Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota.

Periodontitis has been implicated as a risk factor for metabolic disorders such as type 2 diabetes, atherosclerotic vascular diseases, and non-alcoholic fatty liver disease. Although bacteremias from dental plaque and/or elevated circulating inflammatory cytokines emanating from the inflamed gingiva are suspected mechanisms linking periodontitis and these diseases, direct evidence is lacking. We hypothesize that disturbances of the gut microbiota by swallowed bacteria induce a metabolic endotoxemia leading metabolic disorders. To investigate this hypothesis, changes in the gut microbiota, insulin and glucose intolerance, and levels of tissue inflammation were analysed in mice after oral administration of Porphyromonas gingivalis, a representative periodontopathogens. Pyrosequencing revealed that the population belonging to Bacteroidales was significantly elevated in P. gingivalis-administered mice which coincided with increases in insulin resistance and systemic inflammation. In P. gingivalis-administered mice blood endotoxin levels tended to be higher, whereas gene expression of tight junction proteins in the ileum was significantly decreased. These results provide a new paradigm for the interrelationship between periodontitis and systemic diseases

A Practical Study on School Volunteer Promotion Supports in cooperation with Student Staffs

　2013年10月よりスクールボランティアビューローに「学生スタッフ制度」を新たに設け，活動開始後2年が経過した。その間，学生スタッフと大学教職員が協働し，スクールボランティアフェアの開催，スクールボランティア活動事例集の作成・編集・発行と各教育委員会等への配布，スクールボランティアツアーの実施等様々な学生目線のスクールボランティア推進支援事業に取り組んできた。それぞれの事業では，学生スタッフが学生らしい工夫を随所に凝らしており，企画・準備から実施・反省に至るまで多大な尽力・努力をした。これらの活動を通して，スクールボランティア活動に参加しようと思っている学生やなかなか一歩が踏み出せない学生に対する啓発活動として大変効果的な事業であったことは成果と言えるが，学生の参加減少や学生への周知の難しさ，また，学生スタッフのなり手不足や大学教職員からの学生への働きかけの重要性など課題も残っている

A New Support Program to Urge University Students to Participate in School Volunteer Activities

　教員養成における学校現場での実践的・体験的活動が昨今一層求められている。教育再生実行会議での提言 や中央教育審議会での報告でも，採用前の学生の学校現場でのボランティア活動を推奨している。こうした中， 2013 年度の岡山大学におけるスクールボランティア活動の登録者数が大幅に減少した。要因としては学校現場 でのインターンシップ活動が必修化された点が大きいが，インターンシップとボランティアの長短を学生は理解 し参加していく必要がある。こうした社会的要請や大学における課題などを踏まえ，スクールボランティアビュー ローに新たに「学生スタッフ制度」を設けた。学生の立場から，スクールボランティア活動を多面的に支援し， 関連事業の企画・参画・連携を学生と教職員が協働して実施するものである。最初の取り組みとして，2014 年4 月には「スクールボランティアフェア2014」を開催した

日本人男性における携帯式尿流量計(P-Flowdiary®)を用いた排尿量/尿流量に関する年齢階層別ノモグラムの作成

Background: To develop a nomogram of urinary volume and flow based on the data of Japanese men without lower urinary tract symptoms and multiple flows per participant whose characteristics were clear. Methods: Overall, 101 Japanese male volunteers without lower urinary tract symptoms aged between 20 and 59 years were enrolled. A portable uroflowmeter (P-Flowdiary®) was used to record urinary information (flow rate and volume) for 2 successive days. The model (quadratic, linear, or logarithmic regression) most fit for the relationship between maximum flow rate and voided volume was determined. The maximum flow rate at > 150 mL was compared among the 20-29-, 30-39-, 40-49-, and 50-59-year age groups. Nomograms appropriate for the age groups were created. Results: The mean age, International Prostate Symptom Score, and Overactive Bladder Symptom Score were 38.5 years, 0.42, and 0.24, respectively. The quadratic regression model was the most fit because its mean coefficient determination was 0.93 ± 0.06. The mean maximum flow rate was significantly lower in the 50-59-year age group (21.8 ± 5.05 mL/s, P < 0.01) than in the younger groups (24.14 ± 4.94, 24.05 ± 6.99, and 24.64 ± 5.72 mL/s). The 2 nomograms are Y = 28.99 {1 - exp(- 0.01 × X)} and Y = 25.67 {1 - exp(- 0.01 × X)} for the 20-49- and 50-59-year age groups, respectively. Conclusions: The nomogram can predict maximum flow rate based on voided volume in Japanese men aged 20-59 years without lower urinary tract symptoms.博士（医学）・甲第858号・令和4年12月22日© 2022. The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data

ラット膀胱での水吸収におけるアクアポリン-2の役割

AIM: We investigated the role of the bladder wall in permeating water, focusing on aquaporins. METHODS: Female Sprague-Dawley rats weighing 300 g were used to investigate the role of the bladder wall in saline permeation. Changes in intravesical fluid volume and sodium concentration were measured in the desmopressin acetate hydrate-loaded and control groups 3 h after administration. Bladders were resected to measure aquaporin-1, 2, and 3 gene expression using qRT-PCR. Additionally, the change of aquaporin-2 expression was measured using Western blotting and immunohistochemistry in intravesical aquaporin-2 siRNA-treated and control groups. RESULTS: Although the intravesical fluid volume and sodium concentration significantly decreased from 0 to 3 h (1.00 ± 0.00 vs 0.83 ± 0.08 mL, 157.80 ± 1.30 vs 146.8 ± 1.92 mEq/mL, P < 0.01, respectively in the control group), administration of desmopressin did not affect the extent of volume change. Aquaporin-2 expression was significantly higher in the 3-h distended bladders than in the empty bladder. Aquaporin-2 siRNA treatment suppressed aquaporin-2 expression and the change of intravesical fluid volume from 0 to 3 h (1.00 ± 0.00 and 0.99 ± 0.02 mL), which was related to the suppression of sodium concentration change in comparison with control siRNA treatment (149.6 ± 2.4 vs 143.6 ± 3.67 mEq/mL, P < 0.05). CONCLUSIONS: The rat urinary bladder absorbs water and salts under the full-filled condition. Aquaporin-2 plays an important role in the transport of water, accompanied by sodium concentration change. We demonstrated a part of the bladder absorption mechanism, which may lead to development of a new method for regulating bladder storage function.博士（医学）・甲第697号・平成31年3月15日© 2018 Wiley Periodicals, Inc.This is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1002/nau.23715], which has been published in final form at [http://dx.doi.org/10.1002/nau.23715]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

Life sciences

Aims: To examine the circadian expression changes in bladder clock genes in Dahl salt-sensitive rats following high salt intake. Main methods: Eighteen rats were divided into three groups: the high-salt diet group (HS group), the normal-salt diet group (NS group), and the salt-load interruption group (from a 4 % salt diet to a normal diet; salt-load interruption group [SI group]). Each rat was placed in an individual metabolic cage for 24 h twice weekly. Water intake, urine production, voiding frequency, and voided volume per micturition were recorded. Furthermore, 108 control rats were prepared. Bladders were harvested every 4 h at six time points. Furthermore, the mRNA expression of clock genes and mechanosensors was analyzed. Key findings: In the HS group, the bladder clock genes showed lower mRNA levels than in the NS group. The amplitude of circadian expression changes in bladder clock genes in the HS group was lower than that in the NS group. However, after changing from a 4 % salt diet to a normal diet, the waveforms of the clock gene expression in the SI group were closer to those of the NS group. The 24-h water intake and urinary volume of the SI group decreased to levels comparable to those of the NS group. Significance: Reduced salt intake partially restored the circadian rhythms of bladder clock genes.博士（医学）・甲第857号・令和4年12月22日Copyright © 2022 Elsevier Inc. All rights reserved

PDE5阻害薬であるタダラフィルは糖尿病ラットの膀胱血流を改善し、初期段階に低下する下部尿路機能を回復する

AIMS: To investigate the effect of tadalafil on bladder blood flow and lower urinary tract function in a rat model of diabetes. MATERIALS AND METHODS: We studied female Sprague-Dawley rats and induced diabetes in some using a single intraperitoneal injection of streptozotocin. We divided the rats into nondiabetes (ND), diabetes (D), and diabetes with tadalafil (DT) groups. The rats were raised for an additional 7 weeks after diabetes induction. The DT group received oral tadalafil (2 mg/kg/day) for 7 days before the experiments. At 7 weeks after diabetes induction, we performed cystometry, resected the bladders for immunohistochemistry (hypoxia-inducible factor-1α [HIF-1α] and 8-oxo-2'-deoxyguanosine [8-OHdG] staining), and measured bladder blood supply using a laser blood flow meter. RESULTS: The opening pressure, when the urethra opens and urine flow starts, was significantly lower in the DT group than in the D group (24.9 ± 5.9 vs 43.6 ± 12.3 cmH2 O). The inter-contraction interval was significantly longer in the D group than in the ND and DT groups (1566.2 ± 168.7 vs 702.9 ± 165.2 and 787.4 ± 148.8 s). Immunohistochemistry showed positive staining of the urothelial layer for both HIF-1α and 8-OHdG in the D group, but not in the ND or DT groups. Bladder blood flow was significantly lower in the D group than in the ND or DT groups. CONCLUSIONS: Tadalafil improves bladder blood supply and lower urinary tract function in diabetic rats. Tadalafil may be a promising drug that restores lower urinary tract dysfunction in the early phase of diabetes.博士（医学）・甲第677号・平成30年3月15日© 2017 Wiley Periodicals, Inc.This is the peer reviewed version of the following article: "http://dx.doi.org/10.1002/nau.23372", which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

Pretreatment Platelet-to-Lymphocyte Ratio as Biomarker for Neoadjuvant Chemotherapy Prior to Radical Cystectomy in Muscle-Invasive Bladder Cancer.

Objectives : To evaluate the clinical benefit of neoadjuvant chemotherapy with gemcitabine and cisplatin (GC) in patients with muscle-invasive bladder cancer treated with radical cystectomy and to identify patients who may benefit from neoadjuvant chemotherapy and predictors of therapeutic response to it. Methods : In this prospective study, we enrolled 37 patients with muscle-invasive bladder cancer (cT2-4aNanyM0). The primary endpoint was the pathological response rate at cystectomy after receiving neoadjuvant GC chemotherapy. Univariable and multivariable analyses were used to determine predictive factors of pT0N0 and ≦pT1N0. The secondary endpoints were adverse events during chemotherapy, surgical complications, as well as overall, disease-specific, and recurrence-free survival. Results : A mean of 2.7 cycles of neoadjuvant GC was administered. Pathological complete response (pT0N0), partial response (pTisN0/pT1N0), and pathological response (≦pT1N0) rates were 24.3%, 27.0%, and 5l.3%, respectively. Grade 3 or 4 non-hematologic adverse events were rare. Three-year overall, disease-specific, and recurrence-free survival rates were 70.7%, 8l.3%, and 63.9%, respectively. Patients with pathological response (≦pT1N0) demonstrated a significantly improved 3-year overall survival rate (94.7% vs. 42.8%), disease-specific survival rate (94.7% vs.62.9%), and recurrence-free survival rate (80.6% vs.45.5%), compared with pathological non-responders (≦pT2Nany). Clinical stage cT2 and low pre-chemotherapy platelet-to-lymphocyte ratios were significant indicators of favorable pathological response to neoadjuvant Gc. Conclusions : Neoadjuvant chemotherapy using GC is safe and effective in patients with muscle-invasive bladder cancer, Pretreatment clinical T2 stage and low platelet-to-lymphocyte ratios were predictive markers for successful neoadjuvant treatment of muscle-invasive bladder cancer with GC

限局性腎細胞癌における腫瘍浸潤性リンパ球と関連サイトカインの予後因子としての意義

Renal cell carcinoma (RCC) is an immunogenic tumor and pathological specimen generally contain large quantities of tumor-infiltrating lymphocytes (TILs). Numerous cell types and cytokines could affect the immune escape mechanism of tumor cells. The aim of the present study was to investigate the prognostic impact of TILs and the associated circulating cytokines on localized clear cell RCC following radical nephrectomy. A total of 87 patients who had undergone radical nephrectomy and were pathologically diagnosed with localized clear cell RCC were included. The present study evaluated the profile of TILs with immunohistochemical analysis of tumor specimens using a panel of antibodies [cluster of differentiation (CD)-4, CD8, CD80, CD86, CD276, and Forkhead box p3 (Foxp3)]. Counts of each TIL were compared with clinicopathological variables. Based on the results of immunohistochemical analyses, putative cytokines, including interleukin (IL)-6, IL-10, IL-17, interferon-γ, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β, were selected, and their levels in preoperative serum were measured by ELISA. The levels were compared with TIL counts in tumor specimens. High counts of the CD276+ and Foxp3+ TILs were identified as independent factors for poor prognosis for metastasis and local recurrence following radical nephrectomy (P=0.033 and 0.006, respectively). A high CD276+ TIL count was associated with preoperative serum levels of TNF-α and IFN-γ (P=0.027 and P=0.035, respectively), whereas a high count of Foxp3+ TILs was associated with preoperative serum levels of TGF-β (P=0.021). High levels of TNF-α and TGF-β were associated with recurrence-free survival (P=0.035 and P=0.031, respectively). Topical intra-tumoral immunoreaction and systemic immune status may be associated with patients with localized RCC. The topical induction of the CD276+ and Foxp3+ TILs was suggested to be associated with high levels of serum TNF-α and IFN-γ. Preoperative serum levels of TNF-α and TGF-β could be simple and non-invasive biomarkers for risk stratification before radical surgery.博士（医学）・甲第741号・令和2年3月16日Copyright © Spandidos Publications 2019. All rights reserved.Articles from Oncology Letters are provided here courtesy of Spandidos Publications