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Objectives: We aimed to obtain information on the degree of knowledge and understanding about the current systems of health care and welfare held by the elderly, in order to achieve comprehensiveness in family practice.Method: We conducted a study on the awareness of healthy elderly persons by direct interview. The study was carried out in Kuni Village in a remote mountainous region in Japan, where the elderly population accounts for 24.8% of the total population. The subjects were self-dependent in their daily living activities and were aged 65 years and older.Results: The subjects' knowledge of health care and welfare systems was generally good, and the degree of their utilization of these systems was also good. But 83.3% of those who did not want to utilize the welfare system indicated their preference to depend on their family for support.Conclusion: Family physicians must endeavour to offer comprehensive care to their patients by including these systems for rapidly ageing communities. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate the usefulness of mutual rotation by family physicians in providing an evaluation of rural medical practices.Methods: Between June and October 1994, each of four family physicians rotated to the practices of the other three, where they worked as a transient locum for 4-5 days and evaluated each practice. They were field faculty physicians of the Department of Community and Family Medicine, Jichi Medical School, and based at general practices accredited for undergraduate and postgraduate training. Two school-based faculty physicians also participated in the study as spare members.Results: The rotation was conducted four times to complete the mutual rotation programme. There was some difference in evaluation among the practices, which indicated the characteristics of the practices. The evaluation accorded relatively well among the participants.Conclusions: Mutual rotation by family physicians provides an objective and practicable evaluation of general practices and contribute to upholding their quality, which is crucial to medical education. [ABSTRACT FROM AUTHOR]

Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by various combinations of autonomic failure, parkinsonism, and cerebellar ataxia. To elucidate variants associated with MSA, we have been conducting short-read-based whole-genome sequence analysis. In the process of the association studies, we initially focused on GBA1, a previously proposed susceptibility gene for MSA, to evaluate whether GBA1 variants can be efficiently identified despite its extraordinarily high homology with its pseudogene, GBA1LP. To accomplish this, we conducted a short-read whole-genome sequence analysis with alignment to GRCh38 as well as Sanger sequence analysis and compared the results. We identified five variants with inconsistencies between the two pipelines, of which three variants (p.L483P, p.A495P-p.V499V, p.L483_M489delinsW) were the results of misalignment due to minor alleles in GBA1P1 registered in GRCh38. The miscalling events in these variants were resolved by alignment to GRCh37 as the reference genome, where the major alleles are registered. In addition, a structural variant was not properly identified either by short-read or by Sanger sequence analyses. Having accomplished correct variant calling, we identified three variants pathogenic for Gaucher disease (p.S310G, p.L483P, and p.L483_M489delinsW). Of these variants, the allele frequency of p.L483P (0.003) in the MSA cases was higher than that (0.0011) in controls. The meta-analysis incorporating a previous report demonstrated a significant association of p.L483P with MSA with an odds ratio of 2.85 (95% CI; 1.05 - 7.76, p = 0.0400)., Competing Interests: Competing interests: The authors declare no competing interests. Ethical approval: This study was approved by the Institutional Review Board of the University of Tokyo., (© 2024. The Author(s).)

Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic nervous system dysfunction and cerebellar ataxia or parkinsonism. Recently, expanded GAA repeats (≥250 repeat units) in intron 1 of FGF14 have been shown to be responsible for spinocerebellar ataxia type 27B (SCA27B), a late-onset ataxia with an autosomal dominant inheritance. Patients with SCA27B may also exhibit autonomic nervous system dysfunction, potentially overlapping with the clinical presentations of MSA patients. In this study, to explore the possible involvement of expanded GAA repeats in MSA, we investigated the frequencies of expanded GAA repeats in FGF14 in 548 patients with MSA, 476 patients with undiagnosed ataxia, and 455 healthy individuals. To fully characterize the structures of the expanded GAA repeats, long-range PCR products suggesting the expansion of GAA repeats were further analyzed using a long-read sequencer. Of the 548 Japanese MSA patients, we identified one MSA patient (0.2%) carrying an expanded repeat with (GAA) ≥250 . Among the 476 individuals with undiagnosed ataxia, (GAA) ≥250 was observed in six (1.3%); this frequency was higher than that in healthy individuals (0.2%). The clinical characteristics of the MSA patient with (GAA) ≥250 were consistent with those of MSA, but not with SCA27B. Further research is warranted to explore the possibility of the potential association of expanded GAA repeats in FGF14 with MSA., Competing Interests: Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: Written informed consent was obtained from all the patients. This study was approved by the institutional review board of the University of Tokyo and participating institutions., (© 2024. The Author(s).)

Background/Objective: Multiple system atrophy (MSA) is often associated with dysphagia and esophageal dysmotility (ED). However, ED in patients with MSA is poorly understood. To assess the relationship between ED, dysphagia, and other clinical findings in such patients and investigate the details of ED in MSA using high-resolution manometry (HRM). Methods: Patients from The University of Tokyo Hospital with MSA who underwent swallowing examinations, esophagography, and HRM between 2017 and 2022 were enrolled. A retrospective chart review of patients' backgrounds, swallowing function, and esophageal motility was performed. ED was evaluated using the Chicago Classification version 4.0. Results: Seventy-four patients with MSA were identified. The median age was 64 years, 48 patients (65%) were male, and the cerebellar variant type was predominant (69%). Abnormal upper esophageal sphincter (UES) resting pressure was observed in 34 patients (46%) and intraesophageal stasis in 65 (88%). High-severity MSA was a risk factor for developing dysphagia, vocal fold movement impairment, and abnormal UES function ( p < 0.05). However, no overt clinical risk factors for ED were identified. Various types of ED were detected using HRM, and ineffective esophageal motility was the most frequent disorder. Conclusions: ED is a common occurrence in patients with MSA. Although a high-severity MSA may be a risk factor for developing dysphagia and vocal fold motion impairment, ED can occur regardless of clinical severity. Since ED is rarely detected based on subjective symptoms, careful evaluation of esophageal motility by esophagography or HRM is warranted in patients with MSA.

Background: Idiopathic basal ganglia calcification (IBGC), also known as Farh's disease, is a rare neurodegenerative disorder characterized by calcification of the basal ganglia and other brain regions. This disease usually occurs in middle-aged patients and presents with various neurological and psychiatric symptoms. The exact prevalence is unknown; however, population genomic data analysis suggests a prevalence of at least 4.5/10,000 to 3.3/1000, indicating that the disease is more common than previously thought and remains underdiagnosed., Case Presentation: We report the case of a middle-aged Japanese man who attempted suicide twice because of obsessive-compulsive ideation caused by trivial triggers. The patient's psychiatric symptoms resolved relatively quickly after hospitalization, and imaging and genetic testing led to a diagnosis of IBGC., Conclusion: This case report illustrates the importance of including IBGC in the differential diagnosis of psychiatric symptoms that initially develop in middle-aged patients., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Cytokines employ downstream Janus kinases (JAKs) to promote chronic inflammatory diseases. JAK1-dependent type 2 cytokines drive allergic inflammation, and patients with JAK1 gain-of-function (GoF) variants develop atopic dermatitis (AD) and asthma. To explore tissue-specific functions, we inserted a human JAK1 GoF variant (JAK1 GoF ) into mice and observed the development of spontaneous AD-like skin disease but unexpected resistance to lung inflammation when JAK1 GoF expression was restricted to the stroma. We identified a previously unrecognized role for JAK1 in vagal sensory neurons in suppressing airway inflammation. Additionally, expression of Calcb/CGRPβ was dependent on JAK1 in the vagus nerve, and CGRPβ suppressed group 2 innate lymphoid cell function and allergic airway inflammation. Our findings reveal evolutionarily conserved but distinct functions of JAK1 in sensory neurons across tissues. This biology raises the possibility that therapeutic JAK inhibitors may be further optimized for tissue-specific efficacy to enhance precision medicine in the future., Competing Interests: Declaration of interests B.S.K. is founder of KliRNA Biotech; he has served as a consultant for 23andMe, ABRAX Japan, AbbVie, Almirall, Amgen, Arcutis Biotherapeutics, Arena Pharmaceuticals, argenx, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Clexio Biosciences, Eli Lilly and Company, Escient Pharmaceuticals, Evommune, Galderma, Genentech, GlaxoSmithKline, Granular Therapeutics, Incyte Corporation, Innovaderm Research, Janssen, Kiniksa, LEO Pharma, Maruho, Novartis, Pfizer, Recens Medical, Regeneron Pharmaceuticals, Sanofi, Septerna, Triveni Bio, Vial, and WebMD; he has stock in ABRAX Japan, KliRNA Biotech, Locus Biosciences, and Recens Medical; he holds a patent for the use of JAK1 inhibitors for chronic pruritus; and he has a patent pending for the use of JAK inhibitors for interstitial cystitis. D.A. has contributed to scientific advisory boards at Pfizer, Takeda, FARE, and the KRF. D.B. is the founder of Lab11 Therapeutics.., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Epidemiological studies demonstrated that cleaning work and frequent use of cleaning products are risk factors for asthma. Laundry detergents have been reported to have epithelial barrier-opening effects. However, whether laundry detergents directly induce airway inflammation and its mechanisms in vivo remain to be elucidated., Methods: Two commercial laundry detergents and two commonly used surfactants for cleaning and cosmetics (sodium lauryl sulfate and sodium dodecyl benzene sulfonate) were intranasally administered to mice. Lungs were analyzed using flow cytometry, histology, ELISA, and quantitative PCR. Human bronchial epithelial cells were stimulated with laundry detergents and analyzed using quantitative PCR and western blotting. Involvement of oxidative stress was assessed using an antioxidant. Dust samples from homes were analyzed to determine their detergent content by measuring their critical micelle concentration (CMC)., Results: The administered laundry detergents and surfactants-induced eosinophilic airway inflammation accompanied by increased IL-33 expression and activation of group 2 innate lymphoid cells (ILC2s). Detergent-induced eosinophilic airway inflammation was significantly attenuated in Rag2 -/- Il2rg -/- , Il33 -/- mice, and also in wild-type mice treated with NAC. Detergent-induced IL-33 expression in airways was attenuated by NAC treatment, both in vivo and in vitro. CMCs were found in all of the tested dust extracts, and they differed significantly among the homes., Conclusion: The laundry detergents and surfactants-induced eosinophilic airway inflammation in vivo through epithelial cell and ILC2 activation. They induced IL-33 expression in airway epithelial cells through oxidative stress. Furthermore, detergent residues were present in house dust and are presumably inhaled into the airway in daily life., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

A 36-year-old man developed polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome after conversion from solitary plasmacytoma of bone to multiple myeloma. Twenty-four days following the neurological onset, he lost his independent walking ability. The level of serum vascular endothelial growth factor (VEGF) at diagnosis was 5,250 pg/mL. Three months after initiating treatment, he regained his independent walking ability in line with a reduction in the elevated serum VEGF level. Due to their genomic instability gained during conversion, myeloma cells may overproduce humoral factors and cytokines, possibly contributing to the development of neuropathy as well as the production of VEGF.

Background: Platelets are thought to be involved in the pathophysiology of asthma, presumably through direct adhesion to inflammatory cells, including group 2 innate lymphoid cells (ILC2s). Here, we tried to elucidate the effects of platelet adhesion to ILC2s in vitro and in vivo, as well as the mechanisms involved., Methods: Alternaria-induced ILC2-dependent airway inflammation models using wild-type and c-mpl -/- mice were evaluated. Both purified CD41 + and CD41 - ILC2s were cultured with IL-2 and IL-33 to determine in vitro Type 2 (T2) cytokine production and cell proliferation. RNA-seq data of flow-cytometry-sorted CD41 + and CD41 - ILC2s were used to isolate ILC2-specific genes. Flow cytometry was performed to determine the expression of CD41 and adhesion-related molecules on ILC2s in both mouse and human tissues., Results: T2 inflammation and T2 cytokine production from ILC2s were significantly reduced in the c-mpl -/- mice compared to wild-type mice. Platelet-adherent ILC2s underwent significant proliferation and showed enhanced T2 cytokine production when exposed to IL-2 and IL-33. The functions of ILC2-specific genes were related to cell development and function. Upstream regulator analysis identified 15 molecules, that are thought to be involved in ILC2 activation. CD41 expression levels were higher in ILC2s from human PBMCs and mouse lung than in those from secondary lymphoid tissues, but they did not correlate with the P-selectin glycoprotein ligand-1 or CD24 expression level., Conclusion: Platelets spontaneously adhere to ILC2s, probably in the peripheral blood and airways, thereby potentiating ILC2s to enhance their responses to IL-33., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Discovery of innate lymphoid cells (ILCs), which are non-T and non-B lymphocytes that have no antigen-specific receptors, changed the classical concept of the mechanism of allergy, which had been explained mainly as antigen-specific acquired immunity based on IgE and Th2 cells. The discovery led to dramatic improvement in our understanding of the mechanism of non-IgE-mediated allergic inflammation. Numerous studies conducted in the past decade have elucidated the characteristics of each ILC subset in various organs and tissues and their ontogeny. We now know that each ILC subset exhibits heterogeneity. Moreover, the functions and activating/suppressing factors of each ILC subset were found to differ among both organs and types of tissue. Therefore, in this review, we summarize our current knowledge of ILCs by focusing on the organ/tissue-specific features of each subset to understand their roles in various organs. We also discuss ILCs' involvement in human inflammatory diseases in various organs and potential therapeutic/preventive strategies that target ILCs., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Anti-leucine-rich glioma-inactivated 1 (LGI1) antibody is associated with limbic encephalitis. We herein report a patient with anti-LGI1 encephalitis who developed severe orthostatic hypotension (OH) responsive to immunoglobulin therapy five years after developing symptoms of encephalitis. A 71-year-old man presented with amnesia caused by limbic encephalitis. The symptoms of encephalitis improved partially without any immunotherapy. Five years later, he developed severe OH, and anti-LGI1 antibody was positive. The catecholamine dynamics indicated that the central autonomic nervous system was the lesion of his OH. Intravenous immunoglobulin therapy improved the OH. This case suggests that anti-LGI1 antibody can be associated with severe OH.

Exposure to various antigens derived from house dust mites (HDM) is considered to be a risk factor for development of certain allergic diseases such as atopic asthma, atopic dermatitis, rhinitis and conjunctivitis. Chitin is an insoluble polysaccharide (β-(1-4)-poly-N-acetyl-D-glucosamine) and a major component in the outer shell of HDMs. Mice exposed to chitin develop asthma-like airway eosinophilia. On the other hand, several lines of evidence show that the effects of chitin on immune responses are highly dependent on the size of chitin particles. In the present study, we show that chitin induced production of IL-33 and TSLP by alveolar and bronchial epithelial cells, respectively, in mice. IL-25, IL-33 and TSLP were reported to be important for group 2 innate lymphoid cell (ILC2)-, but not Th2 cell-, dependent airway eosinophilia in a certain model using chitin beads. Here, we show that-in our murine models-epithelial cell-derived IL-33 and TSLP, but not IL-25, were crucial for activation of resident lung Th2 cells as well as group 2 innate lymphoid cells (ILC2s) to produce IL-5, resulting in development of chitin-induced airway eosinophilia. Our findings provide further insight into the underlying mechanisms of development of HDM-mediated allergic disorders.

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.

Objective Epidemic myalgia associated with human parechovirus type 3 (EM-HPeV3) is characterized by severe muscle pain and weakness on the limbs and trunk with a fever. No outbreak of EM-HPeV3 has been reported since 2016, and its clinical characteristics have not been sufficiently clarified. We herein report a series of EM-HPeV3 cases during the summer of 2019 and clarify the clinical characteristics of EM-HPeV3. Methods The diagnosis of EM-HPeV3 was established when the patients met both of the following criteria: (1) Patients developed severe muscle pain and weakness with a fever within a week, and those symptoms resolved within a month; and (2) HPeV3 was detected in either a throat swab or fecal specimen of the patient by polymerase chain reaction. We reviewed the medical records of these patients retrospectively. Results Seven patients met the criteria (6 men and 1 woman, age 34 to 47 years old). Myalgia was observed on the thigh, lower legs, upper arms, and forearms in seven, five, two, and five patients, respectively. Four patients showed distal dominant weakness on the arms, while none of the patients showed proximal dominant weakness on the arms. Of the six patients examined, five showed reduced tendon reflexes on all four limbs. One patient showed slight myogenic change and increased insertion activities on needle electromyography. Conclusion We observed seven cases of EM-HPeV3 during the summer of 2019. Reduced tendon reflexes and distal dominancy of muscle pain and weakness on the arms are considered its distinct clinical features.

Since the airways are constantly exposed to various pathogens and foreign antigens, various kinds of cells in the airways-including structural cells and immune cells-interact to form a precise defense system against pathogens and antigens that involve both innate immunity and acquired immunity. Accumulating evidence suggests that innate lymphoid cells (ILCs) play critical roles in the maintenance of tissue homeostasis, defense against pathogens and the pathogenesis of inflammatory diseases, especially at body surface mucosal sites such as the airways. ILCs are activated mainly by cytokines, lipid mediators and neuropeptides that are produced by surrounding cells, and they produce large amounts of cytokines that result in inflammation. In addition, ILCs can change their phenotype in response to stimuli from surrounding cells, which enables them to respond promptly to microenvironmental changes. ILCs exhibit substantial heterogeneity, with different phenotypes and functions depending on the organ and type of inflammation, presumably because of differences in microenvironments. Thus, ILCs may be a sensitive detector of microenvironmental changes, and analysis of their phenotype and function at local sites may enable us to better understand the microenvironment in airway diseases. In this review, we aimed to identify molecules that either positively or negatively influence the function and/or plasticity of ILCs and the sources of the molecules in the airways in order to examine the pathophysiology of airway inflammatory diseases and facilitate the issues to be solved., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2020 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Background: Group 2 innate lymphoid cells (ILC2s) play critical roles in induction and exacerbation of allergic airway inflammation. Thus clarification of the mechanisms that underlie regulation of ILC2 activation has received significant attention. Although innate lymphoid cells are divided into 3 major subsets that mirror helper effector T-cell subsets, counterpart subsets of regulatory T cells have not been well characterized., Objective: We sought to determine the factors that induce regulatory innate lymphoid cells (ILCregs)., Methods: IL-10 + ILCregs induced from ILC2s by using retinoic acid (RA) were analyzed with RNA-sequencing and flow cytometry. ILCregs were evaluated in human nasal tissue from healthy subjects and patients with chronic rhinosinusitis with nasal polyps and lung tissue from house dust mite- or saline-treated mice., Results: RA induced IL-10 secretion by human ILC2s but not type 2 cytokines. IL-10 + ILCregs, which were converted from ILC2s by means of RA stimulation, expressed a regulatory T cell-like signature with expression of IL-10, cytotoxic T lymphocyte-associated protein 4, and CD25, with downregulated effector type 2-related markers, such as chemoattractant receptor-homologous molecule on T H 2 cells and ST2, and suppressed activation of CD4 + T cells and ILC2s. ILCregs were rarely detected in human nasal tissue from healthy subjects or lung tissue from saline-treated mice, but numbers were increased in nasal tissue from patients with chronic rhinosinusitis with nasal polyps and in lung tissue from house dust mite-treated mice. Enzymes for RA synthesis were upregulated in airway epithelial cells during type 2 inflammation in vivo and by IL-13 in vitro., Conclusion: We have identified a unique immune regulatory and anti-inflammatory pathway by which RA converts ILC2s to ILCregs. Interactions between airway epithelial cells and ILC2s play an important roles in the generation of ILCregs., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Chitin, which is a major component of house dust mites (HDM), fungi, crustaceans, etc., can activate immune cells, suggesting that it contributes to development of allergic disorders such as asthma. Although the pathophysiological sensitization route of asthmatic patients to allergens is considered via the respiratory tract, the roles of intranasally-administered chitin in development of asthma remain unclear. After ovalbumin (OVA) challenge, development of airway inflammation was profoundly exacerbated in mice sensitized with OVA in the presence of chitin. The exacerbation was dependent on IL-33, but not IL-25, thymic stromal lymphopoietin or IL-17A. Chitin enhanced IL-33-dependent IL-1β production by dendritic cells (DCs). Furthermore, chitin- and IL-33-stimulated DC-derived IL-1β promoted OVA-specific Th2 cell activation, resulting in aggravation of OVA-induced airway inflammation. These findings indicate the adjuvant activity of chitin via a new mechanism and provide important clues for development of therapeutics for allergic disorders caused by HDM, fungi and crustaceans.

Background: Direct contact of food proteins with eczematous lesions is thought to be the main cause of epicutaneous sensitization. To further investigate the development and pathogenesis of food allergy in vivo, a good mouse model of epicutaneous sensitization is needed. However, a fundamental problem in that regard is that the optimal age for epicutaneous sensitization of mice is unknown. In this study, we attempted to elucidate that optimal age., Methods: Dorsal skin of wild-type BALB/c female mice (1, 3, 8 and 24 weeks old) was shaved, depilated and tape-stripped. A Finn chamber containing a 20-μl-aliquot of 20-mg/ml (OVA) was applied to the tape-stripped skin on 3 consecutive days/week, for 3 weeks. The body temperature was measured after intraperitoneal OVA challenge. Serum OVA-specific IgE titers and OVA-induced cytokine production by spleen cells were measured by ELISA. Dendritic cells (DCs) that migrated to the draining lymph nodes were quantified by FITC-labeled OVA and flow cytometry. The mRNA expression levels in the dorsal skin were measured by qPCR., Results: A significant age-dependent body temperature decline was observed after OVA challenge. The serum OVA-specific IgE titer, OVA-induced cytokine production (i.e., IL-4, IL-5 and IL-13) by spleen cells, and number of FITC-OVA-engulfing DCs increased with age. In addition, mRNA for IL-33, but not TSLP or IL-25, was significantly induced in the skin by tape-stripping and increased with age., Conclusions: Twenty-four-week-old mice showed the greatest DC migration, Th2 polarization, IgE production and body temperature decline. Skin-derived IL-33 is likely to play key roles in those changes., (Copyright © 2018 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Although human term placenta-derived primary cytotrophoblasts (pCTBs) represent a good human syncytiotrophoblast (STB) model, in vitro culture of pCTBs is not always easily accomplished. Y-27632, a specific inhibitor of Rho-associated coiled-coil containing kinases (ROCK), reportedly prevented apoptosis and improved cell-to-substrate adhesion and culture stability of dissociated cultured human embryonic stem cells and human corneal endothelial cells. The Rho kinase pathway regulates various kinds of cell behavior, some of which are involved in pCTB adhesion and differentiation. In this study, we examined Y-27632's potential for enhancing pCTB adhesion, viability and differentiation. pCTBs were isolated from term, uncomplicated placentas by trypsin-DNase I-Dispase II treatment and purified by HLA class I-positive cell depletion. Purified pCTBs were cultured on uncoated plates in the presence of epidermal growth factor (10 ng/ml) and various concentrations of Y-27632. pCTB adhesion to the plates was evaluated by phase-contrast imaging, viability was measured by WST-8 assay, and differentiation was evaluated by immunofluorescence staining, expression of fusogenic genes and hCG-β production. Ras-related C3 botulinum toxin substrate 1 (Rac1; one of the effector proteins of the Rho family) and protein kinase A (PKA) involvement was evaluated by using their specific inhibitors, NSC-23766 and H-89. We found that Y-27632 treatment significantly enhanced pCTB adhesion to plates, viability, cell-to-cell fusion and hCG-β production, but showed no effects on pCTB proliferation or apoptosis. Furthermore, NSC-23766 and H-89 each blocked the effects of Y-27632, suggesting that Y-27632 significantly enhanced pCTB differentiation via Rac1 and PKA activation. Our findings suggest that Rac1 and PKA may be interactively involved in CTB differentiation, and addition of Y-27632 to cultures may be an effective method for creating a stable culture model for studying CTB and STB biology in vitro.

Background: Psychiatrists in clinical practice face a number of stressors related to patient care, such as overwork. On the other hand, they gain satisfaction from their work. We quantified and assessed the potential relationship between levels of occupational stress, satisfaction, and depressive symptoms among Japanese clinical psychiatrists. We surveyed 206 psychiatrists with up to 15 years of clinical experience who primarily worked in patient care. Levels of occupational stress and occupational satisfaction were measured using the Visual Analogue Scale and the level of depressive symptoms was measured by the Center for Epidemiologic Studies Depression Scale. Workplace stressors and satisfiers were also evaluated., Results: Out of 206 psychiatrists, 154 (74.8%) responded to the survey. The respondents' mean (SD) age was 34.3 (5.2) years. The estimated prevalence of significant depressive symptoms was 34.4% (n = 53), and the experienced frequent violence was 14.9% (n = 23). The level of depressive symptoms was inversely correlated with the level of occupational satisfaction. In respondents who reported a moderate level of occupational stress, having fewer depressive symptoms was associated with higher occupational satisfaction, but this association was not significant in those who reported a high level of stress. In addition, high occupational satisfaction was associated with interest towards work content, ability to work at one's discretion, opportunities for growth and career development, and ease of communication with supervisors and colleagues., Conclusions: Nearly one-third of the psychiatrists screened positive for significant depressive symptoms. Having fewer depressive symptoms was associated with higher occupational satisfaction in those who reported a moderate level of stress. Implications from the present findings may be to enhance occupational satisfaction by discussing work interests with a supervisor, as well as increased opportunities for career development, which may prevent depression among psychiatrists.

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a very aggressive embryonal central nervous system (CNS) tumor, histologically featuring ependymoblastic rosettes and neuronal differentiation in a neuropil-like background. 19q13.42 amplification was identified in ETANTR and epndymoblastoma, suggesting that these tumors constitute a single entity, called embryonal tumor with multilayered rosettes (ETMR). Here, we report a case involving a 2-year-old boy with a pontine embryonal tumor composed of clusters of poorly differentiated neuroepithelial cells, and smaller neuroblastic/neurocytic cells in a fibrillary and paucicellular neuropil-like matrix, where clear ependymoblastic rosettes were not detected but only one structure suggestive of an ependymoblastic multilayered rosette was found. Fluorescence in situ hybridazation analysis revealed 19q13.42 amplification, supporting the diagnosis of ETANTR. This report indicates that rare ependymoblasic rosettes found in embryonal tumors, which are otherwise CNS primitive neuroectodermal tumors or medulloblastomas, are significant for considering the examination of 19q13.42 amplification to confirm the diagnosis of ETMR., (© 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.)

Aim: The aim of this study was to develop a simple staging classification to measure leisure activity and social communication among the elderly at geriatric health care facilities., Methods: In order to construct a staging scale for measuring the participation of the elderly subjects, we developed a list of 28 items for three domains: leisure activities, social participation and communication. Data were obtained from users of institutional and day care services at geriatric health service facilities. The Rasch model was applied to test the degree of item fit and difficulty. Simple staging scales were constructed based on 12 leisure activity and nine social communication items. The validity and reliability were tested using these newly developed scales according to the Rasch model and assessments of the test-retest reliability., Results: The participants were 3,458 elderly persons, of whom 1,560 were currently using institutional services and 1,898 were using day care services. Among the 28 items, "traveling" was identified as the most difficult and "watching television" was identified as the easiest. Because items related to "social participation," such as volunteer activities, exhibited a low frequency, they were not used in the further analyses. Simple staging scales were constructed by analyzing the remaining items of leisure activities and social communication according to the Rasch model. The thresholds within the scales were determined in order of item difficulty. Cohen's kappa, as assessed by two different evaluators, was 0.75 for leisure activities and 0.77 for social communication., Conclusions: In this study, we developed staging scales for leisure activity and social communication. The construct validity and test-retest reliability were adequate for both scales. Service providers can improve service quality by using these scales for individual case management of elderly persons in conjunction with existing scales of activities of daily living.

We report a 3-year-old boy with enterohemorrhagic Escherichia coli (EHEC) O157-associated hemolytic uremic syndrome (HUS). His anemia was associated with decreased reticulocyte count and persisted after the recovery from HUS. Superinfection of parvovirus B19 (PVB19) was proven by a transient febrile episode associated with IgM antibodies to the virus and the delayed appearance of IgG antibodies and typical rashes. We conclude that PVB19 infection could induce severe persistent anemia in EHEC-associated HUS. Reticulocytopenia is a clue to the diagnosis in such cases.

Ropivacaine has a high threshold for systemic toxicity. We report and highlight a rare case in which an overdose of ropivacaine was suspected of leading to a generalized convulsion following the injection of this agent for axillary brachial plexus block (ABPB). A 25-year-old woman (height, 153 cm; weight, 48 kg; American Society of Anesthesiologists physical status I) was scheduled for finger surgery with ABPB. The perivascular sheath was identified by fascial clicks. We administered 300 mg (6.25 mg x kg(-1)) ropivacaine, while confirming that no blood flow was observed in the injection line by repeated negative aspiration tests. Ten minutes after the injection, most sensory and motor nerves were blocked effectively. Thirteen minutes after the administration, the patient lost consciousness and convulsed suddenly. No severe symptoms of cardiovascular toxicity occurred. The concentration of ropivacaine in a venous blood sample taken 28 min after the ropivacaine injection was 3.65 microg x ml(-1). She recovered with no sequelae. Limited cases have indicated high efficacy and sufficient safety for the use of 300 mg ropivacaine for ABPB. However, the toxic threshold of ropivacaine remains unclear, and the dose should be calculated in relation to the weight of the patient to prevent severe toxic complications.

The peanut agglutinin (PNA) receptors isolated from a tumor cell line could elicit antitumor activity by an active immunization. We report here the results of active immunization with a human PNA receptor glycoprotein on the tumor progression of cancer patients. A remarkable regression of cancer and a prolonged life span in patients were obtained after active immunization with a tumor cell-associated carbohydrate antigen.