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1.
PLoS One ; 16(12): e0260517, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34851999

RESUMO

OBJECTIVES: To develop a prediction model of spontaneous ureteral stone passage (SSP) using machine learning and logistic regression and compare the performance of the two models. Indications for management of ureteral stones are unclear, and the clinician determines whether to wait for SSP or perform active treatment, especially in well-controlled patients, to avoid unwanted complications. Therefore, suggesting the possibility of SSP would help make a clinical decision regarding ureteral stones. METHODS: Patients diagnosed with unilateral ureteral stones at our emergency department between August 2014 and September 2018 were included and underwent non-contrast-enhanced computed tomography 4 weeks from the first stone episode. Predictors of SSP were applied to build and validate the prediction model using multilayer perceptron (MLP) with the Keras framework. RESULTS: Of 833 patients, SSP was observed in 606 (72.7%). SSP rates were 68.2% and 75.6% for stone sizes 5-10 mm and <5 mm, respectively. Stone opacity, location, and whether it was the first ureteral stone episode were significant predictors of SSP. Areas under the curve (AUCs) for receiver operating characteristic (ROC) curves for MLP, and logistic regression were 0.859 and 0.847, respectively, for stones <5 mm, and 0.881 and 0.817, respectively, for 5-10 mm stones. CONCLUSION: SSP prediction models were developed in patients with well-controlled unilateral ureteral stones; the performance of the models was good, especially in identifying SSP for 5-10-mm ureteral stones without definite treatment guidelines. To further improve the performance of these models, future studies should focus on using machine learning techniques in image analysis.

2.
Nano Lett ; 21(22): 9772-9779, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34766778

RESUMO

Metal thin films with a specific orientation play vital roles in electronics, catalysts, and epitaxial templates. Although oriented metal films have been produced in the recent years, ultrathin oriented metal films (<10 nm) have not been achieved owing to the interfacial instability of the ultrathin films during the thermal annealing process. This study investigates chemical conversion of randomly oriented multigrain Au ultrathin films into (111)-oriented Au ultrathin films. A novel chemical process, termed pseudoequilibrium of etching and selective grain growth, is presented for the chemical conversion by using a quaternary ammonium halide. The reaction variables (reaction time, reaction temperature, species of halide ions) for the chemical conversion process are systematically investigated. This study reveals the in-plane rotational degeneracy in the Au(111) thin film epitaxially grown on a Si(111) substrate. The chemical process can be applied to a broad range of thicknesses from 9 to 100 nm.

3.
Epilepsy Behav ; 125: 108407, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34785411

RESUMO

PURPOSE: We investigated the long-term efficacy and safety of perampanel as a first add-on therapy in patients with focal epilepsy. METHODS: This retrospective study represented the 3-year extension phase of a multicenter, open-label, phase 4, prospective study of perampanel as a first add-on therapy in patients with focal epilepsy. Seizure and safety outcomes were assessed annually from the start of the extension study, and the retention rate was calculated from the start of perampanel exposure in the original study. RESULTS: The 50% responder and seizure freedom rates were 84.8% and 58.7%, respectively, during the third year and 71.7% and 32.6%, respectively, during the entire 3-year period of the extension study. The 1-, 2-, and 3-year retention rates were 62.5%, 53.1%, and 52.1%, respectively. Efficacies were higher in patients that were aged >55 years, male, and receiving ≤4 mg of perampanel. Perampanel was generally well tolerated; 47.3% of patients experienced at least one adverse event during the 3 years of extension (46 adverse events (AEs) in 35 patients). The most common AEs were dizziness (33.8%), somnolence (5.4%), anger (4.1%), and irritability (4.1%). AEs were resolved with perampanel dose reduction or discontinuation in 10 (13.5%) and 12 (16.2%) patients, respectively. CONCLUSION: Long-term treatment with perampanel as a first add-on therapy did not raise new safety signals in patients with focal epilepsy. Especially at low perampanel doses (≤4 mg/day), sustained improvement in seizure control was achieved, which could potentially avoid adverse drug reactions.

4.
Phys Med ; 91: 131-139, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34800907

RESUMO

A new tandem applicator with tungsten shield for Ir-192 radiation source used in intra-cavitary brachytherapy (ICBT) enabled intensity modulated brachytherapy (IMBT) in cervical cancer treatment through fluence-modulation by rotating shield. Our previous work employed group-wise and element-wise sparsity constraints for plan optimization of tandem applicator to minimizes the number of activated angles and source dwell points for delivery efficiency. It, however, did not incorporate the ovoid applicators into the optimizing process, which is generally used to prevent cancer recurrence. To integrate ovoid applicators to the new tandem applicator, this work proposed a comprehensive framework that modifies 1) dose deposition matrix for inverse planning, and 2) plan optimizing algorithm. The dose deposition matrix was newly formulated by the Monte-Carlo simulated dose distribution for 10 positions of ovoid applicators, followed by combining those with tandem-associated dose deposition matrix. The plan optimizing algorithm decomposed entire elements into tandem and ovoid applicators, which were governed by different constraints adaptive to specified plan objectives. The integrated framework was compared against conventional ICBT, and IMBT with tandem only for three patients with asymmetric dose distributions. Integrated IMBT framework resulted in the most optimal plans. Including fluence-modulation by rotating-shield outperformed conventional ICBT in dose sparing to critical organs. Adopting ovoid applicators to the optimization yielded more conformal dose distribution around inferior, laterally expanded region of target volume. The resulting plans reduced D5cc and D2cc by 30.9% and 27.8% for critical organs over conventional ICBT, and by 20.6% and 21.5% for target volume over IMBT with tandem only.


Assuntos
Braquiterapia , Neoplasias do Colo do Útero , Feminino , Humanos , Método de Monte Carlo , Recidiva Local de Neoplasia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Neoplasias do Colo do Útero/radioterapia
5.
Asian J Surg ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34844831

RESUMO

BACKGROUND/OBJECTIVE: Laparoscopic totally extraperitoneal (TEP) herniorrhaphy is among the current leading inguinal hernia repair methods. This study aimed to investigate the safety and feasibility of a junior surgeon's first experience with laparoscopic TEP herniorrhaphy. METHODS: A retrospective review was performed between January 2017 and December 2019 to analyze the medical records of patients with inguinal hernia who underwent laparoscopic TEP herniorrhaphy. The operative outcomes and complications of patients undergoing surgery by an experienced surgeon (group A, n = 100) were compared with those undergoing surgery by a junior surgeon (group B, n = 100). RESULTS: The mean operative time for group B was significantly longer than that for group A (52.0 ± 15.1 min vs 60.1 ± 17.4 min; P = 0.03). A statistical difference was also found in the mean postoperative stay (1.1 ± 0.3 d vs 1.4 ± 0.7 d; P = 0.02) between the two groups. There were 2 and 3 cases of recurrence in these two groups respectively (P = 0.72). Considering the operating time as a variable of learning curve, significant stabilization can be achieved after 30 cases (67.3 ± 17.8 min vs 53.1 ± 11.1 min; P = 0.02). CONCLUSIONS: The surgical outcomes of laparoscopic TEP herniorrhaphy performed by a well-trained junior surgeon were similar to the outcomes of an experience surgeon.

6.
Adv Mater ; : e2106625, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34825405

RESUMO

Conventional gating in transistors uses electric fields through external dielectrics that require complex fabrication processes. Various optoelectronic devices deploy photogating by electric fields from trapped charges in neighbor nanoparticles or dielectrics under light illumination. We demonstrate orbital gating driven by giant Stark effect in tunneling phototransistors based on 2H-MoTe2 without using external gating bias or slow charge trapping dynamics in photogating. The original self-gating by light illumination modulates the interlayer potential gradient by switching on and off the giant Stark effect where the dz 2-orbitals of molybdenum atoms play the dominant role. The orbital gating shifts the electronic bands of the top atomic layer of the MoTe2 by up to 100 meV, which is equivalent to modulation of a carrier density of 7.3×1011 cm-2 by electrical gating. Suppressing conventional photoconductivity, the orbital gating in tunneling phototransistors achieves low dark current, practical photo-responsivity (3357 AW-1 ), and fast switching time (0.5 ms) simultaneously. This article is protected by copyright. All rights reserved.

7.
Sci Rep ; 11(1): 21656, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737340

RESUMO

As sarcopenia research has been gaining emphasis, the need for quantification of abdominal muscle on computed tomography (CT) is increasing. Thus, a fully automated system to select L3 slice and segment muscle in an end-to-end manner is demanded. We aimed to develop a deep learning model (DLM) to select the L3 slice with consideration of anatomic variations and to segment cross-sectional areas (CSAs) of abdominal muscle and fat. Our DLM, named L3SEG-net, was composed of a YOLOv3-based algorithm for selecting the L3 slice and a fully convolutional network (FCN)-based algorithm for segmentation. The YOLOv3-based algorithm was developed via supervised learning using a training dataset (n = 922), and the FCN-based algorithm was transferred from prior work. Our L3SEG-net was validated with internal (n = 496) and external validation (n = 586) datasets. Ground truth L3 level CT slice and anatomic variation were identified by a board-certified radiologist. L3 slice selection accuracy was evaluated by the distance difference between ground truths and DLM-derived results. Technical success for L3 slice selection was defined when the distance difference was < 10 mm. Overall segmentation accuracy was evaluated by CSA error and DSC value. The influence of anatomic variations on DLM performance was evaluated. In the internal and external validation datasets, the accuracy of automatic L3 slice selection was high, with mean distance differences of 3.7 ± 8.4 mm and 4.1 ± 8.3 mm, respectively, and with technical success rates of 93.1% and 92.3%, respectively. However, in the subgroup analysis of anatomic variations, the L3 slice selection accuracy decreased, with distance differences of 12.4 ± 15.4 mm and 12.1 ± 14.6 mm, respectively, and with technical success rates of 67.2% and 67.9%, respectively. The overall segmentation accuracy of abdominal muscle areas was excellent regardless of anatomic variation, with CSA errors of 1.38-3.10 cm2. A fully automatic system was developed for the selection of an exact axial CT slice at the L3 vertebral level and the segmentation of abdominal muscle areas.

8.
Acta Histochem ; 123(8): 151800, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34673438

RESUMO

Stage- and cell type-specific biomarkers are important for understanding spermatogenesis in mammalian testis. The present study identified several testicular cell marker proteins in 6- and 24-month old bovine testes. In 6-month old bovine testes, spermatogonia and spermatocytes were detected but complete spermatogenesis occurred in 24-month old testes. The diameters of the seminiferous tubules increased significantly in the 24-month old testes compared with those in the 6-month old testes. Protein Gene Product 9.5 (PGP9.5), also known as the undifferentiated spermatogonium marker, and GATA4 (GATA binding protein 4), vimentin, and SOX9 (SRY-Box Transcription Factor 9) were detected in the basement membrane region. Interestingly, ID4 (inhibitor of DNA binding protein 4; previously known as the undifferentiated cell marker) proteins were located in the basement membrane region but their expression patterns were different from those of PGP9.5. Co-immunohistochemistry results showed that ID4 was detected in the Sertoli cells expressing vimentin and SOX9 in 6- and 24-month old bovine testes. This result indicated that ID4 is a putative biomarker of Sertoli cell in the bovine system, which is different from the rodent models. Thus, these results will contribute in understanding the process of spermatogenesis that is different in bovines compared to other species.

9.
Leuk Res ; 111: 106690, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34673442

RESUMO

The recommended starting dose of bosutinib is 500 mg/day for chronic-phase (CP) or accelerated-/blast-phase Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) resistant/intolerant to prior therapy. However, some patients may require dose reductions to manage the occurrences of adverse events (AEs). Bosutinib efficacy and safety were evaluated following dose reductions in a phase I/II study of Ph+ patients with CP CML resistant/intolerant to imatinib or imatinib plus dasatinib and/or nilotinib, and those with accelerated-/blast-phase CML or acute lymphoblastic leukemia after at least imatinib treatment. In all, 570 patients with ≥4 years' follow-up were included in this analysis. Among 144 patients who dose-reduced to bosutinib 400 mg/day (without reduction to 300 mg/day), 22 (15 %) had complete cytogenetic response (CCyR) before and after reduction, 40 (28 %) initially achieved CCyR after reduction, and 4 (3 %) only had CCyR before reduction. Among 95 patients who dose-reduced to bosutinib 300 mg/day, 23 (24 %) had CCyR before and after reduction, 13 (14 %) initially achieved CCyR after reduction, and 3 (3 %) only had CCyR before reduction. Results were similar to matched controls who remained on 500 mg/day, indicating dose reductions had not substantially affected efficacy. The incidence of treatment-emergent AEs was lower after dose reductions, particularly for gastrointestinal events. The incidence of hematologic toxicities generally was similar before and after dose reduction. The management of AEs with bosutinib through dose reduction can lead to improved/maintained efficacy and better tolerability; still, approximately half of patients on treatment at year 4 maintained a dose of ≥500 mg/day. ClinicalTrials.gov: NCT00261846.

10.
SAGE Open Med ; 9: 20503121211047386, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616555

RESUMO

Purpose: To evaluate efficacy of 0.4 mg tamsulosin monotherapy in patients with benign prostatic hyperplasia with moderate-to-severe International Prostate Symptom Score. Material and methods: From May 2015 to May 2017, 102 patients were analyzed, retrospectively. The patients were classified into three groups according to the combination of medication (tamsulosin 0.4 mg vs tamsulosin 0.4 mg + solifenacin 5 mg vs tamsulosin 0.4 mg + mirabegron 50 mg). Baseline characteristics (e.g. age, body weight, height, and underlying medical disease) were collected. International Prostate Symptom Score, prostate specific antigen, prostate volume, peak urinary flow rate (Qmax), voided volume, and post-voided volume before after treatment were evaluated. Results: We classified and analyzed the patients into three groups depending on the medication. And there were no significant differences between all parameters among the groups. Voided volume at 3 months after treatment in each group was 170.54 ± 125.83, 121.55 ± 46.19, and 274.63 ± 132.30 (p = 0.019). Differences of voiding symptom score and difference of post-voided volume among the groups before after treatment was 5.00 ± 5.42, 1.92 ± 3.92, and 0.11 ± 5.11 and 8.37 ± 34.32, 0.78 ± 14.86, -33.63 ± 28.58 (p = 0.037, p = 0.007). Conclusion: We think tamsulosin monotherapy will be feasible as a first-line therapy for the patients with benign prostatic hyperplasia who has struggled with moderate-to-severe lower urinary tract symptoms.

11.
Appl Opt ; 60(24): 7391-7399, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34613028

RESUMO

We propose a new learning and inferring model that generates digital holograms using deep neural networks (DNNs). This DNN uses a generative adversarial network, trained to infer a complex two-dimensional fringe pattern from a single object point. The intensity and fringe patterns inferred for each object point were multiplied, and all the fringe patterns were accumulated to generate a perfect hologram. This method can achieve generality by recording holograms for two spaces (16 Space and 32 Space). The reconstruction results of both spaces proved to be almost the same as numerical computer-generated holograms by showing the performance at 44.56 and 35.11 dB, respectively. Through displaying the generated hologram in the optical equipment, we proved that the holograms generated by the proposed DNN can be optically reconstructed.

12.
Yonsei Med J ; 62(11): 997-1004, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34672133

RESUMO

PURPOSE: This study aimed to determine whether the use of drugs in the treatment of inflammatory bowel disease is related to the risk of colorectal cancer using a Cox proportional hazards model with the landmark method to minimize immortal time bias. MATERIALS AND METHODS: This study was conducted as national cohort-based study using data from Korea's Health Insurance Corporation. Newly diagnosed patients with inflammatory bowel disease from 2006 to 2010 were monitored for colorectal cancer until 2015. Hazard ratios and 95% confidence intervals were calculated and compared with the incidence of colorectal cancer with or without medications by applying various landmark points. RESULTS: In patients with Crohn's disease, the prevention of colorectal cancer in the group exposed to immunomodulators was significant in the basic Cox model; however, the effect was not statistically significant in the model using the landmark method. The preventive effect of 5-aminosalicylic acid in patients with ulcerative colitis was significant in the basic and 6-month landmark point application models, but not in the remaining landmark application models. CONCLUSION: In patients with inflammatory bowel disease, the preventive effect of drug exposure on colorectal cancer varies depending on the application of the landmark method. Hence, the possibility of immortal time bias should be considered.


Assuntos
Colite Ulcerativa , Neoplasias Colorretais , Doença de Crohn , Doenças Inflamatórias Intestinais , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico
13.
Sensors (Basel) ; 21(20)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34696057

RESUMO

In this study, we aimed to develop a new automated method for kidney volume measurement in children using ultrasonography (US) with image pre-processing and hybrid learning and to formulate an equation to calculate the expected kidney volume. The volumes of 282 kidneys (141 subjects, <19 years old) with normal function and structure were measured using US. The volumes of 58 kidneys in 29 subjects who underwent US and computed tomography (CT) were determined by image segmentation and compared to those calculated by the conventional ellipsoidal method and CT using intraclass correlation coefficients (ICCs). An expected kidney volume equation was developed using multivariate regression analysis. Manual image segmentation was automated using hybrid learning to calculate the kidney volume. The ICCs for volume determined by image segmentation and ellipsoidal method were significantly different, while that for volume calculated by hybrid learning was significantly higher than that for ellipsoidal method. Volume determined by image segmentation was significantly correlated with weight, body surface area, and height. Expected kidney volume was calculated as (2.22 × weight (kg) + 0.252 × height (cm) + 5.138). This method will be valuable in establishing an age-matched normal kidney growth chart through the accumulation and analysis of large-scale data.


Assuntos
Inteligência Artificial , Tomografia Computadorizada por Raios X , Adulto , Criança , Humanos , Processamento de Imagem Assistida por Computador , Rim/diagnóstico por imagem , Ultrassonografia , Adulto Jovem
14.
J Am Coll Cardiol ; 78(15): 1485-1495, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34620404

RESUMO

BACKGROUND: Benefits of intensive blood pressure lowering on health outcomes have been demonstrated in high-risk patients. However, little is known about such benefits in patients with left ventricular hypertrophy (LVH). OBJECTIVES: This study sought to investigate the association of on-treatment blood pressure with cardiovascular disease (CVD) risk in adults with hypertension and LVH. METHODS: From a nationwide health examination database, this study identified 95,545 participants aged 40-79 years who were taking antihypertensive medication and had LVH on baseline electrocardiography. Using Cox models, HRs and 95% CIs for CVD events were calculated according to systolic blood pressure (SBP) or diastolic blood pressure (DBP). RESULTS: Over a median follow-up of 11.5 years, 12,035 new CVD events occurred. An SBP of <130 mm Hg and DBP of <80 mm Hg were associated with the lowest risk for CVD events in cubic spline models. When the group with SBP of 120-129 mm Hg was the reference, multivariable-adjusted HRs were 1.31 (95% CI: 1.24-1.38) in the ≥140 mm Hg group, 1.08 (95% CI: 1.02-1.15) in the 130-139 mm Hg group, and 1.03 (95% CI: 0.93-1.15) in the <120 mm Hg group. Likewise, when the group with DBP of 70-79 mm Hg was the reference, multivariable-adjusted HRs were 1.30 (95% CI: 1.24-1.37) in the ≥90 mm Hg group, 1.06 (95% CI: 1.01-1.12) in the 80-89 mm Hg group, and 1.08 (95% CI: 0.96 to 1.20) in the <70 mm Hg group. CONCLUSIONS: In adults with hypertension and LVH, the risk for CVD events was the lowest at SBP <130 mm Hg and DBP <80 mm Hg. Further randomized trials are warranted to establish optimal blood pressure-lowering strategies for these patients.

15.
Foods ; 10(10)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34681291

RESUMO

Tebuconazole (TEB), a triazole fungicide, is frequently applied to agriculture for the increase of food production. Although TEB causes liver toxicity, its effects on cellular lipid accumulation are rarely investigated. Therefore, this study aimed to study the effects of TEB on lipid metabolism and accumulation in HepG2 cells. HepG2 cells were exposed to 0-320 µM TEB for 1-24 h. TEB (20-80 µM, 24 h)-treated cells showed lipid accumulation. Further, TEB (20-80 µM, 1-12 h) increased the nuclear translocation of peroxisome proliferator-activated receptors and the expression of lipid uptake and oxidation-related markers such as cluster of differentiation 36, fatty acid transport protein (FATP) 2, FATP5, and carnitine palmitoyltransferase 1. Oxidative stress levels in TEB-treated cells (20-80 µM, 24 h) were higher, compared to those in the control. TEB (20-80 µM, 24 h) also induced the loss of mitochondrial membrane potential and lower levels of microsomal triglyceride transfer protein in the cells. Thus, TEB can induce lipid accumulation by altering the expression of lipid-metabolizing molecules and can therefore impair lipid metabolism. Our data suggest that human exposure to TEB may be a risk factor for non-alcoholic fatty liver disease.

16.
PLoS One ; 16(10): e0258567, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34618874

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0256978.].

17.
PLoS One ; 16(9): e0256978, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34492059

RESUMO

Kenaf (Hibiscus cannabinus L.) is an industrial crop used as a raw material in various fields and is cultivated worldwide. Compared to high potential for its utilization, breeding sector is not vigorous partially due to laborous breeding procedure. Thus, efficient breeding methods are required for varieties that can adapt to various environments and obtain optimal production. For that, identifying kenaf's characteristics is very important during the breeding process. Here, we investigated if RGB based vegetative index (VI) could be associated with traits for biomass. We used 20 varieties and germplasm of kenaf and RGB images taken with unmanned aerial vehicles (UAVs) for field selection in early and late growth stage. In addition, measuring the stem diameter and the number of nodes confirmed whether the vegetative index value obtained from the RGB image could infer the actual plant biomass. Based on the results, it was confirmed that the individual surface area and estimated plant height, which were identified from the RGB image, had positive correlations with the stem diameter and node number, which are actual growth indicators of the rate of growth further, biomass could also be estimated based on this. Moreover, it is suggested that VIs have a high correlation with actual growth indicators; thus, the biomass of kenaf could be predicted. Interstingly, those traits showing high correlation in the late stage had very low correlations in the early stage. To sum up, the results in the current study suggest a more efficient breeding method by reducing labor and resources required for breeding selection by the use of RGB image analysis obtained by UAV. This means that considerable high-quality research could be performed even with a tight budget. Furthermore, this method could be applied to crop management, which is done with other vegetative indices using a multispectral camera.


Assuntos
Produtos Agrícolas/anatomia & histologia , Hibiscus/anatomia & histologia , Melhoramento Vegetal , Biomassa , Fenótipo , Banco de Sementes/normas
18.
Pharmaceutics ; 13(9)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34575544

RESUMO

Lidocaine, a commonly used local anesthetic, has recently been developed into a number of ointment products to treat hemorrhoids. This study examined its efficient delivery to the dermis through the pharmaceutical improvement of hemorrhoid treatment ointments. We attempted to increase the amount of skin deposition of lidocaine by forming a nanoemulsion through the self-nanoemulsifying effect that occurs when glycerol monostearate (GMS) is saturated with water. Using Raman mapping, the depth of penetration of lidocaine was visualized and confirmed, and the local anesthetic effect was evaluated via an in vivo tail-flick test. Evaluation of the physicochemical properties confirmed that lidocaine was amorphous and evenly dispersed in the ointment. The in vitro dissolution test confirmed that the nanoemulsifying effect of GMS accelerated the release of the drug from the ointment. At a specific concentration of GMS, lidocaine penetrated deeper into the dermis; the in vitro permeation test showed similar results. When compared with reference product A in the tail-flick test, the L5 and L6 compounds containing GMS had a significantly higher anesthetic effect. Altogether, the self-nanoemulsifying effect of GMS accelerated the release of lidocaine from the ointment. The compound with 5% GMS, the lowest concentration that saturated the dermis, was deemed most appropriate.

19.
Pharmaceutics ; 13(9)2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34575594

RESUMO

Coronavirus disease 2019 (COVID-19), caused by a new strain of coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly worldwide. Nafamostat mesylate (NFM) suppresses transmembrane serine protease 2 and SARS-CoV-2 S protein-mediated fusion. In this study, pharmacokinetics and lung distribution of NFM, administered via intravenous and intratracheal routes, were determined using high performance liquid chromatography analysis of blood plasma, lung lumen using bronchoalveolar lavage fluid, and lung tissue. Intratracheal administration had higher drug delivery and longer residual time in the lung lumen and tissue, which are the main sites of action, than intravenous administration. We confirmed the effect of lecithin as a stabilizer through an ex vivo stability test. Lecithin acts as an inhibitor of carboxylesterase and delays NFM decomposition. We prepared inhalable microparticles with NFM, lecithin, and mannitol via the co-spray method. The formulation prepared using an NFM:lecithin:mannitol ratio of 1:1:100 had a small particle size and excellent aerodynamic performance. Spray dried microparticles containing NFM, lecithin, and mannitol (1:1:100) had the longest residual time in the lung tissue. In conclusion, NFM-inhalable microparticles were prepared and confirmed to be delivered into the respiratory tract, such as lung lumen and lung tissue, through in vitro and in vivo evaluations.

20.
Front Microbiol ; 12: 691895, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566903

RESUMO

Genomic information can be used to predict major pathogenic traits of pathogens without the need for laboratory experimentation. However, no Vibrio cholerae genome-based trait identification tools currently exist. The aim of this study was to develop a web-based prediction tool to identify Vibrio pathogenic traits using publicly available 796 whole-genome sequences of V. cholerae. Using this application, 68 structural O-antigen gene clusters belonging to 49 serogroups of V. cholerae were classified, and the composition of the genes within the O-antigen cluster of each serogroup was identified. The arrangement and location of the CTX prophage and related elements of the seventh cholera pandemic strains were also revealed. With the versatile tool, named VicPred, we analyzed the assemblage of various SXTs (sulfamethoxazole/trimethoprim resistance element) and major genomic islands (GIs) of V. cholerae, and the increasing trend in drug-resistance revealing high resistance of the V. cholerae strains to certain antibiotics. The pathogenic traits of newly sequenced V. cholerae strains could be analyzed based on these characteristics. The accumulation of further genome data will expedite the establishment of a more precise genome-based pathogenic traits analysis tool.

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