RESUMEN
Severity of deceased donor kidney fibrosis impacts graft survival in deceased-donor kidney transplantation. Our aim was to identify potential miRNA biomarkers in urinary exosomes that mirror interstitial fibrosis and tubular atrophy (IFTA) severity. Among 109 urine samples from deceased donors, 34 displayed no IFTA in the zero-day biopsy (No IFTA group), while the remaining 75 deceased donor kidneys exhibited an IFTA score ≥ 1 (IFTA group). After analyzing previous reports and electronic databases, six miRNAs (miR-19, miR-21, miR-29c, miR-150, miR-200b, and miR-205) were selected as potential IFTA biomarker candidates. MiR-21, miR-29c, miR-150, and miR-205 levels were significantly higher, while miR-19 expression was significantly lower in the IFTA group. MiR-21 (AUC = 0.762; P < 0.001) and miR-29c (AUC = 0.795; P < 0.001) showed good predictive accuracy for IFTA. In the No IFTA group, the eGFR level at 1 week after transplantation was significantly higher compared to the IFTA group (41.34 mL/min/1.73m2 vs. 28.65 mL/min/1.73m2, P = 0.012). These findings signify the potential of urinary exosomal miRNAs as valuable biomarker candidates for evaluating the severity of IFTA in deceased donor kidneys before they undergo recovery.
Asunto(s)
Aloinjertos , Biomarcadores , Exosomas , Fibrosis , Trasplante de Riñón , MicroARNs , Humanos , Biomarcadores/orina , Masculino , Exosomas/metabolismo , Femenino , Trasplante de Riñón/efectos adversos , Persona de Mediana Edad , Estudios Prospectivos , MicroARNs/orina , MicroARNs/genética , Adulto , Riñón/patología , Tasa de Filtración GlomerularRESUMEN
BACKGROUND: Clustering lifestyle risk behaviors is important for predicting cardiovascular disease risk. However, it is unclear which behavior mediates other ones to influence cardiovascular disease risk. We aimed to assess the causal inference of each lifestyle risk behavior for the atherosclerotic cardiovascular disease (ASCVD) risk of the general population. METHODS: We performed a Bayesian network mediation analysis using data from the Korea National Health and Nutrition Examination Survey from 2014 to 2019. The main exposure was a combination of lifestyle risk behaviors including unhealthy weight, heavy alcohol consumption, inadequate sleep, physical inactivity, excessive sodium intake, and current smoking among subjects 40 to 79 years of age. The high risk of ASCVD (≥7.5% for the 10-year risk) was assessed using logistic regression, Bayesian networks, and structural equational models to examine the causal relationships between these six lifestyle risk behaviors. RESULTS: Among all participants, the most prevalent lifestyle risk behavior for those at high risk for ASCVD was excessive sodium intake (95.6%), followed by inadequate sleep (49.9%) and physical inactivity (43.8%). Older age (65-79 years) and male sex were directly associated with a high risk for ASCVD. Physical inactivity, current smoking, excessive sodium intake, and unhealthy weight indirectly mediated the effects of older age (8.2% of the older age) and male sex (39.9% of males) to high ASCVD risk. Physical inactivity, current smoking, excessive sodium intake, and unhealthy weight particularly mediated the high ASCVD risk sequentially. Heavy alcohol consumption and inadequate sleep were not directly associated with high ASCVD risk and did not indirectly mediate the effects of older age and males on the high ASCVD risk. CONCLUSION: Lifestyle risk behaviors mediated the atherosclerotic cardiovascular disease risk in a different manner. Especially, physical inactivity preceded current smoking, excessive sodium intake, and unhealthy weight in relation to high ASCVD risk, and this causal relationship was different according to age and sex. Therefore, tailored strategies according to specific target populations may be needed to effectively reduce the high ASCVD risk.
Asunto(s)
Aterosclerosis , Estilo de Vida , Encuestas Nutricionales , Humanos , Masculino , Persona de Mediana Edad , Femenino , República de Corea/epidemiología , Anciano , Adulto , Aterosclerosis/epidemiología , Fumar/epidemiología , Factores de Riesgo , Consumo de Bebidas Alcohólicas/epidemiología , Teorema de Bayes , Asunción de Riesgos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiologíaRESUMEN
Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder influenced by various factors, including liver function, which may impact the clearance of amyloid-ß (Aß) in the brain. This study aimed to explore how the apolipoprotein E (APOE) ε4 allele affects the relationship of liver function markers with AD pathology and cognition. Methods: We analyzed data from two independent cohorts, including 732 participants from the Hallym University Medical Center and 483 from the Alzheimer's Disease Neuroimaging Initiative, each group consisting of individuals with and without the APOE ε4 allele. Cross-sectional analyses evaluated the associations of liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, total bilirubin, and albumin) with AD diagnosis, amyloid positron emission tomography (PET) burden, and cerebrospinal fluid biomarkers for AD (Aß42, total tau, and phosphorylated tau181) at baseline. Longitudinally, we investigated the associations between these liver enzymes and changes in cognitive performance over the course of a year. Logistic and linear regression models were used to analyze these associations and mediation analyses were conducted to assess whether age and amyloid PET burden mediated these associations. Results: Only in the APOE ε4 carrier group, a high AST to ALT ratio and low ALT levels were significantly associated with AD diagnosis, increased amyloid PET burden, and faster longitudinal decline in cognitive function in both cohorts. In particular, the AST to ALT ratio was associated with cerebrospinal fluid Aß42 levels exclusively in the APOE ε4 carrier group in the Alzheimer's Disease Neuroimaging Initiative cohort but not with phosphorylated tau181 or total tau levels. Moreover, mediation analyses from both cohorts revealed that in the APOE ε4 carriers group, age did not mediate the associations between liver enzymes and AD diagnosis or amyloid PET burden. However, amyloid PET burden partially mediated the association between liver enzymes and AD diagnosis exclusively in the APOE ε4 carriers group. Conclusion: This study provides valuable insights into the significant association of the APOE ε4 allele with liver enzymes and their potential role in Aß-related pathogenesis and cognition in AD. Further research is required to elucidate the underlying mechanisms and potential therapeutic implications of these findings.
RESUMEN
This study aimed to create and validate a predictive model for renal function following live kidney donation, using pre-donation factors. Accurately predicting remaining renal function post live kidney donation is currently insufficient, necessitating an effective assessment tool. A multicenter retrospective study of 2318 live kidney donors from two independent centers (May 2007-December 2019) was conducted. The primary endpoint was the reduction in eGFR to below 60 mL/min/m2 6 months post-donation. The primary endpoint was achieved in 14.4% of the training cohort and 25.8% of the validation cohort. Sex, age, BMI, hypertension, preoperative eGFR, and remnant kidney proportion (RKP) measured by computerized tomography (CT) volumetry were found significant in the univariable analysis. These variables informed a scoring system based on multivariable analysis: sex (male: 1, female: 0), age at operation (< 30: 0, 30-39: 1, 40-59: 2, ≥ 60: 3), preoperative eGFR (≥ 100: 0, 90-99: 2, 80-89: 4, < 80: 5), and RKP (≥ 52%: 0, < 52%: 1). The total score ranged from 0 to 10. The model showed good discrimination for the primary endpoint in both cohorts. The prediction model provides a useful tool for estimating post-donation renal dysfunction risk, factoring in the side of the donated kidney. It offers potential enhancement to pre-donation evaluations.
Asunto(s)
Tasa de Filtración Glomerular , Trasplante de Riñón , Riñón , Donadores Vivos , Nefrectomía , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Riñón/diagnóstico por imagen , Nefrectomía/efectos adversos , Factores de Riesgo , Medición de Riesgo/métodos , Pruebas de Función RenalRESUMEN
OBJECTIVES: This study aimed to investigate the longitudinal relationship between social frailty and cognitive impairment among community-dwelling older adults. DESIGN: This retrospective cohort study is based on the first to eighth waves of the Korean Longitudinal Study of Ageing (2006-2020). SETTING AND PARTICIPANTS: The participants were 2106 community-dwelling older adults aged 65 years or older and without cognitive impairment in 2006. METHODS: Social frailty was assessed with 5 items including social support, social activity, social network, loneliness, and living alone (0 = social nonfrailty, 1 = social prefrailty, 2 or more = social frailty). Cognitive function was assessed using the Korean Mini-Mental State Examination, and scores below 24 indicated cognitive impairment. We used the generalized estimating equation to assess the longitudinal relationship between social frailty and cognitive impairment. RESULTS: Of the 2106 participants, 515 (24.4%) had social frailty, 669 (31.8%) had social prefrailty, and 922 (43.8%) were social nonfrailty based on the baseline assessments. Relative to the social nonfrailty group, the odds ratios of the social prefrailty and social frailty groups for cognitive impairment were 1.30 (95% CI 1.10-1.54) and 1.41 (95% CI 1.16-1.71), respectively, during the follow-up. Subgroup analysis showed that social inactivity and loneliness were significantly associated with cognitive impairment. CONCLUSIONS AND IMPLICATIONS: These findings highlight the need for health care providers to introduce and use available social resources for older adults with social frailty to increase the relationships between individual and social context. Social inactivity and loneliness were the major domains associated with cognitive impairment, and loneliness can be resolved by participating in social activities. Therefore, health care providers especially provide opportunities for social activities, such as group-based programs in the community, to reduce social frailty and cognitive impairment.
Asunto(s)
Disfunción Cognitiva , Humanos , Anciano , Masculino , Femenino , Disfunción Cognitiva/epidemiología , República de Corea/epidemiología , Estudios Longitudinales , Estudios Retrospectivos , Anciano de 80 o más Años , Vida Independiente , Evaluación Geriátrica , Fragilidad/psicología , Fragilidad/epidemiología , Anciano Frágil/psicología , Anciano Frágil/estadística & datos numéricos , Estudios de Seguimiento , Apoyo Social , Soledad/psicologíaRESUMEN
BACKGROUND: Homologous recombination deficiency (HRD) stands as a clinical indicator for discerning responsive outcomes to platinum-based chemotherapy and poly ADP-ribose polymerase (PARP) inhibitors. One of the conventional approaches to HRD prognostication has generally centered on identifying deleterious mutations within the BRCA1/2 genes, along with quantifying the genomic scars, such as Genomic Instability Score (GIS) estimation with scarHRD. However, the scarHRD method has limitations in scenarios involving tumors bereft of corresponding germline data. Although several RNA-seq-based HRD prediction algorithms have been developed, they mainly support cohort-wise classification, thereby yielding HRD status without furnishing an analogous quantitative metric akin to scarHRD. This study introduces the expHRD method, which operates as a novel transcriptome-based framework tailored to n-of-1-style HRD scoring. RESULTS: The prediction model has been established using the elastic net regression method in the Cancer Genome Atlas (TCGA) pan-cancer training set. The bootstrap technique derived the HRD geneset for applying the expHRD calculation. The expHRD demonstrated a notable correlation with scarHRD and superior performance in predicting HRD-high samples. We also performed intra- and extra-cohort evaluations for clinical feasibility in the TCGA-OV and the Genomic Data Commons (GDC) ovarian cancer cohort, respectively. The innovative web service designed for ease of use is poised to extend the realms of HRD prediction across diverse malignancies, with ovarian cancer standing as an emblematic example. CONCLUSIONS: Our novel approach leverages the transcriptome data, enabling the prediction of HRD status with remarkable precision. This innovative method addresses the challenges associated with limited available data, opening new avenues for utilizing transcriptomics to inform clinical decisions.
Asunto(s)
Recombinación Homóloga , Neoplasias , Transcriptoma , Humanos , Transcriptoma/genética , Recombinación Homóloga/genética , Neoplasias/genética , Algoritmos , Femenino , Perfilación de la Expresión Génica/métodosRESUMEN
Background: Preterm birth (PTB) is a significant challenge in contemporary obstetrics, affecting over one in ten infants worldwide and accounting for 75% of perinatal mortality. Short cervical length during mid-trimester is well known to be associated with an increased risk of spontaneous preterm birth (sPTB). Ultrasound-indicated cerclage (UIC) is recommended to prevent sPTB in women with a short cervix at mid-trimester and a history of sPTB. Objectives: This retrospective observational study aimed to examine the impact of diabetes and obesity on the occurrence of sPTB in women who underwent UIC due to mid-trimester cervical shortening. Methods/Results: The analysis revealed that cervical length at the time of operation, preoperative erythrocyte sedimentation rate levels, and diabetes were independent risk factors for sPTB. Additionally, the presence of diabetes, particularly when combined with obesity, significantly elevated the risk of sPTB. Women with pregestational diabetes or those requiring insulin treatment had a higher propensity for preterm delivery compared to those with gestational diabetes managed through diet control alone. Conclusions: These findings emphasize the importance of considering maternal metabolic factors, such as diabetes and obesity, in women with a short cervix when planning for UIC and highlight the crucial role of optimizing maternal glucose control and weight management in reducing the risk of sPTB.
RESUMEN
HCC (Hepatocellular carcinoma) is the most common malignant tumor; however, the molecular pathogenesis of these tumors is not well understood. Sorafenib, an approved treatment for HCC, inhibits angiogenesis and tumor cell proliferation. However, only ~30% of patients are sensitive to sorafenib and most show disease progression, indicating resistance to sorafenib. The present study used machine learning to investigate several mechanisms related to sorafenib resistance in liver cancer cells. This revealed that unphosphorylated interferon-stimulated genes (U-ISGs) were upregulated in sorafenib-resistant liver cancer cells, and the unphosphorylated ISGF3 (U-ISGF3; unphosphorylated STAT1, unphosphorylated STAT2 and IRF9) complex was increased in sorafenib-resistant liver cancer cells. Further study revealed that the knockdown of the U-ISGF3 complex downregulated U-ISGs. In addition, inhibition of the U-ISGF3 complex downregulated cell viability in sorafenib-resistant liver cancer cells. These results suggest that U-ISGF3 induced sorafenib resistance in liver cancer cells. Also, this mechanism may also be relevant to patients with sorafenib resistance.
RESUMEN
BACKGROUND: Despite the important clinical issue of cognitive impairment after moderate traumatic brain injury (TBI), there is currently no suitable treatment. Here, we used in vitro and in vivo models to investigate the effect of Donepezil-an acetylcholinesterase (AChE) inhibitor-on cognitive impairment in the acute period following injury, while focusing on neuroinflammation and autophagy- and mitophagy-related markers. METHODS: The purpose of the in vitro study was to investigate potential neuroprotective effects in TBI-induced cells after donepezil treatment, and the in vivo study, the purpose was to investigate therapeutic effects on cognitive impairment in the acute period after injury by analyzing neuroinflammation and autophagy- and mitophagy-related markers. The in vitro TBI model involved injuring SH-SY5Y cells using a cell-injury controller and then investigating the effect of donepezil at a concentration of 80 µM. The in vivo TBI model was made using a stereotaxic impactor for male C57BL/6J mice. Immuno-histochemical markers and cognitive functions were compared after 7 days of donepezil treatment (1 mg/kg/day). Mice were divided into four groups: sham operation with saline treatment, sham operation with donepezil treatment, TBI with saline treatment, and TBI with donepezil treatment (18 mice in each group). Donepezil treatment was administered within 4 h post-TBI. RESULTS: In vitro, donepezil was found to lead to increased cell viability and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimi-dazolylcarbocyanine iodide (JC-1), along with decreased reactive oxygen species (ROS), lactate-dehydrogenase (LDH), 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA)-positive cells, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. The mRNA and protein expressions of neuroinflammation (Cyclooxygenase-2, COX-2; NOD-like receptor protein 3, NLRP3; Caspase-1; and Interleukin-1 beta, IL-1ß), as well as autophagy- and mitophagy-related markers (death-associated protein kinase 1, DAPK1; PTEN-induced kinase 1, PINK1; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like, BNIP3L; Beclin-1, BECN1; BCL2-associated X protein, BAX; microtubule-associated protein 1A/1B-light chain 3B (LC3B); Sequestosome-1; and p62) were all found to decrease after donepezil treatment. The in vivo study also showed that donepezil treatment resulted in decreased levels of cortical tissue losses and brain swelling in TBI compared to the TBI group without donepezil treatment. Donepezil treatment was also shown to decrease the mRNA and Western blotting expressions of all markers, and especially COX-2 and BNIP3L, which showed the most significant decreases. Moreover, TBI mice showed an decreased escape latency, increased alteration rate, and improved preference index, altogether pointing to better cognitive performance after donepezil treatment. CONCLUSIONS: Donepezil treatment may be beneficial in improving cognitive impairment in the early phase of moderate traumatic brain injury by ameliorating neuroinflammation, as well as autophagy and mitophagy.
RESUMEN
OBJECTIVES: The occurrence of cognitive deficits after subarachnoid hemorrhage (SAH) is highly possible, leading to vascular dementia. We performed a novel longitudinal genome-wide association study (GWAS) to identify genetic modifications associated with cognitive impairment following SAH in a long-term prospective cohort study. MATERIALS AND METHODS: This GWAS involved 153 patients with SAH sharing 5,971,372 markers after high-throughput imputation. Genome-wide Cox proportional hazard regression testing was performed to estimate the hazard ratio (HR) and 95% confidence interval (CI). Subsequently, a weighted polygenetic risk score (wPRS) was determined, based on GWAS-driven loci and risk stratification. RESULTS: Cognitive impairment was observed in 65 patients (42.5%) during a mean follow-up of 37.7 ± 12.4 months. Five genome-wide signals, including rs138753053 (PDCD6IP-LOC101928135, HR = 28.33, p = 3.4 × 10-8), rs56823384 (LINC00499, HR = 12.47, p = 2.8 × 10-9), rs145397166 (CASC15, HR = 11.16, p = 1.7 × 10-8), rs10503670 (LPL-SLC18A1, HR = 2.88, p = 4.0 × 10-8), and rs76507772 (IRS2, HR = 5.99, p = 3.5 × 10-8), were significantly associated with cognitive impairment following SAH. In addition, the well-constructed wPRS containing five markers showed nominal ability to predict cognitive impairment (AUROC = 0.745, 95% CI: 0.667-0.824). Tertile stratification showed a higher effectiveness in predicting cognitive impairment, especially in those with haptoglobin 2-1 (HR = 44.59, 95% CI: 8.61-231.08). CONCLUSIONS: Our study revealed novel susceptible loci for cognitive impairment, longitudinally measured in patients with SAH. The clinical utility of these loci will be evaluated in further follow-up studies.
RESUMEN
BACKGROUND: Target systolic blood pressure (SBP) levels for older adults with hypertension vary across countries, leading to challenges in determining the appropriate SBP level. OBJECTIVE: This study aims to identify the optimal SBP level for minimizing all-cause and cardiovascular disease (CVD) mortality in older Korean adults with hypertension. METHODS: This retrospective cohort study used data from the National Health Insurance Service database. We included older adults aged 65 years or older who were newly diagnosed with hypertension and underwent a National Health Insurance Service health checkup in 2003-2004. We excluded patients who had a history of hypertension or CVD, were not prescribed medication for hypertension, had missing blood pressure or any other covariate values, and had fewer than 2 health checkups during the follow-up period until 2020. We categorized the average SBP levels into 6 categories in 10 mm Hg increments, from <120 mm Hg to ≥160 mm Hg; 130-139 mm Hg was the reference range. Cox proportional hazards models were used to examine the relationship between SBP and all-cause and CVD mortalities, and subgroup analysis was conducted by age group (65-74 years and 75 years or older). RESULTS: A total of 68,901 older adults newly diagnosed with hypertension were included in this study. During the follow-up period, 32,588 (47.3%) participants had all-cause mortality and 4273 (6.2%) had CVD mortality. Compared to older adults with SBP within the range of 130-139 mm Hg, individuals who fell into the other SBP categories, excluding those with SBP 120-129 mm Hg, showed significantly higher all-cause and CVD mortality. Subgroup analysis showed that older adults aged 65-74 years had higher all-cause and CVD mortality rates according to SBP categories than those aged 75 years or older. CONCLUSIONS: The SBP levels within the range of 120-139 mm Hg were associated with the lowest all-cause and CVD mortality rates among older Korean adults with hypertension. It is recommended to reduce SBP to <140 mm Hg, with 120 mm Hg as the minimum value for SBP, for older Korean adults with hypertension. Additionally, stricter SBP management is required for adults aged 65-74 years.
Asunto(s)
Presión Sanguínea , Enfermedades Cardiovasculares , Hipertensión , Humanos , Anciano , Hipertensión/epidemiología , Masculino , Femenino , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , República de Corea/epidemiología , Estudios Retrospectivos , Presión Sanguínea/fisiología , Anciano de 80 o más Años , Estudios de Cohortes , Causas de Muerte/tendenciasRESUMEN
BACKGROUND: The association between tuberculous fibrosis and lung cancer development has been reported by some epidemiological and experimental studies; however, its underlying mechanisms remain unclear, and the role of macrophage (MФ) polarization in cancer progression is unknown. The aim of the present study was to investigate the role of M2 Arg-1+ MФ in tuberculous pleurisy-assisted tumorigenicity in vitro and in vivo. METHODS: The interactions between tuberculous pleural effusion (TPE)-induced M2 Arg-1+ MФ and A549 lung cancer cells were evaluated. A murine model injected with cancer cells 2 weeks after Mycobacterium bovis bacillus Calmette-Guérin pleural infection was used to validate the involvement of tuberculous fibrosis to tumor invasion. RESULTS: Increased CXCL9 and CXCL10 levels of TPE induced M2 Arg-1+ MФ polarization of murine bone marrow-derived MФ. TPE-induced M2 Arg-1+ MФ polarization facilitated lung cancer proliferation via autophagy signaling and E-cadherin signaling in vitro. An inhibitor of arginase-1 targeting M2 Arg-1+ MФ both in vitro and in vivo significantly reduced tuberculous fibrosis-induced metastatic potential of lung cancer and decreased autophagy signaling and E-cadherin expression. CONCLUSION: Tuberculous pleural fibrosis induces M2 Arg-1+ polarization, and M2 Arg-1+ MФ contribute to lung cancer metastasis via autophagy and E-cadherin signaling. Therefore, M2 Arg-1+ tumor associated MФ may be a novel therapeutic target for tuberculous fibrosis-induced lung cancer progression.
Asunto(s)
Arginasa , Autofagia , Progresión de la Enfermedad , Neoplasias Pulmonares , Macrófagos , Transducción de Señal , Animales , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/microbiología , Humanos , Ratones , Autofagia/fisiología , Arginasa/metabolismo , Transducción de Señal/fisiología , Macrófagos/metabolismo , Macrófagos/patología , Tuberculosis Pleural/patología , Tuberculosis Pleural/metabolismo , Células A549 , Ratones Endogámicos C57BL , Derrame Pleural/metabolismo , Derrame Pleural/patología , Polaridad Celular/fisiologíaRESUMEN
We have developed a fluorescent probe DBT-Cl ((E)-2-(2-(4-(diphenylamino)benzylidene) hydrazinyl)-N,N,N-trimethyl-2-oxoethan-1-aminium chloride) for ClO- with an aggregation-induced emission (AIE) strategy depending on solvent polarity. DBT-Cl possessed a prominent solvatochromic emission property with intramolecular charge transfer (ICT) from the TPA (triphenylamine) to the amide group, which was studied by spectroscopic analysis and DFT calculations. These unique AIE properties of DBT-Cl led to the recognition of ClO- with high fluorescent selectivity. DBT-Cl quickly detected ClO- in less than 1 sec with a fluorescent color change from green to cyan. DBT-Cl had a low detection limit of 9.67 µM to ClO-. Detection mechanism of DBT-Cl toward ClO- was illustrated to be oxidative cleavage of DBT-Cl by 1H NMR titrations, ESI-mass, and DFT calculations. We established the viability for dependable detection of ClO- in actual water samples, as well as zebrafish and plant imaging. In particular, DBT-Cl was capable of easily monitoring ClO- through a smartphone application. Therefore, DBT-Cl assured a promising approach for a fast-responsive and multi-applicable ClO- probe in environmental and living organism systems.
Asunto(s)
Colorantes Fluorescentes , Ácido Hipocloroso , Teléfono Inteligente , Espectrometría de Fluorescencia , Pez Cebra , Ácido Hipocloroso/análisis , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Animales , Espectrometría de Fluorescencia/métodos , Agua/química , Límite de Detección , Contaminantes Químicos del Agua/análisis , Teoría Funcional de la DensidadRESUMEN
Diabetes mellitus (DM) predisposes individuals to vascular injury, leading to poor outcomes after ischemic stroke and symptomatic hemorrhagic transformation (SHT) after thrombolytic and endovascular treatment (EVT). Metformin (MET), an oral antidiabetic drug, has shown potential neuroprotective effects, but its impact on stroke prognosis in DM patients undergoing EVT remains unclear. In a multicenter study, 231 patients with DM undergoing EVT for acute ischemic stroke were enrolled. Prior MET use was identified, and patients were stratified into MET+ and MET- groups. Demographics, clinical data, and outcomes were compared between groups. Multivariate analysis was used to assess the effect of MET on stroke prognosis. Of the enrolled patients, 59.3% were previously on MET. MET+ patients had lower initial infarct volumes and NIHSS scores compared to MET-taking patients. Multivariate analysis showed that MET+ was associated with a lower risk of stroke progression and SHT (with stroke progression as follows: odd ratio [OR] 0.24, 95% confidence interval [CI] [0.12-0.48], p < 0.001; SHT: OR 0.33, 95% CI [0.14-0.75], p = 0.01) and was also associated with better 3-month functional outcomes (mRS 0-2) after EVT. Prestroke MET use in DM patients undergoing EVT is associated with improved stroke prognosis, including reduced risk of stroke progression and SHT and better functional outcomes. These findings suggest the potential neuroprotective role of MET in this population and highlight its clinical utility as an adjunctive therapy in the management of ischemic stroke. Further research is warranted to elucidate the underlying mechanisms and to optimize MET therapy in this setting.
RESUMEN
Microplastics can cause environmental pollution and ecosystem destruction as well as human health problems. Among the types of microplastics, polyurethane (PU) is particularly resistant to heat and difficult to decompose, causing disposal problems, and is evaluated as one of the most hazardous polymers. We present a novel colorimetric and near-infrared (NIR) fluorescence dye, (E)-N-(2-((4-(diphenylamino)benzylidene)amino)phenyl)- 7-nitrobenzo[c][1,2,5]oxadiazol-4-amine (DPNA), designed for selective visual PU microplastic staining. The intramolecular charge transfer (ICT) properties of DPNA are demonstrated through density functional theory (DFT) calculations along with solvatochromic shift. DPNA exhibits red color and red fluorescence emission, showing promising potential as a staining dye. To achieve selective PU microplastic staining, we establish an optimized experimental procedure with the staining dye DPNA by evaluating the staining efficiency under different staining solvent compositions and staining times. DPNA can distinguish PU by both red fluorescence signal and red coloration among different types of microplastics. In addition, DPNA well stain fresh PUs with diverse sizes and at various pH range of 5-9, and the aged PUs can also be dyed as effectively as the fresh PU. Most importantly, DPNA selectively stains PU among 11 types of microplastics and 5 types of natural particles in environmental water and soil with and without any pre-treatments. The adsorption mechanism of DPNA on PU microplastic is demonstrated through field emission scanning electron microscopes (FE-SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), and non-covalent interaction (NCI)-reduced density gradient (RDG) analyses, and proposed that intermolecular hydrogen bonding has a significant effect.
RESUMEN
A water-soluble colorimetric chemosensor NHOP ((E)-1-(2-(2-(2-hydroxy-5-nitrobenzylidene)hydrazineyl)-2-oxoethyl)pyridin-1-ium) chloride) was developed for the sequential probing of Cu2+ and S2-. NHOP underwent a color change from pale yellow to colorless in the presence of Cu2+ in pure water. The binding ratio between NHOP and Cu2+ was confirmed to be 1:1 by the Job plot and ESI-MS (electrospray ionization mass spectrometry). The detection limit of NHOP for Cu2+ was calculated as 0.15 µM, which was far below the EPA (Environmental Protection Agency) standard (20 µM). The NHOP-coated test strip was able to easily monitor Cu2+ in real-time. Meanwhile, the NHOP-Cu2+ complex reverted from colorless to pale yellow in the presence of S2- through the demetallation. The stoichiometric ratio between NHOP-Cu2+ and S2- was determined to be 1:1 by analyzing the Job plot and ESI-MS. The detection limit of NHOP-Cu2+ for S2- was calculated as 0.29 µM, which was very below the WHO (World Health Organization) guideline (14.7 µM). NHOP successfully achieved the quantification for Cu2+ and S2- in water samples. NHOP could work as a sequential probe for Cu2+ and S2- at the biological pH range (7.0-8.4). Moreover, NHOP could successively probe Cu2+ and S2- at least three cycles because of its reversible property. The detection mechanisms of NHOP for Cu2+ and NHOP-Cu2+ for S2- were demonstrated with Job plot, ESI-MS, and DFT (density functional theory) calculations. Therefore, NHOP could work as an efficient sequential probe for Cu2+ and S2- in environmental systems.
Asunto(s)
Colorimetría , Cobre , Cobre/análisis , Cobre/química , Colorimetría/métodos , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/química , Agua/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Límite de DetecciónRESUMEN
OBJECTIVE: Using endoscopic images, we have previously developed computer-aided diagnosis models to predict the histopathology of gastric neoplasms. However, no model that categorizes every stage of gastric carcinogenesis has been published. In this study, a deep-learning-based diagnosis model was developed and validated to automatically classify all stages of gastric carcinogenesis, including atrophy and intestinal metaplasia, in endoscopy images. DESIGN: A total of 18,701 endoscopic images were collected retrospectively and randomly divided into train, validation, and internal-test datasets in an 8:1:1 ratio. The primary outcome was lesion-classification accuracy in six categories: normal/atrophy/intestinal metaplasia/dysplasia/early /advanced gastric cancer. External-validation of performance in the established model used 1427 novel images from other institutions that were not used in training, validation, or internal-tests. RESULTS: The internal-test lesion-classification accuracy was 91.2% (95% confidence interval: 89.9%-92.5%). For performance validation, the established model achieved an accuracy of 82.3% (80.3%-84.3%). The external-test per-class receiver operating characteristic in the diagnosis of atrophy and intestinal metaplasia was 93.4 ± 0% and 91.3 ± 0%, respectively. CONCLUSIONS: The established model demonstrated high performance in the diagnosis of preneoplastic lesions (atrophy and intestinal metaplasia) as well as gastric neoplasms.
Asunto(s)
Diagnóstico por Computador , Gastroscopía , Metaplasia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/diagnóstico por imagen , Estudios Retrospectivos , Diagnóstico por Computador/métodos , Masculino , Femenino , Metaplasia/patología , Metaplasia/diagnóstico por imagen , Gastroscopía/métodos , Persona de Mediana Edad , Aprendizaje Profundo , Lesiones Precancerosas/patología , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/diagnóstico por imagen , Atrofia , Carcinogénesis/patología , Anciano , Curva ROC , Estadificación de Neoplasias , Mucosa Gástrica/patología , Mucosa Gástrica/diagnóstico por imagen , Reproducibilidad de los ResultadosRESUMEN
This study aimed to compare the video laryngoscope views facilitated by curved blades 3 and 4 with an exploration of the relationship between these views and patient height. Conducted as a randomized controlled trial, this study enrolled adults scheduled for surgery under general anesthesia. Intubation procedures were recorded, and the percentage of glottic opening was measured before tube insertion. Multivariate analysis validated the impact of various factors, including blade size and patient height, on the percentage of glottic opening scores. A total of 192 patients were included. The median percentage of glottic opening scores for curved blades 3 and 4 were 100 and 83, respectively (p < 0.001). The unstandardized coefficient indicated a significant negative impact of blade 4 on the percentage of glottic opening scores (-13, p < 0.001). In the locally estimated scatterplot smoothing analysis, blade 3 exhibited a steady rise in glottic opening scores with increasing height, whereas blade 4 showed a peak followed by a decline around 185 cm. The unstandardized coefficient of height showed no significant association (0, p = 0.819). The study observed superior laryngoscopic views with blade 3 compared to blade 4. However, no significant association was found between laryngoscopic views and patient height.
RESUMEN
In this study, we developed a dual-channel fluorescent dye ((E)-N'-(4-(diphenylamino)benzylidene)pyrazine-2-carbohydrazide) DPC for visual detection of 8 types of microplastics (MPs; HDPE, MDPE, LDPE, PET, PU, PVC, PS, and PP) and selective PU. The intramolecular charge transfer (ICT) and aggregation-induced emission (AIE) properties of DPC were demonstrated by the spectroscopic analysis, DFT calculations, and Tyndall effect. MPs and nonplastics (cellulose, chitin, sand, shell, and wood) were stained with DPC in water and their respective fluorescence signals in the blue and green channels were analyzed. The staining procedure using DPC was optimized with the concentration of DPC and staining time as parameters. DPC was able to effectively stain 8 types of MPs and only PU in blue and green fluorescence signals, respectively. Furthermore, false positive detections of DPC were minimized through additional ethanol treatment after staining. Moreover, the effects of temperature, pH, and salinity on the staining ability of DPC were investigated. Surprisingly, DPC was able to selectively detect PU through the green fluorescence signal even in a single environment where various MPs existed. Most importantly, DPC is the first fluorescent dye capable of selectively monitoring PU in the green channel as well as staining 8 types of MPs in the blue channel. DPC showed promising potential to be used for MP monitoring on real environmental samples.
RESUMEN
A novel staining agent, (5-(4-(diethylamino)benzylidene)- 1,3-dimethylpyrimidine-2,4,6(1 H,3 H,5 H)-trione) (DDB) was developed for the effective detection of environmentally harmful microplastics. DDB has competitive cost advantages, namely its facile synthesis and high yield, over Nile Red (NR), which is commonly used for microplastic staining. The unique photophysical properties of DDB, including emissive twisted intramolecular charge transfer (TICT) and aggregation-induced emission (AIE), were corroborated via spectroscopic investigations and density functional theory (DFT) calculations. Notably, DDB demonstrated superior selectivity for staining microplastics (polyethylene (PE), polyurethane (PU), polypropylene (PP), polyvinyl chloride (PVC), polystyrene (PS), and polyethylene terephthalate (PET)) over non-plastic materials in water. Furthermore, modulation of the solvent environment during the staining process yielded distinct fluorescence in both the green and red channels for specific types of plastic with the interplay between locally excited (LE) and TICT states. Treatment with 5% ethanol results in the selective staining of PE and PET with the emission of red fluorescence, whereas treatment with 30% ethanol facilitates the selective staining of PU, PVC, and PET with the emission of green fluorescence. Additionally, DDB could selectively stain microplastics in spiked soil and river water samples. Furthermore, a smartphone-based fluorescence microscope was developed at a cost below $100, validating the effective detection of microplastics stained with the newly synthesized DDB. The outcomes of this research demonstrate the potential of DDB as an economical and efficient agent for selective microplastic detection.