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1.
Sensors (Basel) ; 24(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38339532

RESUMO

Visual localization refers to the process of determining an observer's pose by analyzing the spatial relationships between a query image and a pre-existing set of images. In this procedure, matched visual features between images are identified and utilized for pose estimation; consequently, the accuracy of the estimation heavily relies on the precision of feature matching. Incorrect feature matchings, such as those between different objects and/or different points within an object in an image, should thus be avoided. In this paper, our initial evaluation focused on gauging the reliability of each object class within image datasets concerning pose estimation accuracy. This assessment revealed the building class to be reliable, while humans exhibited unreliability across diverse locations. The subsequent study delved deeper into the degradation of pose estimation accuracy by artificially increasing the proportion of the unreliable object-humans. The findings revealed a noteworthy decline started when the average proportion of the humans in the images exceeded 20%. We discuss the results and implications for dataset construction for visual localization.

2.
Int J Mol Sci ; 25(10)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38791396

RESUMO

The Hippo pathway controls organ size and homeostasis and is linked to numerous diseases, including cancer. The transcriptional enhanced associate domain (TEAD) family of transcription factors acts as a receptor for downstream effectors, namely yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), which binds to various transcription factors and is essential for stimulated gene transcription. YAP/TAZ-TEAD facilitates the upregulation of multiple genes involved in evolutionary cell proliferation and survival. TEAD1-4 overexpression has been observed in different cancers in various tissues, making TEAD an attractive target for drug development. The central drug-accessible pocket of TEAD is crucial because it undergoes a post-translational modification called auto-palmitoylation. Crystal structures of the C-terminal TEAD complex with small molecules are available in the Protein Data Bank, aiding structure-based drug design. In this study, we utilized the fragment molecular orbital (FMO) method, molecular dynamics (MD) simulations, shape-based screening, and molecular mechanics-generalized Born surface area (MM-GBSA) calculations for virtual screening, and we identified a novel non-covalent inhibitor-BC-001-with IC50 = 3.7 µM in a reporter assay. Subsequently, we optimized several analogs of BC-001 and found that the optimized compound BC-011 exhibited an IC50 of 72.43 nM. These findings can be used to design effective TEAD modulators with anticancer therapeutic implications.


Assuntos
Simulação de Dinâmica Molecular , Fatores de Transcrição de Domínio TEA , Fatores de Transcrição , Humanos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/química , Sítios de Ligação , Descoberta de Drogas/métodos , Ligação Proteica , Simulação de Acoplamento Molecular , Desenho de Fármacos
3.
J Radiol Prot ; 42(3)2022 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-35921807

RESUMO

In line with the activities of Task Group 103 under the International Commission on Radiological Protection (ICRP), the present study was conducted to develop a new set of alimentary tract organs consisting of the oral cavity, oesophagus, stomach, small intestine, and colon for the newborn, 1 year-old, 5 year-old, 10 year-old, and 15 year-old males and females for use in the pediatric mesh-type reference computational phantoms (MRCPs). The developed alimentary tract organs of the pediatric MRCPs, while nearly preserving the original topology and shape of those of the pediatric voxel-type reference computational phantoms (VRCPs) of ICRPPublication 143, present considerable anatomical improvement and include all micrometre-scale target and source regions as prescribed in ICRPPublication 100. To investigate the dosimetric impact of the developed alimentary tract organs, organ doses and specific absorbed fractions were computed for certain external exposures to photons and electrons and internal exposures to electrons, respectively, which were then compared with the values computed using the current ICRP models (i.e. pediatric VRCPs and ICRP-100 stylised models). The results showed that for external exposures to penetrating radiations (i.e. photons >0.04 MeV), there was generally good agreement between the compared values, within a 10% difference, except for the oral mucosa. For external exposures to weakly penetrating radiations (i.e. low-energy photons and electrons), there were significant differences, up to a factor of ∼8300, owing to the geometric difference caused by the anatomical enhancement in the MRCPs. For internal exposures of electrons, there were significant differences, the maximum of which reached a factor of ∼73 000. This was attributed not only to the geometric difference but also to the target mass difference caused by the different luminal content mass and organ shape.


Assuntos
Proteção Radiológica , Telas Cirúrgicas , Criança , Pré-Escolar , Simulação por Computador , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Método de Monte Carlo , Imagens de Fantasmas , Fótons , Doses de Radiação , Proteção Radiológica/métodos , Radiometria/métodos
4.
Medicina (Kaunas) ; 58(9)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36143868

RESUMO

Background and Objectives: Evidence regarding the prevalence of neuropathic pain in patients with cervical radicular pain is limited. This study aimed to investigate the prevalence of neuropathic pain components in patients with cervical radicular pain using established screening tools and identify the relationship between neuropathic pain components and clinical factors. Materials and Methods: Data from 103 patients (aged ≥ 20 years) with cervical radicular pain who visited our pain clinic were analyzed retrospectively. Demographic characteristics, history of neck surgery, pain intensity using numeric rating score, dominant pain site, duration of symptoms, and neck disability index were assessed. The prevalence of neuropathic pain components was defined according to the Douleur Neuropathique 4 questions and painDETECT questionnaire tools. Patient characteristics were compared using the chi-square test or Fisher's exact test for categorical variables and the independent t-test or Mann−Whitney U test for continuous variables. The correlation between neck disability index and other variables was analyzed using Pearson's correlation coefficient. Results: Of the 103 patients, 29 (28.1%) had neuropathic pain components. The neck disability index was significantly higher (p < 0.001) for patients in the neuropathic pain group (23.79 ± 6.35) than that in the non- neuropathic pain group (18.43 ± 7.68). The Douleur Neuropathique 4 questions (r = 0.221, p < 0.025) and painDETECT questionnaire (r = 0.368, p < 0.001) scores positively correlated with the neck disability index score. Conclusions: The prevalence of neuropathic pain components in patients with cervical radicular pain was low. The patients in our study showed a strong correlation between functional deterioration and their neuropathic pain screening score. This study may be useful in understanding the characteristics of cervical radicular pain.


Assuntos
Neuralgia , Radiculopatia , Humanos , Neuralgia/epidemiologia , Neuralgia/etiologia , Medição da Dor , Radiculopatia/complicações , Radiculopatia/epidemiologia , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento
5.
J Radiol Prot ; 41(2)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33401263

RESUMO

In 2016, the International Commission on Radiological Protection (ICRP) launched Task Group 103 (TG 103) for the explicit purpose of developing a new generation of adult and pediatric reference computational phantoms, named 'mesh-type reference computational phantoms (MRCPs)', that can overcome the limitations of voxel-type reference computational phantoms (VRCPs) of ICRPPublications 110and143due to their finite voxel resolutions and the nature of voxel geometry. After completing the development of the adult MRCPs, TG 103 has started the development of pediatric MRCPs comprising 10 phantoms (male and female versions of the reference newborn, 1-year-old, 5-year-old, 10-year-old, and 15-year-old). As part of the TG 103 project, within the present study, the skeletal systems, one of the most important and complex organ systems of the body, were developed for each phantom age and sex. The developed skeletal systems, while closely preserving the original bone topology of the pediatric VRCPs, present substantial improvements in the anatomy of complex and/or small bones. In order to investigate the dosimetric impact of the developed skeletons, the average absorbed doses and the specific absorbed fractions for radiosensitive skeletal tissues (i.e. active marrow and bone endosteum) were computed for some selected external and internal exposure cases, which were then compared with those calculated with the skeletons of pediatric VRCPs. The comparison result showed that the dose values of the pediatric MRCPs were generally similar to those of the pediatric VRCPs for highly penetrating radiations (e.g. photons >200 keV); however, for weakly penetrating radiations (e.g. photons ⩽200 keV and electrons), significant differences up to a factor of 140 were observed.


Assuntos
Proteção Radiológica , Telas Cirúrgicas , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Método de Monte Carlo , Imagens de Fantasmas , Fótons , Doses de Radiação , Radiometria
6.
J Radiol Prot ; 41(2)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33882468

RESUMO

The International Commission on Radiological Protection (ICRP) recently reduced the dose limit for the eye lens for occupational exposure from 150 mSv yr-1to 20 mSv yr-1, as averaged over defined periods of five years, with no annual dose in a single year exceeding 50 mSv, emphasizing the importance of the accurate estimation of lens dose. In the present study, for more accurate lens dosimetry, detailed eye models were developed for children and adolescents (newborns and 1, 5, 10, and 15 year olds), which were then incorporated into the pediatric mesh-type reference computational phantoms (MRCPs) and used to calculate lens dose coefficients (DCs) for photon and electron exposures. Finally, the calculated values were compared with those calculated with the adult MRCPs in order to determine the age dependence of the lens DCs. For photon exposures, the lens DCs of the pediatric MRCPs showed some sizable differences from those of the adult MRCPs at very low energies (10 and 15 keV), but the differences were all less than 35%, except for the posterior-anterior irradiation geometry, for which the lens dose is not of primary concern. For electron exposures, much larger differences were found. For the anterior-posterior (AP) and isotropic irradiation geometries, the largest differences between the lens DCs of the pediatric and adult phantoms were found in the energy range of 0.6-1 MeV, where the newborn lens DCs were larger by up to a factor of ∼5 than the adult. The lens DCs of the present study, which were calculated for the radiosensitive region of the lens, also were compared with those for the entire lens in the AP irradiation geometry. Our results showed that the DCs of the entire lens were similar to those of the radiosensitive region for 0.02-2 MeV photons and >2 MeV electrons, but that for the other energy ranges, significant differences were noticeable, i.e. 10%-40% for photons and up to a factor of ∼5 for electrons.


Assuntos
Cristalino , Radiometria , Adolescente , Adulto , Criança , Humanos , Recém-Nascido , Método de Monte Carlo , Imagens de Fantasmas , Fótons , Doses de Radiação
7.
J Radiol Prot ; 41(4)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33647886

RESUMO

For use in electron paramagnetic resonance dosimetry with tooth enamel, in the present study, very detailed mesh-type tooth models composed of 198 individual tooth models (i.e. newborn: 20; 1 year: 28; 5 years: 48; 10 years: 38; 15 years: 32; and adult: 32) were developed for each sex. The developed tooth models were then implanted in the International Commission on Radiological Protection pediatric and adult mesh-type reference computational phantoms and used to calculate tooth enamel doses, by Monte Carlo simulations with Geant4, for external photon exposures in several idealized irradiation geometries. The calculated dose values were then compared to investigate the dependency of the enamel dose on the age and sex of the phantom and the sites of the teeth. The results of the present study generally show that, if the photon energy is low (i.e. <0.1 MeV), the enamel dose is significantly affected by the age and sex of the phantom and also the sites of the teeth used for dose calculation; the differences are frequently greater than a few times or even orders of magnitude. However, with a few exceptions, the enamel dose was hardly affected by these parameters for energies between 0.1 and 3 MeV. For energies >3 MeV, moderate differences were observed (i.e., up to a factor of two), due to the existence of dose build-up in the head of the phantom for high-energy photons. The calculated dose values were also compared with those of the previous studies where voxel and mathematical models were used to calculate the enamel doses. The results again show significant differences at low energies, e.g., up to ∼3500 times at 0.015 MeV, which are mainly due to the differences in the level of tooth-modeling detailedness.


Assuntos
Radiometria , Telas Cirúrgicas , Adulto , Criança , Humanos , Recém-Nascido , Método de Monte Carlo , Imagens de Fantasmas , Doses de Radiação
8.
J Radiol Prot ; 40(4): 962-979, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32964861

RESUMO

As a geometrical format for computational human phantoms, tetrahedral mesh (TM) is known to have significant advantages over polygonal mesh (PM), including higher compatibility with Monte Carlo radiation transport codes, higher computation speed, and the capability of modeling heterogeneous density variation in an organ of the phantom. In the present study, a computer program named POLY2TET was developed to convert the format of computational human phantoms from PM to TM and generate a sample source code or input file, as applicable, for the converted phantom to be used in some general-purpose Monte Carlo radiation transport codes (i.e. Geant4, PHITS, and MCNP6). The developed program was then tested using four existing high-fidelity PM phantoms. The computation speed, memory requirement, and initialisation time of the generated TM phantoms were also measured and compared with those of the original PM phantoms in Geant4. From the results of our test, it was concluded that the developed program successfully converts PM phantoms into the TM format. The organ doses calculated using the generated TM phantom for the three Monte Carlo codes all produced essentially identical dose values to those for the original PM phantoms in Geant4. The comparison of computation speed showed that compared to the original PM phantoms in Geant4, the TM phantoms in the three Monte Carlo codes were much faster in transporting the particles considered in the present study, i.e. by up to ∼2600 times for electron beams simulated in PHITS. The comparison of the memory requirement showed that the TM phantoms required more memory than the original PM phantoms, but, except for MCNP6, the memory required for the TM phantoms was still less than 12 GB, which typically is available in personal computers these days. For MCNP6, the required memory was much higher, i.e. 60-70 GB.

9.
J Radiol Prot ; 40(4)2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33045695

RESUMO

In a recent epidemiologic risk assessment on late health effects of patients treated with radioactive iodine (RAI), organ/tissue doses of the patients were estimated based on iodine-131Svalues derived from the reference computational phantoms of the International Commission on Radiological Protection (ICRP). However, the use of theSvalues based on the reference phantoms may lead to significant biases in the estimated doses of patients whose body sizes (height and weight) are significantly different from the reference body sizes. To fill this critical gap, we established a comprehensive dataset of body-size-dependent iodine-131Svalues (rT← thyroid) for 30 radiosensitive target organs/tissues by performing Monte Carlo dose calculations coupled with a total of 212 adult male and female computational phantoms in different heights and weights. We observed that theSvalues tend to decrease with increasing body height; for example, theSvalue (gonads ← thyroid) of the 160 cm male phantom is about 3 times higher than that of the 190 cm male phantom at the 70 kg weight. We also observed that theSvalues tend to decrease with increasing body weight for some organs/tissues; for example, theSvalue (skin ← thyroid) of the 45 kg female phantom is about two times higher than that of the 130 kg female phantom at the 160 cm height. For other organs/tissues, which are relatively far from the thyroid, in contrast, theSvalues tend to increase with increasing body weight; for example, theSvalue (bladder ← thyroid) of the 45 kg female phantom is about 2 times lower than that of the 130 kg female phantom. Overall, the majority of the body-size-dependentSvalues deviated to within 25% from those of the reference phantoms. We believe that the use of body-size-dependentSvalues in dose reconstructions should help quantify the dosimetric uncertainty in epidemiologic investigations of RAI-treated patients.


Assuntos
Iodo , Neoplasias da Glândula Tireoide , Adulto , Tamanho Corporal , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Método de Monte Carlo , Imagens de Fantasmas , Doses de Radiação , Radiometria
10.
EMBO Rep ; 18(1): 72-86, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27979971

RESUMO

YAP is the major downstream effector of the Hippo pathway, which controls cell growth, tissue homeostasis, and organ size. Aberrant YAP activation, resulting from dysregulation of the Hippo pathway, is frequently observed in human cancers. YAP is a transcription co-activator, and the key mechanism of YAP regulation is its nuclear and cytoplasmic translocation. The Hippo pathway component, LATS, inhibits YAP by phosphorylating YAP at Ser127, leading to 14-3-3 binding and cytoplasmic retention of YAP Here, we report that osmotic stress stimulates transient YAP nuclear localization and increases YAP activity even when YAP Ser127 is phosphorylated. Osmotic stress acts via the NLK kinase to induce YAP Ser128 phosphorylation. Phosphorylation of YAP at Ser128 interferes with its ability to bind to 14-3-3, resulting in YAP nuclear accumulation and induction of downstream target gene expression. This osmotic stress-induced YAP activation enhances cellular stress adaptation. Our findings reveal a critical role for NLK-mediated Ser128 phosphorylation in YAP regulation and a crosstalk between osmotic stress and the Hippo pathway.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Nucleares/metabolismo , Pressão Osmótica , Proteínas Serina-Treonina Quinases/metabolismo , Serina/metabolismo , Fatores de Transcrição/metabolismo , Ciclo Celular , Proteínas de Ciclo Celular , Nucléolo Celular , Citoplasma/metabolismo , Ativação Enzimática , Células HEK293 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/química , Fosforilação , Ligação Proteica , Proteínas Serina-Treonina Quinases/química , Transporte Proteico , Serina/química , Transdução de Sinais
11.
EMBO Rep ; 18(1): 61-71, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27979972

RESUMO

Hippo signaling controls organ size by regulating cell proliferation and apoptosis. Yes-associated protein (YAP) is a key downstream effector of Hippo signaling, and LATS-mediated phosphorylation of YAP at Ser127 inhibits its nuclear localization and transcriptional activity. Here, we report that Nemo-like kinase (NLK) phosphorylates YAP at Ser128 both in vitro and in vivo, which blocks interaction with 14-3-3 and enhances its nuclear localization. Depletion of NLK increases YAP phosphorylation at Ser127 and reduces YAP-mediated reporter activity. These results suggest that YAP phosphorylation at Ser128 and at Ser127 may be mutually exclusive. We also find that with the increase in cell density, nuclear localization and the level of NLK are reduced, resulting in reduction in YAP phosphorylation at Ser128. Furthermore, knockdown of Nemo (the Drosophila NLK) in fruit fly wing imaginal discs results in reduced expression of the Yorkie (the Drosophila YAP) target genes expanded and DIAP1, while Nemo overexpression reciprocally increased the expression. Overall, our data suggest that NLK/Nemo acts as an endogenous regulator of Hippo signaling by controlling nuclear localization and activity of YAP/Yorkie.


Assuntos
Proteínas 14-3-3/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Animais , Contagem de Células , Proteínas de Ciclo Celular , Linhagem Celular , Movimento Celular , Núcleo Celular/metabolismo , Drosophila , Humanos , Camundongos , Proteínas Nucleares/química , Fosforilação , Ligação Proteica , Transporte Proteico , Serina/química , Serina/metabolismo , Fatores de Transcrição/química , Transcrição Gênica
12.
Cell Mol Life Sci ; 75(13): 2303-2319, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29602952

RESUMO

The Hippo tumor suppressor pathway, which is well conserved from Drosophila to humans, has emerged as the master regulator of organ size, as well as major cellular properties, such as cell proliferation, survival, stemness, and tissue homeostasis. The biological significance and deregulation of the Hippo pathway in tumorigenesis have received a surge of interest in the past decade. In the current review, we present the major discoveries that made substantial contributions to our understanding of the Hippo pathway and discuss how Hippo pathway components contribute to cellular signaling, physiology, and their potential implications in anticancer therapeutics.


Assuntos
Neoplasias/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/fisiologia , Animais , Proliferação de Células/fisiologia , Homeostase/fisiologia , Humanos
13.
Urol Case Rep ; 46: 102292, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36483449

RESUMO

We report a case of transurethral resection of the prostate (TURP) syndrome with mild hyponatremia, severe lactic acidosis, and hypotension. A 73-year-old man with benign prostatic hyperplasia underwent monopolar TURP. Two episodes of hypotension occurred during the operation. These were corrected after injection of a bolus of ephedrine. After the operation, the hypotension persisted and lactic acidosis worsened. Abdominal distension was evident postoperatively. Abdominal ultrasound and computerized tomography revealed a large amount of fluid in the abdominal cavity. We suspected the leakage of sorbitol-containing irrigating fluid. After percutaneous drainage, the lactic acidosis resolved and hypotension stabilized.

14.
Foot Ankle Int ; 44(2): 130-138, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36576025

RESUMO

BACKGROUND: Recurrence of the hallux valgus deformity has various causes, and the incomplete reduction of sesamoids may be one of the important issues. However, we have seen several patients with postoperative lateral sesamoid displacement on anteroposterior (AP) standing radiographs who did not experience hallux valgus recurrence. Therefore, we hypothesized that lateral displacement of the sesamoid on AP standing radiographs does not cause hallux valgus recurrence. METHODS: The study included 269 feet (185 patients) with hallux valgus treated with distal chevron metatarsal osteotomy. Mean patient age was 64.26 (range, 15-80) years. Patients were followed up for an average of 33.85 (range, 12-228) months between April 2002 and December 2019. The patients were divided into 4 groups, according to the presence or absence of hallux valgus recurrence and sesamoid reduction. RESULTS: During outpatient follow-up, we discovered 99 feet (42.1%) in which hallux valgus did not recur despite lateral sesamoid displacement (grade IV-VII) on AP standing radiographs. Hallux valgus angle (HVA, 2.7 to 7.9 degrees), intermetatarsal angle (IMA, 4.6 to 6.2 degrees), and sesamoid grades (2.1 to 3.5) all deteriorated over time after surgery, and each indicator was statistically significantly altered, and changes in the 3 indicators had a statistically significant positive correlation. Changes in HVA and IMA between feet with and without sesamoid reduction on AP standing radiographs increased over time, with the differences in HVA (2.9 degrees) and IMA (0.9 degrees) being significant at final follow-up (P < .05 for each). Regardless of whether sesamoid reduction was achieved on AP standing radiographs, the final analysis showed that HVA and IMA in both groups worsened over time. Further, there were no differences between the 2 groups in the patterns of change over time. CONCLUSION: In our cohort, postoperative sesamoid position on AP standing radiographs was not associated with hallux valgus recurrence based on radiographic criteria. LEVEL OF EVIDENCE: Level III, retrospective comparative study.


Assuntos
Joanete , Hallux Valgus , Ossos do Metatarso , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Hallux Valgus/diagnóstico por imagem , Hallux Valgus/cirurgia , Estudos Retrospectivos , Ossos do Metatarso/diagnóstico por imagem , Ossos do Metatarso/cirurgia , Radiografia , Osteotomia , Resultado do Tratamento
15.
Phys Med Biol ; 67(18)2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-35981551

RESUMO

Objective.The red bone marrow (RBM) and bone endosteum (BE), which are required for effective dose calculation, are macroscopically modeled in the reference phantoms of the international commission on radiological protection (ICRP) due to their microscopic and complex histology. In the present study, the detailed bone models were developed to simplify the dose calculation process for skeletal dosimetry.Approach.The detailed bone models were developed based on the bone models developed at the University of Florida. A new method was used to update the definition of BE region by storing the BE location indices using virtual sub-voxels. The detailed bone models were then installed in the spongiosa regions of the ICRP mesh-type reference computational phantoms (MRCPs) via the parallel geometry feature of the Geant4 code.Main results.Comparing the results between the detailed-bone-installed MRCPs and the original MRCPs with the absorbed dose to spongiosa and fluence-to-dose response function (DRF)-based methods, the DRF-based method showed much smaller but still significant differences. Compared with the values given in ICRPPublications116 and 133, the differences were very large (i.e. several orders of magnitudes), due mainly to the anatomical improvement of the skeletal system in the MRCPs; that is, spongiosa and medullary cavity are fully enclosed by cortical bone in the MRCPs but not in the ICRP-110 phantoms.Significance.The detailed bone models enable the direct calculation of the absorbed doses to the RBM and BE, simplifying the dose calculation process and potentially improving the consistency and accuracy of skeletal dosimetry.


Assuntos
Proteção Radiológica , Adulto , Humanos , Método de Monte Carlo , Imagens de Fantasmas , Doses de Radiação , Radiometria/métodos , Microtomografia por Raio-X
16.
Cancers (Basel) ; 13(16)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34439400

RESUMO

The Hippo pathway is an important signaling pathway modulating growth control and cancer cell proliferation. Dysregulation of the Hippo pathway is a common feature of several types of cancer cells. The modulation of the interaction between yes-associated protein (YAP) and transcriptional enhancer associated domain (TEAD) in the Hippo pathway is considered an attractive target for cancer therapeutic development, although the inhibition of PPI is a challenging task. In order to investigate the hot spots of the YAP and TEAD1 interacting complex, an ab initio Fragment Molecular Orbital (FMO) method was introduced. With the hot spots, pharmacophores for the inhibitor design were constructed, then virtual screening was performed to an in-house library. Next, we performed molecular docking simulations and FMO calculations for screening results to study the binding modes and affinities between PPI inhibitors and TEAD1. As a result of the virtual screening, three compounds were selected as virtual hit compounds. In order to confirm their biological activities, cellular (luciferase activity, proximity ligation assay and wound healing assay in A375 cells, qRT-PCR in HEK 293T cells) and biophysical assays (surface plasmon resonance assays) were performed. Based on the findings of the study, we propose a novel PPI inhibitor BY03 and demonstrate a profitable strategy to analyze YAP-TEAD PPI and discover novel PPI inhibitors.

17.
Sci Rep ; 11(1): 20075, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625606

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to dementia and behavioral changes. Extracellular deposition of amyloid plaques (Aß) and intracellular deposition of neurofibrillary tangles in neurons are the major pathogenicities of AD. However, drugs targeting these therapeutic targets are not effective. Therefore, novel targets for the treatment of AD urgently need to be identified. Expression of the mesoderm-specific transcript (Mest) is regulated by genomic imprinting, where only the paternal allele is active for transcription. We identified hypermethylation on the Mest promoter, which led to a reduction in Mest mRNA levels and activation of Wnt signaling in brain tissues of AD patients. Mest knockout (KO) using the CRIPSR/Cas9 system in mouse embryonic stem cells and P19 embryonic carcinoma cells leads to neuronal differentiation arrest. Depletion of Mest in primary hippocampal neurons via lentivirus expressing shMest or inducible KO system causes neurodegeneration. Notably, depletion of Mest in primary cortical neurons of rats leads to tau phosphorylation at the S199 and T231 sites. Overall, our data suggest that hypermethylation of the Mest promoter may cause or facilitate the progression of AD.


Assuntos
Doença de Alzheimer/patologia , Metilação de DNA , Células-Tronco Embrionárias/patologia , Neurônios/patologia , Regiões Promotoras Genéticas , Proteínas/genética , Via de Sinalização Wnt , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Animais , Células-Tronco de Carcinoma Embrionário/metabolismo , Células-Tronco de Carcinoma Embrionário/patologia , Células-Tronco Embrionárias/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Camundongos , Neurônios/metabolismo , Fosforilação , Proteínas/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismo
18.
Anesth Pain Med (Seoul) ; 15(1): 88-95, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33329796

RESUMO

BACKGROUND: This clinical trial was conducted to determine whether combined use of magnesium sulfate and vitamin C more significantly reduced postoperative fentanyl consumption and pain than magnesium sulfate or vitamin C alone. METHODS: The prospective, double-blinded, randomized controlled study enrolled 132 patients scheduled for laparoscopic gynecologic surgery. The patients were randomly allocated to one of the four groups (n = 33 for each group; Group M [magnesium sulfate 40 mg/kg], Group V [vitamin C 50 mg/kg], Group MV [magnesium sulfate 40 mg/kg and vitamin C 50 mg/kg] and Group C [isotonic saline 40 ml]). Cumulative postoperative fentanyl consumption (primary endpoint measure), postoperative pain score by numeric rating scale, and postoperative nausea and vomiting were recorded at 1, 6, 24, and 48 h after discharge from the postanesthesia care unit. RESULTS: Cumulative postoperative fentanyl consumption was significantly less in Groups M, V, and MV than in Group C at all time points. Group MV showed significantly less cumulative postoperative fentanyl consumption than Group M at postoperative 24 h (mean ± standard deviation, 156.6 ± 67.5 vs. 235.6 ± 94.6 µg, P = 0.001), as well as significantly less consumption than Groups M and V at postoperative 48 h (190.8 ± 74.6 vs. 301.0 ± 114.8 or 284.1 ± 128.6 µg, P < 0.001, P = 0.003, respectively). CONCLUSIONS: Combined use of magnesium sulfate and vitamin C provides an additional benefit in postoperative pain management after laparoscopic gynecologic surgery in comparison to single administration of magnesium sulfate or vitamin C.

19.
Anesth Pain Med (Seoul) ; 15(2): 217-225, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33329817

RESUMO

BACKGROUND: Higher levels of anxiety increase the risks of surgery, including morbidity and mortality. The objectives of this study were to measure anxiety and depression during the preoperative period and to identify the degree of knowledge and concerns of older patients and their family protectors regarding anesthesia, and the causes of these concerns. METHODS: We administered a questionnaire to older patients scheduled to undergo surgery and their family protectors one day prior to the surgery. The questionnaire included tools for quantifying anxiety and depression (Anxiety-Visual Analogue Scale, the Amsterdam Preoperative Anxiety and Information Scale, State-Trait Anxiety Inventory Korean YZ Form, and Short Form Geriatric Depression Scale). We also asked about the concrete causes of anxiety using pre-created forms. RESULTS: There were 140 older patients and family protectors who participated in the study. The majority of older patients (n = 114, 81.4%) undergoing surgery and their family protectors (n = 114, 81.4%) indicated that they were anxious. Most of the older patients and their family protectors responded that they had insufficient knowledge about anesthesia, and they were mostly worried about failure to awaken following surgery, and postoperative pain. Older patients with higher anxiety scores showed higher depression scores. There were significant differences in depression scores depending on the presence of cohabitating family members. CONCLUSIONS: It is important to remember that older patients with higher depression scores have higher anxiety during the preoperative period.

20.
Anesth Pain Med (Seoul) ; 15(2): 226-232, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33329818

RESUMO

BACKGROUND: Vocal cord paralysis (VCP) is one of the most stressful experiences for patients undergoing general anesthesia. Moreover, it is a risk factor for aspiration pneumonia and may increase morbidity and mortality. We examined several clinical features of the condition by reviewing the medical records of patients who experienced VCP following general anesthesia. METHODS: We reviewed the medical records of 321 patients who consulted an otolaryngologist owing to hoarseness, sore throat, throat discomfort, or dysphagia after general anesthesia. Among these, we included in the present study 43 patients who were diagnosed with VCP by laryngoscopy, who did not have symptoms of suspected VCP before surgery, who had no past history of VCP, and for whom endotracheal intubation was not continued after surgery. RESULTS: The mean age of patients with VCP was 51.3 years. With respect to surgical site, the most common was upper limb surgery, performed in 12 cases (9 cases were performed in sitting posture. With respect to surgical duration, only 11 cases lasted less than 3 h, whereas 32 cases required a surgical duration longer than 3 h. The most common symptom of VCP was hoarseness. Nine of the patients with VCP recovered spontaneously, but VCP persisted in 13 cases until the final follow-up examination. CONCLUSIONS: We hope that this study might call attention to the occurrence of VCP following general anesthesia. Moreover, it is necessary to further evaluate the reasons for the higher incidence of VCP in upper limb surgery performed in sitting posture.

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