Effect of bovine milk fermented with Lactobacillus rhamnosus L8020 on periodontal disease in individuals with intellectual disability: a randomized clinical trial

Studies on the oral health of individuals with intellectual disability (ID) have identified problems that include a high prevalence of periodontal disease. The use of probiotics to treat periodontal disease has been the focus of considerable research, and bovine milk fermented with Lactobacillus rhamnosus L8020 (L8020 yogurt) has been shown to reduce the oral prevalence of four periodontal pathogens. Objective: The aim of this randomized, double-blind, placebo-controlled trial was to compare the effects of L8020 yogurt (test group) with those of placebo yogurt (placebo group) on the papillary-marginal-attached (PMA) index, gingival index (GI), and probing depth (PD) in 23 individuals with ID. Methodology: All patients were required to consume the allocated yogurt after breakfast for 90 days. PMA index and GI scores as well as PDs were assessed before the start of yogurt consumption (baseline), after 45 and 90 days of consumption, and 30 days after the cessation of consumption. Student’s t-test, Mann–Whitney U test or Fisher’s exact test was used for inter-group comparisons, and the mixed effect model of repeated measurements was used for data analysis. Results: The decrease in PMA index score was significantly greater in the test group than in the placebo group (p<0.001). The GI score also decreased during the study, with a tendency for greater decrease in the test group. Furthermore, decreases in PD between baseline, 45 and 90 days tended to be greater in the test group than in the placebo group. Conclusion: These results suggest that regular consumption of bovine milk fermented with L. rhamnosus L8020 can lower the risk of periodontal disease in individuals with ID

DNAH6 and Its Interactions with PCD Genes in Heterotaxy and Primary Ciliary Dyskinesia.

Heterotaxy, a birth defect involving left-right patterning defects, and primary ciliary dyskinesia (PCD), a sinopulmonary disease with dyskinetic/immotile cilia in the airway are seemingly disparate diseases. However, they have an overlapping genetic etiology involving mutations in cilia genes, a reflection of the common requirement for motile cilia in left-right patterning and airway clearance. While PCD is a monogenic recessive disorder, heterotaxy has a more complex, largely non-monogenic etiology. In this study, we show mutations in the novel dynein gene DNAH6 can cause heterotaxy and ciliary dysfunction similar to PCD. We provide the first evidence that trans-heterozygous interactions between DNAH6 and other PCD genes potentially can cause heterotaxy. DNAH6 was initially identified as a candidate heterotaxy/PCD gene by filtering exome-sequencing data from 25 heterotaxy patients stratified by whether they have airway motile cilia defects. dnah6 morpholino knockdown in zebrafish disrupted motile cilia in Kupffer\u27s vesicle required for left-right patterning and caused heterotaxy with abnormal cardiac/gut looping. Similarly DNAH6 shRNA knockdown disrupted motile cilia in human and mouse respiratory epithelia. Notably a heterotaxy patient harboring heterozygous DNAH6 mutation was identified to also carry a rare heterozygous PCD-causing DNAI1 mutation, suggesting a DNAH6/DNAI1 trans-heterozygous interaction. Furthermore, sequencing of 149 additional heterotaxy patients showed 5 of 6 patients with heterozygous DNAH6 mutations also had heterozygous mutations in DNAH5 or other PCD genes. We functionally assayed for DNAH6/DNAH5 and DNAH6/DNAI1 trans-heterozygous interactions using subthreshold double-morpholino knockdown in zebrafish and showed this caused heterotaxy. Similarly, subthreshold siRNA knockdown of Dnah6 in heterozygous Dnah5 or Dnai1 mutant mouse respiratory epithelia disrupted motile cilia function. Together, these findings support an oligogenic disease model with broad relevance for further interrogating the genetic etiology of human ciliopathies

Generation of medaka gene knockout models by target-selected mutagenesis

We have established a reverse genetics approach for the routine generation of medaka (Oryzias latipes) gene knockouts. A cryopreserved library of N-ethyl-N-nitrosourea (ENU) mutagenized fish was screened by high-throughput resequencing for induced point mutations. Nonsense and splice site mutations were retrieved for the Blm, Sirt1, Parkin and p53 genes and functional characterization of p53 mutants indicated a complete knockout of p53 function. The current cryopreserved resource is expected to contain knockouts for most medaka genes

Effects of nitrous oxide sedation on sympathetic batireflex sesensitivity.

笑気吸入鎮静法（IS）は不安，恐怖心の強い患者，知的障害者，内部障害等を有する患者などに応用される精神鎮静法である．動脈圧は圧受容器反射により維持・調整されているが，亜酸化窒素（N2O）吸入が圧受容器反射感受性（BRS）に影響するかは不明である．そこで，IS中に連続血圧と，マイクロニューログラフィーを用いて筋交感神経活動（Muscle Sympathetic Nerve Activity：MSNA）を同時測定し，動脈圧の変動に対する末梢血管調節性交感神経活動の変化量からBRSを検証した．健常成人男性10名［31±2歳］を対象に，水平仰臥位でルームエアー，100％酸素（O2），30％N2O，40％N2Oをそれぞれ20分間吸入した後，各条件下で心拍数（HR），心拍出量（CO），1回拍出量（SV），連続血圧およびMSNAを5分間測定した．さらに，O2を20分間吸入した後に回復期を設け，ルームエアーで5分間同様の測定をした．BRSの評価のために，まず，連続血圧の拡張期血圧（DBP）を3mmHgごとにグルーピングを行い，各グループのDBP平均値をDBPの代表値とし，100拍あたりのMSNAのバースト数（BI）とバースト面積（Total MSNA）をMSNA代表値とした．各グループのDBPとBIおよびTotal MSNA代表値から求めた直線回帰の傾きを交感神経性圧受容器反射感受性（sBRS）とした．各IS条件間でHR，CO，血圧に差はなかった．また，DBPとBIおよびTotal MSNAで求めたsBRSは両者ともIS濃度による変動を示さなかった．以上から，笑気吸入中に圧受容器反射のオペレーティングポイント，感受性とも維持されることが示唆された．2019博士（歯学）松本歯科大

Possibility of Integrated Data Mining of Clinical Data

In this paper, we introduce integrated data mining. Because of recent rapid progress in medical science as well as clinical diagnosis and treatment, integrated and cooperative research among medical researchers, biology, engineering, cultural science, and sociology is required. Therefore, we propose a framework called Cyber Integrated Medical Infrastructure (CIMI). Within this framework, we can deal with various types of data and consequently need to integrate those data prior to analysis. In this study, for medical science, we analyze the features and relationships among various types of data and show the possibility of integrated data mining

Hot water extract of Agaricus blazei Murrill specifically inhibits growth and induces apoptosis in human pancreatic cancer cells

Abstract Background Pancreatic cancer is one of the most aggressive human malignancies. The development of a novel drug to treat pancreatic cancer is imperative, and it is thought that complementary and alternative medicine (CAM) could yield such a candidate. Agaricus blazei Murrill is a CAM that has been tested as an anticancer drug, but its efficacy against pancreatic cancer is poorly understood. To study the potential of A. blazei in the treatment of pancreatic cancer, we examined the effects of its hot water extract on the proliferation and global gene expression profile of human pancreatic cancer cells. Methods Three distinct human pancreatic cancer cell lines, MIAPaCa-2, PCI-35, and PK-8, and the immortalized human pancreatic duct-epithelial cell line, HPDE, were employed. The cells were incubated with the appropriate growth medium supplemented with the hot water extract of A. blazei at final concentrations of 0.005, 0.015%, or 0.045%, and cellular proliferation was assessed for five consecutive days using an MTT assay. Apoptosis was examined by using flow cytometry and the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Caspase-dependent apoptosis was assayed using immunoblotting. Global gene expression profiles were examined using a whole human genome 44 K microarray, and the microarray results were validated by using real-time reverse transcription PCR. Results The hot water extract of A. blazei significantly inhibited the proliferation of cultured pancreatic cancer cells through the induction of G0/G1 cell cycle arrest and caspase-dependent apoptosis; the effect was the smallest in HPDE cells. Furthermore, significant alterations in the global gene expression profiles of pancreatic cancer cells occurred following treatment with the hot water extract of A. blazei. Genes associated with kinetochore function, spindle formation, and centromere maintenance were particularly affected, as well as cyclins and cyclin-dependent kinases that are essential for cell cycle progression. In addition, proapoptotic genes were upregulated. Conclusions The hot water extract of A. blazei may be useful for the treatment of pancreatic cancer and is a potential candidate for the isolation of novel, active compounds specific for mitotic spindle dysfunction