Improved syntheses of D-ribo- and 2-deoxy-D-ribofuranose phospho sugars from methyl β-D-ribopyranoside

Methyl 4-deoxy-4-dimethoxyphosphinoyl-2,3-O-isopropylidene-beta-D-ribopyranoside (12a) and methyl 2,4-dideoxy-4-dimethoxyphosphinoyl-beta-D-erythro-pentopyranoside (20) were efficiently prepared respectively from methyl 2,3-O-isopropylidene-beta-D-ribopyranoside (7a) and its 3,4-O-isopropylidene isomer (7b) in appreciably improved total yields compared with those via previously reported routes. Compounds (12a, 20) were led to D-ribofuranose and 2-deoxy-D-ribofuranose phospho sugars (4, 5)

Genetic screening for malignant hyperthermia and comparison of clinical symptoms in Japan

Malignant hyperthermia (MH) is an anaesthetic complication that causes an abnormal hypermetabolic state. RYR1 encoding ryanodine receptors of the sarcoplasmic reticulum and CACNA1S encoding α subunits of dihydropyridine receptors are known to be associated with MH pathogenicity. We performed genetic screening using next-generation sequencing to evaluate the prevalence of genes associated with MH pathogenicity and clinical symptoms. This was a retrospective cohort study wherein next-generation sequencing data of 77 families diagnosed with MH predisposition by calcium-induced calcium release (CICR) tests from 1995 to 2019 was used to search for RYR1 and CACNA1S variants. Furthermore, the clinical symptoms and predisposition tests in participants with RYR1 and CACNA1S variants were compared. In the 77 families, 44.2%, 7.8%, and 48.1% individuals had RYR1, CACNA1S, and neither RYR1 nor CACNA1S variants, respectively. Clinically significant differences were found in the maximum body temperature, maximum elevated body temperature for 15 min, creatinine kinase level, and CICR rate between the RYR1 and CACNA1S groups. The prevalence of pathogenic CACNA1S variants appears to be prominent in Japan. The severity of clinical symptoms and the CICR rate were greater in individuals with RYR1 variants than in those with CACNA1S variants, likely due to more direct regulation of calcium levels by ryanodine receptors than by dihydropyridine receptors. Genetic analysis of MH in future studies may help identify other genes associated with MH, which will further clarify the relationship between genotypes and MH symptoms and contribute to safer anaesthesia practice.This study was supported by a Grant-in-Aid for Young Scientists (grant number: 17K16733 to Y.N. and 20K17783 to R.K.) from the Japan Society for the Promotion of Science and by the Takeda Science Foundation (H.K.)

Identification of cell cycle–arrested quiescent osteoclast precursors in vivo

Osteoclasts are multinucleated cells that resorb bone. Although osteoclasts originate from the monocyte/macrophage lineage, osteoclast precursors are not well characterized in vivo. The relationship between proliferation and differentiation of osteoclast precursors is examined in this study using murine macrophage cultures treated with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB (RANK) ligand (RANKL). Cell cycle–arrested quiescent osteoclast precursors (QuOPs) were identified as the committed osteoclast precursors in vitro. In vivo experiments show that QuOPs survive for several weeks and differentiate into osteoclasts in response to M-CSF and RANKL. Administration of 5-fluorouracil to mice induces myelosuppression, but QuOPs survive and differentiate into osteoclasts in response to an active vitamin D3 analogue given to those mice. Mononuclear cells expressing c-Fms and RANK but not Ki67 are detected along bone surfaces in the vicinity of osteoblasts in RANKL-deficient mice. These results suggest that QuOPs preexist at the site of osteoclastogenesis and that osteoblasts are important for maintenance of QuOPs

Triglycerides and blood pressure in relation to circulating CD34-positive cell levels among community-dwelling elderly Japanese men: a cross-sectional study

Background: Triglycerides are reported to be positively associated with blood pressure (both systolic and diastolic). However, in a previous study, we reported a significant positive association between triglycerides and circulating CD34-positive cells (endothelial repair) among non-hypertensive, but not hypertensive, participants. Since hypertension and endothelial dysfunction have a bi-directional association (vicious cycle), the status of circulating CD34-positive cells may influence the association between triglycerides and hypertension. Methods: Since antihypertensive medication use may influence results of the present study, we conducted a cross-sectional study of 327 community dwelling elderly (aged 60-69 years) Japanese participants who were not taking anti-hypertensive medication and who had participated in a general health check-up in 2013-2015. Results: Participants were classified into two groups based on median values of circulating CD34-positive cells (0.93 cells/μL). For participants with lower circulating CD34-positive cells (n = 165), a significant positive association was seen between triglycerides and blood pressure, but not for participants with higher circulating CD34-positive cells (n = 162). The multivariable standardized parameter estimates (β) and p values of systolic blood pressure and diastolic blood pressure were 0.23 (p = 0.007) and 0.18 (p = 0.036) for participants with lower circulating CD34-positive cells and 0.08 (p = 0.409) and 0.03 (p = 0.786) for those with higher circulating CD34-positive cells. Conclusion: A significant positive association between triglycerides and blood pressure exists among those with lower, but not higher, circulating CD34-positive cells. The level of circulating CD34-positive cells acts as a determinant factor for the association between triglycerides and blood pressure

Influence on the death view which a life image does

The purpose of this research is to clarify the relationship between life image and views on death during adolescence, and to investigate how the form of the life image gives rise to differences in views on death. In this research, based on prior research, we conducted a survey hypothesizing two main types of life image: circular and linear. The subjects of the survey were 78 female students enrolled at University A. The method used was a survey comprising life image graphics and a 14-item measure of views on death.Based on the results of this survey, the following points were indicated: 1) No clear relationship was seen between life image and views on death. 2) One of the unique characteristics of views on death as held by adolescents is that these views can be categorized into one of three types: Fear/Immortality High; Fear/Immortality Medium; and Fear/Immortality Low; and 3) life image is not limited to either "circular" or "linear"; in some cases, the life image has characteristics of both

The image of the death of the elderly people from the viewpoint of the relationship with significant others

本研究は,高齢者にとって死を考える上で重要となる他者との関係における死のイメージについて検討を行った。その結果,重要な他者が子どもの場合には,子どもに対して「役割を託す」「繋がりを感じる」関係性,死のイメージとして次の生への視点が見出され,子どもの中に自分の存在が内在化され,死を迎えた後にも重要な他者と繋がる感覚を有していることが示唆された。重要な他者が配偶者の場合には,「生きがい」「支えあう」関係性,死のイメージとして次の生への視点がみられた。重要な他者が親の場合には,親から託された「役割を引き受ける」関係性,肯定的な来世のイメージがみられた。重要な他者によって異なる関係性と死のイメージが存在することが示された

Anesthetic Management for Hemophilia A Carrier Who Underwent Caesarean Section Procedures Twice with Subarachnoid Anesthesia

Hemophilia A carriers are usually asymptomatic and their risk of bleeding when giving birth is not necessarily high, since the level of coagulation factor VIII (FVIII) increases during the perinatal period.　However, for mothers whose FVIII activity remains low, bleeding risk is increased and a Caesarean section is required when the fetus is a male. We report here anesthetic management for a hemophilia A carrier who underwent a selective Caesarean section procedure on two separate occasions during birth of male infants.　The level of FVIII was noted to be increased during the perinatal period, thus management by spinal subarachnoid anesthesia alone was used for the first childbirth and combined spinal-epidural anesthesia for the second.　FVIII remained within a normal range throughout both procedures, and no complications occurred in either the mother or the newborns.本稿の要旨は第１１９回日本産科麻酔学会学術集会（２０１５年，東京）において発表した