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1.
Br J Surg ; 108(8): 968-975, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-33829254

RESUMO

BACKGROUND: Most current models for predicting survival after resection of colorectal liver metastasis include largest diameter and number of colorectal liver metastases as dichotomous variables, resulting in underestimation of the extent of risk variation and substantial loss of statistical power. The aim of this study was to develop and validate a new prognostic model for patients undergoing liver resection including largest diameter and number of colorectal liver metastases as continuous variables. METHODS: A prognostic model was developed using data from patients who underwent liver resection for colorectal liver metastases at MD Anderson Cancer Center and had RAS mutational data. A Cox proportional hazards model analysis was used to develop a model based on largest colorectal liver metastasis diameter and number of metastases as continuous variables. The model results were shown using contour plots, and validated externally in an international multi-institutional cohort. RESULTS: A total of 810 patients met the inclusion criteria. Largest colorectal liver metastasis diameter (hazard ratio (HR) 1.11, 95 per cent confidence interval 1.06 to 1.16; P < 0.001), number of colorectal liver metastases (HR 1.06, 1.03 to 1.09; P < 0.001), and RAS mutation status (HR 1.76, 1.42 to 2.18; P < 0.001) were significantly associated with overall survival, together with age, primary lymph node metastasis, and prehepatectomy chemotherapy. The model performed well in the external validation cohort, with predicted overall survival values almost lying within 10 per cent of observed values. Wild-type RAS was associated with better overall survival than RAS mutation even when liver resection was performed for larger and/or multiple colorectal liver metastases. CONCLUSION: The contour prognostic model, based on diameter and number of lesions considered as continuous variables along with RAS mutation, predicts overall survival after resection of colorectal liver metastasis.


Assuntos
Neoplasias Colorretais/patologia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
3.
Br J Surg ; 107(3): 258-267, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31603540

RESUMO

BACKGROUND: Traditional classifications for open liver resection are not always associated with surgical complexity and postoperative morbidity. The aim of this study was to test whether a three-level classification for stratifying surgical complexity based on surgical and postoperative outcomes, originally devised for laparoscopic liver resection, is superior to classifications based on a previously reported survey for stratifying surgical complexity of open liver resections, minor/major nomenclature or number of resected segments. METHODS: Patients undergoing a first open liver resection without simultaneous procedures at MD Anderson Cancer Center (Houston cohort) or the University of Tokyo (Tokyo cohort) were studied. Surgical and postoperative outcomes were compared among three grades: I (wedge resection for anterolateral or posterosuperior segment and left lateral sectionectomy); II (anterolateral segmentectomy and left hepatectomy); III (posterosuperior segmentectomy, right posterior sectionectomy, right hepatectomy, central hepatectomy and extended left/right hepatectomy). RESULTS: In both the Houston (1878 patients) and Tokyo (1202) cohorts, duration of operation, estimated blood loss and comprehensive complication index score differed between the three grades (all P < 0·050) and increased in stepwise fashion from grades I to III (all P < 0·001). Left hepatectomy was associated with better surgical and postoperative outcomes than right hepatectomy, extended right hepatectomy and right posterior sectionectomy, although these four procedures were categorized as being of medium complexity in the survey-based classification. Surgical outcomes of minor open liver resections also differed between the three grades (all P < 0·050). For duration of operation and blood loss, the area under the curve was higher for the three-level classification than for the minor/major or segment-based classification. CONCLUSION: The three-level classification may be useful in studies analysing open liver resection at Western and Eastern centres.


ANTECEDENTES: Las clasificaciones tradicionales de la resección hepática abierta (open liver resection, OLR) por número de segmentos resecados, no siempre se asocian con la complejidad quirúrgica y la morbilidad postoperatoria. El objetivo de este estudio fue comprobar si una clasificación de 3 niveles para estratificar la complejidad quirúrgica en función de los resultados quirúrgicos y postoperatorios, ideada originalmente para la resección hepática laparoscópica, es superior a las clasificaciones basadas en una encuesta descrita previamente para estratificar la complejidad quirúrgica de los procedimientos de OLR, nomenclatura menor/mayor, o número de segmentos resecados. MÉTODOS: Se estudiaron pacientes sometidos a una primera OLR sin otros procedimientos quirúrgicos concomitantes en el hospital MD Anderson (cohorte de Houston) o en la Universidad de Tokio (cohorte de Tokio). Se compararon los resultados quirúrgicos y postoperatorios entre 3 grados: I (resección limitada para el segmento anterolateral o posterosuperior y seccionectomía izquierda); II (segmentectomía anterolateral y hepatectomía izquierda); III (segmentectomía posterosuperior, seccionectomía posterior derecha, hepatectomía derecha, hepatectomía central y hepatectomía ampliada izquierda/derecha). RESULTADOS: En ambas cohortes de Houston (n = 1.878) y Tokio (n = 1.202), el tiempo operatorio, las pérdidas estimadas de sangre, y el índice de complejidad integral (comprehensive complication index) variaba en los 3 grados (todos P < 0,05) y aumentaba paso a paso desde los grados I a III (todos P < 0,05). La hepatectomía izquierda se asociaba con mejores resultados quirúrgicos y postoperatorios que la hepatectomía derecha, hepatectomía derecha ampliada, y seccionectomía posterior derecha, aunque estos cuatro procedimientos fueron categorizados como de complejidad intermedia en la clasificación basada en la encuesta. Los resultados quirúrgicos de las OLRs menores también variaron en los 3 grados (todos P < 0,05). Para el tiempo operatorio y la pérdida sanguínea, el área bajo la curva fue mayor para la clasificación de 3 niveles en el estudio actual, que para la clasificación menor/mayor o la clasificación basada en los segmentos. CONCLUSIÓN: La clasificación en 3 niveles puede ser útil en estudios que analizan las resecciones hepáticas abiertas en centros occidentales y orientales.


Assuntos
Hepatectomia/classificação , Laparoscopia/classificação , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Feminino , Hepatectomia/métodos , Humanos , Japão/epidemiologia , Laparoscopia/métodos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Estudos Retrospectivos , Taxa de Sobrevida/tendências
4.
Phys Rev Lett ; 123(13): 137203, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31697552

RESUMO

The organizing of magnetic skyrmions shows several forms similar to atomic arrays of solid states. Using Lorentz transmission electron microscopy, we report the first direct observation of a stable liquid-crystalline structure of skyrmions in chiral magnet Co_{8.5}Zn_{7.5}Mn_{4}(110) thin film, caused by magnetic anisotropy and chiral surface twist. Elongated skyrmions are oriented and periodically arranged only in the ⟨110⟩ directions, whereas they exhibit short-range order along the ⟨001⟩ directions, indicating a smectic skyrmion state. In addition, skyrmions possess anisotropic interaction with an opposite sign depending on the crystal orientation, in contrast to existing isotropic interaction.

5.
Lupus ; 28(8): 986-994, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31246559

RESUMO

OBJECTIVE: We aimed to study the usefulness of serum soluble CD163 (sCD163) as a biomarker for macrophage activation syndrome (MAS) associated with systemic lupus erythematosus (SLE). METHODS: Serum sCD163 levels were retrospectively measured by enzyme-linked immunosorbent assay for SLE patients associated with MAS (SLE-MAS), lupus nephritis (LN), or autoimmune hemolytic anemia (AIHA) and/or immune thrombocytopenia (ITP) and healthy controls (HCs). Posttreatment samples were also evaluated in the available SLE-MAS patients. The associations between serum sCD163 levels and clinical information were statistically analyzed. RESULTS: The serum sCD163 levels in SLE-MAS, LN and SLE-AIHA/ITP groups were significantly higher than those in HCs (n = 17, 29, 13, and 68, respectively; p < 0.01 for all comparisons). In addition, the serum sCD163 levels in the SLE-MAS group were even higher than those in the LN and SLE-AIHA/ITP groups (p < 0.01 for both comparisons). Serum sCD163 levels were correlated with the SLE Disease Activity Index 2000 scores (r = 0.53), whereas they were not correlated with the serum ferritin levels. With the determined cut-off value, the sensitivity and specificity of serum sCD163 for the diagnosis of SLE-MAS were 59% and 86%, respectively. Retesting showed that the serum sCD163 levels decreased significantly following treatment in parallel with disease amelioration in the SLE-MAS group (p < 0.01). CONCLUSIONS: The present study suggests the usefulness of serum sCD163 as a diagnostic and disease-activity biomarker for SLE-associated MAS. Serum sCD163 might also have a different role as a biomarker for SLE-associated MAS than serum ferritin does.


Assuntos
Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Lúpus Eritematoso Sistêmico/complicações , Síndrome de Ativação Macrofágica/sangue , Receptores de Superfície Celular/sangue , Adulto , Anemia Hemolítica Autoimune/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Nefrite Lúpica/sangue , Síndrome de Ativação Macrofágica/diagnóstico , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/sangue , Curva ROC , Estudos Retrospectivos
6.
Sci Adv ; 4(12): eaav0618, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30547091

RESUMO

After brain injury, neural stem cell-derived neuronal precursors (neuroblasts) in the ventricular-subventricular zone migrate toward the lesion. However, the ability of the mammalian brain to regenerate neuronal circuits for functional recovery is quite limited. Here, using a mouse model for ischemic stroke, we show that neuroblast migration is restricted by reactive astrocytes in and around the lesion. To migrate, the neuroblasts use Slit1-Robo2 signaling to disrupt the actin cytoskeleton in reactive astrocytes at the site of contact. Slit1-overexpressing neuroblasts transplanted into the poststroke brain migrated closer to the lesion than did control neuroblasts. These neuroblasts matured into striatal neurons and efficiently regenerated neuronal circuits, resulting in functional recovery in the poststroke mice. These results suggest that the positioning of new neurons will be critical for functional neuronal regeneration in stem/progenitor cell-based therapies for brain injury.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neurogênese , Neuroglia/metabolismo , Neurônios/metabolismo , Receptores Imunológicos/metabolismo , Regeneração , Transdução de Sinais , Citoesqueleto de Actina/química , Citoesqueleto de Actina/metabolismo , Animais , Astrócitos/metabolismo , Encéfalo/metabolismo , Movimento Celular , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Camundongos , Camundongos Knockout , Ligação Proteica , Multimerização Proteica , Receptores Imunológicos/genética , Proteína cdc42 de Ligação ao GTP/metabolismo
7.
J Oral Rehabil ; 45(5): 393-398, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29420835

RESUMO

Self-reported measures of oral health are often used to assess oral health in populations or groups, but their validity or reliability needs repeated confirmation. The objective of this cross-sectional study was to evaluate the validity of self-reported tooth counts and masticatory status, using data obtained from a sample of Japanese adults. A total of 2356 adults aged 40 to 75 years participated in a questionnaire survey and a clinical oral examination from 2013 through 2016. Self-reported measures were compared with clinically measured values. For tooth counts, mean clinical and self-reported tooth counts in all participants were 23.68 and 23.78 teeth, and no significant difference was detected. Spearman's, Pearson's and intra-class correlation coefficients between clinical and self-reported tooth counts were 0.771, 0.845 and 0.843, respectively. According to the Bland-Altman analysis, the mean difference between clinical and self-reported tooth counts was -0.098 (95% CI: -0.242, 0.047). The upper limit of agreement was 6.919 (95% CI: 6.669, 7.169), and the lower limit of agreement was -7.115 (95% CI: -7.365, -6.865). No significant fixed or proportional bias was observed. For masticatory status, the crude or age- and gender-adjusted mean numbers of total teeth, posterior teeth and 3 kinds of functional tooth units significantly decreased with the deterioration of masticatory status. This study indicated that self-reports were within an acceptable range of clinical measures. Therefore, self-reports were considered valid alternatives to clinical measures to estimate tooth counts and masticatory status in a current Japanese adult population.


Assuntos
Inquéritos de Saúde Bucal/normas , Saúde Bucal/estatística & dados numéricos , Autorrelato/normas , Perda de Dente/epidemiologia , Adulto , Idoso , Envelhecimento , Estudos Transversais , Feminino , Humanos , Japão/epidemiologia , Masculino , Mastigação/fisiologia , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
8.
Phys Rev Lett ; 121(25): 250401, 2018 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-30608846

RESUMO

We demonstrate synthetic azimuthal gauge potentials for Bose-Einstein condensates from engineering atom-light couplings. The gauge potential is created by adiabatically loading the condensate into the lowest energy Raman-dressed state, achieving a coreless vortex state. The azimuthal gauge potentials act as effective rotations and are tunable by the Raman coupling and detuning. We characterize the spin textures of the dressed states, in agreements with the theory. The lowest energy dressed state is stable with a 4.5-s half-atom-number-fraction lifetime. In addition, we exploit the azimuthal gauge potential to demonstrate the Hess-Fairbank effect, the analogue of Meissner effect in superconductors. The atoms in the absolute ground state has a zero quasiangular momentum and transits into a polar-core vortex when the synthetic magnetic flux is tuned to exceed a critical value. Our demonstration serves as a paradigm to create topological excitations by tailoring atom-light interactions where both types of SO(3) vortices in the |⟨F[over →]⟩|=1 manifold, coreless vortices and polar-core vortices, are created in our experiment. The gauge field in the stationary Hamiltonian opens a path to investigating rotation properties of atomic superfluids under thermal equilibrium.

9.
Lupus ; 27(3): 407-416, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28795653

RESUMO

We aimed to validate the reliability of the Medical Outcomes Study Short Form-36 (SF-36) among Japanese patients with systemic lupus erythematosus (SLE). Japanese patients with SLE ( n = 233) completed the SF-36 and other related demographic questionnaires, and physicians simultaneously completed the SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Patients were prospectively followed for a repeat assessment the following year. The SF-36 subscales demonstrated acceptable internal consistency (Cronbach's α of 0.85-0.89), and an overall good test-retest reliability (intraclass correlation coefficient >0.70). The average baseline SF-36 subscale/summary scores except for "bodily pain" were significantly lower than those of the Japanese general population ( p < 0.05). The SDI showed an inverse correlation with the SF-36 subscale/summary scores except for "vitality" and "mental component summary" at baseline, whereas the SLEDAI-2K did not. In the second year, "social functioning" and "mental component summary" of the SF-36 deteriorated among patients whose SDI or SLEDAI-2K score increased (effect sizes < -0.20). In conclusion, the SF-36 demonstrated acceptable reliability among Japanese patients with SLE. Health-related quality of life measured by the SF-36 was reduced in Japanese patients with SLE and associated with disease damage, rather than disease activity.


Assuntos
Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/psicologia , Qualidade de Vida , Inquéritos e Questionários , Adulto , Idoso , Povo Asiático , Feminino , Humanos , Japão , Idioma , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Adulto Jovem
10.
Int J Dent Hyg ; 16(1): 144-150, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28436148

RESUMO

OBJECTIVES: To apply a self-administered assessment form about dental plaque level and gingival condition to Japanese adolescents and to examine the extent to which they can evaluate their own dental plaque and gingivae by comparing with dentists' clinical evaluation. METHODS: Participants were 151 senior high school students (adolescents) who observed their own mouths and recorded dental plaque seen on their 12 anterior teeth, and gingival inflammation condition of 10 anterior interdental papillae, on a self-assessment form. Dentists clinically evaluated dental plaque using the, modified Debris Index (modified DI) and gingival condition, modified PMA index (P-index). "Recognition score" of dental plaque and gingival condition was the total number of agreement between the adolescents' self-assessment and dentists' evaluation. RESULTS: Proportion of agreement on dental plaque between the adolescents' self-assessment and dentists' evaluation with modified DI was 37.4%, and agreement on modified DI score 1, 2 or 3 was significantly lower than that on score 0 (P<.01). Agreement on gingivae was 47.3% in total, and agreement was significantly lower on gingival condition with inflammation than gingivae without inflammation (P<.01). Recognition scores of dental plaque or gingival condition were significantly lower in adolescents with fair or poor modified DI or P-index than in those with good condition (P<.01). CONCLUSION: Most adolescents could not recognize their dental plaque and gingival condition. Adolescents with poorer dental plaque level or gingival condition had lower recognition scores compared to those with better oral health. Improving oral health self-assessment skills could help adolescents achieve better oral health.


Assuntos
Índice de Placa Dentária , Índice Periodontal , Autoavaliação (Psicologia) , Adolescente , Assistência Odontológica , Feminino , Humanos , Japão , Masculino , Saúde Bucal
11.
Oncogene ; 36(37): 5231-5242, 2017 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-28504719

RESUMO

Group3 medulloblastoma (MBG3) that predominantly occur in young children are usually associated with MYC amplification and/or overexpression, frequent metastasis and a dismal prognosis. Physiologically relevant MBG3 models are currently lacking, making inferences related to their cellular origin thus far limited. Using in utero electroporation, we here report that MBG3 mouse models can be developed in situ from different multipotent embryonic cerebellar progenitor cells via conditional expression of Myc and loss of Trp53 function in several Cre driver mouse lines. The Blbp-Cre driver that targets embryonic neural progenitors induced tumors exhibiting a large-cell/anaplastic histopathology adjacent to the fourth ventricle, recapitulating human MBG3. Enforced co-expression of luciferase together with Myc and a dominant-negative form of Trp53 revealed that GABAergic neuronal progenitors as well as cerebellar granule cells give rise to MBG3 with their distinct growth kinetics. Cross-species gene expression analysis revealed that these novel MBG3 models shared molecular characteristics with human MBG3, irrespective of their cellular origin. We here developed MBG3 mouse models in their physiological environment and we show that oncogenic insults drive this MB subgroup in different cerebellar lineages rather than in a specific cell of origin.


Assuntos
Neoplasias Cerebelares/genética , Cerebelo/embriologia , Cerebelo/patologia , Meduloblastoma/genética , Proteínas Proto-Oncogênicas c-myc/genética , Animais , Neoplasias Cerebelares/metabolismo , Neoplasias Cerebelares/patologia , Cerebelo/citologia , Cerebelo/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Meduloblastoma/metabolismo , Meduloblastoma/patologia , Camundongos , Camundongos Transgênicos , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transfecção
12.
Br J Surg ; 104(7): 898-906, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28239843

RESUMO

BACKGROUND: Three-dimensional (3D) imaging has facilitated liver resection with excision of hepatic veins by estimating the liver volume of portal and hepatic venous territories. However, 3D imaging cannot be used for real-time navigation to determine the liver transection line. This study assessed the value of indocyanine green (ICG) fluorescence imaging with hepatic vein clamping for navigation during liver transection. METHODS: Consecutive patients who underwent liver resection with excision of major hepatic veins between 2012 and 2013 were evaluated using ICG fluorescence imaging after clamping veins and injecting ICG. Regional fluorescence intensity (FI) values of non-veno-occlusive regions (FINon ), veno-occlusive regions (FIVO ) and ischaemic regions (FIIS ) were calculated using luminance analysing software. RESULTS: Of the 21 patients, ten, four and seven underwent limited resection, monosegmentectomy/sectionectomy and hemihepatectomy respectively, with excision of major hepatic veins. Median veno-occlusive liver volume was 80 (range 30-458) ml. Fluorescence imaging visualized veno-occlusive regions as territories with lower FI compared with non-veno-occlusive regions, and ischaemic regions as territories with no fluorescence after intravenous ICG injection. Median FIIS /FINon was lower than median FIVO /FINon (0·22 versus 0·59; P = 0·002). There were no deaths in hospital or within 30 days, and only one major complication. CONCLUSION: ICG fluorescence imaging with hepatic vein clamping visualized non-veno-occlusive, veno-occlusive and ischaemic regions. This technique may guide liver transection by intraoperative navigation, enhancing the safety and accuracy of liver resection.


Assuntos
Constrição , Corantes Fluorescentes , Hepatectomia/métodos , Veias Hepáticas/diagnóstico por imagem , Veias Hepáticas/cirurgia , Verde de Indocianina , Imagem Óptica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão
13.
Ultrasonics ; 72: 195-200, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27567038

RESUMO

Steatosis is a critical feature of liver disease and is considered to play a pivotal role in the progression of nonalcoholic fatty liver disease, as well as being a surrogate marker of metabolic syndrome. The purpose of this study was to develop a non-invasive diagnostic method for assessment of liver steatosis. It is well known that ultrasonic velocity depends on materials and temperature. For example, the ultrasonic velocity in water is 1530m/s at 37°C and 1534m/s at 39°C, while that in fat is 1412m/s at 37°C and 1402m/s at 39°C. On this basis, we thought that the percentage of fat in hepatic steatosis could be assessed by detecting changes of ultrasonic in the liver, caused by warming. In order to confirm the effectiveness of this method, we obtained the ultrasonic velocity changes of tissue phantom including lard oil and the liver of living rabbit by ultrasonic warming, and then succeeded in 2-D imaging of ultrasonic velocity changes of the phantom and the liver of living rabbit. We named this the ultrasonic velocity-change method. The experimental results show the possibility that hepatic steatosis could be characterized using our novel, non-invasive method.


Assuntos
Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Ultrassonografia/métodos , Animais , Biomarcadores , Gorduras na Dieta , Progressão da Doença , Imagens de Fantasmas , Coelhos , Temperatura
14.
Oncogenesis ; 5(8): e253, 2016 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-27526107

RESUMO

KRAS mutations occur in 30-40% of all cases of human colorectal cancer (CRC). However, to date, specific therapeutic agents against KRAS-mutated CRC have not been developed. We previously described the generation of mouse models of colon cancer with and without Kras mutations (CDX2P-G22Cre;Apc(flox/flox); LSL-Kras(G12D) and CDX2P-G22Cre;Apc(flox/flox) mice, respectively). Here, the two mouse models were compared to identify candidate genes, which may represent novel therapeutic targets or predictive biomarkers. Differentially expressed genes in tumors from the two mouse models were identified using microarray analysis, and their expression was compared by quantitative reverse transcription-PCR (qRT-PCR) and immunohistochemical analyses in mouse tumors and surgical specimens of human CRC, with or without KRAS mutations, respectively. Furthermore, the functions of candidate genes were studied using human CRC cell lines. Microarray analysis of 34 000 transcripts resulted in the identification of 19 candidate genes. qRT-PCR analysis data showed that four of these candidate genes (Clps, Irx5, Bex1 and Rcan2) exhibited decreased expression in the Kras-mutated mouse model. The expression of the regulator of calcineurin 2 (RCAN2) was also observed to be lower in KRAS-mutated human CRC. Moreover, inhibitory function for cancer cell proliferation dependent on calcineurin was indicated with overexpression and short hairpin RNA knockdown of RCAN2 in human CRC cell lines. KRAS mutations in CRC lead to a decrease in RCAN2 expression, resulting in tumor proliferation due to derepression of calcineurin-nuclear factor of activated T cells (NFAT) signaling. Our findings suggest that calcineurin-NFAT signal may represent a novel molecular target for the treatment of KRAS-mutated CRC.

15.
Lupus ; 25(5): 486-95, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26589578

RESUMO

The Systemic Lupus Activity Questionnaire (SLAQ) is a patient-reported outcome for systemic lupus erythematosus (SLE). We aimed to translate it into Japanese and further investigate its validity and reliability. The English version of the SLAQ was translated into Japanese and administered to Japanese SLE patients at our university clinic. Physicians assessed disease activity using the SLE Disease Activity Index 2000 (SLEDAI-2K). The patients were prospectively followed for repeat assessment a year later. Ultimately, 255 patients participated. The patients' 10-point ratings of disease activity and SLAQ scores were significantly correlated (Spearman's ρ = 0.53). The SLAQ score was weakly correlated with the SLE Disease Activity Index 2000 (SLEDAI-2K)-nolab (omitting laboratory items; ρ = 0.18) but not with the SLEDAI-2K (ρ = 0.02). These results suggested its convergent and discriminant validity. The SLAQ demonstrated acceptable internal consistency (Cronbach's α = 0.80), and good test-retest reliability (intraclass correlation coefficient = 0.85). The effect sizes and the standardized response means of the SLAQ were as follows: clinical worsening, 0.26 and 0.31, and improvement, -0.39 and -0.41, respectively, which indicated a small but significant responsiveness. The Japanese version of the SLAQ demonstrated acceptable reliability and validity; its performance was comparable to that of the original version.


Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , Papel do Médico , Inquéritos e Questionários , Adulto , Idoso , Análise Discriminante , Feminino , Humanos , Japão , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Fatores de Tempo , Tradução , Adulto Jovem
16.
Oncogene ; 35(18): 2407-12, 2016 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-26257060

RESUMO

Intraductal papillary mucinous neoplasm (IPMN), the most common pancreatic cystic neoplasm, is known to progress to invasive ductal adenocarcinoma. IPMNs commonly harbor activating somatic mutations in GNAS and KRAS, primarily GNAS(R201H) and KRAS(G12D). GNAS encodes the stimulatory G-protein α subunit (Gsα) that mediates a stimulatory signal to adenylyl cyclase to produce cyclic adenosine monophosphate (cAMP), subsequently activating cAMP-dependent protein kinase A. The GNAS(R201H) mutation results in constitutive activation of Gsα. To study the potential role of GNAS in pancreatic tumorigenesis in vivo, we generated lines of transgenic mice in which the transgene consisted of Lox-STOP-Lox (LSL)-GNAS(R201H) under the control of the CAG promoter (Tg(CAG-LSL-GNAS)). These mice were crossed with pancreatic transcription factor 1a (Ptf1a)-Cre mice (Ptf1a(Cre/+)), generating Tg(CAG-LSL-GNAS);Ptf1a(Cre/+) mice. This mouse line showed elevated cAMP levels, small dilated tubular complex formation, loss of acinar cells and fibrosis in the pancreas; however, no macroscopic tumorigenesis was apparent by 2 months of age. We then crossed Tg(CAG-LSL-GNAS);Ptf1a(Cre/+) mice with LSL-Kras(G12D) mice, generating Tg(CAG-LSL-GNAS);LSL-Kras(G12D);Ptf1a(Cre/+) mice. We used these mice to investigate a possible cooperative effect of GNAS(R201H) and Kras(G12D) in pancreatic tumorigenesis. Within 5 weeks, Tg(CAG-LSL-GNAS);LSL-Kras(G12D);Ptf1a(Cre/+) mice developed a cystic tumor consisting of marked dilated ducts lined with papillary dysplastic epithelia in the pancreas, which closely mimicked the human IPMN. Our data strongly suggest that activating mutations in GNAS and Kras cooperatively promote murine pancreatic tumorigenesis, which recapitulates IPMN. Our mouse model may serve as a unique in vivo platform to find biomarkers and effective drugs for diseases associated with GNAS mutations.


Assuntos
Carcinogênese/genética , Carcinoma Ductal Pancreático/patologia , Cromograninas/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Mutação , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Animais , Feminino , Humanos , Masculino , Camundongos , Neoplasias Pancreáticas/genética
17.
Int J Dent Hyg ; 14(2): 135-41, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26098532

RESUMO

OBJECTIVE: To assess oral malodour level and its association with health behaviour, oral health behaviour and oral health status among adolescents. METHOD: A questionnaire survey and clinical examination that included tongue coating and oral malodour status were conducted on 665 senior high school students in Saitama, Japan. Analyses of Pearson chi-square, independent samples t-test and logistic regression were conducted using SPSS 19.0 with the significance level set at P < 0.05. RESULTS: There were 173 (26.0%) subjects who had oral malodour and 54.7% of subjects reported they were conscious of their own oral malodour. Logistic regression analysis showed that subjects who skipped breakfast were 1.7 times more likely to have oral malodour than those who had breakfast. Subjects who did not have the habit of cleaning their tongue daily were also 1.7 times more likely to have oral malodour compared to those who had the habit. The odds of having oral malodour increased as the area of tongue coating widened. CONCLUSION: Tongue coating, daily tongue cleaning and breakfast are significant factors for oral malodour among adolescents. Proper tongue coating management together with other healthy lifestyle behaviours, especially having breakfast, should be advocated in adolescents' health education.


Assuntos
Halitose/diagnóstico , Comportamentos Relacionados com a Saúde , Nível de Saúde , Saúde Bucal , Adolescente , Comportamento Alimentar , Feminino , Halitose/etiologia , Humanos , Japão , Masculino , Língua
18.
Lupus ; 25(5): 463-71, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26527504

RESUMO

OBJECTIVE: Psychological distress, such as depression and anxiety, has been intensively studied in patients with systemic lupus erythematosus (SLE). However, those studies have mostly included patients who were treated with corticosteroids, which might themselves induce mood disturbances. We investigated psychological distress in corticosteroid-naive patients with SLE who did not exhibit any overt neuropsychiatric manifestations. METHODS: Forty-three SLE in-patients with no current or past abnormal neuropsychiatric history participated in the study. Patients and 30 healthy control subjects with similar demographic and personality characteristics were administered a comprehensive battery of psychological/neuropsychological tests. The Profile of Mood States (POMS) was used to assess depression and anxiety. Results of clinical, laboratory, and neurological tests were compared with regard to their presence. RESULTS: Prevalence of depression was higher in patients (n = 11, 25.6%) than in controls (n = 2, 6.7%; p = 0.035), although prevalence of anxiety did not differ across groups (patients: 34.9%, n = 15; controls: 16.7%, n = 5; p = 0.147). Using multiple logistic regression analysis, we identified avoidance coping methods (OR, 1.3; 95% CI 1.030-1.644; p = 0.027) as an independent risk factor for depression. CONCLUSION: Our results indicate that depression presents more frequently in corticosteroid-naive patients with early-stage, active SLE than in the normal population, but anxiety does not. Depression may be related to psychological reactions to suffering from the disease.


Assuntos
Ansiedade/psicologia , Depressão/psicologia , Lúpus Eritematoso Sistêmico/psicologia , Estresse Psicológico/psicologia , Adaptação Psicológica , Adulto , Afeto , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Estudos de Casos e Controles , Estudos Transversais , Depressão/diagnóstico , Depressão/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Modelos Logísticos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Análise Multivariada , Testes Neuropsicológicos , Razão de Chances , Prevalência , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Fatores de Risco , Estresse Psicológico/diagnóstico , Estresse Psicológico/epidemiologia , Adulto Jovem
19.
Community Dent Health ; 32(3): 148-52, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26513849

RESUMO

OBJECTIVES: To explore the level of oral health literacy among adults in Belarus, a former part of the Soviet Union, and to analyse the associations between oral health literacy, socio-demographics, health behaviour and oral health status. BASIC RESEARCH DESIGN: A cross-sectional study. Participants: 281 adult (18-60 years old) dental patients. MAIN OUTCOME MEASURE: The participants completed a self-administered questionnaire collecting information about socio-demographics and health behaviours, and oral health literacy test (the R-OHLI). Clinical oral examination followed the questionnaire survey. RESULTS: Among participants, 68.7% had adequate, 18.9% had marginal and 12.4% inadequate oral health literacy levels. Females and those with higher education were more likely to have adequate oral health literacy (p<0.05 and p<0.001). Participants with adequate oral health literacy had fewer missing and more filled teeth than those with inadequate literacy (p<0.001). This association remained significant after adjusting for socio-demographics, behavioural characteristics and oral hygiene status (p<0.05 and p<0.001). CONCLUSIONS: Adequate oral health literacy was strongly related with better oral health status. Improvement of oral health literacy should be addressed when developing community oral health promotions.


Assuntos
Comportamentos Relacionados com a Saúde , Letramento em Saúde , Nível de Saúde , Saúde Bucal , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República de Belarus
20.
Br J Surg ; 102(7): 796-804, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25873161

RESUMO

BACKGROUND: Laparoscopic major hepatectomy (LMH) is evolving as an important surgical approach in hepatopancreatobiliary surgery. The present study aimed to evaluate the learning curve for LMH at a single centre. METHODS: Data for all patients undergoing LMH between January 1998 and September 2013 were recorded in a prospective database and analysed. The learning curve for operating time (OT) was evaluated using the cumulative sum (CUSUM) method. RESULTS: Of 173 patients undergoing major hepatectomy, left hepatectomy was performed in 28 (16·2 per cent), left trisectionectomy in nine (5·2 per cent), right hepatectomy in 115 (66·5 per cent), right trisectionectomy in 13 (7·5 per cent) and central hepatectomy in eight (4·6 per cent). Median duration of surgery was 270 (range 100-540) min and median blood loss was 300 (10-4500) ml. There were 20 conversions to an open procedure (11·6 per cent). Vascular clamping was independently associated with conversion on multivariable analysis (hazard ratio 5·95, 95 per cent c.i. 1·24 to 28·56; P = 0·026). The CUSUMOT learning curve was modelled as a parabola (CUSUMOT = 0·2149 × patient number(2) - 30·586 × patient number - 1118·3; R(2) = 0·7356). The learning curve comprised three phases: phase 1 (45 initial patients), phase 2 (30 intermediate patients) and phase 3 (the subsequent 98 patients). Although right hepatectomy was most common in phase 1, a significant decrease was observed from phase 1 to 3 (P = 0·007) in favour of more complex procedures. CONCLUSION: The learning curve for LMH consisted of three characteristic phases identified by CUSUM analysis. The data suggest that the learning phase of LMH included 45 to 75 patients.


Assuntos
Educação Médica Continuada , Hepatectomia/educação , Laparoscopia/educação , Curva de Aprendizado , Hepatopatias/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepatectomia/métodos , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Adulto Jovem
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