RESUMO
In this paper, a quadratic convolution neural network (QCNN) using both audio and vibration signals is utilized for bearing fault diagnosis. Specifically, to make use of multi-modal information for bearing fault diagnosis, the audio and vibration signals are first fused together using a 1 × 1 convolution. Then, a quadratic convolution neural network is applied for the fusion feature extraction. Finally, a decision module is designed for fault classification. The proposed method utilizes the complementary information of audio and vibration signals, and is insensitive to noise. The experimental results show that the accuracy of the proposed method can achieve high accuracies for both single and multiple bearing fault diagnosis in the noisy situations. Moreover, the combination of two-modal data helps improve the performance under all conditions.
RESUMO
In this work, NiCo2S4-graphene hybrids (NCS@G) with high electrochemical performance were prepared using a hydrothermal method. The response surface methodology (RSM), along with a central composite design (CCD), was used to investigate the effect of independent variables (G/NCS, hydrothermal time, and S/Ni) on the specific capacitances of the NCS@G/Ni composite electrodes. RSM analysis revealed that the developed quadratic model with regression coefficient values of more than 0.95 could be well adapted to represent experimental results. Optimized preparation conditions for NCS@G were G/NCS = 6.0%, hydrothermal time = 10.0, and S/Ni = 6.0 of NCS@G (111) sample. The maximum specific capacitance of NCS@G (111)/Ni fabricated at the optimal condition is about 216% higher than the best result obtained using the conventional experimental method. The enhanced capacitive performance of the NCS@G (111) sample can be attributed to the synergistic effect between NCS nanoparticles and graphene, which has the meso/macropores conductive network and low diffusion resistance. Notably, the NCS@G (111) could not only provide numerous reaction sites but also prevent the restacking of graphene layers. Furthermore, a supercapattery cell was fabricated with an (G + AC)/Ni anode, a NCS@G (111)/Ni cathode, and a carboxymethyl cellulose-potassium hydroxide (CMC-KOH) gel electrolyte. The NCS@G (111)//(G + AC) demonstrates an outstanding energy density of 80 Wh kg-1 at a power density of 4 kW kg-1, and a good cycling performance of 75% after 5000 cycles at 2 A g-1. Applying the synthesis strategy of RSM endows remarkable capacitive performance of the hybrid materials, providing an economical pathway to design promising composite electrode material and fabricate high-performance energy storage devices.
RESUMO
BACKGROUND: Inappropriate management of medications is a major threat to homebound patients with chronic conditions. Despite many efforts in improving medication reconciliation in ambulatory and inpatient settings, little research has focused on home care settings. In 2016, Taiwan initiated the Integrated Home Health Care programme, which was intended to reduce potentially inappropriate medication management and risks of uncontrolled polypharmacy through the integration of different medication sources for chronic conditions among homebound patients. This study investigated factors associated with having home care physicians as an integrated source of medications for chronic conditions among homebound patients. METHOD: This retrospective cohort study enrolled 3142 community-dwelling homebound patients from Taipei City Hospital. Homebound patients' adherence to using home care physicians as an integrated source of chronic condition medications was defined as having all prescriptions for their chronic conditions prescribed by a single home care physician for at least 6 months. Both patient and home care physician characteristics were analysed. Multivariable logistic regression was applied. RESULTS: Of the 3142 patients with chronic conditions, 1002 (31.9%) had consistently obtained all medications for their chronic illnesses from their home care physicians for 6 months and 2140 (68.1%) had not. The most common chronic diseases among homebound patients were hypertension, diabetes mellitus, dementia, cerebrovascular disease and constipation. Oldest-old patients with poor functional status, fewer daily medications, no co-payment exemption and no recent inpatient experience were more likely to adhere to this medication integration system. In addition, patients whose outpatient physicians were also their home care physicians were more likely to adhere to the system. CONCLUSIONS: The finding suggests that building trust and enhancing communication among homebound patients, caregivers and home care physicians are critical. Patient and provider variations highlight the need for further improvement and policy modification for medication reconciliation and management in home care settings. The improvement in medication management and care integration in home care settings may reduce misuse and polypharmacy and improve homebound patients' safety.
Assuntos
Serviços de Assistência Domiciliar , Pacientes Domiciliares , Médicos , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Humanos , Polimedicação , Estudos RetrospectivosRESUMO
Background: Palliative family conference (PFC) was included in the reimbursement of National Health Insurance to promote palliative care in Taiwan in 2012. Objectives: This study aimed to evaluate the impact of PFC on death in intensive care unit (ICU) and receiving cardiopulmonary resuscitation (CPR) within three days before death. Design: This is a cross-sectional study. Subjects: All patients who died in a public hospital and were admitted to ICU within 30 days before death, from 2013 to 2018, were included. Measurements: The medical records were analyzed to identify information on causes of death, receiving PFC, receiving palliative care consultation, death in ICU, and receiving CPR within three days before death. Multivariate logistic regression was used to assess the independent effects of receiving PFC on the risk of death in ICU and receiving CPR within three days before death. Results: For patients who died and those who did not die in ICU, the proportion of receiving PFC was 45.8% (1818/3973) and 55.0% (808/1468), respectively. For patients who received and those who did not receive CPR within three days before death, the proportion of receiving PFC was 23.9% (140/585) and 51.2% (2486/4856), respectively. PFC was associated with a reduced risk of death in ICU (adjusted odds ratio [AOR]: 0.842; 95% confidence interval [CI]: 0.717-0.988) and a reduced risk of receiving CPR within three days before death (AOR: 0.361; 95% CI: 0.286-0.456). Conclusion: PFC reduces the risk of receiving nonbeneficial aggressive intervention and may improve the quality of end-of-life care.
Assuntos
Reanimação Cardiopulmonar , Assistência Terminal , Estudos Transversais , Morte , Humanos , Unidades de Terapia Intensiva , Cuidados PaliativosRESUMO
A series of heteroatom-containing porous carbons with high surface area and hierarchical porosity were successfully prepared by hydrothermal, chemical activation, and carbonization processes from soybean residues. The initial concentration of soybean residues has a significant impact on the textural and surface functional properties of the obtained biomass-derived porous carbons (BDPCs). SRAC5 sample with a BET surface area of 1945 m2 g-1 and a wide micro/mesopore size distribution, nitrogen content of 3.8 at %, and oxygen content of 15.8 at % presents the best electrochemical performance, reaching 489 F g-1 at 1 A g-1 in 6 M LiNO3 aqueous solution. A solid-state symmetric supercapacitor (SSC) device delivers a specific capacitance of 123 F g-1 at 1 A g-1 and a high energy density of 68.2 Wh kg-1 at a power density of 1 kW kg-1 with a wide voltage window of 2.0 V and maintains good cycling stability of 89.9% capacitance retention at 2A g-1 (over 5000 cycles). The outstanding electrochemical performances are ascribed to the synergistic effects of the high specific surface area, appropriate pore distribution, favorable heteroatom functional groups, and suitable electrolyte, which facilitates electrical double-layer and pseudocapacitive mechanisms for power and energy storage, respectively.
Assuntos
Biomassa , Carbono/química , Capacitância Elétrica , Glycine max/química , Adsorção , Eletroquímica , Eletrodos , Nitrogênio/química , Espectroscopia Fotoeletrônica , Porosidade , Análise Espectral RamanRESUMO
Hypoxia has been shown to be related to osteosarcoma development and progression. Pseudogene MSTO2P was reported to be dysregulated in hepatocellular carcinoma and lung cancer. However, the mechanism by which MSTO2P-modulated osteosarcoma remains unclear. MSTO2P and PD-L1 expression levels were examined by RT-qPCR and westernblot. Tumor cell invasion was determined by tranwell assay. EMT process was probed by determining E-cadherin and Vimentin levels. Soft agar assay was used to examine anchorage-independent growth of osteosarcoma cells. In vivo tumor growth was measured by xenografting tumor experiment. Hypoxia treatment promoted cell growth, invasion and EMT of osteosarcoma cells. MSTO2P knockdown led to attenuated cell growth, invasion and EMT of osteosarcoma cells under hypoxia condition. More interestingly, our data revealed that MSTO2P was positively associated with tumor growth in immunodeficient mice and human clinical tissues. PD-L1 was shown to act as a key effector for MSTO2P-regulated osteosarcoma progression under hypoxia condition. In conclusion, we unravel a novel mechanism for explaining MSTO2P-involved osteosarcoma progression under hypoxia condition, which will facilitate development of potential diagnostic and therapeutical strategies for osteosarcoma.
Assuntos
Antígeno B7-H1/genética , Neoplasias Ósseas/genética , Osteossarcoma/genética , RNA Longo não Codificante/genética , Animais , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Endogâmicos NOD , Camundongos SCID , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Osteossarcoma/patologia , Pseudogenes , Hipóxia TumoralRESUMO
CONTEXT: Patients who died of cancers and those who died of noncancer diseases may receive different end-of-life care. OBJECTIVES: This study aimed to evaluate the trends of utilization of palliative care and aggressive end-of-life care for patients who died of cancers and those who died of noncancer diseases in hospitals. METHODS: The medical records of patients who died in a public hospital because of cancer or other diseases were reviewed. The proportion of those who received palliative care, admitted to intensive care unit (ICU) within 30 days of death, died in ICU, and received cardiopulmonary resuscitation (CPR) within three days of death in 2013-2014, 2015-2016, and 2017-2018, respectively, was investigated. Multivariate logistic regression was applied to evaluate the independent effects of various factors on the risk of receiving aggressive end-of-life care. RESULTS: Significant trends of increase in receiving palliative care were found. The proportion of patients who died of noncancer diseases and received palliative care was lower than that of those who died of cancers. Palliative care was associated with a reduced risk of ICU admission within 30 days of death (adjusted odds ratio [AOR] 0.361), death in ICU (AOR 0.208), and receiving CPR within three days of death (AOR 0.057). Patients who died of noncancer diseases had a higher risk of ICU admission within 30 days of death (AOR 5.016), death in ICU (AOR 5.086), and receiving CPR within three days of death (AOR 3.274). CONCLUSION: Utilization of palliative care is increasing. Patients who died of noncancer diseases received less palliative care but more aggressive end-of-life care than those who died of cancers.
Assuntos
Cuidados Paliativos na Terminalidade da Vida , Neoplasias , Assistência Terminal , Hospitais , Humanos , Neoplasias/terapia , Cuidados Paliativos , Estudos RetrospectivosRESUMO
BACKGROUND/PURPOSE: Very few studies have investigated the screening tools that aim to identify the need of palliative care services among patients with advanced cancer or chronic non-malignant diseases. This study validated the one-page Taiwanese version-Palliative Care Screening Tool (TW-PCST) for screening inpatients with potential palliative care needs. METHOD: ROC curves were produced to examine the sensitivities and specificities at varying cut-off points. The optimal cut-off value to predict mortality was justified using the Youden's index. The screening was conducted on the first day of admission. Patients were prospectively followed-up after the baseline assessment. Three followed-up periods, namely 14 days, 90 days, and 180 days were analyzed. RESULTS: A total of 21,596 patients were screened. AUCs for all cut-off scores varied from 0.84 to 0.88. A total-ABCD score ≥2 gave the highest Youden's index for 90 days and 180 days follow-up periods. The optimal cut-point for 14 days was score ≥3. CONCLUSION: The TW-PCST demonstrated a good sensitivity and specificity in identification of inpatients with palliative care needs. A total-ABCD score ≥2 may be considered as a trigger for further referral.
Assuntos
Doença Crônica/terapia , Pacientes Internados , Avaliação das Necessidades , Neoplasias/terapia , Cuidados Paliativos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Encaminhamento e Consulta , Sensibilidade e Especificidade , Análise de Sobrevida , Taiwan/epidemiologia , Fatores de TempoRESUMO
The home-based medical care integrated plan under Taiwan National Health Insurance has changed from paying for home-based medical care, home-based nursing, home-based respiratory treatment, and palliative care to paying for a single, continuous home-based care service package. Formerly, physician-visit regulations limited home visits for home-based nursing to providing medical related assessments only. This limitation not only did not provide practical assistance to the public but also caused additional problems for those with mobility problems or who faced difficulties in making visits hospital. This 2016 change in regulations opens the door for doctors to step out their 'ivory tower', while offering the public more options to seek medical assistance in the hope that patients may change their health-seeking behavior. The home-based concept that underlies the medical service system is rooted deeply in the community in order to set up a sound, integrated model of community medical care. It is a critical issue to proceed with timely job handover confirmation with the connecting team and to provide patients with continuous-care services prior to discharge through the discharge-planning service and the connection with the connecting team. This is currently believed to be the only continuous home-based medical care integrated service model in the world. This model not only connects services such as health literacy, rehabilitation, home-based medical care, home-based nursing, community palliative care, and death but also integrates community resources, builds community resources networks, and provides high quality community care services.
Assuntos
Recursos em Saúde , Assistência de Longa Duração , Prestação Integrada de Cuidados de Saúde , Promoção da Saúde , Hospitais Urbanos , Humanos , TaiwanRESUMO
Mesoporous Mn1.5Co1.5O4 (MCO) spinel films were prepared directly on a conductive nickel (Ni) foam substrate via electrodeposition and an annealing treatment as supercapacitor electrodes. The electrodeposition time markedly influenced the surface morphological, textural, and supercapacitive properties of MCO/Ni electrodes. The (MCO/Ni)-15 min electrode (electrodeposition time: 15 min) exhibited the highest capacitance among three electrodes (electrodeposition times of 7.5, 15, and 30 min, respectively). Further, an asymmetric supercapacitor that utilizes (MCO/Ni)-15 min as a positive electrode, a plasma-treated activated carbon (PAC)/Ni electrode as a negative electrode, and carboxymethyl cellulose-lithium nitrate (LiNO3) gel electrolyte (denoted as (PAC/Ni)//(MCO/Ni)-15 min) was fabricated. In a stable operation window of 2.0 V, the device exhibited an energy density of 27.6 Wh·kg-1 and a power density of 1.01 kW·kg-1 at 1 A·g-1. After 5000 cycles, the specific energy density retention and power density retention were 96% and 92%, respectively, demonstrating exceptional cycling stability. The good supercapacitive performance and excellent stability of the (PAC/Ni)//(MCO/Ni)-15 min device can be ascribed to the hierarchical structure and high surface area of the (MCO/Ni)-15 min electrode, which facilitate lithium ion intercalation and deintercalation at the electrode/electrolyte interface and mitigate volume change during long-term charge/discharge cycling.
RESUMO
Three kinds of MnO2/Ni foam composite electrode with hierarchical meso-macroporous structures were prepared using potentiodynamic (PD), potentiostatic (PS), and a combination of PS and PD(PS + PD) modes of electrodeposition. The electrodeposition mode markedly influenced the surface morphological, textural, and supercapacitive properties of the MnO2/Ni electrodes. The supercapacitive performance of the MnO2/Ni electrode obtained via PS + PD(PS + PD(MnO2/Ni)) was found to be superior to those of MnO2/Ni electrodes obtained via PD and PS, respectively. Moreover, an asymmetric supercapacitor device, activated carbon (AC)/PS + PD(MnO2/Ni), utilizing PS + PD(MnO2/Ni) as a positive electrode and AC as a negative electrode, was fabricated. The device exhibited an energy density of 7.7 Wh·kg-1 at a power density of 600 W·kg-1 and superior cycling stability, retaining 98% of its initial capacity after 10,000 cycles. The good supercapacitive performance and excellent stability of the AC/PS + PD(MnO2/Ni) device can be ascribed to its high surface area, hierarchical structure, and interconnected three-dimensional reticular configuration of the nickel metal support, which facilitates electrolyte ion intercalation and deintercalation at the electrode/electrolyte interface and mitigates volume change during repeated charge/discharge cycling. These results demonstrate the great potential of the combination of PS and PD modes for MnO2 electrodeposition for the development of high-performance electrodes for supercapacitors.
RESUMO
Chitin grafted poly (acrylic acid) (chi-g-PAA) is synthesized and characterized as an adsorbent of toxic organic compounds. Chi-g-PAA copolymers are prepared using of ammonium cerium (IV) nitrate (Ce(4+)) as the initiator. The highest grafting percentage of AA in chitin obtained using the traditional technique is 163.1%. A maximum grafting percentage of 230.6% is obtained using central composite design (CCD). Experimental results are consistent with theoretical calculations. The grafted copolymer is characterized by Fourier transform Infrared spectroscopy and solid state (13)C NMR. A representative chi-g-AA copolymer is hydrolyzed to a type of sodium salt (chi-g-PANa) and used in the adsorption of malachite green (MG), methyl violet (MV), and paraquat (PQ) in aqueous. The monolayer adsorption capacities of these substances are 285.7, 357.1, and 322.6 mg/g-adsorbent, respectively. Thermodynamic calculations show that the adsorption of MG, MV, and PQ are more favored at diluted solutions. The high adsorption capacity of chi-g-PANa for toxic matter indicates its potential in the treatment of wastewater and emergency treatment of PQ-poisoned patients.
Assuntos
Acrilatos/química , Resinas Acrílicas/síntese química , Quitina/análogos & derivados , Quitina/química , Poluentes Ambientais/isolamento & purificação , Compostos Orgânicos/isolamento & purificação , Absorção , Resinas Acrílicas/química , Adsorção , Quitina/síntese química , Poluentes Ambientais/toxicidade , Violeta Genciana/isolamento & purificação , Violeta Genciana/toxicidade , Espectroscopia de Ressonância Magnética , Modelos Teóricos , Estrutura Molecular , Compostos Orgânicos/toxicidade , Paraquat/isolamento & purificação , Paraquat/toxicidade , Corantes de Rosanilina/isolamento & purificação , Corantes de Rosanilina/toxicidade , Espectroscopia de Infravermelho com Transformada de Fourier , Eliminação de Resíduos Líquidos/métodosRESUMO
The visible-light active silver vanadates with different types of crystallines (Ag(4)V(2)O(7) and Ag(3)VO(4) phases) were synthesized by an environmentally friendly aqueous process. The parameters of hydrothermal temperature and hydrothermal time were tuned to maximize the photocatalytic efficiency for the decomposition of benzene vapor under visible-light irradiation. The quantum efficiencies of the photocatalysts are compared on the basis of the crystalline phases, surface area, intensity of surface hydroxyl groups, and Brönsted acid sites. From the results of DRIFTS studies, the photocatalytic activities strongly depend on the intensities of the Brönsted acidity and hydroxyl groups presented on the silver vanadates. The sample synthesized at 140 degrees C and 4h (HM140) exhibits the best photocatalytic activity; it has a reaction rate constant (k(app)) of 1.42 min(-1), much higher than that of P25 (k(app)=0.13 min(-1)). For an irradiation time of 720 min, the mineralization yields of benzene were 48% and 11% for HM140 and P25, respectively. Based on the short-term decrease of benzene concentration and the long-term increase of CO(2) concentration, the photocatalytic ability of the HM140 sample is significantly superior to that of P25. The highest activity can be attributed to the synergetic effects of the richest Brönsted acid sites, and a favorable crystalline phase combined with abundant surface hydroxyl groups.
Assuntos
Benzeno/química , Compostos de Prata/química , Vanadatos/química , Dióxido de Carbono/química , Catálise , Cromatografia Gasosa-Espectrometria de Massas , Gases , Concentração de Íons de Hidrogênio , Radical Hidroxila/química , Cinética , Luz , Oxirredução , Fenol/química , Fotoquímica , Compostos de Amônio Quaternário/química , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Difração de Raios XRESUMO
This study developed a Pupils' Nature of Science Scale, including the subscales of the invented and changing nature of science, the role of social negotiation on science, and cultural context on science, to assess early adolescents' views about the nature of science. More than 6,000 fifth and sixth graders in Taiwan responded to the Scale. The study revealed that the adolescents had quite different perspectives toward different subscales of the nature of science. Moreover, male adolescents tended to express more constructivist-oriented views toward the nature of science than did their female counterparts. The adolescents of different grades and races also displayed varying views toward the nature of science.
Assuntos
Atitude , Disciplinas das Ciências Naturais , Estudantes/psicologia , Adolescente , Fatores Etários , Criança , Feminino , Humanos , Masculino , Fatores Sexuais , Inquéritos e Questionários , TaiwanRESUMO
The optical properties and surface morphologies of sputtering films both without and with use of the ion-assisted deposition (IAD) technique are investigated and compared. Optimal antireflection (AR) coating films with SiO2/Nb2O5 layers, which are grown at 80 degrees C with a 15 cm distance between target and substrate, 55 SCCM oxygen flow (SCCM denotes cubic centimeters per minute at STP), and 1250 W magnetron sputtering power with use of the IAD technique, are used to study the optical performance. By using an atomic force microscope to investigate the surface of the sputtered Nb2O5 films, we find that the films' roughness is 0.185 nm. On a flexible hardness polycarbonate (HPC) substrate with the multilayer AR films, the peak transmittances measured in the visible range are 95.89% and 93.40%, respectively, for coatings with and without use of the IAD sputtering technology. These results are better than those measured with a bare HPC substrate (91.25%) and are well above the commercial liquid-crystal display standard (90%) and flexible application.
RESUMO
PURPOSE: This study compares the difference in dose-volume data between three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for patients with hepatocellular carcinoma (HCC) and previously documented radiation-induced liver disease (RILD) after 3D-CRT. MATERIALS AND METHODS: Between November 1993 and December 1999, 68 patients with HCC were treated with 3D-CRT at our institution. Twelve of them were diagnosed with RILD within 4 months of completion of 3D-CRT. RILD was defined as either anicteric elevation of alkaline phosphatase level of at least twofold and nonmalignant ascites, or elevated transaminases of at least fivefold the upper limit of normal or of pretreatment levels. Three-dimensional treatment planning using dose-volume histograms of normal liver was used to obtain the dose-volume data. These 12 patients with RILD were replanned with an IMRT planning system using the five-field (gantry angles 0 degrees, 72 degrees, 144 degrees, 216 degrees, and 288 degrees ) step-and-shoot technique to compare the dosimetric difference in targets and organs at risk between 3D-CRT and IMRT. Mean dose and normal tissue complication probability with literature-cited volume effect parameter of 0.32, curve steepness parameter of 0.15, and TD(50)(1) of 40 Gy, were used for the liver, whereas volume fraction at a given dose level was used for other critical structures. Paired Student t-test with 2-tailed p < 0.05 was used to assess the statistical difference between the two techniques. RESULTS: With comparable target coverage between 3D-CRT and five-field step-and-shoot IMRT, IMRT was able to obtain a large dose reduction in the spinal cord (5.7% vs. 33.2%, p = 0.007), and achieved at least similar organ sparing for kidneys and stomach. IMRT had diverse dosimetric effect on liver, with significant reduction in normal tissue complication probability (23.7% vs. 36.6%, p = 0.009), but significant increase in mean dose (2924 cGy vs. 2504 cGy, p = 0.009), as compared with 3D-CRT. CONCLUSIONS: IMRT is capable of preserving acceptable target coverage and improving or at least maintaining the nonhepatic organ sparing for patients with HCC and previously diagnosed RILD after 3D-CRT. The true impact of this technique on the liver remains unsettled and may depend on the exact volume effect of this organ.
Assuntos
Carcinoma Hepatocelular/radioterapia , Imageamento Tridimensional , Hepatopatias/etiologia , Neoplasias Hepáticas/radioterapia , Fígado/efeitos da radiação , Lesões por Radiação/etiologia , Radiometria , Planejamento da Radioterapia Assistida por Computador , Radioterapia Conformacional/métodos , Adulto , Idoso , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Ascite/etiologia , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Relação Dose-Resposta à Radiação , Feminino , Humanos , Rim/efeitos da radiação , Fígado/lesões , Hepatopatias/sangue , Masculino , Pessoa de Meia-Idade , Radioterapia Conformacional/efeitos adversos , Estudos Retrospectivos , Medula Espinal/efeitos da radiaçãoRESUMO
Advanced glycosylation end products (AGEs) have been implicated in the pathogenesis of diabetic complications. Treatment of RAW 264.7 macrophages with bovine serum albumin (BSA)-derived AGEs caused dose- and time-dependent increases in nitrite production and inducible nitric oxide synthase (iNOS) expression. These effects were blocked by the nuclear factor-kappa B (NF-kappaB) inhibitor, pyrrolidone dithiocarbamate (PDTC). BSA-AGEs also stimulated the translocation of p65 NF-kappaB from cytosol to the nucleus. Electrophoretic mobility shift assay revealed that the NF-kappaB DNA-protein-binding activity was enhanced by AGEs. The tyrosine kinase inhibitor, genistein, the phosphatidylinositol-3-kinase (PI 3-K) inhibitor, LY 294002, the protein kinase C (PKC) inhibitor, Ro 31-8220, and the p38 mitogen-activated protein kinase (MAPK) inhibitor, SB 203580, all inhibited AGEs-stimulated iNOS expression, NO release, NF-kappaB translocation and NF-kappaB DNA binding activity. These results suggest that AGEs may activate NF-kappaB via an upstream signaling cascade composed of tyrosine kinase, PI 3-K, PKC, and p38 MAPK, resulting in the induction of iNOS expression in RAW 264.7 macrophages.
Assuntos
Produtos Finais de Glicação Avançada/farmacologia , NF-kappa B/fisiologia , Óxido Nítrico Sintase/biossíntese , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Anticorpos/farmacologia , Extratos Celulares , Linhagem Celular , Macrófagos/metabolismo , Camundongos , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/efeitos dos fármacos , Óxido Nítrico Sintase/imunologia , Óxido Nítrico Sintase Tipo II , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
PURPOSE: To analyze the correlation of radiation-induced liver disease (RILD) with patient-related and treatment-related dose-volume factors and to describe the probability of RILD by a normal tissue complication probability (NTCP) model for patients with hepatocellular carcinoma (HCC) treated with three-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: Between November 1993 and December 1999, 93 patients with intrahepatic malignancies were treated with 3D-CRT at our institution. Sixty-eight patients who were diagnosed with HCC and had complete 3D dose-volume data were included in this study. Of the 68 patients, 50 had chronic viral hepatitis before treatment, either type B or type C. According to the Child-Pugh classification for liver cirrhosis, 53 patients were in class A and 15 in class B. Fifty-two patients underwent transcatheter arterial chemoembolization with an interval of at least 1 month between transcatheter arterial chemoembolization and 3D-CRT to allow adequate recovery of hepatic function. The mean dose of radiation to the isocenter was 50.2 +/- 5.9 Gy, in daily fractions of 1.8-2Gy. No patient received whole liver irradiation. RILD was defined as Grade 3 or 4 hepatic toxicity according to the Common Toxicity Criteria of the National Cancer Institute. All patients were evaluated for RILD within 4 months of RT completion. Three-dimensional treatment planning with dose-volume histogram analysis of the normal liver was used to compare the dosimetric difference between patients with and without RILD. Maximal likelihood analysis was conducted to obtain the best estimates of parameters of the Lyman NTCP model. Confidence intervals of the fitted parameters were estimated by the profile likelihood method. RESULTS: Twelve of the 68 patients developed RILD after 3D-CRT. None of the patient-related variables were significantly associated with RILD. No difference was found in tumor volume (780 cm(3) vs. 737 cm(3), p = 0.86), normal liver volume (1210 cm(3) vs. 1153 cm(3), p = 0.64), percentage of normal liver volume with radiation dose >30 Gy (V(30 Gy); 42% vs. 33%, p = 0.05), and percentage of normal liver volume with >50% of the isocenter dose (V(50%); 45% vs. 36%, p = 0.06) between patients with and without RILD. The mean hepatic dose was significantly higher in patients with RILD (2504 cGy vs. 1965 cGy, p = 0.02). The probability of RILD in patients could be expressed as follows: probability = 1/[1 + exp(-(0.12 x mean dose - 4.29))], with coefficients significantly different from 0. The best estimates of the parameters in the Lyman NTCP model were the volume effect parameter of 0.40, curve steepness parameter of 0.26, and 50% tolerance dose for uniform irradiation of whole liver [TD(50)(1)] of 43 Gy. Patients with RILD had a significantly higher NTCP than did those with no RILD (26.2% vs. 15.8%; p = 0.006), using the best-estimated parameters. CONCLUSION: Dose-volume histogram analysis can be effectively used to quantify the tolerance of the liver to RT. Patients with RILD had received a significantly higher mean dose to the liver and a significantly higher NTCP. The fitted volume effect parameter of the Lyman NTCP model was close to that from the literature, but much lower in our patients with HCC and prevalent chronic viral hepatitis than that reported in other series with patients with normal liver function. Additional efforts should be made to test other models to describe the radiation tolerance of the liver for Asian patients with HCC and preexisting compromised hepatic reserve.
Assuntos
Carcinoma Hepatocelular/radioterapia , Hepatopatias/etiologia , Neoplasias Hepáticas/radioterapia , Radioterapia Conformacional/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Probabilidade , Dosagem RadioterapêuticaRESUMO
Twelve patients with hepatocellular carcinoma and chronic hepatitis developed radiation-induced liver disease (RILD) after three-dimensional conformal radiotherapy. Six patients died of RILD and six recovered. Mean prescribed dose was 50.6+/-4.3Gy, in a daily fraction of 1.8-2.0Gy. Commonly used dosimetric parameters, such as fraction volume of normal liver with radiation dose >30Gy, prediction score, and normal tissue complication probability, failed to differentiate the fatality and clinical types of this complication. Elevated transaminases are more frequently seen than ascites and elevated alkaline phosphamide are seen in patients with RILD.