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The high specificity of the human skin microbiome is expected to provide a new marker for personal identification. Metagenomic sequencing of clustered regularly interspaced short palindromic repeats (CRISPRs), which we call metaCRISPR typing, was shown to achieve personal identification accurately. However, the intra-individual variability observed in previous studies, which may be due to poor DNA yields from skin samples, has resulted in non-reproducible results. Furthermore, whether metaCRISPR typing can assist in the forensic human DNA analysis of low-biomass samples, from which the information obtained is insufficient, is unknown. In the present study, we sequenced serially diluted control streptococcal CRISPRs cloned into plasmids to determine the minimum copy number required to obtain reproducible results from metaCRISPR typing. We found that at least 10 2 copies of CRISPRs are necessary to obtain reproducible results. We then analyzed the skin swab samples using both metaCRISPR typing and human DNA typing. When the DNA extracted from the skin swabs was diluted, no information was obtained from six out of eight samples by human DNA typing. On the other hand, beta diversity indices of spacer sequences compared with reference samples were below 0.8 for three out of six samples, for which no information was obtained from human DNA analysis, indicating that the spacers observed in these samples were similar to those in the references. These results indicate that metaCRISPR typing may contribute to the identification of individuals from whom the samples were obtained, even in cases where human DNA yields are insufficient to perform human DNA analysis.IMPORTANCEPrevious studies have developed new personal identification methods utilizing personal differences in the skin microbiome. However, intra-individual diversity of skin microbiome may preclude the application of microbiome-based personal identification. Moreover, no study has compared microbiome-based personal identification and practical human DNA analysis. Here, we revealed that the results of metaCRISPR typing, a previously developed microbiome-based personal identification method, are stable if the copy number of the marker gene is sufficient. We then analyzed the skin swab samples using both metaCRISPR typing and human DNA analysis. Our results indicate that metaCRISPR typing may provide additional information for personal identification using low-biomass samples that cannot be used for conventional human DNA analysis.

Objectives: To explore the predictive performance on the need for surgical intervention in patients with adhesive small bowel obstruction (ASBO) using machine-learning (ML) algorithms and investigate the optimal timing for transition to surgery., Methods: One hundred and six patients with ASBO who initially underwent long transnasal intestinal tube (LT) decompression were enrolled in this retrospective study. Traditional logistic regression analysis and ML algorithms were used to evaluate the risk of need for surgical intervention., Results: Non-operative management (NOM) by LT decompression failed in 28 patients (26%). Multivariate logistic regression analysis identified a drainage volume ≥665 ml via LT on day 1, interval between ASBO diagnosis and LT intubation, and small bowel dilatation at 48 h after LT intubation to be independent predictors of transition to surgery (odds ratios 7.10, 1.42, and 19.81, respectively; 95% confidence intervals 1.63-30.94, 1.00-2.02, and 3.04-129.10; P -values 0.009, 0.047, and 0.002). The random forest algorithm showed the best predictive performance of five ML algorithms tested, with an area under the curve of 0.889, accuracy of 0.864, and precision of 0.667 in the test set. 97.4% of patients without transition to surgery (n=78) had passes of first flatus until three days., Conclusions: This is the first study to demonstrate that ML algorithm can predict the need for surgery in patients with ASBO. The guideline recommended period for initial NOM of 72 h seems to be reasonable. These findings can be used to develop a framework for earlier clinical decision-making in these patients., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2024 The Japan Society of Coloproctology.)

Spontaneous complete chorioamniotic membrane separation (cCMS) is rare and associated with adverse perinatal outcomes, such as intrauterine fetal death. Herein, we present a case of spontaneous cCMS in a fetus with ileal atresia and umbilical cord ulcers. In our case, we detected spontaneous cCMS on ultrasonography at 35 weeks of gestation. On the same day, a female infant weighing 2134 g was delivered via cesarean section. Pathological examination of the placenta confirmed cCMS and umbilical cord ulcers. When cCMS is evident in late preterm infants, the fetus should be carefully monitored and considered for delivery., (© 2024 Wiley Periodicals LLC.)

We report a case of BPS combined with CPAM prenatally diagnosed as having two aberrant arteries from the celiac artery by fetal 3D-US. Although the pattern of arterial feeding vessels was extremely rare in our case, the vasculature images obtained using fetal 3D-US were comparable to those obtained using postnatal CT angiography., (© 2024 Wiley Periodicals LLC.)

Purpose: Self-expandable metallic stent (SEMS) placement is widely used as a bridge to surgery (BTS) procedure for obstructive colorectal cancer. However, evidence regarding the optimal interval between SEMS placement and elective surgery is lacking., Methods: We retrospectively collected data from patients with BTS between January 2013 and October 2021. Inverse probability treatment-weighted propensity score analyses were used to compare short- and long-term outcomes between the short-interval (SI) and long-interval (LI) groups, using a cutoff of 20 days., Results: In total, 138 patients were enrolled in this study (SI group, n = 63; LI group, n = 75). In the matched cohort, the patients' backgrounds were well balanced. The incidence of Clavien-Dindo grade ≥ II postoperative complications was not significantly different between the SI and LI groups (19.0% vs. 14.0%, P = 0.47). There were no significant differences between the SI and LI groups in the 3-year recurrence-free survival (68.0% vs. 76.4%, P = 0.73) or 3-year overall survival rates (86.0% vs. 90.6%, P = 0.72)., Conclusions: A longer interval did not deteriorate the oncological outcomes. Individual perioperative management with an appropriate interval to improve the patient's condition is required to ensure safe surgery., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

The mineralocorticoid receptor (MR) is a member of the nuclear receptor family that was initially identified to regulate blood pressure through its ability to modulate kidney sodium handling in response to aldosterone. MR can be regulated by signals other than aldosterone; however, the detailed mechanisms remain to be elucidated. We found that MR is controlled in a Rho-associated coiled-coil-containing protein kinase 2 (ROCK2)-dependent manner. Mice with a specific deletion of ROCK2 in the kidney tubules showed decreased MR expression levels and increased urinary excretion of sodium. Mechanistically, signal transducer and activator of transcription 3 (STAT3) is a key molecule that mediates MR expression in these mice. This study highlights an important role of tubular ROCK2 in electrolyte homeostasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The treatment strategies for either human or animal babesiosis have been established and used for many years. With the rising indications of drug resistance and adverse side effects, finding effective and alternative therapies is urgently needed. Sitamaquine (SQ) is an 8-aminoquinoline that was first synthesized as a part of the collaborative anti-malarial program that led to primaquine. In this study, we evaluated the inhibitory effects of SQ on Babesia spp. in vitro and in vivo. The half-maximal inhibitory concentration (IC 50 ) on in vitro cultured Babesia gibsoni was 8.04 ± 1.34 μM. Babesia gibsoni parasites showed degenerative morphological changes following SQ treatment. The in vivo growth inhibitory effects of SQ were evaluated in BALB/c mice infected with B. microti and atovaquone (ATV)-resistant B. microti strain. Oral administration of SQ at a dose of 20 mg/kg significantly inhibited the growth of B. microti and ATV-resistant B. microti. Meanwhile, SQ also showed inhibitory effects on the growth of B. rodhaini, a lethal rodent Babesia species. All mice infected with B. rodhaini treated with SQ survived, whereas the mice in the control group succumbed to the disease. The results obtained in this study indicate that SQ has potent inhibition effects against Babesia spp., which support SQ as a prospective alternative candidate for babesiosis treatment., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Although neurology department ward rounds are among the most important medical education exercises in Japan, they have several issues. Patients may find it unpleasant to undergo repeated neurological tests, especially when in the presence of several students. Only the front row of students can closely observe the examination findings; moreover, students were prohibited from contacting patients altogether during the COVID-19 pandemic. One possible solution is to use commercial videoconferencing systems. However, Japanese patients are reluctant to have their medical information or video footage of them sent outside of the hospital via the internet., Objective: The study aimed to confirm the feasibility of conducting remote teaching rounds using an in-house web conferencing system in which the patients' personal data are securely protected. This study also explored whether using remote rounds alongside face-to-face participation would enhance learning., Methods: We created an on-premises videoconferencing system using an open-source app. To perform video ward rounds, the professor wore a wireless microphone while leading routine in-person rounds and the attending physician carried a tablet device linked to a web conference, allowing students in another room to watch the rounds on a live stream. In total, 112 of 5th-year students who entered their 1-week neurology rotation between 2021 and 2022 were instructed to participate in 1-hour in-person and remote rounds. Students were given questionnaires to evaluate their satisfaction and the educational effects of the remote rounds., Results: The remote ward rounds were conducted easily with no interference with the in-person rounds, nor any complaints from the patients. Each examination technique was explained by another teacher to the students who participated in remote rounds in the conference room. Characteristic neurological findings, such as plantar reflexes (Babinski sign), which are usually seen only by close observers during in-person rounds, could be visualized under magnification by all students. The postexperience survey (82/112, 73% response rate) showed that the mean score of participants' satisfaction was 3.94 (SD 0.83; excellent 5 and poor 1). No participant scoring 1 was noted. The proportion of students who observed 6 representative abnormal neurological findings (Babinski sign, hyperreflexia, cerebellar ataxia, involuntary movement, muscular weakness, and abnormality in sensory examination) increased by 22% (18/82, range 13-24) compared to in-person rounds alone. When self-rating the learning value, 43% (35/82) of the students answered that remote rounds are equally as valuable as in-person rounds, while 32% (26/82) preferred remote rounds., Conclusions: Live-streaming of neurology ward rounds using a secure in-house web conferencing system provides additional learning experience without concerns regarding leakage of patient information. This initiative could enhance neurology learning before entering a clinical clerkship., (©Kenji Sekiguchi, Seiji Kawano, Norio Chihara, Seimi Satomi-Kobayashi, Eiichi Maeda, Riki Matsumoto. Originally published in JMIR Formative Research (https://formative.jmir.org), 22.08.2024.)

Background: Policies, such as stay home, bubbling, and stay with your community, recommending that individuals reduce contact with diverse communities, including families and schools, have been introduced to mitigate the spread of the COVID-19 pandemic. However, these policies are violated if individuals from various communities gather, which is a latent risk in a real society where people move among various unreported communities., Objective: We aimed to create a physical index to assess the possibility of contact between individuals from diverse communities, which serves as an indicator of the potential risk of SARS-CoV-2 spread when considered and combined with existing indices., Methods: Moving direction entropy (MDE), which quantifies the diversity of moving directions of individuals in each local region, is proposed as an index to evaluate a region's risk of contact of individuals from diverse communities. MDE was computed for each inland municipality in Tokyo using mobility data collected from smartphones before and during the COVID-19 pandemic. To validate the hypothesis that the impact of intercommunity contact on infection expansion becomes larger for a virus with larger infectivity, we compared the correlations of the expansion of infectious diseases with indices, including MDE and the densities of supermarkets, restaurants, etc. In addition, we analyzed the temporal changes in MDE in municipalities., Results: This study had 4 important findings. First, the MDE values for local regions showed significant invariance between different periods according to the Spearman rank correlation coefficient (>0.9). Second, MDE was found to correlate with the rate of infection cases of COVID-19 among local populations in 53 inland regions (average of 0.76 during the period of expansion). The density of restaurants had a similar correlation with COVID-19. The correlation between MDE and the rate of infection was smaller for influenza than for COVID-19, and tended to be even smaller for sexually transmitted diseases (order of infectivity). These findings support the hypothesis. Third, the spread of COVID-19 was accelerated in regions with high-rank MDE values compared to those with high-rank restaurant densities during and after the period of the governmental declaration of emergency (P<.001). Fourth, the MDE values tended to be high and increased during the pandemic period in regions where influx or daytime movement was present. A possible explanation for the third and fourth findings is that policymakers and living people have been overlooking MDE., Conclusions: We recommend monitoring the regional values of MDE to reduce the risk of infection spread. To aid in this monitoring, we present a method to create a heatmap of MDE values, thereby drawing public attention to behaviors that facilitate contact between communities during a highly infectious disease pandemic., (©Yukio Ohsawa, Yi Sun, Kaira Sekiguchi, Sae Kondo, Tomohide Maekawa, Morihito Takita, Tetsuya Tanimoto, Masahiro Kami. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 21.08.2024.)

Objective: Many artificial intelligence approaches to muscle ultrasound image analysis have not been implemented on usable devices in clinical neuromuscular medicine practice, owing to high computational demands and lack of standardised testing protocols. This study evaluated the feasibility of using real-time texture analysis to differentiate between various pathological conditions., Methods: We analysed 17,021 cross-sectional ultrasound images of the biceps brachii of 75 participants, including 25 each with neurogenic disorders, myogenic disorders, and healthy controls. The size and location of the regions of interest were randomly selected to minimise bias. A random forest classifier utilising texture features such as Dissimilarity and Homogeneity was developed and deployed on a mobile PC, enabling real-time analysis., Results: The classifier distinguished patients with an accuracy of 81 %. Echogenicity and Contrast from the Co-Occurrence Matrix were significant predictive features. Validation on 15 patients achieved accuracies of 78 %/93 % per image/patient over 15-second videos, respectively. The use of a mobile PC facilitated real-time estimation of the underlying pathology during ultrasound examination, without influencing procedures., Conclusions: Real-time automatic texture analysis is feasible as an adjunct for the diagnosis of neuromuscular disorders., Significance: Artificial intelligence using texture analysis with a light computational load supports the semi-quantitative evaluation of neuromuscular ultrasound., (© 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.)

Volatile organic compounds (VOCs) are representative indoor air pollutants that negatively affect the human body owing to their toxicity. One of the most promising methods for VOC removal is photocatalytic degradation using TiO 2 . In this study, the addition of carbon black (CB) and heavy metal nanoparticles (NPs) was investigated to improve the efficiency of a TiO 2 -based photocatalytic VOC decomposition system combined with ultrasonic atomization and ultraviolet irradiation, as described previously. The addition of CB and Ag NPs significantly improved the degradation efficiency. A comparison with other heavy metal nanoparticles and their respective roles are discussed.

Objective In randomized clinical trials and real-world studies, calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs), including erenumab, have demonstrated efficacy for migraine prevention. However, there have been no real-world studies focusing on erenumab in East Asia that investigated its efficacy on migraine-associated symptoms and patient-reported satisfaction levels. Methods This single-center, observational, retrospective, real-world study examined patients who received at least three doses of erenumab at Keio University Hospital, Tokyo, Japan, between December 2021 and March 2023 as their first CGRP mAb treatment in a real-world setting. The patients were administered 70 mg of erenumab monthly. We assessed changes in monthly migraine days (MMDs), responder rates, migraine-associated symptoms including photophobia, phonophobia, nausea/vomiting, and patient-reported satisfaction levels. In addition, injection site reactions and other adverse events were recorded to investigate safety. Results Nineteen patients were considered eligible for the analysis. At 3 months, erenumab decreased MMDs by 6.6 (95% confidence interval, 2.3-10.8; p<0.01). The 50% responder rate was 42%. A total of 83% (n=15), 56% (n=10), and 71% (n=10) of patients reported either improvement in or disappearance of photophobia, phonophobia, and nausea/vomiting, respectively, and 44% (n=8) and 28% (n=5) answered "very satisfied" and "somewhat satisfied", respectively, with erenumab treatment, leaving only 28% (n=5) as "unsatisfied". Injection site reactions (n=6, 32%) and constipation (n=4, 21%) were frequent adverse events. Conclusion In a real-world setting in Japan, erenumab proved to be effective in not only reducing migraine and headache frequency but also improving migraine-associated symptoms and satisfying the majority of patients.

Every year, Hanoi suffers from several episodes (periods with daily concentration of PM 2.5 higher than 50 µg m -3 during at least two consecutive days). These episodes are of health concern because of the high concentration of PM 2.5 and/or PM 0.1 and the presence of PM-bound toxic components, such as, PAHs. In this study, the concentrations of PAHs bound to PM 2.5 and PM 0.1 in night-time and day-time samples during episode and non-episode periods in December 2021 were determined. The concentrations of PAHs bound to PM 2.5 were found to increase significantly from day-time samples of 3.24 ± 0.83 ng m -3 to night-time samples of 10.8 ± 4.45 ng m -3 in episode periods. However, PAHs bound to PM 0.1 increased slightly from day-time samples of 0.58 ± 0.12 ng m -3 to night-time samples of 0.89 ± 0.30 ng m -3 in episode periods. Diagnostic ratios of PAHs indicate that biomass/coal combustion and vehicular emission are the primary sources of PAHs. The incremental lifetime cancer risk was estimated to vary from 8.7E-09 to 2.5E-08 for children and 6.7E-08 to 2.2E-07 for adults, respectively. Accordingly, loss of life expectancy was estimated at 0.11 min and 0.82 min for children and adults, respectively. These findings imply that the carcinogenic impact induced by PAHs via inhalation is negligible during the episode period., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Some neurological complications are associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A 74-year-old man was diagnosed with infection by SARS-CoV-2. Eighteen days after SARS-CoV-2 infection, he developed disturbed consciousness and aseptic meningoencephalitis. An analysis of cerebrospinal flood revealed an elevated cell count (184/μL) and protein level (260 mg/dL). Cranial magnetic resonance imaging showed no abnormalities. By contrast, 123 I-N-isopropyl-p-iodoamphetamine single-photon emission computed tomography showed a significant decrease in cerebral blood flow (CBF) in the left parietal and occipital lobes. He died suddenly 3 months after being transferred to a rehabilitation clinic without any clear cause of death. The SARS-CoV-2 infection can cause aseptic meningoencephalitis with a distinctive decrease in CBF pattern without magnetic resonance image abnormality or intracranial artery stenosis., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

To search for low-energy resonant structures in isospin T=3/2 three-body systems, we have performed the experiments ^{3}H(t,^{3}He)3n and ^{3}He(^{3}He,t)3p at intermediate energies. For the 3n experiment, we have newly developed a thick Ti-^{3}H target that has the largest tritium thickness among targets of this type ever made. The 3n experiment for the first time covered the momentum-transfer region as low as 15  MeV/c, which provides ideal conditions for producing fragile systems. However, in the excitation-energy spectra we obtained, we did not observe any distinct peak structures. This is in sharp contrast to tetraneutron spectra. The distributions of the 3n and 3p spectra are found to be similar, except for the displacement in energy due to Coulomb repulsion. Comparisons with theoretical calculations suggest that three-body correlations exist in the 3n and 3p systems, although not enough to produce a resonant peak.

Human-induced pluripotent stem cells (hiPSCs) have great therapeutic potential. The cell source differentiated from hiPSCs requires xeno-free and robust methods for lineage-specific differentiation. Here, a system is described for differentiating hiPSCs on new generation laminin fragments (NGLFs), a recombinant form of a laminin E8 fragment conjugated to the heparan sulfate chains (HS) attachment domain of perlecan. Using NGLFs, hiPSCs are highly promoted to direct differentiation into a paraxial mesoderm state with high-efficiency muscle lineage generation. HS conjugation to the C-terminus of Laminin E8 fragments brings fibroblast growth factors (FGFs) bound to the HS close to the cell surface of hiPSCs, thereby facilitating stronger FGF signaling pathways stimulation and initiating HOX gene expression, which triggers the paraxial mesoderm differentiation of hiPSCs. This highly efficient differentiation system can provide a roadmap for paraxial mesoderm development and an infinite source of myocytes and muscle stem cells for disease modeling and regenerative medicine., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

The energy partition in high Mach number collisionless shock waves is central to a wide range of high-energy astrophysical environments. We present a new theoretical model for electron heating that accounts for the energy exchange between electrons and ions at the shock. The fundamental mechanism relies on the difference in inertia between electrons and ions, resulting in differential scattering of the particles off a decelerating magnetically dominated microturbulence across the shock transition. We show that the self-consistent interplay between the resulting ambipolar-type electric field and diffusive transport of electrons leads to efficient heating in the magnetic field produced by the Weibel instability in the high Mach number regime and is consistent with fully kinetic simulations.

Since the identification of vacuolar protein sorting (VPS) 35, as a causative molecule for familial Parkinson's disease (PD), retromer-mediated endosomal machinery has been a rising factor in the pathogenesis of the disease. The retromer complex cooperates with sorting nexin (SNX) dimer and DNAJC13, another causal molecule in PD, to transport cargoes from endosomes to the trans-Golgi network, and is also involved in mitochondrial dynamics and autophagy. Retromer dysfunction may induce neuronal death leading to PD via several biological cascades, including misfolded, insoluble α-synuclein (aS) accumulation and mitochondrial dysfunction; however, the detailed mechanisms remain poorly understood. In this study, we showed that the stagnation of retromer-mediated retrograde transport consistently occurs in different PD-mimetic conditions, i.e., overexpression of PD-linked mutant DNAJC13, excess aS induction, or toxin-induced mitochondrial dysfunction. Mechanistically, DNAJC13 was found to be involved in clathrin-dependent retromer transport as a functional modulator of SNX1 together with heat shock cognate 70 kDa protein (Hsc70), which was controlled by the binding and dissociation of DNAJC13 and SNX1 in an Hsc70 activity-dependent manner. In addition, excess amount of aS decreased the interaction between SNX1 and VPS35, the core component of retromer. Furthermore, R33, a pharmacological retromer chaperone, reduced insoluble aS and mitigated rotenone-induced neuronal apoptosis. These findings suggest that retrograde transport regulated by SNX1-retromer may be profoundly involved in the pathogenesis of PD and is a potential target for disease-modifying therapy for the disease., (© 2024. The Author(s).)

Introduction: Recently, there have been a few reports of atypical post-coronavirus disease 2019 (COVID-19) myelopathy manifesting tract-specific lesions similar to those due to vitamin B 12 deficiency. However, the precise characteristics of imaging or clinical course remain not well understood., Methods: A retrospective analysis of the clinical and imaging characteristics of four patients who were referred to our hospital with a unique post-COVID-19 myelopathy was performed., Results: Four-to-six weeks following COVID-19 infection in the summer of 2023, four middle-aged men developed paraparesis, hypo/dysesthesia and bladder/bowel disturbance, suggesting myelopathy. Although spinal MRI showed no abnormalities in the early stages, tract-specific longitudinal lesions along the dorsal and lateral columns became apparent as the symptoms progressed. Owing to the lack of MRI findings at the early stage, all cases were challenging to diagnose. However, the patients remained partially responsive to aggressive immunosuppressive therapies, even in the advanced stage., Discussion: We termed these tract-specific longitudinal lesions in the presented case series 'Grasshopper sign' because brain coronal and spine axial MRI findings looked like a grasshopper's antennae and face. Early identification of the characteristic MRI abnormality could allow for early intervention using intensive immunosuppressive therapy, which could improve patient outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aim: To explore the survival benefit of adjuvant chemotherapy for obstructive colorectal cancer (OCRC) managed by self-expandable metallic stent (SEMS) placement as a bridge to surgery (BTS)., Patients and Methods: One hundred twenty-nine patients with pathological stage II/III OCRC who underwent BTS using a SEMS were included in this multicenter retrospective study. Patients were divided into the no-adjuvant chemotherapy group (No-Adj group) (n=52) and adjuvant chemotherapy group (Adj group) (n=77), and relapse-free survival (RFS) was compared., Results: The No-Adj group had more fragile patient background factors, such as higher age, higher American Society of Anesthesiologists score, and lower preoperative albumin compared with the Adj group. The 3-year RFS rates for the overall cohort were significantly different between the No-Adj and Adj groups (56.4% and 78.5%, respectively; p=0.003). Significant RFS benefits of adjuvant chemotherapy were observed in both pathological stage II and III cancer. Characteristics of more advanced cancer, such as high carcinoembryonic antigen (CEA), pathological T4, and lymphovascular invasion, were associated with survival improvement by adjuvant chemotherapy. T4 and adjuvant chemotherapy were significantly associated with RFS in the multivariate Cox proportional analysis., Conclusion: To our knowledge, this is the first study to show a survival benefit of adjuvant chemotherapy in patients with OCRC undergoing BTS using a SEMS. Adjuvant chemotherapy is basically recommended regardless of the cancer stage and is strongly recommended with more advanced characteristics, such as high CEA, T4, and lymphovascular invasion., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune inflammatory disease that can affect multiple generations and cause complications with long-term prednisolone treatment. This study aimed to evaluate the efficacy and safety of mycophenolate mofetil (MMF) in preventing NMOSD relapse while reducing prednisolone dosage. The trial involved nine patients with NMOSD who received MMF along with prednisolone dose reduction. MMF was effective in achieving prednisolone dose reduction without relapse in 77.8% of patients, with a significant decrease in mean annualized relapse rate. All adverse events were mild. The findings suggest that MMF could be a viable treatment option for middle-aged and older patients who require steroid reduction. Clinical trial registration number: jRCT, jRCTs051180080. Registered February 27th, 2019-retrospectively registered, https://jrct.niph.go.jp/en-latest-detail/jRCTs051180080.

Introduction: We aimed to determine whether unfractionated heparin (UH) and low molecular weight heparin (LH) contribute to aberrant carnitine metabolism in patients receiving hemodialysis., Methods: The rate of increase in serum free fatty acids (FFAs) and the ratio of acylcarnitine to free carnitine (AC/FC) from before to after hemodialysis were determined in patients receiving UH and LH. Additionally, the effect of switching patients to UH from LH was examined., Results: AC/FC was significantly higher in the UH group. In addition, serum FFAs in that group increased to 0.825 ± 0.270 after dialysis from 0.172 ± 0.160 before dialysis, showing a positive correlation with AC/FC. Furthermore, AC/FC was observed to be significantly higher in patients who were switched to UH from LH at 3 months after the change., Conclusion: Compared with UH, LH has a lesser effect on lipid metabolism, suggesting that it also has a lesser effect on carnitine metabolism., (© 2023 International Society for Apheresis and Japanese Society for Apheresis.)

Cysteinyl RGD-peptidyl cysteinyl prolyl esters, which have different configurations at the cysteine and proline residues, were synthesized by the solid-phase method and cyclized by the native chemical ligation reaction. Cyclization efficiently proceeded to give cyclic peptides, regardless of the difference in the configuration. The peptides were further derivatized to the corresponding desulfurized or methylated cyclic peptides at the Cys residues. The inhibition activity to αvβ6 integrin binding was then analyzed by ELISA. The results showed that the activity varied depending on the difference in the configuration and modification of the cysteinyl prolyl ester (CPC) moiety, demonstrating the usefulness of this method in the search for a good inhibitor of the protein-protein interaction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yamada, Takei, Kawakami, Taniguchi, Sekiguchi and Hojo.)

Cerebral venous thrombosis (CVT) is challenging to diagnose, as it presents with variable symptoms. We encountered a complicated case of CVT that mimicked limbic encephalitis due to sensory aphasia. Based on the characteristic magnetic resonance imaging findings, this 72-year-old Japanese man was later confirmed to have CVT, the cause of which was periodontitis due to Eikenella corrodens, a Gram-negative facultative anaerobic that is part of the mouth's normal flora. The symptoms improved without sequelae following anticoagulation treatment and antibiotics. Clinicians should consider CVT as a differential diagnosis when unexplainable neurological symptoms suggesting limbic encephalitis are observed.

Background and Objectives: Anti-IgLON5 disease is an autoimmune neurodegenerative disorder characterized by various phenotypes, notably sleep and movement disorders and tau pathology. Although the disease is known to be associated with the neuronal cell adhesion protein IgLON5, the physiologic function of IgLON5 remains elusive. There are conflicting views on whether autoantibodies cause loss of function, activation of IgLON5, or inflammation-associated neuronal damage, ultimately leading to the disease. We generated IgLON5 knockout (-/-) mice to investigate the functions of IgLON5 and elucidate the pathomechanism of anti-IgLON5 disease., Methods: IgLON5 knockout (-/-) mice underwent behavioral tests investigating motor function, psychiatric function (notably anxiety and depression), social and exploratory behaviors, spatial learning and memory, and sensory perception. Histologic analysis was conducted to investigate tau aggregation in mice with tauopathy., Results: IgLON5 -/- mice had poorer performance in the wire hang and rotarod tests (which are tests for motor function) than wild-type mice. Moreover, IgLON5-/- mice exhibited decreased anxiety-like behavior and/or hyperactivity in behavior tests, including light/dark transition test and open field test. IgLON5-/- mice also exhibited poorer remote memory in the contextual fear conditioning test. However, neither sleeping disabilities assessed by EEG nor tau aggregation was detected in the knockout mice., Discussion: These results suggest that IgLON5 is associated with activity, anxiety, motor ability, and contextual fear memory. Comparing the various phenotypes of anti-IgLON5 disease, anti-IgLON5 disease might partially be associated with loss of function of IgLON5; however, other phenotypes, such as sleep disorders and tau aggregation, can be caused by gain of function of IgLON5 and/or neuronal damage due to inflammation. Further studies are needed to elucidate the role of IgLON5 in the pathogenesis of anti-IgLON5 diseases.

Objective This study examined the prevalence of migraine in nurses in Japan, which, to our knowledge, has not been documented in English. Methods From April to May 2021, we administered a questionnaire to 229 nurses working at Keio University Hospital to investigate the prevalence and characteristics of headache among nurses in Japan. Headaches were classified as migraine or tension-type headache (TTH) based on the International Classification of Headache Disorders 3rd edition (ICHD-3). Results In total, 80 patients (34.9%) had primary headaches, including 47 (20.5%) with migraine and probable migraine and 33 (14.4%) with TTH and probable TTH. We found a significant difference in the Numerical Rating Scale score, nausea and vomiting, photophobia, phonophobia, and aggravation by routine physical activity between migraine and TTH. The specificities for a migraine diagnosis were 100% and 93.9% for nausea/vomiting and photophobia, respectively. Only 8.8% of patients had their headaches diagnosed by a physician. Conclusion Migraines have a high prevalence (>20%) among nurses and are often under-diagnosed. In many cases, headache-associated symptoms are more important than laterality or other characteristics for the diagnosis. Many nurses are treated for headaches without a correct diagnosis. Further education regarding primary headaches may be necessary for health practitioners as well as society.

Myasthenia gravis (MG), primarily caused by acetylcholine receptor (AChR) autoantibodies, is a chronic autoimmune disorder causing severe muscle weakness and fatigability. In particular, seronegative MG constitutes 10%-15% of MG cases and presents diagnostic challenges especially in early-onset female patients who often show severe disease and resistance to immunosuppressive therapy. Furthermore, the immunopathology of seronegative MG remains unclear. Thus, in this study, we aimed to elucidate the pathogenic mechanism of seronegative MG using scRNA-seq analysis and plasma proteome analysis; in particular, we investigated the relationship between immune dysregulation status and disease severity in refractory seronegative MG. Employing single-cell RNA-sequencing and plasma proteome analyses, we analyzed peripheral blood samples from 30 women divided into three groups: 10 healthy controls, 10 early-onset AChR-positive MG, and 10 refractory early-onset seronegative MG patients, both before and after intravenous immunoglobulin treatment. The disease severity was evaluated using the MG-Activities of Daily Living (ADL), MG composite (MGC), and revised 15-item MG-Quality of Life (QOL) scales. We observed numerical abnormalities in multiple immune cells, particularly B cells, in patients with refractory seronegative MG, correlating with disease activity. Notably, severe MG cases had fewer regulatory T cells without functional abnormalities. Memory B cells were found to be enriched in peripheral blood cells compared with naïve B cells. Moreover, plasma proteome analysis indicated significantly lower plasma protein levels of soluble CD22, expressed in the lineage of B-cell maturation (including mature B cells and memory B cells), in refractory seronegative MG patients than in healthy donors or patients with AChR-positive MG. Soluble CD22 levels were correlated with disease severity, B-cell frequency, and RNA expression levels of CD22. In summary, this study elucidates the immunopathology of refractory seronegative MG, highlighting immune disorders centered on B cells and diminished soluble CD22 levels. These insights pave the way for novel MG treatment strategies focused on B-cell biology., Competing Interests: YO, SM, TI, MS, MI, DW, and YK were employed by the company Takeda Pharmaceutical Company Limited. 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 © 2024 Okuzono, Miyakawa, Itou, Sagara, Iwata, Ishizuchi, Sekiguchi, Motegi, Oyama, Warude, Kikukawa and Suzuki.)

Objective: The companion diagnosis for olaparib, a poly (ADP-ribose) polymerase inhibitor for prostate cancer, aims to detect BRCA1/2 gene variants. In clinical practice, the frequency of germline BRCA1/2 variants in patients receiving castration-resistant prostate cancer treatment is unknown. We aimed to evaluate the prevalence of germline BRCA1/2 variants and their relationship to prognosis and treatment efficacy in castration-resistant prostate cancer., Methods: Between June 2021 and 2023, 92 patients receiving castration-resistant prostate cancer treatment were examined for germline BRCA1/2 variants using BRACAnalysis CDx®. Furthermore, the associations between BRCA1/2 pathogenic variants and clinical outcomes were assessed., Results: Of the 92 patients referred for genetic testing, 6 (6.5%) carried germline pathogenic variants in BRCA1/2. The BRCA2 variant was the most frequent (n = 5), followed by BRCA1 variant (n = 1). Among the five variants in BRCA2, the p.Asp427Thrfs*3 variant was identified for the first time in prostate cancer. Overall survival from castration-resistant prostate cancer for patients with BRCA1/2 variants was significantly shorter than for patients without BRCA1/2 variants (P = 0.043). Progression-free survival of androgen receptor signaling inhibitors for patients with BRCA1/2 variants was significantly shorter than for those without (P = 0.003). Progression-free survival of taxane chemotherapy was significantly shorter in patients with BRCA1/2 variants than in those without (P = 0.0149)., Conclusions: In clinical practice, 6.5% of patients treated with castration-resistant prostate cancer carried germline BRCA1/2 pathogenic variants. Japanese castration-resistant prostate cancer patients with germline BRCA1/2 mutants have a poor prognosis and may be less responsive to treatment with androgen receptor signaling inhibitors and taxane-based chemotherapy for castration-resistant prostate cancer., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Focal segmental glomerulosclerosis (FSGS) shares podocyte damage as an essential pathological finding. Several mechanisms underlying podocyte injury have been proposed, but many important questions remain. Rho-associated, coiled-coil-containing protein kinase 2 (ROCK2) is a serine/threonine kinase responsible for a wide array of cellular functions. We found that ROCK2 is activated in podocytes of adriamycin (ADR)-induced FSGS mice and cultured podocytes stimulated with ADR. Conditional knockout mice in which the ROCK2 gene was selectively disrupted in podocytes (PR2KO) were resistant to albuminuria, glomerular sclerosis, and podocyte damage induced by ADR injection. In addition, pharmacological intervention for ROCK2 significantly ameliorated podocyte loss and kidney sclerosis in a murine model of FSGS by abrogating profibrotic factors. RNA sequencing of podocytes treated with a ROCK2 inhibitor proved that ROCK2 is a cyclic nucleotide signaling pathway regulator. Our study highlights the potential utility of ROCK2 inhibition as a therapeutic option for FSGS., (© 2024. The Author(s).)

Aim: Circulated histones play a crucial role in the pathogenesis of infectious diseases and severe trauma, and it is one of the potential molecular targets for therapeutics. Recently, we reported that histone is one of the causative agents for urinary L-FABP increase. However, the mechanism is still unclear, especially in severe cases. We further investigated the mechanism of urinary L-FABP increase using a more severe mouse model with histone-induced kidney injury. This study also aims to evaluate the therapeutic responsiveness of urinary L-FABP as a preliminary study., Methods: Human L-FABP chromosomal transgenic mice were administrated 30 mg/kg histone from a tail vein with a single dose. We also performed a comparative study in LPS administration model. For the evaluation of the therapeutic responsiveness of urinary L-FABP, we used heparin and rolipram., Results: The histological change with cast formation as a characteristic of the models was observed in proximal tubules. Urinary L-FABP levels were significantly elevated and these levels tended to be higher in those with more cast formation. Heparin and rolipram had the ameliorative effect of the cast formation induced by histone and urinary L-FABP levels significantly decreased., Conclusion: Histone is one of the causative agents for the increase of urinary L-FABP at an early stage of AKI. In addition, it suggested that urinary L-FABP may be useful as a subclinical AKI marker reflecting kidney damage induced by histone. Furthermore, urinary L-FABP reflected the degree of the damage after the administration of therapeutic agents such as heparin and PDE4 inhibitor., (© 2023 Asian Pacific Society of Nephrology.)

Background: Ureaplasma spp. is an endemic microorganism that causes placental chorioamnionitis or preterm delivery in pregnant women, and the occurrence of bronchopulmonary dysplasia or intraventricular hemorrhaging in preterm infants after birth, although the pathogenicity of Ureaplasma remains controversial. The association between Ureaplasma exposure and the symptoms or outcomes of infected mothers or their infants born at term remains poorly understood. We investigated the clinical characteristics of preterm and term infants with or without Ureaplasma in their gastric fluid., Methods: Gastric fluid samples were collected from 47 newborns in the neonatal intensive-care unit immediately after birth and tested using multiplex polymerase chain reaction (PCR) assays targeting Ureaplasma spp., Ureaplasma parvum, and Ureaplasma urealyticum. The clinical findings and outcomes of the neonates and their mothers were retrospectively evaluated., Results: Ureaplasma spp. were detected in 9/47 samples (19%) by multiplex PCR assays. In all cases, the subspecies was U. parvum. The Ureaplasma-positive group had a significantly higher incidence of chorioamnionitis in utero than the Ureaplasma-negative group. Regarding preterm infants, the IgM levels in the Ureaplasma-positive group were significantly higher than in the Ureaplasma-negative group. In contrast, in term infants, the rates of a non-reassuring fetal status, a maternal fever, and maternal leukocyte counts and maternal C-reactive protein levels within five days before delivery in the Ureaplasma-positive group were significantly higher than those in the Ureaplasma-negative group. All three extremely-low-birth-weight infants with Ureaplasma developed bronchopulmonary dysplasia. The length of hospitalization in the Ureaplasma-positive group was almost same as that in the Ureaplasma-negative group for term infants., Conclusion: Mothers or their fetuses with exposure to Ureaplasma expressed characteristic clinical features during pregnancy and after birth., (Copyright © 2023 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Polycyclic aromatic hydrocarbons (PAHs) associated with indoor PM pose a high risk to human health because of their toxicity. A total of 160 daily samples of indoor PM 2.5 and PM 0.1 were collected in Hanoi and analysed for 15 PAHs. In general, the concentrations of carcinogenic PAHs (car-PAHs) accounted for 21% ± 2%, 19.1% ± 2%, and 26% ± 3% of the concentrations of 15 PAHs in PM 2.5 , PM 0.1-2.5 , and PM 0.1 , respectively. Higher percentages of car-PAHs were found in smaller fractions (PM 0.1 ), which can be easily deposited deep in the pulmonary regions of the human respiratory tract. The concentrations of 15 PAHs were higher in winter than in summer. The most abundant PAH species were naphthalene and phenanthrene, accounting for 11%-21% and 19%-23%, respectively. The PAH content in PM 0.1 was almost twice as high as those in PM 2.5 and PM 0.1-2.5 . Principal component analysis found that vehicle emissions and the combustion of biomass and coal were the main outdoor sources of PAHs, whereas indoor sources included cooking activities, the combustion of incense, scented candles, and domestic uses in houses. According to the results, 60%-90% of the PM 0.1 -bound BaP (eq) was deposited in the alveoli region, whereas 63%-75% of the PM 2.5 -bound BaP (eq) was deposited in head airways (HA), implying that most of the particles deposited in the HA region were PM 0.1-2.5 . The contributions of dibenz[a,h]anthracene and benzo[a]pyrene were dominant and contributed from 36% to 51% and 31%-50%, respectively, to the carcinogenic potential, whereas benzo[a]pyrene contributed from 30% to 49% to the mutagenic potential for both size fractions. The incremental lifetime cancer risk, simulated by Monte Carlo simulation, was within the limits set by the US EPA, indicating an acceptable risk for the occupants. These results provide an additional scientific basis for protecting human health from exposure to indoor PAHs., 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 Ltd. All rights reserved.)

Background: We previously developed an optimized q-space diffusional MRI technique (normalized leptokurtic diffusion [NLD] map) to delineate the demyelinated lesions of multiple sclerosis (MS) patients. Herein, we evaluated the utility of NLD maps to discern the white matter abnormalities in normal-appearing white matter (NAWM) and the abnormalities' possible associations with physical and cognitive disabilities in MS., Methods: We conducted a retrospective observational study of MS patients treated at our hospital (Jan. 2012 to Dec. 2022). Clinical and MRI data were collected; Processing Speed Test (PST) data were obtained when possible. For a quantitative analysis of the NLD maps, we calculated the NLD index as GV ROI /GV REF , where GV is a mean grayscale value in the regions of interest (ROIs) and the reference area (REF; cerebrospinal fluid)., Results: One hundred-one individuals with MS were included. The lower corpus callosum and non-lesional WM NLD index were associated with worse Expanded Disability Status Scale (EDSS) and PST scores. The NLD indexes in the corpus callosum (p < 0.0001) and non-lesional white matter (p < 0.0001) were significantly reduced in progressive MS compared to relapsing-remitting MS. We categorized MS severity as moderate/severe (EDSS score ≥ 4 points) and mild (EDSS score < 4 points). The NLD indexes in the corpus callosum (p < 0.0001) and non-lesional white matter (p < 0.0001) were significantly lower in the moderate/severe MS group compared to the mild MS group., Conclusion: The NLD map revealed abnormalities in the non-lesional white matter, providing valuable insights for evaluating manifestations in MS patients., Competing Interests: Declaration of Competing Interest H.O. is a founding Scientist of SanBio Co. Ltd. and K Pharma Inc. Y.I. has received speaker honoraria from Abbvie, Alexion, Amagen Biogen, Bristol Myers Squibb, Chugai, CSL-Behring, Daiichi-Sankyo, Eisai, Fujimoto Pharma, JB, Mitsubishi-Tanabe, Novartis, Otsuka, Pfizer, Sumitomo Dainippon, and Takeda, and his research is supported from Böehringer-Ingelheim, Fujimoto Pharma, Chugai, JB Daiichi-Sankyo, Mitsubishi-Tanabe, MedicalConcierge, Shionogi, and Otsuka. J.N. has received speaker honoraria from Abbvie, Alexion, Astellas, Biogen, Chugai, CSL-Behring, Daiichi-Sankyo, Eisai, Fujimoto Pharma, JB, Mitsubishi-Tanabe, Novartis, Otsuka, Sanofi, Sumitomo Dainippon, and Takeda; he has also served as a paid consultant for Alexion, Biogen, Chugai, Mitsubishi-Tanabe, and Novartis, and his research is supported from Abbvie, Biogen, Böehringer-Ingelheim, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, JB, Keio University, Kyowa-Kirin, Mitsubishi-Tanabe, MEXT, MHLW, MSD, Otsuka, Pfizer, Shionogi, Sumitomo Dainippon, Takeda, and Tsumura., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Basic fibroblast growth factor (bFGF, FGF2) and integrin α6β1 are important for maintaining the pluripotency of human pluripotent stem cells (hPSCs). Although bFGF-integrin binding contributes to biofunctions in cancer cells, the relationship in hPSCs remains unclear., Methods: To investigate the relationship between bFGF and integrin in human induced pluripotent stem cells (hiPSCs), we generated recombinant human bFGF wild-type and mutant proteins, that do not bind to integrin, FGFR, or both. We then cultured hiPSCs with these recombinant bFGF proteins. To evaluate the abilities of recombinant bFGF proteins in maintaining hPSC properties, pluripotent markers, ERK activity, and focal adhesion structure were analyzed through flow cytometry, immunofluorescence (IF), and immunoblotting (IB)., Result: We identified an interaction between bFGF and integrin α6β1 in vitro and in hiPSCs. The integrin non-binding mutant was incapable of inducing the hPSC properties, such as proliferation, ERK activity, and large focal adhesions at the edges of hiPSC colonies. Signaling induced by bFGF-FGFR binding was essential during the first 24 h after cell seeding for maintaining the properties of hPSCs, followed by a shift towards intracellular signaling via the bFGF-integrin interaction. The mixture of the two bFGF mutants also failed to maintain hPSC properties, indicating that bFGF binds to both FGFR and integrin., Conclusion: Our study demonstrates that the integrin-bFGF-FGFR ternary complex maintains the properties of hPSCs via intracellular signaling, providing insights into the functional crosstalk between bFGF and integrins in hiPSCs., Competing Interests: K. S. is a co-founder and shareholder of Matrixome, Inc. Y.T. holds a position as a Project Leader at Matrixome Inc., (© 2023 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Background: Prostate cancer in the anterior region may be missed on a transrectal systematic biopsy (SBx). Therefore, this study aimed to evaluate the performance of magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion targeted biopsy (TBx) in detecting anterior region cancer in patients with a history of SBxs., Methods: Prostate biopsies were performed in 224 patients after multiparametric MRI, among whom 119 patients with prostate imaging reporting and data system (PI-RADS version 2) scores of 3 to 5 underwent MRI-TRUS fusion TBxs. Afterward, cancer detection rates (CDRs) and TBx-positive core regions were compared by categorizing patients into those with or without a history of SBxs., Results: Total CDR was 68.8% (44/64 cases) in the initial biopsy group (Initial-Bx group) and 47.3% (26/55 cases) in the previous-negative-systematic biopsy group (Pre-Neg-SBx group) ( P  = 0.018). Interestingly, both TBx- and SBx-core positive cases were more common in the Initial-Bx group than in the Pre-Neg-SBx group (Initial-Bx group: 75% [33/44 cases] vs. Pre-Neg-SBx group: 42.3% [11/26 cases], P  = 0.006). However, only TBx-core positive cases were more common in the Pre-Neg-SBx group than in the Initial-Bx group (Initial-Bx group: 11.4% [5/44 cases] vs. Pre-Neg-SBx group: 30.8% [8/26 cases], P  = 0.043). In addition, the proportion of anterior lesions detected by TBx cores was higher in the Pre-Neg-SBx group than in the Initial-Bx group (Initial-Bx group: 26.3% [10/38 cases] vs. Pre-Neg-SBx group: 52.6% [10/19 cases], P  = 0.049)., Conclusion: Using MRI-TRUS fusion TBx in the evaluation of previously negative SBx cases improved the detection rate of anterior lesions, which might have been missed in previous SBxs. Especially in patients with a history of SBxs mpMRI should be performed to screen for anterior lesions., (© 2023 The Asian Pacific Prostate Society. Published by Elsevier B.V.)

Objective: We aimed to evaluate differences in ultrasonographic nerve enlargement sites among typical chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), distal CIDP, multifocal CIDP and multifocal motor neuropathy (MMN) in a Japanese population., Methods: We retrospectively reviewed medical records and selected 39 patients (14 with typical CIDP, 7 with multifocal CIDP, 4 with distal CIDP, and 14 with MMN) who underwent ultrasonography. Median and ulnar nerve cross-sectional areas (CSAs) were measured at the wrist, forearm, elbow, and upper arm. CSA ratios for each nerve were calculated as: wrist-to-forearm index (WFI) = wrist CSA/forearm CSA; elbow-to-upper arm index (EUI) = elbow CSA/upper arm CSA; and intranerve CSA variability (INCV) = maximal CSA/minimal CSA., Results: Significant differences were observed among typical CIDP, multifocal CIDP, distal CIDP, and MMN in CSA at the forearm and upper arm in the median nerves (p < 0.05). Patients with multifocal CIDP had lower WFI and EUI and higher INCV than the other groups (p < 0.05)., Conclusions: Regardless of the untreated period, compared with other CIDP subtypes and MMN, multifocal CIDP showed a focal and marked nerve enlargement in the Japanese population., Significance: Differences in nerve enlargement site may be an underlying feature of multifocal CIDP., 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., (© 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.)

Eccrine sweat glands play an essential role in regulating body temperature. Sweat is produced in the coiled secretory portion of the gland, which is surrounded by obliquely aligned myoepithelial cells; the sweat is then peristaltically transported to the skin surface. Myoepithelial cells are contractile and have been implicated in sweat transport, but how myoepithelial cells contract and transport sweat remains unexplored. Here, we perform ex vivo live imaging of an isolated human eccrine gland and demonstrate that cholinergic stimulation induces dynamic contractile motion of the coiled secretory duct that is driven by gap junction-mediated contraction of myoepithelial cells. The contraction of the secretory duct occurs segmentally, and it is most prominent in the region surrounded by nerve fibers, followed by distension-contraction sequences of the excretory duct. Overall, our ex vivo live imaging approach provides evidence of the contractile function of myoepithelial cells in peristaltic sweat secretion from human eccrine glands., (© 2023. The Author(s).)

The mitochondrial (m.) 3243A>G mutation is known to be associated with various mitochondrial diseases including mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Their clinical symptoms have been estimated to occur with an increased mitochondrial DNA (mtDNA) heteroplasmy and reduced activity of oxidative phosphorylation (OXPHOS) complexes, but their trends in the central nervous system remain unknown. Six autopsied mutant cases and three disease control cases without the mutation were enrolled in this study. The mutant cases had a disease duration of 1-27 years. Five of six mutant cases were compatible with MELAS. In the mutant cases, cortical lesions including a laminar necrosis were frequently observed in the parietal, lateral temporal, and occipital lobes; less frequently in the frontal lobe including precentral gyrus; and not at all in the medial temporal lobe. The mtDNA heteroplasmy in brain tissue samples of the mutant cases was strikingly high, ranging from 53.8% to 85.2%. The medial temporal lobe was preserved despite an inhospitable environment having high levels of mtDNA heteroplasmy and lactic acid. OXPHOS complex I was widely decreased in the mutant cases. The swelling of smooth muscle cells in the vessels on the leptomeninges, with immunoreactivity (IR) against mitochondria antibody, and a decreased nuclear/cytoplasmic ratio of choroidal epithelial cells were observed in all mutant cases but in none without the mutation. Common neuropathological findings such as cortical laminar necrosis and basal ganglia calcification were not always observed in the mutant cases. A high level of mtDNA heteroplasmy was observed throughout the brain in spite of heterogeneous cortical lesions. A lack of medial temporal lesion, mitochondrial vasculopathy in vessels on the leptomeninges, and an increased cytoplasmic size of epithelial cells in the choroid plexus could be neuropathological hallmarks helpful in the diagnosis of mitochondrial diseases., (© 2023 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

Introduction: Functional neurological disorder (FND) has various clinical manifestations. Even though diagnostic criteria for FND have been proposed, FND characteristics with sensory manifestations have not been elucidated. Therefore, we aimed to investigate the association between sensory nerve action potential (SNAP) amplitudes and FND with sensory manifestations., Methods: We included 76 outpatients with FND with sensory manifestations whose nerve conduction studies were performed retrospectively. Additionally, we defined 121 patients with other neurological diseases who did not have peripheral neuropathy as disease controls. The SNAP amplitudes were compared between the two groups. We also explored the relationship between SNAP amplitudes and FND-specific clinical symptoms in patients with FND., Results: No differences were observed in SNAP amplitudes adjusted for age between patients with FND who had sensory manifestations and disease control patients. Additionally, no differences were observed between patients with FND who had and did not have FND-specific clinical symptoms., Conclusion: The SNAP amplitude in patients with FND who had sensory manifestations was equivalent to that in controls., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Morimoto, Sekiguchi and Matsumoto.)

Endometriosis is highly dependent on angiogenesis and lymphangiogenesis. Prostaglandin E2, an arachidonic acid metabolite, has been shown to promote the formation of new blood and lymphatic vessels. However, the role of another arachidonic acid metabolite, thromboxane A 2 (TXA 2 ) in angiogenesis and lymphangiogenesis during endometriosis remains largely unexplored. Using a murine model of ectopic endometrial transplantation, fragments from the endometrium of WT donor mice were transplanted into the peritoneal walls of recipient WT mice (WT→WT), resulting in an increase in both the area and density of blood and lymphatic vessels. Upon transplantation of endometrial tissue from thromboxane prostanoid (TP) receptor (TXA 2 receptor)‑deficient (TP ‑/‑ ) mice into TP ‑/‑ mice (TP ‑/‑ →TP ‑/‑ ), an increase in implant growth, angiogenesis, and lymphangiogenesis were observed along with upregulation of pro‑angiogenic and lymphangiogenic factors, including vascular endothelial growth factors (VEGFs). Similar results were obtained using a thromboxane synthase (TXS) inhibitor in WT→WT mice. Furthermore, TP ‑/‑ →TP ‑/‑ mice had a higher number of F4/80 + cells than that of WT→WT mice, with increased expression of genes related to the anti‑inflammatory macrophage phenotype in endometrial lesions. In cultured bone marrow (BM)‑derived macrophages, the levels of VEGF‑A, VEGF‑C, and VEGF‑D decreased in a TP‑dependent manner. Furthermore, TP signaling affected the polarization of cultured BM‑derived macrophages to the anti‑inflammatory phenotype. These findings imply that inhibition of TP signaling promotes endometrial implant growth and neovascularization.

Polydom is an extracellular matrix protein involved in lymphatic vessel development. Polydom-deficient mice die immediately after birth due to defects in lymphatic vessel remodeling, but the mechanism involved is poorly understood. Here, we report that Polydom directly binds to Tie1, an orphan receptor in the Angiopoietin-Tie axis, and facilitates migration of lymphatic endothelial cells (LECs) in a Tie1-dependent manner. Polydom-induced LEC migration is diminished by PI3K inhibitors but not by an ERK inhibitor, suggesting that the PI3K/Akt signaling pathway is involved in Polydom-induced LEC migration. In line with this possibility, Akt phosphorylation in LECs is enhanced by Polydom although no significant Tie1 phosphorylation is induced by Polydom. LECs also exhibited nuclear exclusion of Foxo1, a signaling event downstream of Akt activation, which was impaired in Polydom-deficient mice. These findings indicate that Polydom is a physiological ligand for Tie1 and participates in lymphatic vessel development through activation of the PI3K/Akt pathway., (© 2023 Sato-Nishiuchi et al.)