Search

Synucleinopathies, including Parkinson's disease and dementia with Lewy bodies, are neurodegenerative disorders characterized by the aberrant accumulation of α-synuclein (α-syn). Although no treatment is effective for synucleinopathies, the suppression of α-syn aggregation may contribute to the development of numerous novel therapeutic targets. Recent research revealed that nicotinic acetylcholine (nACh) receptor activation has neuroprotective effects and promotes the degradation of amyloid protein by activating autophagy. In an in vitro human-derived cell line model, we demonstrated that galantamine, the nAChR allosteric potentiating ligand, significantly reduced the cell number of SH-SY5Y cells with intracellular Lewy body-like aggregates by enhancing the sensitivity of α 7 -nAChR. In addition, galantamine promoted autophagic flux, and prevented the formation of Lewy body-resembled aggregates. In an in vivo synucleinopathy mouse model, the propagation of α-syn aggregation in the cerebral cortex was inhibited by galantamine administration for 90 days. These results suggest that α 7 -nAChR is expected to be a novel therapeutic target, and galantamine is a potential agent for synucleinopathies., (Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

This study aimed to determine whether oral fumonisin exposure contributes to the development of psoriasis. Oral administration of fumonisin B1 (FB1, 0.1 mg/kg) or fumonisin B2 (FB2, 0.1 mg/kg) was conducted for 10 days, in addition to the induction of psoriatic symptoms through topical application of 5% imiquimod cream from day 6 to day 10 (5 days) in female BALB/c mice. The results demonstrated that oral administration of FB2 significantly exacerbated psoriatic symptoms, including skin thickness, itching behavior, transepidermal water loss, immune cell infiltration in the dermis, and proinflammatory cytokine production. However, no changes were observed following exposure to FB1. Our results confirm that oral exposure to FB2 adversely affects the pathogenesis of psoriasis by increasing skin thickness and impairing barrier function.

This study investigated the immunotoxic effects of the mycotoxin nivalenol (NIV) using antigen-presenting cells and a mouse model of atopic dermatitis (AD). In vitro experiments were conducted using a mouse macrophage cell line (RAW 264.7) and mouse dendritic cell line (DC 2.4). After cells were exposed to NIV (0.19-5 µmol) for 24 h, the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNFα) was quantified. To further investigate the inflammatory cytokine production pathway, the possible involvement of mitogen-activated protein kinase (MAPK) pathways, such as ERK1/2, p-38, and JNK, in NIV exposure was analyzed using MAPK inhibitors and phosphorylation analyses. In addition, the pro-inflammatory effects of oral exposure to NIV at low concentrations (1 or 5 ppm) were evaluated in an NC/Nga mouse model of hapten-induced AD. In vitro experiments demonstrated that exposure to NIV significantly enhanced the production of TNFα. In addition, it also directly induced the phosphorylation of MAPK, indicated by the inhibition of TNFα production following pretreatment with MAPK inhibitors. Oral exposure to NIV significantly exacerbated the symptoms of AD, including a significant increase in helper T cells and IgE-produced B cells in auricular lymph nodes and secretion of pro-inflammatory cytokines, such as IL-4, IL-5, and IL-13, compared with the vehicle control group. Our findings indicate that exposure to NIV directly enhanced the phosphorylation of ERK1/2, p-38, and JNK, resulting in a significant increase in TNFα production in antigen-presenting cells, which is closely related to the development of atopic dermatitis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Extramammary Paget's disease (EMPD) is a rare skin cancer that tends to be multicentric, with quadruple EMPD cases being scarcely reported., Case Presentation: We report the case of an 81-year-old man with heterochronous quadruple EMPD. Twelve years after total resection of vulvar EMPD, the patient developed erythematous lesions on the resection margin in the lower abdomen, umbilical region, and both axillae. Histological examination revealed that all lesions were in situ EMPD., Discussion: We reviewed six reported cases of quadruple EMPD with respect to race, sex, site, recurrence, time to recurrence, serum carcinoembryonic antigen, and depth. All patients were elderly Japanese males. In all but one case, the lesions were located in the apocrine region, which is a common site in such as the genital and axillary areas. Our case was the only heterochronous quadruple EMPD. The lesions were limited to the epidermis; therefore, they were unlikely to cause metastasis. It has been reported that the therapeutic effects of imiquimod can be expected in in situ EMPD. Therefore, quadruple EMPD may be a good indication of treatment option., Conclusion: EMPD is a disease whose pathogenesis is not yet clear; however, it is hoped that the origin and aetiology of EMPD will be elucidated from the clinical features of multiple EMPD in the future., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Cardiac magnetic resonance imaging (CMR) often shows discrepancies between right ventricular outflow tract (RVOT) flow and left ventricular outflow tract flow in patients with late-stage repaired tetralogy of Fallot (rTOF), leading to potential errors in pulmonary regurgitation fraction (PRF) assessment. This study aimed to identify the conditions under which RVOT flow can be acutely evaluated using four-dimensional (4D) flow CMR. Twenty-seven consecutive patients with rTOF underwent both two-dimensional phase-contrast (2D PC) and 4D flow CMR between 2016 and 2018, excluding those with peripheral pulmonary artery stenosis, RVOT conduit replacement, unknown surgical method, and an aortic valve regurgitation greater than 20%. Seven healthy controls also underwent only 4D Flow CMR. All healthy controls and fifteen patients with rTOF showed laminar RVOT flow, while seven patients exhibited helical, and four patients exhibited vortical RVOT flow in 4D flow CMR visualization. Flow-volume concordance between the pulmonary artery and aortic flow was significantly lower in patients with rTOF and PRF > 40% in 2D PC CMR. This concordance rate in the suprapulmonary valve was high in both the TOF and control groups, comparing at five RVOT locations in 4D flow CMR. Regarding RVOT flow regurgitation in 4D flow, the whole bulk evaluation exhibited greater variation depending on the flow type compared to the whole pixel-wise evaluation. The study confirmed the flow volume at the upper section of the pulmonary valve as the most accurate correlate of aortic flow volume. Furthermore, the 4D flow CMR using the pixel-wise method demonstrated superior accuracy compared to the traditional bulk flow method., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

In dogs, Porphyromonas gulae is a major periodontal pathogen with 41-kDa proteins polymerizing to form a filamentous structure called fimbriae or pili, termed FimA. FimA is classified into three genotypes: A, B, and C, and there are combinations of types A, B, C, A/B, A/C, B/C, and A/B/C. Periodontal disease is the most common oral disease in small dogs, but the periodontal disease status and P. gulae colonization at each dog age and breed remain unclear. In this study, we stratified 665 small dogs and analyzed the periodontal status and distribution of P. gulae with each FimA genotype. Dogs with periodontal disease and FimA genotype tended to increase with age. The dogs with at least one FimA genotype had significantly more severe periodontal disease compared with P. gulae-negative dogs (P < 0.01). Additionally, periodontal status was significantly associated with specific FimA genotype distribution in Toy Poodles and Chihuahuas (P < 0.05), whereas there was no such association in Dachshunds. These results suggest that the onset of periodontal disease and P. gulae colonization are related and progress with age. The relationship between periodontal disease and FimA genotype may differ depending on the dog breeds., (© 2024. The Author(s).)

Ozone gas is widely used in hospitals as well as homes to control COVID-19 infection owing to its cost-effectiveness. Safety standard value and the tolerable value of ozone gas are set at 0.05 ppm and 0.1 ppm, respectively, in developed countries; however, this value was principally determined for healthy individuals, and the risks associated with ozone gas inhalation in patients with pulmonary diseases remains unknown. Recently, we demonstrated that 0.1 ppm ozone gas exposure significantly aggravates the symptoms of acute lung injury in mice. In the present study, we further examined the influence of ≤ 0.1 ppm ozone gas exposure on percutaneous oxygen saturation (SpO 2 ) and pro-inflammatory responses in a mouse model of asthma. Female BALB/c mice were subjected to repetitive intranasal sensitization of Dermatophagoides farinae to generate a mouse model of asthma. Inhalation exposure of ozone gas (0.1, 0.03, 0.01 ppm), generated using an ultraviolet lamp, was performed for five consecutive days immediately before the final sacrifice. There were no abnormal findings in control mice exposed to 0.1 ppm ozone; however, 0.1 ppm ozone exposure significantly reduced the SpO 2 level in asthmatic mice. Histological evaluation and gene expression analysis revealed that pro-inflammatory cytokine levels were significantly increased in mice exposed to 0.1 ppm ozone, indicating that 0.1 ppm ozone exposure affects the development of asthma symptoms. Notably, 0.03 and 0.01 ppm ozone exposure did not have any effects even in asthmatic mice. Our findings indicate that the tolerable level of ozone gas should be adjusted for individuals based on a history of respiratory disorders., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Currently, ozone water is utilized for antibacterial and antiviral purposes without any reported safety concerns. Therefore, ozone water may have clinical applications in treating staphylococcal-specific cutaneous diseases, such as atopic dermatitis (AD) and pyoderma. This study aimed to verify the bactericidal effects of ozone water at different concentrations (3 and 11 mg/L) against staphylococcal species in vitro, as well as evaluate the anti-inflammatory effects of ozone water in a mouse model of AD and pyoderma. Initially, the bactericidal properties of several concentrations of ozone water were confirmed with Staphylococcus aureus and methicillin-resistant S. pseudintermedius. Both 3 and 11 mg/L of ozone water exhibited a significant bactericidal effect against staphylococci at less than 100 times dilution. We next examined the cellular cytotoxicity and cytokine production (Interleukin (IL)-6 and IL-8) induced by S. pseudintermedius pre-treated with ozone water, and our findings indicated that cytotoxicity and cytokine production induced by staphylococci were significantly inhibited after ozone water pre-treatment. In vivo experiments showed that ozone water-pre-treated S. pseudintermedius significantly inhibited the development of pyoderma in mice; however, limited effects were observed in a therapeutic setting. Interestingly, ozone water at concentrations of 3 and 11 mg/L exhibits dual bactericidal and anti-inflammatory effects in mice with AD. This observation was corroborated by the significant inhibition of cytokine production in interferon-γ/tumor necrosis factor-stimulated human epidermal keratinocyte cells exposed to ozone in vitro. These findings indicate that administering ozone can be a novel therapeutic approach for managing allergic skin diseases, such as AD., 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 © 2023 Elsevier B.V. All rights reserved.)

Contamination with fumonisins produced by Fusarium spp. is rapidly growing in both developing and developed countries. The purpose of this study was to determine whether oral exposure to fumonisin contributed to the development of allergic diseases. We initially examined the immunotoxic potential of short-term, oral administration of fumonisin B1 (FB1, 1 mg/kg) and fumonisin B2 (FB2, 1 mg/kg), both naturally occurring fumonisins, using a BALB/c mouse model of allergic contact dermatitis and Dermatophagoides farina-induced asthma. Using an NC/nga mouse model of atopic dermatitis (AD), we evaluated the adverse effects of subchronic oral exposure to low concentrations of FB2 (2 or 200 μg/kg). Finally, we explored the influence of FB2 on regulatory T cell proliferation and function in mesenteric lymph nodes after 1-week oral exposure to FB2 in BALB/c mice. Oral exposure to FB2 markedly exacerbated the symptoms of allergy, including skin thickness, histological evaluation, immunocyte proliferation, and proinflammatory cytokine production, although no change was observed following exposure to FB1. Furthermore, oral exposure to low concentrations of FB2 considerably exacerbated the AD scores, skin thickness, transepidermal water loss, histological features, and proinflammatory cytokine production. The aggravated allergic symptoms induced by oral exposure to FB2 could be attributed to the direct inhibition of IL-10 production by regulatory T cells in mesenteric lymph nodes. Our findings indicate that the recommended maximum fumonisin level should be reconsidered based on the potential for allergy development., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Citrinin, a mycotoxin produced by Penicillium citrinum and Penicillium verrucosum, mainly contaminates cereals. The aim of study was to investigate the novel immunoreactive effect of citrinin using a mouse model of psoriasis. A mouse model of psoriasis was generated by topical application of 5% imiquimod in female BALB/c mice. Standard rodent diet and rice samples with 3 ppm of citrinin were mixed to obtain a final citrinin concentration of 0.3 ppm, and a citrinin-contaminated diet was fed to mice daily. Skin thickness, scratching behavior, and trans epidermal water loss (TEWL) were monitored continuously during the imiquimod application. Immediately after the final imiquimod application, ear skin and auricular lymph node (LN) were sampled for further analysis. Only a slight increase was observed in skin thickness in the citrinin exposure group; however, citrinin exposure significantly exacerbated hyperkeratinization and inflammatory cell infiltration in histological evaluation. TEWL, which is representative of cutaneous barrier function, was significantly increased by citrinin exposure. In terms of immune function, the number of immune cells in LN (T cells and dendritic cells) and gene expression of interleukin (IL)-17 in skin tissue were significantly increased by citrinin exposure. Direct interaction of dendritic cells (DCs) in citrinin-induced psoriasis development was further examined by proinflammatory cytokine determination in THP-1 cells and murine bone marrow derived DCs. IL-6 and/or tumor necrosis factor α were significantly increased by citrinin exposure. Taken together, our results imply that oral exposure to citrinin exacerbates the symptoms of a mouse model of psoriasis via direct activation of DCs., (© 2023 John Wiley & Sons Ltd.)

Previous research has demonstrated that Porphyromonas gulae (P. gulae) significantly contributes to the development of periodontal disease in dogs. Porphyromonas gulae is divided into three subtypes according to the 41-kDa filamentous appendage ( fimA ), defined as types A, B, and C. This study aimed to elucidate the association between fimA type of P. gulae with the number of permanent teeth, reflecting the severity of periodontal disease. Two hundred twenty-five dogs were categorized by P. gulae fimA type as negative, type A dominant, type B dominant, and type C dominant. The stage of periodontal disease in P. gulae -positive dogs increased with age, particularly in type C dominant dogs. Correspondingly, the number of permanent teeth in P. gulae fimA type C-dominant dogs was significantly lower than that of P. gulae -negative dogs, suggesting there is a significant association between fimA type of P. gulae and the number of permanent teeth resulting from the development of periodontal disease., Competing Interests: NI was employed by Bioalchemis. JY was employed by SPECTRUM LAB. JAPAN Co., LTD. HY was employed by AlphaVets Co., LTD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shirahata, Iwashita, Sasaki, Nomura, Murakami, Yasuda, Yasuda, Nakajima, Inaba, Matsumoto-Nakano, Nakano, Uchiyama and Fukuyama.)

Background: The Patterns of Activity Measure-Pain (POAM-P) is a self-report questionnaire that measures avoidance, overdoing, and pacing in individuals with chronic pain. We aimed to develop and confirm the psychometric properties of the Japanese version of the POAM-P(POAM-P-J) in Japanese individuals with chronic pain., Methods: We recruited 147 Japanese individuals with chronic pain (106 women; mean age 64.89 ± 12.13 years). The individuals completed the POAM-P-J, the Brief Pain Inventory (BPI), and the Hospital Anxiety and Depression Scale (HADS). The following psychometric properties of the POAM-P-J were confirmed: structural validity, internal consistency, test-retest reliability, and concurrent validity., Results: We tested factor structure via confirmatory factor analyses (CFA). We chose the 3-factor model with six covariances. The POAM-P-J's internal consistency and test-retest reliability were acceptable to good (α = 0.79-0.86; ICC = 0.72-0.87). The avoidance and overdoing subscales were positively associated with pain severity, pain interference, and anxiety measures (all p < 0.05), but the pacing subscale was not significantly associated with these pain-related measures., Conclusions: Although the structural validity of the POAM-P-J remains questionable, its internal consistency, test-retest reliability, and concurrent validity were confirmed. The POAM-P-J is useful in both research and clinical practice for evaluating the activity patterns of Japanese patients with chronic pain., (© 2022. The Author(s).)

Background: Cell-free and concentrated ascites reinfusion therapy (CART) is a strategy for improving various intractable symptoms due to refractory ascites, including hypoalbuminemia. CART has recently been applied in the treatment of cancer patients. This study was performed to assess the safety of CART in a single cancer institute., Methods: We retrospectively reviewed 233 CART procedures that were performed for 132 cancer patients in our institute., Results: The median weight of ascites before and after concentration was 4,720 g and 490 g (median concentration rate, 10.0-fold), The median amounts of total protein and albumin were 64.0 g and 32.6 g (median recovery rates, 44.9% and 49.0%), respectively. Thirty-three adverse events (AEs) were observed in 22 (9.4%) of 233 procedures; 30 of these events occurred after reinfusion. The most common reinfusion-related AEs were fever (13 events) and chills (10 events). Univariate analyses revealed no significant relationships between the frequency of AEs and age, sex, appearance of ascites, weight of harvested and concentrated ascites, the ascites processing rate (filtration and concentration), weight of saline used for membrane cleaning, amount of calculated total protein for infusion, or prophylaxis against AEs; the reinfusion rate of ≥ 125 mL/h or ≥ 10.9 g/h of total protein affected the frequency of AEs, regardless of the prophylactic use of steroids., Conclusions: The observed AEs were mainly mild reactions after reinfusion, which were related to a reinfusion rate of volume ≥ 125 mL/h, a simple indicator in practice, or total protein ≥ 10.9 g/h. Although our study was retrospective in nature and undertaken in a single institute, this information may be helpful for the management of cancer patients with refractory malignant ascites using CART., (© 2022. The Author(s).)

Streptococcus mutans, a major pathogen of dental caries, is also known as a causative agent of cardiovascular disease. A 120 kDa collagen-binding protein (Cnm) of S. mutans is an important contributor to the pathogenicity of cardiovascular disease. Although dead bacteria have been detected in cardiovascular specimens by molecular biological methods, the pathogenicity of the bacteria remains unknown. Here, we analyzed the pathogenicity of killed S. mutans by focusing on collagen-binding ability and the effects on silkworms. In live S. mutans, Cnm-positive S. mutans had high collagen-binding activity, while Cnm-negative S. mutans had no such activity. After treatment with killed Cnm-positive S. mutans, amoxicillin-treated bacteria still had collagen-binding ability, while lysozyme-treated bacteria lost this ability. When live and amoxicillin-treated S. mutans strains were administered to silkworms, the survival rates of the silkworms were reduced; this reduction was more pronounced in Cnm-positive S. mutans infection than in Cnm-negative S. mutans infection. However, the administration of any of the lysozyme-treated bacteria did not reduce the survival rate of the silkworms. These results suggest that amoxicillin-killed Cnm-positive S. mutans strains maintain collagen-binding properties and pathogenicity in the silkworm model, and are possibly associated with pathogenicity in cardiovascular diseases., (© 2022. The Author(s).)

Surface pre-reacted glass-ionomer (S-PRG) filler is a bioactive functional glass that releases six different ions. Although several dental materials containing S-PRG filler have been developed, few self-care products containing S-PRG filler have been reported. We investigated the inhibitory effects of PRG gel paste containing S-PRG filler on Streptococcus mutans, a major pathogen of dental caries. PRG gel paste inhibited bacterial growth of S. mutans in a concentration-dependent manner, and all S. mutans were killed in the presence of ≥ 1% PRG gel paste. Additionally, it was difficult for S. mutans to synthesize insoluble glucan from sucrose in the presence of 0.1% PRG gel paste. A biofilm formation model was prepared in which slices of bovine enamel were infected with S. mutans after treatment with or without PRG gel paste. Biofilm formation was inhibited significantly more on the enamel treated with PRG gel paste than on enamel without PRG gel paste (P < 0.001). The inhibitory effects on bacterial growth and biofilm formation were more prominent with PRG gel paste than with S-PRG-free gel paste, suggesting that PRG gel paste may be effective as a self-care product to prevent dental caries induced by S. mutans., (© 2021. The Author(s).)

Background: As the number of patients with skin allergies, including atopic dermatitis, has increased rapidly, therapeutic options such as anti-IL-31 antibody and Janus kinase inhibitor have been developed recently. However, many concerns remain regarding the adverse effects and cost of these drugs; therefore, development of supplements that could support the effect of therapeutic agents is always required., Purpose: The aim of this study was to develop preventive and supportive options for skin allergies by focusing on a natural product called "Mastic"., Methods: Initially, the anti-inflammatory and anti-pruritic responses of 3% and 30% Mastic topical treatment were investigated in a mouse model of allergic contact dermatitis, generated by topical application of toluene-2,4-diisocyanate (TDI), a hapten that induces type 2 helper T cells. After itch behaviour and ear-swelling response were monitored, serum, auricular lymph nodes, and skin tissues were collected to analyse immunocyte differentiation, cytokine determination, and histological changes., Results: Our findings indicated that topical treatment with mastic significantly ameliorated ear swelling, itch behaviour, immunocyte infiltration, and cytokine production. Histological evaluation confirmed the occurrence of anti-inflammatory responses. The anti-inflammatory and anti-pruritic effects of topical treatment with mastic (3% and 5%) were further confirmed in a mouse model of atopic dermatitis which was generated by topical application of TDI in NC/Nga mice. Thickness of the back skin, AD score, transepidermal water loss (TEWL), and itch behaviour were measured weekly, and immunocyte differentiation, cytokine determination, and histological changes were also analysed. Mastic treatment significantly attenuated the skin thickness, AD score, TEWL, and itch behaviour. Corroborated reduction was observed in the numbers of T cells and IgE-B cells, as well as in pro-inflammatory cytokine production. The reproducibility of the effects of mastic was confirmed with 1% mastic ointment in a setting similar to the AD mouse model. In vitro evaluation of keratinocytes indicated that mastic pre-exposure induced a significant dose-dependent decrease in cytokine production., Conclusion: Our findings thus demonstrate that topical treatment with mastic significantly ameliorate inflammatory and pruritic responses in a mouse model of allergic dermatitis., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Objective: The purpose of this study was to determine the effects of 2-h moderately prolonged exercise with carbohydrate intake or water placebo on salivary and urinary α-amylase isoenzyme activity in trained men., Materials and Methods: Eleven aerobically fit men participated in this study. On two different occasions, participants performed 2-h cycling corresponding to a constant power output at 60% peak oxygen uptake. The study design involved a random order, placebo-controlled and cross-over assignment. Participants consumed either 6.2% carbohydrate solution or water placebo every twenty minutes thereafter (2 ml/kg body mass) over 2-h endurance exercise. Unstimulated whole salivary samples were collected using the passive drooling method at the 10-min period before and after exercise for the quantification of salivary α-amylase, immunoglobulin A (IgA) and total protein. Two-hour urinary samples were obtained at three time points before (-2-0h), immediately (0-2 h) after and 24-26 h after exercise for the analysis of α-amylase isoenzyme activity (pancreas- and saliva-derived types)., Results: The activity of α-amylase in saliva and urine was significantly increased in connect with salivary total protein concentration immediately after moderately long-lasting exercise, but salivary IgA concentration was not statistically significant with or without exogenous carbohydrate intake., Conclusion: These findings suggest that 2-h moderate exercise appears to lead to the enhanced α-amylase activity in saliva and urine regardless of exogenous carbohydrate availability, demonstrating enhanced mucosal immune defense.

Introduction: In autologous peripheral blood stem cell harvest (APBSCH), CD34-positive cells have been measured to assess the numbers of hematopoietic stem cells, but measurement requires specialized equipment. Recently, there was a report that peripheral blood hematopoietic progenitor cells (HPCs) are useful indicators of the presence of hematopoietic stem cells. We examined the usefulness of HPC monitoring to predict APBSCH timing., Methods: We retrospectively analyzed the relationship between HPC and collected CD34-positive cells in 84 consecutive patients who underwent APBSCH., Results: According to the receiver operating characteristics curve for the collection of ≥2 × 106 CD34-positive cells/kg, the HPC cut-off value on the day before collection was 21/μL, while that on the day of collection was 41/μL. No significant factors were found in the univariate analysis except for the HPC count on the day before collection (p < 0.001) and the day of collection (p < 0.001). According to the multivariate analysis, the HPC count on the day before collection (p < 0.001) and the day of collection (p < 0.001) were also factors that strongly influenced the quantity of CD34-positive cells collected., Conclusion: Our results suggest that the HPC count on not only the day of collection but also the day before collection is a good indicator for appropriate APBSCH timing., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We reviewed blood product use in 729 consecutive allogeneic hematopoietic cell transplantation (allo-HCT) recipients at our center to assess the volume of red blood cells (RBCs) and platelets required after allo-HCT. The median number of bags required by day 30 was 4 for RBCs (range 0-22) and 9.5 for platelets (0-53). Multivariate analysis showed that related peripheral blood stem cell transplantation (PBSCT) required a significantly lower RBC transfusion volume by day 30 compared to unrelated bone marrow transplantation (UBMT). PBSCT from haplo-identical related donors and cord blood transplantation (CBT) required a significantly greater RBC transfusion volume. For platelet transfusion, related and unrelated PBSCT required a significantly lower volume than UBMT, and CBT a greater volume. Other factors independently associated with greater RBC transfusion volume were male sex, disease status other than complete remission, and major ABO mismatch. For platelet transfusion, these were male sex, disease status, and HCT-specific comorbidity index of 1. Although the burden of blood transfusions may not be the most important factor when choosing a donor type, our findings may provide a foundation for nationwide strategies to prepare blood products and inform aspects of national healthcare expenditures.

Previously, researchers have demonstrated that mycotoxin deoxynivalenol (DON) significantly enhances immunocyte activation. However, the interaction between DON exposure and immune disorders remains unclear. In this study, we aimed to investigate whether acute and subacute oral exposure to DON exacerbates the development of respiratory allergy using a mite allergen (Dermatophagoides farina, Derf)-induced mouse model of asthma. The direct relationship between DON exposure and asthma development was examined following acute oral DON administration (0, 0.1, or 0.3 mg/kg body weight), immediately before the final mite allergen challenge. Simultaneously, the influence of subacute oral exposure via low dose DON contaminated wheat (0.33 ppm) was evaluated using the same settings. To detect the proinflammatory effects of DON exposure, we examined the total and Derf-specific serum IgE levels, histology, number of immunocytes, and cytokine and chemokine secretion. Acute oral DON significantly enhanced the inflammatory responses, including cellular infiltration into bronchoalveolar lavage fluid, infiltration of immunocytes and cytokine production in local lymph nodes, and cytokine levels in lung tissues. Corresponding proinflammatory responses were observed in a mouse group exposed to subacute oral DON. In vivo results were validated by in vitro experiments using the human bronchial epithelial (BEAS-2B) and human eosinophilic leukemia (EOL-1) cell lines. Following exposure to DON, the secretion of interleukin (IL)-1β, IL-6, IL-8, and/or tumor necrosis factor-α in BEAS-2B cells, as well as EoL-1 cells, increased significantly. Our findings indicate that DON exposure is significantly involved in the proinflammatory response observed in respiratory allergy., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Deoxynivalenol (DON) contamination in food is a public health concern; however, the effect of DON exposure on immune disorders including allergies remains unclear. The aim of this study is to elucidate the effect of oral exposure to DON on pro-inflammatory and pro-pruritic responses in a mouse model of allergic dermatitis, which was generated by topical application of toluene-2,4-diisocyanate (TDI), a hapten that induces type-2 helper T cells. To evaluate acute exposure to DON, the mice were orally administered vehicle alone, 0.1 mg/kg DON, or 0.3 mg/kg DON 48, 24, and 1 h before the final challenge with TDI. To study subacute exposure, the mice were fed DON-contaminated rodent diet (0.3 ppm) during the experimental period. After the itch behavior and ear-swelling response were monitored, the serum, auricular lymph node, and skin tissue were collected for analyzing immunocyte differentiation, cytokine determination, and histological changes. Acute oral administration of DON significantly enhanced pro-inflammatory responses including ear-swelling response, immunocyte infiltration, and cytokine productions. Histological evaluation supported the occurrence of pro-inflammatory responses. In contrast, acute DON exposure only slightly increased itch behavior. Subacute oral exposure to DON significantly up-regulated the inflammatory responses, but showed almost no effect on pruritic response. In vitro evaluation in dendritic cells and keratinocytes indicated that DON pre-exposure induced a dose-dependent significant increase in cytokine production. Our results imply that both acute and subacute exposures to DON are associated with pro-inflammatory responses in cutaneous allergy.

Streptococcus mutans, a significant contributor to dental caries, is occasionally isolated from the blood of patients with infective endocarditis. We previously showed that S. mutans strains expressing collagen-binding protein (Cnm) are present in the oral cavity of approximately 10-20% of humans and that they can effectively invade human umbilical vein endothelial cells (HUVECs). Here, we investigated the potential molecular mechanisms of HUVEC invasion by Cnm-positive S. mutans. The ability of Cnm-positive S. mutans to invade HUVECs was significantly increased by the presence of serum, purified type IV collagen, and fibrinogen (p < 0.001). Microarray analyses of HUVECs infected by Cnm-positive or -negative S. mutans strains identified several transcripts that were differentially upregulated during invasion, including those encoding the small G protein regulatory proteins ARHGEF38 and ARHGAP9. Upregulation of these proteins occurred during invasion only in the presence of serum. Knockdown of ARHGEF38 strongly reduced HUVEC invasion by Cnm-positive S. mutans. In a rat model of infective endocarditis, cardiac endothelial cell damage was more prominent following infection with a Cnm-positive strain compared with a Cnm-negative strain. These results suggest that the type IV collagen-Cnm-ARHGEF38 pathway may play a crucial role in the pathogenesis of infective endocarditis.

Our recent study has reported that estrogen receptors (ERs) are involved in several types of allergy development. This study aims to investigate the possible relationship between ER activation and development of imiquimod-induced psoriasis-like dermatitis. A mouse model of imiquimod-induced psoriasis-like dermatitis was generated by 5 days of topical application of 5% of imiquimod cream on the back of the ear and the shaved back skin of male BALB/c mice. From the second day of applying 5% imiquimod cream, either ERα selective agonist (propylpyrazoletriol [PPT] 2.5 mg/kg) or ERβ selective agonist (diarylpropionitrile, DPN; 2.5 mg/kg) was administered orally for four consecutive days. Immediately after the final imiquimod cream application, scratching behavior was video monitored for 2 hours. The ear-swelling response was determined by comparing ear thickness before and after the final application of imiquimod cream. Twenty-four hours after the final imiquimod application, back skin tissue and auricular lymph nodes were isolated under isoflurane anesthesia. Oral administration of PPT significantly induced itch behavior and proinflammatory responses, including the levels of interleukin (IL)-17 and IL-22, whereas DPN treatment did not influence either pruritic or proinflammatory responses. In addition, IL-23 contribution by dendritic cells was identified using ER agonists on pretreated lipopolysaccharide (LPS)-stimulated murine bone marrow derived dendritic cells (BMDCs). PPT also significantly enhanced IL-23 secretion by LPS-stimulated BMDCs. Our findings indicate that the activation of ERα, but not ERβ, is directly associated with inflammatory and pruritic responses in a mouse model of the imiquimod-induced psoriasis by enhancing the secretion of IL-23 by dendritic cells., (© 2020 John Wiley & Sons, Ltd.)

Helicobacter pylori is presumed to infect gastric tissue via the oral cavity in childhood, whereas risk factors for H. pylori infection in the oral cavity are unknown. In this study, we analysed the effects of Streptococcus mutans, a major cariogenic bacterial species, on H. pylori colonisation in the oral cavity, as well as gastric tissue. Rats in the weaning period were infected with S. mutans in the oral cavity, then fed a caries-inducing diet to facilitate S. mutans colonisation. One month after S. mutans infection, rats were infected with H. pylori in the oral cavity; rats were then euthanised at 1 month after H. pylori infection. H. pylori was detected in the oral cavities of rats infected with both S. mutans and H. pylori, but not in rats infected with H. pylori alone. In addition, H. pylori colonisation in the gastric tissue and typical gastrointestinal damage were observed in rats infected with both S. mutans and H. pylori. When H. pylori was co-cultured with in vitro biofilm formed by S. mutans, a large number of H. pylori bacteria invaded the biofilm formed by S. mutans. Our results suggest that S. mutans is involved in the establishment of H. pylori infection.

Porphyromonas gulae is a major periodontal pathogen in dogs, which can be transmitted to their owners. A major virulence factor of P. gulae consists of a 41-kDa filamentous appendage (FimA) on the cell surface, which is classified into three genotypes: A, B, and C. Thus far, inhibition of periodontal disease in dogs remains difficult. The present study assessed the inhibitory effects of a combination of clindamycin and interferon alpha (IFN-α) formulation against P. gulae and periodontal disease. Growth of P. gulae was significantly inhibited by clindamycin; this inhibition had a greater effect on type C P. gulae than on type A and B isolates. In contrast, the IFN-α formulation inhibited the expression of IL-1β and COX-2 elicited by type A and B isolates, but not that elicited by type C isolates. Furthermore, periodontal recovery was promoted by the administration of both clindamycin and IFN-α formulation to dogs undergoing periodontal treatment; moreover, this combined treatment reduced the number of FimA genotypes in oral specimens from treated dogs. These results suggest that a combination of clindamycin and IFN-α formulation inhibit P. gulae virulence and thus may be effective for the prevention of periodontal disease induced by P. gulae.

An 18-year-old male who had a past medical history of an intracardiac total cavopulmonary connection (TCPC) operation was referred to our hospital for radiofrequency catheter ablation (RFCA) of supraventricular tachycardia (SVT). Two types of SVTs were induced, and 3-dimensional (3D) maps were created using an ultra-high-density 3-dimensional mapping system (Rhythmia). The earliest atrial activation site (EAAS) of SVT1 was at the superior part of the conduit, and the EAAS of SVT2 was at the inferior part of the single atrium (SA). The SVTs were terminated by energy deliveries to the EAAS from the conduit in SVT1 and from inside the single atrium in SVT2. Detailed maps of the SVTs were important to understand the mechanisms of the SVTs. The Rhythmia system was useful for the detailed mapping of complex arrhythmias. The use of Rhythmia in patients after a TCPC is difficult, because puncturing the TCPC conduit and proceeding and manipulating the Orion catheter via a narrow puncture hole are difficult. We were the first to succeed in ablating two atrial tachycardias (ATs) originating from the inside and outside of the conduit after a TCPC operation by using an ultra-high-density 3-dimensional mapping system.

Objectives: The Multidimensional Pain Readiness to Change Questionnaire 2 (MPRCQ2) is a reliable and valid measure that assesses readiness to adopt a variety of discrete pain self-management responses. We sought to translate and evaluate psychometric properties of the Japanese version of the MPRCQ2 (MPRCQ2-J) in individuals with chronic pain., Methods: One hundred seventy-three individuals with chronic pain were asked to complete the MPRCQ2-J, as well as measures assessing pain intensity, pain interference, self-efficacy, and general readiness to adopt a self-management approach for pain. Forty-eight of these participants provided additional MPRCQ2-J data to assess test-retest reliability., Results: The findings supported a 2-factor structure of the MPRCQ2-J when error covariances between the some of the nine primary scales were allowed. Adequate internal consistencies of the MPRCQ2-J scales (Cronbach's α ranged 0.71 to 0.86), except for the total score (α = 0.68), were observed. However, adequate test-retest reliabilities (intraclass correlation coefficients ≥ 0.60) were found for only 59% of the MPRCQ2-J scales. The MPRCQ2-J evidenced its construct validity via confirmation of the predicted patterns of associations with validity criterion measures and the anticipated effects of participation in an exercise treatment., Discussion: The findings support the internal consistency (except for the total score) and construct validity for MPRCQ2-J scales. However, potential limitations with respect to test-retest reliability of some of the scales were also suggested. The MPRCQ2-J can be used to examine the role that specific readiness domains of pain self-management responses may play in an adjustment process in Japanese individuals with chronic pain., (© 2019 World Institute of Pain.)

Background: A new mapping system (Rhythmia) using a 64 mini-electrode small basket array (Orion) was developed that enables rapid high-density mapping in a short time. However, there are few reports about the usefulness of this system in pediatric cases., Objective: The purpose of this study was to investigate the safety and accuracy of the Rhythmia system and Orion catheter in children., Methods: Catheter ablation was performed using the Rhythmia system and Orion catheter in 23 patients younger than 20 years (body weight >20 kg) without a past medical history of cardiac disease. Mapping time, number of mapping beats, and number of mapping electrodes were compared for left atrium, right atrium and right ventricular outflow tract., Results: Twenty-three maps of the right atrium were acquired in 12.6 minutes (range 8.9-15.1), consisting of 709 beats (range 492-1163) and 7132 electrograms (range 4618-10,533). Twelve maps of the left atrium were acquired in 12.1 minutes (range 9.8-14.6), consisting of 565 beats (range 446-881) and 6412 electrograms (range 4912-11,402). There were no significant difference in mapping time, accepted beats, and electrograms between the 2 chambers. Manual annotation was needed in 53 of 293,185 electrograms (0.01%) due to far-field ventricular electrogram sensing and artifact. No adverse events occurred in any of the cases., Conclusion: The Orion catheter and Rhythmia mapping system were safe and accurate for mapping various arrhythmias in pediatric patients. Detailed geometry and high-resolution activation mapping were acquired without the need for manual reannotation., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Although evidence supports efficacy of treatments that enhance self-management of chronic pain, the efficacy of these treatments has been hypothesized to be influenced by patient readiness for self-management. The Pain Stage of Change Questionnaire (PSOCQ) is a reliable and valid measure of patient readiness to self-manage pain. However, there is not yet a Japanese version of the PSOCQ (PSOCQ-J), which limits our ability to evaluate the role of readiness for pain self-management in function and treatment response in Japanese patients with chronic pain., Objective: Here, we sought to develop the PSOCQ-J and evaluate its psychometric properties., Methods: We recruited 201 patients with chronic pain. The study participants were asked to complete the PSOCQ-J and other measures assessing pain severity, pain interference, catastrophizing, self-efficacy, and pain coping strategies., Results: The results supported a 4-factor structure of the PSOCQ-J. We also found good to excellent internal consistencies and good test-retest reliabilities for the 4 scales. The Precontemplation scale had weak to moderate positive correlations with measures of pain-related dysfunction and maladaptive coping. The Action and Maintenance scales had weak to moderate positive correlations with measures of self-efficacy and adaptive coping. The Contemplation scale had weak positive correlations with measures of pain interference and both adaptive and maladaptive coping., Conclusions: The PSOCQ-J demonstrated adequate psychometric properties in a sample of Japanese patients with chronic pain. This measure can be used to evaluate the role that readiness to self-manage pain may play in adjustment to chronic pain in Japanese pain populations., Competing Interests: Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Porphyromonas gulae, a Gram-negative black-pigmented anaerobe, is one of several major periodontal pathogens of animals. P. gulae isolates from dogs have been classified into three genotypes based on a 41-kDa filamentous appendage (FimA) on the cell surface, which is closely related to virulence in periodontal disease. However, other specific bacterial virulence factors contributing to the aggravation of periodontal disease in cats remain elusive. In the present study, we assessed FimA diversity in P. gulae isolates from cats and examined whether this diversity influenced periodontal condition. The putative amino acid sequences of FimA from 15 P. gulae isolates from 13 cats were classified into three genotypes (types A, B, and C), which showed 95-100% identity and similarity to the fimA types in dogs. The type C isolate showed greater adhesion and invasion properties in periodontal ligament fibroblasts as well as stronger inhibition of scratch closure of the cells compared with type A and B isolates. Next, a PCR-based method for identification of fimA genotype was developed and used to analyze 99 oral swab specimens from cats. High fimA type A detection rates were observed regardless of the periodontal condition, whereas types B and C were frequently detected from subjects with moderate and severe periodontitis, respectively. These results suggest that P. gulae isolates from cats can be classified into three types based on fimA genotype, which may be closely related to virulence in periodontitis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A 74-year-old woman was found to have a hepatic mass based on CT findings. She was diagnosed as having cecum cancer, and it was difficult to distinguish whether the hepatic mass was liver metastasis or biliary cystadenocarcinoma. We proceeded with the surgery for cecum cancer, and laparoscopic ileocecal resection with D3 lymph node dissection was performed. The histopathological diagnosis was mucinous adenocarcinoma, and the pathological stage was T3N2H1P0M1a, Stage IV. After the surgery, her CEA level was elevated, and we diagnosed the hepatic mass as a liver metastasis. A CapeOX plus bevacizumab regimen was administered but was discontinued for 2 courses due to the development of adverse effects and her decision. Gd-EOB-DTPA-enhanced MRI revealed a multilocular and lobulated mass, which was a low-intensity area in T1WI and high-intensity area in T2WI, and the mass had no significant contrast effects. These images were unspecific for liver metastasis of colorectal cancer, and we performed segmental 6 hepatectomy for diagnosis and curative surgery. A histopathological diagnosis of liver metastasis of cecum cancer was made. Here, we report a case of liver metastasis of colorectal cancer that was undifferentiated from biliary cystadenocarcinoma.