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In this study, we numerically investigate the spin transfer torque oscillation (STO) in a magnetic orthogonal configuration by introducing a strong biquadratic magnetic coupling. The orthogonal configuration consists of top and bottom layers with in-plane and perpendicular magnetic anisotropy sandwiching a nonmagnetic spacer. The advantage of an orthogonal configuration is the high efficiency of spin transfer torque leading a high STO frequency; however, maintaining the STO in a wide range of electric current is challenging. By introducing biquadratic magnetic coupling into the orthogonal structure of FePt/spacer/Co90Fe10, Ni80Fe20 or Ni, we were able to expand the electric current region in which the stable STO is realized, resulting in a relatively high STO frequency. For example, approximately 50 GHz can be achieved in an Ni layer at a current density of 5.5 × 107 A/cm2. In addition, we investigated two types of initial magnetic state: out-of-plane and in-plane magnetic saturation; this leads to a vortex and an in-plane magnetic domain structure after relaxation, respectively. The transient time before the stable STO was reduced to between 0.5 and 1.8 ns by changing the initial state from out-of-plane to in-plane.
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Neoplasias Encefálicas , Glioblastoma , Neurofibromatosis 1 , Humanos , Glioblastoma/complicaciones , Glioblastoma/diagnóstico , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/diagnóstico , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patología , Bulbo Raquídeo/diagnóstico por imagen , Bulbo Raquídeo/patología , Cognición , Imagen por Resonancia MagnéticaRESUMEN
AIMS: This study aimed to evaluate the anti-adiposity effect of heat-killed Lactobacillus brevis KB290 originating from traditional Japanese fermented pickles in mice fed a high-fat diet (HFD). METHODS AND RESULTS: C57BL/6J mice were fed a normal-fat diet, HFD or HFD supplemented with heat-killed KB290 for 8 weeks. Epididymal and renal adipose tissue weights, as well as areas of epididymal adipocytes, were significantly lower in the mice fed a HFD supplemented with KB290 than in those fed an unsupplemented HFD. Mice whose diets were supplemented with KB290 had elevated adiponectin and ß3-adrenergic receptor expression in epididymal adipose tissue and an accompanying higher serum free fatty acid level. Furthermore, the HFD-induced elevations in serum glucose, insulin and HOMA-IR were significantly suppressed by dietary supplementation with KB290. Amplicon sequencing of 16S rRNA genes revealed that KB290 ingestion altered the composition of the intestinal microbiota. CONCLUSIONS: Heat-killed L. brevis KB290 suppressed diet-induced visceral fat accumulation and ameliorated diet-induced metabolic symptoms and intestinal gut microbiota modifications, suggesting possibility of novel paraprobiotic. SIGNIFICANCE AND IMPACT OF THE STUDY: Heat-killed L. brevis KB290 is useable as a material to develop functional foods that attenuate visceral fat accumulation.
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Dieta Alta en Grasa , Levilactobacillus brevis , Animales , Dieta Alta en Grasa/efectos adversos , Calor , Grasa Intraabdominal , Levilactobacillus brevis/genética , Ratones , Ratones Endogámicos C57BL , ARN Ribosómico 16SRESUMEN
OBJECTIVE: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage degeneration, abnormal bone remodeling, and chronic pain. In this study, we aimed to investigate effective therapies to reverse or suppress TMJOA progression. DESIGN: To this end, we performed intravenous administration of serum free conditioned media from human exfoliated deciduous teeth stem cells (SHED-CM) into a mechanical-stress induced murine TMJOA model. RESULTS: SHED-CM administration markedly suppressed temporal muscle inflammation, and improved bone integrity and surface smoothness of the destroyed condylar cartilage. Moreover, SHED-CM treatment decreased the number of IL-1ß, iNOS, and MMP-13 expressing chondrocytes, whereas it specifically increased PCNA-positive cells in the multipotent polymorphic cell layer. Notably, the numbers of TdT-mediated dUTP nick end labeling (TUNEL)-positive apoptotic chondrocytes in the SHED-CM treated condyles were significantly lower than in those treated with DMEM, whereas the proteoglycan positive area was restored to a level similar to that of the sham treated group, demonstrating that SHED-CM treatment regenerated the mechanical-stress injured condylar cartilage and subchondral bone. Secretome analysis revealed that SHED-CM contained multiple therapeutic factors that act in osteochondral regeneration. CONCLUSIONS: Our data demonstrated that SHED-CM treatment promoted the regeneration and repair of mechanical-stress induced mouse TMJOA. Our observations suggest that SHED-CM has potential to be a potent tissue-regenerating therapeutic agent for patients with severe TMJOA.
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Productos Biológicos/metabolismo , Productos Biológicos/uso terapéutico , Pulpa Dental/citología , Osteoartritis/terapia , Células Madre/metabolismo , Articulación Temporomandibular , Animales , Modelos Animales de Enfermedad , Humanos , Masculino , RatonesRESUMEN
BACKGROUND: Noninvasive and child-friendly biomarkers are important tools for understanding the various phenotypes of childhood asthma. Objective: The aim of this study was to examine the usefulness of salivary surfactant protein (SP) D in assessing the pathophysiology of childhood asthma. METHODS: We measured salivary concentrations of SP-D and forced oscillation technique (FOT) indexes in 19 healthy controls and 21 asthmatic children. Regression equations for the predictive values of FOT indexes were generated from healthy controls. We analyzed the correlations between salivary SP-D concentration and percentages of the predictive values of FOT indexes, as well as the severity of exacerbation. RESULTS: We found that salivary SP-D levels were higher in asthmatic children than in healthy controls. In the asthmatic children, salivary SP-D levels correlated with the percentages of predicted differences in resistance between 5 Hz and 20 Hz (%R5-R20), which represented the resistance of peripheral airways, and with the severity of asthma exacerbation. CONCLUSIONS: Salivary SP-D may reflect asthmatic inflammation in peripheral small airways and may be a useful marker for monitoring the degree of exacerbation in childhood asthma.
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Asma/diagnóstico , Asma/metabolismo , Proteína D Asociada a Surfactante Pulmonar/metabolismo , Saliva/metabolismo , Adolescente , Biomarcadores , Estudios de Casos y Controles , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Humanos , Inflamación/diagnóstico , Inflamación/metabolismo , Masculino , Valor Predictivo de las Pruebas , Proteína D Asociada a Surfactante Pulmonar/sangre , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: The storage stability of serum formulations containing ofloxacin for autologous serum eardrop therapy was evaluated for microbiological quality and component stability. METHODS: Sterile serum formulations were prepared by mixing human serum and ofloxacin otic solution (1:1, v/v). To simulate eardrop contamination with external ear surface substances, prepared serum formulations were contaminated with a cotton swab that was rubbed sufficiently on the human external ear. Formulations were stored at 4 °C or room temperature in the dark. Colony forming units (CFUs), ofloxacin, and basic fibroblast growth factor (bFGF) concentrations in the stored serum formulations were determined. RESULTS: The growth of microorganisms derived from the external ear was not detected in serum formulations after storage for 14 days, regardless of temperature. However, microbial growth was detected in serum formulations stored without ofloxacin, indicating that this is necessary for storage. In addition, concentrations of ofloxacin and bFGF did not decrease over 14 days, indicating that ofloxacin and bFGF in serum formulations are stable for this time period. CONCLUSION: The present study indicates that the efficacy and safety of serum formulations used as a therapy for perforated eardrums are stable and safe for at least 14 days.
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Antibacterianos/administración & dosificación , Ofloxacino/administración & dosificación , Suero , Antibacterianos/química , Recuento de Colonia Microbiana , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Humanos , Ofloxacino/química , Temperatura , Factores de TiempoRESUMEN
Background: Noninvasive and child-friendly biomarkers are important tools for understanding the various phenotypes of childhood asthma. Objective: The aim of this study was to examine the usefulness of salivary surfactant protein (SP) D in assessing the pathophysiology of childhood asthma. Methods: We measured salivary concentrations of SP-D and forced oscillation technique (FOT) indexes in 19 healthy controls and 21 asthmatic children. Regression equations for the predictive values of FOT indexes were generated from healthy controls. We analyzed the correlations between salivary SP-D concentration and percentages of the predictive values of FOT indexes, as well as the severity of exacerbation. Results: We found that salivary SP-D levels were higher in asthmatic children than in healthy controls. In the asthmatic children, salivary SP-D levels correlated with the percentages of predicted differences in resistance between 5 Hz and 20 Hz (%R5-R20), which represented the resistance of peripheral airways, and with the severity of asthma exacerbation. Conclusion: Salivary SP-D may reflect asthmatic inflammation in peripheral small airways and may be a useful marker for monitoring the degree of exacerbation in childhood asthma (AU)
Antecedentes: El empleo de biomarcadores no invasivos es una buena herramienta para estudiar la fisiopatología de los diferentes fenotipos del asma infantil. Objetivo: El objetivo de este estudio fue examinar la utilidad de la proteína salival surfactante (SP) D en la evaluación de la fisiopatología del asma infantil. Métodos: Se midieron las concentraciones en la saliva de SP-D y se realizaron oscilometrías forzadas de impulsos (FOT) en 21 niños asmáticos y 19 controles sanos. Las ecuaciones de regresión para los valores predictivos de los índices FOT se generaron a partir de controles sanos. Se analizaron las correlaciones entre la concentración de SP-D salival y los porcentajes de los valores predictivos de los índices FOT, así como la gravedad de las exacerbaciones. Resultados: Se encontró que los niveles en la saliva de la SP-D fueron más elevados en los niños asmáticos en comparación con los controles sanos. En los niños asmáticos, los niveles de SP-D salival se correlacionaron con los porcentajes de las diferencias predichas en la resistencia entre 5Hz y 20Hz (% R5-R20), que representan la resistencia de las vías respiratorias periféricas y la gravedad de la exacerbación del asma. Conclusión: La SP-D salival puede reflejar la inflamación asmática en las vías respiratorias pequeñas y puede ser un marcador útil para monitorizar el grado de exacerbación en el asma infantil (AU)
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Humanos , Masculino , Femenino , Niño , Asma/diagnóstico , Asma/inmunología , Biomarcadores/análisis , Saliva/química , Valor Predictivo de las Pruebas , Estudios de Casos y Controles , Brote de los Síntomas , Asma/fisiopatología , Oscilometría/métodos , Proteínas y Péptidos Salivales/análisis , Modelos Lineales , 28599RESUMEN
We previously reported that a rotation/revolution pulverizer (NP-100) could mill a small amount of a drug (0.1 g) into nanoparticles in several minutes. In this investigation, scale up from the milligram to the kilogram scale of the nano-milling process by the rotation/revolution pulverizer was studied. Phenytoin was used as a model drug with low solubility in water. After confirming the improvement of the phenytoin bioavailability by milling to nanoparticles using NP-100, scaling parameters were evaluated using NP-100 and the middle scale model of NP-100 (ARV-3000T). A theoretical equation for the specific collisional energy was adapted for wet milling; this suggested that the relative centrifugal acceleration of revolution (revolution G) and the drug concentration in the suspension were the two most important parameters. The results obtained using NP-100 and ARV-3000T correlated well when these two parameters were identical. These results were applied to the large scale model of NP-100 (ARV-10KT), where 2 kg (1 kg x 2) of phenytoin nanoparticles were obtained in 60 min. The results from PXRD and DSC indicated that the milled phenytoin by ARV-3000T and ARV-10KT maintained its crystallinity. These results suggest nano-milling using a rotation/revolution pulverizer will be widely applicable to the development of nano-medicine.
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Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/farmacocinética , Composición de Medicamentos/instrumentación , Nanotecnología/instrumentación , Fenitoína/administración & dosificación , Fenitoína/farmacocinética , Animales , Anticonvulsivantes/química , Química Farmacéutica , Excipientes , Masculino , Nanopartículas , Tamaño de la Partícula , Fenitoína/química , Ratas , Ratas Sprague-Dawley , Solubilidad , Difracción de Rayos XRESUMEN
Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.
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Encéfalo/fisiopatología , Esquizofrenia/fisiopatología , Adulto , Amígdala del Cerebelo , Ganglios Basales , Mapeo Encefálico , Estudios de Cohortes , Estudios Transversales , Femenino , Lateralidad Funcional/fisiología , Hipocampo , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Putamen , TálamoRESUMEN
AIMS: Primary central nervous system lymphoma (PCNSL) manifest aggressive clinical behaviour and have poor prognosis. Although constitutive activation of the nuclear factor-κB (NF-κB) pathway has been documented, knowledge about the genetic alterations leading to the impairment of the NF-κB pathway in PCNSLs is still limited. This study was aimed to unravel the underlying genetic profiles of PCNSL. METHODS: We conducted the systematic sequencing of 21 genes relevant to the NF-κB signalling network for 71 PCNSLs as well as the pyrosequencing of CD79B and MYD88 mutation hotspots in a further 35 PCNSLs and 46 glioblastomas (GBMs) for validation. RESULTS: The results showed that 68 out of 71 PCNSLs had mutations in the NF-κB gene network, most commonly affecting CD79B (83%), MYD88 (76%), TBL1XR1 (23%), PRDM1 (20%) and CREBBP1 (20%). These mutations, particularly CD79B and MYD88, frequently coincided within each tumour in various combinations, simultaneously affecting diverse pathways within the network. No GBMs had hotspot mutation of CD79B Y196 and MYD88 L265. CONCLUSIONS: The prevalence of CD79B and MYD88 mutations in PCNSLs was considerably higher than reported in systemic diffuse large B-cell lymphomas. This observation could reflect the paucity of antigen stimuli from the immune system in the central nervous system (CNS) and the necessity to substitute them by the constitutive activation of CD79B and MYD88 that would initiate the signalling cascades. These hotspot mutations may serve as a genetic hallmark for PCNSL serving as a genetic marker for diagnose and potential targets for molecular therapy.
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Antígenos CD79/genética , Neoplasias del Sistema Nervioso Central/genética , Linfoma de Células B Grandes Difuso/genética , Factor 88 de Diferenciación Mieloide/genética , Anciano , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Reacción en Cadena de la PolimerasaAsunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Hipersensibilidad a los Alimentos/etiología , Hipersensibilidad a los Alimentos/inmunología , Enfermedades Hematológicas/inmunología , Enfermedades Hematológicas/terapia , Adolescente , Adulto , Aloinjertos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND AND PURPOSE: Noninvasive radiologic evaluation of glioma can facilitate correct diagnosis and detection of malignant transformation. Although positron-emission tomography is considered valuable in the care of patients with gliomas, (18)F-fluorodeoxyglucose and (11)C-methionine have reportedly shown ambiguous results in terms of grading and prognostication. The present study compared the diagnostic and prognostic capabilities of diffusion tensor imaging, FDG, and (11)C-methionine PET in nonenhancing gliomas. MATERIALS AND METHODS: Thirty-five consecutive newly diagnosed, histologically confirmed nonenhancing gliomas that underwent both FDG and (11)C-methionine PET were retrospectively investigated (23 grade II and 12 grade III gliomas). Apparent diffusion coefficient, fractional anisotropy, and tumor-to-normal tissue ratios of both FDG and (11)C-methionine PET were compared between grade II and III gliomas. Prognostic values of these parameters were also tested by using progression-free survival. RESULTS: Grade III gliomas showed significantly higher average tumor-to-normal tissue and maximum tumor2-to-normal tissue than grade II gliomas in (11)C-methionine (P = .013, P = .0017, respectively), but not in FDG-PET imaging. There was no significant difference in average ADC, minimum ADC, average fractional anisotropy, and maximum fractional anisotropy. (11)C-methionine PET maximum tumor-to-normal tissue ratio of 2.0 was most suitable for detecting grade III gliomas among nonenhancing gliomas (sensitivity, 83.3%; specificity, 73.9%). Among patients not receiving any adjuvant therapy, median progression-free survival was 64.2 ± 7.2 months in patients with maximum tumor-to-normal tissue ratio of <2.0 for (11)C-methionine PET and 18.6 ± 6.9 months in patients with maximum tumor-to-normal tissue ratio of >2.0 (P = .0044). CONCLUSIONS: (11)C-methionine PET holds promise for World Health Organization grading and could offer a prognostic imaging biomarker for nonenhancing gliomas.
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Neoplasias Encefálicas/diagnóstico por imagen , Glioma/diagnóstico por imagen , Clasificación del Tumor/métodos , Tomografía de Emisión de Positrones/métodos , Anciano , Neoplasias Encefálicas/mortalidad , Radioisótopos de Carbono , Supervivencia sin Enfermedad , Femenino , Glioma/mortalidad , Humanos , Masculino , Metionina , Persona de Mediana Edad , Pronóstico , Radiofármacos , Estudios Retrospectivos , Adulto JovenRESUMEN
Liquid lithium (Li) is a candidate material for a target of intense neutron source, heat transfer medium in space engines and charges stripper. For a medical application of BNCT, epithermal neutrons with least energetic neutrons and γ-ray are required so as to avoid unnecessary doses to a patient. This is enabled by lithium target irradiated by protons at 2.5 MeV range, with utilizing the threshold reaction of (7)Li(p,n)(7)Be at 1.88 MeV. In the system, protons at 2.5 MeV penetrate into Li layer by 0.25 mm with dissipating heat load near the surface. To handle it, thin film flow of high velocity is important for stable operation. For the proton accelerator, electrostatic type of the Schnkel or the tandem is planned to be employed. Neutrons generated at 0.6 MeV are gently moderated to epithermal energy while suppressing accompanying γ-ray minimum by the dedicated moderator assembly.
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Terapia por Captura de Neutrón de Boro , Litio/química , NeutronesRESUMEN
OBJECTIVE: Expression of taste-related genes in the tongue was analysed to develop a technique for genetic diagnosis of umami taste disorders. MATERIALS AND METHODS: Tissue samples were collected from healthy volunteers by scraping the foliate papillae of the tongue. Immunocytochemistry staining of gustducin, a taste-cell-specific G protein, and gene expression analysis by real-time polymerase chain reaction of ß-actin, gustducin (GNAT3) and umami receptors (T1R1, T1R3 and mGluR1) were performed. Changes in umami receptor expression following application of umami substances onto the tongue were analysed. RESULTS: Gustducin-positive cells were observed in the samples, indicating the presence of taste cells. Gene expression of ß-actin, GNAT3, T1R1 and T1R3 was detected in all seven samples tested, while that of mGluR1 was detected in four samples. Sequence analysis by NCBI Blast showed that each polymerase chain reaction product had a 99% rate of identification of its target sequence. Stimulation of the tongue with monosodium glutamate significantly upregulated the gene expression levels of T1R1 and T1R3, indicating that this method can detect alterations in umami-related gene expression. CONCLUSION: Evaluation of the expression of the umami receptor genes, T1R1 and T1R3, in the tongue may be clinically useful for objective genetic diagnosis of umami taste disorders.
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Receptores Acoplados a Proteínas G/genética , Receptores de Glutamato Metabotrópico/genética , Percepción del Gusto/genética , Gusto/genética , Transducina/genética , Actinas/genética , Adulto , Femenino , Expresión Génica/efectos de los fármacos , Humanos , Masculino , Proyectos Piloto , Glutamato de Sodio/farmacología , Lengua/química , Lengua/efectos de los fármacos , Transducina/análisisRESUMEN
We assessed the efficacy and safety of sitagliptin compared with α-glucosidase inhibitor (αGI) in 120 of Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on stable ≤2 mg/day glimepiride alone [mean hemoglobin A1c (HbA1c) 7.7%] by the randomized, active-controlled, non-inferiority trial. Patients were randomly assigned to receive additional sitagliptin or αGI for 24 weeks. The primary endpoint was change in HbA1c from baseline to week 12. After 12 weeks, sitagliptin reduced HbA1c by -0.44% (p < 0.001) relative to αGI. At 24 weeks, the reduction was almost identical between the groups (-0.091%, p = 0.47). Gastrointestinal disorders were more common with αGI than with sitagliptin, but only minor hypoglycaemia occurred in both groups at similar frequency. These data suggested that sitagliptin was not inferior to αGI for reduction of HbA1c in Japanese T2DM patients receiving glimepiride alone, and well tolerated with minimum risk of gastrointestinal symptoms and hypoglycaemia.
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1-Desoxinojirimicina/análogos & derivados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Inhibidores de Glicósido Hidrolasas/uso terapéutico , Hiperglucemia/prevención & control , Inositol/análogos & derivados , Pirazinas/uso terapéutico , Triazoles/uso terapéutico , 1-Desoxinojirimicina/efectos adversos , 1-Desoxinojirimicina/uso terapéutico , Anciano , Diabetes Mellitus Tipo 2/sangre , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Quimioterapia Combinada/efectos adversos , Femenino , Fármacos Gastrointestinales/efectos adversos , Fármacos Gastrointestinales/uso terapéutico , Hemoglobina Glucada/análisis , Inhibidores de Glicósido Hidrolasas/efectos adversos , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Inositol/efectos adversos , Inositol/uso terapéutico , Japón , Masculino , Persona de Mediana Edad , Pirazinas/efectos adversos , Fosfato de Sitagliptina , Compuestos de Sulfonilurea/uso terapéutico , Triazoles/efectos adversos , alfa-Glucosidasas/química , alfa-Glucosidasas/metabolismoRESUMEN
Aims. To evaluate the effectiveness of a brief suicide management training programme for Japanese medical residents compared with the usual lecture on suicidality. Methods. In this multi-center, clustered randomized controlled trial, the intervention group attended a structured suicide management programme and the control group, the usual lecture on depression and suicidality. The primary outcome was the difference in residents' cumulative competency score to manage suicidal persons from baseline (T0) to 1 month after the intervention (T2), determined using the Suicide Intervention Response Inventory (SIRI-1) score, at individual level. Results. Analysis of 114 residents (intervention group n = 65, control group n = 49) assigned to two clusters in each group revealed no change in SIRI-1 score from T0 to T2 or immediately after the intervention (T1) between the two groups. As a secondary analysis, discrepancy in judgement between the participants and Japanese suicidologists was examined immediately after the intervention in the adjusted model, with a mean difference in score of 9.98 (95% confidence interval: 4.39-15.56; p = 0.001). Conclusions. The structured programme was not proven to improve competency in suicide management when measured by the SIRI-1 score. Further elaboration of the programme and valid measurement of its outcome would be needed to show the program's effectiveness.
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PURPOSE: To retrospectively analyze treatment outcomes after particle therapy using protons or carbon ions for mucosal melanoma of the head and neck (HNMM) at the Hyogo Ion Beam Medical Center, as well as to compare proton therapy (PT) and carbon ion therapy (CIT). PATIENTS AND METHODS: Data from 62 HNMM patients without metastasis, treated with PT or CIT between October 2003 and April 2011 were analyzed. Median patient age was 70.5 years (range 33-89 years). Of the total patients, 33 (53 %) had received PT and 29 (47 %) had undergone CIT. Protocols for 65 or 70.2 GyE in 26 fractions were used for both ion types. RESULTS: Median follow-up was 18.0 months (range 5.2-82.7 months). The 1-/2-year overall survival (OS) and local control (LC) rates were 93 %/61 % and 93 %/78 % for all patients, 91 %/44 % and 92 %/71 % for the PT patients and 96 %/62 % and 95 %/59 % for the CIT patients, respectively. No significant differences were observed between PT and CIT. Local recurrence was observed in 8 patients (PT: 5, CIT: 3) and 29 (PT: 18, CIT: 11) experienced distant metastases. Acute reactions were acceptable and all patients completed the planned radiotherapy. Regarding late toxicity, grade 3 or greater events were observed in 5 patients (PT: 3, CIT: 2), but no significant difference was observed between PT and CIT. CONCLUSION: Our single-institution retrospective analysis demonstrated that particle therapy for HNMM achieved good LC, but OS was unsatisfactory. There were no significant differences between PT and CIT in terms of either efficacy or toxicity.
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Radioterapia de Iones Pesados/métodos , Melanoma/radioterapia , Neoplasias de Oído, Nariz y Garganta/radioterapia , Terapia de Protones/métodos , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Neoplasias de la Boca/radioterapia , Recurrencia Local de Neoplasia/etiología , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Neoplasias Nasales/mortalidad , Neoplasias Nasales/patología , Neoplasias Nasales/radioterapia , Neoplasias de Oído, Nariz y Garganta/mortalidad , Neoplasias de Oído, Nariz y Garganta/patología , Neoplasias de los Senos Paranasales/mortalidad , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/radioterapia , Traumatismos por Radiación/etiología , Estudios RetrospectivosRESUMEN
AIM: To compare the accuracy of computer software analysis using three different target-definition protocols to detect tumour feeder vessels for transarterial chemoembolization of hepatocellular carcinoma. MATERIALS AND METHODS: C-arm computed tomography (CT) data were analysed for 81 tumours from 57 patients who had undergone chemoembolization using software-assisted detection of tumour feeders. Small, medium, and large-sized targets were manually defined for each tumour. The tumour feeder was verified when the target tumour was enhanced on selective C-arm CT of the investigated vessel during chemoembolization. The sensitivity, specificity, and accuracy of the three protocols were evaluated and compared. RESULTS: One hundred and eight feeder vessels supplying 81 lesions were detected. The sensitivity of the small, medium, and large target protocols was 79.8%, 91.7%, and 96.3%, respectively; specificity was 95%, 88%, and 50%, respectively; and accuracy was 87.5%, 89.9%, and 74%, respectively. The sensitivity was significantly higher for the medium (p = 0.003) and large (p < 0.001) target protocols than for the small target protocol. The specificity and accuracy were higher for the small (p < 0.001 and p < 0.001, respectively) and medium (p < 0.001 and p < 0.001, respectively) target protocols than for the large target protocol. CONCLUSION: The overall accuracy of software-assisted automated feeder analysis in transarterial chemoembolization for hepatocellular carcinoma is affected by the target definition size. A large target definition increases sensitivity and decreases specificity in detecting tumour feeders. A target size equivalent to the tumour size most accurately predicts tumour feeders.
Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Carcinoma Hepatocelular/diagnóstico por imagen , Medios de Contraste , Humanos , Hígado/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Programas InformáticosRESUMEN
OBJECTIVE: This study retrospectively evaluated the efficacy and toxicity of particle therapy using carbon ions or protons for primary sacral chordomas. METHODS: We evaluated 23 patients with primary sacral chordoma treated with carbon ion therapy (CIT) or proton therapy (PT) between July 2005 and June 2011 at the Hyogo Ion Beam Medical Center, Hyogo, Japan. The median patient age was 72 years. 14 patients were treated with 70.4 Gy equivalents (GyE) in 16 fractions and 9 were treated with 70.4 GyE in 32 fractions. CIT was used for 16 patients, and PT was used for 7 patients. RESULTS: The median follow-up period was 38 months. At 3 years, local control (LC), overall survival (OS) and progression-free survival (PFS) for all patients were 94%, 83% and 68%, respectively. The log-rank test revealed that male sex was significantly related to better PFS (p=0.029). No other factors, including dose fractionation and ion type, were significant for LC, OS or PFS. In nine patients, ≥ Grade 3 acute dermatitis was observed, and ≥ Grade 3 late toxicities were observed in nine patients. The 32-fraction protocol reduced severe toxicities in both the acute and late phases compared with the 16-fraction protocol. CONCLUSION: Particle therapy for patients with sacral chordoma showed favourable LC and OS. Severe toxicities were successfully reduced by modifying the dose fractionation and treatment planning in the later treatment era. Thus, this therapeutic modality should be considered useful and safe. ADVANCES IN KNOWLEDGE: This is the first study including both CIT and PT for sacral chordomas.
Asunto(s)
Cordoma/terapia , Radioterapia de Iones Pesados/métodos , Terapia de Protones , Sacro , Neoplasias de la Columna Vertebral/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carbono/uso terapéutico , Cordoma/mortalidad , Cordoma/secundario , Dermatitis/etiología , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Femenino , Estudios de Seguimiento , Radioterapia de Iones Pesados/efectos adversos , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Protones/efectos adversos , Dosificación Radioterapéutica , Estudios Retrospectivos , Factores Sexuales , Neoplasias de la Columna Vertebral/mortalidad , Tasa de SupervivenciaRESUMEN
Signal transduction and activator of transcription (STAT) proteins are extracellular ligand-responsive transcription factors that mediate cell proliferation, apoptosis, differentiation, development and the immune response. Aberrant signals of STAT induce uncontrolled cell proliferation and apoptosis resistance and are strongly involved in cancer. STAT has been identified as a promising target for antitumor drugs, but to date most trials have not been successful. Here, we demonstrated that a novel STAT inhibitor, OPB-31121, strongly inhibited STAT3 and STAT5 phosphorylation without upstream kinase inhibition, and induced significant growth inhibition in various hematopoietic malignant cells. Investigation of various cell lines suggested that OPB-31121 is particularly effective against multiple myeloma, Burkitt lymphoma and leukemia harboring BCR-ABL, FLT3/ITD and JAK2 V617F, oncokinases with their oncogenicities dependent on STAT3/5. Using an immunodeficient mouse transplantation system, we showed the significant antitumor effect of OPB-31121 against primary human leukemia cells harboring these aberrant kinases and its safety for normal human cord blood cells. Finally, we demonstrated a model to overcome drug resistance to upstream kinase inhibitors with a STAT inhibitor. These results suggested that OPB-31121 is a promising antitumor drug. Phase I trials have been performed in Korea and Hong Kong, and a phase I/II trial is underway in Japan.