iCOD : an integrated clinical omics database based on the systems-pathology view of disease

<p>Abstract</p> <p>Background</p> <p>Variety of information relating between genome and the pathological findings in disease will yield a wealth of clues to discover new function, the role of genes and pathways, and future medicine. In addition to molecular information such as gene expression and genome copy number, detailed clinical information is essential for such systematic omics analysis.</p> <p>Results</p> <p>In order to provide a basic platform to realize a future medicine based on the integration of molecular and clinico-pathological information of disease, we have developed an integrated clinical omics database (iCOD) in which comprehensive disease information of the patients is collected, including not only molecular omics data such as CGH (Comparative Genomic Hybridization) and gene expression profiles but also comprehensive clinical information such as clinical manifestations, medical images (CT, X-ray, ultrasounds, etc), laboratory tests, drug histories, pathological findings and even life-style/environmental information. The iCOD is developed to combine the molecular and clinico-pathological information of the patients to provide the holistic understanding of the disease. Furthermore, we developed several kinds of integrated view maps of disease in the iCOD, which summarize the comprehensive patient data to provide the information for the interrelation between the molecular omics data and clinico-pathological findings as well as estimation for the disease pathways, such as three layer-linked disease map, disease pathway map, and pathome-genome map.</p> <p>Conclusions</p> <p>With these utilities, our iCOD aims to contribute to provide the omics basis of the disease as well as to promote the pathway-directed disease view. The iCOD database is available online, containing 140 patient cases of hepatocellular carcinoma, with raw data of each case as supplemental data set to download. The iCOD and supplemental data can be accessed at</p> <p><url>http://omics.tmd.ac.jp/icod_pub_eng</url></p

Evaluation of Source Generators in Partial Seizures : Availability of Neuroradiological Images Superimposed on the Dipole Tracing

To clarify the anatomical localization of epileptic foci in childhood partial seizures, the source generators of interictal focal spikes were analyzed using a dipole tracing method and the effectiveness of a composite image diagnostic technique using neuroradiological images obtained by magnetic resonance imaging and single photon emission computed tomography was evaluated. The localization of electric source generators approximately reflects the abnormal lesions on neuroradiological images. However, the source generators tended to be located in the deep and/or peripheral parts of the abnormal regions. Even though systemic shifts in the position of optimal dipoles from their true positions is a limitation that must be taken into consideration, composite image diagnostic technique may be useful for evaluating the epileptogenic regions in partial seizures, and particularly, in children where noninvasive methods are preferable

Prenatal Diagnosis of Ventriculocoronary Communication in a Fetus with Pulmonary Atresia with Intact Ventricular Septum : a Case Report

純型肺動脈閉鎖（pulmonary atresia with intact ventricular septum：以下PAIVS）の治療方針の決定には右室の大きさ，肺動脈の閉鎖様式に加え，冠動脈が右室内腔と繋がる異常交通（類洞交通）の有無や程度が重要とされる．今回胎児期に類洞交通を評価できたPAIVSの一例を経験したので報告する． 超音波検査にて胎児の右室が小さいことを指摘され妊娠23週に紹介となった．初診時の超音波検査にてPAIVSと診断した．また右室心尖部に心筋を貫通する両方向性血流を認め，類洞交通の存在が疑われた．その後冠動脈を起始部から系統的に描出することで，左冠動脈前下行枝からの大きな類洞交通であることを確認した．右室が高度の低形成でかつ大きな類洞交通があることから単心室修復が必要となることが予想された．児は出生後，心臓超音波検査，心臓血管造影にて同様の診断がなされ，単心室修復に至った． 胎児超音波で冠動脈を起始部から系統的に観察することで，類洞交通の評価が可能となりそれにより，出生前から治療方針の検討ができ，家族への説明に有用であった．Abnormal coronary connections between the ventricles and aorta can have significant impacts on myocardial perfusion and consequently on the approach for surgical intervention．Presence of ventriculocoronary communication（VCC），or ventriculo-coronary fistula，may be critical to peri- and postpartum management．We report the prenatal diagnosis of VCC associated with pulmonary atresia with intact ventricular septum（PAVIS）． A24-year-old woman was referred to our institution at 23＋3weeks’ gestation because of an abnormally small right ventricle（RV）in the fetus．Fetal echocardiography showed a small RV with trivial diastolic filling flow，an intact ventricular septum，and a hypoplastic pulmonary trunk with retrograde perfusion through the ductus arteriosus．Color and pulsed Doppler sonography revealed bidirectional flow at the right ventricular apex，which was confirmed as large VCC between the left anterior descending（LAD）coronary artery and RV by delineating coronary arteries from the aortic origin with color Doppler sonography． A3，070g male infant was vaginally delivered at 40＋1 weeks’ gestation．Postnatal echocardiography，computed tomography and angiography confirmed PAIVS and large VCC between the LAD coronary artery and RV．A BIalock-Taussig shunt was placed on postnatal day 11．Subsequently，a Glenn shunt was inserted at the age of 13 months，and Fontan procedure was performed at the age of 3 years． In summary，we accurately diagnosed fetal PAIVS and VCC accurately by meticulous echocardiography．Thus，we could provide appropriate counseling to parents and optimize peri- and postpartum management

A地域住民の食に関する意識と行動 －体験型栄養教育SATシステムの食事診断を用いて－

　研究目的は，効果的な生活習慣病予防保健指導介入プログラムの作成に向けての基礎資料とするために，体験型栄養教育食育SATシステムで得られた食事診断結果との関連から，A地域住民の食に関する意識と行動の実態を明らかにすることである．A地域住民を対象に，無記名自記式質問紙調査および食育SATシステムによる食事診断を実施した．その結果，地域住民の食育への関心は高かったが，自分の適正な食事の目安量を知っている人は少なく，目安量を学ぶ機会も少なかった．食事を選択する時には，「おいしさ・好み・安全安心」を重視しており，目安量・適正量・食育への関心と食事のバランスや適正摂取量との関連がみられなかった．食事のバランス・摂取量の適正な選択は，エネルギー摂取量，脂質摂取量が適正に判断できることと関連があった．地域住民が自分の食事摂取量の目安を知り，適正な食事を選択できるようになるためには，住民のニーズに沿った，わかりやすくて実践・継続しやすい保健指導介入プログラムの開発が必要である．また，身近で気軽に専門家に相談できる継続的な機会の必要性が示唆された

看護基礎教育にコミュニティ・オブ・プラクティスの考えを採り入れた「学びのグループゼミ」での学生の学び

　看護基礎教育カリキュラムの中に，学生がコミュニティを育みながら，看護実践を学び合えるしかけ（授業「学びのグループゼミ」）を組み入れた．本研究の目的は，「学びのグループゼミ」において学生の学習がどのように促進されたか，そのプロセスを明らかにすることである．2016 年度に「学びのグループゼミ」を受講した学生178 人（2 年生86 人，1 年生92 人）のうち，研究参加に同意が得られた学生162 人のなかから，同意が得られた26 名にインタビューを実施し，質的に分析を行った.　本研究の結果，「学びのグループゼミ」で学生は，以下1．～ 3．を学んでいたことが明らかになった．1．2 年生コアメンバーは，グループメンバーが参加しやすい＜場を創るために試行錯誤する＞，＜グループの変化をとらえる＞，＜グループの成長の役に立てたことを，自身の成長ととらえる＞という学びをしていた．2．2 年生アクティブグループメンバーと周辺グループメンバーは，グループメンバーを＜場に馴染ませ，相互交流を促進する＞，＜自らの実習経験を伝える＞ことを通してグループの役に立てていることを認識し，自らの＜実習経験を共有し，問い直す＞という学びをしていた．3．1 年生コアメンバーとアクティブグループメンバー・周辺グループメンバーは，＜学びのグループゼミへの戸惑いを感じつつ，参加のしかたを模索する＞＜緊張と戸惑いを乗り越え，学びのグループゼミで安心感と充実感を得る＞，＜ 2 年生と自身の体験を重ね合わせ，思考を広げる＞，＜教えられる対象としてだけではない，グループ内での自らの存在価値を見出す＞という学びをしていた．　「学びのグループゼミ」において学生の学びを促進した重要な相互作用として，次の2 点が考察できた．1 点目は，場を創るために試行錯誤したり，グループメンバーを場に馴染ませたり，経験を伝えるなどすることを通して，安心できる場を創ることを学んでいたこと．2 点目は，実習経験を問い直したり，学びのグループにおける存在価値を自ら見出したりすることによって，グループやグループメンバーの役に立てていることを学んでいたことである．学生が共同参加することで学習が促進するようなしかけを看護基礎教育カリキュラムに設けることができれば，知識提供型の学習とは異なる学習が促進される可能性が示唆された

高校生の食に関する認識と食育プログラム介入前後の変化 －体験型栄養教育SATシステムの食事診断を用いて－

　生活習慣病予防保健指導介入プログラムの作成に向けての基礎資料とするために，高校生の食や健康に関する認識や関心および体験型栄養教育SATシステムと健康教育を組み合わせた食育プログラムの効果を明らかにすることを目的とする．研究方法は，A市内高校3年生10名を対象に食育プログラムの介入とグループでの話し合い，無記名自記式質問紙調査を実施した．その結果，高校生の食育への関心は高かったが，食に関する学ぶ機会はなかった．食事を選択する時には，「おいしさ・好み・安全安心・満足感」を重視しており，情報入手方法はテレビ・ラジオやインターネットのメディア情報で，内容に共感することを重視していた．食育プログラム介入により，栄養バランスやエネルギー等の総合評価があがり，エネルギー摂取量，総脂質摂取量，炭水化物摂取量，野菜摂取量が基準値に入った．高校生は食に関する認識や関心は高く，食育SATシステムと健康教育を組み合わせた食育プログラムは高校生にとっても理解しやすく，生活習慣病予防保健指導介入プログラムとして活用できることが示唆された

Auditory-induced response in the primary sensory cortex of rodents.

The details of auditory response at the subthreshold level in the rodent primary somatosensory cortex, the barrel cortex, have not been studied extensively, although several phenomenological reports have been published. Multisensory features may act as neuronal representations of links between inputs from one sensory modality to other sensory modalities. Here, we examined the basic multisensory postsynaptic responses in the rodent barrel cortex using in vivo whole-cell recordings of neurons. We observed robust responses to acoustic stimuli in most barrel cortex neurons. Acoustically evoked responses were mediated by hearing and reached approximately 60% of the postsynaptic response amplitude elicited by strong somatosensory stimuli. Compared to tactile stimuli, auditory stimuli evoked postsynaptic potentials with a longer latency and longer duration. Specifically, auditory stimuli in barrel cortex neurons appeared to trigger "up states", episodes associated with membrane depolarization and increased synaptic activity. Taken together, our data suggest that barrel cortex neurons have multisensory properties, with distinct synaptic mechanisms underlying tactile and non-tactile responses

Creation and validation of a semi-quantitative instrument to assess the confidence of pharmacists in medication consultation for patients with depression: The Pharmacists' Confidence scale about Medication Consultation for Depressive patients (PCMCD)

Objectives: To develop a semi-quantitative instrument to assess pharmacists’ confidence in medication counseling for patients with depression, The Pharmacists' Confidence scale about Medication Consultation for Depressive patients (PCMCD), and investigated its validity. Methods: Following discussions with practicing pharmacists, we developed a 12-item questionnaire to assess pharmacists’ confidence in medication counseling for patients with depression. We launched web-based cross-sectional survey during November and December 2018 to 77 pharmacists employed at drug chain stores in Kansai area. Factor analysis was performed to evaluate the configuration concept validity. The least-squares method was used for factor extraction, and the resulting factors were subjected to direct oblimin rotation, with a factor loading cut-off of 0.4. To assess internal consistency, Cronbach’s alpha values were calculated for each of the extracted factors (subscales). A multiple regression analysis was performed using simultaneous forced entry, with the scores obtained for each subscale as dependent variables and responder attributes as independent variables in order to investigate the factors associated with each subscale. Results: During the factor analysis procedure, four questions were excluded by the cut-off rule. Eventually, a model with three subscales was identified, with a cumulative sum of squared loadings being 61.9%. The subscales were termed “relationship building,” “comprehension of condition,” and “information provision” based on the nature of the questions relevant for each of them. The Cronbach’s alpha values for these subscales were 0.92, 0.73, and 0.72, respectively. The average inter-item correlation was 0.378. In addition, multiple regression analysis revealed that there were significant correlations between pharmacist career and both relationship building and information provision. Conclusions: The PCMCD model demonstrated a satisfactory construct validity and internal consistency. This model will provide an excellent tool for assessing pharmacists’ confidence in depression care

Expression profiles of miRNA in A549 cell line exposed to carbon ion irradiation

Changes in microRNA (miRNA) expression in response to photon irradiation have been analyzed in a variety of cell lines including cells derived from breast, lung, prostate, and oral cancers. Several different miRNAs were responsive to the irradiation. Interestingly, individual miRNA species showing a response in specific cell types were not identified in other cells. These previous studies therefore suggested that selected miRNAs are regulated in a cell- or tumor-specific manner.C-ions with high energy transfer (LET) have a major big advantage over X-rays in treating tumors, and comprehensive gene expression analyses have identified C-ion- or X-ray-specific gene expression profiles. However, no detailed miRNA expression analysis after C-ion irradiation has been reported. We recently demonstrated X-ray irradiation-induced expression of selected miRNAs in the A549 cell line, which is derived from human non-small cell lung cancer (NSCLC). One of these miRNAs, miR-574-3p, has been implicated in suppressing the enhancer of rudimentary homolog (ERH) gene, which has a role in cell cycle control. This study examined C-ion induced expression of miRNAs in the A549 cell line. We found that four miRNA molecules were induced by 1 Gy of C-ion irradiation, compared to 2 Gy of X-ray irradiation needed for the same result. These data suggested that these four miRNA genes use common transcriptional machinery in responding to both X-ray and C-ion irradiation.BMB201

Influence of multiple genetic polymorphisms on early adverse reaction in the gastrointestinal tract of patients with cervical cancer treated with pelvic radiation therapy

[Objectives] Cancer patients experience individual variation in normal tissue reactions after radiotherapy (RT). Such reactions to RT are quite complex, with multiple genetic factors contributing to a patient\u27 s susceptibility for the reactions to RT. A risk of intestinal toxicity could be related to individual differences in radiosensitivities of the mitogenic crypt cells. We hypothesized that gene variation likely to affect cell-cycle regulation could contribute to heterogeneity in the risk of adverse intestinal reactions in CC patients undergoing RT.[Methods] We examined 208 cervical cancer patients who have treated with pelvic radiotherapy as eligible for the genetic investigation. An early gastrointestinal reaction was graded using the NCICTC. The subjects were dichotomized into a lower-grade group (n = 150) and a higher-grade group (n = 58). Genomic DNA was genotyped, and association with the risk of adverse reaction for 49 functional SNPs of 22 candidate gens was assessed by single-locus, haplotype, and multilocus analysis.[Results] Our analysis revealed two haplotypes of NPAT-ATM and AURKA and two single loci of PSMB8 and CASP7 contribute to the risk of adverse intestinal reaction after RT. Patients who had two or more of the risk genotype of these four genes showed higher risk than other patients.[Conclusions] Genetic variations in the genes functioned on cell-cycle regulation may contribute to individual radiosensitivity of intestine. Identification of the novel risk genotypes would improve our understanding into the contribution of genetic factors to individual radiosensitivity and could be used to stratify the genetic risk in CC patients.The 2nd Japan-China Symposium on Cancer Researc