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Here, we investigated the usefulness of silk fibroin nanofibers obtained via mechanical grinding of degummed silkworm silk fibers as an additive in bioinks for extrusion three-dimensional (3D) bioprinting of cell-laden constructs. The nanofibers could be sterilized by autoclaving, and addition of the nanofibers improved the shear thinning of polymeric aqueous solutions, independent of electric charge and the content of cross-linkable moieties in the polymers. The addition of nanofibers to bioinks resulted in the fabrication of hydrogel constructs with higher fidelity to blueprints. Mammalian cells in the constructs showed >85% viability independent of the presence of nanofibers. The nanofibers did not affect the morphologies of enclosed cells. These results demonstrate the great potential of silk fibroin nanofibers obtained via mechanical grinding of degummed silkworm silk fibers as an additive in bioinks for extrusion 3D bioprinting.

Background: Chronic mechanical stress on the second metatarsal head (2 MH) can be a risk factor for osteoarthritis (OA) and dislocation of the second metatarsophalangeal joint (2MTPJ) in hallux valgus (HV). This study aimed to investigate the stress distribution of the 2 MH in HV patients and determine the factors associated with dislocation and OA of the 2MTPJ., Methods: In total, 115 feet with HV were retrospectively reviewed and divided into two groups: those with subluxation or dislocation of the 2MTPJ (group D, 27 feet) and those without (group N, 88 feet). The control group (group C) included 33 feet without HV. Group N was divided into OA and non-OA (NOA) groups according to the presence or absence of OA of the 2MTPJ. The Hounsfield Unit (HU) value of the subchondral bone of the 2 MH was measured on sagittal slices of the preoperative computed tomography images and divided by the HU value of the navicular region (HU ratio). The relationship between the HU ratios and radiographic parameters was compared., Results: The HU ratios were significantly higher in group N than those in groups C and D. In group N, the protrusion of the second metatarsal relative to the third and fourth metatarsals (M2-M3, M2-M4) was positively correlated with the dorsal and central HU ratios, respectively. Group D had a significantly larger HV angle (HVA) and M2-M3 than group N. HVA, the first-second intermetatarsal angle, M2-M3, M2-M4, and dorsal and central HU ratios were significantly larger in the OA group than in the NOA group. The cutoff value of M2-M3 was 5.5 mm when comparing groups D and N, and 4.4 mm when comparing the OA and NOA groups., Conclusions: Severe HV and a longer M2-M3 and M2-M4 may be associated with a high risk of dislocation and OA of the 2MTPJ., Level of Evidence: Ⅲ., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: During surgery for osteochondral lesions of the talus (OLT), preservation or excision of the osteochondral fragment is chosen based on the cartilage condition which influences the indication and clinical outcomes of surgical treatments. However, it is difficult to predict arthroscopic and histological findings of the cartilage on osteochondral fragments by radiographic evaluation. We focused on osteoarthritis (OA) changes on plain radiographs to predict the cartilage condition of the OLT. This study aimed to evaluate whether OA changes, including osteophyte and joint space narrowing, could predict arthroscopic and histological findings of the cartilage in OLT., Methods: Seventy ankles with OLT were included in this study. Osteophytes and joint space narrowing were scored on plain radiographs. Lesion sizes were measured on computed tomography images. The cartilage surfaces of fragments were arthroscopically assessed using the International Cartilage Repair Society (ICRS) grade. Biopsy specimens from 32 ankles were histologically analyzed using the Mankin score. The relationships between OA scores, lesion size, ICRS grades, and Mankin score were analyzed., Results: OA changes were frequently observed with increasing ICRS grades, especially in the medial tibiotalar joint. OA scores in patients with ICRS grade 1 were significantly lower than those in ICRS grades 2,3, and 4. The lesion sizes in patients with ICRS grade 3 and 4 were significantly smaller than those in patients with ICRS grade 1 and 2. Histological analysis showed increasing Mankin scores as the ICRS grade worsened. A mild correlation existed between the OA and Mankin scores (rs = 0.494)., Conclusions: OA changes, such as osteophyte formation and joint space narrowing, are associated with arthroscopic findings of the articular surface and cartilage degeneration in osteochondral fragment in OLT. Articular cartilage conditions can be predicted by OA changes on plain radiographs, which is useful for choosing the appropriate treatment for patients with OLT., Level of Evidence: Level Ⅳ, case series., Competing Interests: Declaration of competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

A 47-year-old woman was diagnosed with myotonic dystrophy when admitted for traumatic subarachnoid hemorrhage. Her glycemic control was poor despite administration of pioglitazone, a PPARɤ agonist, and subcutaneous insulin infusion. However, adding a GLP-1 receptor (GLP-1R) agonist markedly improved blood glucose levels, resulting in eventual insulin withdrawal. Genetic testing revealed a heterozygous variant, p.R131Q, in the GLP1R (rs3765467), a common variant in Asia. This variant is known to be associated with increased endogenous insulin from beta cells in response to exogenous GLP-1 infusion. This is the first report and short review of a Japanese case of myotonic dystrophy accompanied by GLP-1R gene polymorphism., 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 © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Arthroscopic ankle arthrodesis (AAA) has become popular because of its higher rate of bone union, lower invasiveness, and shorter hospital stays compared to those of open arthrodesis. However, postoperative malalignment is often observed for severe varus deformity, which can cause nonunion, pain, and adjacent joint arthrosis. A compression staple can provide a persistent, strong compressive force on the bone surface. This study aimed to clarify the difference in alignment correction in AAA by comparing a compression staple and screws fixation with screws-only fixation pre- and postoperatively., Methods: Seventy ankles in 67 patients undergoing AAA were retrospectively reviewed. AAA with three screws through the distal tibia was performed in 53 ankles, and 17 ankles underwent AAA with a compression staple and two screws. After the preparation of the joint surface arthroscopically, patients in the S group had three canulated cancellous screws inserted through the medial tibia. Patients in the CS group had a compression staple placed at the lateral aspect of the tibiotalar joint and two screws inserted through the medial side. Clinical scores and pre-and postoperative alignment on plain radiographs were compared between the two procedures., Results: There were no significant differences in the pre-and postoperative Japanese Society for Surgery of the Foot scale. One ankle in the S group exhibited nonunion. There were no significant differences in talar tilt and tibiotalar angles between the groups. The tibial plafond angle in the CS group was significantly lower than that in the S group (p < 0.05). Postoperatively, talar tilt and tibiotalar angles on the coronal image, and the lateral tibiotalar angle in the CS group were significantly lower than those in the S group (p < 0.05)., Conclusion: AAA with a compression staple and two-screw fixations could obtain more optimal alignments than AAA with screw-only fixation, even in cases with severe varus deformity., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Progressive multifocal leukoencephalopathy (PML) has been reported as the development of drugs with immunomodulatory properties, such as anticancer, immunosuppressive, and biological agents, has accelerated. To clarify an incidence profile of drug-associated PML in real-world clinical practice, we analyzed reported patients with PML using the Japanese Adverse Drug Event Report (JADER) database., Methods: We analyzed PML reports extracted from the JADER database based on the preferred term of "progressive multifocal leukoencephalopathy" from between 2004 and 2021. This was a retrospective, observational study. We evaluated the effects of causative drugs, underlying diseases, and the age of the patients on the annual number of PML reports., Results: The JADER database contained 773,966 reports published between April 2004 and March 2022, from which we identified 361 PML events. These PML events may include multiple counts of the same case reported by different pathways and patients diagnosed with probable or possible PML. The number of PML reports and reporting ratios have gradually increased over the past decade. The annual number of PML reports associated with biologics, immunosuppressants, and antineoplastic drugs showed an increasing trend. Females aged ≥30 years showed an increase in PML reports; in contrast, there the number of reports for males aged ≥50 years increased., Conclusions: The number of PML reports and reporting ratios have gradually increased in the past decade in Japan, and it considered that it was related to change in the treatment of malignancies and autoimmune diseases, and the increasing use of biologics, immunosuppressive agents, and antineoplastic agents., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Tyrosylprotein sulfotransferases (TPSTs) catalyze the transfer of a sulphonate moiety from 3'-Phosphoadenosine 5'-Phosphosulfate (PAPS) to the hydroxyl group of a tyrosine residue in substrate proteins. The positively charged substrate binding region of TPST homodimer interacts with acidic residues located in N-terminal region from the sulfated tyrosine in substrates. However, the sequence pattern in TPST substrate recognition remains unclear. Therefore, we aimed to determine the minimum recognition chain length required for tyrosine sulfation. We prepared His-tagged polypeptide, His-TPST1 43-370 and His-TPST2 43-377 , form 43-370 of TPST1 and 43-377 of TPST2. Next, we prepared a series of synthesized ADYAE peptides and used a combination of reverse phase high-performance liquid chromatography (RP-HPLC) and mass spectrometric analysis to show that the tripeptide amino acid sequence, ADY, was sulfated by TPST1 and TPST2. Furthermore, we found that the acidic residue, located two residues C-terminal region from the tyrosine residue, may be involved in the TPST-induced sulfation regulation. The results in our study propose that proteins with the ADY sequence may be useful for searching the novel TPST tyrosine sulfated substrates., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shinichi Asada reports equipment, drugs, or supplies was provided by Japan Society for the Promotion of Science., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Cough and sputum are the significant symptoms of nontuberculous mycobacteriosis (NTM) and impair quality of life (QOL). However, the relationship between these symptoms and clinical features is not fully understood. This study aimed to investigate cough-related QOL in NTM patients., Methods: The study subjects included 78 patients with NTM at our hospital from October to December 2015. They completed the Leicester Cough Questionnaire (LCQ) and the Cough and Sputum Assessment Questionnaire (CASA-Q) (both questionnaires: the higher, the better); the Frequency Scale for the Symptoms of gastroesophageal reflux disease (GERD) (FSSG), a validated Japanese questionnaire for GERD (the higher, the worse), was also assessed. The FSSG consists of 12 items, including the reflux-related symptoms and dysmotility symptoms domains, each of which is quantified on a scale of 0-4 points, and the cut-off score for GERD is set at 8 points. Associations between these scores and clinical parameters were assessed., Results: The total LCQ score was reduced-the physical domain was dominant. The total LCQ and CASA-Q scores were reduced, with dominance in the physical and symptoms domains, respectively. The reflux-related symptoms score was higher than the dysmotility symptoms score. A multivariate linear regression analysis revealed that the mean total LCQ score was independently associated with current smoking, fibrocavitary type, bilateral cavitary lesion, and FSSG total score., Conclusions: Cough-related QOL was impaired in NTM patients who currently smoked, had radiological characteristics, and had GERD., Competing Interests: Conflict of Interest The authors have no conflicts of interest., (Copyright © 2022 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the characteristics and outcomes of patients who experienced cardiac arrest in nursing homes compared with those in private residences and determine prognostic factors for survival., Design: This was a retrospective study that analyzed data from an Utstein-style registry of the Tokyo Fire Department., Setting and Participants: We identified patients aged ≥65 years who experienced cardiac arrest in a nursing home or private residence from the population-based registry of out-of-hospital cardiac arrests in Tokyo, Japan, from 2014 to 2018., Methods: Patients were grouped into the nursing home or the private residence groups according to their cardiac arrest location. We compared the characteristics and outcomes between the 2 groups and determined prognostic factors for survival in the nursing home group. The primary outcome was 1-month survival after cardiac arrest., Results: In total, 37,550 patient records (nursing home group = 6271; private residence group = 31,279) were analyzed. Patients in the nursing home group were significantly older and more often had witnessed arrest, bystander cardiopulmonary resuscitation (CPR), and shock delivery using an automated external defibrillator. The 1-month survival rate was significantly higher in the nursing home group (2.6% vs 1.8%, P < .001). In the best scenario (daytime emergency call, witnessed cardiac arrest, bystander CPR provided), the 1-month survival rate after cardiac arrest in the nursing home group was 8.0% (95% confidence interval 6.4-9.9%), while none survived if they had neither witness nor bystander CPR., Conclusions and Implications: Survival outcome was significantly better in the nursing home group than in the private residence group and was well stratified by 3 prognostic factors: emergency call timing, witnessed status, and bystander CPR provision. Our results suggest that a decision to withhold vigorous treatment solely based on nursing home residential status is not justified, while termination of resuscitation may be determined by considering significant prognostic factors., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

As an emerging additive manufacturing (AM) technique, melt electrospinning writing (MEW) is used to fabricate three-dimensional (3D) submicron filament-based scaffolds with adjustable pore size and customized structure for bone regeneration. Poly(L-lactic acid) (PLLA) scaffold with excellent biodegradability and biocompatibility is first successfully manufactured using our self-assembled MEW device. However, the ultralow cell affinity and poor bioactivity severely hamper their practical applications in bone tissue engineering. These issues are caused by the severe inherent biologically inert, hydrophobicity as well as the smooth surface of the MEW PLLA filaments. In this study, a green and robust alkaline method is applied to modify the scaffold surface and to improve the bioactivity of the MEW PLLA scaffold. Without deterioration in mechanical property but robust surface hydrophilicity, the optimal MEW PLLA scaffold shows promoted surface roughness, enhanced filament tensile modulus (~ 2 folds of the as-prepared sample), and boosted crystallizability (ultrahigh WAXD intensity). Moreover, after being cultured with KUSA-A1 cells, the 0.5 M NaOH, 2 h treated MEW PLLA scaffold exhibits higher osteoinductive ability and increased immature bone tissue amounts (3 times of controlled scaffold). Thus, the flexible surface functionalization by the specific alkaline treatment was found to be an effective method for the preparation of bioactivated MEW PLLA scaffolds with promoted bone regeneration., (Copyright © 2022. Published by Elsevier B.V.)

The prevalence of sleep disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously believed, with patients having moderate-to-severe OSA accounting for approximately 20% of adult males and 10% of postmenopausal women not only in Western countries but also in Eastern countries, including Japan. Since 1998, when health insurance coverage became available, the number of patients using continuous positive airway pressure (CPAP) therapy for sleep apnea has increased sharply, with the number of patients about to exceed 500,000 in Japan. Although the "Guidelines for Diagnosis and Treatment of Sleep Apnea Syndrome (SAS) in Adults" was published in 2005, a new guideline was prepared in order to indicate the standard medical care based on the latest trends, as supervised by and in cooperation with the Japanese Respiratory Society and the "Survey and Research on Refractory Respiratory Diseases and Pulmonary Hypertension" Group, of Ministry of Health, Labor and Welfare and other related academic societies, including the Japanese Society of Sleep Research, in addition to referring to the previous guidelines. Because sleep apnea is an interdisciplinary field covering many areas, this guideline was prepared including 36 clinical questions (CQs). In the English version, therapies and managements for SAS, which were written from CQ16 to 36, were shown. The Japanese version was published in July 2020 and permitted as well as published as one of the Medical Information Network Distribution Service (Minds) clinical practice guidelines in Japan in July 2021., Competing Interests: Conflict of Interest Yuichi Inoue is receiving daily allowances (lecture fees, etc.) from Alfresa Pharma Corporation, Eisai Corporation, MSD Corporation, Takeda Pharmaceutical Company Limited, along with research expenses from Astellas Pharma Corporation, Eisai Corporation, Takeda Pharmaceutical Company Limited, and Jassen Pharmaceutical K,K. He is also affiliated with the donated courses provided by Astellas Pharma Corporation, Alfresa Pharma Corporation, Eisai Corporation, MSD Corporation, Otsuka Pharmaceutical Co., Ltd., Koike Medical Co., Ltd., Takeda Pharmaceutical Company Limited, and Philips Japan, Ltd. Naohisa Uchimura is receiving daily allowances (lecture fees, etc.) from Eisai Co., Ltd., MSD Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Mitsubishi Electric Co., Ltd., and Meiji Seika Furuma Co., Ltd.; manuscript fees from Eisai Co., Ltd., MSD Co., Ltd. and Otsuka Pharmaceutical Co., Ltd.; and scholarship (incentives) donations from Eisai Co., Ltd., MSD Co., Ltd., Otsuka Pharmaceutical Co., Ltd., and Pfizer Japan Inc. Takatoshi Kasai is receiving research funding from Asahi Kasei Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Paramount Bed Co., Ltd., and ResMed Co., Ltd., along with scholarship (incentives) donations from Philips Japan Co., Ltd. He is also affiliated with the donated courses provided by Philips Japan, Ltd., Fukuda Denshi Co., Ltd., and ResMed Co., Ltd. Fusae Kawana is an officer of the Japan Sleep Comprehensive Examination Association, and is affiliated with the donated courses provided by Philips Japan, Ltd., Fukuda Denshi Co., Ltd., and ResMed Co., Ltd. Shigeru Sakurai is receiving scholarship (incentives) donations from Philips Japan, Ltd. and Kitara Co., Ltd. Takeshi Tanigawa is receiving research funding from Tokyo Electric Power Company Holdings, Inc. Kazuo Chin is receiving daily allowances (lecture fees, etc.) from Philips Japan, Ltd. and Teijin Home Medical Care, and is affiliated with the donated courses provided by Teijin Pharma Limited, Philips Japan, Ltd., Fukuda Denshi Co., Ltd., and ResMed Co., Ltd. Morio Tonogi is receiving research funding from GC Ortholy Corporation. Takeo Nakayama is receiving daily allowances (lecture fees, etc.) from Nippon Boehringer Ingelheim Co., Ltd., Pfizer Co., Ltd., and Janssen Pharmaceutical K.K., as well as receiving scholarship (incentives) donations from JMDC Co., Ltd. Motoo Yamauchi is receiving research funding from Koike Medical Co., Ltd. Toru Oga is affiliated with the donated courses provided by Teijin Pharma Limited, Philips Japan, Ltd., Fukuda Denshi Co., Ltd., and Fukuda Lifetech Keiji Co., Ltd. Yasuhiro Tomita is affiliated with the donated courses provided by Teijin Pharma Limited, Philips Japan, Ltd., Fukuda Denshi Co., Ltd., and ResMed Co., Ltd. Satoshi Hamada is affiliated with a donated course provided by Teijin Pharma Limited. Kimihiko Murase is affiliated with the donated courses provided by Teijin Pharma Limited, Philips Japan, Ltd., Fukuda Denshi Co., Ltd., Fukuda Lifetech Keiji Co., Ltd., and ResMed Co., Ltd. Makoto Uchiyama is receiving daily allowances (lecture fees, etc.) from Eisai Co., Ltd., MSD Co., Ltd., and Takeda Pharmaceutical Company Limited, along with scholarship (incentives) donations from Eisai Co., Ltd. and Meiji Seika Pharma Co., Ltd. Hiromasa Ogawa is affiliated with a donated course provided by Fukuda Lifetech Co., Ltd. Kazuo Mishima is receiving daily allowances (lecture fees, etc.) from Eisai Co., Ltd., MSD Co., Ltd., and Takeda Pharmaceutical Company Limited; research funds from Taisho Pharmaceutical Co., Ltd. and Nobelpharma Co., Ltd.; and scholarship (incentives) donations from Eisai Co., Ltd. and Takeda Pharmaceutical Company Limited. Tsuneto Akashiba, Motoharu Ohi, Misa Takegami, Ryo Tachikawa, Shintaro Chiba, Satoru Tsuiki, Hiroshi Nakamura, Koji Narii, Asako Yagi, Yoshihiro Yamashiro, Masahiro Yoshida, Hiroyuki Mori, Hiroo Wada, Kazumichi Sato, Seiichi Nakata, and Shinichi Momomura have no COIs to declare., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Exploration of biodegradable materials for conventional application has taken a rising interest across the world. The presented work primarily focused on exploring the effectiveness of isolated CNCs from marine de-oiled green algae biomass residue (Dunaliella tertiolecta) in synthesized poly(ɛ-caprolactone) (PCL). The washed algae biomass residue (WABR) and algae derived CNCs were explored as two different bio-fillers incorporated into PCL for comparison and development of biodegradable and flexible bio-composites with varying bio-filler loading. FTIR, XRD, TGA, UTM, DSC, POM, and SAXS characterized the developed PCL/WABR and PCL/CNC bio-composites. Improved thermal stability was observed in PCL/CNC bio-composites by ~10 °C rise. Besides, increased modulus of 18.38 MPa and tensile strength was obtained in PCL/CNC/1 bio-composites. However, the isothermal kinetics study (at 45 °C) revealed the reduction in the degree of crystallinity of bio-composites, and the axialite formation was visualized via POM. Moreover, CNCs was found as an excellent nucleating agent and effective bio-filler as compared to WABR., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Follicular helper T (Tfh) cells represent a unique subset of helper CD4 + T cells in lymphoid follicles. Recently, Tfh cells were shown to play an important role in asthma through B cell differentiation. Conventional lung DCs are classified into two major subsets: conventional type 1 (cDC1) and type 2 (cDC2). Although the two subsets are different in driving particular T cell responses, the subset that induces Tfh cells in the asthmatic lung primarily has yet to be fully elucidated., Methods: We evaluated Tfh cells, defined by the expression of CD4 and CXCR5, in HDM-challenged mice. Next, we characterized cDC1 and cDC2 purified from antigen-primed lung and examined their Tfh cell-inducing capacity. Additionally, the ability of lung DC-induced Tfh cells to cause germinal center B (GCB) cells to produce antigen-specific IgE was assessed., Results: In HDM-challenged mice, Bcl-6-expressing Tfh cells were significantly increased in the mediastinal lymph nodes. Lung cDC2, but not lung cDC1, increased after HDM priming, and cDC2 secreted larger amounts of IL-6 with higher ICOS-L expression than cDC1. In the co-cultures with OVA-specific naïve CD4 + T cells, cDC2 from OVA-primed lung induced Bcl-6-expressing Tfh cells more efficiently, together with larger amounts of IL-6 and IL-21, than cDC1. Blockage of IL-6 or ICOS-L significantly reduced Tfh cell induction. Finally, cDC2-induced Tfh cells enabled GCB cells to produce OVA-specific IgE., Conclusions: In asthmatic lung, cDC2 is the primary DC subset responsible for Tfh cell differentiation and plays an important role in humoral immunity in asthma by inducing Tfh cells., (Copyright © 2021 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background and Aims: Sodium/glucose cotransporter 2 (SGLT2) inhibitors decrease plasma triglyceride levels and slightly increase low-density lipoprotein (LDL-c) and high-density lipoprotein cholesterol (HDL-c). However, the mechanisms underlying such changes in the blood lipid profile remain to be determined. We investigated how empagliflozin affects plasma markers of cholesterol absorption and synthesis, and evaluated the relationship between changes in these markers and blood lipids in patients with type 2 diabetes., Methods and Results: In a randomized, active-controlled, open-label trial, 51 patients were randomly allocated in 2:1 ratio to receive empagliflozin 10 mg/day (n = 32) or standard therapy (n = 19) for 12 weeks. We measured plasma levels of lathosterol as a marker of cholesterol synthesis, and campesterol and sitosterol as markers of cholesterol absorption, at baseline and 12 weeks after treatment. In the empagliflozin group, serum HDL-c, but not LDL-c, significantly increased between baseline and 12 weeks (54.4 ± 16.3 vs. 58.8 ± 19.6 mg/dl; p = 0.0006), whereas in the standard therapy group, HDL-c and LDL-c remained unchanged. In the empagliflozin group, plasma campesterol also increased significantly (4.14 ± 1.88 vs. 4.90 ± 2.26 μg/ml, p = 0.0008), whereas no change in plasma campesterol or sitosterol was found in the control group. Although plasma lathosterol showed no change in the whole empagliflozin group, it decreased significantly in patients who were not taking statins. In statin non-users, plasma lathosterol decreased significantly after treatment with empagliflozin (2.71 ± 0.99 vs. 1.91 ± 0.99 μg/ml, p < 0.05). In the empagliflozin group, changes in plasma campesterol correlated positively with changes in HDL-c., Conclusion: Empagliflozin increases serum campesterol, a marker of cholesterol absorption, in patients with type 2 diabetes. This increase may be associated with SGLT2 inhibitor-induced increases in HDL cholesterol., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Dipeptidyl peptidase-4 (DPP-4) rapidly inactivates incretin hormones and several chemokines, thus influencing chemokine function. There have recently been several reports that DPP-4 inhibitor therapy is associated with an increased risk of bullous pemphigoid (BP), an autoimmune skin disease. Previous studies have demonstrated an increase of CCL11/Eotaxin, a DPP-4 substrate, in serum and blister fluid from patients with BP. Serum levels of CCL22/macrophage-derived chemokine (MDC) and CXCL10/IP-10, other DPP-4 substrates, are also elevated in BP patients., Materials and Methods: In patients with type 2 diabetes, we investigated the effect of treatment with teneligliptin (a DPP-4 inhibitor) for 24 weeks on plasma levels of CCL11/Eotaxin, CCL22/MDC and CXCL10/IP-10 during a meal test. Ten consecutive patients with type 2 diabetes who showed inadequate glycemic control by metformin and/or sulfonylureas were recruited. A standard meal test was performed at baseline and after 24 weeks of treatment with teneligliptin at 20 mg/day. Blood samples were collected at 0, 30, 60 and 120 minutes after ingestion of the meal. In addition to plasma levels of the 3 chemokine, plasma DPP-4 enzyme activity and soluble DPP-4 antigen were measured., Results: Treatment with teneligliptin decreased hemoglobin A1c and reduced fasting plasma DPP-4 activity by 90.1% compared with baseline. Unexpectedly, plasma levels of all 3 chemokines (including CCL11/Eotaxin) were not increased after teneligliptin treatment, and instead were significantly lower at every point during the meal test., Conclusions: Teneligliptin reduced the plasma concentrations of 3 chemokines (DPP-4 substrates) that may be related to the occurrence of DPP4 inhibitor-associated BP (UMIN000012508)., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to reveal the midterm and long-term mortality rates among patients with thoracoabdominal aortic aneurysm (TAAA) after open TAAA repair and to clarify the effect of aneurysm type on mortality., Methods: We retrospectively analyzed data for 393 patients (290 men; age, 63.2 ± 12.7 years) who underwent open TAAA repair of elective Crawford extent I, II, or III TAAAs (62, 197, and 134 patients, respectively) between June 2003 and December 2015. The overall survival probability and differences according to aneurysm type were assessed using the Kaplan-Meier product limit method. Also, the effect of aneurysm type on mortality was assessed using the hazard ratio and Cox proportional hazards regression., Results: The overall survival probabilities at 3 months, 1 year, 5 years, and 10 years were 90%, 84%, 78%, and 75%, respectively. The age-adjusted relative mortality rate was significantly higher for patients with dissecting aneurysms than for those with nondissecting aneurysms (relative risk, 1.62; 95% confidence interval, 1.03 to 2.55). In the multivariate Cox proportional hazard regression model, the hazard ratio for all-cause mortality did not differ between patients with dissecting and those with nondissecting aneurysms. However, those with dissecting aneurysms had increased mortality rates as their percentage vital capacity decreased (hazard ratio, 0.7; 95% confidence interval, 0.5 to 1.0); a similar trend was not observed for those with nondissecting aneurysms., Conclusions: Open TAAA repair can be safely performed with acceptable midterm and long-term results. Poor pulmonary function can impair the survival outcome of patients with dissecting aneurysms., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Multisensory integration of visuo-tactile information presented on the body or a dummy body has a strong impact on body image. Previous researches show that alteration of body image induced by visuo-tactile integration is closely related to the activation of the parietal cortex, a sensory association area. The expression of brain-derived neurotrophic factor (BDNF) in the parietal area of macaque monkeys is thought to modulate the activation of the parietal cortex and alter the extension of body image during tool-use learning. However, the relationship between parietal cortex activation related to body image alterations and BDNF levels in humans remains unclear. We investigated the relationship between human serum BDNF levels and electroencephalography responses during a visuo-tactile integration task involving a rubber hand. We found cortical oscillatory components in the high frequency (gamma) band in the left parietal cortex. Moreover, the power values of these oscillations were positively correlated (p<0.05) with serum BDNF levels. Our results suggest that serum BDNF could play a role in modulating the cortical activity in response to visuo-tactile integration processes related to body image alteration in humans., (Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.)

Background: This study compared adenosine stress computed tomography myocardial perfusion (CTP) with single-photon emission computed tomography (SPECT) in the diagnosis of functionally significant coronary artery stenosis using fractional flow reserve (FFR) as reference standard., Methods: We included a total of 93 coronary arteries from 31 patients in whom at least one vessel with ≥50% stenosis was detected with computed tomography coronary angiography. All patients underwent both SPECT and adenosine stress CTP, followed by invasive coronary angiography (ICA) and FFR. Diagnostic accuracy between CTP and SPECT was compared according to positive findings of either ≥99% stenosis on ICA or FFR ≤0.8., Results: Among 78 vessels eligible for the quantitative analyses, significant coronary artery disease (CAD) was diagnosed in 22 vessels of 19 patients. Comparison of CTP vs. SPECT for sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy in detecting significant CAD were 59% vs. 18%, 96% vs. 93%, 87% vs. 50%, 86% vs. 74%, and 86% vs. 72%, respectively., Conclusions: CTP demonstrated a significant diagnostic advantage over SPECT in the identification of significant CAD, especially in terms of sensitivity and PPV. Adenosine stress CTP is useful for the noninvasive diagnosis of functionally significant CAD., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Although carbapenem is the recommended for urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing organisms, non-carbapenems have been reported to be effective for adult patients with UTI caused by ESBL-producing organisms. The purpose of this study was to evaluate the efficacy of non-carbapenems for pediatric patients with UTI due to ESBL-producing Escherichia coli (E. coli) based on the microbiologic and clinical outcomes. Fifteen children, who were treated for first febrile UTI caused by ESBL-producing E. coli were enrolled in this study. Antimicrobial susceptibilities and ESBL production were determined according to the Clinical and Laboratory Standards Institute guidelines. To detect CTX-M genes, polymerase chain reaction was performed with specific primers for bla CTX-M detection. Of the 15 enrolled patients, 10 (66.7%) were boys and 5 (33.3%) were girls, with a median age of four months. VUR was detected in six patients (40%). For detection of bla CTX-M by PCR, CTX-M-3, CTX-M-8, CTX-M-14, and CTX-M-15 were detected in five, one, eight, and one patient, respectively. Overall, 14 of the 15 isolates (93.3%) were susceptible for fosfomycin (FOM), and all isolates were susceptible for cefmetazole (CMZ), flomoxef (FMOX), and imipenem/cilastatin (IPM/CS). Of the 15 patients, 12 (80%) clinically improved without the use of carbapenems. In conclusion, even if isolates of ESBL-producing E. coli are multidrug resistant based on MIC assessment, clinical susceptibility to non-carbapenems, such as CMZ, FMOX, and FOM, is possible. Accordingly, carbapenems may not be required all the time for treatment of pediatric UTI in clinical practice., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The increasing incidence and prevalence of atopic dermatitis (AD) demands new therapeutic approaches for treating the disease. We investigated the therapeutic efficacy of immunomodulator FTY720 ointment (fingolimod) for mite-induced intractable AD using an NC/Nga mouse model., Methods: Female NC/Nga mice that developed severe AD were divided into four groups: (1) FTY720 (0.001% FTY720 ointment), (2) tacrolimus (tacrolimus hydrate ointment) (3) betamethasone (betamethasone ointment), and (4) ointment base (hydrophilic petrolatum), all of which received treatment six times per week. Therapeutic efficacy after two weeks was evaluated in terms of AD severity, histochemical observations (epidermal hypertrophy, mast cell accumulation, and CD3(+) T cell infiltration), transepidermal water loss (TEWL), and epidermal barrier function (filaggrin expression)., Results: Betamethasone treatment showed little effect, confirming that the AD was intractable. In the FTY720 group, AD improved significantly compared with the ointment base group, as did epidermal hypertrophy, mast cell accumulation, and CD3(+) T cell infiltration. In contrast, AD in the tacrolimus and betamethasone groups did not improve significantly, nor did epidermal hypertrophy or mast cell accumulation. Furthermore, in the FTY720 group, TEWL decreased significantly compared with the ointment base group, and filaggrin expression significantly increased compared with the betamethasone and ointment base groups., Conclusions: FTY720 ointment is a promising candidate for treatment of intractable AD. These findings also provide the first evidence that FTY720 ointment ameliorates epidermal barrier function., (Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Techniques used in hybrid repair of proximal aortic arch diseases are associated with perioperative complications such as cerebrovascular emboli. We present an easy and safe technique of total debranching thoracic endovascular aortic repair for arch diseases using axilloaxillary arterial bypass. The placement of the axilloaxillary arterial bypass enables perfusion of the brachiocephalic artery even when the artery is clamped. After reconstruction of the brachiocephalic artery and the left common carotid artery, the left subclavian artery is proximally ligated, and it is perfused through the bypass. This procedure is simple, safe, and useful for the prevention of neurologic complications., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Although functional ischemia identification is important when determining revascularization, angiographic assessment alone is challenging in intermediate coronary stenosis. Previous studies have reported that lesion-specific characteristics affected the fractional flow reserve (FFR). However, the relationship between morphological lesion complexity and FFR has not yet been fully evaluated. This study aimed to evaluate the impact of morphological lesion complexity on FFR in intermediate coronary stenosis., Methods: A total of 109 consecutive patients with 136 intermediate coronary stenoses (visually estimated diameter stenosis: 40-70%) were assessed via quantitative coronary angiography, lesion-specific characteristics, and FFR. Indexed lesions were assessed according to 6 morphological lesion characteristics: eccentricity, bend, irregularity, calcification, bifurcation, and diffuse. The lesions were then classified into 3 groups according to the morphological severity count represented by the number of present characteristics (mild-complex: 0-1, moderate-complex: 2-3, and severe-complex: 4-6), and their functional severities were evaluated. Lesions with an FFR <0.80 were considered functionally significant coronary stenoses., Results: Of the 136 lesions, 51% were located in the left anterior descending artery (LAD) and 47% had an FFR <0.80. The FFR differed significantly among the 3 lesion complexity groups (0.84±0.10 vs. 0.79±0.10 vs. 0.73±0.07, for mild-, moderate-, and severe-complex, respectively; p<0.01). In a multivariate logistic analysis, LAD lesions, moderate- and severe-complex, and diameter stenosis were independently associated with an FFR <0.80 [odds ratio (OR): 5.65, 95% confidence interval (CI): 2.50-12.80, p<0.01; OR: 2.96, 95% CI: 1.30-6.72, p<0.01; OR: 7.11, 95% CI: 1.25-40.37, p=0.03, and OR: 2.65, 95% CI: 1.04-6.72, p=0.04, respectively]., Conclusions: Both indexed vessels and the degree of diameter stenosis affected the FFR. In addition, the severity of morphological lesion complexity correlated with the degree of functional severity in intermediate coronary stenosis., (Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Aims: To examine the effects of cariporide, a Na(+)/H(+) exchanger-1 inhibitor, on cardiac norepinephrine (NE) and myoglobin release during myocardial ischemia/reperfusion by applying a microdialysis technique to the rabbit heart., Main Methods: In anesthetized rabbits, two dialysis probes were implanted into the left ventricular myocardium and were perfused with Ringer's solution. Cariporide (0.3mg/kg) was injected intravenously, followed by occlusion of the left circumflex coronary artery. During 30-min coronary occlusion followed by 30-min reperfusion, four consecutive 15-min dialysate samples (two during ischemia and two during reperfusion) were collected in vehicle and cariporide-treated groups. Dialysate myoglobin and NE concentrations were measured by immunochemistry and high-performance liquid chromatography, respectively., Key Findings: Dialysate myoglobin and NE concentrations increased significantly during myocardial ischemia/reperfusion in both vehicle and cariporide-treated groups (P<0.01 vs. baseline). In cariporide-treated group, dialysate myoglobin concentrations were significantly lower than those in vehicle group throughout ischemia/reperfusion (P<0.01 at 0-15 min of ischemia, P<0.05 at 15-30 min of ischemia, P<0.01 at 0-15 min of reperfusion, and P<0.01 at 15-30 min of reperfusion). However, dialysate NE concentrations in cariporide-treated group were lower than those in vehicle group only during ischemia (P<0.01 at 0-15 min of ischemia, and P<0.05 at 15-30 min of ischemia)., Significance: When administered before ischemia, cariporide reduces myoglobin release during ischemia/reperfusion and decreases NE release during ischemia., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to investigate the possible influence of single-dose 2.0-g azithromycin (AZ-ER) on anticoagulation in patients taking warfarin., Study Design: Eighteen consecutive patients receiving long-term stable warfarin therapy were enrolled in this study. AZ-ER was administered 1 hour prior to tooth extraction. The international normalized ratio (INR) value was measured prior to AZ-ER administration as well as during, 1 day after, and 7 days after the tooth extraction. Additionally, the azithromycin concentration in the extraction wound as well as in the peripheral venous blood was assessed., Results: The changes in INR throughout the study period were not statistically significant (2-factor analysis of variance, NS). The azithromycin concentration in extraction wounds was higher than that in peripheral veins., Conclusions: The results of this study suggest that prophylactic administration of AZ-ER to patients receiving daily warfarin therapy with a stable coagulation status has no relevant effect on the anticoagulant effect of warfarin., (Copyright © 2013 Elsevier Inc. All rights reserved.)

During larval-pupal transformation, the anterior silk glands (ASGs) of the silkworm Bombyx mori undergo programmed cell death (PCD) triggered by 20-hydroxyecdysone (20E). Under standard in vitro culture conditions (0.3 ml of medium with 1 μM 20E), ASGs of the fourth-instar larvae do not undergo PCD in response to 20E. Similarly, larvae of the fifth instar do not respond to 20E through day 5 of the instar (V5). However, ASGs of V6 die when challenged by 20E, indicating that the glands might be destined to die before V6 but that a death commitment is not yet present. When we increased the volume of culture medium for one gland from 0.3 to 9 ml, V5 ASGs underwent PCD. We examined the response of ASGs to 20E every day by culturing them in 9 ml of medium and found that ASGs on and after V2 were fully responsive to 20E. Because pupal commitment is associated with juvenile hormone (JH), the corpora allata (a JH secretory organ) were removed on day 3 of the fourth larval instar (IV3), and their ASGs on V0 were cultured with 20E. Removal of the corpora allata allowed the V0 larval ASGs to respond to 20E with PCD. In contrast, topical application of a JH analogue inhibited the response to 20E when applied on or before V5. We conclude that the acquisition of responsiveness to 20E precedes the loss of JH sensitivity, and that the death commitment in ASGs occurs between V5 and 6., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The cardiac plexus contains sympathetic and parasympathetic cardiac nerves. Our goal was to assess the hemodynamic and functional effects of stimulating the cardiac autonomic nervous system (CANS) at the epivascular surfaces of the cardiac plexus. Although CANS therapy to modulate cardiovascular function has drawn widespread interest, research has focused only on stimulating parasympathetic or sympathetic nerves, not both at once., Methods: Using general anesthesia and an open-chest surgical procedure, 12 dogs received epivascular stimulation of the cardiac plexus. A bipolar electrode was placed between the right pulmonary artery (PA) and the ascending aorta, with the stimulation frequency/pulse width held constant (20 Hz/4 ms) and the voltage varied (10-50 V). Left ventricular (LV) pressure-volume loops and hemodynamic data were recorded with and without stimulation., Results: In all dogs, aortic and LV systolic pressures, maximum rate of change of LV pressure, and LV stroke work increased (p<0.0001), as did cardiac output (2.9±1.0-0.4±1.0 L/min; p=0.001), end-systolic elastance (1.2±0.4-1.5±0.5 mm Hg/mL; p=0.0001), preload recruitable stroke work (30.1±11.0-39.3±7.8 mm Hg; p=0.003), and LV ejection fraction (p=0.012). Systemic vascular resistance increased slightly (p=0.04), and pulmonary vascular resistance decreased (p=0.01). Mean heart rate and pulmonary arterial, central venous, and left atrial pressures remained unchanged (p>0.1)., Conclusions: In contrast to inotropic drugs, epivascular CANS stimulation induced a significant and selective increase in LV contractility with no increase in heart rate., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Programmed cell death (PCD) plays a critical role during animal development through the destruction of unneeded cells and tissues. In some insects, the prothoracic glands (PGs) and anterior silk glands (ASGs) are larval-specific tissues that are normally eliminated by PCD after pupation. Previous studies report that juvenile hormone analog (JHA) terminates the larval diapause of Omphisa fuscidentalis by increasing the hemolymph ecdysteroids that trigger PCD. Because JHA may indirectly induce the PCD of the PGs and ASGs of Omphisa diapausing larvae, the effects of JHA on the induction of PCD were determined. The application of 1μg JHA induced PCD in the PGs and ASGs of larvae identified as stage G0 (prior to pupation). The injection of 1μg 20E triggered the PCD of the ASGs when the larvae expressed a G0-G1 morphology, whereas PCD occurred in the PGs on day 1 post-injection. Histological studies revealed similar patterns of morphological changes during the PG and ASG PCD in the JHA- and 20E-treated larvae. Furthermore, to confirm that PCD was induced by a high ecdysteroid level that increases after JHA application, the expression profiles of EcR-A and EcR-B1 in the PGs and ASGs from the JHA-treated larvae were examined, and the results showed that the expression levels of EcR-A and EcR-B1 mRNA increased during the G0 stage. These results suggest that JHA may be involved in PCD by increasing the ecdysteroid titer, leading to termination of the larval diapause period in Omphisa fuscidentalis., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We propose a molecular network, incorporating both adaptation and phosphorylation, to account for the spontaneous cAMP oscillation of Dictyostelium discoideum. We have modified the scheme previously proposed by Loomis and his collaborators so as to include adaptation by the cAMP receptor and such that extracellular cAMP is formed by the secreted intracellular cAMP instead of being directly produced by adenylyl cyclase. Furthermore, our scheme provides better robustness, and can be applied to spontaneous cAMP production by a cluster of cells., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We determined concentrations of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), linear alkylbenzenes (LABs), and hopanes in coastal sediments collected from Jakarta Bay and Tokyo Bay. PAH concentrations in sediments from Jakarta Bay (257-1511 ng/g-dry) were lower than or comparable to those from Tokyo Bay (1372-1615 ng/g-dry). Ratios of alkyl-PAHs to parent PAHs showed a greater contribution of petrogenic inputs in Jakarta Bay than in Tokyo Bay. This difference is consistent with the higher ratio of hopanes to PAHs in Jakarta Bay. LAB concentrations in Jakarta Bay (geometric mean, 1400 ng/g-dry) were higher than those in Tokyo Bay (661 ng/g-dry). The internal to external (I/E) ratios of LABs in Jakarta Bay (0.92-2.88) were lower than those in Tokyo Bay (2.8-4.8), indicating that Jakarta Bay receives untreated or poorly treated sewage. Significant amounts of tetrapropylene-based alkylbenzenes were detected in several locations in Jakarta Bay, suggesting current usage of the non-degradable surfactants alkylbenzene sulfonates that are banned in many countries. The PCB concentration in Jakarta Bay was 1 order of magnitude lower than in Tokyo Bay, suggesting minimal usage of PCBs in industrial or commercial products in Jakarta. Analyses of a sediment core indicate increasing inputs of PAHs, hopanes, and LABs into Jakarta Bay during recent decades., (Copyright © 2012 Elsevier B.V. All rights reserved.)

In holometabolus insects, morphology of the larval fat body is remodeled during metamorphosis. In higher Diptera, remodeling of the fat body is achieved by cell death of larval fat body cells and differentiation of the adult fat body from primordial cells. However, little is known about remodeling of the fat body at pupal metamorphosis in Lepidoptera. In this study, we found that cell death of the larval fat body in Bombyx mori occurs at shortly after pupation. About 30% of the fat body cells underwent cell death on days 1 and 2 after pupation. The cell death involved genomic DNA fragmentation, a characteristic of apoptosis. Surgical manipulation and in vitro culture of fat body cells revealed that 20-hydroxyecdysone and juvenile hormone had no effect on either initiation or progression of cell death. During cell death, a large increase in activity of caspase-3, a key enzyme of cell death, was observed. Western blot analysis of the active form of caspase-3-like protein revealed that the length of caspase-3 of B. mori was much larger than that of caspase-3 in other species. The results suggest that larval fat body cells of B. mori are removed through cell death, which is mediated by a caspase probably categorized in a novel family., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Blood sugar is an essential energy source for growth and development and is maintained at a constant level through precise regulation of formation and utilization. Sugars are produced from dietary carbohydrates by enzymatic hydrolysis in the digestive tract, which are under the homeostatic control of paracrine and prandial mechanisms in mammals. Here, we show that dietary carbohydrates hydrolyzing activity of the digestive tract is developmentally regulated by the steroid hormone ecdysone in the silkworm, Bombyx mori. The dietary carbohydrates hydrolyzing activity remained high throughout the last larval period and then decreased to negligible levels until the pupal period. However, dietary carbohydrates digestive activities were constitutively high when the steroidogenic organ, prothoracic glands were ablated. The prothoracic glands produced and released a large amount of ecdysone at the end of the larval period, suggesting that ecdysone is responsible for the decrease in dietary carbohydrates hydrolyzing activity. In fact, ecdysone decreased the activity to negligible levels in silkworms lacking the prothoracic glands. The present results indicate that the dietary carbohydrates hydrolyzing activity is regulated by ecdysone and that an increase in ecdysone titer decreases that activity at the end of the larval period, suggesting that ecdysone is essential for metabolic coordination during development., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: The associations between alcohol consumption and sleep-disordered breathing in women are uncertain., Methods: We conducted a cross-sectional study of 3113 women aged 30-69 years. The 3% oxygen desaturation index (3% ODI), based on overnight pulse oximetry findings, was selected as an indicator of sleep-disordered breathing., Results: 3% ODI frequencies of ≥5 were higher for drinking women with ethanol intakes of ≥23.0 g/d than for never drinkers: the respective multivariable odds ratios and 95% confidence intervals was 1.8(1.0-3.4). The corresponding odds ratio was 3.0(1.6-5.8) for habitual snoring. The associations of ethanol intakes of ≥23.0 g/d with 3% ODI ≥ 5 was more evident among women with BMI <23.0 kg/m(2) (median) than those with higher BMI but did not vary by habitual snoring. The multivariable odds ratios of 3%ODI ≥ 5 for women with ethanol intakes of ≥23.0 g/d versus never drinkers were 2.7(1.0-6.7) for lower BMI and 1.5(0.6-3.3) for higher BMI and the corresponding odds ratio were 2.8(1.6-7.2) and 3.2(1.3-7.9) for habitual snoring, respectively., Conclusion: Alcohol consumption was associated with higher prevalence of sleep-disordered breathing among Japanese women., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Successful insect development is achieved via appropriate fluctuation of ecdysteroid levels. When an insect's ecdysteroid level is disrupted, physiological and developmental defects occur. In the pupa of the silkworm, Bombyx mori, the rectal sac is an essential organ that operates as a repository for degraded ecdysteroids, and it can be distended by administration of 20-hydroxyecdysone (20E). Our previous study showed that rectal sac distention appears 4 days after 20E administration. Hemolymph ecdysteroid levels, however, decrease to lower level during this period. Thus, the timing of the rectal sac distention does not match with that of ecdysteroid elevation. Here, we examine how 20E induces rectal sac distention. A ligature experiment and ecdysteroid quantification showed that continuous 20E stimulation induces rectal sac distention. Thorax tissue contributed to the continuous 20E stimulation needed to induce distention. Ecdysteroid released from the thorax tissue may be converted to 20E by ecdysone 20-hydroxylase to produce continuous 20E stimulation. Thus, the ecdysone metabolic pathway plays a critical role in rectal sac distention., (Copyright 2010 Elsevier Ltd. All rights reserved.)

The determination of uranium isotope ratios in individual particles is of great importance for nuclear safeguards. In the present study, an analytical technique by inductively coupled plasma mass spectrometry (ICP-MS) with a desolvation sample introduction system was applied to isotope ratio analysis of individual uranium particles. In ICP-MS analysis of individual uranium particles with diameters ranging from 0.6 to 4.2 microm in a standard reference material (NBL CRM U050), the use of the desolvation system for sample introduction improved the precision of (234)U/(238)U and (236)U/(238)U isotope ratios. The performance of ICP-MS with desolvation was compared with that of a conventionally used method, i.e., secondary ion mass spectrometry (SIMS). The analysis of test swipe samples taken at nuclear facilities implied that the performance of ICP-MS with desolvation was superior to that of SIMS in a viewpoint of accuracy, because the problems of agglomeration of uranium particles and molecular ion interferences by other elements could be avoided. These results indicated that ICP-MS with desolvation has an enough ability to become an effective tool for nuclear safeguards.

Background: Transforming growth factor beta1 (TGF beta 1) is an important factor in immunomodulation. The expression of TGF beta 1 has been shown to be influenced by the C-509T polymorphism in the TGF beta 1 gene. We investigated age-related changes of plasma TGF beta 1 levels in a birth-cohort study. In addition, the genotypes of the C-509T polymorphism were investigated in allergic and non-allergic subjects., Methods: Sixty-four neonates who met the following criteria were enrolled in this cohort study: 1) full-term vaginally delivery; 2) underwent DNA polymorphism analysis; and 3) questionnaire forms were filled out by parents at 0, 6 and 14 months of age. The umbilical cord blood at 0 months and peripheral blood at 6, and 14 months were collected. Plasma TGF beta1 levels were measured at 0, 6 and 14 months of age. Genomic DNA was extracted from their umbilical cord blood. The genotype of the subjects was examined for the presence of C-509T., Results: The plasma TGF beta 1 level at 6 months was the highest of the 3 measurements (at 0, 6, and 14 months of age). The TGF beta 1 levels at 14 months in allergic subjects were significantly higher than those in non-allergic subjects (p = 0.03). All subjects with bronchial asthma (n = 3) had the TT genotype of the C-509T polymorphism., Conclusions: The plasma TGF beta 1 levels change with age. In addition, TGF beta 1 may play a role in the pathogenesis of bronchial asthma.

Holometabolous insects do not excrete but store metabolic wastes during the pupal period. The waste is called meconium and is purged after adult emergence. Although the contents of meconium are well-studied, the developmental and physiological regulation of meconium accumulation is poorly understood. In Bombyx mori, meconium is accumulated in the rectal sac; thereby, the rectal sac distends at the late pupal stage. Here, we show that rectal sac distention occurs between 4 and 5 days after pupation. The distention is halted by brain-removal just after larval-pupal ecdysis but not by brain-removal 1 day after pupation. In the pupae, brain-removal just after ecdysis kept the hemolymph ecdysteroid titer low during early and mid-pupal stages. An injection of 20-hydroxyecdysone (20E) evoked the distention that was halted by brain-removal in a dose-dependent manner. Therefore, brain-removal caused the lack of ecdysteroid, and rectal sac distention did not appear in the brain-removed pupae because of the lack of ecdysteroid. We conclude that rectal sac distention is one of the developmental events regulated by 20E during the pupal period in B. mori.