環境刺激により蓄積され,癌化へと導く食道上皮の遺伝子変化の解析

金沢大学医薬保健研究域医学系食道癌において蓄積される形質変化を遺伝子発現変化として検索した結果,以下の癌特異的遺伝子を得た。1,補体分子complement component 6(C6)及びcomplement component 7(C7)の局所発現の癌特異的低下(Rie Oka et al., European Journal of Cancer, in press)differential display法を用いて,C7遺伝子発現が正常粘膜に豊富に発現しているのに対し癌組織においては高頻度に著明な発現低下があることを見い出した。さらに組織化学的に検討した結果,C7の局所産生は食道上皮のkeratinocyteであり,発癌に伴って発現が低下することが示された。さらに他の補体分子について局所産生を調べた結果,C3,C5分子は正常,癌粘膜両方で豊富な発現が見られるのに対し,C6がC7に伴い減少していた。これらの結果から食道癌においては局所の補体産生が減少し,それが癌の補体活性化の抑制機構に関与する可能性が示唆された。2,keratin 4(K4)の発現低下(投稿準備中)非角化性の重層扁平上皮の分化マーカーであるケラチン分子(K4)も同じく癌特異的に発現変化する遺伝子として検出された。この結果は従来の免疫組織化学的研究の報告とよく一致するものである。他のケラチン分子について同時に発現変化を調べた結果,K13が共に低下している一方,基底細胞特異的なK14は逆にup-regulationされていた。3,高感度differential display法の開発(Rie Oka et al.,Journal of Health Science,2001)効率よく癌関連遺伝子を得るために従来のdifferential displayに改良を加え,他にもKIAA1160やESTに属する未知遺伝子を得た。出典：「 環境刺激により蓄積され,癌化へと導く食道上皮の遺伝子変化の解析 」研究成果報告書　課題番号11770180（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （ https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-11770180/ ）を加工して作成研究課題/領域番号:11770180, 研究期間 (年度):1999 – 200

Long-term Follow-up of Orthodontic Patient with Cervical Lymphangioma

Aim: To report a treatment case of mandibular deviation caused by congenital cervical lymphangioma with traditional orthodontic techniques, following-up by 10-year retention. Background: Lymphangiomas, developmental anomalies, can induce various disturbances of swallowing, mastication, speech, breathing, and skeletal deformities as well as psychological stress and anxiety for the patient and their family. Lymphangiomas are benign with virtually no possibility of turning into a malignant lesion, so clinical management aims to treat the patient functionally. Case description: A girl, aged 6 years and 4 months, complained about facial asymmetry and anterior crossbite caused by congenital cervical lymphangioma. Her facial profile was the straight type with an adequate lip position. Anterior and right-side posterior crossbites were observed. On the frontal cephalogram, the menton shifted 3.0 mm to the right. A functional appliance with an expander was placed to correct her dental midline deviation and posterior crossbite. After 2-year treatment, the anterior and right-side posterior crossbites were improved. Multibracket treatment began after the growth spurt. After 44-month active treatment, a functional occlusion, including a Class I molar relationship with a proper interincisal relationship, was achieved. A functional occlusion was maintained during a 10-year retention period, while a mandibular downward growth was observed through the retention period. Conclusion: Conventional orthodontic techniques enable functional and stable occlusion even in patients with mandibular deviation caused by congenital cervical lymphangioma, although only using early orthodontic management by itself may have some limitations. Clinical significance: The hybrid technique combining functional appliance and intermaxillary elastics proves to be an effective therapy for correcting occlusal cant and mandibular deviation caused by cervical lymphangioma

Contribution of visceral adiposity and insulin resistance to metabolic risk factors in Japanese men

金沢大学大学院医学系研究科北陸中央病院内科We investigated the relative impacts of visceral adiposity and insulin resistance on the metabolic risk profile in middle-aged Japanese men. A cross-sectional study was conducted in 636 nondiabetic Japanese men with a mean age of 51.6 years. Visceral adipose tissue (AT) was assessed using computed tomography, and insulin resistance was determined by the homeostasis model assessment of insulin resistance (HOMA-IR). Metabolic risk factors were diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome criteria: (1) hypertriglyceridemia, (2) low high-density lipoprotein cholesterol, (3) hypertension, (4) impaired fasting glucose, and (5) impaired glucose tolerance. Visceral AT and HOMA-IR were significantly and positively correlated with each other (r = 0.41, P < .001). Using the 75th percentile value as a cut point, those with isolated large visceral AT showed significantly greater odds ratios for each of the 5 risk factors measured except impaired fasting glucose, whereas those with isolated high HOMA-IR showed significantly greater odds ratios for each of the 5 risk factors except hypertriglyceridemia and impaired glucose tolerance, compared with the control group. The combined group (increased visceral AT and HOMA-IR) had the highest odds ratios for all studied risk factors. On logistic regression analysis using visceral AT and HOMA-IR as continuous independent variables, they were each independently associated with most of the metabolic risk factors and their clustering. In conclusion, neither visceral AT nor HOMA-IR stands out as the sole driving force of the risk profile; each makes a significant contribution to metabolic abnormalities in Japanese men. © 2010 Elsevier Inc. All rights reserved

A survey of problems in the care and support of infants born at very low birth weight

Orientador: Prof. Dr. Clodomiro Unsihuay-VilaCoorientadora: Prof.a Dr. a Thelma Solange P. FernandesDissertação (mestrado) - Universidade Federal do Paraná, Setor de Tecnologia, Programa de Pós-Graduação em Engenharia Elétrica. Defesa : Curitiba, 29/08/2019Inclui referências: p. 127-133Área de concentração: Sistema de energiaResumo: A frota de veículo elétrico (VE) cresce rapidamente no mundo, em 2018 já superou a marca de 5,1 milhões. A inserção de VE nas redes ativas de distribuição significa uma evolução nos sistemas de energia elétrica, mas essa evolução requer avanços no planejamento da operação, de maneira a considerar o aumento da complexidade que esses novos elementos podem causar na rede. Por isso, se faz necessário ferramentas computacionais que permitam analisar os impactos que o VE causa na operação de redes ativas de distribuição, de maneira a auxiliar na definição de estratégias operativas apropriadas e garantir a otimização de todos os recursos energéticos do sistema. Dessa forma, nesta dissertação foi desenvolvido um modelo computacional, formulado como um problema de otimização capaz de determinar a programação diária da operação de redes ativas de distribuição, considerando a inserção do VE na rede. O problema foi abordado através de um Fluxo de Potência Ótimo (FPO) multiperíodo. A intertemporalidade do problema é formulada através da introdução de uma função de acoplamento representada pela energia armazenada pelas baterias do VE. A resolução do FPO foi através do Métodos dos Pontos Interiores versão Primal-Dual. O horizonte de planejamento é de 24 períodos, divididos em horas. Também é considerado a geração distribuída fotovoltaica e um sistema de tarifação horária de energia. O veículo elétrico é incorporado no problema por meio da adição de uma variável de otimização à função objetivo que além de alterar as restrições de balanço de potência também é usada para monitorar a energia armazenada nas baterias. Como resultado, têm-se um FPO multiperíodo que busca, além da minimização dos custos operativos e perdas de transmissão, também a maximização da energia armazenada nas baterias dos veículos elétricos conectados à rede visando a injeção ótima de energia à rede ativa. Nas simulações realizadas, foram utilizados cenários determinísticos de conexão do VE para avaliar seus impactos nas perdas, custos operacionais e perfil de tensão do sistema elétrico. Os resultados de simulações demonstraram que, no cenário de perfil residencial, que possibilitam o carregamento/descarregamento, é perceptível uma melhora no perfil de tensão do sistema. Isso mostra que a apropriada operação dos VEs com possibilidade de injeção de energia à rede podem ser uma boa alternativa para deslocar picos de carga e reduzir custos operacionais da rede ativa de distribuição. Para o perfil comercial, é perceptível uma redução do perfil de tensão para o seu instante de conexão. Entretanto, esse comportamento pode ser complementado através de uma geração fotovoltaica, que apresenta seus picos de geração nos mesmos instantes em que o VE carrega. Para os cenários que consideram uma alta inserção de VE na rede, os impactos no perfil de tensão do sistema são bastante significativos, demonstrando que para que a rede seja capaz de atender uma grande frota de VEs devem ser feitos investimentos na infraestrutura da rede de distribuição. O impacto da inserção do VE à rede pode aumentar em até 40% as perdas do sistema. Os impactos no custo de operação são significativos, podendo aumentar em até 19%, para cenários de alta penetração de VE. Palavras-chave: Planejamento da Operação. Redes Ativas de Distribuição. Veículo Elétrico. Fluxo de Potência Ótimo. Método dos Pontos Interiores versão Primal-Dual. Armazenamento de energia em baterias.Abstract: The electric vehicle (EV) fleet is growing rapidly in the world, by 2018, it has already surpassed the 5.1 million mark. The insertion of EV into active distribution grids means an evolution in power systems, but this evolution requires advances in operation planning in order to consider the increased complexity that these new elements in the grid may cause. Therefore, computational tools are needed to analyze the impacts that EV has on the operation of active distribution networks, in order to help define appropriate operating strategies and ensuring the optimization of all energy resources in the system. Thus, in this dissertation a computational model was developed, formulated as an optimization problem capable of determining the daily programming of the active distribution networks operation, considering the insertion of the EV in the network. The problem was addressed through a Multi-Period Optimal Power Flow (OPF). The intertemporality of the problem is formulated by introducing a coupling function represented by the energy stored by LV batteries. The resolution of the OPF was through the Primal-Dual Interior Point Method. The planning horizon is 24 periods, divided into hours, under the influence of photovoltaic generation and an hourly energy hourly charging system. The electric vehicle is incorporated into the problem by adding an optimization variable to the objective function which in addition to changing the power balance restrictions is also used to monitor the energy stored in the batteries. As a result, there is a MultiPeriod OPF that seeks, in addition to minimizing operating costs and transmission losses, also maximizing the energy stored in the batteries of electric vehicles connected to the grid for optimal injection of power to the grid at peak hours. In the simulations performed, deterministic EV connection scenarios were used to assess their impacts on losses, operating costs and voltage profile. Simulation results showed that, in the residential profile scenario, which enables loading / unloading, an improvement in the system voltage profile is noticeable. Showing that appropriate EV operation can be a good alternative for shifting power generation from light load moments of the system to high load moments, optimizing the use of system energy resources, reducing operating costs of active distribution. For the commercial profile, a reduction of the voltage profile is noticeable for its connection time. However, this behavior can be complemented by a photovoltaic generation, which presents its generation peaks at the same time that the EV charges. For scenarios that consider a high insertion of EV in the grid, the impacts on the system voltage profile are quite significant, demonstrating that for the grid to be able to serve a large fleet of EVs, investments in the distribution network infrastructure must be made. The impacts of EV insertion into the network can increase system losses by up to 40%. The impacts on operating costs are significant and may increase by up to 19% for high EV penetration scenarios. Keywords: Operation Planning. Active Distribution Networks. Electric Vehicle. Optimal Power Flow. Primal-Dual Interior Point Method. Energy storage in batteries

Comparison of effects of bezafibrate and fenofibrate on circulating proprotein convertase subtilisin/kexin type 9 and adipocytokine levels in dyslipidemic subjects with impaired glucose tolerance or type 2 diabetes mellitus: Results from a crossover study

金沢大学医学系研究科Background: Bezafibrate and fenofibrate show different binding properties against peroxisome proliferator-activated receptor subtypes, which could cause different clinical effects on circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and on various metabolic markers. Methods: An open, randomized, four-phased crossover study using 400 mg of bezafibrate or 200 mg of fenofibrate was performed. Study subjects were 14 dyslipidemia with impaired glucose tolerance or type 2 diabetes mellitus (61 ± 16 years, body mass index (BMI) 26 ± 3 kg/m2, total cholesterol (TC) 219 ± 53 mg/dL, triglyceride (TG) 183 ± 83 mg/dL, high-density lipoprotein-cholesterol (HDL-C) 46 ± 8 mg/dL, fasting plasma glucose 133 ± 31 mg/dL and HbA1c 6.2 ± 0.8%). Subjects were given either bezafibrate or fenofibrate for 8 weeks, discontinued for 4 weeks and then switched to the other fibrate for 8 weeks. Circulating PCSK9 levels and other metabolic parameters, including adiponectin, leptin and urine 8-hydroxy-2′-deoxyguanosine (8-OHdG) were measured at 0, 8, 12 and 20 weeks. Results: Plasma PCSK9 concentrations were significantly increased (+39.7% for bezafibrate and +66.8% for fenofibrate, p < 0.001) in all patients except for one subject when treated with bezafibrate. Both bezafibrate and fenofibrate caused reductions in TG (-38.3%, p < 0.001 vs. -32.9%, p < 0.01) and increases in HDL-C (+18.0%, p < 0.001 vs. +11.7%, p < 0.001). Fenofibrate significantly reduced serum cholesterol levels (TC, -11.2%, p < 0.01; non-HDL-C, -17.3%, p < 0.01; apolipoprotein B, -15.1%, p < 0.01), whereas bezafibrate significantly improved glucose tolerance (insulin, -17.0%, p < 0.05) and metabolic markers (γ-GTP, -38.9%, p < 0.01; adiponectin, +15.4%, p < 0.05; urine 8-OHdG/Cre, -9.5%, p < 0.05). Conclusion: Both bezafibrate and fenofibrate increased plasma PCSK9 concentrations. The addition of a PCSK9 inhibitor to each fibrate therapy may achieve beneficial cholesterol lowering along with desirable effects of respective fibrates. © 2011 Elsevier Ireland Ltd. All rights reserved

Study Protocol for the Effects of Artificial Intelligence (AI)-Supported Automated Nutritional Intervention on Glycemic Control in Patients with Type 2 Diabetes Mellitus

金沢大学附属病院代謝内科Nutritional intervention is effective in improving glycemic control in patients with type 2 diabetes but requires large inputs of manpower. Recent improvements in photo analysis technology facilitated by artificial intelligence (AI) and remote communication technologies have enabled automated evaluations of nutrient intakes. AI- and mobile-supported nutritional intervention is expected to be an alternative approach to conventional in-person nutritional intervention, but with less human resources, although supporting evidence is not yet complete. The aim of this study is to test the hypothesis that AI-supported nutritional intervention is as efficacious as the in-person, face-to-face method in terms of improving glycemic control in patients with type 2 diabetes

Associations between Sleep-Disordered Breathing and Metabolic Risk Factors beyond Obesity

金沢大学附属病院代謝内科Objective. Individuals with multiple metabolic risk factors often experience concomitant sleep-disordered breathing (SDB). We aimed to determine the associations of SDB with individual components of metabolic syndrome independent of obesity. Methods. A cross-sectional study was conducted in 1137 employees aged 30–64 years. Apnea-hypopnea index (AHI) was assessed using a portable monitor for obstructive sleep apnea by admission. Of these, 451 participants took an oral glucose tolerance test to assess homeostatic model assessment of insulin resistance (HOMA-IR) and Matsuda insulin sensitivity index (ISI). Results. The odds ratio (OR) of the highest category of the AHI (≥15 episodes per hour) compared to the lowest one (<5 episodes per hour) was significantly elevated for hypertension, for hypertriglyceridemia, and for low HDL-cholesterolemia when adjusted for age, sex, and alcohol and smoking status (). After further adjustment for body mass index (BMI) or waist circumference, the associations for hypertension still remained statistically significant () while those for hypertriglyceridemia and low HDL-cholesterolemia were no longer significant. The association between higher insulin resistance as assessed by HOMA-IR and Matsuda ISI and higher categories of the AHI was also lost after adjustment for BMI. Conclusion. Obesity was a strong confounding factor in the association between SDB and most metabolic risk factors including insulin resistance, except for hypertension. Further longitudinal study is needed to examine the temporal or causal relationships between SDB and metabolic risk factors. This trial is registered with UMIN-CTR UMIN000028067

Accuracy of 1-Hour Plasma Glucose During the Oral Glucose Tolerance Test in Diagnosis of Type 2 Diabetes in Adults : A Meta-analysis

OBJECTIVE One-hour plasma glucose (1-h PG) during the oral glucose tolerance test (OGTT) is an accurate predictor of type 2 diabetes. We performed a meta-analysis to determine the optimum cutoff of 1-h PG for detection of type 2 diabetes using 2-h PG as the gold standard. RESEARCH DESIGN AND METHODS We included 15 studies with 35,551 participants from multiple ethnic groups (53.8% Caucasian) and 2,705 newly detected cases of diabetes based on 2-h PG during OGTT. We excluded cases identified only by elevated fasting plasma glucose and/or HbA(1c). We determined the optimal 1-h PG threshold and its accuracy at this cutoff for detection of diabetes (2-h PG >= 11.1 mmol/L) using a mixed linear effects regression model with different weights to sensitivity/specificity (2/3, 1/2, and 1/3). RESULTS Three cutoffs of 1-h PG, at 10.6 mmol/L, 11.6 mmol/L, and 12.5 mmol/L, had sensitivities of 0.95, 0.92, and 0.87 and specificities of 0.86, 0.91, and 0.94 at weights 2/3, 1/2, and 1/3, respectively. The cutoff of 11.6 mmol/L (95% CI 10.6, 12.6) had a sensitivity of 0.92 (0.87, 0.95), specificity of 0.91 (0.88, 0.93), area under the curve 0.939 (95% confidence region for sensitivity at a given specificity: 0.904, 0.946), and a positive predictive value of 45%. CONCLUSIONS The 1-h PG of >= 11.6 mmol/L during OGTT has a good sensitivity and specificity for detecting type 2 diabetes. Prescreening with a diabetes-specific risk calculator to identify high-risk individuals is suggested to decrease the proportion of false-positive cases. Studies including other ethnic groups and assessing complication risk are warranted.Peer reviewe