子宮内膜側に発症する (Subtypel) 子宮腺筋症は黄体ホルモン療法による多量性器出血の危険因子である

We aimed to retrospectively analyze the risk factors of a continuous dienogest (DNG) therapy for serious unpredictable bleeding in patients with symptomatic adenomyosis. This is a retrospective study based on data extracted from medical records of 84 women treated with 2 mg of DNG orally each day between 2008 and 2017. 47 subjects were excluded from the original analyses due to an inadequate subcategorization into subtype I and subtype II and a lack of hemoglobin levels. The influence of various independent variables on serious unpredictable bleeding was assessed. Of the 37 eligible patients who received the continuous DNG therapy, 14 patients experienced serious unpredictable bleeding. Univariate analysis revealed that the serious bleeding group had subtype I adenomyosis (P = 0.027). There was no correlation between age, parity, minimum hemoglobin level before treatment, previous endometrial curettage, and duration of DNG administration, or uterine or adenomyosis size and the serious bleeding. A DNG-related serious unpredictable bleeding is associated with the structural type of adenomyosis (subtype I) in patients with symptomatic adenomyosis.博士（医学）・甲第800号・令和3年9月29日© The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

卵巣子宮内膜症性嚢胞の嚢胞液鉄濃度が不妊に及ぼす影響について

The causes of infertility in women with endometriosis may range from anatomical distortions to various pathophysiological disturbances. The aim of the present study was to examine the effects of the cyst fluid (CF) concentration of iron on infertility in patients with ovarian endometrioma (OMA). Patients with histologically confirmed OMA were enrolled at the Department of Obstetrics and Gynecology, Nara Medical University Hospital between 2013 and 2019. The patients were divided into 2 groups, namely women experiencing current infertility (infertile group) and those without complaints of infertility (non‑infertile group). There were 2 types of patients in the infertile group: Patients who failed to achieve a clinical pregnancy following ≥12 months of regular unprotected sexual intercourse and those who had already been treated at fertility clinics. The CF concentration of iron was measured by the inductively coupled plasma‑optical emission spectrometry (ICP‑OES) method. The clinical data were analyzed retrospectively. A total of 77 patients were enrolled in the present study. Among these, 32 (41.6%) patients had infertility. When compared with the non‑infertile women, the infertile women were significantly younger (median age, 35 years; range, 24‑47 years; vs. median age, 40 years; range, 21‑53 years; respectively; P=0.003). The CF concentrations of iron (median, 324.8 mg/l; range, 71.3‑1046.3 mg/l; vs. median, 226.5 mg/l; range, 65.3‑737.5 mg/l; respectively; P=0.019) were significantly higher in the infertile group compared with the non‑infertile group. Multivariate logistic regression analysis indicated that age at diagnosis (≤38 years), the CF concentrations of iron (>326.6 mg/l) and the infertility index (iron/age ratio, >8.37) were independent risk factors for endometriosis‑related infertility. Multivariate analysis revealed that age (HR, 6.44; 95% CI, 2.06‑20.12) and iron (HR, 4.90; 95% CI, 1.48‑16.22) were independent factors for the identification of patients with OMA who presented with a complaint of infertility. In addition, the infertility index (iron/age ratio, >8.37; HR, 4.85; 95% CI, 1.01‑23.27) was an important predictor of infertility. ROC curve analysis also revealed that the areas under the ROC (AUC) for age, iron and infertility index were 0.699, 0.666 and 0.731, respectively. On the whole, the findings of the present study demonstrate that age at diagnosis and the CF concentration of iron may be potentially effective markers for predicting infertility in women with OMA.博士（医学）・乙第1500号・令和3年3月15日Copyright © Nagayasuet al. This is an open access article distributed under theterms of CreativeCommons Attribution License(https://creativecommons.org/licenses/by-nc-nd/4.0/)

Uniform Silica Coated Fluorescent Nanoparticles: Synthetic Method, Improved Light Stability and Application to Visualize Lymph Network Tracer

BACKGROUND: The sentinel lymph node biopsy (SLNB) was developed as a new modality in the surgical diagnosis of lymph node metastases. Dye and radioisotope are major tracers for the detection of sentinel lymph nodes (SLN). Dye tends to excessively infiltrate into the interstitium due to their small size (less than several nanometers), resulting in difficulties in maintaining clear surgical fields. Radioisotopes are available in limited number of hospitals. Fluorescent nanoparticles are good candidates for SLN tracer to solve these problems, as we can choose suitable particle size and fluorescence wavelength of near-infrared. However, the use of nanoparticles faces safety issues, and many attempts have been performed by giving insulating coats on nanoparticles. In addition, the preparation of the uniform insulating layer is important to decrease variations in the quality as an SLN tracer. METHODOLOGY/PRINCIPAL FINDINGS: We herein succeeded in coating fluorescent polystyrene nanoparticles of 40 nm with uniform silica layer of 13 nm by the modified Stöber method. The light stability of silica coated nanoparticles was 1.3-fold greater than noncoated nanoparticles. The popliteal lymph node could be visualized by the silica coated nanoparticles with injection in the rat feet. CONCLUSIONS/SIGNIFICANCE: The silica coated nanoparticles in lymph nodes could be observed by transmission electron microscope, suggesting that our silica coating method is useful as a SLN tracer with highly precise distribution of nanoparticles in histological evaluation. We also demonstrated for the first time that a prolonged enhancement of SLN is caused by the phagocytosis of fluorescent nanoparticles by both macrophages and dendritic cells

RacGAP α2-Chimaerin Function in Development Adjusts Cognitive Ability in Adulthood

SummaryA major concern in neuroscience is how cognitive ability in adulthood is affected and regulated by developmental mechanisms. The molecular bases of cognitive development are not well understood. We provide evidence for the involvement of the α2 isoform of Rac-specific guanosine triphosphatase (GTPase)-activating protein (RacGAP) α-chimaerin (chimerin) in this process. We generated and analyzed mice with global and conditional knockouts of α-chimaerin and its isoforms (α1-chimaerin and α2-chimaerin) and found that α-chimaerin plays a wide variety of roles in brain function and that the roles of α1-chimaerin and α2-chimaerin are distinct. Deletion of α2-chimaerin, but not α1-chimaerin, beginning during early development results in an increase in contextual fear learning in adult mice, whereas learning is not altered when α2-chimaerin is deleted only in adulthood. Our findings suggest that α2-chimaerin acts during development to establish normal cognitive ability in adulthood

Frail patients with respiratory failure

Background : Older patients with severe respiratory failure have higher mortality rates and are more likely to experience impairments in activities of daily living (ADL). Methods : We retrospectively reviewed patients (≥ 75 years) who received intubation and artificial ventilation for respiratory failure at Shimane University Hospital between November 2014 and December 2020. We compared the outcomes of frail patients with those of self-sufficient patients. Results : Thirty-two patients were included. ADL ability before respiratory failure was rated self-sufficient in 18 patients (self-sufficient group) and not self-sufficient in 14 patients (frail group). None of the patients in either group underwent advanced care planning prior to the onset of respiratory failure. In the self-sufficient and frail groups, the in-hospital mortality rates were 33% and 50%, and the incidence of bedridden patients at discharge was 6% and 43%, respectively. Most patients in the frail group (93%) died or were bedridden. The median hospitalization cost was JPY 2,984,000 for the self-sufficient group and JPY 3,008,000 for the frail group. Conclusion : The overall prognosis of frail older patients who underwent intubation and artificial ventilation was poor. When providing intensive care to such patients, it is important to carefully consider their suitability for the treatment

Cognitive and Emotional Changes in Peer Educators of Type 2 Diabetes Patients After Starting Peer-Support Activities

Background: Diabetes self-management education through peer support has beneficial effects, especially in regions with limited medical resources. To ensure peer educators continue to provide peer-led education programs, it is important that they remain motivated to instruct patients. Here, to explore measures to enhance peer-educators’ motivation toward such programs, we examined the cognitive and emotional changes in Filipino type 2 diabetics after 7-month activities as peer educators. Methods: We individually performed semi-structured interviews with 13 peer educators with 20 years of age or above in August 2017 (immediately before starting their peer-education activities) and in March 2018 (7 months after the start). The first interview was performed after the peer educators had received 2-day training of diabetes self-management. In both interviews, we asked the peer educators about their feelings toward peer-led educational activities (e.g., satisfaction, difficulty, reward, confidence, and challenges). Their replies about their own cognition and emotions were interpreted and integrated, and then analyzed qualitatively. Results: Four and seven categories were extracted from the first and second interviews, respectively. The category “Cognition of patients’ active learning attitudes and of positive changes in patients’ physical conditions and behavior” observed in the second interview led to “Cognition of growth as a peer educator” and “Satisfaction with supporting patients as a peer educator.” These two feelings gave the peer educators’ “Increased motivation to continue the activities as a peer educator.” This motivation was also associated with “Active collaboration among peer educators,” which was affected by “Difficulties and concerns in working as a peer educator.” Conclusion: To sustain diabetic peer-led education programs, we suggest that interventions be implemented that increase peer educators’ motivation toward their activities and stimulate their awareness of the importance of collaborating with one another. Such collaboration should help to overcome the difficulties they may face in providing peer-led education