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PURPOSE: During the preoperative evaluation of parotid gland tumors, one of the main concerns is to determine the location of the tumors in relation to the facial nerve. This study aims to assess the value of ultrasound for determining the location of parotid gland tumors in relation to the facial nerve using Stensen's duct. METHODS: This is a retrospective cross-sectional study at a single institute. The subjects who underwent preoperative ultrasound and parotidectomy for parotid gland tumors were included. The subjects with incomplete operative records or no reference standard for the location of parotid gland tumor were excluded. The primary predictor was ultrasound tumor location, which was defined as the location of parotid gland tumors determined by preoperative ultrasound as to whether the tumors were superficial or deep to the facial nerve. The operative records were used as the reference standard for the location of parotid gland tumors. The primary outcome was diagnostic performances of preoperative ultrasound in predicting the location of parotid gland tumors, which were calculated by comparing ultrasound tumor location to the reference standard. Covariates were sex, age, type of surgery, tumor size, and tumor histology. Data analysis involved descriptive and analytic statistics; P < .05 was considered statistically significant. RESULTS: One hundred and two of 140 eligible subjects met inclusion and exclusion criteria. There were 50 male and 52 female, with a mean age of 53.3 years. Ultrasound tumor location was classified as deep in 29 subjects, superficial in 50, and indeterminate in 23. The reference standard was deep in 32 subjects and superficial in 70. Indeterminate ultrasound tumor location results were grouped as either deep or superficial to make every possible cross table in which ultrasound tumor location results were presented as a dichotomy. The mean sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the ultrasound to predict the deep location of parotid tumors were 87.5, 82.1, 70.2, 93.6, and 83.8%, respectively. CONCLUSIONS: Stensen's duct on ultrasound can be a useful criterion to determine the location of parotid gland tumor relative to the facial nerve.
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Neoplasias Parotídeas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Parotídeas/diagnóstico por imagem , Neoplasias Parotídeas/cirurgia , Neoplasias Parotídeas/patologia , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/cirurgia , Glândula Parótida/patologia , Nervo Facial/diagnóstico por imagem , Nervo Facial/patologia , Ductos Salivares , Estudos Retrospectivos , Estudos TransversaisRESUMO
We report the first search results for axion dark matter using an 18 T high-temperature superconducting magnet haloscope. The scan frequency ranges from 4.7789 to 4.8094 GHz. No significant signal consistent with the Galactic halo dark matter axion is observed. The results set the best upper bound of axion-photon-photon coupling (g_{aγγ}) in the mass ranges of 19.764 to 19.771 µeV (19.863 to 19.890 µeV) at 1.5×|g_{aγγ}^{KSVZ}| (1.7×|g_{aγγ}^{KSVZ}|), and 19.772 to 19.863 µeV at 2.7×|g_{aγγ}^{KSVZ}| with 90% confidence level, respectively. This remarkable sensitivity in the high mass region of dark matter axion is achieved by using the strongest magnetic field among the existing haloscope experiments and realizing a low-noise amplification of microwave signals using a Josephson parametric converter.
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PURPOSE: Tobramycin shows synergistic antibacterial activity with colistin and can reduce the toxic effects of colistin. The purpose of this study is to prepare pulmonary powder formulations containing both colistin and tobramycin and to assess their in vitro aerosol performance and storage stability. METHODS: The dry powder formulations were manufactured using a lab-scale spray dryer. In vitro aerosol performance was measured using a Next Generation Impactor. The storage stability of the dry powder formulations was measured at 22°C and two relative humidity levels - 20 and 55%. Colistin composition on the particle surface was measured using X-ray photoelectron spectroscopy. RESULTS: Two combination formulations, with 1:1 and 1:5 molar ratios of colistin and tobramycin, showed fine particle fractions (FPF) of 85%, which was significantly higher than that of the spray dried tobramycin (45%). FPF of the tobramycin formulation increased significantly when stored for four weeks at both 20% and 55% RH. In contrast, FPF values of both combination formulations and spray dried colistin remained stable at both humidity levels. Particle surface of each combination was significantly enriched in colistin molecules; 1:5 combination showed 77% by wt. colistin. CONCLUSIONS: The superior aerosol performance and aerosolization stability of 1:1 and 1:5 combination formulations of colistin and tobramycin could be attributed to enrichment of colistin on the co-spray dried particle surface. The observed powder properties may be the result of a surfactant-like assembly of these colistin molecules during spray drying, thus forming a hydrophobic particle surface.
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Colistina , Tobramicina , Colistina/química , Pós/química , Secagem por Atomização , Administração por Inalação , Tamanho da Partícula , Aerossóis/química , Inaladores de Pó Seco/métodosRESUMO
PURPOSE: Most therapeutic agents have limitations owing to low selectivity and poor solubility, resulting in post-treatment side effects. Therefore, there is a need to improve solubility and develop new formulations to deliver therapeutic agents specifically to the target site. Gelatin is a natural protein that is composed of several amino acids. Previous studies revealed that gelatin contains arginyl-glycyl-aspartic acid (RGD) sequences that become ligands for the integrin receptors expressed on cancer cells. Thus, in this study, we aimed to increase the efficiency of drug delivery into cancer cells by coating drug-encapsulating liposomes with gelatin (gelatin-coated liposomes, GCLs). METHODS: Liposomes were coated with gelatin using electrostatic interaction and covalent bonding. GCLs were compared with PEGylated liposomes in terms of their size, zeta potential, encapsulation efficiency, stability, dissolution profile, and cell uptake. Results: Small-sized and physically stable GCLs were prepared, and they showed high drug-encapsulation efficiency. An in vitro dissolution study showed sustained release depending on the degree of gelatin coating. Cell uptake studies showed that GCLs were superior to PEGylated liposomes in terms of cancer cell-targeting ability. CONCLUSIONS: GCLs can be a novel and promising carrier system for targeted anticancer agent delivery. GCLs, which exhibited various characteristics depending on the coating degree, could be utilized in various ways in future studies.
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Antineoplásicos/administração & dosagem , Gelatina/química , Lipossomos/química , Antineoplásicos/química , Antineoplásicos/farmacocinética , Liberação Controlada de Fármacos , Células HeLa , Humanos , Polietilenoglicóis/química , SolubilidadeRESUMO
Eperisone is an oral muscle relaxant used to treat musculoskeletal diseases, which exhibits high pharmacokinetic (PK) variability in bioequivalence studies. The aim of this study was to characterize the PKs of eperisone following its oral administration to Korean volunteers through the conduct of a noncompartmental and population analysis. A total of 360 concentration-time measurements collected on two separate occasions from 15 healthy volunteers during a bioequivalent study of eperisone 50 mg (Murex® ) were used in the PK analysis. Noncompartmental analysis was performed using WinNonLinTM and population analysis was performed using NONMEM® . The possible influence of thirty demographic and pathophysiological characteristics on the PKs of eperisone were explored. Based on noncompartmental analysis mean eperisone elimination half-life, apparent clearance (CL/F), and apparent volume of distribution were estimated to be 3.81 h, 39.24 × 103 l/h × 103 L, respectively. During population PK modeling a two-compartment model with first-order absorption rate constant (typical population K a = 1.5 h-1 ) and first-order elimination (typical population CL/F and apparent volume of distribution in the central compartment [V c /F] = 30.8 × 103 l/h and 86.2 × 103 l, respectively) best described the PKs of eperisone. Interindividual variability in CL/F and V c /F were estimated to be 87.9% and 130.3%, respectively and interoccasion variability in CL/F and V c /F were estimated to be 23.8% and 30.8%, respectively. Aspartate aminotransferase level and smoking status were identified as potential covariates that may influence the CL/F of eperisone. This is the first study to develop a disposition model for eperisone and investigate the potential influence of covariate factors on it PK variability.
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Modelos Biológicos , Relaxantes Musculares Centrais/farmacocinética , Propiofenonas/farmacocinética , Administração Oral , Adulto , Estudos Cross-Over , Voluntários Saudáveis , Humanos , Masculino , Relaxantes Musculares Centrais/sangue , Propiofenonas/sangue , República da Coreia , Equivalência Terapêutica , Adulto JovemRESUMO
The objective of this study is to achieve a fundamental understanding of polymorphic interconversion during the tableting process, including during compaction, dwell, decompression/unloading, and ejection using an in situ mechanical Raman spectroscopy. The fit-for-purpose in situ mechanical Raman spectroscopy developed herein can provide simultaneous measurement of Raman spectra and densification for the powder compacts. Chlorpropamide (CPA), an antidiabetic drug, was selected as a model pharmaceutical compound because of its mechanical shear-induced polymorphic conversions. The results confirm that CPA polymorph A (CPA-A) was transformed to CPA polymorph C (CPA-C) under different compaction stresses. We also observed that the converted polymorph CPA-C could be reverted to the CPA-A due to the elastic recovery of powder compacts as detected during dwelling and unloading. This study is the first depiction of the dynamics of CPA polymorphic interconversion during compression, dwell, unloading, and ejection. Mechanistically, this study illustrates a correlation between the change in the powder compact's relative density and polymorphic interconversion of the drug substance in different solid-state forms. The present research suggests that the process-induced polymorph conversion is a complicated dynamic process, which could be affected by the compaction pressure, the elasticity/plasticity of the material, the level of elastic recovery, and the dissipation of residual stress. In summary, this study demonstrates that the in situ mechanical Raman spectroscopy approach enables the simultaneous detection of mechanical and chemical information of the powder compact throughout the tableting process.
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Clorpropamida/química , Hipoglicemiantes/química , Comprimidos/química , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Pós/química , Pressão , Análise Espectral Raman/métodos , Difração de Raios X/métodosRESUMO
PURPOSE: This study aims to understand the impact of spray drying nozzles on particle surface composition and aerosol stability. METHODS: The combination formulations of colistin and azithromycin were formulated by 2-fluid nozzle (2 N) or 3-fluid (3 N) spray drying in a molar ratio of 1:1. A 3-factor, 2-level (23) factorial design was selected to investigate effects of flow rate, inlet temperature and feed concentration on yield of spray drying and the performance of the spray dried formulations for the 3 N. RESULTS: FPF values for the 2 N formulation (72.9 ± 1.9% for azithromycin & 73.4 ± 0.8% for colistin) were higher than those for the 3 N formulation (56.5 ± 3.8% for azithromycin & 55.1 ± 1.6% for colistin) when stored at 20% RH for 1 day, which could be attributed to smaller physical size for the 2 N. There was no change in FPF for both drugs in the 2 N formulation after storage at 75% RH for 90 days; however, there was a slight increase in FPF for colistin in the 3 N formulation at the same storage conditions. Surface enrichment of hydrophobic azithromycin was measured by X-ray photoelectron spectroscopy for both 2 N and 3 N formulations and interactions were studied using FTIR. CONCLUSIONS: The 3-fluid nozzle provides flexibility in choosing different solvents and has the capability to spray dry at higher feed solid concentrations. This study highlights the impact of hydrophobic azithromycin enrichment on particle surface irrespective of the nozzle type, on the prevention of moisture-induced deterioration of FPF for hygroscopic colistin.
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Antibacterianos/química , Azitromicina/química , Colistina/química , Tecnologia Farmacêutica/instrumentação , Administração por Inalação , Aerossóis , Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Colistina/administração & dosagem , Composição de Medicamentos , Estabilidade de Medicamentos , Desenho de Equipamento , Umidade , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Pós , Solubilidade , Solventes/química , Propriedades de Superfície , Fatores de TempoRESUMO
In this paper, a new small antenna is suggested for 5G Sub-6-GHz band mobile communication. It can change the channel among the three given bands (called the 3.5-GHz area), as a wide-band antenna is connected to a small multiplexer comprising three metamaterial channel filters. The function of channel selection of this antenna system is experimentally demonstrated to prove the validity of the presented scheme. The channel selection for 5G mobile communication is conducted from f1 (channel 1) through f2 (channel 2) to f3 (channel 3), when TX and RX antennas with gains over 0 dBi and S11 less than -10 dB are located far-field apart (RFar â« 2.1 cm), and result in the transmission coefficient (S21) being the greatest at the selected channel, which is detected by a vector network analyzer.
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In this paper, a new design method is proposed for a planar and compact dual-band dipole antenna. The dipole antenna has arms as a hybrid CRLH (Composite right- and left-handed) transmission-line comprising distributed and lumped elements for the dual-band function. The two arms are fed by the outputs of a compact and printed CRLH dual-band balun which consists of a CRLH hybrid coupler and an additional CRLH phase-shifter. Its operational frequencies are 2.4 and 5.2 GHz as popular mobile applications. Verifying the method, the circuit approach, EM (Electromagnetics) simulation and measurement are conducted and their results turn out to agree well with each other. Additionally, the CRLH property is shown with the dispersion diagram and the effective size-reduction is mentioned.
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The development of new electrocatalysts for electrochemical oxygen reduction to replace expensive and rare platinum-based catalysts is an important issue in energy storage and conversion research. In this context, conductive and porous metal-organic frameworks (MOFs) are considered promising materials for the oxygen reduction reaction (ORR) due to not only their high surface area and well-developed pores but also versatile structural features and chemical compositions. Herein, the preparation of bimetallic conductive 2D MOFs (Cox Niy -CATs) are reported for use as catalysts in the ORR. The ratio of the two metal ions (Co2+ and Ni2+ ) in the bimetallic Cox Niy -CATs is rationally controlled to determine the optimal composition of Cox Niy -CAT for efficient performance in the ORR. Indeed, bimetallic MOFs display enhanced ORR activity compared to their monometallic counterparts (Co-CAT or Ni-CAT). During the ORR, bimetallic Cox Niy -CATs retain an advantageous characteristic of Co-CAT in relation to its high diffusion-limiting current density, as well as a key advantage of Ni-CAT in relation to its high onset potential. Moreover, the ORR-active bimetallic Cox Niy -CAT with excellent ORR activity is prepared at a large scale via a convenient method using a ball-mill reactor.
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A robust lung segmentation method using a deep convolutional neural network (CNN) was developed and evaluated on high-resolution computed tomography (HRCT) and volumetric CT of various types of diffuse interstitial lung disease (DILD). Chest CT images of 617 patients with various types of DILD, including cryptogenic organizing pneumonia (COP), usual interstitial pneumonia (UIP), and nonspecific interstitial pneumonia (NSIP), were scanned using HRCT (1-2-mm slices, 5-10-mm intervals) and volumetric CT (sub-millimeter thickness without intervals). Each scan was segmented using a conventional image processing method and then manually corrected by an expert thoracic radiologist to create gold standards. The lung regions in the HRCT images were then segmented using a two-dimensional U-Net architecture with the deep CNN, using separate training, validation, and test sets. In addition, 30 independent volumetric CT images of UIP patients were used to further evaluate the model. The segmentation results for both conventional and deep-learning methods were compared quantitatively with the gold standards using four accuracy metrics: the Dice similarity coefficient (DSC), Jaccard similarity coefficient (JSC), mean surface distance (MSD), and Hausdorff surface distance (HSD). The mean and standard deviation values of those metrics for the HRCT images were 98.84 ± 0.55%, 97.79 ± 1.07%, 0.27 ± 0.18 mm, and 25.47 ± 13.63 mm, respectively. Our deep-learning method showed significantly better segmentation performance (p < 0.001), and its segmentation accuracies for volumetric CT were similar to those for HRCT. We have developed an accurate and robust U-Net-based DILD lung segmentation method that can be used for patients scanned with different clinical protocols, including HRCT and volumetric CT.
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Doenças Pulmonares Intersticiais/diagnóstico por imagem , Redes Neurais de Computação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Humanos , Pulmão/diagnóstico por imagemRESUMO
This study aimed to develop dry powder inhaler (DPI) combination formulations of ciprofloxacin and colistin for use in respiratory infections. Effects of colistin on physical stability and aerosolization of spray-dried ciprofloxacin were examined. The combination DPI formulations were produced by co-spray drying colistin and ciprofloxacin in mass ratios of 1:1, 1:3, and 1:9. Colistin and ciprofloxacin were also co-sprayed with l-leucine in the mass ratio of 1:1:1. The physical and aerosolization stability of the selected co-sprayed formulations stored at 20, 55, and 75% relative humidity (RH) were examined. Formulation characterizations were carried out using powder X-ray diffraction (PXRD) for crystallinity, scanning electron microscopy for morphology and particle size distribution, and dynamic vapor sorption for moisture sorption. Particle surface analysis was performed using X-ray photoelectron spectroscopy, energy dispersive X-ray spectrometry, and nano-time-of-flight secondary ion mass spectrometry. Potential intermolecular interactions were studied using Fourier-transform infrared spectroscopy (FTIR). Aerosol performance was evaluated using a multistage liquid impinger with a RS01 monodose inhaler device. PXRD diffractograms showed that the co-spray-dried colistin-ciprofloxacin formulation in the mass ratio (1:1) was amorphous at 55% RH for up to 60 days; whereas the co-spray-dried colistin-ciprofloxacin (1:3) and colistin-ciprofloxacin (1:9) crystallized after storage for 3 days at 55% RH. However, the extent of crystallization for the combination formulations was less as compared to the spray-dried ciprofloxacin alone formulation. Surface morphology of the co-spray-dried formulations at different concentrations did not change even after storage at 55% RH for 60 days, unlike the spray-dried ciprofloxacin alone powder which became rougher after 3 days of storage at 55% RH. Surface analysis data indicated surface enrichment of colistin in the co-spray-dried formulations. Increasing colistin concentration on the composite particles surfaces improved aerosol performance of ciprofloxacin. FTIR data demonstrated intermolecular interactions between colistin and ciprofloxacin, thereby delaying and/or preventing crystallization of ciprofloxacin when co-spray-dried. Co-spray drying ciprofloxacin with colistin in the mass ratio (1:1) completely prevented crystallization of ciprofloxacin at 55% RH for up to 60 days. However, the colistin-ciprofloxacin formulation (1:1) began to fuse when stored at 75% RH due to moisture absorption resulting in a compromised aerosol performance. In contrast, the colistin-ciprofloxacin-leucine (1:1:1) formulation demonstrated no particle fusion, enabling a stable aerosol performance at 75% RH for 7 days. This study demonstrated that incorporation of colistin in the spray-dried formulations can improve physical stability and aerosolization of amorphous ciprofloxacin at 55% RH. At 75% RH, further addition of l-leucine in the formulation prevented particle fusion and deterioration in aerosol performance, attributed to the enrichment of nonhygroscopic l-leucine on the particle surface.
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Aerossóis/química , Ciprofloxacina/química , Colistina/química , Administração por Inalação , Estabilidade de Medicamentos , Sinergismo Farmacológico , Inaladores de Pó Seco , Excipientes/química , Leucina/química , Tamanho da Partícula , Difração de Raios XRESUMO
PURPOSE: Dissolution behavior of dry powder inhaler (DPI) antibiotic formulations in the airways may affect their efficacy especially for poorly-soluble antibiotics such as azithromycin. The main objective of this study was to understand the effects of surface composition on the dissolution of spray dried azithromycin powders by itself and in combination with colistin. METHODS: Composite formulations of azithromycin (a poorly water-soluble molecule) and colistin (a water-soluble molecule) were produced by spray drying. The resultant formulations were characterized for particle size, morphology, surface composition, solid-state properties, solubility and dissolution. RESULTS: The results demonstrate that surfaces composition has critical impacts on the dissolution of composite formulations. Colistin was shown to increase the solubility of azithromycin. For composite formulations with no surface colistin, azithromycin released at a similar dissolution rate as the spray-dried azithromycin alone. An increase in surface colistin concentration was shown to accelerate the dissolution of azithromycin. The dissolution of colistin from the composite formulations was significantly slower than the spray-dried pure colistin. In addition, FTIR spectrum showed intermolecular interactions between azithromycin and colistin in the composite formulations, which could contribute to the enhanced solubility and dissolution of azithromycin. CONCLUSIONS: Our study provides fundamental understanding of the effects of surface concentration of colistin on azithromycin dissolution of co-spray-dried composite powder formulations.
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Azitromicina/química , Colistina/química , Composição de Medicamentos/métodos , Pós/química , Administração por Inalação , Aerossóis/química , Antibacterianos/administração & dosagem , Antibacterianos/química , Azitromicina/administração & dosagem , Química Farmacêutica , Colistina/administração & dosagem , Inaladores de Pó Seco , Humanos , Tamanho da Partícula , Pós/administração & dosagem , Propriedades de SuperfícieRESUMO
Saxifragin, the 5-glucoside of the flavonoid quercetin, is found in plants and insects. It has been reported that saxifragin has peroxynitrite-scavenging effects. However, the mechanism of anti-inflammatory effects of saxifragin has not yet been clearly identified. In this study, we investigated the anti-inflammatory effects of saxifragin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and animal models of inflammation. We found that saxifragin suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-activated RAW 264.7 macrophages by suppressing the level of protein and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively. Furthermore, saxifragin inhibited mRNA expression of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß. We studied the inhibitory effects of saxifragin on the nuclear translocation of nuclear factor (NF)-κB, activation of caspase-1, and phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). Furthermore, pretreatment with saxifragin increased the survival rate of mice with LPS-induced septic death. Collectively, these findings suggest that saxifragin exerts anti-inflammatory activity by inhibiting NF-κB, caspase-1, and mitogen-activated protein kinase (MAPK) activation.
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Anti-Inflamatórios/farmacologia , Caspase 1/efeitos dos fármacos , Flavonoides/farmacologia , NF-kappa B/antagonistas & inibidores , Animais , Anti-Inflamatórios/química , Caspase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Flavonoides/química , Proteínas I-kappa B/metabolismo , Inflamação/tratamento farmacológico , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Estrutura Molecular , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacosRESUMO
Chicoric acid (dicaffeoyl-tartaric acid), is a natural phenolic compound found in a number of plants, such as chicory (Cichorium intybus) and Echinacea (Echinacea purpurea), which possesses antioxidant, anti-inflammatory, antiviral, and analgesic activities. Although these biological effects of chicoric acid have been investigated, there are no reports of its antiallergic-related anti-inflammatory effects in human mast cells (HMC)-1 or anaphylactic activity in a mouse model. Therefore, we investigated the antiallergic-related anti-inflammatory effect of chicoric acid and its underlying mechanisms of action using phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated HMC-1 cells. Chicoric acid decreased the mRNA expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß. We studied the inhibitory effects of chicoric acid on the nuclear translocation of nuclear factor kappa B (NF-κB) and activation of caspase-1. However, mitogen-activated protein kinase (MAPK) activation was not sufficient to abrogate the stimulus. In addition, we investigated the ability of chicoric acid to inhibit compound 48/80-induced systemic anaphylaxis in vivo. Oral administration of chicoric acid at 20 mg/kg inhibited histamine release and protected mice against compound 48/80-induced anaphylactic mortality. These results suggest that chicoric acid has an antiallergic-related anti-inflammatory effect that involves modulating mast cell-mediated allergic responses. Therefore, chicoric acid could be an efficacious agent for allergy-related inflammatory disorders.
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Antialérgicos/farmacologia , Ácidos Cafeicos/farmacologia , Inflamação/tratamento farmacológico , Mastócitos/efeitos dos fármacos , Succinatos/farmacologia , Animais , Caspase 1/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Liberação de Histamina/efeitos dos fármacos , Humanos , Interleucina-1beta/antagonistas & inibidores , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Estrutura Molecular , NF-kappa B/antagonistas & inibidores , Ésteres de Forbol/farmacologia , p-Metoxi-N-metilfenetilamina/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The tissue inclusion parameter estimation method is proposed to measure the stiffness as well as geometric parameters. The estimation is performed based on the tactile data obtained at the surface of the tissue using an optical tactile sensation imaging system (TSIS). A forward algorithm is designed to comprehensively predict the tactile data based on the mechanical properties of tissue inclusion using finite element modeling (FEM). This forward information is used to develop an inversion algorithm that will be used to extract the size, depth, and Young's modulus of a tissue inclusion from the tactile data. We utilize the artificial neural network (ANN) for the inversion algorithm. The proposed estimation method was validated by a realistic tissue phantom with stiff inclusions. The experimental results showed that the proposed estimation method can measure the size, depth, and Young's modulus of a tissue inclusion with 0.58%, 3.82%, and 2.51% relative errors, respectively. The obtained results prove that the proposed method has potential to become a useful screening and diagnostic method for breast cancer.
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Técnicas Biossensoriais , Neoplasias da Mama/diagnóstico , Redes Neurais de Computação , Neoplasias da Mama/patologia , Feminino , Humanos , Óptica e FotônicaRESUMO
Three triarylboron- (Mes2BAr-) functionalized dipicolinic acids, namely, 4-(4-(dimesitylboranyl)-2,3,5,6-tetramethylphenyl)pyridine-2,6-dicarboxylic acid (H2L1), 4-(4-(4-dimesitylboranyl)-2,3,5,6-tetramethylphenyl)-1H-1,2,3-triazol-1-yl)pyridine-2,6-dicarboxylic acid (H2L2), and 4-(4-(4-dimesitylboranyl) phenyl)-1H-1,2,3-triazol-1-yl)pyridine-2,6-dicarboxylic acid (H2L3), have been designed and synthesized. Lanthanide(III) complexes with the general formula of [NBu4]3[LnL3] (Ln = Eu or Tb; L = L1, L2, or L3) were obtained. The new triarylboron-functionalized ligands were found to be effective in the selective sensitization of the emissions of Eu(III) and Tb(III) ions with a high quantum efficiency (e.g., 0.54 for [NBu4]3[TbL13] in the solid state) upon excitation at â¼330 nm. An intraligand charge-transfer (ILCT) transition from the mesityl or aryl group to the boron or boron-aryl unit was found to play a key role in the activation of the Eu(III) and Tb(III) emissions, based on TD-DFT computational data and luminescence titration experiments performed using fluoride and cyanide ions.
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Four BMes2Ar (Mes = mesityl, Ar = phenyl or duryl) functionalized 1,3-diketonato ligands have been investigated for use in selective sensitization of Tb(III) and Eu(III) emission. These ligands have the general formula of [R1C(O)CR2C(O)R3](-) (R1 = Ph, R2 = H, R3 = p-Ph-BMes2, L1; R1 = R3 = p-Ph-BMes2, R2 = H, L2; R1 = R3 = Me, R2 = p-Ph-BMes2, L3; R1 = R3 = Me, R2 = p-duryl-BMes2, L4) and belong to class I (L1 and L2) and class II (L3 and L4), respectively. In class I, the boron unit is conjugated with the phenyl linker and the diketone backbone, while in class II, the boron unit, the linker unit, and the diketone unit are nonconjugated with a mutually orthogonal arrangement. To understand the impact of the location of the BMes2Ar unit on the electronic properties of the 1,3-diketone molecules and their ability in activating lanthanide emission, the difluoroboron chelate compounds (1-BF2 to 4-BF2) of ligands L1-L4 were synthesized and examined. The class I ligands were effective in activating Eu(III) emission, while the class II ligands were effective in activating Tb(III) emission. Four Ln(III) complexes, 1Eu, 2Eu, 3Tb, and 4Tb, based on the L1-L4 ligands, respectively, were prepared and examined. The emission quantum efficiency of 1Eu and 2Eu is low (Φ(Eu) ≤ 0.01 in THF, 0.07-0.13 in the solid state), but can be greatly enhanced by the addition of fluoride ions. In contrast, the complex 4Tb has a moderate emission efficiency (Φ(Tb) = 0.14 in THF, 0.47 in the solid state) and experiences a distinct emission quenching upon the addition of fluoride. The selective sensitization of Eu(III) and Tb(III) by L1-L4 and the distinct luminescent response of their Ln(III) complexes toward fluoride ions are caused by the distinct intraligand charge transfer transitions of the two different classes of ligands involving the BMes2 unit.
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In this study, protein-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared via supercritical fluid extraction of emulsion (SFEE) technology. To understand the correlation between process parameters and the main quality characteristics of PLGA microspheres, a comprehensive prior study on the influence of process variables on encapsulation efficiency (EE), initial drug burst release (IBR), morphology, surface property, and particle size distribution (PSD) was conducted within a wide process condition range of each unit process step, from the double-emulsion preparation step to the extraction step. Bovine serum albumin (BSA), a high-molecular weight-protein that is difficult to control the IBR and EE of PLGA microspheres with, was used as a model material. As double-emulsion manufacturing process parameters, the primary (W/O) and secondary emulsion (W/O/W) homogenization speed and secondary emulsification time were evaluated. In addition, the effect of the SFEE process parameters, including the pressure (70-160 bar), temperature (35-65 °C), stirring rate (50-1000 rpm), and flow rate of supercritical carbon dioxide, SC-CO2 (1-40 mL/min), on PLGA microsphere quality properties were also evaluated. An increase in the homogenization speed of the primary emulsion resulted in an increase in EE and a decrease in IBR. In contrast, increasing the secondary emulsification speed resulted in a decrease in EE and an increase in IBR along with a decrease in microsphere size. The insufficient secondary emulsification time resulted in excessive increases in particle size, and excessive durations resulted in decreased EE and increased IBR. Increasing the temperature and pressure of SFEE resulted in an overall increase in particle size, a decrease in EE, and an increase in IBR. It was observed that, at low stirring rates or SC-CO2 flow rates, there was an increase in particle size and SPAN value, while the EE decreased. Overall, when the EE of the prepared microspheres is low, a higher proportion of drugs is distributed on the external surface of the microspheres, resulting in a larger IBR. In conclusion, this study contributes to the scientific understanding of the influence of SFEE process variables on PLGA microspheres.
RESUMO
Construction workers face a high risk of various occupational accidents, many of which can result in fatalities. This study aims to develop a prediction model for nine prevalent types of construction accidents, utilizing construction tasks, activities, and tools/materials as input features, through the application of machine learning-based multi-class classification algorithms. 152,867 construction accident summary reports, composed of both structured (construction task, construction activity, accident type) and unstructured data (tools/materials) were used for the study. The study employed several data processing techniques, including keyword extraction through text mining, Boruta feature selection, and SMOTE data resampling enhance model accuracy. Three performance metrics (Multi-class area under the receiver operating characteristic curve (MAUC), Multi-class Matthews Correlation Coefficient (MMCC), Geometric-mean (G-mean)) were used to compare the predictive performance of four machine learning algorithms, including Decision tree, Random forest, Naïve bayes, and XGBoost. Of the four algorithms, XGBoost showed the highest performance in predicting accident type (MAUC: 0.8603, MMCC: 0.3523, G-mean: 0.5009). Furthermore, a Shapley additive explanation (SHAP) analysis was conducted to visualize feature importance. The findings of this study make a valuable contribution to improving construction safety by presenting a prediction model for accident types derived from real-world big data.