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The emergence of rice black-streaked dwarf virus (RBSDV) poses a significant threat to global cereal crop cultivation, necessitating the urgent development of reliable detection and quantification techniques. This study introduces a reliable approach for the precise and sensitive quantification of the RBSDV in cereal crop samples, employing a reverse transcription digital polymerase chain reaction (RT-dPCR) assay. We assessed the specificity and sensitivity of the RT-dPCR assay proposed for precise RBSDV detection and quantification. Our findings demonstrate that RT-dPCR was specific for detection of RBSDV, with no cross-reactivity observed with other viruses infecting cereal crops. The RT-dPCR sensitivity was over 10 times that of RT-quantitative PCR (RT-qPCR). The detection limit of RT-dPCR was 0.096 copies/µl. In addition, evaluation of RT-dPCR assay with field samples was conducted on 60 different cereal crop samples revealed that RT-dPCR (45/60) exhibited superior accuracy compared with RT-qPCR (23/60). In this study, we present a specific and accurate RT-dPCR assay for the detection and quantification of RBSDV.
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The objective of this study was to examine the impact of lactitol on constipation caused by loperamide in Sprague Dawley rats, with a particular emphasis on its underlying mechanisms and potential health advantages. The lactitol effectively improved fecal parameters, intestinal tissue structure, and the expression of constipation-related gene expression and proteins. Lactitol alleviated fecal weight and water content altered by loperamide and enhanced gastrointestinal transit. The administration also restored mucosal and muscular layer thickness. Mechanistically, lactitol upregulated the mRNA expression and/or protein levels of mucins (MUC2 and MUC4), occludin, claudin-1, and zonula occludens, indicating improved intestinal barrier function. Lactitol positively regulated the composition of cecal microbiota, leading to an increased relative abundance of Bifidobacterium, Lactobacillus, and Romboutsia. Conversely, lactitol decreased the relative abundance of Prevotella, Aerococcus, Muribaculum, Blautia, and Ruminococcus. This study demonstrated the potential of lactitol to relieve constipation by modulating the gut microbiota. These findings suggest that lactitol is an alternative to traditional laxatives and has potential as a health-promoting food sweetener.
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STUDY OBJECTIVE: Asystole is the most common initial rhythm in out-of-hospital cardiac arrest (OHCA) but indicates a low likelihood of neurologic recovery. This study aimed to develop a novel scoring system to be easily applied at the time of emergency department arrival for identifying favorable neurologic outcomes in OHCA survivors with an asystole rhythm. METHODS: This study is a secondary analysis based on a previously collected nationwide database, targeting nontraumatic adult OHCA patients aged ≥18 years with an asystole rhythm who achieved return of spontaneous circulation (ROSC) between January 2016 and December 2020. The primary outcome was a favorable neurologic outcome defined as Cerebral Performance Categories scores of 1 or 2 at hospital discharge. A prediction model was developed through multivariable logistic regression analysis in a derivation cohort in the form of a scoring system (WBC-ASystole). The performance and calibration of the model were tested using an internal validation cohort. RESULTS: Among 19,803 OHCA patients with survival to hospital admission, 6,322 had asystole, and 285 (4.5%) achieved good neurologic outcomes. Factors associated with favorable outcomes included age, witness arrest, bystander cardiopulmonary resuscitation, time from call to hospital arrival, and out-of-hospital ROSC achievement. The WBC-ASystole score, totaling 11 points, exhibited a predictive performance with an area under the receiver operating characteristic curve of 0.80 (95% confidence interval [CI] 0.76 to 0.83) and 0.79 (95% CI 0.74 to 0.83) in the derivation and validation cohorts, respectively. After categorizing patients into 3 groups based on probability for good neurologic outcomes, the sensitivity and specificity were as follows: 0.98 (95% CI 0.97 to 0.99) and 0.09 (95% CI 0.09 to 0.10) for the very low predicted probability group (WBC-ASystole ≤2), 0.85 (95% CI 0.82 to 0.89) and 0.54 (95% CI 0.53 to 0.55) for the low predicted probability group (WBC-ASystole 3 to 4), and 0.36 (95% CI 0.34 to 0.39) and 0.93 (95% CI 0.92 to 0.93) for fair predicted probability group (WBC-ASystole≥5), respectively. CONCLUSIONS: Although external validation studies must be performed, among OHCA patients with asystole, the WBC-ASystole scoring system may identify those patients who are likely to have a favorable neurologic outcome.
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This study investigated the role of O-GlcNAc cycling in Alzheimer's disease-related changes in brain pathophysiology induced by chronic REM sleep deprivation (CSD) in mice. CSD increased amyloid beta (Aß) and p-Tau accumulation and impaired learning and memory (L/M) function. CSD decreased dendritic length and spine density. CSD also increased the intensity of postsynaptic density protein-95 (PSD-95) staining. All of these Alzheimer's disease (AD) pathogenic changes were effectively reversed through glucosamine (GlcN) treatment by enhancing O-GlcNAcylation. Interestingly, the lelvel of O-GlcNAcylated-Tau (O-Tau) exhibited an opposite trend compared to p-Tau, as it was elevated by CSD and suppressed by GlcN treatment. CSD increased neuroinflammation, as indicated by elevated levels of glial fibrillary acidic protein and IBA-1-positive glial cells in the brain, which were suppressed by GlcN treatment. CSD promoted the phosphorylation of GSK3ß and led to an upregulation in the expression of endoplasmic reticulum (ER) stress regulatory proteins and genes. These alterations were effectively suppressed by GlcN treatment. Minocycline not only suppressed neuroinflammation induced by CSD, but it also rescued the decrease in O-GlcNAc levels caused by CSD. Minocycline also reduced AD neuropathy without affecting CSD-induced ER stress. Notably, overexpressing O-GlcNAc transferase in the dentate gyrus region of the mouse brain rescued CSD-induced cognitive dysfunction, neuropathy, neuroinflammation, and ER stress responses. Collectively, our findings reveal that dysregulation of O-GlcNAc cycling underlies CSD-induced AD pathology and demonstrate that restoration of OGlcNAcylation protects against CSD-induced neurodegeneration.
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Enfermedad de Alzheimer , Encéfalo , Privación de Sueño , Animales , Ratones , Privación de Sueño/metabolismo , Privación de Sueño/complicaciones , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Encéfalo/metabolismo , Encéfalo/patología , Masculino , Ratones Endogámicos C57BL , Proteínas tau/metabolismo , Acetilglucosamina/metabolismo , N-Acetilglucosaminiltransferasas/metabolismo , Sueño REM/fisiología , Péptidos beta-Amiloides/metabolismoRESUMEN
Iliac artery angioplasty with stenting is an effective alternative treatment modality for aortoiliac occlusive diseases. Few randomized controlled trials have compared the efficacy and safety between self-expandable stent (SES) and balloon-expandable stent (BES) in atherosclerotic iliac artery disease. In this randomized, multicenter study, patients with common or external iliac artery occlusive disease were randomly assigned in a 1:1 ratio to either BES or SES. The primary end point was the 1-year clinical patency, defined as freedom from any surgical or percutaneous intervention due to restenosis of the target lesion after the index procedure. The secondary end point was a composite event from major adverse clinical events at 1 year. A total of 201 patients were enrolled from 17 major cardiovascular intervention centers in South Korea. The mean age of the enrolled patients was 66.8 ± 8.5 years and 86.2% of the participants were male. The frequency of critical limb ischemia was 15.4%, and the most common target lesion was in the common iliac artery (75.1%). As the primary end point, the 1-year clinical patency as primary end point was 99% in the BES group and 99% in the SES group (p > 0.99). The rate of repeat revascularization at 1 year was 7.8% in the BES group and 7.0% in the SES group (p = 0.985; confidence interval, 1.011 [0.341-2.995]). In our randomized study, the treatment of iliac artery occlusive disease with self-expandable versus balloon-expandable stent was comparable in 12-month clinical outcomes without differences in the procedural success or geographic miss rate regardless of the deployment method in the distal aortoiliac occlusive lesion (ClinicalTrials.gov, NCT01834495).
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Glutathione (GSH) is indispensable for maintaining redox homeostasis in biological fluids and serves as a key component in cellular defense mechanisms. Accurate assessment of GSH relative to its oxidized counterpart, glutathione disulfide (GSSG), is critical for the early diagnosis and understanding of conditions related to oxidative stress. Despite existing methods for their quantification, the label-free and simultaneous measurement of GSH and GSSG in biological fluid presents significant challenges. Herein, we report the use of an alpha-hederin (Ah) nanopore for the direct measurement of the GSH:GSSG ratio in simulated biological fluid, containing fetal bovine serum (FBS). This system hinges on detecting characteristic relative ion blockades (ΔI/Io) as GSH and GSSG molecules pass through the Ah nanopore under an applied electric field. The distinct current blockage signals derived from the translocation of GSH and GSSG enabled us to determine the molar ratio of GSH and its oxidized form. Notably, the interactions between the hydroxyl groups of the sugar moiety lining the nanopore's inner surface and the sulfhydryl group of GSH significantly influence the translocation dynamics, resulting in a longer translocation time for GSH compared to GSSG. The Ah nanopore technology proposed in this study offers a promising approach for real-time, single molecule-level monitoring of glutathione redox status in biological fluids, eliminating the need for labeling or extensive sample preparation.
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Técnicas Biosensibles , Disulfuro de Glutatión , Glutatión , Nanoporos , Oxidación-Reducción , Glutatión/química , Glutatión/análisis , Glutatión/sangre , Técnicas Biosensibles/métodos , Disulfuro de Glutatión/análisis , Disulfuro de Glutatión/química , Disulfuro de Glutatión/sangre , Animales , Humanos , Bovinos , Estrés OxidativoRESUMEN
BACKGROUND: Cardiopulmonary resuscitation (CPR) is the cornerstone intervention for cardiac arrest, with extracorporeal CPR (ECPR) demonstrating enhanced survival and neurologic outcomes in in-hospital cardiac arrest. This study explores the time interval between CPR initiation and the onset of extracorporeal membrane oxygenation (ECMO) in ECPR recipients, investigating its impact on survival outcomes. METHODS: This retrospective analysis included 1950 adults who received CPR at a single medical center between March 2019 and April 2023. Data from 198 adult patients who had ECMO inserted during CPR were analyzed. The interval from CPR initiation to ECMO initiation was quantified and categorized as ≤20, 20-40, and >40 min. Cox regression analysis assessed associations between CPR-to-ECMO time and short- and long-term mortalities. RESULTS: Among the 198 patients who underwent ECPR, 116 (58.6%) experienced 30-day mortality. Initiation of ECMO within 20 min occurred in 46 (23.2%), whereas 74 (37.4%) had ECMO initiated after 40 min. Cox regression revealed a significant association between time from CPR to ECMO initiation and 30-day mortality (adjusted hazard ratio [HR]: 2.20 in >40 min, HR: 2.63 in 20-40 min, p = 0.006) and 6-month mortality (HR: 1.81, in >40 min, HR: 1.99 in 20-40 min, p = 0.021). CONCLUSIONS: This study revealed that, in ECPR recipients, a shorter duration between CPR initiation and ECMO flow commencement is associated with improved short- and long-term patient prognoses. These findings emphasize the critical role of timely ECMO application in optimizing outcomes for patients undergoing ECPR.
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Research on prognostic factors for good outcomes in out-of-hospital cardiac arrest (OHCA) survivors is lacking. We assessed whether normal levels of normal neuron-specific enolase (NSE) value would be useful for predicting good neurological outcomes in comatose OHCA survivors treated with targeted temperature management (TTM). This registry-based observational study with consecutive adult (≥18 years) OHCA survivors with TTM who underwent NSE measurement 48 hours after cardiac arrest was conducted from October 2015 to November 2022. Normal NSE values defined as the upper limit of the normal range by the manufacturer (NSE <16.3 µg/L) and guideline-suggested (NSE < 60 µg/L) were examined for good neurologic outcomes, defined as Cerebral Performance Categories ≤2, at 6 months post-survival. Among 226 OHCA survivors with TTM, 200 patients who underwent NSE measurement were enrolled. The manufacturer-suggested normal NSE values (<16.3 µg/L) had a specificity of 99.17% for good neurological outcomes with a very low sensitivity of 12.66%. NSE <60 µg/L predicted good outcomes with a sensitivity of 87.34% and specificity of 72.73%. However, excluding 14 poor-outcome patients who died from multi-organ dysfunction excluding hypoxic brain injury, the sensitivity and specificity of normal NSE values were 12.66% and 99.07% of NSE < 16.3 µg/L, and 87.34% and 82.24% of NSE < 60 µg/L. The manufacturer-suggested normal NSE had high specificity with low sensitivity, but the guideline-suggested normal NSE value had a comparatively low specificity for good outcome prediction in OHCA survivors. Our data demonstrate normal NSE levels can be useful as a tool for multimodal appropriation of good outcome prediction.
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Coma , Paro Cardíaco Extrahospitalario , Fosfopiruvato Hidratasa , Humanos , Fosfopiruvato Hidratasa/sangre , Paro Cardíaco Extrahospitalario/mortalidad , Paro Cardíaco Extrahospitalario/terapia , Paro Cardíaco Extrahospitalario/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Coma/etiología , Anciano , Sobrevivientes , Pronóstico , Hipotermia Inducida , AdultoRESUMEN
The likelihood of neurological recovery after out-of-hospital cardiac arrest (OHCA) may be influenced by advanced age. This study aims to evaluate the impact of advanced age on neurological recovery in elderly OHCA survivors treated with targeted temperature management (TTM). This retrospective observational study, using a nationwide population-based OHCA registry, was conducted from January 2016 to December 2020. Non-traumatic elderly (≥ 65 years) comatose OHCA survivors treated with TTM were categorized according to age (65-69, 70-74, 75-79, and ≥ 80 years). Among 23,336 admitted OHCA patients, 3,398 were treated with TTM. Excluding 2,033 non-elderly patients, 1,365 were analyzed. Among the four groups, the rate of good neurological outcomes decreased by advanced age (24.2%, 16.1%, 11.4%, and 5.9%, respectively), which was also observed after subgroup analysis based on the initial shockable (40.6%, 31.5%, 28.6%, and 14.9%, respectively) and non-shockable rhythm (10.6%, 7.2%, 4.1%, and 3.4%, respectively). Multivariate analysis showed the adjusted odds ratio (aOR) for good neurological outcome decreased as age increased (65-69: reference, 70-74: aOR 0.70, 75-79: aOR 0.49, and ≥ 80 years: aOR 0.25). The optimal age cutoffs for good outcomes in elderly OHCA survivors with shockable and non-shockable rhythm were 77 and 72 years, respectively. The neurologic recovery rate in OHCA survivors treated with TTM gradually decreased with increasing age. However, even patients aged ≥ 80 years with shockable rhythm had a good neurologic outcome of 14.9% compared with patients aged 65-69 years with non-shockable rhythm (10.6%).
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Importance: Data are limited regarding the effects of intravascular imaging guidance during complex percutaneous coronary intervention (PCI) in patients with diabetes. Objective: To compare the clinical outcomes of intravascular imaging-guided vs angiography-guided complex PCI in patients with or without diabetes. Design, Setting, and Participants: This prespecified secondary analysis of a subgroup of patients in RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance Versus Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention), an investigator-initiated, open-label multicenter trial, analyzed enrolled patients who underwent complex PCI at 20 sites in Korea from May 2018 through May 2021. Eligible patients were randomly assigned in a 2:1 ratio to undergo either the intravascular imaging-guided PCI or angiography-guided PCI. Data analyses were performed from June 2023 to April 2024. Interventions: Percutaneous coronary intervention was performed either under the guidance of intravascular imaging or angiography alone. Main Outcomes and Measures: The primary end point was target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. Results: Among the 1639 patients included in the analysis (mean [SD] age, 65.6 [10.2] years; 1300 males [79.3%]), 617 (37.6%) had diabetes. The incidence of TVF was significantly higher in patients with diabetes than patients without diabetes (hazard ratio [HR], 1.86; 95% CI, 1.33-2.60; P < .001). Among patients without diabetes, the intravascular imaging-guided PCI group had a significantly lower incidence of TVF compared with the angiography-guided PCI group (4.7% vs 12.2%; HR, 0.41 [95% CI, 0.25-0.67]; P < .001). Conversely, in patients with diabetes, the risk of TVF was not significantly different between the 2 groups (12.9% vs 12.3%; HR, 0.97 [95% CI, 0.60-1.57]; P = .90). There was a significant interaction between the use of intravascular imaging and diabetes for the risk of TVF (P for interaction = .02). Among patients with diabetes, only those with good glycemic control (hemoglobin A1c level ≤7.5%) and who achieved stent optimization by intravascular imaging showed a lower risk of future ischemic events (HR, 0.31; 95% CI, 0.12-0.82; P = .02). Conclusions and Relevance: In this secondary analysis of a subgroup of patients in the RENOVATE-COMPLEX-PCI trial, intravascular imaging guidance reduced the risk of TVF compared with angiography guidance in patients without diabetes (but not in patients with diabetes) during complex PCI. In patients with diabetes undergoing complex PCI, attention should be paid to stent optimization using intravascular imaging and glycemic control to improve outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03381872.
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Angiografía Coronaria , Intervención Coronaria Percutánea , Humanos , Intervención Coronaria Percutánea/métodos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Angiografía Coronaria/métodos , Diabetes Mellitus , República de Corea , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Resultado del TratamientoRESUMEN
BACKGROUND: Wasabi, a Brassicaceae member, is well-known for its unique pungent and hot flavor which is produced from glucosinolate (GSL) degradation. Myrosinase (MYR) is a principle enzyme catalyzing the primary conversion of GSLs to GSL hydrolysis products (GHPs) which is responsible for plant defense system and food quality. Due to the limited information in relation to MYRs present in wasabi (Wasabia japonica M.), this study aimed to identify the MYR isogenes in W. japonica and analyze their roles in relation to GSL metabolism. RESULTS: In results, WjMYRI-1 was abundantly expressed in all organs, whereas WjMYRI-2 showed only trace expression levels. WjMYRII was highly expressed in the aboveground tissues. Interestingly, WjMYRII expression was significantly upregulated by certain abiotic factors, such as methyl jasmonate (more than 40-fold in petioles and 15-fold in leaves) and salt (tenfold in leaves). Young leaves and roots contained 97.89 and 91.17 µmolâ§g-1 of GSL, whereas less GSL was produced in mature leaves and petioles (38.36 and 44.79 µmolâ§g-1, respectively). Similar pattern was observed in the accumulation of GHPs in various plant organs. Notably, despite the non-significant changes in GSL production, abiotic factors treated samples enhanced significantly GHP content. Pearson's correlation analysis revealed that WjMYRI-1 expression significantly correlated with GSL accumulation and GHP formation, suggesting the primary role of WjMYRI-1-encoding putative protein in GSL degradation. In contrast, WjMYRII expression level showed no correlation with GSL or GHP content, suggesting another physiological role of WjMYRII in stress-induced response. CONCLUSIONS: In conclusions, three potential isogenes (WjMYRI-1, WjMYRI-2, and WjMYRII) encoding for different MYR isoforms in W. japonica were identified. Our results provided new insights related to MYR and GSL metabolism which are important for the implications of wasabi in agriculture, food and pharmaceutical industry. Particularly, WjMYRI-1 may be primarily responsible for GSL degradation, whereas WjMYRII (clade II) may be involved in other regulatory pathways induced by abiotic factors.
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Acetatos , Glucosinolatos , Glicósido Hidrolasas , Glucosinolatos/metabolismo , Glicósido Hidrolasas/metabolismo , Glicósido Hidrolasas/genética , Regulación de la Expresión Génica de las Plantas , Brassicaceae/genética , Brassicaceae/metabolismo , Brassicaceae/enzimología , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Hojas de la Planta/metabolismo , Hojas de la Planta/genéticaRESUMEN
BACKGROUND: It is unclear whether the beneficial effects of intravascular imaging-guided stent optimization vary by clinical presentation during complex percutaneous coronary intervention (PCI). OBJECTIVES: In this prespecified, stratified subgroup analysis from RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance versus Angiography-Guidance on Clinical Outcomes After Complex PCI), we sought to compare the outcomes between intravascular imaging vs angiography guidance according to clinical presentation. METHODS: Patients with complex coronary artery lesions were randomly assigned to undergo either intravascular imaging-guided PCI or angiography-guided PCI in a 2:1 ratio. The primary endpoint was target vessel failure (TVF), which is a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. RESULTS: Of 1,639 patients, 832 (50.8%) presented with acute coronary syndrome (ACS) and 807 (49.2%) with chronic coronary syndrome. During a median follow-up of 2.1 years (Q1-Q3: 1.4-3.0 years), there was no significant interaction between the treatment effect of intravascular imaging and clinical presentation (P for interaction = 0.19). Among patients with ACS, the incidences of TVF were 10.4% in the intravascular imaging group and 14.6% in the angiography group (HR: 0.74; 95% CI: 0.48-1.15; P = 0.18). Among patients with CCS, the incidences of TVF were 5.0% in the intravascular imaging group and 10.4% in the angiography group (HR: 0.46; 95% CI: 0.27-0.80; P = 0.006). Achieving stent optimization by intravascular imaging resulted in a reduced risk of TVF among patients with ACS who were randomly assigned to intravascular imaging-guided PCI for complex coronary lesions (optimized vs unoptimized, 6.5% vs 14.1%; HR: 0.49; 95% CI: 0.27-0.87; P = 0.02) but not those with CCS (5.4% vs 4.7%, HR: 1.18; 95% CI: 0.53-2.59; P = 0.69). CONCLUSIONS: No significant interaction was observed between the benefits of intravascular imaging and clinical presentation in the risk of TVF. Stent optimization by intravascular imaging was particularly important for ACS patients. (Intravascular Imaging- Versus Angiography-Guided Percutaneous Coronary Intervention For Complex Coronary Artery Disease [RENOVATE]; NCT03381872).
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Síndrome Coronario Agudo , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Valor Predictivo de las Pruebas , Stents , Humanos , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Masculino , Femenino , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/mortalidad , Factores de Tiempo , Factores de Riesgo , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/terapia , Ultrasonografía Intervencional , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/etiología , Enfermedad CrónicaRESUMEN
This study aimed to elucidate the role of O-GlcNAc cycling in 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD)-like neurodegeneration and the underlying mechanisms. We observed dose-dependent downregulation of O-GlcNAcylation, accompanied by an increase in O-GlcNAcase following 6-OHDA treatment in both mouse brain and Neuro2a cells. Interestingly, elevating O-GlcNAcylation through glucosamine (GlcN) injection provided protection against PD pathogenesis induced by 6-OHDA. At the behavioral level, GlcN mitigated motor deficits induced by 6-OHDA, as determined using the pole, cylinder, and apomorphine rotation tests. Furthermore, GlcN attenuated 6-OHDA-induced neuroinflammation and mitochondrial dysfunction. Notably, augmented O-GlcNAcylation, achieved through O-GlcNAc transferase (OGT) overexpression in mouse brain, conferred protection against 6-OHDA-induced PD pathology, encompassing neuronal cell death, motor deficits, neuroinflammation, and mitochondrial dysfunction. These collective findings suggest that O-GlcNAcylation plays a crucial role in the normal functioning of dopamine neurons. Moreover, enhancing O-GlcNAcylation through genetic and pharmacological means could effectively ameliorate neurodegeneration and motor impairment in an animal model of PD. These results propose a potential strategy for safeguarding against the deterioration of dopamine neurons implicated in PD pathogenesis.
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Ratones Endogámicos C57BL , N-Acetilglucosaminiltransferasas , Oxidopamina , Enfermedad de Parkinson , Animales , Oxidopamina/farmacología , Ratones , N-Acetilglucosaminiltransferasas/metabolismo , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Masculino , Glucosamina/farmacología , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/patología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Acetilglucosamina/metabolismo , Acetilglucosamina/farmacología , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/efectos de los fármacos , beta-N-Acetilhexosaminidasas/metabolismo , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: The early prediction of the need for massive transfusions (MTs) and the preparation of blood products are essential for managing patients with primary postpartum hemorrhage (PPH). Thromboelastography (TEG) enables a thorough evaluation of coagulation status and is useful for guiding the treatment of hemorrhagic events in various diseases. We investigated the role of TEG in predicting the need for MT in patients with primary PPH. METHODS: A retrospective observational study was conducted in the emergency department (ED) of a university-affiliated, tertiary referral center between November 2015 and August 2023. TEG was performed upon admission. We defined MT as the requirement for transfusion of more than 10 units of packed red blood cells within the first 24 h. The primary outcome was the need for MT. RESULTS: Among the 184 patients with initial TEG, 34 (18.5%) required MT. Except for lysis after 30 min, the MT and non-MT groups had significantly different TEG values. Based on multivariate analysis, an angle < 60 was an independent predictor of MT (odds ratio (OR) 7.769; 95% confidence interval (CI), 2.736-22.062), along with lactate (OR, 1.674; 95% CI, 1.218-2.300) and shock index > 0.9 (OR, 4.638; 95% CI, 1.784-12.056). Alpha angle < 60 degrees indicated the need for MT with 73.5% sensitivity, 72.0% specificity, and 92.3% negative predictive value. CONCLUSIONS: Point-of-care testing of TEG has the potential to be a useful tool in accurately predicting the necessity for MT in ED patients with primary PPH at an early stage.
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Importance: There have been heterogeneous results related to sex differences in prognosis after percutaneous coronary artery intervention (PCI) for complex coronary artery lesions. Objective: To evaluate potential differences in outcomes with intravascular imaging-guided PCI of complex coronary artery lesions between women and men. Design, Setting, and Participants: This prespecified substudy evaluates the interaction of sex in the investigator-initiated, open-label, multicenter RENOVATE-COMPLEX-PCI randomized clinical trial, which demonstrated the superiority of intravascular imaging-guided PCI compared with angiography-guided PCI in patients with complex coronary artery lesions. The trial was conducted at 20 sites in Korea. Patients with complex coronary artery lesions undergoing PCI were enrolled between May 2018 and May 2021, and the median (IQR) follow-up period was 2.1 (1.4-3.0) years. Data were analyzed from December 2022 to December 2023. Interventions: After diagnostic coronary angiography, eligible patients were randomly assigned in a 2:1 ratio to receive intravascular imaging-guided PCI or angiography-guided PCI. The choice and timing of the intravascular imaging device were left to the operators' discretion. Main Outcomes and Measures: The primary end point was target vessel failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. Secondary end points included individual components of the primary end point. Results: Of 1639 included patients, 339 (20.7%) were women, and the mean (SD) age was 65.6 (10.2) years. There was no difference in the risk of the primary end point between women and men (9.4% vs 8.3%; adjusted hazard ratio [HR], 1.39; 95% CI, 0.89-2.18; P = .15). Intravascular imaging-guided PCI tended to have lower incidence of the primary end point than angiography-guided PCI in both women (5.2% vs 14.5%; adjusted HR, 0.34; 95% CI, 0.15-0.78; P = .01) and men (8.3% vs 11.7%; adjusted HR, 0.72; 95% CI, 0.49-1.05; P = .09) without significant interaction (P for interaction = .86). Conclusions and Relevance: In patients undergoing complex PCI, compared with angiographic guidance, intravascular imaging guidance was associated with similar reduction in the risk of target vessel failure among women and men. The treatment benefit of intravascular imaging-guided PCI showed no significant interaction between treatment strategy and sex. Trial Registration: ClinicalTrials.gov Identifier: NCT03381872.
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Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Humanos , Masculino , Intervención Coronaria Percutánea/métodos , Femenino , Anciano , Persona de Mediana Edad , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Factores Sexuales , Ultrasonografía Intervencional/métodosRESUMEN
BACKGROUND AND OBJECTIVES: Accumulating evidence shows that sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce adverse cardiovascular outcomes. However, whether SGLT2i, compared with other antidiabetic drugs, reduce the new development of atrial fibrillation (AF) is unclear. In this study, we compared SGLT2i with dipeptidyl peptidase-4 inhibitors (DPP-4is) in terms of reduction in the risk of AF in individuals with type 2 diabetes. METHODS: We included 42,786 propensity score-matched pairs of SGLT2i and DPP-4i users without previous AF diagnosis using the Korean National Health Insurance Service database between May 1, 2016, and December 31, 2018. RESULTS: During a median follow-up of 1.3 years, SGLT2i users had a lower incidence of AF than DPP-4i users (1.95 vs. 2.65 per 1,000 person-years; hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55-0.97; p=0.028]). In individuals without heart failure, SGLT2i users was associated with a decreased risk of AF incidence (HR, 0.70; 95% CI, 0.52-0.94; p=0.019) compared to DPP-4i users. However, individuals with heart failure, SGLT2i users was not significantly associated with a change in risk (HR, 1.04; 95% CI, 0.44-2.44; p=0.936). CONCLUSIONS: In this nationwide cohort study of individuals with type 2 diabetes, treatment with SGLT2i was associated with a lower risk of AF compared with treatment with DPP-4i.
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Lightweight structural materials are commonly used as effective fillers for advanced composites with high toughness. This study focused on enhancing the toughness of direct-spun carbon nanotube yarns (CNTYs) by controlling the micro-textural structure using a water-gap-based direct spinning. Drawing inspiration from the structural features of natural spider silk fibroin, characterized by an α-helix in the amorphous region and ß-sheet in the crystalline region, multiscale bundles within CNTYs are reorganized into a unique nano-coil-like structure. This nano-coiled structure facilitated the efficient dissipation of external mechanical loads through densification with the rearrangement of multiscale bundles, improving specific strength and strain. The resulting CNTYs exhibited exceptional mechanical properties with toughness reaching 250 J g-1, making them promising alternatives to commercially available fibers in lightweight, high-toughness applications. These findings highlight the significance of nano-coiling engineering for emulating bio-inspired micro-textural structures, achieving remarkable enhancement in the toughness of CNTYs.
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BACKGROUND The modified shock index (MSI) is calculated as the ratio of heart rate (HR) to mean arterial pressure (MAP) and has been used to predict the need for massive transfusion (MT) in trauma patients. This retrospective study from a single center aimed to compare the MSI with the traditional shock index (SI) to predict the need for MT in 612 women diagnosed with primary postpartum hemorrhage (PPH) at the Emergency Department (ED) between January 2004 and August 2023. MATERIAL AND METHODS The patients were divided into the MT group and the non-MT group. The predictive power of MSI and SI was compared using the areas under the receiver operating characteristic curve (AUC). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated. RESULTS Out of 612 patients, 105 (17.2%) required MT. The MT group had higher median values than the non-MT group for MSI (1.58 vs 1.07, P<0.001) and SI (1.22 vs 0.80, P<0.001). The AUC for MSI, with a value of 0.811 (95% confidence interval [CI], 0.778-0.841), did not demonstrate a significant difference compared to the AUC for SI, which was 0.829 (95% CI, 0.797-0.858) (P=0.066). The optimal cutoff values for MSI and SI were 1.34 and 1.07, respectively. The specificity and PPV for MT were 77.1% and 40.2% for MSI, and 83.2% and 45.9% for SI. CONCLUSIONS Both MSI and SI were effective in predicting MT in patients with primary PPH. However, MSI did not demonstrate superior performance to SI.
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Hemorragia Posparto , Embarazo , Humanos , Femenino , Estudios Retrospectivos , Hemorragia Posparto/terapia , Transfusión Sanguínea , Servicio de Urgencia en Hospital , Frecuencia CardíacaRESUMEN
BACKGROUND: Although clinical benefits of intravascular imaging-guided percutaneous coronary intervention (PCI) in patients with complex coronary artery lesions have been observed in previous trials, the cost-effectiveness of this strategy is uncertain. METHODS: RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance vs Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention) was conducted in Korea between May 2018 and May 2021. This prespecified cost-effectiveness substudy was conducted using Markov model that simulated 3 states: (1) post-PCI, (2) spontaneous myocardial infarction, and (3) death. A simulated cohort was derived from the intention-to-treat population, and input parameters were extracted from either the trial data or previous publications. Cost-effectiveness was evaluated using time horizon of 3 years (within trial) and lifetime. The primary outcome was incremental cost-effectiveness ratio (ICER), an indicator of incremental cost on additional quality-adjusted life years (QALYs) gained, in intravascular imaging-guided PCI compared with angiography-guided PCI. The current analysis was performed using the Korean health care sector perspective with reporting the results in US dollar (1200 Korean Won, â©=1 dollar, $). Willingness to pay threshold was $35 000 per QALY gained. RESULTS: A total of 1639 patients were included in the trial. During 3-year follow-up, medical costs ($8661 versus $7236; incremental cost, $1426) and QALY (2.34 versus 2.31; incremental QALY, 0.025) were both higher in intravascular imaging-guided PCI than angiography-guided PCI, resulting incremental cost-effectiveness ratio of $57 040 per QALY gained within trial data. Conversely, lifetime simulation showed total cumulative medical cost was reversed between the 2 groups ($40 455 versus $49 519; incremental cost, -$9063) with consistently higher QALY (8.24 versus 7.89; incremental QALY, 0.910) in intravascular imaging-guided PCI than angiography-guided PCI, resulting in a dominant incremental cost-effectiveness ratio. Consistently, 70% of probabilistic iterations showed cost-effectiveness of intravascular imaging-guided PCI in probabilistic sensitivity analysis. CONCLUSIONS: The current cost-effectiveness analysis suggests that imaging-guided PCI is more cost-effective than angiography-guided PCI by reducing medical cost and increasing quality-of-life in complex coronary artery lesions in long-term follow-up. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03381872.
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Análisis de Costo-Efectividad , Intervención Coronaria Percutánea , Humanos , Análisis Costo-Beneficio , Calidad de Vida , Vasos Coronarios/diagnóstico por imagenRESUMEN
Although percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) has been increasing in recent years, CTO PCI is still one of the most challenging procedures with relatively higher rates of procedural complications and adverse clinical events after PCI. Due to the innate limitations of invasive coronary angiography, intravascular imaging (IVI) has been used as an adjunctive tool to complement PCI, especially in complex coronary artery disease. Considering the complexity of CTO lesions, the role of IVI is particularly important in CTO intervention. IVI has been a useful adjunctive tool in every step of CTO PCI including assisted wire crossing, confirmation of wire location within CTO segment, and stent optimization. The meticulous use of IVI has been one of the greatest contributors to recent progress of CTO PCI. Nevertheless, studies evaluating the role of IVI during CTO PCI are limited. The current review provides a comprehensive overview of the mechanistic advantages of IVI in CTO PCI, summarizes previous studies and trials, and presents future perspective of IVI in CTO PCI.