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1.
Dermatol Surg ; 50(6): 527-533, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38518110

RESUMO

BACKGROUND: Despite the widespread use of botulinum toxin (BTX) injection for the treatment of masseter muscle hypertrophy (MMH), there is no standard treatment option. OBJECTIVE: We report the efficacy and safety for BTX in MMH over a period of 48 weeks. METHODS: In double-blinded, placebo-controlled phase 3 trials, 180 patients (randomized 1:1) received treatment with placebo (normal saline) or prabotulinumtoxinA (48 units). Masseter muscle thickness (at maximal clenching and resting positions), 3D imaging analysis, and masseter muscle hypertrophy scale grades were analyzed at each time point. After the 24-week CORE study, all patients who met the same criteria of the CORE study at week 24 ( n = 114) received only prabotulinumtoxinA, regardless of previous treatment, for an additional 24 weeks (48 weeks in total) for the open-label extension study. RESULTS: The largest differences in mean and percent changes from baseline in masseter muscle thickness were observed at 12 weeks, and there were significant differences between the 2 groups at all time points (all p < .001). The effect was independent of the number of injections. No serious adverse event was observed. CONCLUSION: PrabotulinumtoxinA could effectively ameliorate MMH without major complications.


Assuntos
Toxinas Botulínicas Tipo A , Hipertrofia , Músculo Masseter , Humanos , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/efeitos adversos , Método Duplo-Cego , Hipertrofia/tratamento farmacológico , Músculo Masseter/efeitos dos fármacos , Músculo Masseter/patologia , Músculo Masseter/anormalidades , Feminino , Pessoa de Meia-Idade , Adulto , Masculino , Resultado do Tratamento , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/efeitos adversos , Injeções Intramusculares
2.
J Neuroeng Rehabil ; 21(1): 43, 2024 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-38555417

RESUMO

BACKGROUND: Conventional diagnostic methods for dysphagia have limitations such as long wait times, radiation risks, and restricted evaluation. Therefore, voice-based diagnostic and monitoring technologies are required to overcome these limitations. Based on our hypothesis regarding the impact of weakened muscle strength and the presence of aspiration on vocal characteristics, this single-center, prospective study aimed to develop a machine-learning algorithm for predicting dysphagia status (normal, and aspiration) by analyzing postprandial voice limiting intake to 3 cc. METHODS: Conducted from September 2021 to February 2023 at Seoul National University Bundang Hospital, this single center, prospective cohort study included 198 participants aged 40 or older, with 128 without suspected dysphagia and 70 with dysphagia-aspiration. Voice data from participants were collected and used to develop dysphagia prediction models using the Multi-Layer Perceptron (MLP) with MobileNet V3. Male-only, female-only, and combined models were constructed using 10-fold cross-validation. Through the inference process, we established a model capable of probabilistically categorizing a new patient's voice as either normal or indicating the possibility of aspiration. RESULTS: The pre-trained models (mn40_as and mn30_as) exhibited superior performance compared to the non-pre-trained models (mn4.0 and mn3.0). Overall, the best-performing model, mn30_as, which is a pre-trained model, demonstrated an average AUC across 10 folds as follows: combined model 0.8361 (95% CI 0.7667-0.9056; max 0.9541), male model 0.8010 (95% CI 0.6589-0.9432; max 1.000), and female model 0.7572 (95% CI 0.6578-0.8567; max 0.9779). However, for the female model, a slightly higher result was observed with the mn4.0, which scored 0.7679 (95% CI 0.6426-0.8931; max 0.9722). Additionally, the other models (pre-trained; mn40_as, non-pre-trained; mn4.0 and mn3.0) also achieved performance above 0.7 in most cases, and the highest fold-level performance for most models was approximately around 0.9. The 'mn' in model names refers to MobileNet and the following number indicates the 'width_mult' parameter. CONCLUSIONS: In this study, we used mel-spectrogram analysis and a MobileNetV3 model for predicting dysphagia aspiration. Our research highlights voice analysis potential in dysphagia screening, diagnosis, and monitoring, aiming for non-invasive safer, and more effective interventions. TRIAL REGISTRATION: This study was approved by the IRB (No. B-2109-707-303) and registered on clinicaltrials.gov (ID: NCT05149976).


Assuntos
Transtornos de Deglutição , Feminino , Humanos , Masculino , Algoritmos , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Aprendizado de Máquina , Estudos Prospectivos , Aspiração Respiratória/diagnóstico , Aspiração Respiratória/etiologia , Adulto
3.
Dermatol Ther ; 35(5): e15420, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35249260

RESUMO

Periorbital, perioral, and neck wrinkles are one of the most common concerns of aging skin. We evaluated the efficacy and safety of high-intensity focused ultrasound (HIFU) device with a 5.5-MHz transducer and a 2.0-mm focal depth for improving periorbital, perioral, and neck wrinkles. A total of 102 participants were enrolled, and 34 each were assigned to the periorbital, perioral, and neck groups. All subjects were treated with HIFU three times at 2-week intervals at the corresponding treatment site. Objective measurements and clinical evaluations were performed at 10 and 16 weeks after treatment. Based on the primary efficacy evaluation, the mean Cutometer R7 value was significantly increased at 10 weeks post-treatment compared to baseline in all treated groups. In addition, all other Cutometer values, PRIMOS and Antera 3D camera evaluation results, classification of wrinkle assessment results, and Subject Global Aesthetic Improvement Scale also showed that the periorbital, perioral, and neck wrinkles were significantly improved at 10 and 16 weeks post-treatment. No permanent adverse effects were observed during the follow-up period. HIFU treatment using 5.5-MHz transducers (2.0-mm focal depth) could be an effective and safe treatment modality for the treatment of periorbital, perioral, and neck wrinkles.


Assuntos
Técnicas Cosméticas , Envelhecimento da Pele , Face , Humanos , Estudos Prospectivos , Resultado do Tratamento
4.
Dermatol Ther ; 35(7): e15508, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35419911

RESUMO

Polycaprolactone (PCL)-based fillers are widely used for skin rejuvenation and wrinkle reduction. The objective of this study is to compare the efficacy and safety of newly developed PCL-based fillers (SYB filler®; SF-01) and widely used existing PCL-based fillers (Ellansé-M®) for correction of moderate-to-severe nasolabial folds. In a randomized, participant-and evaluator-blinded, matched-pair, prospective study, participants were randomized for injections of SF-01 or Ellansé-M® in both nasolabial folds. Efficacy was evaluated using the Wrinkle Severity Rating Scale (WSRS), Global Esthetic Improvement Scale (GAIS), and a three-dimensional (3D) scanner. All adverse events (AEs) were examined and reported. At month 12, both SF-01-and Ellansé-M®-treated groups showed statistically significant improvements in the WSRS, GAIS, and 3D scanner scores compared to baseline. The difference in changes in WSRS scores at month 12 between the two groups was 0.08 ± 0.34 compared to baseline. The upper limit of the 95.0% confidence interval was 0.0031, which was lower than the predefined margin for non-inferiority (0.35). All AEs were injection site-related (swelling, pain, and erythema) and disappeared within 30 min after the procedure. SF-01 was non-inferior to Ellansé-M® and demonstrated favorable efficacy and safety at 12 months after correcting moderate-to-severe nasolabial folds.


Assuntos
Técnicas Cosméticas , Preenchedores Dérmicos , Envelhecimento da Pele , Técnicas Cosméticas/efeitos adversos , Preenchedores Dérmicos/efeitos adversos , Humanos , Ácido Hialurônico , Sulco Nasogeniano , Poliésteres , Estudos Prospectivos , Resultado do Tratamento
5.
Dermatol Ther ; 35(9): e15717, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35837791

RESUMO

Various treatment methods are used for noninvasive body contouring. To evaluate the efficacy and safety of a newly designed cryolipolysis device using a three-dimensional cooling method for abdominal fat reduction. Twenty-five participants with clinically apparent abdominal fat tissue participated in the study. The thickness of fat tissue below the umbilicus level was measured using a caliper at baseline and 12 weeks after the first treatment. The height of abdominal subcutaneous fat tissue on ultrasonography and participant satisfaction were assessed at every visit for 16 weeks. All adverse events (AEs) during the study period were recorded. p values <0.05 were considered statistically significant. Twenty-four participants completed this study; the mean BMI of participants was 29.34 ± 2.36 kg/m2 . The mean thickness of abdominal subcutaneous fat was significantly lower at 12 weeks (40.4 ± 6.8 mm, p < 0.001) than at baseline (49.3 ± 8.5 mm). Differences in the height of abdominal subcutaneous fat compared to that at baseline were 1.02 ± 0.41 cm (12 weeks, p < 0.001) and 1.13 ± 0.44 cm (16 weeks, p < 0.001). Rates of abdominal subcutaneous fat reduction at 12 and 16 weeks compared to that at baseline were 28.45% and 31.13%, respectively. The ratio of abdominal circumference to hip circumference at 12 and 16 weeks was significantly decreased compared to that at baseline. Most participants (95.8%) reported improvement in satisfaction scores at 16 weeks. There were no serious AEs during the entire study period. The study demonstrated the efficacy of a noninvasive cryolipolysis device using a three-dimensional cooling method for reducing abdominal subcutaneous fat.


Assuntos
Contorno Corporal , Lipectomia , Contorno Corporal/efeitos adversos , Contorno Corporal/métodos , Humanos , Lipectomia/efeitos adversos , Lipectomia/métodos , Satisfação do Paciente , Estudos Prospectivos , Gordura Subcutânea Abdominal/diagnóstico por imagem , Gordura Subcutânea Abdominal/cirurgia , Resultado do Tratamento
6.
J Nanobiotechnology ; 20(1): 387, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35999603

RESUMO

The plant toxin ricin, especially its cytotoxic A chain (RTA), can be genetically engineered with targeting ligands to develop specific anti-cancer recombinant immunotoxins (RITs). Here, we used affibody molecules targeting two cancer biomarkers, the receptors HER2 and EGFR, along with the KDEL signal peptide to construct two cancer-specific ricin-based RITs, HER2Afb-RTA-KDEL and EGFRAfb-RTA-KDEL. The affibodies successfully provided target-specificity and subsequent receptor-mediated endocytosis and the KDEL signal peptide routed the RITs through the retrograde transport pathway, effectively delivering RTA to the cytosol as well as avoiding the alternate recycling pathway that typical cancer cells frequently have. The in vivo efficacy of RITs was enhanced by introducing the albumin binding domain (AlBD) to construct AlBD/HER2Afb/RTA-KDEL. Systemic administration of AlBD-containing RITs to tumor-bearing mice significantly suppressed tumor growth without any noticeable side-effects. Collectively, combining target-selective affibody molecules, a cytotoxic RTA, and an intracellularly designating peptide, we successfully developed cancer-specific and efficacious ricin-based RITs. This approach can be applied to develop novel protein-based "magic bullets" to effectively suppress tumors that are resistant to conventional anti-cancer drugs.


Assuntos
Imunotoxinas , Neoplasias , Ricina , Animais , Apoptose , Endocitose , Imunotoxinas/metabolismo , Imunotoxinas/farmacologia , Camundongos , Neoplasias/tratamento farmacológico , Sinais Direcionadores de Proteínas , Ricina/farmacologia , Ricina/toxicidade
7.
Int J Mol Sci ; 23(17)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36076991

RESUMO

Contrary to many reports that antiplatelet agents inhibit cancer growth and metastasis, new solid tumors have been reported in patients receiving long-term antiplatelet therapy. We investigated the effects of these agents directly on cancer cells in the absence of platelets to mimic the effects of long-term therapy. When four antiplatelet agents (aspirin, clopidogrel, prasugrel, and ticagrelor) were administered to colon cancer cells, cancer cell proliferation was inhibited similarly to a previous study. However, surprisingly, when cells were treated with a purinergic P2Y12 inhibitor (purinergic antiplatelet agent), the motility of the cancer cells was significantly increased. Therefore, gene expression profiles were identified to investigate the effect of P2Y12 inhibitors on cell mobility, and Serpin family 1 (SERPINE1) was identified as a common gene associated with cell migration and cell death in three groups. Antiplatelet treatment increased the level of SERPINE1 in cancer cells and also promoted the secretion of SERPINE1 into the medium. Increased SERPINE1 was found to induce MMP1 and, thus, increase cell motility. In addition, an increase in SERPINE1 was confirmed using the serum of patients who received these antiplatelet drugs. With these results, we propose that SERPINE1 could be used as a new target gene to prevent the onset and metastasis of cancer in patients with long-term antiplatelet therapy.


Assuntos
Neoplasias do Colo , Inibidores da Agregação Plaquetária , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Humanos , Metaloproteinase 1 da Matriz , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticlopidina
8.
BMC Cancer ; 20(1): 504, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32487089

RESUMO

BACKGROUND: The decision of transarterial chemoembolization (TACE) initiation and/or repetition remains challenging in patients with unresectable hepatocellular carcinoma (HCC). The aim was to develop a prognostic scoring system to guide TACE initiation/repetition. METHODS: A total of 597 consecutive patients who underwent TACE as their initial treatment for unresectable HCC were included. We derived a prediction model using independent risk factors for overall survival (OS), which was externally validated in an independent cohort (n = 739). RESULTS: Independent risk factors of OS included Albumin-bilirubin (ALBI) grade, maximal tumor size, alpha-fetoprotein, and tumor response to initial TACE, which were used to develop a scoring system ("ASAR"). C-index values for OS were 0.733 (95% confidence interval [CI] = 0.570-0.871) in the derivation, 0.700 (95% CI = 0.445-0.905) in the internal validation, and 0.680 (95% CI = 0.652-0.707) in the external validation, respectively. Patients with ASAR< 4 showed significantly longer OS than patients with ASAR≥4 in all three datasets (all P < 0.001). Among Child-Pugh class B patients, a modified model without TACE response, i.e., "ASA(R)", discriminated OS with a c-index of 0.788 (95% CI, 0.703-0.876) in the derivation, and 0.745 (95% CI, 0.646-0.862) in the internal validation, and 0.670 (95% CI, 0.605-0.725) in the external validation, respectively. Child-Pugh B patients with ASA(R) < 4 showed significantly longer OS than patients with ASA(R) ≥ 4 in all three datasets (all P < 0.001). CONCLUSIONS: ASAR provides refined prognostication for repetition of TACE in patients with unresectable HCC. For Child-Pugh class B patients, a modified model with baseline factors might guide TACE initiation.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/terapia , Idoso , Bilirrubina/análise , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/fisiopatologia , Tomada de Decisão Clínica/métodos , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Fígado/patologia , Fígado/fisiopatologia , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Cirrose Hepática/fisiopatologia , Testes de Função Hepática , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Critérios de Avaliação de Resposta em Tumores Sólidos , Medição de Risco/métodos , Fatores de Risco , Albumina Sérica/análise , Índice de Gravidade de Doença , Análise de Sobrevida
9.
Eur Radiol ; 30(8): 4201-4211, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32270317

RESUMO

OBJECTIVES: This study aimed to evaluate the efficiency of imaging features and texture analysis (TA) based on baseline rectal MRI for the early prediction of therapeutic response to neoadjuvant chemoradiotherapy (nCRT) and tumor recurrence in patients with locally advanced rectal cancer (LARC). METHODS: Consecutive patients with LARC who underwent rectal MRI between January 2014 and December 2015 and surgical resection after completing nCRT were retrospectively enrolled. Imaging features were analyzed, and TA parameters were extracted from the tumor volume of interest (VOI) from baseline rectal MRI. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the optimal TA parameter cutoff values to stratify the patients. Logistic and Cox regression analyses were performed to assess the efficacy of each imaging feature and texture parameter in predicting tumor response and disease-free survival. RESULTS: In total, 78 consecutive patients were enrolled. In the logistic regression, good treatment response was associated with lower tumor location (OR = 13.284, p = 0.012), low Conv_Min (OR = 0.300, p = 0.013) and high Conv_Std (OR = 3.174, p = 0.016), Shape_Sphericity (OR = 3.170, p = 0.015), and Shape_Compacity (OR = 2.779, p = 0.032). In the Cox regression, a greater risk of tumor recurrence was related to higher cT stage (HR = 5.374, p = 0.044), pelvic side wall lymph node positivity (HR = 2.721, p = 0.013), and gray-level run length matrix_long-run low gray-level emphasis (HR = 2.268, p = 0.046). CONCLUSIONS: Imaging features and TA based on baseline rectal MRI could be valuable for predicting the treatment response to nCRT for rectal cancer and tumor recurrence. KEY POINTS: • Imaging features and texture parameters of T2-weighted MR images of rectal cancer can help to predict treatment response and the risk for tumor recurrence. • Tumor location as well as conventional and shape indices of texture features can help to predict treatment response for rectal cancer. • Clinical T stage, positive pelvic side wall lymph nodes, and the high-order texture parameter, GLRLM_LRLGE, can help to predict tumor recurrence for rectal cancer.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/terapia , Quimiorradioterapia Adjuvante , Imageamento por Ressonância Magnética , Terapia Neoadjuvante , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Neoplasias Retais/patologia , Estudos Retrospectivos , Resultado do Tratamento
10.
Dermatol Ther ; 33(6): e13963, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32621657

RESUMO

The elasticity of the skin and its capacity to hold water decrease with aging because of the loss of hyaluronic acid (HA) in the skin. Therefore, there is an increasing interest in the use of HA fillers in skin rejuvenation beyond its conventional use which is supplementing decreased dermis volume and filling deep wrinkles. We investigated the efficacy and safety of a novel device (Dermashine balance) that injects HA into the dermis using a stamp-type microneedle for maintenance of hydration and elasticity of the skin. A single-center randomized double-blinded parallel-group clinical study was conducted, and 60 participants enrolled in this study. The subjects were randomized to receive HA injections or a placebo three times across the face using an automatic intradermal injector. At 4, 8, and 12 weeks after the treatment, skin hydration was measured using a corneometer. The patients who received HA showed significantly greater skin hydration than those who received the placebo. However, a significant difference was not noted in skin elasticity between the groups. No severe adverse event was reported. Intradermal supplementation of HA using mesogun multineedle injector may be a safe and effective treatment for improving skin hydration.


Assuntos
Técnicas Cosméticas , Envelhecimento da Pele , Técnicas Cosméticas/efeitos adversos , Humanos , Ácido Hialurônico/efeitos adversos , Agulhas , Rejuvenescimento , Pele
11.
Dermatol Surg ; 46(2): 213-219, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31490305

RESUMO

BACKGROUND: Demand for noninvasive body contouring has increased. OBJECTIVE: We evaluated the efficacy and safety of a thermal high-intensity focused ultrasound (HIFU) device for abdominal body shaping. PATIENTS AND METHODS: Adults with a body mass index ≤30 kg/m and an abdominal subcutaneous fat tissue thickness ≥2.5 cm were enrolled for HIFU treatment at energy levels of 150 J/cm (first session) and 135 J/cm (second session). The primary end point was a change from baseline waist circumference at post-treatment Week 8. Secondary efficacy end points were: changes in body weight, waist/hip ratio, and fat thickness assessed by ultrasound, caliper, and a fat CT scan. The Global Aesthetic Improvement Scale was evaluated by both investigators and subjects. RESULTS: The primary assessment achieved statistical significance, showing a reduction of 3.43 cm in mean waist circumference. The treatment effect was cumulative, with a steady decrease in waist circumference and fat thickness. The mean pain scores immediately after treatment were 4.45 ± 2.74 on a scale of 1 to 10 with 10 being the most painful, which decreased to 1.10 ± 1.33 after 1 week. CONCLUSION: High-intensity focused ultrasound is an effective and safe treatment modality for reducing waist circumference in nonobese individuals with focal fat accumulation.


Assuntos
Contorno Corporal/métodos , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Obesidade Abdominal/terapia , Dor Processual/diagnóstico , Gordura Subcutânea Abdominal/efeitos da radiação , Adulto , Contorno Corporal/efeitos adversos , Estética , Feminino , Ablação por Ultrassom Focalizado de Alta Intensidade/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Processual/etiologia , Satisfação do Paciente , Resultado do Tratamento , Circunferência da Cintura/efeitos da radiação
12.
Ann Diagn Pathol ; 44: 151433, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31785538

RESUMO

BACKGROUND: Most urothelial neoplasms of the bladder show an exophytic papillary pattern, but some show an inverted growth pattern. In 2004, the World Health Organization (WHO) released a detailed histologic classification system for papillary urothelial neoplasms, but not for inverted forms. The International Consultation on Urologic Disease (ICUD) recommendations of 2012 are applicable to inverted/endophytic papillary lesions as follows: 1) inverted papilloma (IP), 2) inverted papillary urothelial neoplasm of low malignant potential (IPUNLMP), 3) inverted papillary urothelial carcinoma, low grade, non-invasive (IPUCLG-NI), 4) inverted papillary urothelial carcinoma, high grade, non-invasive (IPUCHG-NI), 5) inverted papillary urothelial carcinoma, high grade, invasive (IPUCHG-I). However, only atypical cellular morphology was considered for classification in the 2012 ICUD recommendations, and data to support to validate this new grading system are lacking. METHODS: Sixty cases of inverted urothelial papillary tumors were classified into 5 categories according to 2012 ICUD and 2016 WHO/ISUP recommendations to evaluate their clinical, pathological, and immunohistochemical characteristics. Two subgroups were defined as subgroup 1, IP and IPUNLMP, and subgroup 2, IPUCLG-NI, IPUCHG-NI, and IPUCHG-I. Clinical features (age, sex, history of urothelial carcinoma, smoking history, size, and multifocality) and histologic features (nuclear pleomorphism, mitotic count, mitosis level, apoptosis, luminal necrosis, trabecular thickening, anastomosing trabeculae, hypercellularity, loss of polarity, peripheral palisading, palisading with central streaming, and discohesiveness) were evaluated. Immunohistochemical stains for CK20, CD44, P53, p16, Ki-67, cyclin D1 and c-erbB2 were performed. RESULTS: A total of 60 cases were classified as 10 cases of IP, 29 cases of IPUNLMPs, 15 cases of IPUCLG-NI, 4 cases of IPUCHG-NI, and 2 cases of IPUCHG-I. Compared to subgroup 1, subgroup 2 showed larger tumor size, more nuclear irregularity, higher mitotic count (hot spot and per 10 high power fields), more upper level mitosis (>1/2), and more frequent apoptosis, luminal necrosis, surface papillary component, trabecular thickening, anastomosing irregular trabeculae, hypercellularity, loss of polarity, peripheral palisading with central streaming, and discohesiveness, and absence of umbrella cells and urothelial eddies. CK20, Ki67, and c-erbB2 were the only markers that were differently expressed in the two subgroups, with more expression in subgroup 2. CONCLUSIONS: The 2012 ICUD recommendations are valid to classify inverted papillary urothelial tumors. However, other histologic features besides atypical cellular morphology should also be considered to distinguish subgroup 1 and subgroup 2 inverted papillary urothelial tumors.


Assuntos
Biomarcadores Tumorais/metabolismo , Hiperplasia/classificação , Doenças Urológicas/classificação , Neoplasias Urológicas/classificação , Adulto , Idoso , Carcinoma Papilar/patologia , Feminino , Humanos , Hiperplasia/patologia , Imuno-Histoquímica , Queratina-20/metabolismo , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Papiloma Invertido , Receptor ErbB-2/metabolismo , Bexiga Urinária/patologia , Doenças Urológicas/patologia , Neoplasias Urológicas/patologia , Urotélio/patologia
13.
J Cell Physiol ; 234(2): 1643-1658, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30132871

RESUMO

Sarcopenia, which refers to the muscle loss that accompanies aging, is a complex neuromuscular disorder with a clinically high prevalence and mortality. Despite many efforts to protect against muscle weakness and muscle atrophy, the incidence of sarcopenia and its related permanent disabilities continue to increase. In this study, we found that treatment with human placental hydrolysate (hPH) significantly increased the viability (approximately 15%) of H2 O2 -stimulated C2C12 cells. Additionally, while H2 O2 -stimulated cells showed irregular morphology, hPH treatment restored their morphology to that of cells cultured under normal conditions. We further showed that hPH treatment effectively inhibited H2 O2 -induced cell death. Reactive oxygen species (ROS) generation and Mstn expression induced by oxidative stress are closely associated with muscular dysfunction followed by atrophy. Exposure of C2C12 cells to H2 O2 induced abundant production of intracellular ROS, mitochondrial superoxide, and mitochondrial dysfunction as well as myostatin expression via nuclear factor-κB (NF-κB) signaling; these effects were attenuated by hPH. Additionally, hPH decreased mitochondria fission-related gene expression (Drp1 and BNIP3) and increased mitochondria biogenesis via the Sirt1/AMPK/PGC-1α pathway and autophagy regulation. In vivo studies revealed that hPH-mediated prevention of atrophy was achieved predominantly through regulation of myostatin and PGC-1α expression and autophagy. Taken together, our findings indicate that hPH is potentially protective against muscle atrophy and oxidative cell death.


Assuntos
Antioxidantes/farmacologia , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Placenta , Extratos de Tecidos/farmacologia , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos Pelados , Mitocôndrias Musculares/efeitos dos fármacos , Mitocôndrias Musculares/metabolismo , Mitocôndrias Musculares/patologia , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Miostatina/metabolismo , NF-kappa B/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Gravidez
14.
Planta ; 249(1): 181-193, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30078076

RESUMO

MAIN CONCLUSION: Photosynthetic production of isoprenoids in cyanobacteria is considered in terms of metabolic engineering and biological importance. Metabolic engineering of photosynthetic bacteria (cyanobacteria) has been performed to construct bio-solar cell factories that convert carbon dioxide to various value-added chemicals. Isoprenoids, which are found in nature and range from essential cell components to defensive molecules, have great value in cosmetics, pharmaceutics, and biofuels. In this review, we summarize the recent engineering of cyanobacteria for photosynthetic isoprenoids production as well as carbon molar basis comparisons with heterotrophic isoprenoids production in engineered Escherichia coli.


Assuntos
Dióxido de Carbono/metabolismo , Cianobactérias/metabolismo , Engenharia Metabólica/métodos , Fotossíntese/fisiologia , Terpenos/metabolismo
15.
Opt Express ; 27(3): 1922-1928, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30732238

RESUMO

We report on a mode-locked Tm,Ho:CLNGG laser emitting in the 2 µm spectral range using single-walled carbon nanotubes (SWCNTs) as a saturable absorber (SA). Pulses with duration of 98 fs are generated at 99.28 MHz repetition rate with an average output power of 123 mW, yielding a pulse energy of 1.24 nJ. Using a 0.5% output coupling, pulses as short as 67 fs, i.e., 10 optical cycles, are produced after extracavity compression with a 3-mm-thick ZnS plate.

16.
Opt Express ; 27(2): 1488-1496, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30696213

RESUMO

Both direct- and evanescent-field interactions with carbon nanotubes (CNTs) are applied to achieve stable Q-switched operation of Yb:KYW planar waveguide lasers. The performance characteristics were investigated in a same cavity configuration and analyzed in detail in the following three cases, CNTs deposited onto end mirror (M-coating), output coupler (OC-coating) and top surface of the planar waveguide (WG-coating). Maximum output powers, repetition rates, and minimum pulse durations are 61 mW, 1103 kHz and 215 ns for OC-coating, 39 mW, 1052 kHz and 275 ns for WG-coating, and 26 mW, 1119 kHz and 217 ns for M-coating, respectively. From the calculation of the configuration-dependent stability range, the beam size and the electric field distribution in the Yb:KYW planar waveguide, it is confirmed that the evanescent-field interaction scheme makes stable Q-switching possible with much lower intensities at saturable absorber compared to the direct-field interaction scheme in the presented waveguide laser operation.

17.
J Vasc Interv Radiol ; 30(3): 358-369, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30819478

RESUMO

PURPOSE: To evaluate efficacy of cone-beam CT-based liver perfusion mapping obtained immediately following conventional transarterial chemoembolization of hepatocellular carcinoma (HCC) for assessing tumor vascularity, technical success of chemoembolization, and treatment response. MATERIALS AND METHODS: From July 2015 to June 2016, 35 patients with 57 HCCs who underwent cone-beam CT with post-processing software via conventional transarterial chemoembolization for HCC and follow-up examination were included. Three reviewers evaluated technical success on angiography, unenhanced cone-beam CT, contrast-enhanced cone-beam CT, and cone-beam CT-based liver perfusion mapping after transarterial chemoembolization per tumor and per patient. Parenchymal blood volume (PBV) was measured. Treatment response was determined on follow-up CT, MR imaging, or histopathology according to modified Response Evaluation Criteria In Solid Tumors. Diagnostic performance for detection of a viable tumor was evaluated using multiple logistic regression with C-statistics. RESULTS: Treatment response was 38, 17, 2, and 0 for complete response, partial response, stable disease, and progressive disease per tumor and 18, 15, 2, and 0 per patient. In multiple logistic regression, unenhanced cone-beam CT, contrast-enhanced cone-beam CT, cone-beam CT-based liver perfusion mapping, mean value of PBV, and maximum value of PBV of tumor were significant in response assessment for per tumor and per patient (per tumor, all P < .001; per patient, P = .015, P = .001, P < .001, P = .020, and P = .032). Mean value of PBV of tumor was excellent for evaluating technical success with the highest C-statistic (0.880 and 0.920 for per tumor and per patient), followed by that of visual assessment of cone-beam CT-based liver perfusion mapping (0.864 and 0.908). CONCLUSIONS: Cone-beam CT-based liver perfusion mapping provided reliable images to evaluate technical success after transarterial chemoembolization of HCC by qualitative visual assessment and quantitative perfusion values.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Tomografia Computadorizada de Feixe Cônico , Circulação Hepática , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Imagem de Perfusão/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia , Biópsia , Carcinoma Hepatocelular/irrigação sanguínea , Feminino , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
18.
Platelets ; 30(5): 631-636, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30059640

RESUMO

Previous studies have reported that various factors affect ADP-induced platelet reactivity during clopidogrel therapy. The aim of this study was to determine whether clinical and laboratory variables for platelet reactivity during dual antiplatelet therapy (DAPT) are dependent on the assay used. We enrolled 904 patients receiving DAPT following coronary intervention. Platelet reactivity was measured using three methods: the VerifyNow P2Y12 assay, multiple electrode aggregometry (MEA) ADP assay, and the light transmittance aggregometry (LTA) ADP assay at 24-48 h following coronary intervention. The VerifyNow results demonstrated a significant inverse correlation with hematocrit value (r = -0.268, p < 0.0001); however, MEA results had no such correlation with hematocrit (r = 0.044, p = 0.188). There was a positive correlation between the MEA results and platelet count (r = 0.255, p < 0.0001). LTA was weakly influenced by hematocrit (r = -0.064, p = 0.057) and platelet count (r = 0.069, p = 0.040). Gender (odds ratio 1.53, 95% CI 1.10-2.14, p = 0.013) and hematocrit (odds ratio 0.91,95% CI 0.88-0.94, p < 0.0001) were the independent variables for HPR by VerifyNow. Smoking (odds ratio 0.38, 95% CI 0.16-0.94, p = 0.036) and platelet count (odds ratio 1.01, 95% CI 1.00-1.01, p < 0.0001) were independent factors for HPR when using the MEA assay, whereas platelet count (odds ratio 1.00, 95% CI 1.00-1.01, p = 0.006) was identified as the only independent variable for HPR when using LTA. The incidence of HPR and the influencing variables involved are dependent on the platelet function test used.


Assuntos
Plaquetas/metabolismo , Ativação Plaquetária , Testes de Função Plaquetária , Difosfato de Adenosina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/farmacologia , Plaquetas/efeitos dos fármacos , Clopidogrel/farmacologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Contagem de Plaquetas , Ticlopidina/farmacologia
19.
BMC Pulm Med ; 19(1): 117, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31248409

RESUMO

BACKGROUND: Although infections caused by nontuberculous mycobacteria (NTM) are increasing in prevalence, there are few data about hemoptysis in patients with NTM lung disease. This study investigated the characteristics and prognosis of hemoptysis secondary to NTM infection. METHODS: Following a retrospective review of cases managed between 2006 and 2016, 183 patients with NTM lung disease were enrolled and analyzed. RESULTS: Among 183 patients with NTM lung disease, Mycobacterium intracellulare (n = 64, 35%) was the major cause of NTM infection, followed by M. avium (n = 59, 32.2%) and M. abscessus complex (n = 40, 21.9%). Hemoptysis developed in 78 patients (42.6%), among whom 33 (42.3%) required bronchial artery embolization (BAE). Between patients with and without hemoptysis, there were no significant differences with respect to sex, radiographic manifestations, distribution over 3 lobes on chest computed tomography, history of pulmonary tuberculosis, antiplatelet or anticoagulation therapy, and species of NTM. However, mean age at diagnosis was significantly lower in the hemoptysis group in univariate and multivariate analyses (65.7 ± 12.8 vs. 59.7 ± 11.8, P = 0.002, odds ratio: 0.969, 95% confidence interval: 0.944-0.996). Among patients with hemoptysis, those requiring medical therapy and those requiring BAE were not significantly different in terms of demographic characteristics, radiographic manifestations, and distribution over 3 lobes. All patients who received BAE showed immediate clinical improvement, no procedure-related complications, and none of them died during the period under review. CONCLUSIONS: NTM lung disease patients commonly experienced hemoptysis without specific risk factors except for relatively young age. Although some patients with hemoptysis needed BAE, the success rate of BAE was high, and there were no serious complications associated with BAE.


Assuntos
Artérias Brônquicas , Embolização Terapêutica/métodos , Hemoptise/etiologia , Hemoptise/terapia , Infecção por Mycobacterium avium-intracellulare/complicações , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Small ; 14(15): e1704116, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29520994

RESUMO

2D layered materials with sensitive surfaces are promising materials for use in chemical sensing devices, owing to their extremely large surface-to-volume ratios. However, most chemical sensors based on 2D materials are used in the form of laterally defined active channels, in which the active area is limited to the actual device dimensions. Therefore, a novel approach for fabricating self-formed active-channel devices is proposed based on 2D semiconductor materials with very large surface areas, and their potential gas sensing ability is examined. First, the vertical growth phenomenon of SnS2 nanocrystals is investigated with large surface area via metal-assisted growth using prepatterned metal electrodes, and then self-formed active-channel devices are suggested without additional pattering through the selective synthesis of SnS2 nanosheets on prepatterned metal electrodes. The self-formed active-channel device exhibits extremely high response values (>2000% at 10 ppm) for NO2 along with excellent NO2 selectivity. Moreover, the NO2 gas response of the gas sensing device with vertically self-formed SnS2 nanosheets is more than two orders of magnitude higher than that of a similar exfoliated SnS2 -based device. These results indicate that the facile device fabrication method would be applicable to various systems in which surface area plays an important role.

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