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Advanced materials leveraging water control are garnering considerable interest, with the state of water emerging as a critical aspect of material design. This study explored the impact of microphase separation on water using aqueous solutions of double zwitterionic diblock copolymers, specifically poly(carboxybetaine methacrylate) and poly(sulfobetaine methacrylate) (PCB2- b -PSB4). These copolymers form a mesoscale periodic ordered lattice structure consisting of two distinct aqueous phases. Through differential scanning calorimetry and X-ray emission spectroscopy, it was found that water in these PCB2- b -PSB4 aqueous solutions exhibits pronounced cold crystallization and subtle distortions in hydrogen-bonding configurations.

A 65-year-old woman with a history of peritoneal dialysis undergoing hemodialysis at our hospital presented with a fever after experiencing gastroenteritis symptoms. She had an implanted peritoneal dialysis catheter for draining chylous ascites. After commencing empirical treatment with meropenem, peritoneal effluent samples revealed an increased white blood cell count, and peritonitis was diagnosed. Enterococcus gallinarum was detected in blood and effluent cultures. Meropenem was changed to vancomycin based on susceptibility testing but subsequently restarted and thereafter changed to ampicillin following exacerbation of peritonitis. Finally, catheter removal led to complete recovery. E. gallinarum is vancomycin-resistant and a rare cause of peritonitis.

Purpose: To assess the impact of gait training with rhythmic auditory stimulation (RAS) on enhancing gait speed in older people admitted to a convalescent rehabilitation ward (CRW), compared to conventional gait training methods., Methods: The study was designed as a single-center, open-label, pilot, randomized, parallel-group study. Thirty older people admitted to CRW were divided into two groups: the experimental group, which received gait training with RAS (n = 15, females = 53.3%, mean age = 83.9, SD = 6.5), and the control group, which underwent usual gait training (n = 15, females = 60.0%, mean age = 81.3, SD = 8.4). Regardless of their assigned group, all participants underwent 30 min training sessions, five times a week, for 3 weeks. The primary outcome was the 10 m walk test (10mWT), and the secondary outcomes included the Medical Outcome Study 8-Item Short-Form Health Survey and the Japanese version of the modified Gait Efficacy Scale. All measurements were taken at baseline and again at week 3., Results: Results indicated that older people in CRWs in the experimental group showed significant improvements in their 10mWT (effect size - 1.02) compared to the control group. None of the secondary outcomes were significant., Conclusions: This study suggests the preliminary effectiveness and feasibility of a gait practice intervention using RAS in a CRW., Trial Registration: The University Hospital Medical Information Network (UMIN) Registered 1 October 2022 (UMIN000049089)., (© 2024. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Background: We aimed to quantify the tortuosity of the middle cerebral artery (MCA) and assess its effects on radiological and clinical outcomes in patients with acute MCA occlusions who received mechanical thrombectomy (MT)., Methods: This retrospective study enrolled 53 patients with acute ischemic stroke due to MCA M1 or M2 segment occlusion who underwent MT using stent retrievers (SRs). Tortuosity index (TI) was defined to quantify the tortuosity of the MCA M1 segment using the following formula: (actual distance / straight distance) × 100. For each patient, four TIs were measured in the anteroposterior and caudal views for both ipsilateral and contralateral sides to the occluded site (TI-APi, TI-APc, TI-CAUi, and TI-CAUc, respectively) using magnetic resonance angiography (MRA) or computed tomography angiography (CTA). We defined the first-pass effect (FPE) as first-pass mTICI classification ≥2b reperfusion., Results: Patients who did not achieve FPE had significantly higher TI-APi (112 vs. 106; P  = 0.004), TI-APc (111 vs. 105; P  = 0.005), TI-CAUi (110 vs. 105; P  = 0.002), and TI-CAUc (110 vs. 105; P  = 0.001) than those who achieved FPE. In multivariable analysis, higher TI-APi, TI-CAUi, and TI-APc were independently associated with an increased rate of unsuccessful FPE (odds ratio (OR) [95% confidence interval (CI)]: 1.25 [1.02-1.61], 1.21 [1.01-1.45], and 1.27 [1.03-1.73], respectively). TI-CAUi, TI-APc, and TI-CAUc were also independent predictors of the occurrence of intracranial hemorrhage after MT (OR [95% CI]: 1.15 [1.01-1.38], 1.14 [1.01-1.38], 1.25 [1.02-1.52], respectively)., Conclusions: The TIs of the MCA M1 segment on both ipsilateral and contralateral sides were associated with unfavourable outcomes after MT., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Menstrual blood, containing high iron levels, can undergo retrograde transport into the abdominal cavity. Excess iron causes oxidative stress and inflammation. Iron metabolism is regulated by hepcidin, and serum hepcidin levels are increased in patients with endometriosis; however, the functions of hepcidin in normal endometrium remain unclear. We therefore aimed to examine hepcidin concentrations in patients with endometriosis and to determine if iron accumulation and hepcidin increased the production of reactive oxygen species (ROS) and inflammation in normal endometrial cells. We determined hepcidin levels in peritoneal fluid and menstrual blood from patients with and without endometriosis (25/16 and 15/15 patients, respectively). We also examined the effects of hepcidin on ferroportin expression, iron accumulation, and ROS generation in normal endometrial stromal cells (NESCs) from 20 women who underwent surgery for uterine leiomyoma, using immunohistochemistry and immunofluorescence analyses and analyzed its effect on the expression of inflammatory cytokines by real-time polymerase chain reaction. There was no significant difference in iron concentrations in menstrual blood or peritoneal fluid between women with and without endometriosis; however, women with endometriosis had significantly higher hepcidin levels in menstrual blood. Hepcidin reduced the expression of ferroportin in NESCs and promoted the accumulation of ferrous iron. Hepcidin plus ferrous iron increased the production of ROS and inflammatory cytokines compared with ferrous iron alone. These results indicate that women with endometriosis have high hepcidin levels in menstrual blood, leading to increased iron production, oxidative stress, and inflammation, which may, in turn, promote the development of endometriosis., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Using the transverse sinus as a conduit to treat a transverse sigmoid sinus dural arteriovenous fistula is uncommon. This report describes a minimally invasive direct puncture technique for the transverse sinus to treat a complex dural arteriovenous fistula in a hybrid operating room., Case: The patient was a 64-year-old man with intractable status epilepticus. Digital subtraction angiography demonstrated a right transverse sigmoid sinus dural arteriovenous fistula (Borden type II, Cognard type IIa+b). We performed a transcranial direct puncture because the femoral vein approach was not feasible due to bilateral thrombosed sinuses. Under general anesthesia and park-bench patient positioning, the transverse sinus was exposed and catheterized, and the affected sinus was embolized using microcoils. The fistula was completely obliterated, resolving the status epilepticus., Conclusions: Direct puncture of the transverse sinus can be effective for treating a transverse sigmoid sinus dural arteriovenous fistula. In a hybrid operating room, combined treatments can be performed comfortably and safely in a single session of general anesthesia. This treatment option is a viable alternative when other methods are unsuccessful., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hydrophilic materials display "bio-inert properties", meaning that they are less recognized as foreign substances by proteins and cells. Such materials are often water soluble; therefore, one general approach to enable the use of these materials in various applications deals with copolymerizing hydrophilic monomers with hydrophobic ones to facilitate such resulting copolymers water insoluble. However, reducing the hydrophilic monomer amount may reduce the bio-inert properties of the material. The decrease in bio-inert properties can be avoided when small amounts of fluorine are used in copolymers with hydrophilic monomers, as presented in this article. Even in small quantities (7.9 wt%), the fluorinated monomer, 1,1,1,3,3,3-hexafluoropropan-2-yl 2-fluoroacrylate (FAHFiP), contributed to the improved hydrophobicity of the polymers of the long side-chain poly(ethylene glycol) methyl ether methacrylate (mPEGMA) bearing nine ethylene glycol units turning them water insoluble. As evidenced by the AFM deformation image, a phase separation between the FAHFiP and mPEGMA domains was observed. The copolymer with the highest amount of the fluorinated monomer (66.2 wt%) displayed also high (82 %) FAHFiP amount at the polymer-water interface. In contrast, the hydrated sample with the lowest FAHFiP/highest mPEGMA amount was enriched of three times more hydrophilic domains at the polymer-water interface compared to that of the sample with the highest FAHFiP content. Thus, by adding a small FAHFiP amount to mPEGMA copolymers, water insoluble in the bulk too, could be turned highly hydrophilic at the water interface. The high content of intermediate water contributed to their excellent bio-inert properties. Platelet adhesion and fibrinogen adsorption on their surfaces were even more decreased as compared to those on poly(2-methoxyethyl acrylate), which is typically used in medical devices., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) pandemic impacted various parts of society, including Japanese children with allergies., Objective: This study investigated risk factors for pediatric allergic diseases associated with the state of emergency owing to the COVID-19 pandemic in Japan, including during school closures., Methods: Parents of pediatric patients (0-15 years) with allergies were enrolled and queried regarding the impact of school closure on pediatric allergies compared to that before the COVID-19 pandemic., Results: A valid response was obtained from 2302 parents; 1740 of them had children with food allergies. Approximately 4% (62/1740) of the parents reported accidental food allergen ingestion was increased compared to that before the COVID-19 pandemic. Accidental ingestion during school closures was associated with increased contact with meals containing allergens meant for siblings or other members of the family at home. The exacerbation rate during the pandemic was highest for atopic dermatitis at 13% (127/976), followed by allergic rhinitis at 8% (58/697), and bronchial asthma at 4% (27/757). The main risk factors for worsening atopic dermatitis, allergic rhinitis, and bronchial asthma were contact dermatitis of the mask area (34/120 total comments); home allergens, such as mites, dogs, and cats (15/51 total comments); and seasonal changes (6/25 total comments), respectively., Conclusion: The main factors affecting allergic diseases were likely related to increased time at home, preventive measures against COVID-19, and refraining from doctor visits. Children with allergies were affected by changes in social conditions; however, some factors, such as preventing accidental ingestion and the management of allergens at home, were similar to those before the COVID-19 pandemic. Patients who had received instructions on allergen avoidance at home before the pandemic were able to manage their disease better even when their social conditions changed., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2023. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

Problem: Endometriosis is a proliferative disease characterized by cytokine-induced inflammation. The objective of this study was to assess cell growth and PGE 2 production induced by TNF-α in endometriotic stromal cells (ESCs) in spheroid cell culture and to identify the signaling pathway involved with a view to finding new therapeutic targets for endometriosis., Method of Study: Tissue samples were collected from patients with and without endometriosis. ESCs were isolated from ovarian endometrioma (OE). Gene expression was evaluated by real-time PCR and DNA microarray analysis, the proliferative effect on ESCs by WST-8 assay, and PGE 2 production by ELISA. Protein phosphorylation was detected using western blotting., Results: COX-2, aromatase and VEGFA mRNA expression and PGE 2 production were significantly elevated in spheroid cell cultures compared to monolayer cell cultures. TNF-α receptor (TNFR) 1 and TNFR2 mRNA was also significantly increased. TNF-α promoted the proliferation and PGE 2 production of ESCs in spheroid cell cultures significantly more than in monolayer cell cultures. TNF-α increased the expression of several genes related to the pathophysiology of endometriosis in spheroid ESCs. DNA microarray analysis revealed that the Tpl2 gene, which codes for a MAPK upstream of MEK, was upregulated in OE and endometrium with endometriosis compared to normal endometrium. TNF-α increased the phosphorylation and expression of Tpl2 and MEK, and Tpl2 and MEK inhibitors inhibited TNF-α-induced proliferation and PGE 2 production in spheroid ESCs., Conclusion: The Tpl2-MEK signaling pathway may play a critical role in the cell growth and PGE 2 production induced by TNF-α in spheroid ESCs., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Decreased walking speed in older patients admitted to convalescent rehabilitation wards (CRWs) is one of the factors that inhibit home discharge. Therefore, interventions to improve gait speed in older patients admitted to CRWs are important, and rhythmic auditory stimulation (RAS) may be an effective intervention strategy. However, the effect of RAS on gait speed in older patients admitted to CRWs is not well known. Therefore, this study protocol aims to determine the feasibility of the RAS-based gait practice for older patients admitted to the CRW., Methods: The study is designed as a single-center, open-label, pilot, randomized, parallel-group study. Participants will be 30 patients aged ≥65 years admitted to the CRW and randomly assigned to the experimental group (RAS-based gait practice; n = 15) or the control group (normal gait practice; n = 15). In both groups, interventions will be conducted for 30 min per session, 5 times per week for 3 weeks. The primary outcome is the change in the 10-m walk test 3 weeks after the baseline assessment. Secondary outcome is the change in the score of the Medical Outcome Study 8-Item Short-Form Health Survey and the Japanese version of the modified Gait Efficacy Scale from baseline assessment to 3 weeks later., Discussion: This exploratory RCT was developed using strict scientific standards and is based on defined protocols. Thus, this study will be used to assess the viability of a larger investigation into RAS-based gait practice. If our theory is accurate, this study could serve as a foundation for establishing RAS-based gait practice in CRWs as a common rehabilitation strategy., Trial Registration: This study was registered in the University Hospital Medical Information Network (UMIN) clinical trials registry in Japan (UMIN000049089)., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Although nutrient status plays an important role in cell metabolism, its significance in endometriosis is obscure. Herein, we investigated the effects of a low-nutrient microenvironment on endometriosis. Stromal cells (SCs) from ovarian endometrioma (OESCs) or normal endometrium without endometriosis (NESCs) were isolated and cultured. A low-nutrient microenvironment was replicated by replacing the culture medium with Hank's balanced salt solution. OESC and NESC proliferation under the low-nutrient condition was measured. The expression of exacerbating factors in endometriosis under the low-nutrient condition was examined at the mRNA and protein levels. OESCs showed higher proliferation than NESCs under the low-nutrient condition. In OESCs, the low-nutrient condition upregulated the mRNA expression of vascular endothelial growth factor (VEGF), interleukin-6 and -8, aromatase, Bcl-2, and peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and downregulated that of BAX and induced transcription of PI.3, PII, and exon II. Western blotting revealed elevated VEGF and PGC-1α expression under the low-nutrient condition in OESCs. These changes coincided with the elevated expression of PGC-1α, which was reduced at the mRNA level upon nutrient status rescue. Endometriosis is exacerbated by altered angiogenesis, inflammation, anti-apoptosis, and local estrogen production while trying to survive under a low-nutrient microenvironment; it may be attributed to PGC-1α-mediated metabolic mechanisms., (© 2022. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Endometriosis is a serious disorder that can lead to infertility. The immune system, particularly regulatory T cells (Tregs), is involved in endometriosis and infertility; however, endometriosis-associated infertility is poorly understood. Tregs, which have an immunosuppressive function, fluctuate during the menstrual cycle. They are functionally heterogeneous and can be divided into subsets, with only activated Tregs (aTregs) having a true immunosuppressive function. The purpose of this study is to investigate the role of aTregs in endometriosis and how they contribute to endometriosis-associated infertility. We enrolled 72 women with (n = 39) and without (n = 33) endometriosis. Subpopulations of Tregs were examined in normal endometrium (NE), eutopic endometrium from women with endometriosis (EE), normal peritoneal fluid (N-PF), and peritoneal fluid from women with endometriosis (E-PF) via flow cytometry. The proportion of aTregs during the ovulatory phase was higher in NE than in EE (P < 0.05), and that during ovulatory and secretory phases was significantly higher in NE than in N-PF (P < 0.01 and 0.05, respectively). aTreg populations did not significantly differ between EE and E-PF. During the ovulatory phase, the proportion of resting Treg (rTreg) in the N-PF was significantly higher than during the proliferative phase (P < 0.05). The E-PF of rTreg populations did not differ significantly throughout the menstrual cycle. We found that Treg subsets were altered in the endometrium and PF of patients with endometriosis during the menstrual cycle. Our findings, particularly the reduction of aTregs in the EE, may provide an insight into the mechanism of endometriosis-associated infertility., Competing Interests: Conflict of interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Here we aimed to establish a simple detection method for detecting circulating tumor cells (CTCs) in the blood sample of colorectal cancer (CRC) patients using poly(2-methoxyethyl acrylate) (PMEA)-coated plates. Adhesion test and spike test using CRC cell lines assured efficacy of PMEA coating. A total of 41 patients with pathological stage II-IV CRC were enrolled between January 2018 and September 2022. Blood samples were concentrated by centrifugation by the OncoQuick tube, and then incubated overnight on PMEA-coated chamber slides. The next day, cell culture and immunocytochemistry with anti-EpCAM antibody were performed. Adhesion tests revealed good attachment of CRCs to PMEA-coated plates. Spike tests indicated that ~75% of CRCs from a 10-mL blood sample were recovered on the slides. By cytological examination, CTCs were identified in 18/41 CRC cases (43.9%). In cell cultures, spheroid-like structures or tumor-cell clusters were found in 18/33 tested cases (54.5%). Overall, CTCs and/or growing circulating tumor cells were found in 23/41 CRC cases (56.0%). History of chemotherapy or radiation was significantly negatively correlated with CTC detection ( p = 0.02). In summary, we successfully captured CTCs from CRC patients using the unique biomaterial PMEA. Cultured tumor cells will provide important and timely information regarding the molecular basis of CTCs.

Background: Symptomatic cerebral vasospasm after subarachnoid hemorrhage (SAH) is a significant cause of delayed cerebral ischemia that leads to poor outcomes. Selective intra-arterial administration of fasudil hydrochloride (IAF) has been adopted for its vasodilatory effect on spasm arteries to prevent delayed cerebral ischemia. However, its effect on clinical outcomes and predictive factors for good recovery are not fully understood. This study aimed to investigate the outcomes of selective IAF and identify predictive factors for good outcomes in patients with cerebral vasospasm after SAH., Methods: A retrospective study of 36 patients with cerebral vasospasm following SAH who underwent selective IAF at our institution between January 2014 and May 2022 was conducted. We evaluated the improvements in neurological findings before and after selective IAF. Statistical analyses were performed to determine factors associated with good outcomes., Results: Selective IAF improved the neurological findings in 26 patients (72.2%). Pre-therapeutic absence of cerebral infarction in more than 1/3 of the spasm artery perfusion area was significantly associated with an improvement in neurological findings ( p  < 0.0001). Furthermore, there was a tendency for a good outcome when the age was younger ( p  = 0.093), and the spasm was limited to peripheral vessels ( p  = 0.065)., Conclusion: Our study indicates that selective IAF has a promising effect in improving symptomatic vasospasm, except when a large cerebral infarction exists in the spasm artery perfusion area. Early consideration of selective IAF could be recommended once patients experience symptomatic cerebral vasospasm after SAH.

This study assessed the validity of dietary balance scores (DBSs) by investigating the association between DBSs and nutrient adequacy (NA) in two Japanese populations. The participants were 65 community-dwelling Japanese from Tokushima Prefecture and 2,330 community-dwelling Japanese from Aichi Prefecture. Based on food frequency questionnaires or 3-day dietary records, we obtained 18 food groups. The NA score integrates nine beneficial nutrients and two nutrients that should be limited. We calculated four different DBSs: DBS1 consisted of five food groups (score range:0?20), DBS2 consisted of nine food groups (score range:0?36), DBS3 consisted of eight food groups (score range:0?32), and DBS4 consisted of 10 food groups (score range:0?40). Both the Spearman rank correlation coefficient with NA and the area under the receiver operating characteristic curve (AUC-ROC) for the nine beneficial nutrients were then estimated to test the performance of each DBS in predicting nutrient intake. The results showed that DBS1 and DBS4 were positively correlated with NA, while the AUC-ROC showed that DBS4 could moderately discriminate individuals with adequate intake levels of all nine nutrients. These findings suggest DBSs (especially DBS4) are useful in assessing dietary balance in middle-aged and older community-dwelling Japanese. J. Med. Invest. 70 : 377-387, August, 2023.

Introduction: Oral immunotherapy (OIT) imposes a burden on parents and their children with food allergies (FAs). We already developed a questionnaire for OIT-related Parental Burden (OIT-PB) scale. However, the previous questionnaire had some problems. This study modified OIT-PB and verified its reliability and validity., Methods: A 20-item draft covering the physical and mental burdens caused by OIT was prepared jointly with multiple allergists. The Food Allergy Quality of Life Questionnaire-Parental Burden (FAQLQ-PB) and Stress Response Scale-18 (SRS-18) were used to verify concurrent validity. A questionnaire survey was administered during treatment to parents of FA children who had started OIT for the first time. An additional OIT-PB survey was performed at one specific institution 1 week after the posttreatment survey., Results: The responses of 64 of the 76 recruited parents were analyzed. Of the 20 questions, 1 item was excluded owing to the floor effect, 1 was excluded because its commonality was less than 0.2, and 2 were excluded because their factor loading values were less than 0.4. Factor analysis was used to classify the OIT-PB into the following 4 subscales: "burden caused by adherence to treatment plan," "anxiety about symptom-induced risk," "burden due to patient's eating behavior," and "anxiety about treatment effect." The Cronbach's α for all 16 items of the OIT-PB was 0.893; Cronbach's α for each subscale was 0.876, 0.898, 0.874, and 0.717. The re-test reliability coefficient was 0.864 (95% confidence interval [CI]: 0.720-0.937, p &lt; 0.001). A significant positive correlation was found between the OIT-PB and FAQLQ-PB (R = 0.610 [95% CI: 0.422-0.747], p &lt; 0.001) and the SRS-18 (R = 0.522 [95% CI: 0.306-0.687], p &lt; 0.001). A significant negative correlation was found between the rate of increase in OIT food intake and the "anxiety about treatment effect" score (R = -0.355 [95% CI: -0.558-0.112], p &lt; 0.001). Parents of children on the hen's egg OIT treatment scored higher on the "burden due to patient's eating behavior" subscale than did parents of children on the milk and wheat OIT treatment., Conclusion: The burden of OIT experienced by parents can be broadly classified into four categories. The modified OIT-PB was able to evaluate them individually and was shown to have reliability and validity. This scale is expected to be useful in the development of OIT that considers not only therapeutic effect but also the burden experienced by FA children and their parents., (© 2023 S. Karger AG, Basel.)

Cellulose-based crystalline assemblies artificially constructed in a bottom-up manner are attracting increasing attention as chemically stable and functionally designable nano- to macroscale materials. However, basic knowledge of how such crystalline assemblies interact with biomolecules and how to control them via molecular design is still limited. In this study, we investigated the protein adsorption properties of crystalline lamella assemblies composed of alkyl β-cellulosides (namely, ethyl, n-butyl, and n-hexyl β-cellulosides) or plain cellulose, which all have an antiparallel molecular arrangement. It was found that the adsorption of proteins was observed only for the n-hexyl β-celluloside assembly, while it was hardly observed for other assemblies. The n-hexyl groups appeared to be ordinarily embedded in the assembly surface in an aqueous phase, while, when in contact with proteins, n-hexyl groups appeared to be tethered to promote protein adsorption. All-atom molecular dynamics simulations supported the contradictory protein adsorption properties. The basic knowledge obtained herein is highly valuable for controlling the interactions of cellulose-based synthetic assemblies with proteins for designing new biological applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Problem: Regulatory T cells (Tregs) play important roles in diseases occurring in women of reproductive age and pregnancy. Tregs are functionally heterogeneous and can be divided into activated Tregs (aTregs), resting Tregs (rTregs), and non-suppressive Tregs (non-Tregs). The purpose of this study is to investigate the change of Treg subpopulations during the menstrual cycle and early pregnancy., Method of Study: Two groups of women were enrolled: healthy women aged 20 to 39 years with normal menstrual cycles and patients scheduled to undergo frozen-thawed blastocyst transfer (FT-BT) (subfertile women). Peripheral blood samples were collected at day 5 of the onset of menstruation (follicular phase), 0-2 days after luteinizing hormone (LH) surge (periovulatory phase), and 7-11 days after LH surge (luteal phase) from 20 healthy women. From 23 subfertile women, samples were collected at day 5 (the day of BT) and day 14 (the day of pregnancy testing) of progestogen administration during FT-BT cycle and 9 weeks of gestation if the patient got pregnant. The proportion of total Treg and its subpopulations among CD4 + T cells was analyzed., Results: TTreg and aTreg proportion expanded during periovulatory phase (p < .01) and after pregnancy (p < .05 for tTreg and p < .01 for aTreg). rTreg proportion was significantly high during periovulatory phase (p < .01) and during luteal phase (p < .01). Non-Tregs showed no significant change., Conclusions: RTregs and aTregs, especially in luteal phase and after getting pregnant, showed significant changes and may play important roles in women of reproductive age., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The hydration state of bioactive glass materials and its relationship with their biocompatibility have been receiving attention. In this research, silver-containing bioactive glasses (BGAgs) (Ag contents of 0.25, 0.5, and 1.0% in the glass system) were developed using the sol-gel method. Their physicochemical properties, size, morphology, and surface area were characterized by conducting X-rays diffraction (XRD), Fourier transform infrared (FTIR), Transmission electron microscopy (TEM), and Brunauer-Emmett-Teller (BET) surface area analyses. The surface charges of the developed BGAgs were evaluated using the Nano Zetasizer. Moreover, the antibacterial activities and intermediate water (IW) contents of hydrated BGAgs were determined. Finally, BGAgs disks were tested against osteosarcoma (MG63) cell line to evaluate their death modes. The physicochemical characteristics of the BGAgs revealed no modifications after Ag doping. In comparison, relative changes were recorded in the particle size (20-33 to 16-29 nm), surface area (4.3 to 3.7 m 2 /g), and particle charge (-24 to -14.6 mV). Doping the current glass system with silver produced impressive amounts of IW, consistent with recorded proliferation rates of the cells when treated with BGAgs. The determined hydration states correlated with other findings in this research might be helpful in predicting and assessing the biological behaviors of BGAgs., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The endovascular treatment of large, wide-necked basilar apex aneurysms (BAAs) remains challenging. Although horizontal stent deployment across both P1 segments of the posterior cerebral arteries (PCAs) would be an optimal strategy in coil embolization of wide-necked BAAs, this is only feasible in cases with anatomically favorable access. In rare circumstances, large-diameter conduits of extracranial-intracranial (EC-IC) bypass can also provide a good access route for endovascular treatment of complex intracranial aneurysms., Methods: We describe the technique of accessing the PCA via EC-IC bypass grafts and deploying a stent horizontally across the neck of BAA and its coil embolization. We provide a detailed technical review and describe some pitfalls of the procedure., Results: Two patients underwent EC-IC bypass surgery prior to the treatment of a large, wide-necked BAA. The radial artery and saphenous vein were used as grafts, respectively. To facilitate coil embolization for a large BAA, a PCA-to-PCA horizontal stent was deployed via the bypass graft. Trans-cell and jailing techniques were used, respectively. Both aneurysms were completely occluded, and the patients were discharged without any neurological deficit., Conclusion: Horizontal stent deployment via EC-IC bypass grafts can be performed safely, providing proper closure of the aneurysmal neck and apposition to both PCAs, facilitating complete coil embolization., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Introduction: Sepsis is not only the leading cause of death in the intensive care unit (ICU) but also a major risk factor for physical and cognitive impairment and mental disorders, known as postintensive care syndrome (PICS), reduced health-related quality of life (HRQoL) and even mental health disorders in patient families (PICS-family; PICS-F). The ABCDEF bundle is strongly recommended to overcome them, while the association between implementing the bundle and the long-term outcomes is also unknown., Methods and Analysis: This is a multicentre prospective observational study at 26 ICUs. All consecutive patients between 1 November 2020 and 30 April 2022, who are 18 years old or older and expected to stay in an ICU for more than 48 hours due to sepsis or septic shock, are enrolled. Follow-up to evaluate survival and PICS/ PICS-F will be performed at 3, 6 and 12 months and additionally every 6 months up to 5 years after hospital discharge. Primary outcomes include survival at 12 months, which is the primary outcome, and the incidence of PICS defined as the presence of any physical impairment, cognitive impairment or mental disorders. PICS assessment scores, HRQoL and employment status are evaluated. The association between the implementation rate for the ABCDEF bundle and for each of the individual elements and long-term outcomes will be evaluated. The PICS-F, defined as the presence of mental disorders, and HRQoL of the family is also assessed. Additional analyses with data up to 5 years follow-up are planned., Ethics and Dissemination: This study received ethics approvals from Saiseikai Utsunomiya Hospital (2020-42) and all other participating institutions and was registered in the University Hospital Medical Information Network Clinical Trials Registry. Informed consent will be obtained from all patients. The findings will be published in peer-reviewed journals and presented at scientific conferences., Trial Registration Number: UMIN000041433., Competing Interests: Competing interests: The authors declare that they have no competing interests for the submitted work. Some authors report potential conflicts of interest outside of this submitted study. KL reports personal fees from MERA and is the core research member of TXP Medical completely outside the submitted work. KN reports personal fees from Abbott Laboratory, Nestle, TERUMO, GETINGE, Asahi Kasei Pharma, Ono Pharmaceutical, Japan Blood Products Organisation, Nihon Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Toray and Baxter, and grants from Asahi Kasei Pharma outside the submitted work. HK receives a salary from the Japanese Society for Early Mobilisation (non-profit society) as a chair (full time) outside the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Postoperative intracerebral hemorrhage (ICH) after direct bypass surgery for Moyamoya disease could contribute to neurologic deterioration. The aim of this study was to evaluate the effectiveness of 5-day bed rest in reducing the occurrence of postoperative ICH., Methods: This study included 122 consecutive hemispheres in 87 Japanese adult MMD patients, composed of 80 control hemispheres from historical data and 42 hemispheres after 5-day bed rest. They all underwent direct bypass surgery. The incidence of postoperative ICH and neurologic deterioration assessed via the modified Rankin Scale were investigated and statistically analyzed., Results: Postoperative ICH was observed in 9 out of the 80 (11.3%) control patients, but not in the 42 patients with 5-day bed rest. The incidence of postoperative ICH and neurologic deterioration via the modified Rankin Scale were significantly different between the 2 groups (P = 0.0268 and 0.0078, respectively). Univariate logistic analysis revealed that 5-day bed rest significantly reduced the incidence of postoperative ICH (P = 0.0048)., Conclusions: Five-day bed rest after direct bypass surgery dramatically can reduce the incidence of postoperative ICH and neurologic deterioration after direct bypass surgery., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Blood-compatible materials that do not promote reactions in contact with human blood are required to support emerging medical technologies. The interfaces of poly(2-methoxyethyl acrylate) (PMEA), a blood-compatible polymer, and its analogues were investigated by frequency modulation atomic force microscopy (FM-AFM). The grafted polymers exhibited phase separation into polymer-rich and water-rich domains. Thin repulsive layers of hydrated polymer chains were observed in the water-rich domains of the blood-compatible polymers; on the other hand, such layers were not observed for the non-blood-compatible polymers. We report for the first time that FM-AFM enables characteristic repulsive layers composed of hydrated polymer chains in water-rich domains to be observed, which is a significant design factor for blood-compatible polymers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Developing support and an environment for patients with dementia in hospitals is important. This study aims to assess the immediate effect of one-session cognitive stimulation intervention on the mood of patients with dementia in a hospital as preliminary evidence. This study included 33 female patients. The cognitive stimulation intervention was conducted in the day room of the hospital ward by two occupational therapists. The patients participated in one or more sessions. The cognitive stimulation intervention was designed to discuss current affairs that implicitly stimulate memory, executive function, and language skills, according to the cognitive stimulation definition. Outcomes were evaluated using a two-dimensional mood scale. The primary outcome was pleasure. The before and after session scores for the first session and the average score before and after each session at multiple times were compared. The patients' pleasure showed significant improvements in both analyses. These results may indicate that one-session Cognitive stimulation intervention in a hospital effectively improves a mood of pleasure immediately. This study is the first report to provide preliminary evidence on the beneficial alterations of mood after one-session cognitive stimulation intervention for patients with dementia in hospitals. Cognitive stimulation intervention may be an effective non-pharmacotherapy for these patients.

Problem: Innate lymphoid cells (ILCs), a recently discovered family of innate immune cells, are responsible for the early immune response, and control both innate and adapted immune system via cytokine secretion. The role of ILCs in endometriosis has not been investigated; therefore, here, we aimed to investigate how the proportion of ILCs changes in endometriosis., Method of Study: The percentage of each ILC group in CD45 + cells was examined in the peripheral blood, peritoneal fluid, endometrium, and ovarian endometrioma obtained from women with and without endometriosis (ERB-C-1216) using flow cytometry., Results: Specimens were obtained from 19 women with endometriosis and 15 without endometriosis. In the endometrium, patients with endometriosis had lower proportion of ILC2 and 3 compared to control specimens (ILC2: .02±.01% vs .07±.03%; P < .05, ILC3: .31±.14% vs 1.10±.93%; P < .05). There was no significant change in the peripheral blood or the peritoneal fluid between the two groups. Additionally, ovarian endometrioma increased the proportion of ILCs (ILC1: .92±1.12%, ILC2: .08±.08%, ILC3: .70±.39%) compared to the endometrium samples of patients with endometriosis each with P < .05. Immunohistochemistry of IL-1β and IL-23, which are ILC3-inducing factors, showed no significant change in the H-score of the epithelium of the two groups, but a significant increase was found in ovarian endometrioma., Conclusion: The proportion of ILC2 and 3 was reduced in the endometrium of patients with endometriosis, and ILCs were increased in ovarian endometrioma. Our findings may indicate a new immunological approach to understand the pathophysiology of endometriosis., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The validity of dietary variety score (DVS) using a short-form questionnaire has not been investigated using dietary diversity based on a quantitative distribution of consumed foods in older Japanese. We examined the association between DVS and objective dietary diversity using a Quantitative Index for Dietary Diversity (QUANTIDD) based on the quantitative distribution of foods consumed by older Japanese community dwellers. The subjects were 65 older Japanese community dwellers aged 60?79 years. We used two kinds of scores for assessment of dietary diversity. At first, dietary diversity was determined using DVS calculated from answers to a questionnaire about frequencies of intake of 10 food groups. Second, dietary intake was assessed using a 3-day dietary record with photographs, and dietary diversity was determined using QUANTIDD. The relationships between DVS and QUANTIDD were assessed using partial correlation coefficients controlling for confounders. The correlation coefficient between DVS and QUANTIDD was moderate (r=0.212-0.458). After controlling for confounders, those correlation coefficient between DVS and QUANTIDD remained moderate. The findings suggest that there was a moderate relationship between DVS and QUANTIDD, and DVS using a short-form questionnaire may be useful for assessing dietary diversity in older Japanese community dwellers. J. Med. Invest. 69 : 31-37, February, 2022.

Problem: Inflammation and immune responses play crucial roles in the development of endometriosis. Although interleukin-9 (IL-9) has a pro-inflammatory function in chronic inflammatory diseases, its function in endometriosis remains unknown. Here, we aimed to investigate the significance of IL-9 and IL-9-producing lymphocytes in endometriosis., Method of Study: Specimens were obtained from patients with and without endometriosis. Peritoneal fluid (PF), peripheral blood (PB), and ovarian endometrioma (OE) tissues were analyzed for the proportion of CD4 + IL-9 + lymphocytes and IL-9 concentration using flow cytometry and enzyme-linked immunosorbent assay. OE, endometrium with endometriosis (EE), and normal endometrium (NE) were analyzed for IL-9 receptor (IL-9R) expression using immunohistochemical staining. IL-9-dependent changes in Interleukin-8 (IL-8) expression in endometrial stromal cells from OE (OESCs) were evaluated using real-time PCR., Results: The proportion of CD4 + IL-9 + lymphocytes was higher in the PF, but not the PB, of patients with endometriosis than individuals without endometriosis (p < .05). However, IL-9 levels in the PF did not differ between those with and without endometriosis. We detected CD4+ IL-9+ lymphocytes in OE tissues and IL-9R in OE tissues and OESCs. In OESC culture, IL-9 significantly elevated IL-8 expression in a dose-dependent manner (p < .05), which was nullified by the addition of the anti-IL-9 receptor antibody. Furthermore, IL-9 additively stimulated IL-8 expression in the presence of TNF-α (p < .05)., Conclusion: Our findings show that IL-9 produced by helper T cells induces IL-8 expression, suggesting that IL-9 plays an important role in the development of endometriosis by stimulating IL-8 expression., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Intermediate water (IW) in hydrated bioactive glasses remains uninvestigated. We obtained titanium (Ti)-containing bioactive glasses (BGTs) (Ti at 5%, 7.5% and 10% of the glass system) using the sol-gel technique. Their thermal, physicochemical, and morphological properties, before and after Ti-doping, were analysed using DTA, XRD, FTIR, TEM, and SEM accessorised with EDAX, and size distribution and zeta potential surface charges were determined using a NanoZetasizer. The IW in hydrated BGTs was investigated by cooling and heating runs of DSC measurements. Moreover, the mode of death in an osteosarcoma cell line (MG63) was evaluated at different times of exposure to BGT discs. Ti doping had no remarkable effect on the thermal, physicochemical, and morphological properties of BGTs. However, the morphology, size, and charges of BGT nano-powders were slightly changed after inclusion of Ti compared with those of BGT0; for example, the particle size increased with increasing Ti content (from 4-5 to 7-28 nm). The IW content was enhanced in the presence of Ti. The mode of cell death revealed the effect of IW content on the proliferation of cells exposed to BGTs. These findings should help improve the biocompatibility of inorganic biomaterials.

Lobar cerebral microbleeds (CMBs) in Alzheimer's disease (AD) are associated with cerebral amyloid angiopathy (CAA) due to vascular amyloid beta (Aβ) deposits. However, the relationship between lobar CMBs and clinical subtypes of AD remains unknown. Here, we enrolled patients with early- and late-onset amnestic dominant AD, logopenic variant of primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA) who were compatible with the AD criteria. We then examined the levels of cerebrospinal fluid (CSF) biomarkers [Aβ1-42, Aβ1-40, Aβ1-38, phosphorylated tau 181 (P-Tau), total tau (T-Tau), neurofilament light chain (NFL), and chitinase 3-like 1 protein (YKL-40)], analyzed the number and localization of CMBs, and measured the cerebral blood flow (CBF) volume by 99m Tc-ethyl cysteinate dimer single photon emission computerized tomography ( 99m Tc ECD-SPECT), as well as the mean cortical standard uptake value ratio by 11 C-labeled Pittsburgh Compound B-positron emission tomography ( 11 C PiB-PET). Lobar CMBs in lvPPA were distributed in the temporal, frontal, and parietal lobes with the left side predominance, while the CBF volume in lvPPA significantly decreased in the left temporal area, where the number of lobar CMBs and the CBF volumes showed a significant inversely correlation. The CSF levels of NFL in lvPPA were significantly higher compared to the other AD subtypes and non-demented subjects. The numbers of lobar CMBs significantly increased the CSF levels of NFL in the total AD patients, additionally, among AD subtypes, the CSF levels of NFL in lvPPA predominantly were higher by increasing number of lobar CMBs. On the other hand, the CSF levels of Aβ1-38, Aβ1-40, Aβ1-42, P-Tau, and T-Tau were lower by increasing number of lobar CMBs in the total AD patients. These findings may suggest that aberrant brain hypoperfusion in lvPPA was derived from the brain atrophy due to neurodegeneration, and possibly may involve the aberrant microcirculation causing by lobar CMBs and cerebrovascular injuries, with the left side dominance, consequently leading to a clinical phenotype of logopenic variant., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ikeda, Kodaira, Kasahara, Takai, Nagashima, Fujita, Makioka, Hirayanagi, Furuta, Furuta, Sanada, Kobayashi, Harigaya, Nagamine, Hattori, Tashiro, Kishi, Shimada, Suto, Tanaka, Sakai, Yamazaki, Tanaka, Aihara, Amari, Yamaguchi, Okamoto, Takatama, Ishii, Higuchi, Tsushima and Ikeda.)

There are numerous reports on the effects of the coronavirus disease on mothers and fetuses during pregnancy. It is currently unknown whether pregnancy is associated with a high risk of severe coronavirus disease. We report a pregnant patient with coronavirus disease who underwent a cesarean section. A pregnant 39-year-old Japanese woman was diagnosed with coronavirus disease at 25 weeks of gestation. Her breathing condition worsened daily, and she required oxygen administration. On day 6 of her 26th week of gestation, she developed severe pneumonia and required tracheal intubation and artificial ventilation, and an emergency cesarean section was performed under general anesthesia. It is necessary to investigate the risk of increased coronavirus disease severity during pregnancy, the effects of coronavirus disease on perinatal prognosis, and the management of pregnancy with coronavirus disease., (© 2021 Japan Society of Obstetrics and Gynecology.)

Objective: Neurosurgical ablation is an effective treatment for medically refractory motor symptoms of Parkinson's disease (PD). A limited number of studies have reported the effect of ablation of the pallidothalamic tract for PD. In this study, the authors evaluated the safety and efficacy of unilateral pallidothalamic tractotomy for akinetic-rigid (AR)-PD., Methods: Fourteen AR-PD patients, who were enrolled in this prospective open-label study, underwent unilateral pallidothalamic tractotomy. The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III and Part IV (dyskinesia and dystonia) scores and levodopa equivalent daily dose (LEDD) were evaluated at baseline and at 3 and 12 months postoperatively., Results: Of the 14 patients enrolled in the study, 4 were lost to follow-up and 10 were analyzed. The total MDS-UPDRS Part III score significantly improved from 45 ± 4.6 at baseline to 32.9 ± 4.8 at 12 months postoperatively (p = 0.005). Contralateral side rigidity and bradykinesia significantly improved from 4.4 ± 0.5 and 10.4 ± 1.5 at baseline to 1.7 ± 0.4 (p = 0.005) and 5.2 ± 1.4 (p = 0.011) at 12 months, respectively. While posture significantly improved with a 20% reduction in scores (p = 0.038), no significant improvement was found in gait (p = 0.066). Dyskinesia and dystonia were improved with a 79.2% (p = 0.0012) and 91.7% (p = 0.041) reduction in scores, respectively. No significant change was found in the LEDD. Hypophonia was noted in 2 patients, eyelid apraxia was noted in 1 patient, and a reduced response to levodopa, which resulted in an increase in the daily dose of levodopa, was noted in 3 patients. No serious permanent neurological deficits were observed., Conclusions: Unilateral pallidothalamic tractotomy improved contralateral side rigidity and bradykinesia, dyskinesia, and dystonia in patients with AR-PD. Clinical trial registration no.: UMIN000031138 (umin.ac.jp).

Background: Fetal skeletal dysplasia (FSD) comprises a complex group of systemic bone and cartilage disorders. Many FSD phenotypes have indistinct definitions, making definitive prenatal diagnosis difficult. The condition is typically diagnosed using sonography; however, three-dimensional computed tomography (3D-CT) also aids in making a prenatal diagnosis. This study aimed to examine the efficacy of 3D-CT in the prenatal diagnosis of FSD by comparing the diagnostic accuracy of fetal sonography and 3D-CT., Methods: On suspicion of FSD based on ultrasound examination, we performed 3D-CT prenatally to obtain detailed skeletal information on FSD. To minimize exposure of the fetuses to radiation without compromising image quality, we used predetermined 3D-CT settings for volume acquisition., Results: Nineteen fetuses were suspected of having skeletal dysplasia based on ultrasonography findings. Of these, 17 were diagnosed with FSD using 3D-CT. All 17 fetuses diagnosed with FSD prenatally were confirmed postnatally to have the condition. The postnatal diagnosis (campomelic dysplasia) differed from the prenatal diagnosis (osteogenesis imperfecta) in only one infant. Sixteen cases (94.1%) were diagnosed both prenatally and postnatally with FSD. Five infants had lethal skeletal dysplasia; one died in utero, and four died as neonates. We determined the appropriate delivery method for each infant based on the prenatal diagnosis., Conclusions: 3D-CT is a valuable tool for augmenting ultrasound examinations in the diagnosis of FSD. While improving the diagnostic tool of sonography is essential in cases of suspected FSD, 3D-CT imaging is indispensable for diagnosis and classification, enabling better planning for resuscitation of the infant after birth., Trial Registration: University Hospital Medical Information Network (UMIN) Center trial registration number is UMIN000034744 . Registered 1 October, 2018 - Retrospectively registered.

Purpose: This study aimed to evaluate the accuracy of prenatal diagnosis using a spatio-temporal image correlation-based telediagnosis system at a tertiary referral unit in a Japanese prefecture over a 9-year period, and to investigate the validity of delivery hospital selection., Methods: This study retrospectively analyzed telediagnosis cases from 2009 to 2018 in six geographically remote hospitals. We built a telediagnosis system called the Kyoto Fetal Ultrasonographic Telediagnosis System (K-FUTS). Three-dimensional ultrasonographic images from these referral hospitals were forwarded to the Kyoto Prefectural University of Medicine (KPUM) Hospital through an optical fiber network system for analysis. The primary endpoint was accuracy of prenatal diagnosis. Cases with severe congenital heart disease (CHD) that required immediate postnatal treatment were identified using the K-FUTS. These cases were then examined to determine whether they were delivered at appropriate hospitals., Results: During the study period, datasets from 182 cases were transferred to KPUM Hospital. Twenty-one datasets were excluded because of data unavailability or poor image quality. CHD was detected in 14.9% of cases (24/161); the accuracy of prenatal diagnosis was 95.0% (153/161). The K-FUTS identified seven severe cases with CHD requiring immediate postnatal surgical or medical treatment. These cases were delivered at KPUM Hospital with a pediatrician present. The remaining 17 cases considered suitable for delivery at the referral hospitals were delivered there, and they did not require intervention immediately after birth., Conclusion: Our telediagnosis system contributed to the prenatal diagnosis of CHD and management of pregnancies in patients who were geographically remote from a tertiary hospital.

Introduction: Creutzfeldt-Jakob disease (CJD) is an important dementia disorder. However, clinical diagnosis can be difficult and delayed for many primary physicians caring for dementia patients. The aim of the present study was to describe clinical and neuropathological results of an individual with CJD who was seen by a community hospital. Our report may inform many primary physicians on understanding the significance of CJD., Methods: Clinical information was obtained from medical records. Neuropathological and biochemical analyses were performed using autopsied brain., Results: A 58-year-old Japanese man who had worked as a carpenter developed memory and executive function impairments. He was initially diagnosed as having Alzheimer's disease based on clinical and neuroradiological analyses. Myoclonus was observed in the later stage of clinical course. Hyperintense lesions on diffusion-weighted images were observed in the cerebral cortex in later stage. Analysis of cerebrospinal fluid showed increased levels of total tau and phospho-tau protein. However, 14-3-3 protein and amyloid β (1-42) were normal. Genetic analysis of the PRNP gene showed methionine homozygosity at codon 129 and glutamate homozygosity at codon 219. The results of neuropathological analysis were consistent with sporadic CJD (MM2 cortical type with some type 1 pattern of 3F4 immunoreactivity). Western blot analysis of the frontal and cerebellar cortex revealed a type 2 and type 1 pattern of proteinase K (PK)-resistant prion protein, respectively. No Alzheimer's pathology was present., Conclusions: Our experience may help primary physicians to assess dementia patients. Since atypical forms of prion disease are now well-established, we need to consider prion disease in dementia patients. Clinical examination alone is not enough for dementia workup; thus, we must understand the importance of neuropathological study and encourage autopsy to reach a definite diagnosis of dementia., Competing Interests: None, (Copyright © Japan Medical Association.)

Background: Securing food for patients with food allergies may be more difficult during disasters, but reports on the status of household allergen-free food reserves in preparation for disasters are limited. This study investigated the household stock status of allergen-free foods in preparation for disasters in Kobe City after the Great Hanshin-Awaji Earthquake., Methods: The survey targets were 172 parents of patients with a food allergy who underwent in-hospital oral food challenge test for allergies at four hospitals from October 2016 to March 2017. Of these, 158 patients with allergies to eggs, milk and wheat were included in the analysis. The first survey was performed to investigate patient characteristics and stockpiling status of allergen-free foods in parallel with oral food challenge tests. The second survey was performed on the follow-up visit to investigate any changes in behavior., Results: Median patient age was 3 years, with boys comprising 68.4% of the patients. Eggs were the most eliminated food, and the median number of foods avoided was 2. A total of 82.3% of parents had experienced disasters. The proportion of households that stockpiled allergy-free meals was 42.4%, and the median amount was 3 days. The stockpiling situation did not differ according to the parents' disaster experience. In the second survey, 45.3% had modified their stockpiling practice., Conclusions: Even in this area where the Great Hanshin-Awaji Earthquake occurred, household stockpiles of allergen-free foods are inadequate; therefore, all medical staff should educate families about the necessity of stocking allergen-free food for disasters., (© 2019 Japan Pediatric Society.)

Objectives: The pallidothalamic tract connects the globus pallidus internus with the ventroanterior and ventrolateral parts of the thalamus. Lesioning or stimulation of the pallidothalamic tract has ameliorating effects on dyskinesia and dystonia in patients with Parkinson disease. However, the effect of the procedure on dystonia due to other etiologies has not been reported., Methods: We retrospectively analyzed patients with dystonia who underwent unilateral pallidothalamic tractotomy between July 2017 and October 2018 at Tokyo Women's Medical University Hospital. The Burke-Fahn-Marsden Dystonia Rating Scale-Movement Scale was used to evaluate the severity of dystonia at three time points (before surgery, 3 months postoperatively, and the last available follow-up). Adverse events were also evaluated., Results: Eleven patients underwent unilateral pallidothalamic tractotomy, including 5 with generalized dystonia, 4 with segmental dystonia, and 2 with focal (cervical) dystonia. All patients had undergone unilateral pallidotomy before contralateral pallidothalamic tractotomy. The mean interval between the previous surgery (pallidotomy) and pallidothalamic tractotomy was 9.5 ± 3.1 months. The mean follow-up period was 11.5 ± 4.2 months. The Burke-Fahn-Marsden Dystonia Rating Scale-Movement Scale scores at 3 months after pallidothalamic tractotomy (5.8 ± 8.4) and at the last available follow-up (5.6 ± 8.3, P < 0.001) were significantly improved compared with that before pallidothalamic tractotomy (21.8 ± 16.3). The most common adverse event was reduced voice volume (6 patients), which was mild and did not interfere with the patient's daily activities., Conclusions: This study suggests that pallidothalamic tractotomy can be an alternative treatment target for dystonia. A larger and longer prospective study is needed to elucidate the safety and efficacy of pallidothalamic tractotomy for dystonia., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Problem: Intrauterine microbial colonization and its association with the pathogenesis of endometriosis via an innate immune cascade have been reported. As a potential source of microbial transmission, information on microbial colonization in cervical mucus is unknown. We investigated pattern of microbiota in the cervical mucus collected from women with and without endometriosis using next-generation sequencing (NGS) technology., Method of Study: Cervical mucus samples were collected from women with (n = 30) and without (n = 39) endometriosis. The communities of microbiota in cervical mucus in the endometriosis group and the control group were examined by Gram staining and NGS targeting the V5-V6 region of 16S ribosomal RNA gene. Copy number of some target bacteria was detected by real-time PCR., Results: We confirmed visual presence of bacteria in cervical mucus by Gram staining. NGS analysis showed that distribution of microbiota was similar in cervical mucus of women with and without endometriosis regardless of the phases of the menstrual cycle. In addition to predominant Lactobacilli spp., the populations of Corynebacterium, Enterobacteriaceae, Flavobacterium, Pseudomonas, and Streptococcus were increased in the endometriosis group. Of them, Enterobacteriaceae and Streptococcus were identified as the more significant candidates in the endometriosis group than in controls by real-time PCR (P < 0.05 for each)., Conclusion: Our NGS analysis of cervical mucus indicated that among a variable microbiota, two candidates (Enterobacteriaceae and Streptococcus) were more frequently detected in women with endometriosis. Further investigation is needed to elucidate a mechanistic link of these bacteria in the pathophysiology of endometriosis., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Study Question: Is a peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)-mediated pathway involved in the development of endometriosis?, Summary Answer: PGC-1α plays critical roles in inflammation and cell proliferation of endometriotic tissues and may be involved in the development of endometriosis., What Is Known Already: Expression levels of PGC-1α are higher in ovarian endometrioma (OE) than normal endometrium (NE). PGC-1α also stimulates aromatase activity and promotes local estrogen biosynthesis in OE., Study Design, Size, Duration: This is a case-controlled biological study using endometrial cells and tissues derived from 23 women with, and 10 women without, OE., Participants/materials, Setting, Methods: Ectopic endometriotic and eutopic endometrial stromal cells (SCs) were isolated and maintained in culture. PGC-1α was either overexpressed in the cells or knocked down using siRNA. The expression of PGC-1α and other factors during endometriosis was examined using real-time PCR and western blotting, cell proliferation was measured using Cell Counting Kit-8 (WST-8) assays and transcriptional activity was assessed using luciferase reporter assays., Main Results and the Role of Chance: PGC-1α overexpression promoted the proliferation of OESCs in a time-dependent manner (P < 0.01 versus control) but not NESCs. PGC-1α stimulated aromatase (P < 0.01 versus control) and interleukin (IL)-6/IL-8 mRNA expression levels (P < 0.05 versus control for each) and led to inhibitor kappa B phosphorylation protein expression and upregulation of the apoptosis inhibitors X-linked inhibitor of apoptosis protein and survivin at mRNA level (P < 0.05 versus control for each). HX531, a selective retinoid-X receptor-α (RXRα) antagonist, suppressed the PGC-1α-induced cell proliferation (P < 0.05 versus control), aromatase/IL-6/IL-8/survivin mRNA expression (P < 0.05 versus control for each) and transcription reporter activity of PGC-1α in a dose-dependent manner (P < 0.01 versus control). Moreover, HX531 downregulated PGC-1α-induced aromatase-promoter PI.3-II transcripts in OESCs, and PGC-1α knockdown reduced aromatase, IL-6/IL-8 and antiapoptotic factors mRNA expression (P < 0.05 versus control for each). Notably, the Histogram score, which was used for quantifying RXRα status, was markedly higher in OE than in NE tissue (P < 0.01)., Large Scale Data: N/A., Limitations, Reasons for Caution: Only OE tissues were included in this study, while peritoneal and deep infiltrating endometriotic tissues were not. Therefore, these findings might not be generalized to other types of endometriosis., Wider Implications of the Findings: In OESC, PGC-1α stimulated cell proliferation and was involved in local estrogen biosynthesis, inflammation and apoptosis, and these effects of PGC-1α were inhibited by HX531. The suppression of PGC-1α-induced proliferation by HX531 in OESCs but not NESCs suggests that the PGC-1α-RXRα axis could play critical roles in promoting endometriosis. This is the first report of a relationship between PGC-1α and inhibitor of apoptosis proteins in endometriosis. Based on these findings, the PGC-1α-mediated pathway could represent a potential target in molecular therapy of endometriosis., Study Funding/competing Interest(s): The study is supported in part by Grants-in-Aid for Scientific Research (15 K10681 and 15 K10726) from the Ministry of Education, Culture, Sports, Science, and Technology (Japan). The authors have no conflicts of interest to disclose., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The adhesion of monocytes to endothelial cells, which is mediated by adhesion molecules, plays a crucial role in the onset of atherosclerosis. Conjugated equine estrogen, which is widely used for estrogen-replacement therapy, contains both estrone sulfate and various nonhuman estrogens, including equilin. To investigate the association between various estrogen types and atherosclerosis risk, we examined their effect on adhesion-molecule expression in human umbilical vein endothelial cells (HUVECs). In estrogen-treated HUVECs, the mRNA and protein expression levels of adhesion molecules were quantified by real-time polymerase chain reaction and enzyme immunoassay. Additionally, a flow-chamber system was used to assess the effects of estrogens on the adherence of U937 monocytoid cells to HUVECs. Equilin, but not 17β-estradiol (E2) or other types of estrogen, significantly increased the mRNA (P < 0.01) and protein (P < 0.05) expression of the adhesion molecules E-selectin and intercellular adhesion molecule-1 as compared with levels in controls. Equilin treatment increased the adherence of U937 monocytoid cells to HUVECs relative to the that in the control (P < 0.05), decreased estrogen receptor (ER)β expression, and increased the expression of proteins involved in nuclear factor kappa-B (NF-κB) activation relative to levels in controls. Furthermore, the accumulation of NF-κB subunit p65 in HUVEC nuclei was promoted by equilin treatment. By contrast, E2 treatment neither increased the number of adhered monocytoid cells to HUVECs nor altered the expression of ERβ or NF-κB-activating proteins. Our findings suggest that in terms of the adhesion of monocytes at the onset of atherosclerosis, E2 may be preferable for estrogen-replacement therapy. Further studies comparing equilin treatment with that of E2 are needed to investigate their differential impacts on atherosclerosis., Competing Interests: The authors have declared that no competing interests exist.

The aim of this study was to clarify the associations of family members living together with healthrelated behaviors in Japanese young workers. The participants were 300 men and women aged 20-39 years in 2015 who had a job. A web-based self-administered questionnaire on status of partnering and parenting, number of family members living together, dietary habits, drinking habit, smoking habit, self-rated health, employment status, working time and commuting time was conducted through Internet. Multiple logistic regression analysis and general linear models were used to assess the association of family members living together with healthrelated behaviors. The multivariate-adjusted odds ratio (95% confidence interval, p-value) for current drinking in unmarried participants living with their parents compared to unmarried participants living alone was 0.35 (0.13-0.93, p=0.036). The adjusted means of frequency of breakfast skipping and frequency of eating out showed a trend for inverse associations with the presence of a partner and children. However, those associations disappeared after adjustment for age of youngest child. The findings suggest that the presence of parents might affect drinking behavior and that age of youngest child living together might affect the frequency of breakfast skipping in young Japanese workers. J. Med. Invest. 66 : 141-147, February, 2019.

Endometriosis is a common gynecological disease that causes various clinical symptoms, such as chronic pelvic pain, dysmenorrhea and infertility, seriously affecting women's health and their quality of life. The symptoms and endometriotic lesions are relieved, in many cases, after menopause, when estrogen levels are lowered. Therefore, endometriosis is considered to be estrogen-dependent. Aromatase, the enzyme responsible for the last step of estrogen biosynthesis converting testosterone and androgen to estrogen, was previously reported to be more abundant in endometriotic tissues than in the normal endometrium, leading to an increased local estrogen concentration. Therefore, aromatase is considered a key therapeutic target for regulating local estrogen biosynthesis in endometriosis. A more complete understanding of the mechanisms that modulate aromatase and its activity is required to develop novel estrogen-targeted therapies for endometriosis. In this review article, we outline the current understanding of the pathological processes involved in estrogen production in endometriosis and propose novel strategies to treat this disorder., (© 2018 Japan Society of Obstetrics and Gynecology.)

A recent classification analysis of neuropsychiatric symptoms in patients with Alzheimer's disease (AD) revealed a distinct cluster with apathy and eating problems including anorexia that exhibits frailty. The apathy and frailty are risk factors in the disease progresses. However, there is currently no effective drug for treating both anorexia and apathy in AD. Here, we conducted an open-label pilot study to determine whether ninjin'yoeito (NYT, TJ-108), a multicomponent drug, is effective for improving anorexia and apathy in patients with AD, and consequently their cognitive function. Trials were conducted at three sites in Japan. Twenty patients [4 men and 16 women, average age = 82.6±7.7 (mean±SD) years old], including 19 AD and 1 mixed dementia with anorexia/apathy, were examined. NYT (6-9 g/day) was administered for 12 weeks. The changes in scores for "anorexia" using the Neuropsychiatric Inventory (NPI) subcategory for eating disturbance (primary outcome measure), NPI including "apathy", the vitality index, Mini-Mental State Examination (MMSE), and physical and blood nutrition indices were evaluated at baseline (week 0), and weeks 4, 8 and 12. After week 4, significant improvements were observed in the scores for "anorexia" and "apathy" by NPI and meal ingestion amount. Vitality index and MMSE score were significantly improved by week 12. We propose that NYT, a multicomponent drug with several effects including dopamine modulation, is a new-type dementia therapeutic agent with low risk of adverse reactions that can improve simultaneously anorexia/apathy, as well as cognitive dysfunction in frail AD patients.

Context: Endometriosis is a chronic inflammatory disease associated with altered immune response to endometrial cells facilitating the implantation and proliferation of ectopic endometrial tissues. Although regulatory T (Treg) cells play a key role in T cell-mediated immune response and development of immune disorders, their significance in endometriosis remains to be elucidated. Recently, CD4+CD45RA- forkhead box protein 3 (Foxp3)hi T cells, activated Treg cells, have been identified as a functionally true suppressive population of Treg cells., Objective: To investigate the role of Treg cells in endometriosis., Design: Three Treg cell fractions (resting Treg cells, activated Treg cells, and non-Treg cells) were examined using flow cytometry in the endometrioma, endometrium, peritoneal fluid, and peripheral blood obtained from women with (n = 27) and without (n = 28) endometriosis. A mouse model of endometriosis was made in Foxp3tm3Ayr/J (Foxp3DTR) C57BL/6 Treg cell-depleted mice (n = 28)., Results: In women with endometrioma, the proportion of activated Treg cells in the endometrioma and the endometrium, but not in the peritoneal fluid or peripheral blood, was significantly decreased compared with that in women without endometriosis. In Foxp3DTR/diphtheria toxin mice, the number and weight of endometriotic lesions, inflammatory cytokine levels and angiogenetic factors were significantly increased compared with those in control mice., Conclusions: Treg cell deficiency exaggerates local inflammation and angiogenesis and simultaneously facilitates the attachment and growth of endometrial implants. The findings provide an insight into dysregulated immune response for the pathogenesis and development., (Copyright © 2017 Endocrine Society)

Aim: The aim of this study was to elucidate whether the presence of an ovarian endometrioma is associated with impaired vascular flow. We investigated changes in vascular flow on the ipsilateral and contralateral side of the endometrioma, before and after surgery., Methods: This prospective case-control study included 144 women (ovarian endometrioma [n = 40], endometriosis without ovarian endometrioma [n = 33], non-endometriotic ovarian cyst [n = 17], and normal pelvis [n = 54]). The uterine artery (UtA) vascular resistance indices (pulsatility index [PI] and resistance index [RI]) were measured using transvaginal Doppler sonography, and UtA diameters were measured using magnetic resonance imaging., Results: The UtA PI and RI were significantly higher on the ipsilateral side of the endometrioma than on the contralateral unaffected side in the endometrioma group (P < 0.01), as well as in the non-endometriotic ovarian cyst group (P < 0.05), and normal pelvis group (P < 0.01). The UtA PI and RI on the ipsilateral side of the endometrioma were significantly lower after cystectomy than before cystectomy (P < 0.01). The UtA diameters were significantly larger (P < 0.01) on the ipsilateral side of the endometrioma than on the contralateral side., Conclusion: The UtA-vascular resistance might be higher on the ipsilateral side of the endometrioma than on the contralateral unaffected side, indicating a risk of subclinical atherosclerosis in women with endometriosis., (© 2017 Japan Society of Obstetrics and Gynecology.)

Aim: To assess and compare the uterine volume and endometrium length between women with and without endometriosis, using pelvic magnetic resonance imaging scans., Methods: In this case-control study, a total of 75 nulligravid women (aged 20-45 years) with regular menstrual cycles whose uterus were free of any surgically confirmed lesions were enrolled. The endometriosis group underwent surgery for endometrioma (n = 39), and the control group underwent surgery for non-endometrioma ovarian cysts (n = 36). The primary outcome was uterine corpus volume, which was assessed using three-dimensional reconstructions of preoperative pelvic magnetic resonance imaging scans., Results: The mean uterine volume was significantly larger in the endometriosis group than in the control group (mean ± standard deviation, 50.9 ± 14.4 cm 3 vs 41.7 ± 14.3 cm 3 ; P < 0.01). The longitudinal length and transverse diameter of the corpus and the longitudinal length of the endometrium were also significantly greater in the endometriosis group (all, P < 0.01)., Conclusions: An increase in uterine volume and endometrium length was observed in women with endometriosis., (© 2016 Japan Society of Obstetrics and Gynecology.)

Objective: To determine the effectiveness of a 24/4-day regimen of a low-dose combination drospirenone-ethinylestradiol oral contraceptive in alleviating perimenstrual symptoms among Japanese women with endometriosis., Methods: The present prospective, non-randomized study enrolled women diagnosed with endometriosis radiographically or surgically at the Kyoto Prefectural University of Medicine hospital, Japan, between December 1, 2010 and August 31, 2013. Patients received treatment with oral drospirenone-ethinylestradiol for six treatment cycles. Dysmenorrhea, chronic pelvic pain, and dyspareunia severity were assessed using visual analog scale scores after three and six treatment cycles, and changes in perimenstrual symptoms were assessed using the menstrual distress questionnaire (MDQ) scores., Results: In total, 46 patients were recruited for the study. Dysmenorrhea, chronic pelvic pain, and dyspareunia were all significantly reduced after both three and six treatment cycles in comparison with baseline (P<0.001 for all comparisons). After six treatment cycles, significant reductions were observed for all menstrual MDQ measures and for the premenstrual water retention and negative-effect MDQ measures (all P<0.05)., Conclusions: Combination drospirenone-ethinylestradiol was effective in the treatment of dysmenorrhea, chronic pelvic pain, dyspareunia, and somatic/psychological symptoms in Japanese women with endometriosis., (Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: A major concern in hormone replacement therapy is the associated increased risk of cardiovascular diseases. A progestogen without the unfavorable effects on cardiovascular disease should be explored. Monocyte adhesion to endothelial cells is an important initial event in atherosclerosis. In this study, the effects of the alternative progestogen drospirenone (DRSP) on monocyte adhesion in human umbilical venous endothelial cells (HUVECs) were examined., Study Design: In HUVECs treated with estrogens and progestogens, including DRSP and medroxyprogesterone acetate (MPA), the expression of the adhesion molecules E-selectin, P-selectin, ICAM-1, and VCAM-1 were examined by real-time PCR and using an enzyme-linked immunosorbent assay. A flow chamber system was used to investigate the effects of DRSP on U937 monocytoid cell adherence to HUVEC monolayers. All experimental data were compared using one-way Analysis of Variance., Results: Upregulation of adhesion molecule mRNA or protein was not seen in HUVECs treated with DRSP alone or with 17β-estradiol+DRSP. DRSP alone, 17β-estradiol+DRSP or ethinylestradiol+DRSP did not increase the number of adherent monocytoid cells to HUVECs in the flow chamber system. However, MPA significantly enhanced the monocytoid cell adherence (P<0.05)., Conclusions: DRSP did not increase the expression of adhesion molecules or monocytoid cell adherence to endothelial cells, indicating that DRSP could reduce the risk of atherogenesis caused by MPA. These results suggest that DRSP may be an alternative to MPA in hormone replacement therapy., (Copyright © 2016. Published by Elsevier Ireland Ltd.)