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Aim: Suvorexant is an orexin receptor antagonist (ORA) for the treatment of insomnia. The antagonistic action of suvorexant on orexin receptors is associated with an increase in rapid eye movement (REM) sleep, which can potentially lead to nightmares depending on the patient's condition. However, the precise risk factors for nightmares among patients taking ORAs, such as suvorexant, have yet to be identified. In this retrospective study, we aimed to identify the risk factors for the development of nightmares in patients treated with suvorexant., Methods: The risk factors were determined by comparing parameters between the nightmare group and the nonnightmare group. This study included 440 patients who received suvorexant at the University of Miyazaki Hospital from April 2014 to January 2021., Results: We found that 9.1% (n = 40) of the patients experienced suvorexant-induced nightmares. There was a significant difference in the median age, which was lower in the nightmare group than in the nonnightmare group (p < 0.01). Furthermore, both multiple logistic regression analysis and Cox proportional hazards regression analysis revealed increased odds ratios for nightmares for individuals aged 20-39 years., Conclusions: This study revealed that elderly patients taking suvorexant had fewer nightmares than nonelderly patients did., (© 2024 The Author(s). Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Purpose: Periosteal chondrosarcoma (PCS) is the rarest subtype of chondrosarcoma and is recognized as a low-grade malignant tumour, reported to have an 88% ten year overall survival rate. The relationship between surgical margins and clinical outcome is inconsistent; some authors claim that PCS can be successfully treated with marginal resection and others report more local recurrence and distant metastasis with marginal compared to wide resection. This study was intended to report the treatment and prognosis of localized PCS patients from the Japanese National Bone and Soft Tissue Tumor Registry database and to perform a systematic review of the literature to determine the relationship between surgical margins and rates of local recurrence, distant metastasis, and mortality., Methods: Twenty-three patients with pathologically-diagnosed PCS between 2006 and 2022 from the Japanese National Bone and Soft Tissue Tumor Registry database were retrospectively analyzed. Of the 105 studies found through a systematic search using Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases, nine studies were ultimately included., Results: The local recurrence rate after R0 resection was 2.5% (3/118 patients) and after R1 resection was 33.3% (11/33 patients) (p < 0.001). The distant metastasis rate in the R0 resection group was 5.9% (7/118 patients) and in the R1 resection group was 27.3% (9/33 patients) (p = 0.010). Mortality following R0 resection was 4.2% (5/118 patients) but after R1 resection was 18.2% (6/33 patients) (p = 0.040)., Conclusion: Wide resection may be necessary for localized PCS to prevent local recurrence and distant metastasis and improve survival., Competing Interests: Declarations. Ethical approval: The study was conducted according to the guidelines of the Declaration of Helsinki and it was approved by the Investigational Review Board (IRB) of the last author’s institute, and this study using the registry was approved by the Musculoskeletal Tumor Committee of the Japanese Orthopaedic Association. Consent to participate: The IRB waived informed consent because the data extracted from the database were anonymized. Consent to publish: The IRB waived informed consent because the data extracted from the database were anonymized. Competing interests: The authors declare no competing interests., (© 2024. The Author(s) under exclusive licence to SICOT aisbl.)

Thoracic outlet syndrome (TOS) is characterized by intractable cervicobrachial pain caused by strangulation of the brachial plexus and subclavian artery by structures of the superior thoracic outlet. We describe percutaneous epidural adhesiolysis for refractory pain due to TOS. A man in his 40s had received nerve block therapy for right upper extremity pain of unknown origin for 5 years. Although imaging findings were negative for TOS, reproducible pain relieved by injection of a local anesthetic into the anterior scalene muscle suggested TOS due to compression by the muscle. Subsequently, since nerve block treatment had only temporary effect and the pain gradually worsened, right T1 epidural adhesiolysis was performed. Thereafter, the pain improved from a numerical rating scale score of 8-9/10 to 2-3/10, continuing for about 3 months. Epidural adhesiolysis was remarkably effective in treating intractable pain caused by TOS due to strangulation of the brachial plexus by the anterior scalene muscle., 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.)

Bacterial reverse transcriptase coding gene (RT) is essential for the production of a small satellite DNA-RNA complex called multicopy single-stranded DNA (msDNA). In this study, we found a novel retron, retron-Vmi1 (Vm85) from Vibrio mimicus. The retron is comprised of the msr-msd region, orf323, and the ret gene, a genetic organization similar to Salmonella's retron-Sen2 (St85). The protein sequence of the RNA-directed DNA polymerase (RT-Vmi1) is highly homologous to the RTs of Vibrio metoecus, Vibrio parahaemolyticus, and Vibrio vulnificus. Phylogenetic and protein sequence similarity analysis of retron-Vmi1 ORF323 and RT revealed a close relatedness to retron-Sen2. We found that retron-Vmi1 was inserted in the dusA gene, similar to the insertion of the retron-Vpa1 (Vp96) of V. parahaemolyticus AQ3354, suggesting that retrons can be transferred via the tRNA gene. These results are the first convincing evidence that retron is moving across species. The neighboring genes of retron-Vmi1 shared high homology with the genetic environment of V. parahaemolyticus and V. vulnificus retrons. We also found two junction points within the retron-Vmi1 and the dusA gene suggesting that retron-Vmi1 was inserted into this site in a two-step manner., (© 2024 The Author(s). Microbiology and Immunology published by The Societies and John Wiley & Sons Australia, Ltd.)

Most synthetic self-assemblies grow indefinitely into size-unlimited structures, whereas some biological self-assemblies autonomously regulate their size and shape. One mechanism of such self-regulation arises from the chirality of building blocks, inducing their mutual twisting that is incompatible with their long-range ordered packing and thus halts the assembly's growth at a certain stage. This self-regulation occurs robustly in thermodynamic equilibrium rather than kinetic trapping, and therefore is attractive yet elusive. Until now, studies of self-regulating assemblies have focused on non-responsive systems, whose equilibrium point and corresponding size and shape are hardly changeable. Here, we demonstrate a stimuli-responsive, self-regulating assembly. This assembly consists of chiral and magnetically orientable nanorods, where the effective chirality can be changed by balancing chirality-induced twisting and magnet-induced flattening between nanorods. Consequently, the strength of self-regulation in the assembly is modulable by magnetic field intensity, allowing robust, tunable, and reversible control of its size and shape. Our strategy would provide more biomimetic materials with precision and responsiveness., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: This study aimed to measure and compare cerebrospinal fluid neuronal injury biomarkers in the acute phase of complex febrile seizure (CFS) and infection-triggered acute encephalopathy (AE). Furthermore, we determined the pathogenesis of AE with biphasic seizures and late reduced diffusion (AESD)., Methods: Pediatric patients with febrile status epilepticus who visited Hyogo Prefectural Kobe Children's Hospital from November 1, 2016, to December 31, 2022, and whose cerebrospinal fluid samples were collected within 24 h of neurological symptom onset were included. Patients were classified as having CFS or infection-triggered AE according to their definitions. Patients with AE were further categorized into AESD or unclassified AE. Cerebrospinal fluid biomarkers (neuron-specific enolase, growth differentiation factor 15 [GDF-15], S100 calcium-binding protein B [S100B], glial fibrillary acidic protein, and tau protein were measured and compared among the groups., Results: Total of 63 patients (45 with CFS and 18 with AE) were included. Among the AE patients, nine were classified as having AESD and nine as having unclassified AE. S100B levels were significantly higher in patients with AESD than in patients with CFS (485 pg/ml vs. 175.3 pg/ml) and were even higher in patients with AESD and neurological sequelae (702.4 pg/ml). GDF-15 levels were significantly elevated in patients with AE compared to patients with CFS (85.8 pg/ml vs. 23.6 pg/ml)., Conclusions: The elevation of S100B suggests that activated astrocytes may be closely associated with the early pathology of AESD. Elevated GDF-15 levels in infection-triggered AE suggest the activation of defense mechanisms caused by stronger neurological injury., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

For systematic monitoring of radioactive nuclides in marine products, this study aimed at streamlining and simplifying the analysis method for the prominent radioisotope, strontium-90 (90Sr). The DGA chelate solid-phase extraction technique was employed for enhanced efficiency. The study focused on optimizing the necessary pretreatment procedures while minimizing the steps involving HNO3 leaching. This protocol enabled the quantitative recovery of strontium, and it facilitated a rapid analysis without the need for a time-consuming evaporation step and without waiting for secular equilibrium between 90Sr and its progeny to be reached. The method incorporating the optimized pretreatment protocol was applied to three diverse marine fish species and the accurate quantification of 90Sr at background levels in surface seawater was achieved. The method obtained concentrations in bone samples from these species that ranged from 0.036 to 0.120 mBq per kg-dry, and chemical yield values were notably high, ranging from 87.7% to 92.5%., (© The Author(s) 2024. Published by Oxford University Press.)

Key Clinical Message: Chin augmentation by hyaluronic acid filler injection rarely causes abnormal bone resorption in the mentum. Thus, when taking the history of a patient with jaw deformity, it is imperative to check the history of treatment of the mentum., Abstract: Hyaluronic acid (HA) filler injection is a common procedure in nonsurgical cosmetic chin augmentation. Due to its high biocompatibility and simple injection technique, HA filler injection is a popular procedure. However, adverse events such as allergic reactions and foreign body reactions have been reported in some cases. In this study, we report a case of skeletal Class II jaw deformity in which bone resorption was observed in the mentum after HA filler injection. The purpose of this study is to discuss the indications for HA filler injection in skeletal Class II cases that require orthognathic surgery. The patient was a 30-year-old woman. To improve retrusion of the mentum, she has been receiving HA filler injections in the mentum three times every 6 months in the cosmetic surgery clinic since 2015. However, the retrusion of the mentum did not improve, which prompted here to visit the orthodontic clinic. Radiographs and CT revealed bowl-shaped bone resorption surrounding the foreign bodies in the mentum. She was diagnosed with maxillary protrusion, vertical maxillary excess, mandibular retrusion, and bilateral condylar resorption. Bimaxillary orthognathic surgery (BOGS) and removal of residual HA fillers were planned after completion of the preoperative orthodontic treatment. After BOGS, the foreign bodies were completely removed, and the resorption cavities were filled with excess bone segments from the surgical sites. X-ray photoelectron spectroscopy analysis of the foreign bodies suggested the presence of HA. One year after the BOGS, no progression of condylar resorption occurred, and bone healing at the mentum had a good prognosis. Therefore, the patient underwent reduction and advancement genioplasty. She was satisfied with her facial profile and occlusal function. Unexpected bone resorption in the mentum caused by HA filler injection is often discovered incidentally. Although, patients may feel hesitant to confess their history of treatment of the mentum, it is important to ensure that they are carefully interviewed., Competing Interests: The authors of this article claim that they do not have any conflict of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Background & Aims: The diagnostic criteria for cachexia, as proposed by the Asian Working Group for Cachexia (AWGC), include weight loss, a low body mass index, and additional factors such as a low handgrip strength (HGS), anorexia, or elevated CRP levels. This study aimed to evaluate the significance of low HGS as a diagnostic criterion in patients with advanced cancer., Methods: This single-centre, retrospective cohort study was conducted between April 2019 and March 2023. Patients aged ≥18 years with malignant diseases were included. Patients without records on HGS were excluded. Low HGS was defined as a HGS <28 kg for men and <18 kg for women. The overall median survival time (MST) was analysed by univariate and multivariate analyses., Results: A total of 894 patients were analysed. Cachexia was prevalent in 74 %, though only 3.4 % were diagnosed based solely on low HGS. The MST in patients with cachexia was 122 days, and in those with low HGS was 73 days. The associations between low HGS and high mortality remained significant after adjusting for AWGC criteria, modified weight loss grading system, age, gender, performance status, calf circumferenceand fluid retention. The MST varied with the number of additional factors being met: 422 days for one criterion, 92 days for two, and 55 days for all three (p < 0.0001)., Conclusion: This study supports that HGS serve as important prognostic tool in patients with various cancers., Competing Interests: Declaration of competing interest No conflicts of interest to declare., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

In super-aged societies, dementia has become a critical issue, underscoring the urgent need for tools to assess cognitive status effectively in various sectors, including financial and business settings. Facial and speech features have been tried as cost-effective biomarkers of dementia including Alzheimer's disease (AD). We aimed to establish an easy, automatic, and extensive screening tool for AD using a chatbot and artificial intelligence. Smile images and visual and auditory data of natural conversations with a chatbot from 99 healthy controls (HCs) and 93 individuals with AD or mild cognitive impairment due to AD (PwA) were analyzed using machine learning. A subset of 8 facial and 21 sound features successfully distinguished PwA from HCs, with a high area under the receiver operating characteristic curve of 0.94 ± 0.05. Another subset of 8 facial and 20 sound features predicted the cognitive test scores, with a mean absolute error as low as 5.78 ± 0.08. These results were superior to those obtained from face or auditory data alone or from conventional image depiction tasks. Thus, by combining spontaneous sound and facial data obtained through conversations with a chatbot, the proposed model can be put to practical use in real-life scenarios., (© 2024. The Author(s).)

Introduction: Buccal midazolam (buc MDL) is the first buccal mucosal delivery formulation applied for status epilepticus in Japan. Herein, we aimed to investigate the effectiveness and adverse events of buc MDL as a pre-hospital treatment for epileptic seizures in real-world clinical practice., Methods: This study involved a retrospective review based on medical records. We included children who received buc MDL as pre-hospital treatment for epileptic seizures and were subsequently transported to the emergency department between April 2021 and November 2023., Results: This study included 26 patients (136 episodes). The overall efficacy rate, which was defined as seizure cessation within 10 min after buc MDL administration with no recurrence within 30 min, was 43 %. Moreover, 70 % of the episodes did not require additional medications. None of the episodes required bag-mask ventilation or intubation following seizure cessation with buc MDL alone. The efficacy was decreased when buc MDL was administered longer than 15 min from seizure onset. Furthermore, the efficacy did not decrease as long as it was within 0.2-0.5 mg/kg, even if the dose was smaller than the appropriate dose for the specific age., Conclusions: The response rate was significantly higher in episodes where buc MDL was administered within 15 min. Additionally, there was no concern regarding respiratory depression with buc MDL alone., 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. Published by Elsevier B.V.)

Background: Self-expandable metal stent (SEMS) migration after endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is a severe complication. The migration risk could be related to the surface friction of SEMS, assumed to be affected by the wire structure and mechanical properties, including radial force (RF); however, their relevance remains unclear. This experimental study aimed to assess the mechanical properties of SEMS involved in the onset of stent migration by measuring the sliding-resistance force (SF) as the SEMS moves through the stomach wall., Methods: The SF of seven types of 8-mm diameter SEMS (four braided and three laser-cut types) and porcine stomach wall was measured with a universal testing machine. The SF of each SEMS was measured three times, and the average maximum SF (SFmax) was used for analysis. The correlation between SFmax and RF of each SEMS was evaluated., Results: SFmax and RF showed a very strong positive correlation (r = 0.92). Compared to the regression line predictions in the scatter plots of SFmax and RF, the SFmax of laser-cut and braided type SEMSs had positive and negative residuals, respectively., Conclusions: Selecting a laser-cut type SEMS with a higher RF may more effectively prevent the onset of stent migration against the stomach wall in EUS-HGS., (© 2024 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Introduction: Behavioral Activation (BA) is a short-term cognitive behavioral therapy modality that stimulates activities that increase patients' reinforcement experiences. Recent research verified the effect of brief BA. However, despite the short intervention time per session, BA is difficult to implement during hospitalization due to its long implementation period., Objectives: To evaluate the clinical effectiveness of a brief BA program for people with depression in an inpatient setting., Methods: This study employed a single-group pre-post design. Fifteen patients who met the inclusion criteria participated in the trial after providing oral and written informed consent. In addition to their usual care, participants received four weekly sessions administered by a nurse. The primary outcome measures included the Beck Depression Inventory (BDI-II), which indicated patients' subjective depression severity. Clinical outcomes were measured at preintervention, immediate postintervention, and one-month postintervention., Results: Fourteen participants completed the BA program and were receptive to treatment. For the primary endpoint, BDI-II, there was an improvement in scores (25.60 to 22.73 to 22.06) between the baseline, postintervention, and 1-month postassessment, but not a significant change. For EQ VAS score, there was no significant change, but there was an improvement in EQ VAS score (51.53 to 52.20 to 55.13) between the baseline, postintervention, and 1-month postassessment. The mean total Global Assessment of Functioning score increased from 40.20 to 57.00 across the pre- and postassessment points ( p  < .0001)., Conclusion: The study comprised a brief BA intervention, with results suggesting that participants could complete the program without feeling burdened. Although there was no significant improvement in the general outcome, depression levels, and other outcomes improved. Thus, while there is a need to rethink BA intervention, this program may be a practical approach to improving depression and other outcomes., 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.)

Direct compression of the oculomotor nerve (OcN) is usually accompanied by OcN palsy (OcNP), with an abnormal pupillary function. We herein present the case of a 76-year-old man with pupil-sparing paresis of the right inferior rectus muscle. A radiological examination revealed an epidermoid cyst at the right cerebellopontine angle, which came in contact with the right oculomotor nerve. However, surgical intervention revealed compression of the inferomedial aspect of the oculomotor nerve by the right posterior cerebral artery. Decompression of the nerve gradually improved the ocular movement. This unique case offers insights into the potential topographical arrangement of the oculomotor nerve fibers.

In cancer genome analysis, identifying pathogenic alterations and assessing their effects on oncogenic processes is important. Although whole exome sequencing (WES) can effectively detect such changes, driver alterations could not be identified in 27.8% of the cases, according to a previous study. The objectives of the present study were to evaluate the utility of whole genome sequencing (WGS) and clarify its differences with WES in terms of driver alteration detection. For this purpose, WGS analysis was conducted on 177 driverless WES samples, selected from 5,480 fresh frozen samples derived from 5,140 Japanese patients with cancer. These samples were selected as primary tumor, both WES and transcriptome profiling were performed, estimated tumor content of ≥ 30%, and no driver alterations were identified by WES. WGS identified driver and likely driver alterations in 68.4 and 22.6% of the samples, respectively. The most frequent alteration type was oncogene amplification, followed by tumor suppressor gene deletion and small variants located outside the coding region. In the remaining 9.0% of samples, no such signals were identified; therefore, further investigations are required. The current study clearly demonstrated the role and utility of WGS in identifying genomic alterations that contribute to tumorigenesis., (© 2024. The Author(s).)

Dysfunction of primary cilia leads to genetic disorder, ciliopathies, which shows various malformations in many vital organs such as brain. Multiple tongue deformities including cleft, hamartoma, and ankyloglossia are also seen in ciliopathies, which yield difficulties in fundamental functions such as mastication and vocalization. Here, we found these tongue anomalies in mice with mutation of ciliary protein. Abnormal cranial neural crest-derived cells (CNCC) failed to evoke Hh signal for differentiation of mesoderm-derived cells into myoblasts, which resulted in abnormal differentiation of mesoderm-derived cells into adipocytes. The ectopic adipose subsequently arrested tongue swelling formation. Ankyloglossia was caused by aberrant cell migration due to lack of non-canonical Wnt signaling. In addition to ciliopathies, these tongue anomalies are often observed as non-familial condition in human. We found that these tongue deformities could be reproduced in wild-type mice by simple mechanical manipulations to disturb cellular processes which were disrupted in mutant mice. Our results provide hints for possible future treatment in ciliopathies., Competing Interests: MK, KK, FS, TK, JN, MK, TN, VU, YI, FM, AK, AF, TN, YK, SM, JT, YK, TM, SG, RK, PC, PS, MC, BF, AO No competing interests declared, (© 2024, Kawasaki et al.)

Background: In primary aldosteronism (PA), the biochemical outcomes of the Primary Aldosteronism Surgical Outcome study are used to assess aldosterone hypersecretion 6-12 months after surgery. However, few studies have investigated whether the outcomes can be predicted in the early postoperative period. In this retrospective study, we evaluated whether the adrenocorticotropin stimulation test (AST) and oral salt loading test (OST) performed immediately after surgery could predict biochemical outcomes 1 year after surgery., Methods: We assessed 268 patients with PA who underwent adrenalectomy at our hospital between 2008 and 2020, underwent AST and OST within 15 days of surgery, and were assessed for biochemical outcomes 1 year after surgery. Patients were divided into two groups: biochemical complete success (B-com; n = 219) and incomplete success (B-inc; n = 49). Patients were divided into clinical complete and partial success and absent success groups. The relationships between various AST and OST values and outcomes were analyzed., Results: The B-inc group had significantly higher plasma aldosterone concentration (PAC) and PAC/serum cortisol ratio (PAC/Cort) at baseline and after ACTH loading in AST and 24-hour urine aldosterone in OST than the B-com group. PAC/Cort at 30 min after ACTH loading (area under the curve (AUC) = 0.76) and 24-hour urine aldosterone (AUC = 0.77) were relatively superior predictors of the outcome. Parameters after ACTH loading were better predictors of biochemical and clinical outcomes than baseline., Conclusions: AST and OST immediately after surgery can predict biochemical and clinical outcomes 1 year after surgery in patients with PA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Purpose: Post-operative meniscal cyst formation occurs following all-inside device meniscal repair. This study aimed to compare the incidence of cysts in patients who underwent meniscal repair with and without all-inside suture devices., Methods: This retrospective study included 227 knees that underwent meniscal repair between 2021 and 2022. The incidence of post-operative meniscal cysts was compared between patients who underwent repair using an all-inside suture anchor device (Group SA) and those who did not use an anchor (Group NA), based on post-operative magnetic resonance imaging (MRI) findings. Risk factors, such as the number of anchors used, were investigated. Using a subgroup analysis, the incidence of meniscal cysts based on the type of device used was investigated., Results: Groups SA and NA comprised 125 and 102 knees, respectively. Group SA had 11 cases of cysts (9% incidence), whereas Group NA had 7 cases (7% incidence), and no statistically significant difference was observed ( p  = 0.63). Symptomatic cysts were observed in two patients (1.6%) in Group SA, whereas none was observed in Group NA (0%); the difference was not significant ( p  = 0.50). Factors such as the number of anchors and sutures used and MRI timing were not identified as risk factors. Cyst incidence varied according to anchor type: Stryker AIR+ (4 out of 55, 7%), Smith & Nephew Fast-Fix 360 (7 out of 56, 13%) and Arthrex Fiber Stitch (0 out of 26, 0%), with no significant difference found ( p  = 0.14)., Conclusion: The incidence of cysts in patients undergoing meniscal repair with an all-inside suture anchor device was 9%, showing no significant difference compared with Group NA. Cyst incidence was not affected by device type., Level of Evidence: Level III, retrospective comparative study., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Background: Pulmonary vein isolation (PVI) employing cryoballoon (CB) or contact force-guided radiofrequency (CF-RF) catheter ablation has been established as an effective strategy for managing atrial fibrillation (AF). However, its efficacy in hypertrophic cardiomyopathy (HCM) remains to be further explored., Methods: This retrospective study analyzed 60 consecutive AF patients with HCM (average age 67 ± 10 years; 41 men) who were consecutively admitted to our hospital from January 2014 to December 2022 and underwent initial PVI., Results: The patients were treated with CB (26 patients) or CF-RF (34 patients). Successful PVI was achieved in both groups without significant complications. In the CF-RF group, additional ablations were performed on the cavotricuspid isthmus (14.7% of patients) and the anterior line (2.9%). The CB group benefited from reduced procedural times (93 ± 31 vs. 165 ± 60 min, p < 0.05) and decreased saline irrigation requirements (77.5 ± 31.4 vs. 870 ± 281.9 mL, p < 0.0001). Using a contrast medium was exclusive to the CB group (33.8 ± 4.2 mL). In a 12-month follow-up, the atrial tachyarrhythmia recurrence-free rates in the CB and CF-RF groups were comparable (77% and 76%, respectively; p = 0.63 according to the log-rank test). Notably, pulmonary vein reconnection was prevalent in most (7 out of 8) patients requiring a secondary ablation procedure., Conclusion: PVI is feasible as a strategy for AF in patients with HCM employing either CB or CF-RF techniques. While the recurrence-free rates were comparable in both groups, differences were noted in procedure duration, saline usage, and the need for a contrast medium., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Occasionally, patients undergoing dialysis develop acute severe hypotension that requires interruption of dialysis within minutes of initiating every dialysis session. Although the underlying causes of recurrent intradialytic hypotension are evaluated extensively, including dialysis-associated allergic reactions or other possible causes, the definitive cause is sometimes missed. Dialysis is a life-sustaining procedure; therefore, prompt identification and management of the underlying cause of dialysis intolerance are crucial. Herein, we report three cases of patients undergoing dialysis who presented with hypereosinophilia-associated acute intradialytic hypotension. All three patients developed acute severe hypotension within minutes after the start of every dialysis session. The prescriptions for dialysis were changed, but episodes of intradialytic hypotension persisted. Pretreatment with methylprednisolone given intravenously before the dialysis session was also ineffective. All patients had hypereosinophilia (> 1500/μL) of different etiology. Eosinophil-lowering therapy with 0.5 mg/kg of prednisolone given orally daily was initiated, and all of them could restart dialysis without any hypotensive episodes within a few days. Our case report and literature review indicated that hypereosinophilia, regardless of its etiology, could result in severe acute hypotension shortly after the start of dialysis session. The oral administration of prednisolone daily was highly effective on hypereosinophilia-associated intradialytic hypotension, while pretreatment with intravenous corticosteroid therapy just before dialysis had no effect. Hypereosinophilia-associated acute intradialytic hypotension is an under-recognized condition; therefore, clinicians need to be aware of this clinical entity and initiate effective treatment strategies. We also provide a brief summary of previously published cases., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Purpose: The transmembrane serine protease 4 (TMPRSS4) gene is upregulated in various human cancers. However, its biological functions in pancreatic ductal adenocarcinoma remain unclear. We examined the expression of TMPRSS4 in pancreatic ductal adenocarcinoma tissues and its correlation with clinicopathological parameters in patients with pancreatic ductal adenocarcinoma who underwent surgery., Methods: The TMPRSS4 expression was immunohistochemically examined in 81 PDAC patients with pancreatic ductal adenocarcinoma. We analyzed the association between the TMPRSS4 expression and clinicopathological factors, the recurrence-free survival (RFS), and the overall survival (OS) and examined the effect of TMPRSS4 expression on cell migration and sensitivity to 5-fluorouracil., Results: The expression rate of TMPRSS4 in the samples was 62.9% (51/81). The TMPRSS4 expression was not correlated with any clinicopathological feature. The five-year overall and recurrence-free survival rates were significantly lower in the TMPRSS4-positive group than in the TMPRSS4-negative group. On a multivariate analysis, TMPRSS4 positivity, poorly differentiated histology, and non-adjuvant chemotherapy predicted a poor OS, while TMPRSS4 positivity and poorly differentiated histology predicted a poor RFS. TMPRSS4-silenced pancreatic ductal adenocarcinoma cells showed higher sensitivity to 5- fluorouracil than did the control siRNA-transfected cells., Conclusions: TMPRSS4 can be considered a prognostic factor and therapeutic target for pancreatic ductal adenocarcinoma., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

The relative biological effectiveness (RBE) of densely ionizing radiation can depend on the biological context. From a radiological perspective, age is an important factor affecting health risks of radiation exposure, but little is known about the modifying impact of age on the effects of densely ionizing radiation. Herein, we addressed the influence of age on leukemogenesis induced by accelerator-generated fast neutrons (mean energy, ∼2 MeV). Male C3H/HeNrs mice were exposed to 137Cs γ rays (0.2-3.0 Gy) or neutrons (0.0485-0.97 Gy, γ ray contamination 0.0105-0.21 Gy) at 1, 3, 8, or 35 weeks of age and observed over their lifetimes under specific pathogen-free conditions. Leukemia and lymphoma were diagnosed pathologically. Hazard ratio (HR) and RBE for myeloid leukemia mortality as well as the age dependence of these two parameters were modeled and analyzed using Cox regression. Neutron exposure increased HR concordant with a linear dose response. The increase of HR per dose depended on age at exposure, with no significant dose dependence at age 1 or 3 weeks but a significant increase in HR of 5.5 per Gy (γ rays) and 16 per Gy (neutrons) at 8 weeks and 5.8 per Gy (γ rays) and 9 per Gy (neutrons) at 35 weeks. The RBE of neutrons was 2.1 (95% confidence interval, 1.1-3.7), with no dependence on age. The development of lymphoid neoplasms was not related to radiation exposure. The observed increasing trend of radiation-associated mortality of myeloid leukemia with age at exposure supports previous epidemiological and experimental findings. The results also suggest that exposure at the susceptible age of 8 or 35 weeks does not significantly influence the RBE value for neutrons for induction of leukemia, unlike what has been documented for breast and brain tumors., (© 2024 by Radiation Research Society. All rights of reproduction in any form reserved.)

Background: Oral and social problems can exacerbate long-term care. Understanding the relationship between social aspects and oral hypofunction can help identify high-risk factors for long-term care., Objective: This study aimed to investigate the social aspects of oral hypofunction among medical outpatients., Methods: This retrospective cross-sectional study included patients who visited an outpatient clinic for frailty. The oral function was assessed using seven items: oral hygiene, occlusal force, masticatory function, tongue-lip motor function, tongue pressure, oral dryness and swallowing function. Participants with three or more functional declines were classified as having 'oral hypofunction'. Social aspects were assessed using 21 items in four categories: general resources, basic social needs, social resources and social behaviours/activities. We analysed the relationship between oral hypofunction and each social aspect., Results: A total of 316 participants (age 78.5 ± 6.4 years) were included, and 128 (41%) had oral hypofunction. Participants with oral hypofunction were significantly more likely to have limited education, require long-term care, not use transportation, depend on others for shopping, not participate in events, lack association membership and not engage in charity or volunteer work. After logistic regression analysis, 'long-term care' and 'no association membership' remained significantly associated with oral hypofunction (odds ratios 2.3, 2.3; 95% CI 1.1-5.0, 1.1-4.7, respectively)., Conclusion: Participants with oral hypofunction faced challenges in 'general resources' and 'social behaviour/activities', which were linked to oral function issues. Future longitudinal studies are necessary to further investigate this relationship., (© 2024 John Wiley & Sons Ltd.)

Introduction: Peritoneal equilibration test (PET) has been used to monitor peritoneal function. A more convenient marker would be useful in clinical situations including home medical care. Autotaxin is known to leak into the interstitium as vascular permeability increases during the progression of tissue fibrosis. Therefore, we hypothesized that autotaxin concentrations in peritoneal dialysis (PD) effluent might reflect peritoneal function., Methods: This study enrolled 45 patients undergoing PD from 2016 to 2021. Autotaxin concentrations measured in PD effluent were evaluated for their associations with markers obtained from PET., Results: Mean age was 69 years, and 33 patients were men. Univariate and multivariate analyses revealed that autotaxin concentrations are associated with dialysate/plasma creatinine ratio, end/start dialysate glucose ratio, and the dip in the dialysate sodium concentration, a marker of ultrafiltration capacity, at baseline (all p < 0.05)., Conclusions: Autotaxin concentrations in PD effluent might be an adjunct marker that reflects peritoneal function., (© 2024 International Society for Apheresis and Japanese Society for Apheresis.)

Purpose: To characterize the ultrasonographic findings of patients with early knee osteoarthritis (KOA) and determine which findings were associated with the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscale., Methods: The study included 98 knees (35 men, 63 women, 60.3 ± 11.5 years) diagnosed with early KOA with no major deformity radiographically, but with pain during activity and tenderness in the medial knee. Synovial hyperplasia in the suprapatellar bursa, knee joint effusion, horizontal tear of the medial meniscus (MM), osteophytes of the medial condyle of the femur and tibia, blood flow signals in the synovium of the suprapatellar bursa, medial collateral ligament bursa, infrapatellar fat pad, MM extrusion (MME) in the supine and upright positions, and the amount of change in MME were observed using ultrasonography., Results: Correlations (p < 0.05) were found between the presence of synovial hyperplasia of the suprapatellar bursa (r<-0.20) and amount of MME in the upright position (r< - 0.24) and all KOOS subscales. Presence of joint effusion and the four KOOS subscales except quality of life (QOL) were correlated (p < 0.05). Partial correlation coefficients showed correlations (p < 0.05) between knee joint effusion and symptoms (r = 0.299) and activities of daily living (ADL) (r = 0.254) of the KOOS subscales, and between MME in the upright position and symptoms (r= - 0.263), pain (r= - 0.256), and ADL (r= - 0.212)., Conclusion: Quality and difficulty of life of patients with early KOA may be influenced by synovial hyperplasia in the suprapatellar bursa, joint effusion, and MME values in the upright position. Among them, synovial hyperplasia of the suprapatellar bursa and amount of MME in the upright position were independently associated with the KOOS subscales., (© 2024. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

In this study, a new assembly strategy for lyotropic chromonic liquid crystals (LCLCs) is proposed using i π- i π interactions, mainly comprising electrostatic and dispersion forces, between charged π-electronic systems to form stacking structures supported by the hydration of triethylene glycol (TEG) units. The meso-TEG-aryl-substituted porphyrin Au III complex, an amphiphilic π-electronic cation, showed diverse states and assembly modes in ion pairs depending on the coexisting counteranions. The PCCp - ion pair formed a hexagonal columnar (Col h ) LC phase based on a charge-by-charge assembly, suggesting the formation of an ordered arrangement of charged π-electronic systems through i π- i π interactions, with reduced interactions between the TEG chains. Furthermore, in the presence of water, LCLC behavior in the Col h and nematic columnar phases according to the amount of water were observed for the PCCp - ion pair as a result of i π- i π interactions. Magnetic-field-induced orientation of the charge-by-charge columnar structures upon dehydration was observed. Furthermore, single-stranded charge-by-charge columnar structures, as components of the LCLCs, were observed using transmission electron microscopy (TEM)., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Enormous swelling of layered host compounds in an aqueous solution of various amines has been investigated as an important step in the synthesis of molecularly thin 2D nanosheets. However, a complete understanding of the reaction process has not been attained, which is the barrier for producing high-quality unilamellar nanosheets. Here, the swelling and delamination behaviors of platelet single crystals of protonated layered metal oxides are systematically examined with a series of tetraalkylammonium (TAA) hydroxide solutions. Upon contact with the solutions, the crystals immediately underwent massive expansion by several tens to hundreds of times. The swollen crystals can be delaminated into elementary layers by the application of external shear force. The exfoliation behavior is dependent on TAA ions, especially in terms of yield and lateral size/shape of the delaminated nanosheets. The swollen crystals with TAA ions with longer alkyl chains are delaminated almost completely, but irregular and fractured small sheets are yielded. Such long alkyl chains become entangled on the oxide layer and resulting hydrophobic interactions may be responsible for the lateral fragmentation. It is found that replacement of aqueous solutions with organic solvents to suppress the hydrophobic interactions is effective to produce oversized nanosheets in rectangular shape with sharp edges., (© 2024 Wiley‐VCH GmbH.)

Background and Aims: EUS-guided biliary drainage (EUS-BD) has shown promising procedural outcomes in high-volume centers. Although inferior procedural outcomes were reported in inexperienced centers during the early days of EUS-BD, the current outcomes are unknown. This study aimed to clarify the feasibility and safety of EUS-BD in centers that recently introduced EUS-BD., Methods: This multicenter retrospective study was conducted at 22 centers that introduced EUS-BD between 2017 and 2022. A maximum of 20 initial EUS-BD cases at each center were evaluated. The clinical outcomes and experience of 84 endoscopists who performed these procedures were examined. Primary outcomes were the rate of technical success and adverse events (AEs), whereas secondary outcomes were risk factors associated with technical failure and procedure-related AEs., Results: Two hundred fifty-five patients were enrolled. The technical success rate was 91.4% (233/255). Among 22 technical failure cases, guidewire manipulation failure was the most common cause (n = 12) followed by tract dilation failure (n = 5). The AE rate was 10.2% (26/255). Multivariate analysis identified a puncture target diameter of <5 mm (odds ratio, 3.719; 95% CI, 1.415-9.776; P = .008) and moderate ascites extending to the liver surface (odds ratio, 3.25; 95% CI, 1.195-8.653; P = .021) as independent risk factors for technical failure and procedure-related AEs, respectively. Endoscopists' procedural experience was not a risk factor for technical failure or procedure-related AEs., Conclusions: The feasibility and safety of EUS-BD were maintained during the induction phase at inexperienced centers. These data will be helpful to better understand the current status of EUS-BD. (Clinical trial registration number: UMIN 000053615.)., Competing Interests: Disclosure All authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Alzheimer's disease (AD) is the most common form of dementia. Although drugs focusing on reducing amyloid β slow progression, they fail to improve cognitive function. Deficits in glucose metabolism are reflected in FDG-PET and parallel the neurodegeneration and synaptic marker loss closely preceding cognitive decline, but the role of metabolic deficits as a cause or consequence of neurodegeneration is unclear. Pyruvate dehydrogenase (PDH) is lost in AD and an important enzyme connecting glycolysis and the tricarboxylic acid (TCA) cycle by converting pyruvate into acetyl-CoA. It is negatively regulated by pyruvate dehydrogenase kinase (PDHK) through phosphorylation., Methods: In the present study, we assessed the in vitro/ in vivo pharmacological profile of the novel PDHK inhibitor that we discovered, Compound A. We also assessed the effects of Compound A on AD-related phenotypes including neuron loss and cognitive impairment using 5xFAD model mice., Results: Compound A inhibited human PDHK1, 2 and 3 but had no inhibitory activity on PDHK4. In primary neurons, Compound A enhanced pyruvate and lactate utilization, but did not change glucose levels. In contrast, in primary astrocytes, Compound A enhanced pyruvate and glucose utilization and enhanced lactate production. In an efficacy study using 5xFAD mice, Compound A ameliorated the cognitive dysfunction in the novel object recognition test and Morris water maze. Moreover, Compound A prevented neuron loss in the hippocampus and cerebral cortex of 5xFAD without affecting amyloid β deposits., Conclusions: These results suggest ameliorating metabolic deficits by activating PDH by Compound A can limit neurodegeneration and is a promising therapeutic strategy for treating AD., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objectives: Claudin (CLD), a major component of tight junctions, is a four-transmembrane protein, and 24 subtypes have been reported in humans. CLD expression is highly tissue-specific; CLD1 has been reported to be expressed in the skin and mucosa. There have been few reports on CLD1 expression and its function in oral cancer., Materials and Methods: This retrospective study immunohistochemically evaluated CLD1 expression as prognostic predictors in 84 participants with oral squamous cell carcinoma (OSCC). Participants were classified as positive or negative based on staining intensity; the clinicopathologic characteristics and survival rates of the two groups were compared. To clarify the biological role of CLD1 in OSCC cells, we examined the effects of CLD1 overexpression on the invasion and proliferation of the OSCC cell line, SCCKN., Results: We observed the immunohistochemical CLD1 expression in the cell membranes of OSCC cells. The disease-free survival rate was significantly lower in patients with CLD1-positive OSCC than in patients with CLD1-negative OSCC (P < .05). In vitro studies showed that cell proliferative capacity, motility, proteolytic activity, and invasive growth were promoted in CLD1-overexpressing SCCKN cells compared to those in control SCCKN cells., Conclusion: CLD1 may be a useful and potential prognostic factor for OSCC treatment., Competing Interests: DECLARATIONS OF INTEREST The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Sialyl glycans have several biological functions. We have previously reported on the preparation and bifidogenic activity of milk-derived sialylglycopeptide (MSGP) concentrate containing sialyl O -glycans. The current study qualitatively and quantitatively analyzed the sialyl O -glycans present in the MSGP concentrate. Notably, our quantitative analysis indicated that a majority of O -glycopeptides in the MSGP concentrate were derived from glycomacropeptides. The concentrate was found to contain mainly three types of sialyl core 1 O -glycans, with the disialyl core 1 O -glycan being the most abundant. We successfully quantified three types of sialyl core 1 O -glycans using a meticulous method that used homogeneous O -glycopeptides as calibration standards. Our results provide valuable insights into assessment strategies for the quality control of O -glycans in dietary products and underscore the potential applications of MSGP concentrate in the food industry and other industries.

Abstract: To discharge waste liquid containing radioactive iodine into sewage systems, long-term storage or dilution with a large amount of water may be required until the radioactivity concentration reduces below the standard value. Processing the waste liquid could be easier if radioactive iodine could be separated from the water. This study verified the effectiveness of superabsorbent polymer and α-cyclodextrin as treatment agents to separate radioactive iodine from waste liquids. Sodium iodide (Na 125 I) was added to purified water and artificial urine to prepare simulated waste liquids containing iodine equivalent to the urine of patients treated with radioactive iodine. The as-prepared simulated waste liquid was poured into a container with superabsorbent polymer and left for 90 d. The residual iodine rate in the simulated waste liquid was estimated by measuring 125 I radioactivity. When the water was sufficiently dried, residual iodine rates on day 15 were 0.102 and 0.884 in the simulated waste liquids comprising purified water and artificial urine, respectively. The simulated waste liquid comprising purified water with 5% α-cyclodextrin absorbed by 1 g of superabsorbent polymer had a residual rate of 0.980. Moreover, the residual rate of simulated waste liquid comprising artificial urine with 2% α-cyclodextrin absorbed by 1 g of SAP was 0.949. Superabsorbent polymer combined with α-cyclodextrin was an effective treatment agent for separating radioactive iodine from waste liquids., (Copyright © 2024 Health Physics Society.)

Matrix metalloproteinase-9 (MMP-9) is involved in tissue remodeling and in skin wound healing. The present study focuses on the MMP-9 expression in epidermal wound healing within 1 h after injury, to test whether MMP-9 can be used to estimate the time of injury in forensic practice.A sample consisting of 5 individuals undergoing surgery was analyzed. With the consent of the patients, sections of skin were removed from the surgical wound at predefined time intervals. For each subject, 8 sections were taken, one for each time interval defined at 0 '- 1' - 3 '- 5' - 10 '- 15' - 30 '- 60' minutes. The specimens were immunostained with MMP-9, and the number of positively stained cells was examined.The number of positively stained cells showed an increasing trend as a function of time. Less than 30 positively stained cells were found in all cases within 3 min. At the post-infliction time of 5 min, the number of positively stained cells exceeded 30 in 3 out of 5 cases. The number of MMP-positive cells exceeded 40 in all cases in over 10 min.In the light of these results, the count of MMP-9 positive cells might be a useful marker in the wound-age estimation within 1 h in forensic setting. More research is required to collect more samples and to compare samples from the hyperacute phase with those from several days after injury., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Atopic dermatitis (AD), a complex and heterogeneous chronic inflammatory skin disorder, manifests in a spectrum of clinical subtypes. The application of genomics has elucidated the role of genetic variations in predisposing individuals to AD. Transcriptomics, analyzing gene expression alterations, sheds light on the molecular underpinnings of AD. Proteomics explores the involvement of proteins in AD pathophysiology, while epigenomics examines the impact of environmental factors on gene expression. Lipidomics, which investigates lipid profiles, enhances our understanding of skin barrier functionalities and their perturbations in AD. This review synthesizes insights from these omics approaches, highlighting their collective importance in unraveling the intricate pathogenesis of AD. The review culminates by projecting future trajectories in AD research, particularly the promise of multi-omics in forging personalized medicine and novel therapeutic interventions. Such an integrated multi-omics strategy is poised to transform AD comprehension and management, steering towards more precise and efficacious treatment modalities., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Objective: The clinical impact of malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria in patients with kidney dysfunction remains poorly understood. This study investigated the usefulness of GLIM criteria for malnutrition in predicting mortality in patients with kidney dysfunction and different clinical renal states, including no kidney disease (NKD), acute kidney injury (AKI), and chronic kidney disease (CKD)., Methods: This single-center retrospective cohort study included 6,712 patients aged ≥18 admitted between 2018 and 2019. The relationship between the estimated glomerular filtration rate (eGFR) groups, nutritional status based on the GLIM criteria, and the incidence of all-cause mortality was evaluated using a multivariate Cox proportional hazards model. Malnutrition was defined as at least one phenotype (weight loss, low body mass index, or reduced muscle mass) and one etiological criterion (reduced intake/assimilation or disease burden/inflammation)., Results: Multivariate Cox proportional hazards model showed that eGFR ≤29 (vs. eGFR: 60-89, adjusted hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.52-2.22), 30-59 (vs. eGFR: 60-89, adjusted HR = 1.40, 95% CI: 1.20-1.64), and ≥90 (vs. eGFR: 60-89, adjusted HR = 1.40, 95% CI: 1.14-1.71), moderate and severe malnutrition (vs. without malnutrition, adjusted HR = 1.38 [1.18-1.62] and 2.18 [1.86-2.54], respectively) were independently associated with the incidence of death. The all-cause mortality rate was higher in patients with malnutrition or eGFR ≤29 (adjusted HR, 3.31; 95% CI: 2.51-4.35) than in patients without malnutrition or eGFR 60-89. Furthermore, moderate and severe malnutrition (vs. no malnutrition) was independently associated with death in patients with NKD, AKI, and CKD., Conclusion: Malnutrition based on the GLIM criteria was associated with increased all-cause mortality in inpatients, and malnutrition combined with kidney dysfunction was associated with a higher risk of mortality. Furthermore, patients with NKD, AKI, and CKD showed an association between malnutrition based on GLIM criteria and mortality., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Fish skin plays an important role in defending against pathogens in water, primarily through the secretion of skin mucus containing various immune-related factors. Local immune responses in the skin activate systemic immune responses by inflammatory cytokines. However, it remains unclear whether immune responses in the skin occur after systemic immune responses caused by pathogen invasion into the fish body. This study aimed to clarify the relationship between systemic immune responses and skin responses after intraperitoneal injection of formalin-killed cells (FKC) of Vibrio anguillarum. Although systemic inflammatory responses were observed in the spleen after injection, expression changes in the skin did not show significant differences. In contrast, expression of hemoglobin subunit genes significantly increased in the skin after FKC injection, suggesting that erythrocytes infiltrate extravascularly., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to identify factors influencing persistent muscle weakness in knee flexor strength after anterior cruciate ligament (ACL) reconstruction using the hamstring tendon and establish a clear cut-off value at 3 months postoperatively for the limb symmetry index (LSI) to exceed 90% at 6 months postoperatively., Methods: One hundred forty-eight patients undergoing ACL reconstruction were included and categorised into two groups based on knee flexor strength at 6 months postoperatively: patients with LSI of 90% or greater (achieved group: n = 114) and patients with LSI less than 85% (nonachieved group: n = 34). Items with significant differences between the two groups (preoperative waiting period, LSI to body weight ratio of knee flexor and extensor strength at 3 months postoperatively and peak torque angle of knee flexor muscle) were included in the multiple logistic regression analysis. Additionally, a receiver operating characteristic curve was used to calculate the cut-off value of the LSI at 3 months postoperatively, which was required to achieve the LSI criteria for knee flexor strength 6 months postoperatively., Results: Multiple logistic regression analysis extracted the preoperative waiting period and LSI for knee flexor strength at 3 months postoperatively. The cut-off value at 3 months postoperatively was 76.9% (area under the curve value, 0.82; sensitivity, 0.76; and specificity, 0.81) of the LSI., Conclusion: The LSI of at least 76.9% for knee flexor strength at 3 months after ACL reconstruction was an indicator for achieving the 6 months postoperatively. This is a criterion to aim for, considering the stress on the graft and the regeneration process of the semitendinosus tendon., Level of Evidence: Level III., (© 2024 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

The exact relationship between solid papillary carcinoma (SPC) and invasive breast carcinoma of no special type (IBC-NST) with neuroendocrine differentiation and SPC and mucinous carcinoma (MC) of the breast remains unclear. To clarify the relationship, we conducted a comparative study of morphological and neuroendocrine features between ductal carcinoma in situ (DCIS, 72 cases) and SPC in situ (35 cases), and IBC-NST (103 cases) and invasive SPC (92 cases). We also conducted the study between MC associated with and without SPC. Synaptophysin, chromogranin A, and INSM1 were employed for the immunohistochemical study. IBC-NST had occasionally a morphological similarity with invasive SPC. While 123 of 127 cases with SPC demonstrated diffuse staining with one or more of the neuroendocrine markers, the only one case of DCIS and none of IBC-NST showed it. Type B was observed in 16 of 18 cases of MC associated with SPC and in 13 of 33 cases of MC without it. All the cases of MC with SPC and 6 of 33 cases without it showed diffuse staining for at least one of the neuroendocrine markers. In conclusion, a careful distinction between invasive SPC and IBC-NST with neuroendocrine differentiation is required. We assume that SPC in situ is a potential candidate for precursor of IBC-NST with neuroendocrine differentiation. MC of the breast is suggested to have two pathogenetic pathways through SPC in situ or non-SPC in situ. SPC in situ is thought to be less common as a precursor of MC than non-SPC in situ., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To evaluate the efficacy of vitrectomy with epiretinal proliferation (EP) sparing for full-thickness macular hole (FTMH) accompanied by EP., Methods: A multicenter, retrospective study. Eyes were divided into two groups: the sparing group (Group S) included eyes in which the EP around the hole was peeled and preserved, whereas the removal group (Group R) included eyes in which the EP was partially or completely removed. The internal limiting membrane was peeling in all eyes., Results: Forty-six eyes were included. Twenty-five eyes were in Group S, and 21 eyes were in Group R, with no difference in preoperative best-corrected visual acuity (BCVA) (P = 0.96). After primary surgery, MHs were closed in all eyes, and there were no complications in either group. Postoperative 12-month BCVA significantly improved in both groups (both P < 0.01), while Group S had better 12-month BCVA than Group R (P = 0.016). In the multivariable analysis, EP sparing was associated with better BCVA at 12 months (P = 0.006) after accounting for the minimal macular hole size and preoperative BCVA., Conclusions: EP sparing and removal were both safe and effective techniques, while EP sparing may provide a favorable outcome for eyes with FTMH and EP.

Aim: Our goal was to investigate the use of Cyclodextrin in creating an aqueous extract of Cinnamon with a high content of its bioactive ingredients, validated by cell-based assays., Background: Due to their safety and cost-effectiveness, natural compounds have garnered attention for cancer therapy, which often faces challenges related to drug toxicity and resistance. Cinnamon (Cinnamomum verum; also known as Ceylon Cinnamon) is a commonly used spice with a history in folk medicine for treating various ailments. However, its active ingredients suffer from poor solubility, stability, and bioavailability, which limits its use and benefits., Objective: We prepared γCyclodextrin (γCD)-assisted aqueous extract of Cinnamon (CD-CIN) and compared its activity with the DMSO extract (DM-CIN)., Methods: The cells were exposed to CD-CIN and DM-CIN extracts under normal and stressed (oxidative, metal, and hypoxic) conditions and then analyzed for stress and cancerous phenotypes using various molecular assays., Results: We found that CD-CIN possesses considerable anticancer activity that involves the activation of tumor suppressor proteins and DNA damage response. Low, non-toxic concentrations of DM-CIN and CD-CIN caused comparable inhibition of migration and invasion capability of cells, supported by molecular marker analyses. Furthermore, protection against oxidative, metal, and hypoxia stress, as well as induction of differentiation, was recorded in both DM-CIN and CD-CIN treated cells, as compared to the control., Conclusion: We report CD-CIN as a new economic and easy Cinnamon-derived resource that possesses considerable anticancer and antistress activities and hence warrants further chemical, in vitro, and in vivo studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Adaptation to cold was essential for human migration across Eurasia. Non-shivering thermogenesis through brown adipose tissue (BAT) participates in cold adaptation because some genes involved in the differentiation and function of BAT exhibit signatures of positive natural selection in populations at high latitudes. Whether these genes are associated with the inter-individual variability in BAT thermogenesis remains unclear. In this study, we evaluated the potential associations between BAT activity and single nucleotide polymorphisms (SNPs) in candidate gene regions in East Asian populations., Methods: BAT activity induced by mild cold exposure was measured in 399 healthy Japanese men and women using fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT). The capacity for cold-induced thermogenesis and fat oxidation was measured in 56 men. Association analyses with physiological traits were performed for 11 SNPs at six loci (LEPR, ANGPTL8, PLA2G2A, PLIN1, TBX15-WARS2, and FADS1) reported to be under positive natural selection. Associations found in the FDG-PET/CT population were further validated in 84 healthy East Asian men and women, in whom BAT activity was measured using infrared thermography. Associations between the SNP genotypes and BAT activity or other related traits were tested using multiple logistic and linear regression models., Results: Of the 11 putative adaptive alleles of the six genes, two intronic SNPs in LEPR (rs1022981 and rs12405556) tended to be associated with higher BAT activity. However, these did not survive multiple test comparisons. Associations with lower body fat percentage, plasma triglyceride, insulin, and HOMA-IR levels were observed in the FDG-PET/CT population (P < 0.05). Other loci, including TBX15-WARS2, which is speculated to mediate cold adaptation in Greenland Inuits, did not show significant differences in BAT thermogenesis., Conclusions: Our results suggest a marginal but significant association between LEPR SNPs. However, robust supporting evidence was not established for the involvement of other loci under positive natural selection in cold adaptation through BAT thermogenesis in East Asian adults. Given the pleiotropic function of these genes, factors other than cold adaptation through BAT thermogenesis, such as diet adaptation, may contribute to positive natural selection at these loci., (© 2024. The Author(s).)

Background Glioblastoma (GBM) is the most frequent invasive brain tumor and a rapidly progressive disease with a poor prognosis that predominantly affects middle-aged and older adults. The relationship between daily functioning and prognosis in patients with GBM will become more important as advances in multimodality treatment are expected to increase the number of long-term survivors. Methods Sixty-seven patients were initially diagnosed with GBM at our hospital between December 2013 and December 2022. All patients were divided into two groups: those who survived for one year or longer from the date of discharge (Group A) and those who died within one year from the date of discharge (Group B). Muscle strength, nutritional status, and Karnofsky Performance Status (KPS) were examined upon admission (p1), post-surgery (p2), and discharge (p3), and their relationships with prognosis were investigated. Results Group A was significantly younger than Group B, with a significant difference in the total radiation dose. There were no significant differences in the anatomical tumor location, whether the tumor occurred on the left or right side, or tumor size. KPS at discharge (p3) and the degree of improvement in the KPS between p1 and p3 were associated with a good prognosis. Conclusions The KPS varies throughout the treatment. When considering the KPS as a prognostic indicator, the KPS at discharge is the most important, given the structure of the disability and the course of treatment for GBM., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Ethics Committee of Nara Medical University Hospital issued approval 3404. This study was approved by the Ethics Committee of Nara Medical University Hospital, and information was collected from medical records in accordance with the Declaration of Helsinki while maintaining patient anonymity and confidentiality. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: A.K. was funded by by JSPS KAKENHI (grant numbers JP 18K10753 and JP23K10510). . Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sasaki et al.)

Lenvatinib (LEN), a multitarget tyrosine kinase inhibitor used in various cancer treatments, is mainly metabolized by cytochrome P450 3A (CYP3A) enzymes. The importance of therapeutic drug monitoring (TDM) in patients administered LEN has been proposed. Although some biomarkers of endogenous CYP3A activity have been reported, their utility in dosage adjustments has not been well evaluated. This study investigated the correlation between plasma LEN concentrations and endogenous urinary CYP3A biomarkers in clinical practice. Concentrations of plasma LEN (N = 225) and CYP3A biomarkers (cortisol, 6β-hydroxycortisol, deoxycholic acid, and 1β-hydroxydeoxycholic acid) in urine (N = 214) from 20 patients (hepatocellular carcinoma, N = 6; thyroid cancer, N = 3; endometrial cancer, N = 8; and renal cell carcinoma, N = 3) collected for consultation for up to 1 year were evaluated using liquid chromatography-tandem mass spectrometry. Moreover, plasma trough LEN concentrations were predicted using a three-compartment model with linear elimination for outpatients administered LEN before sample collection. Moderate correlations were observed between the quantified actual concentrations and the predicted trough concentrations of LEN, whereas there was no correlation with endogenous urinary CYP3A biomarkers. The utility of endogenous urinary CYP3A biomarkers could not be determined. However, TDM for outpatients administered orally available medicines may be predicted using a nonlinear mixed effect model (NONMEM). This study investigated the utility of endogenous urinary CYP3A biomarkers for personalized medicine and NONMEM for predicting plasma trough drug concentrations. These findings will provide important information for further clinical investigation and detailed TDM., (© 2024 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Objectives: In this study, we aimed to investigate the prevalence of oral frailty and explore its relationship with oral function and sarcopenia among older outpatients., Materials and Methods: In this cross-sectional study, we retrospectively included older patients who visited a frailty outpatient clinic. We assessed total oral frailty employing, among other measures, oral diadochokinesis (/ta/ sound) for tongue-lip movement and tongue pressure. Patients who did not meet the cut-off values for three or more of these were classified as having oral frailty. Sarcopenia was assessed according to Asian Working Group for Sarcopenia 2019 criteria and analyzed for the relationship with oral function., Results: The mean ± standard deviation age of the 111 patients was 77.2 ± 5.7 y; 63 were women (57%). Fifteen patients (14%) had either sarcopenia or dynapenia. The overall prevalence of oral frailty was 38%, with no significant difference in its prevalence between the sarcopenia/dynapenia group (44%) and the robust (no sarcopenia/dynapenia) group (35%). The following oral function assessments significantly differed between the sarcopenia/dynapenia group and the robust group: median (interquartile range) total oral frailty score, 2 (2-4) and 2 (1-3) (P = 0.019); tongue-lip motor function, 5.4 ± 1.2 and 5.9 ± 1.2 times/s (P = 0.049); and tongue pressure, 27.3 ± 8.5 kPa and 31.7 ± 8.0 kPa (P = 0.009)., Conclusions: Approximately 40% of patients exhibited a decline in oral function regardless of the presence of sarcopenia. Sarcopenia and dynapenia may particularly affect tongue function. Although assessing patients for sarcopenia is crucial, separate evaluations of oral function should also be considered., 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.)

Background: This study aimed to investigate the difference in lateral distal femoral angle (LDFA) between knees with medial osteoarthritis (mOA) and knees without osteoarthritis, and to explore the validity of the assumption that there is no bone wear on the femoral articular surface in kinematic alignment total knee arthroplasty (KA-TKA)., Methods: The study included 69 patients with mOA on one side of the knee and but no OA on the other side. LDFA, medial proximal tibial angle (MPTA), mechanical hip-knee-ankle angle (mHKA), and arithmetic hip-knee-ankle angle (aHKA) were measured and compared between the knees. Pearson's correlation coefficient and paired t-tests were used for statistical analysis., Results: The LDFA and MPTA were significantly more varus in mOA knees than in knees non-OA knees, with differences of 1.0° ± 2.3° and 0.9° ± 2.0°, respectively. The difference between mHKA of the non-OA side and aHKA of the mOA side was not significant, indicating that it is appropriate to use aHKA as an estimation of postoperative alignment after kinematically-aligned total knee arthroplasty without anatomical correction. However, there was a significant difference in MPTA and aHKA between male and female patients in both mOA and non-OA knees., Conclusions: The assumption that there is no bone wear on the femoral articular surface is rejectable, and the constant compensation thickness of 2 mm for cartilage wear may not be sufficient. Further research is needed to estimate the amount of bone wear in both femur and tibia side to develop more individualized surgical planning strategies in KA-TKA., 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 B.V. All rights reserved.)

Background: Sympathetic activation of brown adipose tissue (BAT) thermogenesis can ameliorate obesity and related metabolic abnormalities. However, crucial subtypes of the β-adrenergic receptor (AR), as well as effects of its genetic variants on functions of BAT, remains unclear in humans. We conducted association analyses of genes encoding β-ARs and BAT activity in human adults., Methods: Single nucleotide polymorphisms (SNPs) in β1-, β2-, and β3-AR genes (ADRB1, ADRB2, and ADRB3) were tested for the association with BAT activity under mild cold exposure (19 °C, 2 h) in 399 healthy Japanese adults. BAT activity was measured using fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT). To validate the results, we assessed the effects of SNPs in the two independent populations comprising 277 healthy East Asian adults using near-infrared time-resolved spectroscopy (NIR TRS ) or infrared thermography (IRT). Effects of SNPs on physiological responses to intensive cold exposure were tested in 42 healthy Japanese adult males using an artificial climate chamber., Results: We found a significant association between a functional SNP (rs1042718) in ADRB2 and BAT activity assessed with FDG-PET/CT (p < 0.001). This SNP also showed an association with cold-induced thermogenesis in the population subset. Furthermore, the association was replicated in the two other independent populations; BAT activity was evaluated by NIR TRS or IRT (p < 0.05). This SNP did not show associations with oxygen consumption and cold-induced thermogenesis under intensive cold exposure, suggesting the irrelevance of shivering thermogenesis. The SNPs of ADRB1 and ADRB3 were not associated with these BAT-related traits., Conclusions: The present study supports the importance of β2-AR in the sympathetic regulation of BAT thermogenesis in humans. The present collection of DNA samples is the largest to which information on the donor's BAT activity has been assigned and can serve as a reference for further in-depth understanding of human BAT function., (© 2024. The Author(s).)