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OBJECTIVE: This study aimed to identify predictive biomarkers for unscheduled emergency department (ED) revisits within 24 hours of discharge in infants diagnosed with acute bronchiolitis (AB). METHODS: A retrospective observational study was conducted on infants diagnosed with AB who visited 3 emergency medical centers between January 2020 and December 2022. The study excluded infants with comorbidities, congenital diseases, and prematurity and infants who revisited the ED after 24 hours of discharge. Demographic data, vital signs, and laboratory results were collected from the medical records. Univariable and multivariable logistic regression analyses were performed on factors with P of less than 0.1 in univariable analysis. Receiver operator curve analysis was used to assess the accuracy of lactate measurements in predicting ED revisits within 24 hours of discharge. RESULTS: Out of 172 participants, 100 were in the revisit group and 72 in the discharge group. The revisit group was significantly younger and exhibited higher lactate levels, lower pH values, and higher pCO2 levels compared to the discharge group. Univariable logistic regression identified several factors associated with revisits. Multivariable analysis found that only lactate was a variable correlated with predicting ED revisits (odds ratio, 18.020; 95% confidence interval [CI], 5.764-56.334). The receiver operator curve analysis showed an area under the curve of 0.856, with an optimal lactate cutoff value of 2.15. CONCLUSION: Lactate value in infants diagnosed with AB were identified as a potential indicator of predicting unscheduled ED revisits within 24 hours of discharge. The predictive potential of lactate levels holds promise for enhancing prognosis prediction, reducing health care costs, and alleviating ED overcrowding. However, given the study's limitations, a more comprehensive prospective investigation is recommended to validate these findings.
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Flextensional transducers have been widely used as low-frequency projectors, and these characteristics can be used to develop hydrophones with wider receiver bandwidth and higher sensitivity than conventional products in low-frequency ranges. In this work, we designed flextensional hydrophones of all classes, and compared their acoustic receiver performance to select the most suitable class for a low-frequency broadband hydrophone. For this purpose, basic models of the hydrophones were constructed for all classes and the effects of various structural parameters on the acoustic receiver characteristics of the hydrophones were analyzed. Based on the results, the structure of the flextensional hydrophone of each class was designed to have the maximum receiver bandwidth by an optimization technique while maintaining the receiver voltage sensitivity over a certain level. A comparison of the designed performance led to the selection of the class IV flextensional hydrophone as the most promising one with the widest receiver fractional bandwidth and highest sensitivity.
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BACKGROUND AND PURPOSE: α-Pyrrolidinobutiothiophenone (α-PBT) is a chemical derivative of cathinone, a structural analogue of amphetamine. Until now, there have been a few previous neurochemical or neurobehavioural studies on the abuse potential of α-PBT. EXPERIMENTAL APPROACH: We examined the abuse potential of α-PBT by measuring psychomotor, rewarding, and reinforcing properties and methamphetamine-like discriminative stimulus effects in rodents using locomotor activity, conditioned place preference, self-administration, and drug discrimination studies. To clarify the underlying neuropharmacological mechanisms, we measured dopamine levels and neuronal activation in the dorsal striatum. In addition, we investigated the role of the dopamine D1 receptor or D2 receptors in α-PBT-induced hyperlocomotor activity, conditioned place preference, and the methamphetamine-like discriminative stimulus effect of α-PBT in rodents. KEY RESULTS: α-PBT promoted hyperlocomotor activity in mice. α-PBT induced drug-paired place preference in mice and supported self-administration in rats. In a drug discrimination experiment, α-PBT fully substituted for the discriminative stimulus effects of methamphetamine in rats. Furthermore, α-PBT increased dopamine levels and c-Fos expression in the dorsal striatum of mice, which was associated with these behaviours. Finally, pretreatment with the D1 receptor antagonist SCH23390 or the D2 receptors antagonist eticlopride significantly attenuated acute or repeated α-PBT-induced hyperlocomotor activity, place preference, and the methamphetamine-like discriminative stimulus effects in rodents. CONCLUSIONS AND IMPLICATIONS: These findings suggest that α-PBT has abuse potential at the highest dose tested via enhanced dopaminergic transmission in the dorsal striatum of rodents. The results provide scientific evidence for the legal restrictions of the recreational use of α-PBT.
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Dopamina , Metanfetamina , Pirrolidinas , Receptores de Dopamina D1 , Animales , Masculino , Dopamina/metabolismo , Ratones , Ratas , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D1/antagonistas & inhibidores , Receptores de Dopamina D1/agonistas , Metanfetamina/farmacología , Pirrolidinas/farmacología , Pirrolidinas/química , Receptores de Dopamina D2/metabolismo , Actividad Motora/efectos de los fármacos , Autoadministración , Ratas Sprague-Dawley , Ratones Endogámicos C57BL , Benzazepinas/farmacología , Benzazepinas/químicaRESUMEN
There is an unmet need for biomarkers for the diagnosis of lung cancer and decision criteria for lung biopsy. We comparatively investigated the lung microbiomes of patients with lung cancer and benign lung diseases. Patients who underwent bronchoscopy at Chungnam National University Hospital between June 2021 and June 2022 were enrolled. Bronchoalveolar lavage fluid (BALF) was collected from 24 patients each with lung cancer and benign lung diseases. The samples were analyzed using 16S rRNA-based metagenomic sequencing. We found that alpha diversity and the beta diversity distribution (P = 0.001) differed significantly between patients with benign lung diseases and those with lung cancer. Firmicutes was the most abundant phylum in patients with lung cancer (33.39% ± 17.439), whereas Bacteroidota was the most abundant phylum in patients with benign lung disease (31.132% ± 22.505), respectively. In differential abundance analysis, the most differentially abundant microbiota taxon was unclassified_SAR202_clade, belonging to the phylum Chloroflexi. The established prediction model distinguished patients with benign lung disease from those with lung cancer with a high accuracy (micro area under the curve [AUC] = 0.98 and macro AUC = 0.99). The BALF microbiome may be a novel biomarker for the detection of lung cancer.
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Enfermedades Pulmonares , Neoplasias Pulmonares , Microbiota , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Líquido del Lavado Bronquioalveolar , ARN Ribosómico 16S/genética , Biomarcadores , Pulmón/patología , Microbiota/genéticaRESUMEN
The gut microbiome significantly influences immune responses and the efficacy of immune checkpoint inhibitors. We conducted a clinical trial (NCT04264975) combining an anti-programmed death-1 (PD-1) inhibitor with fecal microbiota transplantation (FMT) from anti-PD-1 responder in 13 patients with anti-PD-1-refractory advanced solid cancers. FMT induced sustained microbiota changes and clinical benefits in 6 of 13 patients, with 1 partial response and 5 stable diseases, achieving an objective response rate of 7.7% and a disease control rate of 46.2%. The clinical response correlates with increased cytotoxic T cells and immune cytokines in blood and tumors. We isolated Prevotella merdae Immunoactis from a responder to FMT, which stimulates T cell activity and suppresses tumor growth in mice by enhancing cytotoxic T cell infiltration. Additionally, we found Lactobacillus salivarius and Bacteroides plebeius may inhibit anti-tumor immunity. Our findings suggest that FMT with beneficial microbiota can overcome resistance to anti-PD-1 inhibitors in advanced solid cancers, especially gastrointestinal cancers.