Cocaine enhances resistance to extinction of responding for brain-stimulation reward in adult prenatally stressed rats

The present experiment assessed whether prenatal stress (PS) can alter the ability of acute and chronic cocaine administration to increase and decrease the rewarding effectiveness of the medial forebrain bundle (MFB) using intracranial self-stimulation (ICSS), and also whether PS can affect the extinction of the MFB stimulation response. Adult male offspring of female rats that received PS or no PS (nPS) were implanted with MFB stimulating electrodes, and were then tested in ICSS paradigms. In both nPS and PS offspring, acute cocaine injection decreased ICSS thresholds dose-dependently. However, the threshold-lowering effects at any dose were not significantly different between groups. There was also no group-difference in the threshold-elevating effects of chronic cocaine administration. Nevertheless, chronically drug-administered PS rats exhibited a resistance to the extinguishing of the response for brain-stimulation reward when acutely treated with cocaine, as compared to extinction without cocaine treatment. The results suggest that PS may weaken the ability for response inhibition under cocaine loading in male adult offspring

コレラの三期

Cholera is regarded as the most acute of the acute enteritides. This fact has apparently caused the general impression that there is only one stage in the course of cholera. So acute as it may be, a clear cut shift of pathological changes in the intestinal mucosa of cholera patients are recognizable, if we arrange autopsy cases in time order after onset of the disease. There are 3 stages, the first, stage of inflammation, the second, stage of villus fusing and the third, stage of villus resolution. The materials were 12 cases of infant cholera, which died in 1968 and 1969 in the San Lazaro Hospital, Manila, Philippines.コレラは急性腸炎の中でも最も急性のものとされている.此の事実がコレラには一期しかないと云ふ観念を一般に植え付けたものと思われる.然し,如何に急性の疾患とは云え,コレラの剖検例を発病後の経過時間によって整理して見ると,小腸粘膜の形態学的変化に明かな推移が認められる.我々は此を三期に分類した.第一期,炎症期,発病後十数時間迄.第二期,絨毛癒着期,発病後二十四時間以後.第三期,癒着緩解期,発病後推定二,三週,症例は1968年,1969年に比島,マニラ市,サンラザラロ病院で死亡した小児コレラ12例である

Synthesis and pharmacological characterization of potent, selective, and orally bioavailable isoindoline class dipeptidyl peptidase IV inhibitors

Focused structure-activity relationships of isoindoline class DPP-IV inhibitors have led to the discovery of 4b as a highly selective, potent inhibitor of DPP-IV. In vivo studies in Wistar/ST rats showed that 4b was converted into the strongly active metabolite 4l in high yield, resulting in good in vivo efficacy for antihyperglycemic activity

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

First Data Release of the Hyper Suprime-Cam Subaru Strategic Program

The Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP) is a three-layered imaging survey aimed at addressing some of the most outstanding questions in astronomy today, including the nature of dark matter and dark energy. The survey has been awarded 300 nights of observing time at the Subaru Telescope and it started in March 2014. This paper presents the first public data release of HSC-SSP. This release includes data taken in the first 1.7 years of observations (61.5 nights) and each of the Wide, Deep, and UltraDeep layers covers about 108, 26, and 4 square degrees down to depths of i~26.4, ~26.5, and ~27.0 mag, respectively (5sigma for point sources). All the layers are observed in five broad bands (grizy), and the Deep and UltraDeep layers are observed in narrow bands as well. We achieve an impressive image quality of 0.6 arcsec in the i-band in the Wide layer. We show that we achieve 1-2 per cent PSF photometry (rms) both internally and externally (against Pan-STARRS1), and ~10 mas and 40 mas internal and external astrometric accuracy, respectively. Both the calibrated images and catalogs are made available to the community through dedicated user interfaces and database servers. In addition to the pipeline products, we also provide value-added products such as photometric redshifts and a collection of public spectroscopic redshifts. Detailed descriptions of all the data can be found online. The data release website is https://hsc-release.mtk.nao.ac.jp/.Comment: 34 pages, 20 figures, 7 tables, moderate revision, accepted for publication in PAS

Integrated genetic and clinical prognostic factors for aggressive adult T-cell leukemia/lymphoma

成人T細胞白血病リンパ腫（ATL）におけるゲノム情報と臨床情報を統合したリスクモデルを確立 --ATLの個別化医療を推進--. 京都大学プレスリリース. 2023-04-10.The prognosis of aggressive adult T-cell leukemia/lymphoma (ATL) is poor, and allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a curative treatment. To identify favorable prognostic patients after intensive chemotherapy, and who therefore might not require upfront allo-HSCT, we aimed to improve risk stratification of aggressive ATL patients aged <70 years. The clinical risk factors and genetic mutations were incorporated into risk modeling for overall survival (OS). We generated the m7-ATLPI, a clinicogenetic risk model for OS, that included the ATL prognostic index (PI) (ATL-PI) risk category, and non-silent mutations in seven genes, namely TP53, IRF4, RHOA, PRKCB, CARD11, CCR7, and GATA3. In the training cohort of 99 patients, the m7-ATLPI identified a low-, intermediate-, and high-risk group with 2-year OS of 100%, 43%, and 19%, respectively (hazard ratio [HR] 5.46, p < 0.0001). The m7-ATLPI achieved superior risk stratification compared to the current ATL-PI (C-index 0.92 vs. 0.85, respectively). In the validation cohort of 84 patients, the m7-ATLPI defined low-, intermediate-, and high-risk groups with a 2-year OS of 81%, 30%, and 0%, respectively (HR 2.33, p = 0.0094), and the model again outperformed the ATL-PI (C-index 0.72 vs. 0.70, respectively). The simplified m7-ATLPI, which is easier to use in clinical practice, achieved superior risk stratification compared to the ATL-PI, as did the original m7-ATLPI; the simplified version was calculated by summing the following: high-risk ATL-PI category (+10), low-risk ATL-PI category (−4), and non-silent mutations in TP53 (+4), IRF4 (+3), RHOA (+1), PRKCB (+1), CARD11 (+0.5), CCR7 (−2), and GATA3 (−3)

Prevention of hypoglycemia by intermittent-scanning continuous glucose monitoring device combined with structured education in patients with type 1 diabetes mellitus : A randomized, crossover trial

Aims: We conducted a randomized, crossover trial to compare intermittent-scanning continuous glucose monitoring (isCGM) device with structured education (Intervention) to self-monitoring of blood glucose (SMBG) (Control) in the reduction of time below range. Methods: This crossover trial involved 104 adults with type 1 diabetes mellitus (T1DM) using multiple daily injections. Participants were randomly allocated to either sequence Intervention/Control or sequence Control/Intervention. During the Intervention period which lasted 84 days, participants used the first-generation FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) and received structured education on how to prevent hypoglycemia based on the trend arrow and by frequent sensor scanning (≥10 times a day). Confirmatory SMBG was conducted before dosing insulin. The Control period lasted 84 days. The primary endpoint was the decrease in the time below range (TBR; <70 mg/dL). Results: The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index >5 was significantly reduced (8.6 % vs 23.7 %, P < 0.001). Conclusions: The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM

口腔乾燥の改善に関する研究 : Capparis属植物配合タブレットの味覚特性と口腔内の潤い感について

本研究では、口腔乾燥を自覚したひとへのCapparis masaikai(マビンロウ)を配合したタブレット(MT)の応用にあたって、MTの嗜好性及び口腔内の潤い感を把握するため、成人を対象に官能評価を行った。その結果、1.MTは、甘味・渋味・苦味・粉っぽさがあり、爽やかさが少ないと評価された。2.MTの若年女性の嗜好性に対する評価が低かった。このことから、MTは味の嗜好性の評価や総合評価を向上させる必要性があると考えられた。3.MTは口腔内での潤い感が60分持続し、その効果が特に高齢者群で高かった。このことから、今後口腔乾燥症を有する成人・高齢者に口腔内の潤い感を付与する有効な手立ての一つとなると考えられた。As the taste characteristic of the tablet which mixed Capparis masaikai, a sensory evaluation was carried out among young panelists (23 men, average age 25.5 and 31 women, average age 22.2) and elderly panelists (15 men, average age 72.1 and 17 women, average age 74.3) in order to grasp the preference of taste and moisture sensation in the oral cavity. The sample of the sensory evaluation was made to be two kinds of the tablets of MT (the tablet including the 15% Capparis masaikai extract) and N-MT (the tablet of the identical composition without the Capparis masaikai extract). The sensory evaluation items were made to be the time until the tablets melted in the oral cavity, and strength and weakness and preference, total evaluation of the taste of the tablet in licking and after the licking. The following results were obtained: 1. MT was evaluated that sweetness, astringent taste and bitterness and powder were stronger than N-MT, but it was evaluated that refreshingness was weaker than N-MT. 2. An evaluation for the preference of the young women of MT was low. From this result, there seemed to be a necessity of improving evaluation and total evaluation of the preference of taste of MT. 3. Moisture sensation in the oral cavity kept 60 minutes on MT, and the effect was especially high in the elderly panelists. From this result, MT seemed to be one of the effective ways that gave moisture sensation in the oral cavity to adult and elderly people who would be conscious of the dry mouth in future

The Hyper Suprime-Cam SSP survey: Overview and survey design

Hyper Suprime-Cam (HSC) is a wide-field imaging camera on the prime focus of the 8.2-m Subaru telescope on the summit of Mauna Kea in Hawaii. A team of scientists from Japan, Taiwan, and Princeton University is using HSC to carry out a 300-night multi-band imaging survey of the high-latitude sky. The survey includes three layers: the Wide layer will cover 1400 deg2 in five broad bands (grizy), with a 5 σ point-source depth of r ≈ 26. The Deep layer covers a total of 26 deg2 in four fields, going roughly a magnitude fainter, while the UltraDeep layer goes almost a magnitude fainter still in two pointings of HSC (a total of 3.5 deg2). Here we describe the instrument, the science goals of the survey, and the survey strategy and data processing. This paper serves as an introduction to a special issue of the Publications of the Astronomical Society of Japan, which includes a large number of technical and scientific papers describing results from the early phases of this survey