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BACKGROUND: Kidney transplantation is a complex process requiring extensive preparation and ongoing monitoring. Artificial intelligence (AI)-powered chatbots hold potential for providing accessible health information, but our understanding of their role in offering health advice for kidney transplantation and how individuals assess such advice remains limited. This study investigates how individuals evaluate ChatGPT's responses to kidney transplantation questions in terms of information quality and empathy, focusing on potential differences across race/ethnicity and educational backgrounds. METHODS: We collected Reddit posts (N = 4624) regarding kidney transplantation and selected 86 questions to represent typical clinician inquiries. These questions were used as input prompts for ChatGPT. A total of 565 participants assessed ChatGPT's responses through online surveys, rating information quality and empathy using Likert scales. RESULTS: Multilevel analyses (N = 2825) show that there is a significant interaction between race/ethnicity and education levels in various measures related to perceived information quality, but not perceived empathy of ChatGPT's responses: accuracy (p < 0.05); authenticity (p < 0.01); believability (p < 0.05); informativeness (p = 0.053); usefulness (p < 0.05); recognizing users' feelings (p = 0.70) and understanding feelings and situations (p = 0.65). Among non-White individuals, higher education levels predicted higher perceived quality of ChatGPT's responses across all information quality measures. Notably, this trend was reversed for White individuals, where higher education levels led to lower perceived information quality. CONCLUSIONS: Our results highlight the importance of developing AI tools sensitive to diverse communication styles and information needs.
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Transplante de Rim , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Educação de Pacientes como Assunto , Inquéritos e Questionários , Escolaridade , Grupos Raciais , Prognóstico , Etnicidade , Seguimentos , Mídias SociaisRESUMO
BACKGROUND: This study analyzed the association between depressive symptoms and employment type, by considering both socioeconomic status and job stress factors. METHODS: We analyzed 27,369 participants (13,134 men and 14,235 women) using data from the fifth Korean Working Conditions Survey. The participants were divided into regular and precarious workers. Depressive symptoms were defined using the World Health Organization-5 Well-Being Index. A multivariate logistic regression analysis was performed to assess the association between depressive symptoms and employment type. RESULTS: Of the participants, 71.53% (N = 19578) were regular workers and 28.47% (N = 7791) were precarious workers. The weighted frequencies of participants with depressive symptoms (42.50%) were significantly higher than those of precarious workers (32.54%, p < 0.001). In the univariate and multivariate analyses, precarious workers had a significantly higher risk of depressive symptoms than regular workers (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.42-1.64; OR 1.16, 95% CI 1.07-1.26, respectively). The significant association between depressive symptoms and precarious workers has also been reflected in propensity score matched participants through crude and multivariate analysis (OR 1.54 [95% CI 1.43-1.66] and OR 1.15 [95% CI 1.04-1.26], respectively). CONCLUSIONS: The findings suggest that precarious workers may have a higher risk of depressive symptoms than regular workers. However, this is only a cross-sectional study. Therefore, further study is required to investigate the relevance association between depressive symptoms and employment types.
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Depressão , Emprego , Masculino , Humanos , Feminino , Depressão/epidemiologia , Estudos Transversais , República da Coreia/epidemiologia , Condições de TrabalhoRESUMO
Anithiactin D (1), a 2-phenylthiazole class of natural products, was isolated from marine mudflat-derived actinomycetes Streptomyces sp. 10A085. The chemical structure of 1 was elucidated based on the interpretation of NMR and MS data. The absolute configuration of 1 was determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectral data. Anithiactin D (1) significantly decreased cancer cell migration and invasion activities at a concentration of 5 µM via downregulation of the epithelial-to-mesenchymal transition (EMT) markers in A549, AGS, and Caco-2 cell lines. Moreover, 1 inhibited the activity of Rho GTPases, including Rac1 and RhoA in the A549 cell line, suppressed RhoA in AGS and Caco-2 cell lines, and decreased the mRNA expression levels of some matrix metalloproteinases (MMPs) in AGS and Caco-2 cell lines. Thus 1, which is a new entity of the 2-phenylthiazole class of natural products with a unique aniline-indole fused moiety, is a potent inhibitor of the motility of cancer cells.
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Neoplasias , Streptomyces , Humanos , Linhagem Celular Tumoral , Células CACO-2 , Streptomyces/metabolismo , Células A549 , Proteínas rho de Ligação ao GTP/metabolismo , Movimento Celular , Transição Epitelial-MesenquimalRESUMO
The decline in the function and mass of skeletal muscle during aging or other pathological conditions increases the incidence of aging-related secondary diseases, ultimately contributing to a decreased lifespan and quality of life. Much effort has been made to surmise the molecular mechanisms underlying muscle atrophy and develop tools for improving muscle function. Enhancing mitochondrial function is considered critical for increasing muscle function and health. This study is aimed at evaluating the effect of an aqueous extract of Gloiopeltis tenax (GTAE) on myogenesis and muscle atrophy caused by dexamethasone (DEX). The GTAE promoted myogenic differentiation, accompanied by an increase in peroxisome proliferator-activated receptor γ coactivator α (PGC-1α) expression and mitochondrial content in myoblast cell culture. In addition, the GTAE alleviated the DEX-mediated myotube atrophy that is attributable to the Akt-mediated inhibition of the Atrogin/MuRF1 pathway. Furthermore, an in vivo study using a DEX-induced muscle atrophy mouse model demonstrated the efficacy of GTAE in protecting muscles from atrophy and enhancing mitochondrial biogenesis and function, even under conditions of atrophy. Taken together, this study suggests that the GTAE shows propitious potential as a nutraceutical for enhancing muscle function and preventing muscle wasting.
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Dexametasona , Desenvolvimento Muscular , Atrofia Muscular , Extratos Vegetais , Animais , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/metabolismo , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/patologia , Dexametasona/efeitos adversos , Dexametasona/farmacologia , Desenvolvimento Muscular/efeitos dos fármacos , Camundongos , Extratos Vegetais/farmacologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Diferenciação Celular/efeitos dos fármacos , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Linhagem Celular , Proteínas Musculares/metabolismo , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Camundongos Endogâmicos C57BL , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/genética , RodófitasRESUMO
As in type 1 diabetes, the loss of pancreatic ß-cells leads to insulin deficiency and the subsequent development of hyperglycemia. Exercise has been proposed as a viable remedy for hyperglycemia. Lithium, which has been used as a treatment for bipolar disorder, has also been shown to improve glucose homeostasis under the conditions of obesity and type 2 diabetes by enhancing the effects of exercise on the skeletal muscles. In this study, we demonstrated that unlike in obesity and type 2 diabetic conditions, under the condition of insulin-deficient type 1 diabetes, lithium administration attenuated pancreatic a-cell mass without altering insulin-secreting ß-cell mass, implying a selective impact on glucagon production. Additionally, we also documented that lithium downregulated the hepatic gluconeogenic program by decreasing G6Pase protein levels and upregulating AMPK activity. These findings suggest that lithium's effect on glucose metabolism in type 1 diabetes is mediated through a different mechanism than those associated with exerciseinduced metabolic changes in the muscle. Therefore, our research presents the novel therapeutic potential of lithium in the treatment of type 1 diabetes, which can be utilized along with insulin and independently of exercise.
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Lacquer sap has been traditionally used in coatings and artwork. Suitable types of lacquer are required to preserve and restore artifacts. Recently, unsuitable cashew nut shell liquid (CNSL) has often been mixed with lacquer sap, so it is necessary to identify the characteristics of lacquer sap by the production area. However, research is still focused on urushiol and laccol. In this study, Myanmarese lacquer sap collected from Gluta usitata, which contains thitsiol as the main component, was analyzed by HPLC to quantify thitsiol using the standards 3-(10-phenyldecyl) benzene-1,2-diol (thitsiol 16) and 3-(8Z,11Z-pentadecadienyl)-benzenediol (urushiol 15:2) as markers, and calibration curves were plotted. The coefficients of determination (R2) for thitsiol 16 and urushiol 15:2 were 0.9985 and 0.9983, respectively. In addition, a blind test was conducted to confirm that accurate quantitative analysis was possible even when Myanmarese lacquer was mixed with lacquer from another production area, which contained urushiol as the main component, and CNSL, which contained cardol, a completely different catechol. Quantitative analysis of thitsiol 16 and urushiol 15:2 in Myanmarese lacquer using HPLC can be used to evaluate the quality of lacquer sap and for more sophisticated activities such as restoration by classifying differences in lacquer sap by the production area.
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Evidence for the association between high sodium intake and the onset of nonalcoholic fatty liver disease (NAFLD) is insufficient. This study examined the sex-specific association between sodium intake and the risk of NAFLD. This study included 2582 adults (aged 40-69 years; 1011 males and 1571 females). The total sodium excreted over 24 h was estimated from spot urine specimens using Tanaka's equation. Based on these estimates, participants were categorized into three groups according to their 24-h urinary sodium excretion levels: lowest (T1), middle (T2), and highest (T3). In addition, the participants were divided into non-NAFLD (≤36) and NAFLD (>36) groups based on the hepatic steatosis index. During the follow-up period (14 years), NAFLD was observed in 551 participants. The estimated 24-h urinary sodium excretion levels were positively associated with the incidence of NAFLD in all subjects. Upon sex stratification, females in the T2 and T3 groups exhibited adjusted hazard ratios of 1.35 and 1.51, respectively, compared with the T1 group. However, a significant relationship was not observed in males. High intake of sodium, especially among females, may be an important factor contributing to the development of NAFLD. Individuals with high sodium intake should be appropriately counselled and monitored for the risk of NAFLD.
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Hepatopatia Gordurosa não Alcoólica , Sódio na Dieta , Adulto , Masculino , Feminino , Humanos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Estudos Prospectivos , Sódio/urina , Sódio na Dieta/efeitos adversos , Estado NutricionalRESUMO
Insulin is essential for maintaining normoglycemia and is predominantly secreted in response to glucose stimulation by ß-cells. Incretin hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide, also stimulate insulin secretion. However, as obesity and type 2 diabetes worsen, glucose-dependent insulinotropic polypeptide loses its insulinotropic efficacy, whereas GLP-1 receptor (GLP-1R) agonists continue to be effective owing to its signaling switch from Gs to Gq. Herein, we demonstrated that endoplasmic reticulum (ER) stress induced a transition from Gs to Gq in GLP-1R signaling in mouse islets. Intriguingly, chemical chaperones known to alleviate ER stress, such as 4-PBA and TUDCA, enforced GLP-1R's Gq utilization rather than reversing GLP-1R's signaling switch induced by ER stress or obese and diabetic conditions. In addition, the activation of X-box binding protein 1 (XBP1) or activating transcription factor 6 (ATF6), 2 key ER stress-associated signaling (unfolded protein response) factors, promoted Gs utilization in GLP-1R signaling, whereas Gq employment by ER stress was unaffected by XBP1 or ATF6 activation. Our study revealed that ER stress and its associated signaling events alter GLP-1R's signaling, which can be used in type 2 diabetes treatment.
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Estresse do Retículo Endoplasmático , Receptor do Peptídeo Semelhante ao Glucagon 1 , Ilhotas Pancreáticas , Resposta a Proteínas não Dobradas , Animais , Camundongos , Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Glucose , InsulinaRESUMO
INTRODUCTION: Parental psychological responses during their child's pediatric intensive care unit (PICU) admission are often overlooked. This study aimed to identify pre-existing and peri-traumatic factors explaining parental stress and anxiety during their child's PICU admission and one-month follow-up. METHOD: A prospective pilot study included 60 PICU parents. Parental Stressors Scale and State-trait Anxiety Inventory measured stress and anxiety during PICU admission, and the State-trait Anxiety Inventory and Perceived Stress Scale at a one-month follow-up. RESULTS: During PICU admission, parental stress correlated with age, race, and adverse childhood experiences (ACEs), anxiety was linked to income. At one-month follow-up, anxiety related to child's health worries, perceived stress was linked to parental ACEs and education. Parental ACEs predicted perceived stress (b = 0.83, p = .028). Children's diagnoses explained anxiety, particularly respiratory and cardiac diagnoses (b = -13.44, p = .023; -10.03, p = .045). DISCUSSION: Identifying factors helps teams understand parental vulnerability and provide appropriate support.
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Ansiedade , Unidades de Terapia Intensiva Pediátrica , Pais , Estresse Psicológico , Humanos , Projetos Piloto , Estudos Prospectivos , Pais/psicologia , Masculino , Feminino , Estresse Psicológico/psicologia , Criança , Ansiedade/psicologia , Ansiedade/epidemiologia , Pré-Escolar , Adulto , Experiências Adversas da Infância/psicologia , Experiências Adversas da Infância/estatística & dados numéricos , LactenteRESUMO
BACKGROUND: Firefighters are an at-risk population for multiple psychiatric conditions, including posttraumatic stress disorder (PTSD), depression, alcohol use disorders (AUDs), and insomnia. These disorders are likely to co-occur; however, patterns of comorbidity have scarcely been investigated in firefighters. We aimed to identify subgroups of comorbidity of PTSD, depression, AUDs, and insomnia in a nationwide population of firefighters in South Korea. METHODS: A total of 54,054 firefighters responded to an online survey. Latent classes of comorbidity were categorized using latent profile analysis (LPA) based on the symptom scores of PTSD, depression, AUDs, and insomnia. Analysis of variance was performed to compare the characteristics of the identified classes, and multinomial logistic regression was conducted to examine whether anger reactions, resilience, and number of traumatic events predicted class membership. RESULTS: The LPA identified four subgroups: minimal symptoms (n = 42,948, 79.5 %), predominant PTSD (n = 2858, 5.3 %), subthreshold symptoms and comorbidity (n = 7003, 13.0 %), and high symptoms and comorbidity (n = 1245, 2.3 %). Three comorbidity classes were defined based on severity and one class showed predominant PTSD symptoms. Number of traumatic exposures predicted predominant PTSD, while resilience and anger reactions predicted severity of comorbidities. LIMITATIONS: The cross-sectional design and usage of self-reported questionnaires are limitations of this study. CONCLUSIONS: The severity of PTSD, depression, AUDs and insomnia tend to correlate and co-occur in firefighters. Our findings highlight the need to assess comorbid symptoms in firefighters and need to reduce anger reactions and enhance resilience in those with multiple comorbidities.
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Alcoolismo , Comorbidade , Depressão , Bombeiros , Distúrbios do Início e da Manutenção do Sono , Transtornos de Estresse Pós-Traumáticos , Humanos , Bombeiros/psicologia , Bombeiros/estatística & dados numéricos , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Masculino , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , Feminino , República da Coreia/epidemiologia , Pessoa de Meia-Idade , Alcoolismo/epidemiologia , Alcoolismo/psicologia , Depressão/epidemiologia , Depressão/psicologia , Inquéritos e Questionários , Ira , Análise de Classes Latentes , Resiliência Psicológica , Adulto Jovem , Estudos TransversaisRESUMO
INTRODUCTION AND OBJECTIVES: Delirium, recognized as a crucial prognostic factor in the cardiac intensive care unit (CICU), has evolved in response to the changing demographics among critically ill cardiac patients. This study aimed to create a predictive model for delirium for patients in the CICU. METHODS: This study included consecutive patients admitted to the CICU of the Samsung Medical Center. To assess the candidate variables for the model: we applied the following machine learning methods: random forest, extreme gradient boosting, partial least squares, and Plmnet-elastic.net. After selecting relevant variables, we performed a logistic regression analysis to derive the model formula. Internal validation was conducted using 100-repeated hold-out validation. RESULTS: We analyzed 2774 patients, 677 (24.4%) of whom developed delirium in the CICU. Machine learning-based models showed good predictive performance. Clinically significant and frequently important predictors were selected to construct a delirium prediction scoring model for CICU patients. The model included albumin level, international normalized ratio, blood urea nitrogen, white blood cell count, C-reactive protein level, age, heart rate, and mechanical ventilation. The model had an area under the receiver operating characteristics curve (AUROC) of 0.861 (95%CI, 0.843-0.879). Similar results were obtained in internal validation with 100-repeated cross-validation (AUROC, 0.854; 95%CI, 0.826-0.883). CONCLUSIONS: Using variables frequently ranked as highly important in four machine learning methods, we created a novel delirium prediction model. This model could serve as a useful and simple tool for risk stratification for the occurrence of delirium at the patient's bedside in the CICU.
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Delírio , Aprendizado de Máquina , Humanos , Delírio/epidemiologia , Delírio/diagnóstico , Masculino , Feminino , Idoso , Incidência , Unidades de Cuidados Coronarianos/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Curva ROC , Estado Terminal , Medição de Risco/métodos , Unidades de Terapia Intensiva/estatística & dados numéricos , Fatores de RiscoRESUMO
Although uric acid-lowering agents such as xanthine oxidase inhibitors have potential cardioprotective effects, studies on their use in preventing cardiovascular diseases are lacking. We investigated the genetically proxied effects of reducing uric acid on ischemic cardiovascular diseases in a lipid-level-stratified population. We performed drug-target Mendelian randomization (MR) analyses using UK Biobank data to select genetic instruments within a uric acid-lowering gene, xanthine dehydrogenase (XDH), and construct genetic scores. For nonlinear MR analyses, individuals were stratified by lipid level. Outcomes included acute myocardial infarction (AMI), ischemic heart disease, cerebral infarction, transient cerebral ischemic attack, overall ischemic disease, and gout. We included 474,983 non-gout individuals with XDH-associated single-nucleotide polymorphisms. The XDH-variant-induced uric acid reduction was associated with reduced risk of gout (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.78-0.93; P < 0.001), cerebral infarction (OR, 0.86; 95% CI, 0.75-0.98; P = 0.023), AMI (OR, 0.79; 95% CI, 0.66-0.94; P = 0.010) in individuals with triglycerides ≥ 188.00 mg/dL, and cerebral infarction in individuals with low-density lipoprotein cholesterol (LDL-C) ≤ 112.30 mg/dL (OR, 0.76; 95% CI, 0.61-0.96; P = 0.020) or LDL-C of 136.90-157.40 mg/dL (OR, 0.67; 95% CI, 0.49-0.92; P = 0.012). XDH-variant-induced uric acid reduction lowers the risk of gout, AMI for individuals with high triglycerides, and cerebral infarction except for individuals with high LDL-C, highlighting the potential heterogeneity in the protective effects of xanthine oxidase inhibitors for treating AMI and cerebral infarction depending on the lipid profiles.
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Gota , Infarto do Miocárdio , Humanos , Ácido Úrico , Xantina Oxidase/genética , Análise da Randomização Mendeliana , LDL-Colesterol/genética , Gota/tratamento farmacológico , Gota/genética , Infarto Cerebral/tratamento farmacológico , Infarto Cerebral/genética , Triglicerídeos/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Photoacoustic computed tomography (PACT), an emerging imaging modality in preclinical cancer research, can provide multiparametric 3D information about structures, physiological functions, and pharmacokinetics. Here, we demonstrate the use of high-definition 3D multiparametric PACT imaging of both primary and metastatic tumors in living mice to noninvasively monitor angiogenesis, carcinogenesis, hypoxia, and pharmacokinetics. The high-definition PACT system with a 1024-element hemispherical ultrasound transducer array provides an isotropic spatial resolution of 380 µm, an effective volumetric field-of-view of 12.8 mm × 12.8 mm × 12.8 mm without scanning, and an acquisition time of <30 s for a whole mouse body. Initially, we monitor the structural progression of the tumor microenvironment (e.g., angiogenesis and vessel tortuosity) after tumor cell inoculation. Then, we analyze the change in oxygen saturation of the tumor during carcinogenesis, verifying induced hypoxia in the tumor's core region. Finally, the whole-body pharmacokinetics are photoacoustically imaged after intravenous injection of micelle-loaded IR780 dye, and the in vivo PACT results are validated in vivo and ex vivo by fluorescence imaging. By employing the premium PACT system and applying multiparametric analyses to subcutaneous primary tumors and metastatic liver tumors, we demonstrate that this PACT system can provide multiparametric analyses for comprehensive cancer research.
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Neoplasias , Técnicas Fotoacústicas , Feminino , Animais , Técnicas Fotoacústicas/instrumentação , Técnicas Fotoacústicas/métodos , Tomografia/instrumentação , Tomografia/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Meios de Contraste , Neoplasias Hepáticas/secundário , Pele/patologiaRESUMO
A mid-infrared label-free immunoassay-based biosensor is an effective device to help identify and quantify biomolecules. This biosensor employs a surface-enhanced infrared absorption spectroscopy, which is a highly potent sensing technique for detecting minute quantities of analytes. In this study, a biosensor was constructed using a metamaterial absorber, which facilitated strong coupling effects. For maximum coupling effect, it is necessary to enhance the near-field intensity and the spatial and spectral overlap between the optical cavity resonance and the vibrational mode of the analyte. Due to significant peak splitting, conventional baseline correction methods fail to adequately analyze such a coupling system. Therefore, we employed a coupled harmonic oscillation model to analyze the spectral distortion resulting from the peak splitting induced by the strong coupling effect. The proposed biosensor with a thrombin-binding aptamer-based immunoassay could achieve a limit of detection of 267.4 pM, paving the way for more efficient protein detection in clinical practice.
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Técnicas Biossensoriais , Limite de Detecção , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Imunoensaio/instrumentação , Humanos , Aptâmeros de Nucleotídeos/química , Desenho de Equipamento , Espectrofotometria Infravermelho , Proteínas/análise , Trombina/análiseRESUMO
While empirical studies have observed that homeownership is associated with improved mental health conditions, research indicates that this relationship might vary by race. Moreover, such a White-Black disparity in the impacts of homeownership on mental health could be complexed by poverty status, as maintaining one's homeownership could be a financial burden for people living in poverty status, defined by the US official poverty threshold. We add to the existing literature by analyzing the impacts of homeownership on psychological distress, simultaneously disaggregating by race and poverty status using survey data from the Panel Study on Income Dynamics from the 2017 and 2019 waves (N = 7059). Propensity score weighting and doubly robust estimation are applied to estimate causal inference for the impact of 2017 homeownership on 2019 psychological distress using negative binomial models. First, we found the impacts of homeownership on reducing psychological distress are significant for White Americans, not for Black Americans. Second, we found such a White-Black disparity is only observable for populations not living in poverty. On the other hand, for populations living in poverty, homeownership no longer lowers psychological distress for either race. Findings suggest that financial support and mental health support are needy to address inequality in the impacts of homeownership on mental health, which could simultaneously vary by poverty status and race. Implications are discussed.
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Saúde Mental , Propriedade , Pobreza , Humanos , Pobreza/psicologia , Pobreza/estatística & dados numéricos , Propriedade/estatística & dados numéricos , Saúde Mental/estatística & dados numéricos , Feminino , Negro ou Afro-Americano/psicologia , Negro ou Afro-Americano/estatística & dados numéricos , Masculino , Estados Unidos , População Branca/estatística & dados numéricos , População Branca/psicologia , Adulto , Pessoa de Meia-Idade , Habitação/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricos , Grupos Raciais/psicologiaRESUMO
Bioactive metal-based nanostructures, particularly zinc oxide (ZnO), are promising materials for bone tissue engineering. However, integrating them into 3D-printed polymers using traditional blending methods reduces the cell performance. Alternative surface deposition techniques often require extreme conditions that are unsuitable for polymers. To address these issues, we propose a metal-assisted hydrothermal synthesis method to modify 3D printed polycaprolactone (PCL) scaffolds with ZnO nanoparticles (NPs), facilitating the growth of ZnO nanoarrays (NAs) at a low-temperature (55 °C). Physicochemical characterizations revealed that the ZnO NPs form both physical and chemical bonds with the PCL surface; chemical bonding occurs between the carboxylate groups of PCL and Zn(OH)2 during seed deposition and hydrothermal synthesis. The ZnO NPs and NAs grown for a longer time (18 h) on the surface of PCL scaffolds exhibit significant proliferation and early differentiation of osteoblast-like cells. The proposed method is suitable for the surface modification of thermally degradable polymers, opening up new possibilities for the deposition of diverse metals.
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Eugenol is a principal compound in essential clove oil, known for its anti-inflammatory and antioxidant properties. While recent studies have demonstrated its neuroprotective effects on central nervous system (CNS) injuries, such as brain ischemia/reperfusion injuries, but its potential impact on multiple sclerosis (MS), an autoimmune disease of the CNS, has not yet been explored. We evaluated the therapeutic effects of eugenol on experimental autoimmune encephalomyelitis (EAE), an established animal model of MS. EAE was induced in C57BL/6 mice using the myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. Clinical symptoms, including paralysis, were monitored daily, and levels of pro-inflammatory mediators were evaluated using real-time quantitative polymerase chain reaction, Western blot analyses, and immunohistochemistry. Daily oral administration of eugenol to MOG-induced EAE mice led to a notable decline in the severity of clinical symptoms. Eugenol inhibited EAE-related immune cell infiltration and the production of pro-inflammatory mediators. Histological examinations confirmed its ability to mitigate inflammation and demyelination in the spinal cord post-EAE induction. Eugenol alleviates neuroinflammation in the spinal cords of EAE-induced mice, primarily through anti-inflammatory action.
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Encefalomielite Autoimune Experimental , Esclerose Múltipla , Camundongos , Animais , Eugenol/uso terapêutico , Citocinas/uso terapêutico , Camundongos Endogâmicos C57BL , Medula Espinal/patologia , Esclerose Múltipla/tratamento farmacológico , Glicoproteína Mielina-Oligodendrócito , Anti-Inflamatórios/uso terapêutico , Mediadores da InflamaçãoRESUMO
As semiconductor devices shrink and their manufacturing processes advance, accurately measuring in-cell critical dimensions (CD) becomes increasingly crucial. Traditional test element group (TEG) measurements are becoming inadequate for representing the fine, repetitive patterns in cell blocks. Conventional non-destructive metrology technologies like optical critical dimension (OCD) are limited due to their large spot diameter of approximately 25 µm, which impedes their efficacy for detailed in-cell structural analysis. Consequently, there is a pressing need for small-spot and non-destructive metrology methods. To address this limitation, we demonstrate a microsphere-assisted hyperspectral imaging (MAHSI) system, specifically designed for small spot optical metrology with super-resolution. Utilizing microsphere-assisted super-resolution imaging, this system achieves an optical resolution of 66 nm within a field of view of 5.6 µm × 5.6 µm. This approach effectively breaks the diffraction limit, significantly enhancing the magnification of the system. The MAHSI system incorporating hyperspectral imaging with a wavelength range of 400-790 nm, enables the capture of the reflection spectrum at each camera pixel. The achieved pixel resolution, which is equivalent to the measuring spot size, is 14.4 nm/pixel and the magnification is 450X. The MAHSI system enables measurement of local uniformity in critical areas like corners and edges of DRAM cell blocks, areas previously challenging to inspect with conventional OCD methods. To our knowledge, this approach represents the first global implementation of microsphere-assisted hyperspectral imaging to address the metrology challenges in complex 3D structures of semiconductor devices.
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BACKGROUND: Receptor-interacting protein kinase (RIPK)3 is an essential molecule for necroptosis and its role in kidney fibrosis has been investigated using various kidney injury models. However, the relevance and the underlying mechanisms of RIPK3 to podocyte injury in albuminuric diabetic kidney disease (DKD) remain unclear. Here, we investigated the role of RIPK3 in glomerular injury of DKD. METHODS: We analyzed RIPK3 expression levels in the kidneys of patients with biopsy-proven DKD and animal models of DKD. Additionally, to confirm the clinical significance of circulating RIPK3, RIPK3 was measured by ELISA in plasma obtained from a prospective observational cohort of patients with type 2 diabetes, and estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), which are indicators of renal function, were followed up during the observation period. To investigate the role of RIPK3 in glomerular damage in DKD, we induced a DKD model using a high-fat diet in Ripk3 knockout and wild-type mice. To assess whether mitochondrial dysfunction and albuminuria in DKD take a Ripk3-dependent pathway, we used single-cell RNA sequencing of kidney cortex and immortalized podocytes treated with high glucose or overexpressing RIPK3. RESULTS: RIPK3 expression was increased in podocytes of diabetic glomeruli with increased albuminuria and decreased podocyte numbers. Plasma RIPK3 levels were significantly elevated in albuminuric diabetic patients than in non-diabetic controls (p = 0.002) and non-albuminuric diabetic patients (p = 0.046). The participants in the highest tertile of plasma RIPK3 had a higher incidence of renal progression (hazard ratio [HR] 2.29 [1.05-4.98]) and incident chronic kidney disease (HR 4.08 [1.10-15.13]). Ripk3 knockout improved albuminuria, podocyte loss, and renal ultrastructure in DKD mice. Increased mitochondrial fragmentation, upregulated mitochondrial fission-related proteins such as phosphoglycerate mutase family member 5 (PGAM5) and dynamin-related protein 1 (Drp1), and mitochondrial ROS were decreased in podocytes of Ripk3 knockout DKD mice. In cultured podocytes, RIPK3 inhibition attenuated mitochondrial fission and mitochondrial dysfunction by decreasing p-mixed lineage kinase domain-like protein (MLKL), PGAM5, and p-Drp1 S616 and mitochondrial translocation of Drp1. CONCLUSIONS: The study demonstrates that RIPK3 reflects deterioration of renal function of DKD. In addition, RIPK3 induces diabetic podocytopathy by regulating mitochondrial fission via PGAM5-Drp1 signaling through MLKL. Inhibition of RIPK3 might be a promising therapeutic option for treating DKD.
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Introduction: The formation and function of the corpus luteum (CL) increase the likelihood of pregnancy and efficiently manage implantation. Apoptosis must occur at an appropriate time in the formation of the CL. This also affects its function. However, it is still unclear if the type of apoptosis affects the function. Material and Methods: We conducted morphological analysis of the CL collected on day 15 between the middle and late oestrous phases of Yorkshire pigs and mini-pigs, and measured the difference in hormone expression and apoptosis using an immunoassay method and messenger RNA level. Results: The CL cells were more uniform in the Yorkshire pigs than in the mini-pigs, and the composition of the CL was also fuller. The expression of luteinising hormone was higher in the Yorkshire pigs. Apoptosis and the rate of action of matrix metalloproteinases (MMPs) were different between the two pig types. Expression of MMPs was higher in the Yorkshire pigs than in the mini-pigs. However, the expression of caspase 3 and 20alpha-hydroxysteroid dehydrogenase, a progesterone inhibitor, was potentiated in the mini-pigs. Conclusion: Autophagy throughout the CL was more extensive in the Yorkshire pigs than in the mini-pigs, suggesting that autophagy and cell reorganisation by MMPs were highly correlated. The occurrence of autophagy in the formation and function of the CL may affect the action of hormones and expression of cell reconstitution factors.