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A black phosphorus (BP)-based reusable biosensor platform is developed for the repeated and real-time detection of cortisol using antibody-conjugated magnetic particle (MP) structures as a refreshable receptor. Here, we took advantage of the low-noise characteristics of a mechanically exfoliated BP-based field-effect transistor (FET) and hybridized it with anti-cortisol antibody-functionalized MPs to build a highly sensitive cortisol sensor. This strategy allowed us to detect cortisol down to 1 aM in real time and discriminate cortisol from other hormones. In this case, we could easily remove MPs with used antibodies from the surface of a BP-FET and reuse the chip for up to eight repeated sensing operations. Moreover, since our platform could be fabricated using conventional photolithography techniques and the sensor can be reused multiple times, one should be able to significantly reduce operation costs for practical applications. Furthermore, this method could be utilized to detect different hormones with high sensitivity and selectivity in complex environments such as artificial saliva solutions. In this respect, our reusable BP-FET biosensing platform can be a powerful tool for versatile applications such as clinical diagnosis and basic biological analysis by conjugating various antibodies.
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Técnicas Biossensoriais , Hidrocortisona , Hidrocortisona/análise , Saliva/química , Fósforo , Magnetismo , AnticorposRESUMO
BACKGROUND: Although iron deficiency (ID) is an important and treatable risk factor for heart failure (HF), data on ID are scarce in Asian patients with HF. Therefore, we sought to determine the prevalence and clinical characteristics of ID in hospitalized Korean patients with HF. METHODS: In this prospective, multicenter cohort study, 461 patients with acute HF seen at five tertiary centers from January to November 2019 in Korea were enrolled. ID was defined as serum ferritin < 100 µg/L or ferritin 100-299 µg/L in combination with transferrin saturation < 20%. RESULTS: The patients' mean age was 67.6 ± 14.9 years, and 61.8% were male. Among total 461 patients, ID was present in 248 patients (53.8%). The prevalence of ID was significantly higher in women than in men (65.3% vs. 47.3%, P < 0.001). In a multivariable logistic regression analysis, the independent predictors of ID were female sex (odds ratio [OR], 2.19; 95% confidence interval [CI], 1.47-3.30), valvular heart disease (OR, 2.10; 95% CI, 1.10-4.17), higher heart rate (OR, 1.10; 95% CI, 1.01-1.21), anemia (OR, 1.60; 95% CI, 1.07-2.40), and the use of clopidogrel (OR, 1.56; 95% CI, 1.00-2.45). Among women, the prevalence of ID did not significantly differ between younger and older women (< 65 years: 73.7% vs. ≥ 65 years: 63.0%, P = 0.222), those with low and high body mass index (BMI < 25 kg/m²: 66.2% vs. BMI ≥ 25 kg/m²: 69.6%, P = 0.703), or those with low and high natriuretic peptide (NP) levels (NP < median: 69.8% vs. NP ≥ median: 61.1%, P = 0.295). Only 0.2% patients with acute HF received intravenous iron supplementation in Korea. CONCLUSION: The prevalence of ID is high in hospitalized Korean patients with HF. Because ID cannot be diagnosed by clinical parameters, routine laboratory examinations are necessary to identify patients with ID. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04812873.
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Insuficiência Cardíaca , Deficiências de Ferro , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Prospectivos , Estudos de Coortes , República da Coreia/epidemiologia , Deficiências de Ferro/complicações , Deficiências de Ferro/epidemiologia , Insuficiência Cardíaca/complicações , Prevalência , Modelos Logísticos , Fatores de RiscoRESUMO
BACKGROUND: Data illustrating the impact of atopic dermatitis (AD) on lives of adults with AD in South Korea are limited. OBJECTIVE: To assess the AD disease severity and its impact on quality of life (QoL) in patients with AD from South Korea. METHODS: Patients with AD utilizing the specialist dermatology services of major hospitals in South Korea were assessed for disease severity using Eczema Area and Severity Index (EASI) score, for QoL using Dermatology Life Quality Index (DLQI) (for QoL), and for comorbidities and treatment experience via retrospective review of 12-month medical records. Clinical and sociodemographic characteristics were also measured. RESULTS: Of the 1,163 patients, 695 (59.8%) were men (mean age [years]±standard deviation: 31.6±12.1). Overall, 52.9% (n=615) patients had moderate-to-severe disease (EASI>7). The QoL of 72.3% (n=840) patients was affected moderately-to-severely (DLQI score: 6~30). Systemic immunosuppressants were used ≥1 over past 12 months in 51.9% (n=603) patients, and the most commonly used were cyclosporines (45.7%, n=531) and systemic corticosteroids (40.5%, n=471). Approximately, 10.8% (n=126) patients consulted or received treatment for AD-related eye problem. Of these, 40% (n=50) patients reported poor, very poor, or completely blind status; approximately, 16.7% patients (n=192) reported having depression or anxiety; and 35.5% (n=410) reported suicidal ideation or suicidal attempt. CONCLUSION: A large proportion of patients had moderate-to-severe AD, a compromised QoL, and ocular or mental health comorbidities, indicating a high disease burden despite systemic treatment. These findings highlight the importance of a holistic approach for the evaluation and treatment of patients with AD.
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The objectives of this study were to develop insect-resistant adhesives and apply them to a cardboard packaging system for preventing Plodia interpunctella (Hübner) (Lepidoptera: Pyralidae) larvae infestation. Cinnamon essential oil (CO), an insecticide, was encapsulated with maltodextrin (CS/MD/CO), ß-cyclodextrin (CS/ß-CD/CO), and polyvinyl alcohol (CS/PVA/CO) in corn starch (CS) paste. This resulted in a sustained and gradual release of CO from the starch-based insect-proof adhesives. Penetration pathways of insects into corrugated cardboard boxes were investigated through the use of a screening test for infestation profiling. Microscopic images of encapsulated CO in an oil in water (O/W) emulsion were observed to confirm the morphology of the adhesives. Adhesion forces of CS, CS/CO, CS/MD/CO, CS/ß-CD/CO, and CS/PVA/CO were determined to be 6.2 N, 4.0 N, 3.1 N, 6.0 N, and 5.8 N, respectively. Consequently, significant decreases of adhesion force in the CS/CO and CS/MD/CO were found to be due to the presence of the surfactant (Span® 80) and the low adhesive properties of MD. The duration of the insecticidal activities of the developed adhesives was evaluated by measuring their release rates for 14 days and repellent profiles up to 24 hr and 40 days. As a result, CS/ß-CD/CO and CS/PVA/CO were found to have an inhibited rapid release and sustained repellent profiles. In conclusion, CS/ß-CD/CO and CS/PVA/CO were determined to be suitable for encapsulation models and could be applied to industrial cardboard containers to prevent cases of insect invasion. PRACTICAL APPLICATION: Corn starch-based natural adhesives with an insect-proof property were applied to food containers consisted of corrugated cardboard boxes. Cornflake cereal packaging using insect-proof corrugated cardboard successfully prohibited pest invasion in commercial food distribution simulation model. Developed insecticidal adhesives are able to control insect penetration in distribution and storage steps.
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Cinnamomum zeylanicum/química , Repelentes de Insetos/farmacologia , Mariposas/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Adesivos , Animais , Embalagem de Alimentos/métodos , Repelentes de Insetos/química , Insetos/efeitos dos fármacos , Larva/efeitos dos fármacos , Óleos Voláteis/química , Óleos de Plantas/química , Álcool de Polivinil , AmidoRESUMO
To determine whether the assessment of individual plaques is superior in predicting the progression to obstructive coronary artery disease (CAD) on serial coronary computed tomography angiography (CCTA) than per-patient assessment. From a multinational registry of 2252 patients who underwent serial CCTA at a ≥ 2-year inter-scan interval, patients with only non-obstructive lesions at baseline were enrolled. CCTA was quantitatively analyzed at both the per-patient and per-lesion level. Models predicting the development of an obstructive lesion at follow up using either the per-patient or per-lesion level CCTA measures were constructed and compared. From 1297 patients (mean age 60 ± 9 years, 43% men) enrolled, a total of 3218 non-obstructive lesions were identified at baseline. At follow-up (inter-scan interval: 3.8 ± 1.6 years), 76 lesions (2.4%, 60 patients) became obstructive, defined as > 50% diameter stenosis. The C-statistics of Model 1, adjusted only by clinical risk factors, was 0.684. The addition of per-patient level total plaque volume (PV) and the presence of high-risk plaque (HRP) features to Model 1 improved the C-statistics to 0.825 [95% confidence interval (CI) 0.823-0.827]. When per-lesion level PV and the presence of HRP were added to Model 1, the predictive value of the model improved the C-statistics to 0.895 [95% CI 0.893-0.897]. The model utilizing per-lesion level CCTA measures was superior to the model utilizing per-patient level CCTA measures in predicting the development of an obstructive lesion (p < 0.001). Lesion-level analysis of coronary atherosclerotic plaques with CCTA yielded better predictive power for the development of obstructive CAD than the simple quantification of total coronary atherosclerotic burden at a per-patient level.Clinical Trial Registration: ClinicalTrials.gov NCT0280341.
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Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Placa Aterosclerótica , Idoso , Progressão da Doença , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sistema de Registros , Medição de Risco , Ruptura Espontânea , Fatores de TempoRESUMO
BACKGROUND: Endoplasmic reticulum (ER) calcium depletion-induced ER stress is a crucial signal for keratinocyte differentiation and barrier homeostasis, but its effects on the epidermal tight junction (TJ) have not been characterized. Ultraviolet B (UVB) causes ER calcium release in keratinocytes and disrupts epidermal TJ, however, the involvement of ER stress in the UVB-induced TJ alterations remains unknown. OBJECTIVES: To investigate the effect of ER stress by pharmacological ER calcium depletion or UVB on the TJ integrity in normal human epidermal keratinocytes (NHEK). METHODS: NHEK were exposed to ER calcium pump inhibitor thapsigargin (Tg) or UVB. ER stress markers and TJ molecules expression, TJ and F-actin structures, and TJ barrier function were analyzed. RESULTS: Tg or UVB exposure dose-dependently triggered unfolded protein response (UPR) in NHEK. Low dose Tg induced the IRE1α-XBP1 pathway and strengthened TJ barrier. Contrary, high dose Tg activated PERK phosphorylation and disrupted TJ by F-actin disorganization. UVB disrupted TJ and F-actin structures dose dependently. IRE1α RNase inhibition induced or exacerbated TJ and F-actin disruption in the presence of low dose Tg or UVB. High dose Tg increased RhoA activity. 4-PBA or Rho kinase (ROCK) inhibitor partially prevented the disruption of TJ and F-actin following high dose Tg or UVB. CONCLUSIONS: ER stress has bimodal effects on the epidermal TJ depending on its intensity. The IRE1α pathway is critical for the maintenance of TJ integrity during mild ER stress. Severe ER stress-induced UPR or ROCK signalling mediates the disruption of TJ through cytoskeletal disorganization during severe ER stress.
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Cálcio/metabolismo , Estresse do Retículo Endoplasmático/efeitos da radiação , Queratinócitos/patologia , Junções Íntimas/patologia , Raios Ultravioleta/efeitos adversos , Amidas/farmacologia , Linhagem Celular , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/patologia , Retículo Endoplasmático/efeitos da radiação , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Endorribonucleases/metabolismo , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos da radiação , Fenilbutiratos/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Piridinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Junções Íntimas/efeitos da radiação , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Resposta a Proteínas não Dobradas/efeitos da radiação , Quinases Associadas a rho/antagonistas & inibidores , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
OBJECTIVES: To investigate a way to reduce infectious complication after transrectal ultrasonography-guided prostate biopsy (TRUS-Bx), we planned a randomized trial to determine whether the use of the povidone-iodine suppository is effective in preventing infectious complications. METHODS: This study prospectively assessed 250 patients who underwent TRUS-Bx during December 2014 and May 2016. Clinical questionnaire responses and safety were evaluated. Povidone-iodine suppository after glycerin enema was performed 1 to 2âhours before TRUS-Bx. Both groups received the prophylactic antibiotics (ceftriaxone 2.0âg) 30 to 60 minutes before TRUS-Bx. No antibiotics were prescribed after TRUS-Bx. RESULTS: The 120 were assigned in the treatment group using povidone-iodine suppository and 130 were assigned in the control group. There was no significant difference of clinicopathologic features including age, prostate-specific antigen and cancer detection rate in both groups (Pâ>â.05). No infectious and non-infectious complications were reported in both groups. Povidone-iodine suppository-related side effects were not reported. No significant differences in international prostate symptom score, sexual health inventory for men score, and European Organization for Research and Treatment of Cancer Quality of Life questionnaire scores were found between the 2 groups (Pâ>â.05). No changes in each questionnaire scores between before and after TRUS-Bx were observed. CONCLUSIONS: Despite satisfying the predefined sample size, we could not prove the hypothesis that the use of povidone-iodine suppositories after TRUS-Bx would reduce infectious complications. A large-scale, multicenter, prospective study is needed to fully evaluate the clinical efficacy and safety of povidone-iodine suppository prior to TRUS-Bx.
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Anti-Infecciosos Locais/administração & dosagem , Antibioticoprofilaxia/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Povidona-Iodo/administração & dosagem , Próstata/patologia , Idoso , Anti-Infecciosos Locais/efeitos adversos , Ceftriaxona/administração & dosagem , Ceftriaxona/efeitos adversos , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Povidona-Iodo/efeitos adversos , Estudos Prospectivos , SupositóriosRESUMO
Cobalt-induced cardiomyopathy is a well-known but uncommon disease, and the physician must maintain a high index of suspicion in order to make a timely diagnosis. We report two patients with cobalt-induced cardiomyopathy. Both patients developed progressively worsening symptoms of cobalt toxicity following revision of a fractured ceramic-on-ceramic total hip replacement to a metal-on-polyethylene bearing. In both patients, echocardiography showed LV hypertrophy, biventricular systolic dysfunction, and a large amount of pericardial effusion. Due to decompensated heart failure, both patients were initially considered candidates for heart transplantation. One patient was diagnosed with cobalt-induced cardiomyopathy before transplantation. He received cobalt chelation therapy and revision surgery, which led to complete recovery of heart function. In the other patient, the diagnosis was not made until the time of heart transplantation. The gross examination of the explanted heart revealed typical features of cobalt cardiotoxicity, which was then diagnosed as cobalt-induced cardiomyopathy. These cases emphasise the importance of early diagnosis and prompt treatment of cobalt intoxication.
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Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/instrumentação , Cardiomiopatias/induzido quimicamente , Cobalto/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Prótese de Quadril/efeitos adversos , Disfunção Ventricular Esquerda/induzido quimicamente , Biópsia , Procedimentos Cirúrgicos Cardíacos , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/fisiopatologia , Cardiomiopatias/terapia , Cardiotoxicidade , Quelantes/uso terapêutico , Progressão da Doença , Ecocardiografia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Transplante de Coração , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Recuperação de Função Fisiológica , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/terapiaRESUMO
BACKGROUND: The aim of the study is examine the impact of non-obstructive (<50%stenosis) left main (LM) disease on the natural history of coronary artery disease using serial coronary computed tomography angiography (CTA). METHODS: CTAs from the PARADIGM (Progression of atherosclerotic plaque determined by computed tomographic angiography imaging) study, a prospective multinational registry of patients who underwent serial CTA at a ≥2 year interval were analyzed. Those without evidence of CAD on their baseline scan were excluded, as were those with obstructive left main disease. Coronary artery vessels and their branches underwent quantification of: plaque volume and composition; diameter stenosis; presence of high-risk plaque. RESULTS: Of 944 (62⯱â¯9 years, 60% male) who had evidence of CAD at baseline, 444 (47%) had LM disease. Those with LM disease had a higher baseline plaque volume (194.8⯱â¯221mm3 versus 72.9⯱â¯84.3mm3, pâ¯<â¯0.001) and a higher prevalence of high-risk plaque (17.5% versus 13%, pâ¯<â¯0.001) than those without LM disease. On multivariable general linear model, patients with LM disease had greater annual rates of progression of total (26.5⯱â¯31.4mm3/yr versus 14.9⯱â¯20.1mm3/yr, pâ¯<â¯0.001) and calcified plaque volume (17⯱â¯24mm3/yr versus 7⯱â¯11mm3/yr, pâ¯<â¯0.001), with no difference in fibrous, fibrofatty or necrotic core plaque components. CONCLUSION: The presence of non-obstructive LM disease is associated with greater rates of plaque progression and a higher prevalence of high-risk plaque throughout the entire coronary artery tree compared to CAD without LM involvement. Our data suggests that non-obstructive LM disease may be a marker for an aggressive phenotype of CAD that may benefit from more intensive treatment strategies.
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Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Idoso , Distribuição de Qui-Quadrado , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/patologia , Estenose Coronária/epidemiologia , Estenose Coronária/patologia , Vasos Coronários/patologia , Progressão da Doença , Feminino , Fibrose , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Necrose , Placa Aterosclerótica , Valor Preditivo dos Testes , Prevalência , Sistema de Registros , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Calcificação Vascular/patologiaRESUMO
Ascorbic acid is one of the most well-known nutritional supplement and antioxidant found in fruits and vegetables. Calcium ascorbate has been developed to mitigate the gastric irritation caused by the acidity of ascorbic acid. The aim of this study was to compare calcium ascorbate and ascorbic acid, focusing on their antioxidant activity and effects on gastric juice pH, total acid output, and pepsin secretion in an in vivo rat model, as well as pharmacokinetic parameters. Calcium ascorbate and ascorbic acid had similar antioxidant activity. However, the gastric fluid pH was increased by calcium ascorbate, whereas total acid output was increased by ascorbic acid. In the rat pylorus ligation-induced ulcer model, calcium ascorbate increased the gastric fluid pH without changing the total acid output. Administration of calcium ascorbate to rats given a single oral dose of 100 mg/kg as ascorbic acid resulted in higher plasma concentrations than that from ascorbic acid alone. The area under the curve (AUC) values of calcium ascorbate were 1.5-fold higher than those of ascorbic acid, and the Cmax value of calcium ascorbate (91.0 ng/ml) was higher than that of ascorbic acid (74.8 ng/ml). However, their Tmax values were similar. Thus, although calcium ascorbate showed equivalent antioxidant activity to ascorbic acid, it could attenuate the gastric high acidity caused by ascorbic acid, making it suitable for consideration of use to improve the side effects of ascorbic acid. Furthermore, calcium ascorbate could be an appropriate antioxidant substrate, with increased oral bioavailability, for patients with gastrointestinal disorders.
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Recently, photodynamic therapy (PDT) has been intensively investigated as a useful modality for the treatment of various cancers. In addition, near infrared (NIR) photothermal therapy (PTT) using gold nanocarriers has attracted particular interest as a hyperthermia strategy. In this study, gold nanorod (AuNR)-photosensitizer conjugates with glutathione-sensitive linkages were designed for PDT and PTT. Several kinds of AuNRs with different aspect ratios were synthesized and modified with FA-conjugated block copolymers (FA-PEG-P(Asp)-DHLA) and Chlorin e6 (Ce6) as a photosensitizer. The surface-modified AuNRs showed excellent stability and solubility in aqueous solution. In particular, FA-PEG-P(Asp)-DHLA-AuNR100-SS-Ce6 with a 3.84 aspect ratio exhibited strong photothermal effects, enhanced singlet oxygen generation, and marked phototoxicity. Based on these results, we suggest that AuNR-photosensitizer conjugates with glutathione-sensitive linkages have potential application in PDT/PTT for effective clinical treatment of various cancers.
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Ouro/farmacologia , Hipertermia Induzida/métodos , Terapia de Alvo Molecular/métodos , Nanotubos , Neoplasias/terapia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Células A549 , Terapia Combinada/métodos , Humanos , Células MCF-7 , Modelos BiológicosRESUMO
BACKGROUND: To investigate the feasibility of active surveillance (AS) in biopsy Gleason score (GS) 3 + 4 prostate cancer (PCa), we compared the outcomes of biopsy GS 3 + 3 and 3 + 4 PCa after radical prostatectomy. PATIENTS AND METHODS: We analyzed the data of 1491 patients undergoing radical prostatectomy for biopsy GS 3 + 3 or 3 + 4 PCa who fulfilled the low-risk criteria of the National Comprehensive Cancer Network guidelines regardless of GS. The favorable GS 3 + 4 group was defined as having core involvement ≤ 50%, prostate-specific antigen density ≤ 0.2 ng/mL/cm3, and number of positive cores ≤ 2 (maximal 1 core of GS 3 + 4). RESULTS: The GS 3 + 4 group showed significantly worse pathologic outcomes, including pathologic GS, pathologic stage, and seminal vesicle invasion rate (all P < .001), as well as worse biochemical recurrence-free survival (P < .001) than the GS 3 + 3 group. However, the favorable GS 3 + 4 subgroup showed no significant differences in the pathologic outcomes (all P > .05) and in biochemical recurrence-free survival (P = .817) compared to the GS 3 + 3 group. CONCLUSION: Despite the application of low-risk criteria, GS 3 + 4 PCa patients showed significantly worse outcomes than GS 3 + 3 patients. However, favorable GS 3 + 4 patients showed comparable clinicopathologic outcomes with GS 3 + 3 patients, suggesting possible expansion of AS for the favorable GS 3 + 4 group.
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Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Conduta Expectante/métodos , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Seleção de Pacientes , Prognóstico , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/sangue , Análise de SobrevidaRESUMO
We aimed to identify prognostic factors associated with progression-free survival (PFS) and overall survival (OS) in metastatic renal cell carcinoma (mRCC) patients treated with sorafenib. We investigated 177 patients, including 116 who received sorafenib as first-line therapy, using the Cox regression model. During a median follow-up period of 19.2 months, the PFS and OS were 6.4 and 32.6 months among all patients and 7.4 months and undetermined for first-line sorafenib-treated patients, respectively. Clinical T3-4 stage (hazard ratio [HR] 2.56) and a primary tumor size >7 cm (HR 0.34) were significant prognostic factors for PFS among all patients, as were tumor size >7 cm (HR 0.12), collecting system invasion (HR 5.67), and tumor necrosis (HR 4.11) for OS (p < 0.05). In first-line sorafenib-treated patients, ≥4 metastatic lesions (HR 28.57), clinical T3-4 stage (HR 4.34), collecting system invasion (univariate analysis HR 2.11; multivariate analysis HR 0.07), lymphovascular invasion (HR 13.35), and tumor necrosis (HR 6.69) were significant prognosticators of PFS, as were bone metastasis (HR 5.49) and clinical T3-4 stages (HR 4.1) for OS (p < 0.05). Our study thus identified a number of primary tumor-related characteristics as important prognostic factors in sorafenib-treated mRCC patients.
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Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/secundário , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Neoplasias Ósseas/secundário , Demografia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Niacinamida/uso terapêutico , Prognóstico , Estudos Retrospectivos , SorafenibeAssuntos
Queratinócitos/metabolismo , Melanose/metabolismo , Receptor PAR-2/metabolismo , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Animais , Avaliação Pré-Clínica de Medicamentos , Humanos , Melanose/tratamento farmacológico , Camundongos , Estudos Retrospectivos , Telangiectasia/metabolismo , Regulação para CimaRESUMO
BACKGROUND: The Bonny Method of Guided Imagery and Music uses music and imagery to access and explore personal emotions associated with episodic memories. Understanding the neural mechanism of guided imagery and music (GIM) as combined stimuli for emotional processing informs clinical application. OBJECTIVE: We performed functional magnetic resonance imaging (fMRI) to demonstrate neural mechanisms of GIM for negative emotional processing when personal episodic memory is recalled and re-experienced through GIM processes. METHODS: Twenty-four healthy volunteers participated in the study, which used classical music and verbal instruction stimuli to evoke negative emotions. To analyze the neural mechanism, activated regions associated with negative emotional and episodic memory processing were extracted by conducting volume analyses for the contrast between GIM and guided imagery (GI) or music (M). RESULTS: The GIM stimuli showed increased activation over the M-only stimuli in five neural regions associated with negative emotional and episodic memory processing, including the left amygdala, left anterior cingulate gyrus, left insula, bilateral culmen, and left angular gyrus (AG). Compared with GI alone, GIM showed increased activation in three regions associated with episodic memory processing in the emotional context, including the right posterior cingulate gyrus, bilateral parahippocampal gyrus, and AG. No neural regions related to negative emotional and episodic memory processing showed more activation for M and GI than for GIM. CONCLUSIONS: As a combined multimodal stimulus, GIM may increase neural activations related to negative emotions and episodic memory processing. Findings suggest a neural basis for GIM with personal episodic memories affecting cortical and subcortical structures and functions.
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Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Emoções/fisiologia , Imagens, Psicoterapia , Imageamento por Ressonância Magnética/métodos , Memória Episódica , Música/psicologia , Adulto , Mapeamento Encefálico , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/fisiologia , Feminino , Humanos , Masculino , Rememoração Mental , Musicoterapia , Rede Nervosa/anatomia & histologia , Rede Nervosa/fisiologia , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Giro Para-Hipocampal , Adulto JovemRESUMO
In the present study, we aimed to investigate the anticancer properties of Theracurmin®, a novel form of the yellow curry pigment curcumin, as well as explore the molecular mechanisms of the potential anticancer effects of Theracurmin® on human prostate cancer and bladder cancer cells in vitro. The proliferation of cancer cells was examined by using the Cell Counting Kit-8. The clonogenic growth potential was determined by clonogenic assay. Cell cycle distribution was evaluated by flow cytometry using propidium iodide staining. Western blot analysis was applied to explore the expression patterns of molecules associated with apoptotic cell death and cell cycle checkpoint. We noted that Theracurmin® and curcumin exhibited similar anticancer effects in both androgen-dependent and -independent human prostate cancer cells in a dose- and time-dependent manner. These agents reduced cell viability and clonogenic growth potential by inducing apoptosis and cell cycle disturbance in human prostate cancer cells. Theracurmin® and curcumin also exerted marked anticancer effects on human bladder cancer cells, even in cisplatin-resistant T24R2 cells, in a dose- and time-dependent manner. Moreover, Theracurmin® and curcumin treatment decreased cell viability and clonogenicity via induction of apoptotic cell death and cell cycle dysregulation in human bladder cancer cells. In conclusion, our study suggests that Theracurmin® has potential as an anticancer agent in complementary and alternative medicine for these urological cancers.
Assuntos
Apoptose/efeitos dos fármacos , Curcumina/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Antineoplásicos Fitogênicos/administração & dosagem , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Bexiga Urinária/patologiaRESUMO
OBJECTIVE: To examine the association of food insufficiency with dietary intake and eating and health behaviours. DESIGN: A cross-sectional study. SETTING: Data were obtained from a secondary source, the Fifth Korea National Health and Nutrition Examination Survey (2010-2012). SUBJECTS: The sample size consisted of 15 603 adults over 19 years of age (8898 households). RESULTS: Significant differences in socio-economic factors were observed according to food insufficiency level (P<0·05), but BMI was similar among groups. Regarding macronutrients, lower protein intake and higher carbohydrate intake were found in the severely food-insufficient group, but we found no association with fat intake. Regarding micronutrients, Ca, Fe, vitamin A, thiamin, riboflavin niacin and vitamin C intakes were negatively associated with food insufficiency level (P trend<0·05). Consumption of different food groups, such as meat, fish, eggs and beans, vegetables and fruits, was significantly lower as food insufficiency level decreased after controlling for all possible variables; food group consumption also differed by sex. Overall eating and health behaviours were poorer in the mildly and severely food-insufficient groups, who received more food assistance but less nutritional education. CONCLUSIONS: Our results showed that dietary intake as well as eating and health behaviours are adversely associated with food insufficiency. These findings suggest that specific strategies to help food-insufficient individuals should be developed in order to improve their dietary quality and health status.
Assuntos
Povo Asiático , Dieta , Características da Família , Abastecimento de Alimentos , Fatores Socioeconômicos , Adulto , Idoso , Índice de Massa Corporal , Estudos Transversais , Ovos , Ingestão de Energia , Fabaceae , Feminino , Assistência Alimentar , Frutas , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Carne , Pessoa de Meia-Idade , Avaliação Nutricional , Inquéritos Nutricionais , República da Coreia , Verduras , Adulto JovemRESUMO
OBJECTIVE: To evaluate the efficacy and safety of sorafenib for Korean patients with metastatic renal cell carcinoma (mRCC). METHODS: A total of 177 mRCC patients using sorafenib as first- (N = 116), second- (N = 43), and third-line (N = 18) therapies were enrolled from 11 Korean centers between 2006 and 2012. The patient characteristics, therapy duration, tumor response, disease control rate, and tolerability were assessed at baseline and at routine follow-ups, and the progression-free survival (PFS) and overall survival (OS) times and rates were analyzed. RESULTS: Among all patients, 18 (10.2%) stopped sorafenib treatment for a median of 1.7 weeks, including 15 (8.5%) who discontinued the drug, while 40 (22.6%) and 12 (6.8%) patients required dose reductions and drug interruptions, respectively. Severe adverse events (AEs) or poor compliance was observed in 64 (36.2%) patients, with 118 (7.4%) ≥grade 3 AEs. During the treatment, one myocardial infarction was observed. The number of ≥grade 3 AEs in the first-line sorafenib group was 71 (6.8% of the total 1048 AEs). During a median follow-up of 17.2 months, the radiologically confirmed best objective response rate, disease control rate, median PFS, and median OS were 22.0%, 53.0%, 6.4 months (95% confidence interval [CI], 5.2-8.9), and 32.6 months (95% CI, 27.3-63.8) for the total 177 sorafenib-treated patients, respectively, and 23.2%, 56.0%, 7.4 months (95% CI, 5.5-10.5), and not reached yet (95% CI, 1.0-31.1) for the first-line sorafenib group, respectively. CONCLUSIONS: Sorafenib produced tolerable safety, with a ≥grade 3 AE rate of 7.4% and an acceptable disease control rate (53.0%) in Korean mRCC patients.
Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Niacinamida/análogos & derivados , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/farmacologia , Segurança , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Niacinamida/efeitos adversos , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Estudos Retrospectivos , Sorafenibe , Resultado do TratamentoRESUMO
PURPOSE: Published data have shown heterogeneous outcomes for high-risk prostate cancer. Thus, we tried to identify more precise risk stratification system for contemporary high-risk prostate cancer. METHODS: Classifying patients according to National Comprehensive Cancer Network risk groups, we reviewed data of 1,905 men who underwent radical prostatectomy (RP) at our institution from 2006 to 2013. For our analyses, high-risk prostate cancers meeting at least one of two following factors were categorized as unfavorable high-risk prostate cancer: biopsy primary Gleason pattern 5 and/or multiple (≥2) high-risk criteria present. All other men with high-risk prostate cancer were designated as having favorable high-risk disease. Postoperative outcomes, including biochemical recurrence-free survivals were assessed and compared via log-rank test and Cox proportional hazards model. RESULTS: In multivariable analysis, primary Gleason 5 pattern on biopsy (p = 0.008) and multiple (≥2) high-risk criteria (p < 0.001) were observed to be independent predictors of the risk of biochemical recurrence amongst high-risk group undergoing RP. Favorable high-risk prostate cancer group showed a significantly higher 5-year biochemical recurrence-free survival than unfavorable high-risk group (56.35 vs. 18.75 %; log-rank test: p < 0.001). Favorable high-risk group demonstrated significantly lower 5-year biochemical recurrence-free survival than intermediate-risk group (56.07 vs. 82.05 %; log-rank test: p < 0.001). CONCLUSIONS: A significant heterogeneity existed in biochemical outcomes of contemporary patients with high-risk prostate cancer who underwent definitive RP. According to primary Gleason pattern and number of high-risk criteria present, high-risk group should be stratified further into favorable and unfavorable disease.
Assuntos
Recidiva Local de Neoplasia/diagnóstico , Prostatectomia/mortalidade , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/cirurgia , Idoso , Seguimentos , Humanos , Masculino , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/classificação , Neoplasias da Próstata/mortalidade , Fatores de Risco , Taxa de SobrevidaRESUMO
OBJECTIVE: To identify an appropriate risk stratification system for intermediate-risk prostate cancer (PCa). PATIENTS AND METHODS: We reviewed the data on 1559 patients who were treated with radical prostatectomy (RP) at our institution between 2005 and 2013 and classified them according to National Comprehensive Cancer Network (NCCN) risk groups. For our analyses, intermediate-risk PCa was designated as unfavourable intermediate-risk PCa if it met at least one of the following two criteria: biopsy Gleason score 4 + 3 and/or presence of ≥ 2 intermediate-risk criteria. All other men with intermediate-risk PCa were designated as having favourable intermediate-risk disease. Postoperative outcomes, including biochemical recurrence (BCR)-free survival, were calculated and compared using the log-rank test and Cox proportional hazards model. RESULTS: In multivariable analysis, biopsy Gleason score 4 + 3 and multiple (≥ 2) intermediate-risk criteria were observed to be independent predictors of BCR risk among men in the intermediate-risk group undergoing RP. The favourable intermediate-risk group had a significantly higher 5-year BCR-free survival compared with the unfavourable intermediate-risk group (87.5 vs 66.5%; P < 0.001). The unfavourable intermediate-risk group had significantly higher 5-year BCR-free survival than the high-risk group (66.5 vs 47.9%; P < 0.001) while the favourable intermediate-risk group had significantly lower 5-year BCR-free survival than the low-risk group (87.5 vs 93.5%; P = 0.002). CONCLUSIONS: A marked heterogeneity exists in the biochemical outcomes of contemporary patients with intermediate-risk PCa who undergo definitive RP. According to biopsy Gleason score and number of intermediate-risk criteria present, the intermediate-risk group should be sub-divided into those with favourable and unfavourable intermediate-risk disease.