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1.
Cell ; 184(18): 4753-4771.e27, 2021 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-34388391

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is characterized by notorious resistance to current therapies attributed to inherent tumor heterogeneity and highly desmoplastic and immunosuppressive tumor microenvironment (TME). Unique proline isomerase Pin1 regulates multiple cancer pathways, but its role in the TME and cancer immunotherapy is unknown. Here, we find that Pin1 is overexpressed both in cancer cells and cancer-associated fibroblasts (CAFs) and correlates with poor survival in PDAC patients. Targeting Pin1 using clinically available drugs induces complete elimination or sustained remissions of aggressive PDAC by synergizing with anti-PD-1 and gemcitabine in diverse model systems. Mechanistically, Pin1 drives the desmoplastic and immunosuppressive TME by acting on CAFs and induces lysosomal degradation of the PD-1 ligand PD-L1 and the gemcitabine transporter ENT1 in cancer cells, besides activating multiple cancer pathways. Thus, Pin1 inhibition simultaneously blocks multiple cancer pathways, disrupts the desmoplastic and immunosuppressive TME, and upregulates PD-L1 and ENT1, rendering PDAC eradicable by immunochemotherapy.


Asunto(s)
Inmunoterapia , Terapia Molecular Dirigida , Peptidilprolil Isomerasa de Interacción con NIMA/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/inmunología , Proteínas Adaptadoras Transductoras de Señales/química , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/inmunología , Adenocarcinoma/patología , Aloinjertos/inmunología , Secuencias de Aminoácidos , Animales , Apoptosis/efectos de los fármacos , Antígeno B7-H1/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Desoxicitidina/uso terapéutico , Sinergismo Farmacológico , Endocitosis/efectos de los fármacos , Tranportador Equilibrativo 1 de Nucleósido/metabolismo , Humanos , Terapia de Inmunosupresión , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Ratones , Proteínas de Microfilamentos/química , Proteínas de Microfilamentos/metabolismo , Oncogenes , Organoides/efectos de los fármacos , Organoides/patología , Transducción de Señal/efectos de los fármacos , Análisis de Supervivencia , Microambiente Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Gemcitabina
2.
Nature ; 611(7937): 688-694, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36352223

RESUMEN

Metal halide perovskites are attracting a lot of attention as next-generation light-emitting materials owing to their excellent emission properties, with narrow band emission1-4. However, perovskite light-emitting diodes (PeLEDs), irrespective of their material type (polycrystals or nanocrystals), have not realized high luminance, high efficiency and long lifetime simultaneously, as they are influenced by intrinsic limitations related to the trade-off of properties between charge transport and confinement in each type of perovskite material5-8. Here, we report an ultra-bright, efficient and stable PeLED made of core/shell perovskite nanocrystals with a size of approximately 10 nm, obtained using a simple in situ reaction of benzylphosphonic acid (BPA) additive with three-dimensional (3D) polycrystalline perovskite films, without separate synthesis processes. During the reaction, large 3D crystals are split into nanocrystals and the BPA surrounds the nanocrystals, achieving strong carrier confinement. The BPA shell passivates the undercoordinated lead atoms by forming covalent bonds, and thereby greatly reduces the trap density while maintaining good charge-transport properties for the 3D perovskites. We demonstrate simultaneously efficient, bright and stable PeLEDs that have a maximum brightness of approximately 470,000 cd m-2, maximum external quantum efficiency of 28.9% (average = 25.2 ± 1.6% over 40 devices), maximum current efficiency of 151 cd A-1 and half-lifetime of 520 h at 1,000 cd m-2 (estimated half-lifetime >30,000 h at 100 cd m-2). Our work sheds light on the possibility that PeLEDs can be commercialized in the future display industry.

3.
Nano Lett ; 24(3): 805-813, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38213286

RESUMEN

Over the past few decades, the increased application of nanomaterials has raised questions regarding their safety and possible toxic effects. Organoids have been suggested as promising tools, offering efficient assays for nanomaterial-induced toxicity evaluation. However, organoid systems have some limitations, such as size heterogeneity and poor penetration of nanoparticles because of the extracellular matrix, which is necessary for organoid culture. Here, we developed a novel system for the improved safety assessment of nanomaterials by establishing a 3D floating organoid paradigm. In addition to overcoming the limitations of two-dimensional systems including the lack of in vitro-in vivo cross-talk, our method provides multiple benefits as compared with conventional organoid systems that rely on an extracellular matrix for culture. Organoids cultured using our method exhibited relatively uniform sizing and structural integrity and were more conducive to the internalization of nanoparticles. Our floating culture system will accelerate the research and development of safe nanomaterials.


Asunto(s)
Nanoestructuras , Organoides , Matriz Extracelular
4.
Nano Lett ; 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39404229

RESUMEN

The kinetics of interfacial ion insertion govern the uniformity of electrochemical reactions, playing a crucial role in lithium-ion battery performance. In two-dimensional lithium-conducting layered-oxide battery particles, variation in insertion rates across insertion channels remains unclear due to poorly defined crystal orientation at the solid-liquid interface and solid-state-lithium-diffusion length. This ambiguity complicates understanding inhomogeneous lithium-insertion channels activation. A systematic study requires crystallographically predefined interfaces and in situ lithium-concentration mapping. Here, we fabricated a freestanding, (104)-oriented-LiNi1/3Mn1/3Co1/3O2 single-crystal thin film using dissolution-induced release and performed in situ scanning-transmission-X-ray-microscopy to spatially resolve lithium-insertion at well-defined-interfaces. We observed heterogeneous lithium-concentration evolution due to channel-by-channel insertion rate variation, despite the potential for homogeneous lithium distribution via a solid-solution-phase at equilibrium in NMC111. Increasing current density exacerbates this heterogeneity, highlighting channel-by-channel variation. Our findings provide critical insights into battery electrode utilization and lifetime management, potentially guiding the design of more efficient and durable lithium-ion batteries.

5.
J Neurosci ; 43(33): 5936-5943, 2023 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-37400252

RESUMEN

Despite a recent surge in research examining parent-child neural similarity using fMRI, there remains a need for further investigation into how such similarity may play a role in children's emotional adjustment. Moreover, no prior studies explored the potential contextual factors that may moderate the link between parent-child neural similarity and children's developmental outcomes. In this study, 32 parent-youth dyads (parents: M age = 43.53 years, 72% female; children: M age = 11.69 years, 41% female) watched an emotion-evoking animated film while being scanned using fMRI. We first quantified how similarly emotion network interacts with other brain regions in responding to the emotion-evoking film between parents and their children. We then examined how such parent-child neural similarity is associated with children's emotional adjustment, with attention to the moderating role of family cohesion. Results revealed that higher parent-child similarity in functional connectivity pattern during movie viewing was associated with better emotional adjustment, including less negative affect, lower anxiety, and greater ego resilience in youth. Moreover, such associations were significant only among families with higher cohesion, but not among families with lower cohesion. The findings advance our understanding of the neural mechanisms underlying how children thrive by being in sync and attuned with their parents, and provide novel empirical evidence that the effects of parent-child concordance at the neural level on children's development are contextually dependent.SIGNIFICANCE STATEMENT What neural processes underlie the attunement between children and their parents that helps children thrive? Using a naturalistic movie-watching fMRI paradigm, we find that greater parent-child similarity in how emotion network interacts with other brain regions during movie viewing is associated with youth's better emotional adjustment including less negative affect, lower anxiety, and greater ego resilience. Interestingly, these associations are only significant among families with higher cohesion, but not among those with lower cohesion. Our findings provide novel evidence that parent-child shared neural processes to emotional situations can confer benefits to children, and underscore the importance of considering specific family contexts in which parent-child neural similarity may be beneficial or detrimental to children's development, highlighting a crucial direction for future research.


Asunto(s)
Ajuste Emocional , Emociones , Humanos , Femenino , Adolescente , Adulto , Niño , Masculino , Ansiedad , Encéfalo/diagnóstico por imagen , Relaciones Padres-Hijo
6.
J Biol Chem ; 299(8): 105037, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37442235

RESUMEN

The nucleosome is the fundamental gene-packing unit in eukaryotes. Nucleosomes comprise ∼147 bp DNA wrapped around an octameric histone protein core composed of two H2A-H2B dimers and one (H3-H4)2 tetramer. The strong yet flexible DNA-histone interactions are the physical basis of the dynamic regulation of genes packaged in chromatin. The dynamic nature of DNA-histone interactions also implies that nucleosomes dissociate DNA-histone contacts both transiently and repeatedly. This kinetic instability may lead to spontaneous nucleosome disassembly or histone exchange between nucleosomes. At high nucleosome concentrations, nucleosome-nucleosome collisions and subsequent histone exchange would be a more likely event, where nucleosomes could act as their own histone chaperone. This spontaneous histone exchange could serve as a mechanism for maintaining overall chromatin stability, although it has never been reported. Here we employed three-color single-molecule FRET (smFRET) to demonstrate that histone H2A-H2B dimers are exchanged spontaneously between nucleosomes on a time scale of a few tens of seconds at a physiological nucleosome concentration. We show that the rate of histone exchange increases at a higher monovalent salt concentration, with histone-acetylated nucleosomes, and in the presence of histone chaperone Nap1, while it remains unchanged at a higher temperature, and decreases upon DNA methylation. These results support the notion of histone exchange via transient and repetitive partial disassembly of the nucleosome and corroborate spontaneous histone diffusion in a compact chromatin context, modulating the local concentrations of histone modifications and variants.


Asunto(s)
Histonas , Nucleosomas , Histonas/metabolismo , Cromatina , ADN/metabolismo , Chaperonas de Histonas/genética
7.
Neurobiol Dis ; 191: 106404, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38184014

RESUMEN

Aging is a major risk factor for multiple chronic disorders in the elderly population, including Alzheimer's disease (AD) and Osteoporosis. AD is a progressive neurodegenerative disease characterized by memory loss. In addition to dementia, several studies have shown that AD patients experience an increased rate of musculoskeletal co-morbidities, such as osteoporosis. Since tissue-specific macrophages contribute to both diseases, this study analyzed the microglia transcriptome of AD mice to determine a common gene signature involved in osteoclast biology. After comparing differentially regulated genes from GEO data sets (GSE93824 and GSE212277), there were 35 common upregulated genes and 89 common downregulated genes. Of these common genes, seven genes are known to play an important role in bone homeostasis. CSF1, SPP1, FAM20C, and Cst7 were upregulated and are associated with osteoclastogenesis and inflammation. Among the downregulated genes, LILRA6, MMP9, and COL18A1 are involved in bone formation and osteoclast regulation. We further validated some of these genes (CSF1, Cst7, and SPP1) in the cortex and the bone of AD mice models. The dysregulation of these microglial genes in AD might provide insights into the co-occurrence of AD and osteoporosis and offer potential therapeutic targets to combat disease progression.


Asunto(s)
Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Osteoporosis , Anciano , Humanos , Ratones , Animales , Enfermedad de Alzheimer/genética , Transcriptoma , Microglía , Osteoporosis/genética , Proteínas de Unión al Calcio/genética , Proteínas de la Matriz Extracelular
8.
Biochem Biophys Res Commun ; 691: 149335, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38042032

RESUMEN

C/EBP homologous protein (CHOP) is a key regulator in ER stress-mediated signaling pathway via PERK-dependent unfolded protein response. It has been known that microRNA-616 (miR-616) is produced from the intron of the human DDIT3 gene encoding CHOP and increased by ER stress. However, the role of miR-616 and its targets are not fully addressed yet. Here we try to identify a novel target of miR-616 in human lung epithelial cells. Microarray analysis showed that CXCL5 is the most downregulated gene by miR-616 overexpression in A549 cells. We also found that CXCL5 mRNA and protein levels were significantly reduced by miR-616 mimic in the presence or absence of TNFα, while anti-miR-616 enhanced CXCL5 expression. In addition, miR-616-3p targeting sequence in 3'UTR of CXCL5 was confirmed by luciferase reporter assay suggesting that miR-616-3p directly binds to 3'UTR of CXCL5 and inhibits CXCL5 expression. Finally, we confirmed that conditioned medium from A549 cells treated with TNFα or Streptococcus pneumoniae lysates increased intra-alveolar neutrophil infiltration in a mouse model of pulmonary inflammation, while this induction was significantly reduced in a conditioned medium from cells transfected with miR-616-3p. These results suggest that miR-616-3p can alleviate CXCL5-induced pulmonary inflammatory response via targeting 3'UTR of CXCL5 gene.


Asunto(s)
MicroARNs , Ratones , Animales , Humanos , MicroARNs/metabolismo , Factor de Necrosis Tumoral alfa/genética , Regiones no Traducidas 3'/genética , Medios de Cultivo Condicionados , Ligandos , Quimiocinas/genética
9.
Breast Cancer Res Treat ; 203(2): 205-214, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37833452

RESUMEN

PURPOSE: This study aimed to quantitatively estimate the changes in breast volume associated with radiotherapy in patients undergoing breast-conserving surgery and whole-breast irradiation (WBI). METHODS: Pre-WBI simulation computed tomography (CT) scans and post-WBI follow-up chest CT scans from a total of 1,151 breast cancer patients were analyzed using a deep-learning-driven auto-segmentation approach. The CT-based asymmetry index (CTAI) was calculated by dividing the volume of the irradiated breast by the volume of the contralateral breast. Significant breast shrinkage was defined as a CTAI < 0.85. To quantify changes in CTAI over the follow-up period, the CTAI ratio was determined as the post-WBI CTAI divided by the pre-WBI CTAI. A multivariate logistic regression analysis was conducted to identify potential variables associated with post-WBI significant breast shrinkage. RESULTS: The median CTAI values for pre- and post-WBI CT scans were 0.973 (interquartile range: 0.887-1.069) and 0.866 (interquartile range: 0.773-0.967), respectively. The difference between them was statistically significant (p < 0.001). Following WBI, there was an increase in the rate of significant breast shrinkage from 16.3 to 44.8%. The CTAI ratio showed a negative association with the time interval (p < 0.001, Pearson r = - 0.310). In the multivariate logistic regression analysis, lower pre-WBI CTAI, younger age, and longer interval between CT scans were found to be significantly associated with a higher occurrence of post-WBI significant breast shrinkage. CONCLUSION: Breast volume decreases following WBI, and this decrease is correlated with an increased duration after WBI. These findings highlight the long-term consequences of WBI on breast asymmetry.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Mama/diagnóstico por imagen , Mastectomía Segmentaria , Tomografía Computarizada por Rayos X/métodos
10.
Small ; : e2400959, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38940380

RESUMEN

Synthesis of perovskites that exhibit pure-blue emission with high photoluminescence quantum yield (PLQY) in both nanocrystal solutions and nanocrystal-only films presents a significant challenge. In this work, a room-temperature method is developed to synthesize ultrasmall, monodispersed, Sn-doped methylammonium lead bromide (MAPb1- xSnxBr3) perovskite nanoplatelets (NPLs) in which the strong quantum confinement effect endows pure blue emission (460 nm) and a high quantum yield (87%). Post-treatment using n-hexylammonium bromide (HABr) repaired surface defects and thus substantially increased the stability and PLQY (80%) of the NPL films. Concurrently, high-precision patterned films (200-µm linewidth) are successfully fabricated by using cost-effective spray-coating technology. This research provides a novel perspective for the preparation of high PLQY, highly stable, and easily processable perovskite nanomaterials.

11.
Small ; 20(44): e2403169, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38973079

RESUMEN

Nanopatterning on biomaterials has attracted significant attention as it can lead to the development of biomedical devices capable of performing diagnostic and therapeutic functions while being biocompatible. Among various nanopatterning techniques, electron-beam lithography (EBL) enables precise and versatile nanopatterning in desired shapes. Various biomaterials are successfully nanopatterned as bioresists by using EBL. However, the use of high-energy electron beams (e-beams) for high-resolutive patterning has incorporated functional materials and has caused adverse effects on biomaterials. Moreover, the scattering of electrons not absorbed by the bioresist leads to proximity effects, thus deteriorating pattern quality. Herein, EBL-based nanopatterning is reported by inducing molecular degradation of amorphous silk fibroin, followed by selectively inducing secondary structures. High-resolution EBL nanopatterning is achievable, even at low-energy e-beam (5 keV) and low doses, as it minimizes the proximity effect and enables precise 2.5D nanopatterning via grayscale lithography. Additionally, integrating nanophotonic structures into fluorescent material-containing silk allows for fluorescence amplification. Furthermore, this post-exposure cross-linking way indicates that the silk bioresist can maintain nanopatterned information stored in silk molecules in the amorphous state, utilizing for the secure storage of nanopatterned information as a security patch. Based on the fabrication technique, versatile biomaterial-based nanodevices for biomedical applications can be envisioned.


Asunto(s)
Materiales Biocompatibles , Fibroínas , Seda , Fibroínas/química , Seda/química , Materiales Biocompatibles/química , Nanotecnología/métodos , Bombyx/química , Animales , Nanoestructuras/química
12.
Small ; : e2404958, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136205

RESUMEN

Organic-inorganic hybrid perovskites have attracted significant attention for optoelectronic applications due to their efficient photoconversion properties. However, grain boundaries and irregular crystal orientations in polycrystalline films remain issues. This study presents a method for producing crystalline-orientation-controlled perovskite single-crystal films using retarded solvent evaporation. It is shown that single-crystal films, grown via inverse temperature crystallization within a confined space, exhibit enhanced optoelectronic property. Using interfacial polymer layer, this method produces high-quality perovskite single-crystalline films with varying crystal orientations. Density functional theory calculations confirm favorable adsorption energies for (110) surfaces with methylammonium iodide and PbI2 terminations on poly(3-hexylthiophene), and stronger adsorption for (224) surfaces with I and methylammonium terminations on polystyrene, influenced by repulsive forces between the thiophene group and the perovskite surface. The correlation between charge transport characteristics and perovskite single-crystalline properties highlights potential advancements in perovskite optoelectronics, improving device performance and reliability.

13.
Small ; 20(32): e2309744, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38507730

RESUMEN

The development of hydrogen (H2) gas sensors is essential for the safe and efficient adoption of H2 gas as a clean, renewable energy source in the challenges against climate change, given its flammability and associated safety risks. Among various H2 sensors, gasochromic sensors have attracted great interest due to their highly intuitive and low power operation, but slow kinetics, especially slow recovery rate limited its further practical application. This study introduces Pd-decorated amorphous WO3 nanorods (Pd-WO3 NRs) as an innovative gasochromic H2 sensor, demonstrating rapid and highly reversible color changes for H2 detection. In specific, the amorphous nanostructure exhibits notable porosity, enabling rapid detection and recovery by facilitating effective H2 gas interaction and efficient diffusion of hydrogen ions (H+) dissociated from the Pd nanoparticles (Pd NPs). The optimized Pd-WO3 NRs sensor achieves an impressive response time of 14 s and a recovery time of 1 s to 5% H2. The impressively fast recovery time of 1 s is observed under a wide range of H2 concentrations (0.2-5%), making this study a fundamental solution to the challenged slow recovery of gasochromic H2 sensors.

14.
Small ; : e2405272, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39319479

RESUMEN

Polycrystalline perovskite light-emitting diodes (PeLEDs) have shown great promise with high efficiency and easy processability. However, PeLEDs using single-cation polycrystalline perovskite emitters have demonstrated low efficiency due to defects within the grains and at the interfaces between the perovskite layer and the charge injection contact. Thus, simultaneous defect engineering of perovskites to suppress exciton loss within the grains and at the interfaces is crucial for achieving high efficiency in PeLEDs. Here, 1,8-octanedithiol which is a strong nucleophile, is used to increase the luminescence efficiency of a single-cation perovskite by suppressing non-radiative recombination within the grains of their polycrystalline emitter film as well as at their interface with an anode. The dithiol additive performs a multifunctional role in defect passivation, spatial confinement of excitons, and prevention of exciton quenching at the interface between the perovskite layer and the underlying hole-injection layer. Photoluminescence studies demonstrate that incorporating the dithiol additive significantly enhances the charge carrier dynamics in perovskites, resulting in an external quantum efficiency (EQE) of up to 23.46% even in a simplified PeLED that does not use a hole-injection layer. This represents the highest level of EQE achieved among devices utilizing polycrystalline single-cation perovskites.

15.
Pancreatology ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39277479

RESUMEN

BACKGROUND/OBJECTIVES: Pancreatic cancer is characterized by tissue stiffness due to the high concentration of cancer-associated fibroblasts and extracellular matrix. Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is performed to diagnose pancreatic cancer but yields false-negative results attributed to inadequate specimens. EUS-elastography is a real-time assessment method to pancreatic tissue stiffness. This study aims to investigate the correlation between diagnostic yield and the number of needle passes based on the stiffness measured by elastography. METHODS: Patients who underwent EUS-TA for pancreatic solid mass were retrospectively reviewed and included in this study. The number of needle passes during EUS-TA was determined based on macroscopic on-site evaluation. Tissue stiffness measurements were taken using EUS-elastography. The primary study outcome was the diagnostic yield. The secondary outcome included the number of needle passes required for a diagnosis. RESULTS: A total of 652 patients were included. The average stiffness differed depending on the location of the tumor, and high-stiffness group had more malignant lesions. Although the diagnostic yield was not significantly different between groups, the number of needle passes was significantly higher in the high-stiffness group (3.6 ± 1.0 vs. 3.2 ± 0.9, p < 0.001). CONCLUSIONS: The higher the stiffness of the pancreatic mass in EUS-elastography, the more needle passes are required to achieve a comparable diagnostic yield.

16.
Neuroepidemiology ; 58(4): 247-255, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38295784

RESUMEN

INTRODUCTION: The long-term cognitive outcomes after transient global amnesia (TGA) have been contradictory in the literature. Our study aimed to longitudinally investigate the association between TGA and incident dementia using long-term data from a nationwide population-based cohort in South Korea. METHODS: The study population was recruited between 2002 and 2020 using the International Classification of Diseases (Tenth Revision; ICD-10) codes from the Korean National Health Insurance Service database. The cumulative incidence curve was plotted to compare the incidence of dementia between the TGA (ICD-10 code G45.4; n = 10,276) and non-TGA (n = 27,389) groups, determined using 1:3 propensity score matching. Using Cox proportional hazard regression models, we obtained crude and adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the incident dementia in patients with TGA compared to non-TGA controls. To examine independent variables determining dementia in the TGA group, logistic regression analysis was performed, and adjusted odds ratios (aORs) and 95% CIs were calculated. RESULTS: The TGA group had a significantly higher cumulative incidence of dementia than the non-TGA group (p < 0.001, log-rank test). TGA was significantly associated with incident dementia in the univariate and multivariate Cox models (HR 1.34, 95% CI 1.28-1.39 and aHR 1.40, 95% CI 1.34-1.46, respectively). The adjusted logistic regression for incident dementia in the TGA group showed that age (per 1 year, aOR 1.09, 95% CI 1.09-1.10), female sex (aOR 1.31, 95% CI 1.18-1.45), diabetes (aOR 1.21, 95% CI 1.08-1.35), stroke (aOR 1.30, 95% CI 1.16-1.46), depression (aOR 1.53, 95% CI 1.33-1.76), anxiety (aOR 1.24, 95% CI 1.01-1.39), and rural residence (aOR 1.24, 95% CI 1.10-1.41) were independently associated with incident dementia. CONCLUSION: Our results suggest a longitudinal association of TGA with incident dementia.


Asunto(s)
Amnesia Global Transitoria , Demencia , Humanos , Masculino , Femenino , Demencia/epidemiología , República de Corea/epidemiología , Anciano , Estudios Longitudinales , Persona de Mediana Edad , Amnesia Global Transitoria/epidemiología , Estudios de Seguimiento , Incidencia , Factores de Riesgo , Anciano de 80 o más Años
17.
Gastrointest Endosc ; 100(3): 449-456.e1, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38431102

RESUMEN

BACKGROUND AND AIMS: It is difficult to differentiate between neoplastic and non-neoplastic gallbladder (GB) polyps before surgery. EUS-guided elastography (EUS-EG) is a noninvasive complementary diagnostic method. The utility of EUS-EG in the differential diagnosis of GB polyps has not been investigated. We investigated the diagnostic performance of EUS-EG for the differential diagnosis of GB polyps. METHODS: Patients with GB polyps were prospectively enrolled from June 2020 until November 2022. EUS-EG and semiquantitative evaluation of the strain ratio (SR) were performed for differential diagnosis of GB polyps. Fifty-three eligible patients were divided into 2 groups based on the final diagnosis after surgery. Patient demographics, EUS characteristics, and SR values were compared. A receiver-operating characteristic curve analysis was performed to determine the optimal cutoff SR value that discriminates between neoplastic and non-neoplastic GB polyps. RESULTS: The median SR value for neoplastic polyps (32.93 [interquartile range {IQR}, 22.37-69.02]) was significantly higher than for non-neoplastic polyps (5.40 [IQR, 2.36-14.44], P < .001). Significant differences were found in SR values between non-neoplastic, benign neoplastic (23.38 [IQR, 13.62-39.04]), and malignant polyps (49.25 [IQR, 27.90-82.00]). The optimal cutoff SR value to differentiate between neoplastic and non-neoplastic polyps was 18.4. In multivariable logistic regression, SR value >18.4 (odds ratio, 33.604; 95% confidence interval, 2.588-436.292) was an independent predictor of neoplastic polyps. CONCLUSIONS: EUS-EG and SR values can be used as a supplementary method for evaluating GB polyps. (Clinical trial registration number: NCT04416763.).


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Endosonografía , Enfermedades de la Vesícula Biliar , Neoplasias de la Vesícula Biliar , Pólipos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diagnóstico Diferencial , Diagnóstico por Imagen de Elasticidad/métodos , Endosonografía/métodos , Enfermedades de la Vesícula Biliar/diagnóstico por imagen , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Neoplasias de la Vesícula Biliar/patología , Pólipos/diagnóstico por imagen , Estudios Prospectivos , Curva ROC
18.
Endoscopy ; 56(10): 749-758, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38718833

RESUMEN

BACKGROUND: Disposable digital single-operator cholangioscopy (D-SOC) and direct peroral cholangioscopy (D-POC) using an ultraslim endoscope are established POC modalities for the diagnosis and treatment of various biliary diseases. We compared the usefulness of D-SOC and D-POC for the diagnosis of intraductal superficial lesions of the bile duct (ISL-Bs). METHODS: 38 consecutive patients with suspected biliary diseases who underwent both D-SOC and D-POC were enrolled. The primary outcome was ISL-B detection rate, and the secondary outcomes were technical success of POC and POC-guided forceps biopsy sampling (POC-FB), procedure time, visualization quality, and tissue adequacy. RESULTS: D-SOC had a higher technical success rate than D-POC but the difference was not statistically significant (100% vs. 92.1%, P = 0.25). D-POC had a marginally higher ISL-B detection rate (34.2% vs. 28.9%, P = 0.68) and significantly higher visualization quality (P = 0.03). The mean (SD) procedure time was significantly shorter with D-SOC (11.00 [1.33] vs. 19.03 [2.95] minutes, P<0.001). The technical success rate of POC-FB and tissue adequacy did not differ between the two techniques (D-SOC vs. D-POC: 81.8% vs. 84.6%, P = 0.69 and 77.8% vs. 90.9%, P = 0.57, respectively). CONCLUSIONS: Both POC systems were safe and useful for the detection, characterization, and diagnosis of minute ISL-Bs. While D-SOC displayed a shorter procedure time and a tendency for higher technical success rate, D-POC provided superior visualization quality, allowing detailed observation of the surface structure and microvascular patterns.


Asunto(s)
Endoscopía del Sistema Digestivo , Humanos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Endoscopía del Sistema Digestivo/métodos , Endoscopía del Sistema Digestivo/instrumentación , Equipos Desechables , Tempo Operativo , Anciano de 80 o más Años , Estudios Retrospectivos , Enfermedades de los Conductos Biliares/diagnóstico
19.
Prev Med ; 178: 107793, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38052332

RESUMEN

OBJECTIVE: Many municipal districts in Korea face population decline owing to overall population decreases and aging. We investigated the association between geographic rurality and likelihood of receiving diabetes management education and diabetic retinopathy and diabetes-related kidney disease screenings among adults with diabetes. METHODS: Patient data were obtained from the 2021 Korea Community Health Survey (27,391 individuals; aged ≥19 years and physician-diagnosed with diabetes mellitus). Geographic rurality was categorized based on population decline as follows: with, at risk of, or without population decline. The association between geographic rurality and likelihood of receiving diabetes management education and diabetic retinopathy and diabetes-related kidney disease screenings was examined using multilevel logistic regression analyses. RESULTS: Among 27,391 patients with diabetes, 31.1% received diabetes education; 40.0% and 46.4% were screened for diabetic retinopathy and diabetes-related kidney disease, respectively. Individuals residing in regions with population decline were less likely to receive diabetes education (odds ratio [OR] 0.62, 95% CI 0.50-0.75) and diabetic retinopathy (OR 0.79, 95% CI 0.70-0.90) and diabetes-related kidney disease (OR 0.64, 95% CI 0.55-0.75) screenings, as compared with their counterparts. CONCLUSIONS: Our findings highlight the importance of increased monitoring and providing diabetes education and screenings for patients with diabetes living in rural areas.


Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Enfermedades Renales , Animales , Adulto , Humanos , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/epidemiología , Escolaridad , Encuestas Epidemiológicas , República de Corea/epidemiología , Enfermedades Renales/complicaciones , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología
20.
Prostaglandins Other Lipid Mediat ; 171: 106806, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38185280

RESUMEN

Bacterial endophthalmitis is a blinding infectious disease typically acquired during ocular surgery. We previously reported significant alterations in retinal metabolism during Staphylococcus (S) aureus endophthalmitis. However, the changes in retinal lipid composition during endophthalmitis are unknown. Here, using a mouse model of S. aureus endophthalmitis and an untargeted lipidomic approach, we comprehensively analyzed temporal alterations in total lipids and oxylipin in retina. Our data showed a time-dependent increase in the levels of lipid classes, sphingolipids, glycerolipids, sterols, and non-esterified fatty acids, whereas levels of phospholipids decreased. Among lipid subclasses, phosphatidylcholine decreased over time. The oxylipin analysis revealed increased prostaglandin-E2, hydroxyeicosatetraenoic acids, docosahexaenoic acid, eicosapentaenoic acid, and α-linolenic acid. In-vitro studies using mouse bone marrow-derived macrophages showed increased lipid droplets and lipid-peroxide formation in response to S. aureus infection. Collectively, these findings suggest that S. aureus-infection alters the retinal lipid profile, which may contribute to the pathogenesis of bacterial endophthalmitis.


Asunto(s)
Endoftalmitis , Staphylococcus aureus , Humanos , Staphylococcus aureus/fisiología , Lipidómica , Oxilipinas , Endoftalmitis/microbiología , Endoftalmitis/patología , Retina/patología
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