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Pneumonia stands as the leading infectious cause of childhood mortality annually, underscoring its significant impact on pediatric health. Although dexamethasone (DXMS) is effective for treating pulmonary inflammation, its therapeutic potential is compromised by systemic side effects and suboptimal carrier systems. To address this issue, the current study introduces solid lipid nanoparticles encapsulating hydrophobic dexamethasone palmitate (DXMS-Pal-SLNs) as an anti-inflammatory nanoplatform to treat pneumonia. The specialized nanoparticle formulation is characterized by high drug loading efficiency, low drug leakage and excellent colloidal stability in particular during nebulization and is proficiently designed to target alveolar macrophages in deep lung regions via local delivery with the nebulization administration. In vitro analyses revealed substantial reductions in the secretions of tumor necrosis factor-α and interleukin-6 from alveolar macrophages, highlighting the potential efficacy of DXMS-Pal-SLNs in alleviating pneumonia-related inflammation. Similarly, in vivo experiments showed a significant reduction in the levels of these cytokines in the lungs of mice experiencing lipopolysaccharide-induced pulmonary inflammation after the administration of DXMS-Pal-SLNs via nebulization. Furthermore, the study demonstrated that DXMS-Pal-SLNs effectively control acute infections without causing pulmonary infiltration or excessive recruitment of immunocytes in lung tissues. These findings highlight the potential of nebulized DXMS-Pal-SLNs as a promising therapeutic strategy for mitigating pneumonia-related inflammations.
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Background: Due to its prevalence, recurrence, and the emergence of drug-resistance, Candida vaginitis significantly impacts the well-being of women. Although cinnamon essential oil (CEO) possesses antifungal activity, its hydrophobic properties limit its clinical application. Purpose: To overcome this challenge, a nanoemulsification technology was employed to prepare cinnamon essential oil-nanoemulsion (CEO@NE), and its therapeutic efficacy and action mechanism for Candida vaginitis was investigated in vivo and in vitro. Materials and Methods: CEO@NE, composed of 4% CEO, 78% distilled water, and 18% Tween 80, was prepared by ultrasonic nanoemulsification. The physical properties, anti-Candida activity, cytotoxicity, immunomodulatory potential and storage stability of CEO@NE were explored. Subsequently, the effect of intravaginal CEO@NE treatment on Candida vaginitis was investigated in mice. To comprehend the possible mechanism of CEO@NE, an analysis was conducted to ascertain the production of intracellular reactive oxygen species (ROS) in C. albicans. Results: CEO@NE, with the droplet size less than 100 nm and robust storage stability for up to 8 weeks, exhibited comparable anti-Candida activity with CEO. CEO@NE at the concentration lower than 400 µg/mL had no cytotoxic and immunomodulatory effects on murine splenocytes. Intravaginal treatment of CEO@NE (400 µg/mL, 20 µL/day/mouse for 5 consecutive days) curbed Candida colonization, ameliorated histopathological changes, and suppressed inflammatory cytokine production in mice intravaginally challenged with C. albicans. Notably, this treatment preserved the density of vaginal lactic acid bacteria (LAB) crucial for vaginal health. Co-culturing C. albicans with CEO@NE revealed concentration-dependent augmentation of intracellular ROS generation and ensuing cell death. In addition, co-culturing LPS-stimulated murine splenocytes with CEO@NE yielded a decrease in the generation of cytokines. Conclusion: This discovery provides insight into the conceivable antifungal and anti-inflammatory mechanisms of CEO@NE to tackle Candida vaginitis. CEO@NE offers a promising avenue to address the limitations of current treatments, providing novel strategy for treating Candida vaginitis.
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Antifúngicos , Candida albicans , Candidiasis Vulvovaginal , Cinnamomum zeylanicum , Emulsiones , Aceites Volátiles , Femenino , Animales , Aceites Volátiles/química , Aceites Volátiles/farmacología , Aceites Volátiles/administración & dosificación , Candidiasis Vulvovaginal/tratamiento farmacológico , Candida albicans/efectos de los fármacos , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/administración & dosificación , Ratones , Administración Intravaginal , Cinnamomum zeylanicum/química , Emulsiones/química , Especies Reactivas de Oxígeno/metabolismo , Humanos , Nanopartículas/química , Ratones Endogámicos BALB CRESUMEN
Microbiota tryptophan metabolism and the biosynthesis of indole derivatives play an important role in homeostasis and pathogenesis in the human body and can be affected by the gut microbiota. However, studies on the interplay between gut microbiota and tryptophan metabolites in patients undergoing dialysis are lacking. This study aimed to identify the gut microbiota, the indole pathway in tryptophan metabolism, and significant functional differences in ESRD patients with regular hemodialysis. We performed the shotgun metagenome sequencing of stool samples from 85 hemodialysis patients. Using the linear discriminant analysis effect size (LEfSe), we examined the composition of the gut microbiota and metabolic features across varying concentrations of tryptophan and indole metabolites. Higher tryptophan levels promoted tyrosine degradation I and pectin degradation I metabolic modules; lower tryptophan levels were associated with glutamate degradation I, fructose degradation, and valine degradation modules. Higher 3-indoxyl sulfate concentrations were characterized by alanine degradation I, anaerobic fatty acid beta-oxidation, sulfate reduction, and acetyl-CoA to crotonyl-CoA. Contrarily, lower 3-indoxyl sulfate levels were related to propionate production III, arabinoxylan degradation, the Entner-Doudoroff pathway, and glutamate degradation II. The present study provides a better understanding of the interaction between tryptophan, indole metabolites, and the gut microbiota as well as their gut metabolic modules in ESRD patients with regular hemodialysis.
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Microbioma Gastrointestinal , Indoles , Diálisis Renal , Triptófano , Humanos , Triptófano/metabolismo , Indoles/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Anciano , Fallo Renal Crónico/terapia , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/microbiología , Heces/microbiología , Redes y Vías Metabólicas , Adulto , MetagenomaRESUMEN
The aim of this study was to validate the preventive effects of koumine (KM), a monoterpene indole alkaloid, on gouty arthritis (GA) and to explore its possible mechanisms. C57BL/6 mice were intraperitoneally administered KM (0.8, 2.4 or 7.2 mg/kg), colchicine (3.0 mg/kg) or sterile saline. One hour later, a monosodium urate (MSU) suspension was injected into the right hind paws of the mice to establish an acute gout model. Inflammation symptoms were evaluated at 0, 3, 6, 12 and 24 h, and the mechanical withdrawal threshold was evaluated at 0, 6 and 24 h. After 24 h, the mice were euthanized, and the joint tissue, kidney and blood were collected for subsequent experiments. Histological examination and antioxidant enzyme, kidney index and serum uric acid (UA) measurements were taken. The expression levels of the signalling pathway components were determined. KM effectively alleviated the symptoms of redness, swelling and pain; counteracted inflammatory cell infiltration; and increased antioxidant enzyme levels, reduced kidney index and serum UA levels through regulating UA excretion in MSU-induced mice. The expression of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) signalling pathway proteins and mRNA were reduced in the KM group. These results suggest that KM may be effective in alleviating GA through the TLR4/NF-κB/NLRP3 pathway.
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Artritis Gotosa , Ratones Endogámicos C57BL , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR , Transducción de Señal , Receptor Toll-Like 4 , Ácido Úrico , Animales , Artritis Gotosa/inducido químicamente , Artritis Gotosa/tratamiento farmacológico , Artritis Gotosa/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Receptor Toll-Like 4/metabolismo , FN-kappa B/metabolismo , Ácido Úrico/sangre , Transducción de Señal/efectos de los fármacos , Masculino , Ratones , Alcaloides Indólicos/farmacología , Modelos Animales de Enfermedad , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Colchicina/farmacologíaRESUMEN
BACKGROUND: Older patients with cardiovascular disease (CVD) are highly susceptible to adverse drug reactions due to age-related physiological changes and the presence of multiple comorbidities, polypharmacy, and potentially inappropriate medications (PIMs). OBJECTIVE: This study aimed to develop a predictive model to identify the use of PIMs in older patients with CVD. METHODS: Data from 2012 to 2021 from the Changhua Christian Hospital Clinical Research Database (CCHRD) and the Kaohsiung Medical University Hospital Research Database (KMUHRD) were analyzed. Participants over the age of 65 years with CVD diagnoses were included. The CCHRD data were randomly divided into a training set (80% of the database) and an internal validation set (20% of the database), while the KMUHRD data served as an external validation set. The training set was used to construct the prediction models, and both validation sets were used to validate the proposed models. RESULTS: A total of 48,569 patients were included. Comprehensive data analysis revealed significant associations between the use of PIMs and clinical factors such as total cholesterol, glycated hemoglobin (HbA1c), creatinine, and uric acid levels, as well as the presence of diabetes, hypertension, and cerebrovascular accidents. The predictive models demonstrated moderate power, indicating the importance of these factors in assessing the risk of PIMs. CONCLUSIONS: This study developed predictive models that improve understanding of the use of PIMs in older patients with CVD. These models may assist clinicians in making informed decisions regarding medication safety.
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Enfermedades Cardiovasculares , Lista de Medicamentos Potencialmente Inapropiados , Humanos , Anciano , Femenino , Masculino , Anciano de 80 o más Años , Prescripción Inadecuada/estadística & datos numéricos , Bases de Datos Factuales , PolifarmaciaRESUMEN
INTRODUCTION: Data is limited on influence of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in a large adult population, including individuals with normal spirometry at baseline. METHODS: Using the UK Biobank cohort, a multivariable Cox regression analysis was conducted on 406,424 individuals to examine the association between FEV1 and FVC, categorized into three groups based on their percentage of predicted values (%pred) (≥80, 60-80 and < 60), and overall mortality, cardiovascular mortality, myocardial infarction, stroke, and heart failure over approximately 12.5 years. Moreover, a subgroup analysis was conducted on 295,459 individuals who had normal spirometry. RESULTS: Reduced FEV1 and FVC %pred values were associated with an elevated risk across all studied outcomes. Individuals with the lowest FEV1 and FVC %pred values (<60 %) exhibited HR of 1.83 (95 % CI 1.74-1.93) and 1.98 (95 % CI 1.76-2.22) for overall mortality, and 1.96 (95 % CI 1.83-2.1) and 2.26 (95 % CI 1.94-2.63) for cardiovascular mortality. Moreover, a graded association was observed between lower FEV1 and FVC %pred, even among never smokers and individuals with normal spirometry at baseline. DISCUSSION: Reduced FEV1 and FVC represent robust risk factors for cardiovascular disease and mortality. The fact that the increased risk was evident also at FEV1 and FVC levels exceeding 80 %pred challenges the contemporary classification of lung function categories and the notion that the entire FEV1- and FVC-range above 80 % of predicted represents a normal lung function.
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Enfermedades Cardiovasculares , Espirometría , Humanos , Volumen Espiratorio Forzado/fisiología , Capacidad Vital/fisiología , Masculino , Femenino , Persona de Mediana Edad , Espirometría/métodos , Enfermedades Cardiovasculares/mortalidad , Anciano , Reino Unido/epidemiología , Adulto , Infarto del Miocardio/mortalidad , Infarto del Miocardio/fisiopatología , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/mortalidad , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/fisiopatología , Factores de Riesgo , Estudios de Cohortes , Modelos de Riesgos ProporcionalesRESUMEN
INTRODUCTION: Chronic kidney disease is related to neurodegeneration and structural changes in the brain which might lead to cognitive decline. The Fazekas scale used for assessing white matter hyperintensities (WMHs) was associated with poor cognitive performance. Therefore, this study investigated the associations between the mini-mental status examination (MMSE), Montreal cognitive assessment (MoCA), cognitive abilities screening instrument (CASI), and Fazekas scale in patients under hemodialysis (HD). METHODS: The periventricular (PV) WMHs and deep WMHs (DWMHs) in brain magnetic resonance images of 59 patients under dialysis were graded using the Fazekas scale. Three cognition function tests were also performed, then multivariable ordinal regression and logistic regression were used to identify the associations between cognitive performance and the Fazekas scale. RESULTS: There were inverse associations between the three cognitive function tests across the Fazekas scale of PVWMHs (p = .037, .006, and .008 for MMSE, MoCA, and CASI, respectively), but the associations were attenuated in the DWMHs group. In CASI, significant differences were identified in short-term memory, mental manipulation, abstract thinking, language, spatial construction, and name fluency in the PVWMHs group. However, DWMHs were only significantly correlated with abstract thinking and short-term memory. CONCLUSION: An inverse correlation existed between the Fazekas scale, predominantly in PVWMHs, and cognition in patients undergoing HD. The PVWMHs were associated with cognitive performance assessed by MMSE, MoCA, and CASI, as well as with subdomains of CASI such as memory, language and name fluency in patients undergoing HD.
An inverse correlation existed between the Fazekas scale and cognition in patients undergoing hemodialysis, predominantly in periventricular white matter hyperintensities.The periventricular white matter hyperintensities were associated with cognitive performance assessed by mini-mental status examination (MMSE), Montreal cognitive assessment (MoCA), cognitive abilities screening instrument (CASI), as well as with subdomains of CASI such as memory, language and name fluency in patients undergoing HD.
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Disfunción Cognitiva , Sustancia Blanca , Humanos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Cognición , Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/etiología , Disfunción Cognitiva/diagnóstico , Imagen por Resonancia Magnética , Diálisis Renal/efectos adversosRESUMEN
BACKGROUND: Examining patients with first-episode psychosis (FEP) provides opportunities to better understand the mechanism underlying these illnesses. By incorporating quantitative measures in FEP patients, we aimed to (1) determine the baseline distribution of clinical features; (2) examine the impairment magnitude of the quantitative measures by comparing with external controls and then the counterparts of schizophrenia patients of different familial loadings; and (3) evaluate whether these quantitative measures were associated with the baseline clinical features. METHODS: Patients with FEP were recruited from one medical center, two regional psychiatric centers, and two private clinics in northern Taiwan with clinical features rated using the Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) scale. Quantitative measurements included the Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), niacin response abnormality (NRA), and minor physical anomalies and craniofacial features (MPAs). To evaluate the relative performance of the quantitative measures in our FEP patients, four external comparison groups from previous studies were used, including three independent healthy controls for the CPT, WCST, and NRA, respectively, and one group of treatment-resistant schizophrenia patients for the MPAs. Additionally, patients from simplex families and patients from multiplex families were used to assess the magnitude of FEP patients' impairment on the CPT, WCST, and NRA. RESULTS: Among the 80 patients with FEP recruited in this study (58% female, mean age = 25.6 years, mean duration of untreated psychosis = 132 days), the clinical severity was mild to moderate (mean PANSS score = 67.3; mean PSP score = 61.8). Patients exhibited both neurocognitive and niacin response impairments (mean Z-scores: -1.24 for NRA, - 1.06 for undegraded d', - 0.70 for degraded d', - 0.32 for categories achieved, and 0.44 for perseverative errors) but did not show MPAs indicative of treatment resistance. Among these quantitative measures, three of the four neurocognitive indices were correlated with the baseline clinical features, whereas NRA did not show such correlation. CONCLUSIONS: This FEP study of Taiwanese patients revealed the presence of neurocognitive performance and niacin response and their different relationships with clinical features, rendering this sample useful for future follow-up and incorporation of multiomics investigation.
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Niacina , Trastornos Psicóticos , Esquizofrenia , Humanos , Femenino , Adulto , Masculino , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/complicaciones , Taiwán , Pruebas Neuropsicológicas , Trastornos Psicóticos/psicologíaRESUMEN
Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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Aterosclerosis , Enfermedades de las Arterias Carótidas , Enfermedad de la Arteria Coronaria , Enfisema , Masculino , Humanos , Femenino , Factores de Riesgo , Enfermedades de las Arterias Carótidas/epidemiología , Aterosclerosis/epidemiología , Enfermedad de la Arteria Coronaria/epidemiología , PulmónRESUMEN
Indole-3-acetic acid (IAA), a protein-bound uremic toxin resulting from gut microbiota-driven tryptophan metabolism, increases in hemodialysis (HD) patients. IAA may induce endothelial dysfunction, inflammation, and oxidative stress, elevating cardiovascular and cognitive risk in HD patients. However, research on the microbiome-IAA association is limited. This study aimed to explore the gut microbiome's relationship with plasma IAA levels in 72 chronic HD patients aged over 18 (August 2016-January 2017). IAA levels were measured using tandem mass spectrometry, and gut microbiome analysis utilized 16s rRNA next-generation sequencing. Linear discriminative analysis effect size and random forest analysis distinguished microbial species linked to IAA levels. Patients with higher IAA levels had reduced microbial diversity. Six microbial species significantly associated with IAA levels were identified; Bacteroides clarus, Bacteroides coprocola, Bacteroides massiliensi, and Alisteps shahii were enriched in low-IAA individuals, while Bacteroides thetaiotaomicron and Fusobacterium varium were enriched in high-IAA individuals. This study sheds light on specific gut microbiota species influencing IAA levels, enhancing our understanding of the intricate interactions between the gut microbiota and IAA metabolism.
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Converging evidence indicates the beneficial effects of aerobic exercise on motor learning performance. Underlying mechanisms might be an impact of aerobic exercise on neuroplasticity and cortical excitability. Evidence suggests that motor learning and cortical excitability alterations correlate with the intensity of aerobic exercise and the activity level of participants. Thus, this study aims to investigate the effects of different aerobic exercise intensities on motor learning and cortical excitability in sedentary individuals. The study was conducted in a crossover and double-blind design. Twenty-six healthy sedentary individuals (13 women and 13 men) performed a motor learning task and received a cortical excitability assessment before and after a single session of low-, moderate-, and high-intensity aerobic exercise or a control intervention. The study revealed that motor learning performance and cortical excitability were significantly enhanced in the moderate-intensity aerobic exercise, compared with the other conditions. These findings suggest aerobic exercise intensity-dependent effects on motor learning in sedentary adults. The underlying mechanism might be an exercised-induced alteration of cortical excitability, specifically a reduction of GABA activity.
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Excitabilidad Cortical , Corteza Motora , Adulto , Femenino , Humanos , Masculino , Potenciales Evocados Motores , Ejercicio Físico , Estimulación Magnética Transcraneal , Estudios Cruzados , Método Doble CiegoRESUMEN
We present a scheme to precisely resolve the unperturbed line shape of an optical rubidium clock transition in a high vacuum, by which we avoided the systematic errors of "collision shift" and "modulation shift." The spectral resolution resolved by this scheme is significantly improved such that we can use "Zeeman broadening" to inspect the stray magnetic field, through which we were able to compensate the magnetic field inside the Rb cells to be below 10-3 Gauss. We thus update the absolute frequency of the clock transition and propose a standard operation procedure (SOP) for the clock self-calibration.
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BACKGROUND: Helicobacter pylori (HP) infection is associated with various diseases. Early detection can prevent the onset of illness. We constructed a nomogram to predict groups at high risk of HP infection. METHODS: Patients who underwent regular medical check-ups at hospital in Chaoshan, China from March to September 2022 were randomly allocated to the training and validation cohorts. Risk factors including basic characteristics and lifestyle habits associated with HP infection were analyzed by logistic regression analyses. The independent varieties were calculated and plotted into a nomogram. The nomogram was internally validated by receiver operating characteristic curve, calibration, and decision curve analyses (DCAs). RESULTS: Of the 945 patients, 680 were included in the training cohort and 265 in the validation cohort. 356 patients in training cohort with positive 13 C-UBT results served as the infected group, and 324 without infection were the control group. The multivariate regression analyses showed that the risk factors for HP infection included alcohol consumption (OR = 1.29, 95%CI = 0.78-2.13, P = 0.03), family history of gastric disease (OR = 4.35, 95%CI = 1.47-12.84, P = 0.01), living with an HP-positive individual (OR = 18.09, 95%CI = 10.29-31.82, P < 0.0001), drinking hot tea (OR = 1.58, 95%CI = 1.05-2.48, P = 0.04), and infection status of co-drinkers unknown (OR = 2.29, 95%CI = 1.04-5.06, P = 0.04). However, drinking tea > 3 times per day (OR = 0.56, 95%CI = 0.33-0.95, P = 0.03), using serving chopsticks (OR = 0.30, 95%CI = 0.12-0.49, P < 0.0001) were protective factors for HP infection. The nomogram had an area under the curve (AUC) of 0.85 in the training cohort. The DCA was above the reference line within a large threshold range, indicating that the model was better. The calibration analyses showed the actual occurrence rate was basically consistent with the predicted occurrence rate. The model was validated in the validation cohort, and had a good AUC (0.80), DCA and calibration curve results. CONCLUSIONS: This nomogram, which incorporates basic characteristics and lifestyle habits, is an efficient model for predicting those at high risk of HP infection in the Chaoshan region.
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Infecciones por Helicobacter , Helicobacter pylori , Humanos , China/epidemiología , Infecciones por Helicobacter/epidemiología , Estilo de Vida , Nomogramas , TéRESUMEN
Background: Heart rate recovery (HRR) and N terminal-pro B type natriuretic peptide (NT-proBNP) are markers for survival and cardiac function; however, Little is known about their association. Method: We examined 2540 healthy subjects aged 12-49 years with data from National Health and Nutrition Examination Survey(NHANES) 1999-2002. HRR parameters 1-3 min after exercise were calculated from exercise test results. Baseline characteristics, anthropometric and NT-proBNP, and other risk covariates were obtained. Result: The results showed that NT-proBNP was positively correlated with HRR2(correlation coefficient (cc) = 0.042 [0.029-0.054], P < 0.001) and HRR3(cc = 0.046 [0.029-0.064], P = 0.001); with further adjustment, the associations remained significant between NT-proBNP and HRR2(cc = 0.030 [0.010-0.049], P = 0.004)/HRR3(cc = 0.029[0.004-0.054], P = 0.025). Our study also found significant correlations between NT-pro BNP and SBP(cc = -0.026 [-0.046â¼-0.005], P = 0.017), DBP(cc = -0.037 [-0.062â¼-0.012], P = 0.005), and total cholesterol(cc = -0.065 [-0.12â¼-0.018], P = 0.009). Conclusions: Our results suggest that BNP might reduce heart rate after exercise by inhibiting the sympathetic nervous system (SNS), reducing HRR2 and HRR3, as these phases involve the reduction of heart rate through cardiac sympathetic withdrawal. Moreover, the interaction of BNP on the SNS might be related to the effect of BNP on cardiovascular risks.
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Assessing the condition of every schizophrenia patient correctly normally requires lengthy and frequent interviews with professionally trained doctors. To alleviate the time and manual burden on those mental health professionals, this paper proposes a multimodal assessment model that predicts the severity level of each symptom defined in Scale for the Assessment of Thought, Language, and Communication (TLC) and Positive and Negative Syndrome Scale (PANSS) based on the patient's linguistic, acoustic, and visual behavior. The proposed deep-learning model consists of a multimodal fusion framework and four unimodal transformer-based backbone networks. The second-stage pre-training is introduced to make each off-the-shelf pre-trained model learn the pattern of schizophrenia data more effectively. It learns to extract the desired features from the view of its modality. Next, the pre-trained parameters are frozen, and the light-weight trainable unimodal modules are inserted and fine-tuned to keep the number of parameters low while maintaining the superb performance simultaneously. Finally, the four adapted unimodal modules are fused into a final multimodal assessment model through the proposed multimodal fusion framework. For the purpose of validation, we train and evaluate the proposed model on schizophrenia patients recruited from National Taiwan University Hospital, whose performance achieves 0.534/0.685 in MAE/MSE, outperforming the related works in the literature. Through the experimental results and ablation studies, as well as the comparison with other related multimodal assessment works, our approach not only demonstrates the superiority of our performance but also the effectiveness of our approach to extract and integrate information from multiple modalities.
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Señales (Psicología) , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico , Lingüística , Aprendizaje , AcústicaRESUMEN
BACKGROUND: Residing in a nursing home (NH) may increase emergency department (ED) utilization in patients with dementia; however, evidence regarding the status of and predictors for ED utilization of NH residents with dementia remains unclear, especially in Asia. This study aimed to assess the incidence density of ED visits and associated factors for the risk of ED utilization among NH residents with dementia. METHODS: This one-year cohort study followed 6595 NH residents with dementia aged ⧠40 years from Taiwan's National Health Insurance Research Database between 2012 and 2014. The Andersen-Gill extension of Cox regression analysis with death as a competing risk was applied to investigate the association of the risk of all causes and the most common causes of ED utilization with the predisposing, enabling, and need factors as defined by the Andersen model. RESULTS: All participants encountered 9254 emergency visits in the 5371.49 person-years observed, representing incidence densities of ED visits of 1722.80 per 1000 person-years. Among them, respiratory disease was the most common cause of ED visits. The significant predictors for the risk of all-cause and respiratory-cause ED visits included: (1) predisposing factors (i.e., age and gender); (2) enabling factors (i.e., regional variables); and (3) need factors (i.e., prolonged ventilator dependence and comorbidity status). CONCLUSIONS: Predisposing, enabling, and need factors could influence ED visits among studies patients. NH providers should consider these factors to develop strategies for reducing ED utilization.
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Demencia , Casas de Salud , Humanos , Anciano , Taiwán/epidemiología , Estudios de Cohortes , Servicio de Urgencia en Hospital , Demencia/diagnóstico , Demencia/epidemiología , Demencia/terapiaRESUMEN
BACKGROUND: Patients with remitted psychosis wish to reduce antipsychotic doses yet facing increased risks of relapse. Examining dose-tapering processes may provide insights to re-evaluate the risk-to-benefit balance. We aimed to depict and subgroup tapering trajectories, and explore factors associated with different dose-reduction patterns. METHODS: A 2-year open-label randomized prospective comparative trial from August 2017 to September 2022 in Taiwan. Patients with a history of schizophrenia-related psychotic disorders under stable medications and symptoms were eligible, randomizing a proportion to conduct guided dose reduction. We depicted the trajectories of individual patients and named subgroups based on dose-tapering patterns. Predictors of baseline characteristics for designated subgroups were examined by logistic regression analysis; changes in outcomes were compared by paired t-test. RESULTS: Fifty-one patients undergoing guided dose reduction, 18 (35.3%) reduced 4 steps consecutively (sequential reducers, SR), 14 (27.5%) reduced 1 to 3 steps (modest reducers, MR), 3 (5.9%) re-escalated to previous level (alert reducers, AR), 7 (13.7%) returned to baseline level (baseline returners, BR), 6 (11.7%) relapsed (failed reducers, FR) and 3 (5.9%) withdrew without relapse (early exits, EE). Patients with a history of relapse assumed a conservative dose-tapering pace; only the SR subgroup exhibited significant improvements in functioning and quality of life while failing to identify variables for predicting who would become SR or FR. CONCLUSIONS: Guided dose reduction comprises dynamic processes with differences between individual trajectories. The proposed naming of dose-tapering patterns/subgroups provides a framework depicting patients undergoing dose-tapering. Longer-term observation and more flexible tapering approaches are anticipated to reveal favorable outcomes.
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Antipsicóticos , Reducción Gradual de Medicamentos , Trastornos Psicóticos , Humanos , Masculino , Femenino , Estudios Prospectivos , Trastornos Psicóticos/tratamiento farmacológico , Antipsicóticos/uso terapéutico , Calidad de Vida , Recurrencia , Relación Dosis-Respuesta a Droga , Adulto , Persona de Mediana EdadRESUMEN
BACKGROUND: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography-based measures of coronary atherosclerosis and to explore relevant clinical correlates. METHODS: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of fecal samples, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva. RESULTS: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10-5). Associations were largely similar across coronary computed tomography angiography-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid ß-oxidation, and amino acid degradation were associated with coronary artery calcium score. CONCLUSIONS: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.
Asunto(s)
Aterosclerosis , Enfermedad de la Arteria Coronaria , Humanos , Femenino , Persona de Mediana Edad , Masculino , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Estudios Transversales , Calcio , Aterosclerosis/epidemiología , StreptococcusRESUMEN
Perfluoroalkyl substances (PFAS) have been reported to be harmful to multiple organs in the human body. Based on a previous study suggesting that hemodialysis (HD) may be a means of eliminating PFAS from the human body, we aimed to compare the serum PFAS concentrations of patients undergoing regular HD, patients with chronic kidney disease (CKD) and controls. Additionally, we also investigated the correlation between PFAS and biochemical data, as well as concurrent comorbidities. We recruited 301 participants who had been on maintenance dialysis for >90 days, 20 participants with stage 5 non-dialysis CKD, and 55 control participants who did not have a diagnosis of kidney disease, with a mean creatinine level of 0.77 mg/dl. Eight different PFAS, namely perfluorooctanoic acid (PFOA), total and linear perfluorooctanesulfonic acid (PFOS), perfluoroheptanoic acid (PFHpA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Spearman correlation and multivariable linear regression with 5 % false discovery rate were used to evaluate the relationships between PFAS and clinical parameters in HD patients and controls. Circulating concentrations of seven PFAS, including total and linear PFOS (T-PFOS and L-PFOS) PFDA, PFNA, PFHxS, PFOA, and PFUnDA, were significantly lower in the HD group compared to the CKD and control group. For the interplay between biochemical data and PFAS, all of the studied PFAS were positively correlated with aspartate aminotransferase, alanine aminotransferase, glucose, blood urea nitrogen, ferritin, and vitamin D in the controls, while in HD patients, the PFAS were all positively correlated with albumin, uric acid, iron, and vitamin D. These findings may offer valuable insights for future studies seeking to eliminate PFAS.