; it describes the simultaneous occurrence of the Fabry-Pérot resonance in one diagonal plane and the quarter-wave resonance in another diagonal plane orthogonal to the former with an exact 90° out-of-phase relation. We establish a theory explaining the involved physics and validate it numerically and experimentally. As a potential application of elastic circular polarization, we present simulation results demonstrating that a circularly polarized elastic wave can detect an arbitrarily oriented crack undetectable by a linearly polarized elastic wave.

Abstract A new perspective suggests that a dynamic bidirectional communication system, often referred to as the microbiome-gut-brain axis, exists among the gut, its microbiome, and the central nervous system (CNS). This system may influence brain health and various brain-related diseases, especially in the realms of neurodevelopmental and neurodegenerative conditions. However, the exact mechanism is not yet understood. Metabolites or extracellular vesicles derived from microbes in the gut have the capacity to traverse the intestinal epithelial barrier or blood–brain barrier, gaining access to the systemic circulation. This phenomenon can initiate the physiological responses that directly or indirectly impact the CNS and its function. However, reliable and controllable tools are required to demonstrate the causal effects of gut microbial-derived substances on neurogenesis and neurodegenerative diseases. The integration of microfluidics enhances scientific research by providing advanced in vitro engineering models. In this study, we investigated the impact of microbe-derived metabolites and exosomes on neurodevelopment and neurodegenerative disorders using human induced pluripotent stem cells (iPSCs)-derived neurons in a gut-brain axis chip. While strain-specific, our findings indicate that both microbial-derived metabolites and exosomes exert the significant effects on neural growth, maturation, and synaptic plasticity. Therefore, our results suggest that metabolites and exosomes derived from microbes hold promise as potential candidates and strategies for addressing neurodevelopmental and neurodegenerative disorders.

Abstract Background Air pollution can cause various respiratory and neurological diseases and continuous exposure can lead to death. Previous studies have reported that particulate matter (PM) exposure increases the risk of depression, suicidal thoughts, and suicidal death; however, the results are inconsistent and limited. This study aimed to examine the relationship between short-term PM exposure and suicide deaths, as well as investigate the short-term effects of PM on suicide death within vulnerable groups based on factors such as sex, age group, suicide-related information (note, method, and cause), psychiatric disorders, and physical diseases. Methods Data on a total of 28,670 suicide deaths from 2013 to 2017, provided by the Korea Foundation for Suicide Prevention, were analyzed. The study design employed a time-series analysis with a two-stage approach. In the first step, a generalized additive model combined with a distributed lag nonlinear model was used to estimate the short-term effect of PM exposure on suicide risk specific to each city. In the second step, the estimated results from each city were pooled through a meta-analysis to derive the overall effect. We determined the effects of single lag, cumulative lag, and moving average PM concentrations from days 0–7 before suicide. Results We confirmed an association between exposure to PM10 (≤ 10 μm in diameter) and deaths due to suicide. In particular, among individuals with psychiatric disorders and those who employed non-violent suicide methods, increased exposure to PM10 was associated with a higher risk of death by suicide, with percentage changes of 5.92 (95% confidence interval [CI]: 3.95–7.92) and 11.47 (95% CI: 7.95–15.11), respectively. Furthermore, in the group with psychiatric disorders, there was an observed tendency of increasing suicide risk as PM10 levels increased up to 120 µg/m3, whereas in the group with non-violent suicide deaths, there was a pronounced trend of rapid increase in suicide risk with an increase in PM10 up to 100 µg/m3. Conclusions These results show an association between short-term exposure to PM and suicide. Our study adds evidence for the benefits of reducing PM in preventing diseases and improving mental health.

PurposeGastrointestinal stromal tumor (GIST) is associated with increased risk of additional cancers. In this study, synchronous GIST, and peritoneal mesothelioma (PM) were characterized to evaluate the relationship between these two cancers.MethodsA retrospective chart review was conducted for patients diagnosed with both GIST and PM between July 2010 and June 2021. Patient demographics, past tumor history, intraoperative reports, cross-sectional imaging, peritoneal cancer index (PCI) scoring, somatic next-generation sequencing (NGS) analysis, and histology were reviewed.ResultsOf 137 patients who underwent primary GIST resection from July 2010 to June 2021, 8 (5.8%) were found to have synchronous PM, and 4 patients (50%) had additional cancers and/or benign tumors. Five (62.5%) were male, and the median age at GIST diagnosis was 57 years (range: 45-76). Seventy-five percent of GISTs originated from the stomach. Of the eight patients, one patient had synchronous malignant mesothelioma (MM), and the remaining had well-differentiated papillary mesothelioma (WDPM), which were primarily located in the region of the primary GIST (89%). The median PCI score was 2 in the WDPM patients. NGS of GIST revealed oncogenic KIT exon 11 (62.5%), PDGFRA D842V (25%), or SDH (12.5%) mutations, while NGS of the MM revealed BAP1 and PBRM1 alterations.ConclusionsOne in 17 GIST patients undergoing resection in this series have PM, which is significantly higher than expected if these two diseases were considered as independent events. Our results indicate that synchronous co-occurrence of GIST and PM is an underrecognized finding, suggesting a possible relationship that deserves further investigation.

BackgroundThe number of cancer survivors who develop subsequent primary cancers (SPCs) is expected to increase. ObjectiveWe evaluated the overall and cancer type–specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types considering sex and age. MethodsWe conducted a retrospective cohort study using the Health Insurance Review and Assessment database of South Korea including 5-year cancer survivors diagnosed with an FPC in 2009 to 2010 and followed them until December 31, 2019. We measured the SPC incidence per 10,000 person-years and the standardized incidence ratio (SIR) compared with the incidence expected in the general population. ResultsAmong 266,241 survivors (mean age at FPC: 55.7 years; 149,352/266,241, 56.1% women), 7348 SPCs occurred during 1,003,008 person-years of follow-up (median 4.3 years), representing a 26% lower risk of developing SPCs (SIR 0.74, 95% CI 0.72-0.76). Overall, men with 14 of the 20 FPC types had a significantly lower risk of developing any SPCs; women with 7 of the 21 FPC types had a significantly lower risk of developing any SPCs. The risk of developing any SPC type differed by age; the risk was 28% higher in young (

Abstract Innate immune training involves myelopoiesis, dynamic gene modulation, and functional reprogramming of myeloid cells in response to secondary heterologous challenges. The present study evaluates whether systemic innate immune training can protect tissues from local injury. Systemic pretreatment of mice with β‐glucan, a trained immunity agonist, reduces the mortality rate of mice with bleomycin‐induced lung injury and fibrosis, as well as decreasing collagen deposition in the lungs. β‐Glucan pretreatment induces neutrophil accumulation in the lungs and enhances efferocytosis. Training of mice with β‐glucan results in histone modification in both alveolar macrophages (AMs) and neighboring lung epithelial cells. Training also increases the production of RvD1 and soluble mediators by AMs and efferocytes. Efferocytosis increases trained immunity in AMs by stimulating RvD1 release, thus inducing SIRT1 expression in neighboring lung epithelial cells. Elevated epithelial SIRT1 expression is associated with decreased epithelial cell apoptosis after lung injury, attenuating tissue damage. Further, neutrophil depletion dampens the effects of β‐glucan on macrophage accumulation, epigenetic modification in lung macrophages, epithelial SIRT1 expression, and injury‐mediated fibrosis in the lung. These findings provide mechanistic insights into innate immune training and clues to the potential ability of centrally trained immunity to protect peripheral organs against injury‐mediated disorders.

This study estimates the steady-state performance of a proton exchange membrane fuel cell (PEMFC) under conditions of air depletion in the preferential oxidation reactor (PrOx) and fuel depletion at the anode, which has not been previously studied. Considering the detailed chemical reactions of the reforming process, the composition of the reformed gas at the anode inlet is determined using the temperature and pressure data measured at various state points in the PEMFC system. To calculate the voltage loss at the anode due to the air depletion in PrOx or reformate gas depletion before the anode, the electrochemical reaction of the reformed gas in the anode catalyst layer is studied. The calculations show that when the fuel entering the anode or air entering the PrOx decreases, the amount of CO at the anode increases depending on the reduction, resulting in activation loss at the anode, and thereby leading to power loss. This analysis of the power loss in a PEMFC due to a lack of air or fuel can serve as an auxiliary diagnostic tool to identify faulty parts in the Balance of Plant (BOP).

Prothionamide, a second-line drug for multidrug-resistant tuberculosis (MDR-TB), has been in use for a few decades. However, its pharmacokinetic (PK) profile remains unclear. This study aimed to develop a population PK model for prothionamide and then apply the model to determine the optimal dosing regimen for MDR-TB patients. Multiple plasma samples were collected from 27 MDR-TB patients who had been treated with prothionamide at 2 different study hospitals. Prothionamide was administered according to the weight-band dose regimen (500 mg/day for weight 50 kg) recommended by the World Health Organization. The population PK model was developed using nonlinear mixed-effects modeling. The probability of target attainment, based on systemic exposure and MIC, was used as a response target. Fixed-dose regimens (500 or 750 mg/day) were simulated to compare the efficacies of various dosing regimens. PK profiles adequately described the two-compartment model with first-order elimination and the transit absorption compartment model with allometric scaling on clearance. All dosing regimens had effectiveness >90% for MIC values