長崎国際大学薬学部における早期体験学習の評価 - 学生および医療機関に対する意識調査から -

２００６年度に新設された長崎国際大学薬学部では、２００６、２００７年度の各１年生を対象に早期体験学習を実施してきた。この早期体験学習を評価するために病院や調剤薬局を訪問した学生と、受け入れ医療機関において対応した薬剤師を対象として、それぞれの年度においてアンケート調査を実施した。われわれは将来の早期体験学習をよりよいものにするために調査結果の解析を行なった。学生からのアンケートの回収率は、２００６年度で７７％、２００７年度で８７％であった。また、受け入れ医療機関の薬剤師からのアンケート回収率は、２００６年度で１００％、２００７年度で９８％であった。学生からのアンケート結果から、８８％～９５％の学生が患者や社会に対して奉仕することの素晴らしさを感じ、８５％～９５％の学生が学習に対してのモチベーションが向上したことがわかった。また、受け入れ医療機関の薬剤師からのアンケート結果から、多くの薬剤師がこの早期体験学習を受け入れてよかったと感じ、大学と薬剤師との間で早期体験学習の目的の共通理解がこの１年で着実に進んできていることがわかった。We have been carrying out a call at hospital and pharmacy as an early exposure program for freshmen in these two years, since Faculty of Pharmaceutical Sciences was founded in 2006 at Nagasaki International University. In the present study, we performed questionnaire survey against the students and pharmacists responsible for guidance of students at hospital and pharmacy, and compared with the results of last year, in order to improve the program. The recovery rate of the questionnaire from students in 2006 and 2007 was 77 and 87%, respectively, and that from the pharmacists was 100 and 98%, respectively. The 88-95% of the students gave positive answer that they could find significance and necessity of service to patients and/or society, and 85-95% agreed with the choice that the program would increase motivation for studying at the university. In addition, the rate of the pharmacists who agreed with the significance of the program increased from 88 to 96% in this one year, suggesting improvement of common understanding about the objective of the program between the faculties in the university and the pharmacists during this one year

UBC13-Mediated Ubiquitin Signaling Promotes Removal of Blocking Adducts from DNA Double-Strand Breaks

Chemical modifications and adducts at DNA double-strand break (DSB) ends must be cleaned before re-joining by non-homologous end-joining (NHEJ). MRE11 nuclease is essential for efficient removal of Topoisomerase II (TOP2)-DNA adducts from TOP2 poison-induced DSBs. However, mechanisms in MRE11 recruitment to DSB sites in G1 phase remain poorly understood. Here, we report that TOP2-DNA adducts are expeditiously removed through UBC13-mediated polyubiquitination, which promotes DSB resection in G2 phase. We found that this ubiquitin signaling is required for efficient recruitment of MRE11 onto DSB sites in G1 by facilitating localization of RAP80 and BRCA1 to DSB sites and complex formation between BRCA1 and MRE11 at DSB sites. UBC13 and MRE11 are dispensable for restriction-enzyme-induced "clean" DSBs repair but responsible for over 50% and 70% of NHEJ-dependent repair of γ-ray-induced "dirty" DSBs, respectively. In conclusion, ubiquitin signaling promotes nucleolytic removal of DSB blocking adducts by MRE11 before NHEJ

Preoperative Butyrylcholinesterase Level as an Independent Predictor of Overall Survival in Clear Cell Renal Cell Carcinoma Patients Treated with Nephrectomy

The prognostic factors for the overall survival (OS) of clear cell renal cell carcinoma (ccRCC) patients treated with nephrectomy are not well defined. In the present study, we investigated the prognostic significance of preoperative butyrylcholinesterase (BChE) levels in 400 ccRCC patients undergoing radical or partial nephrectomy from 1992 to 2013 at our institution. Univariate and multivariate analyses were performed to determine the clinical factors associated with OS. Among the enrolled patients, 302 were diagnosed with organ-confined disease only (T1-2N0M0), 16 with lymph node metastases, and 56 with distant metastases. The median preoperative BChE level was 250 U/L (normal range, 168–470 U/L), and median follow-up period was 36 months. The 3-year OS rate in patients with preoperative BChE levels of ≥100 U/L was significantly higher than in those with levels of <100 U/L (89.3% versus 77.7%, P=0.004). On univariate analysis, performance status; anemia; hypoalbuminemia; preoperative levels of BChE, corrected calcium, and C-reactive protein; and distant metastasis status were significantly associated with OS. Multivariate analysis revealed that preoperative BChE levels and distant metastasis status were significantly associated with OS. Our findings suggest a possible role of preoperative BChE levels as an independent predictor of OS after nephrectomy in ccRCC patients

A giant molecular cloud catalogue in the molecular disc of the elliptical galaxy NGC5128 (Centaurus A)

We sincerely thank the referee (Erik Rosolowsky) for the careful reading and useful comments to improve our manuscript. We would also like to show our gratitude to him for the kind assistance with the usage of CPROPS in the early stages of this work. REM was supported by the ALMA Japan Research Grant of NAOJ ALMA Project, NAOJ-ALMA-222. DE was supported by JSPS KAKENHI grant number JP 17K14254. DE was supported by the ALMA Japan Research Grant of NAOJ ALMA Project, NAOJ-ALMA-0093. MINK was supported by JSPS KAKENHI grant number JP 15J04974. KK was supported by JSPS KAKENHI grant number JP17H06130 and the NAOJ ALMA Scientific Research grant number 2017-06B. SV acknowledges support by the research projects AYA2014-53506-P and AYA2017-84897-P from the Spanish Ministerio de Economia y Competitividad, and by the Consejer ' ia de Conocimiento, Investigaci ' on y Universidad, Junta de Andaluc ' ia (FQM108) and European Regional Development Fund (ERDF)". This study has been partially financed by the Consejer ' ia de Conocimiento, Investigaci ' on y Universidad, Junta de Andaluc ' ia and European Regional Development Fund (ERDF), ref. SOMM17/6105/UGR. Part of this work was achieved using the grant of Visiting Scholars Program supported by the Research Coordination Committee, National Astronomical Observatory of Japan (NAOJ), National Institutes ofNatural Sciences (NINS). SM would like to thank the Ministry of Science and Technology (MOST) of Taiwan, MOST 107-2119-M-001-020. This research has made use of NASA's Astrophysics Data System. This research has made use of Astropy, a community-developed core PYTHON (http://www.python.org) package for Astronomy (Astropy Collaboration 2013, 2018); IPYTHON (Perez & Granger 2007); MATPLOTLIB (Hunter 2007); APLPY, an open-source plotting package for PYTHON (Robitaille & Bressert 2012), and NUMPY (van derWalt, Colbert & Varoquaux 2011). Data analysis was in part carried out on the open use data analysis computer system at the Astronomy Data Center, ADC, of the National Astronomical Observatory of Japan. This research has made use of the NASA/IPAC Infrared Science Archive, which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration. This paper makes use of the following ALMA data: ADS/JAO.ALMA#2013.1.00803.S. ALMA is a partnership of ESO (representing its member states), NSF (USA) and NINS (Japan), together with NRC (Canada), MOST and ASIAA (Taiwan), and KASI (Republic ofKorea), in cooperationwith theRepublic of Chile. The Joint ALMA Observatory is operated by ESO, AUI/NRAO and NAOJ. The NationalRadio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc.We present the first census of giant molecular clouds (GMCs) complete down to 106M and within the inner 4 kpc of the nearest giant elliptical and powerful radio galaxy, Centaurus A. We identified 689 GMCs using CO(1–0) data with 1 arcsec spatial resolution (∼20 pc) and 2 kms−1 velocity resolution obtained with the Atacama Large Millimeter/submillimeter Array. The I(CO)-N(H2) conversion factor based on the virial method is XCO = (2 ± 1) × 1020 cm−2(K km s−1)−1 for the entire molecular disc, consistent with that of the discs of spiral galaxies including the Milky Way, and XCO = (5 ± 2) × 1020 cm−2(K km s−1)−1 for the circumnuclear disc (CND; within a galactocentric radius of 200 pc). We obtained the GMC mass spectrum distribution and find that the best truncated power-law fit for the whole molecular disc, with index γ −2.41 ± 0.02 and upper cut-off mass ∼1.3 × 107M , is also in agreement with that of nearby disc galaxies. A trend is found in the mass spectrum index from steep to shallow as we move to inner radii. Although the GMCs are in an elliptical galaxy, the general GMC properties in the molecular disc are as in spiral galaxies. However, in the CND, large offsets in the line-width-size scaling relations (∼0.3 dex higher than those in the GMCs in the molecular disc), a different XCO factor, and the shallowest GMC mass distribution shape (γ = −1.1 ± 0.2) all suggest that there the GMCs are most strongly affected by the presence of the active galactic nucleus and/or shear motions.ALMA Japan Research Grant of NAOJ ALMA Project NAOJ-ALMA-222 NAOJ-ALMA-0093Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of ScienceGrants-in-Aid for Scientific Research (KAKENHI) JP 17K14254 JP 15J04974 JP17H06130NAOJ ALMA Scientific Research grant 2017-06BSpanish Government AYA2014-53506-P AYA2017-84897-PJunta de Andalucia FQM108European Commission SOMM17/6105/UGRResearch Coordination Committee, National Astronomical Observatory of Japan (NAOJ), National Institutes ofNatural Sciences (NINS)Ministry of Science and Technology, Taiwan MOST 107-2119-M-001-020 2013.1.00803.

Protocol for a Randomized, Crossover Trial : ISCHIA study

Objective: Intermittent-scanning continuous glucose monitoring (isCGM) is widely used in type 1 diabetes (T1D) patients; however, the education required to prevent hypoglycemia by using isCGM is not established. This study examines the combined effect of isCGM device usage and the education to reduce the time in hypoglycemia in comparison to conventional self-monitoring of blood glucose (SMBG). Methods: The Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus Study (ISCHIA Study), a randomized, crossover trial, enrolls 104 T1D patients (age, 20-74 years) with T1D. Participants are randomized to use isCGM combined with structured education (Intervention period) or SMBG (Control period) for 84 days, followed by the other for a further 84 days. During the Intervention period, participants have access to the sensor glucose levels and trend arrow of the device. During the Control period, participants conduct SMBG at least three times a day, and retrospective CGM is used to record the blinded sensor glucose levels. The primary endpoint is the decrease of time in hypoglycemia ( < 70 mg/dL) per day (hour/day) during the Intervention period compared with the Control period. The secondary endpoints include other indices of glycemic control, glycoalbumin, accuracy of isCGM, diabetes-related quality of life (QOL), adherence, and cost-effectiveness. The study protocol has received Certified Review Board (CRB) approval from National Hospital Organization Osaka National Hospital (N2018002, February 14, 2019). This study is carried out in accordance with the Declaration of Helsinki and the Clinical Trials Act. The findings will be published in peer-reviewed journals. Conclusion: The ISCHIA study will contribute to the standardization of patient education regarding the prevention of hypoglycemia by using isCGM

Human immune and gut microbial parameters associated with inter-individual variations in COVID-19 mRNA vaccine-induced immunity

COVID-19 mRNA vaccines induce protective adaptive immunity against SARS-CoV-2 in most individuals, but there is wide variation in levels of vaccine-induced antibody and T-cell responses. However, the mechanisms underlying this inter-individual variation remain unclear. Here, using a systems biology approach based on multi-omics analyses of human blood and stool samples, we identified several factors that are associated with COVID-19 vaccine-induced adaptive immune responses. BNT162b2-induced T cell response is positively associated with late monocyte responses and inversely associated with baseline mRNA expression of activation protein 1 (AP-1) transcription factors. Interestingly, the gut microbial fucose/rhamnose degradation pathway is positively correlated with mRNA expression of AP-1, as well as a gene encoding an enzyme producing prostaglandin E2 (PGE2), which promotes AP-1 expression, and inversely correlated with BNT162b2-induced T-cell responses. These results suggest that baseline AP-1 expression, which is affected by commensal microbial activity, is a negative correlate of BNT162b2-induced T-cell responses.journal articl