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日本における小児PCV13導入後2014年-2018年の成人肺炎球菌性髄膜炎
Get PDFWe assessed the impact of the pediatric 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis in adults in Japan in 2014–2018 by comparing epidemiological characteristics of adults with invasive pneumococcal disease with (n = 222) and without (n = 1258) meningitis. The annual incidence of pneumococcal meningitis in 2016–2018 was 0.20–0.26 cases/100,000 population. Age (p < 0.001) and case fatality rate (p = 0.003) were significantly lower in patients with meningitis than in those without meningitis. The odds of developing meningitis were higher in asplenic/hyposplenic or splenectomized patients (adjusted odds ratio [aOR] 2.29, 95% CI 1.27–4.14), for serotypes 10A (aOR 3.26, 95% CI 2.10–5.06) or 23A (aOR 3.91, 95% CI 2.47–6.19), but lower for those aged ≥ 65 years (aOR 0.59, 95% CI 0.44–0.81). PCV13 had an indirect effect on nonmeningitis, but its impact on meningitis was limited because of an increase in non-PCV13 serotypes. Of meningitis isolates, 78 (35.1%) and 3 (1.4%) were penicillin G- or ceftriaxone-resistant, respectively. We also confirmed an association of the pbp1bA641C mutation with meningitis (aOR 2.92, 95% CI 1.51–5.65).権利情報：© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/
日本人HIV感染者集団における腸内細菌叢と有機酸プロファイルの関連性
Get PDFIntroduction: An increased incidence of metabolic syndrome has been observed in human immunodeficiency virus (HIV)-infected individuals. In contrast, gut dysbiosis is involved in various pathogeneses, including vascular endothelial disorders. Organic acids, including short-chain fatty acids (SCFAs), are essential for maintaining gut homeostasis. Therefore, this study aimed to explore the gut microbiome profile and organic acids in a Japanese population infected with HIV. Methods: Forty-nine patients with HIV infection on combination antiretroviral therapy (cART) were enrolled and divided into the high and low CD4 groups based on a CD4 cutoff of 350 cells/μL. Stool samples were analyzed by 16S ribosomal RNA next-generation sequencing and high-performance liquid chromatography. The association between the gut microbiome, including bacterial taxa and organic acids, was statistically analyzed. Results: The fecal microbial community composition was significantly different between HIV patients with CD4 counts above and below 350 cells/μL. The relative abundance of Roseburia, Prevotella, Prevotella_9, and [Clostridium]_methylpentosum_group were significantly enriched in the high CD4 group. Fecal succinic acid tended to be more abundant in the low CD4 group, and acetic, propionic, and butyric acids tended to be more abundant in the high CD4 group. Roseburia was positively correlated with butyric acid levels. Prevotella_9 and Prevotella were negatively correlated with succinic acid levels and positively correlated with acetic and propionic acid levels. Conclusions: This study showed intestinal dysbiosis bordering on a CD4 count of 350 in patients with HIV infection undergoing cART. These findings might help in understanding intestinal damage and systemic inflammation in HIV infection.権利情報：© 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved
自閉スペクトラム症の成人における感覚処理異常と事象関連電位との関連についての予備的観察
Get PDFAim: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is thought to involve a variety of neurophysiological characteristics. Event-related potentials (ERPs) reflect cognitive functions in the brain's cognitive processing. In this study, we investigated differences in P300 and N100 of ERPs between ASD and typically developing groups and focused on the relationship between the components of ERPs and measures of autistic traits and sensory processing characteristics. Methods: ERPs were measured in 96 subjects in the ASD group and 62 subjects in the age- and sex-adjusted typically developing group. Correlations between each component and the scores of the Autism-Spectrum Quotient Japanese version (AQ-J) and the Adolescent and Adult Sensory Profile (AASP) were also evaluated. Results: The ASD group showed a significant decrease in the amplitude of N100 at C3. Furthermore, a negative correlation was found between lower amplitude at C3 of N100 and low registered sensory scores in both groups. Conclusion: Our findings imply that the N100 amplitude at C3 could be a potential indicator for examining the neurophysiological traits of ASD; however, these results should be interpreted with caution due to their preliminary nature. These tentative insights into sensory processing anomalies may be discernible in specific subsets of the ASD population, providing a foundation for future investigative pathways.権利情報：© 2024 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes
Roles of the creatine shuttle in colorectal cancer
No full textThe creatine shuttle is a system that transfers energy generated by oxidative phosphorylation to the cytoplasm by phosphorylating creatine with mitochondrial vreatine kinase (MTCK) and dephosphorylating phosphocreatine with creatine kinase B (CKB) in the cytoplasm. The relevance of this system to cancer has not been clear. The creatine shuttle not only transports ATP generated in the mitochondria to the cytoplasm as phosphocreatine, but also provides ATP that causes phosphorylation in multiple phosphorylation signal systems. By inhibiting these two functions of the creatine shuttle, it is possible to suppress the progression of cancer and the development of cancer stem cells
ADAMTS4は急性呼吸窮迫症候群においてグリコカリックスを介した肺血管透過性亢進を制御する
Get PDFAcute respiratory distress syndrome (ARDS) has no specific and effective treatment, and there is an urgent need to understand its pathogenesis. Therefore, based on the hypothesis that molecules whose expression is upregulated in injured pulmonary vascular endothelial cells (VECs) are involved in the pathogenesis of ARDS, we conducted a study to elucidate the molecular mechanisms and identify target factors for treatment. Primary human lung microvascular endothelial cells (HMVEC-Ls) were stimulated with lipopolysaccharide (LPS) or poly (I:C) and analyzed via a microarray to identify target genes for ARDS. We found that a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) was induced in murine lung VECs in an LPS-mediated ARDS model. Elevated ADAMTS4 was also observed by the immunostaining of lung samples from ARDS patients. The suppression of ADAMTS4 by siRNA in VECs ameliorated LPS-stimulated vascular permeability. The impairment of the cell surface expression of syndecan-1, a marker of the glycocalyx that is an extracellular matrix involved in vascular permeability, was dramatically inhibited by ADAMTS4 suppression. In addition, the suppression of ADAMTS4 protected against LPS-induced reductions in syndecan-1 and the adherens junction protein vascular endothelial cadherin. These results suggest that ADAMTS4 regulates VEC permeability in ARDS and may be a predictive marker and therapeutic target for ARDS.権利情報：© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)
日本人変形性膝関節症高齢者における転倒歴と足指把持力の関連性: 横断的研究
Get PDFBackground: Knee osteoarthritis (KOA), one of the most common musculoskeletal diseases in older adults, is associated with a high incidence of falls. Similarly, toe grip strength (TGS) is associated with a history of falls in older adults; however, the relationship between TGS and falls in older adults with KOA who are at risk of falling is not known. Therefore, this study aimed to determine if TGS is associated with a history of falls in older adults with KOA. Methods: The study participants, older adults with KOA scheduled to undergo unilateral total knee arthroplasty (TKA), were divided into two groups: non-fall (n = 256) and fall groups (n = 74). Descriptive data, fall-related assessments, modified Fall Efficacy Scale (mFES), radiographic data, pain, and physical function including TGS were evaluated. The assessment was conducted on the day before performing TKA. Mann–Whitney and chi-squared tests were performed to compare the two groups. Multiple logistic regression analysis was performed to determine the association of each outcome with the presence or absence of falls. Results: Mann-Whitney U test revealed that the fall group had statistically significantly lower height, TGS on the affected and unaffected sides, and mFES. Multiple logistic regression analysis revealed that the incidence of fall history is associated with TGS on the affected side; the weaker the affected TGS of the KOA, the more likely the individual is to fall. Conclusions: Our results indicate that TGS on the affected side is related to a history of falls in older adults with KOA. The significance of evaluating TGS among patients with KOA in routine clinical practice was demonstrated.権利情報：© 2023 Mawarikado et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
ハイドロキノン曝露による網膜色素上皮細胞のメラニン含量の変化
Get PDFAbnormal pigmentation or depigmentation of the retinal pigment epithelium (RPE) is a precursor to neovascular age-related macular degeneration (nAMD). In this study, we evaluated the effects of hydroquinone (HQ), the most potent reductant in cigarette smoke, on the melanin production in RPE cells. Induced pluripotent stem cell (iPS)-derived RPE and adult retinal pigment epithelial (ARPE-19) cells were cultured with HQ. Real-time reverse transcription polymerase chain reaction revealed that the expression of melanin-related genes decreased due to the addition of HQ for 1 day. Enzyme-linked immunosorbent immunoassay showed that the concentration of melanin significantly decreased due to the addition of HQ for 24 h. A suspension of RPE cells with HQ for 24 h was prepared, and the absorbance was measured. The absorbance decreased particularly under blue light, suggesting that blue light may reach the choroid and cause choroidal inflammation. Additionally, melanin levels significantly decreased due to the addition of HQ for 1 week. After blue light irradiation on the RPE with HQ for 1 week, the vascular endothelial growth factor in the medium was significantly higher in the HQ group than in the control group. HQ-induced changes in melanin production may be responsible for the uneven pigmentation of the RPE, and these changes may cause nAMD.権利情報：© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)
新生児、乳幼児におけるPC経路でのプロテインC、プロテインS、アンチトロンビンの抗凝固作用
Get PDFThe protein C (PC) pathway involves physiological anticoagulant factors (PC, protein S [PS], and factor V) and performs major anticoagulant functions in adults. Variations in the overall PC pathway function due to dynamic changes in PC and PS in early childhood are poorly understood. We aimed to evaluate the contributions of PC pathway function during early childhood by administering protac (a PC activator) and measuring changes in plasma thrombin generation (TG). The correlations between anticoagulant factors and percentage of protac-induced coagulation inhibition (PiCi%) were assessed. Before protac addition, TG in newborns (n=35), infants (n=42), early children (n=35), and adults (n=20) were 525±74, 720±96, 785±53, and 802±64 mOD/min, and the PiCi% were 42.1±9.9, 69.8±11.0, 82.9±4.4, and 86.9±3.4%, respectively. The distribution of PiCi% on the two axes of TG (with or without protac) continuously changed with age and differed from that of warfarin-treated plasma or adult PC- or PS-deficient plasma. PiCi% increased dynamically during infancy and correlated with PS levels in newborns and PC levels in young children. Increment of PC or fresh frozen plasma equivalent to approximately 25% PC in PC-deficient plasma improved PiCi%. This automatic measurement requiring a small sample volume is useful for the analysis of developmental hemostasis.権利情報：© Japanese Society of Hematology 2024. This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s10157-023-02433-
肝細胞癌に対する肝動脈化学塞栓術前の短期間レンバチニブ投与の有効性
Get PDFAim: Transarterial chemoembolization (TACE) combined with lenvatinib, employing a 4-day lenvatinib administration followed by TACE without an interval (short-term LEN-TACE), was performed for hepatocellular carcinoma (HCC). The aim was to assess tumor hemodynamics following the 4-day lenvatinib and to evaluate the treatment outcomes after the short-term LEN-TACE. Methods: 25 unresectable HCC patients received this combined therapy. Lenvatinib (4-12 mg) was administrated for 4 days prior to TACE. Perfusion CT scans were obtained before and after the lenvatinib administration. Either cTACE (76%) or DEB-TACE (24%) were performed. Results: intra-tumor blood flow significantly decreased after the 4-day lenvatinib (p < 0.05). The TACE procedure was successful with no severe adverse events in all patients. The overall complete response (CR) rate was 75% (cTACE 84%, DEB-TACE 40%). The lipiodol-washout ratio between 1 week and 4 months after cTACE correlated with the arterial flow reduction ratio by lenvatinib prior to TACE (r = -0.55). The 12-month progression-free survival (PFS) rate was 75.0%. Conclusions: The short-term LEN-TACE is feasible and safe, demonstrating promising outcomes with a high CR ratio, contributing to lipiodol retention in the tumor after cTACE, and extended PFS. To confirm the advantages of this treatment protocol, a prospective clinical trial is mandatory.権利情報：© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)