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International treatment guidelines recommend tumor resection for patients with oligometastatic colorectal cancer (CRC). Despite this, recurrence occurs in ∼60% of patients post-surgery, indicating that the role and optimal type of perioperative systemic therapy has not been fully defined. In the COSMOS-oligo trials, comprising two studies, we are evaluating the potential role of circulating tumor DNA (ctDNA) analysis in clinical decision making and exploring adjuvant therapy strategies for patients with resectable metastatic CRC. The COSMOS-CRC-03 study aims to evaluate the prognostic value of post-operative minimal residual disease as detected by ctDNA and to explore the role of ctDNA in detecting disease recurrence. We plan to assess the predictive accuracy of ctDNA results for recurrence using blood collected 28 days post-surgery. We will additionally explore whether regular post-operative ctDNA test can detect recurrence earlier than standard imaging. Post-operative adjuvant therapy will not be administered to ctDNA-negative patients. The complementary AURORA trial is a randomized phase II study designed to test whether post-operative mFOLFOXIRI plus bevacizumab is superior to standard mFOLFOX6 for patients with metastatic CRC when the ctDNA status is positive after curative-intent surgery for patients enrolled in the COSMOS-CRC-03 study. Both studies will only include patients with resectable distant metastases of CRC. We designed these studies to stratify patients based on the results of a ctDNA assay and to determine the optimal treatment for patients at the highest risk for recurrence.

Silicon carbide (SiC) and its composites are candidate materials for the blanket components and for the first wall in a fusion reactor. If the SiC is used without any armor materials for the first wall, it is exposed by helium (He) plasma as well as hydrogen plasma. Characteristic surface morphology changes are reported for various materials by He plasma exposure. Thus, we exposed SiC specimens to He or simultaneous deuterium (D) and He (D + He) plasma by various conditions and then observed surface morphology changes by SEM. As a result, needle-like structures and whiskers-like structures at the tip were formed in He plasma and D + He irradiation, while only needle-like structures were formed in D plasma. Therefore, it indicated that the effects of He were attributed to form whiskers-like structures. Although the structures are different among He plasma, simultaneous D + He plasma and D plasma irradiations, sputtering is considered to be a dominant process for the formation of the structure formation. However, the effects of He atoms in the structure could also be attributed to form whiskers-like structures. Keywords: Helium induced nanostructure, Morphology change, Silicon carbide

Antecedentes: La presencia de fibrosis hepática es el denominador común de numerosas enfermedades crónicas del hígado que pueden evolucionar a fibrosis y a hepatocarcinoma. Las más importantes por su frecuencia son las hepatitis virales y el hígado graso no alcohólico, cuya prevalencia aumenta en proporciones epidémicas. La biopsia hepática, aun cuando imperfecta, continúa siendo el estándar de oro que tiende a ser reemplazado en muchas situaciones clínicas por métodos de imagen no invasivos. Objetivos: Describir la experiencia obtenida en nuestro departamento de imagen con la técnica de elastografía por resonancia magnética, analizar y comentar los resultados publicados por otros autores en la literatura reciente en gastroenterología, hepatología y radiología, complementada con una búsqueda en PubMed de los últimos 10 años. Resultados y conclusiones: La elastografía por resonancia magnética es un método no invasivo y eficaz, cuyos resultados tienen concordancia con la biopsia hepática, presenta superioridad sobre los métodos de elastografía por ultrasonido debido a que evalúa un volumen mucho mayor de tejido hepático y muestra la distribución de las lesiones que, a menudo, es heterogénea. La mayor ventaja del protocolo de resonancia magnética descrito estriba en cuantificar en la misma sesión, además de la fibrosis, el contenido de grasa y de hierro, lo cual se realiza en una exploración dirigida específicamente a este fin, en un tiempo de 25 min y a un costo-beneficio favorable para el paciente y la institución.

Background: The presence of liver fibrosis is the common denominator in numerous chronic liver diseases that can progress to fibrosis and hepatocellular carcinoma. Most important, with respect to frequency, are viral hepatitis and non-alcoholic fatty liver disease, the prevalence of which is increasing in epidemic proportions. Liver biopsy, albeit imperfect, continues to be the criterion standard, but in many clinical situations tends to be replaced with noninvasive imaging methods. Objectives: The aim of the present article was to describe our imaging department experience with magnetic resonance elastography and to analyze and discuss recently published results in gastroenterology, hepatology, and radiology from other authors in the literature, complemented with a PubMed search covering the last 10 years. Results and conclusions: Magnetic resonance elastography is an efficacious, noninvasive method with results that are concordant with liver biopsy. It is superior to ultrasound elastography because it evaluates a much greater volume of hepatic tissue and shows the often heterogeneous lesion distribution. The greatest advantage of the magnetic resonance protocol described is the fact that it quantifies fibrosis, fat content, and iron content in the same 25 min examination specifically directed for that purpose, resulting in a favorable cost-benefit ratio for the patient and/or institution.

This study measured chlorine- and chloramine-reactive precursors using formation potential (FP) tests of nine U.S. Environmental Protection Agency (EPA) regulated and 57 unregulated disinfection byproducts (DBPs) in tertiary-filtered wastewater before and after pilot-scale granular activated carbon (GAC) adsorption. Using breakthrough of precursor concentration and of concentration associated calculated cytotoxicity and genotoxicity (by correlating known lethal concentrations reported elsewhere), the performance of three parallel GAC treatment trains were compared against tertiary-filtered wastewater: ozone/GAC, chlorine/GAC, and GAC alone. Results show GAC alone was the primary process, versus ozone or chlorine alone, to remove the largest fraction of total chlorine- and chloramine-reactive DBP precursors and calculated cytotoxicity and genotoxicity potencies. GAC with pre-ozonation removed the most chlorine- and chloramine-reactive DBP precursors followed by GAC with pre-chlorination and lastly GAC without pre-treatment. GAC with pre-ozonation produced an effluent with cytotoxicity and genotoxicity of DBPs from FP that generally matched that of GAC without pre-oxidation; meanwhile removal of toxicity was greater by GAC with pre-chlorination. The cytotoxicity and genotoxicity of DBPs from FP tests did not scale with DBP concentration; for example, more than 90% of the calculated cytotoxicity resulted from 20% of the DBPs, principally from haloacetaldehydes, haloacetamides, and haloacetonitriles. The calculated cytotoxicity and genotoxicity from DBPs associated with FP-chloramination were at times higher than with FP-chlorination though the concentration of DBPs was five times higher with FP-chlorination. The removal of DBP precursors using GAC based treatment was at least as effective as removal of DOC (except for halonitromethanes for GAC without pre-oxidation and with pre-chlorination), indicating DOC can be used as an indicator for DBP precursor adsorption efficacy. However, the DOC was not a good surrogate for total cytotoxicity and genotoxicity breakthrough behavior, therefore, unregulated DBPs could have negative health implications that are disconnected from general water quality parameters, such as DOC, and regulated classes of DBPs. Instead, cytotoxicity and genotoxicity correlate with the concentration of specific classes of unregulated DBPs.

Background: Dysfunctional breathing (DB) is a major asthma comorbidity; however, it is not well recognized in Japan. Moreover, it has rarely been reported in the asthma population, and its clinical characteristics are unclear. We aimed to clarify the clinical characteristics of DB as a comorbidity in patients with asthma in Japan. Questionnaire surveys were conducted among patients with asthma at medical facilities in three regions of Japan (Niigata, Kumamoto, and Tokyo)., Methods: This cross-sectional questionnaire survey targeting patients with asthma who had regularly visited medical institutions and their doctors was conducted from September to November 2021. The questionnaire addressed the control status and method of treatment. The diagnosis of DB was evaluated using the Nijmegen questionnaire (NQ)., Results: There were 2087 eligible participants. Based on their NQ scores, 217 patients were classified into the DB group (NQ ≥ 19). There were significant differences with respect to sex, disease duration, Asthma Control Test (ACT) scores, Patient Health Questionnaire-9 (PHQ-9) scores, type-2 biomarkers, pulmonary function indices, treatment methods, severity, and asthma exacerbations in the previous year between the DB and non-DB groups. In the multivariate analysis, there were significant differences in sex, disease duration (≥15 y), ACT scores (<20), and PHQ-9 scores (≥10). The cluster analysis of cases with DB classified the population into four clusters., Conclusions: The asthma population with DB exhibited several characteristics, including depression and poorly controlled asthma. Further large-scale interventional investigations with longer follow-up periods are necessary to verify these findings., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Author. Published by Elsevier B.V. All rights reserved.)

Randomized controlled trials (RCTs) and studies using real-world data (RWD) each have their strengths and weaknesses, and can effectively complement each other. When RCTs are not feasible, RWD studies offer a valuable alternative. In this narrative review, we examine several types of RWD studies, focusing on studies utilizing administrative claims databases. These include the Diagnosis Procedure Combination databases, commercially available health checkups and healthcare claims databases (such as the JDMC and DeSC databases), and the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). Given that these claims databases cover different populations, patient settings, variables, and levels of accessibility, it is crucial for researchers to select the most appropriate data source to effectively address their research questions. Additionally, it is desirable for readers of studies using these databases to be aware of their characteristics in order to fully understand the context and limitations of the research findings., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Objective: To elucidate the patient's journey to epilepsy surgery and identify the risk factors contributing to surgical delay in pediatric patients with drug-resistant epilepsy (DRE) due to focal cortical dysplasia (FCD)., Methods: A retrospective review was conducted of 93 pediatric patients who underwent curative epilepsy surgery for FCD between January 2012 and March 2023 at a tertiary epilepsy center. The Odyssey plot demonstrated the treatment process before epilepsy surgery, including key milestones of epilepsy onset, first hospital visit, epilepsy diagnosis, MRI diagnosis, DRE diagnosis, and surgery. The primary outcome was surgical delay; the duration from DRE to surgery. Multivariate linear regression models were used to examine the association between surgical delay and clinical, investigative, and treatment characteristics., Results: The median age at seizure onset was 1.3 years (interquartile range [IQR] 0.14-3.1), and at the time of surgery, it was 6 years (range 1-11). Notably, 46% experienced surgical delays exceeding two years. The Odyssey plot visually highlighted that surgical delay comprised a significant portion of the patient journey. Although most patients underwent MRI before referral, MRI abnormalities were identified before referral only in 39% of the prolonged group, compared to 70% of the non-prolonged group. Multivariate analyses showed that delayed notification of MRI abnormalities, longer duration from epilepsy onset to DRE, older age at onset, number of antiseizure medications tried, and moderate to severe intellectual disability were significantly associated with prolonged surgical delay., Conclusion: Pediatric DRE patients with FCD experienced a long journey until surgery. Early and accurate identification of MRI abnormalities is important to minimize surgical delays., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Social inactivity after a stroke leads to adverse outcomes, making social activity after discharge important for chronic stroke survivors. This study aimed to investigate the effects of early rehabilitation services after discharge on social activity among chronic stroke survivors., Methods: The participants were prospectively recruited from 3 convalescent hospitals. Receipt of early rehabilitation services after discharge for chronic stroke survivors was defined as the utilization of day care or home-based rehabilitation services by the Japanese long-term care insurance system. Social activity was assessed using the Frenchay Activities Index (FAI) premorbid and at 3, 6, and 12 months after discharge. In this study, the outcome was defined as the change in the FAI score from 3 to 12 months after discharge. Multivariate regression analysis was performed to examine the effect of access to rehabilitation on changes in FAI., Results: Ninety stroke survivors (age 67.2±11.6 years, 52 male) were enrolled. The FAI showed improvements by 27.4% and 1.4% from 3 to 12 months after discharge in the rehabilitation and nonrehabilitation groups, respectively. Multivariate regression analysis showed that access to rehabilitation after discharge was positively associated with the FAI change from 3 to 12 months after discharge (B=30.3, β=0.38, 95% confidence interval=11.13-49.47, P=0.002)., Conclusions: Early rehabilitation services after discharge were significantly associated with increased social activity., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The clinical importance of skeletal muscle characteristics for improving gait ability of stroke survivors is increasing. We aimed to examine the association between muscle quantity and quality at discharge and changes in gait independence at the time of 1 year after discharge in patients with stroke., Methods: This prospective observational study included 100 patients with stroke who were admitted to a convalescent rehabilitation ward. We defined muscle quantity and quality operationally as muscle thickness and echo intensity observed in ultrasonography images, respectively, and measured quadriceps muscle on the paretic and non-paretic sides at the time of discharge. The outcome measured in our study was changes in gait independence 1 year after discharge, as assessed by the Functional Independence Measure gait assessment tool score., Results: Among the study participants, 23 (23.0 %) were assessed to have reduced gait independence, while 77 (77.0 %) were evaluated to have improved or maintained gait independence. Our multivariate logistic regression analysis revealed that only muscle quantity on the paretic side was significantly associated with an improvement or maintenance of gait independence (odds ratios 3.32; 95 % confidence interval 1.01-10.95; p = 0.049)., Conclusions: Our findings revealed that an improvement in gait independence 1 year after discharge was influenced by quadriceps muscle quantity on the paretic side at the time of discharge in patients with subacute stroke. This finding highlights the importance of lower limb muscle quantity on the paretic side as a clinically significant factor that influences the improvement in gait ability after hospital discharge., Competing Interests: Declaration of competing interest The authors report there are no competing interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Osteoclasts are multinucleated cells with bone resorption activity. Excessive osteoclast activity has been implicated in osteoporosis, rheumatoid arthritis, and bone destruction due to bone metastases from cancer, making osteoclasts essential target cells in bone and joint diseases. C-terminal domain nuclear envelope phosphatase 1 (Ctdnep1, formerly Dullard) is a negative regulator of transforming growth factor (TGF)-β superfamily signaling and regulates endochondral ossification in mesenchymal cells during skeletal development. In this study, we investigated the role of Ctdnep1 in the Receptor activator of nuclear factor-kappa B ligand (RANKL)-induced RAW264.7 osteoclast differentiation. Expression of Ctdnep1 did not change during osteoclast differentiation; Ctdnep1 protein localized to the cytoplasm before and after osteoclast differentiation. Small interfering RNA-mediated knockdown of Ctdnep1 increased tartrate-resistant acid phosphatase-positive multinucleated osteoclasts and the expression of osteoclast marker genes, including Acp5, Ctsk, and Nfatc1. Interestingly, the knockdown of Ctdnep1 increased the protein level of Nfatc1 in cells unstimulated with RANKL. Knockdown of Ctdnep1 also enhanced calcium-resorbing activity. Mechanistically, the knockdown of Ctdnep1 increased the phosphorylation of RANKL signaling components. These results suggest that Ctdnep1 negatively regulates osteoclast differentiation by suppressing the RANKL signaling pathway., 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 and Purpose: Neuromyelitis optica spectrum disorder is a demyelinating and inflammatory affliction that often leads to visual disturbance. Various imaging techniques, including free-water imaging, have been used to determine neuroinflammation and degeneration. Therefore, this study aimed at determining multimodal imaging differences between patients with neuromyelitis optica spectrum disorder, especially those with visual disturbance, and healthy controls., Materials and Methods: Eighty-five neuromyelitis optica spectrum disorder patients and 89 age- and sex-matched healthy controls underwent 3-T magnetic resonance imaging (MRI). We analyzed adjusted brain-predicted age difference, voxel-based morphometry, and free-water-corrected diffusion tensor imaging (DTI) by tract-based spatial statistics in each patient group (MRI-positive/negative neuromyelitis optica spectrum disorder patients with or without a history of visual disturbance) compared with the healthy control group., Results: MRI-positive neuromyelitis optica spectrum disorder patients exhibited reduced volumes of the bilateral thalamus. Tract-based spatial statistics showed diffuse white matter abnormalities in all DTI metrics in MRI-positive neuromyelitis optica spectrum disorder patients with a history of visual disturbance. In MRI-negative neuromyelitis optica spectrum disorder patients with a history of visual disturbance, voxel-based morphometry showed volume reduction of bilateral thalami and optic radiations, and tract-based spatial statistics revealed significantly lower free-water-corrected fractional anisotropy and higher mean diffusivity in the posterior dominant distributions, including the optic nerve radiation., Conclusion: Free-water-corrected DTI and voxel-based morphometry analyses may reflect symptoms of visual disturbance in neuromyelitis optica spectrum disorder., (Copyright © 2023. Published by Elsevier B.V.)

Spectral variations of light-harvesting (LH) proteins of purple photosynthetic bacteria provide insight into the molecular mechanisms underlying spectral tuning of circular bacteriochlorophyll (BChl) arrays, which play crucial roles in photoenergy conversion in these organisms. Here we investigate spectral changes of the Q y band of B850 BChl a in LH2 protein from purple sulfur bacterium Thermochromatium tepidum (tepidum-LH2) by detergents and Ca 2+ . The tepidum-LH2 solubilized with lauryl dimethylamine N-oxide and n-octyl-β-D-glucoside (LH2 LDAO and LH2 OG , respectively) exhibited blue-shift of the B850 Q y band with hypochromism compared with the tepidum-LH2 solubilized with n-dodecyl-β-D-maltoside (LH2 DDM ), resulting in the LH3-like spectral features. Resonance Raman spectroscopy indicated that this blue-shift was ascribable to the loss of hydrogen-bonding between the C3-acetyl group in B850 BChl a and the LH2 polypeptides. Ca 2+ produced red-shift of the B850 Q y band in LH2 LDAO by forming hydrogen-bond for the C3-acetyl group in B850 BChl a, probably due to a change in the microenvironmental structure around B850. Ca 2+ -induced red-shift was also observed in LH2 OG although the B850 acetyl group is still free from hydrogen-bonding. Therefore, the Ca 2+ -induced B850 red-shift in LH2 OG would originate from an electrostatic effect of Ca 2+ . The current results suggest that the B850 Q y band in tepidum-LH2 is primarily tuned by two mechanisms, namely the hydrogen-bonding of the B850 acetyl group and the electrostatic effect., 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.)

Osteoporosis is characterized by weakened bone microstructure and loss of bone mass. Current diagnostic criteria for osteoporosis are based on the T-score, which is a measure of bone mineral density. However, osteoporotic fragility fractures can occur regardless of the T-score, underscoring the need for additional criteria for the early detection of patients at fracture risk. To identify indicators of reduced bone strength, we performed serum proteomic analysis using data-independent acquisition mass spectrometry with serum samples from two patient groups, one with osteoporosis but no fractures and the other with osteopenia and fragility fractures. Collective evaluation of the results identified six serum proteins that changed to a similar extent in both patient groups compared with controls. Of these, extracellular matrix protein 1 (ECM1), which contributes to bone formation, showed the most significant increase in serum levels in both patient groups. An ELISA-based assay suggested that ECM1 could serve as a serum indicator of the need for therapeutic intervention; however, further prospective studies with a larger sample size are necessary to confirm these results. The present findings may contribute to the provision of early and appropriate therapeutic strategies for patients at risk of osteoporotic fractures. SIGNIFICANCE: This study aimed to identify objective serum indicators of the need for therapeutic intervention in individuals at risk of osteoporotic fracture. Comprehensive proteome analyses of serum collected from patients with osteoporosis but no fractures, patients with osteopenia and fragility fractures, and controls were performed by data-independent acquisition mass spectrometry. Collective evaluation of the proteome analysis data and ELISA-based assays identified serum ECM1 as a potential objective marker of the risk of fragility fractures in patients with osteoporosis or osteopenia. The findings are an important step toward the development of appropriate bone health management methods to improve well-being and maintain quality of life., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

A biomembrane-related fibrillogenesis of Amyloid β from Alzheimer' disease (Aβ) is closely related to its accumulation behavior. A binding property of Aβ peptides from Alzheimer' disease to lipid membranes was then classified by a quartz crystal microbalance (QCM) method combined with an immobilization technique using thiol self-assembled membrane. The accumulated amounts of Aβ, Δf max , was determined from the measurement of the maximal frequency reduction using QCM. The plots of Δf max to Aβ concentration gave the slope and saturated value of Δf max , (Δf max ) sat that are the parameters for binding property of Aβ to lipid membranes. Therefore, the Aβ-binding property on lipid membranes was classified by the slope and (Δf max ) sat . The plural lipid system was described as X + Y where X = L 1 , L 1 /L 2 , and L 1 /L 2 /L 3 . The slope and (Δf max ) sat values plotted as a function of mixing ratio of Y to X was classified on a basis of the lever principle (LP). The LP violation observed in both parameters resulted from the formation of the crevice or pothole, as Aβ-specific binding site, generated at the boundary between l d and l o phases. The LP violation observed only in the slope resulted from glycolipid-rich domain acting as Aβ-specific binding site. Furthermore, lipid planar membranes indicating strong LP violation favored strong fibrillogenesis. Especially, lipid planar membranes indicating the LP violation only in the slope induced lateral aggregated and spherulitic fibrillar aggregates. Thus, the classification of Aβ binding property on lipid membranes appeared to be related to the fibrillogenesis with a certain morphology., 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. Toshinori Shimanouchi and Minoru Noda report financial support was provided by JSPS KAKENHI., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Using patient registries or limited regional hospitalization data may result in underestimation of the incidence and prevalence of rare diseases. Therefore, we used the national administrative database to estimate the incidence and prevalence of lymphangioleiomyomatosis over six years (2014-2019) and describe changes in clinical practice and mortality., Methods: We extracted data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan between January 2013 and December 2020. This database covers ≥99% of the population. We used the diagnostic code for lymphangioleiomyomatosis to estimate the incidence and prevalence from 2014 to 2019. Additionally, we examined the demographic characteristics, treatments, comorbidities, and mortality of the patients., Results: In women, the incidence and prevalence of lymphangioleiomyomatosis in 2019 were approximately 3 per 1,000,000 person-years and 28.7 per 1,000,000 persons, respectively. While, in men, the incidence and prevalence of lymphangioleiomyomatosis were <0.2 per 1,000,000 person-years and 0.8 per 1,000,000 persons, respectively. From 2014 to 2019, the proportion of prescriptions of sirolimus and everolimus increased, while the use of home oxygen therapy, chest drainage, comorbid pneumothorax, and bloody phlegm decreased. The mortality rate remained stable at approximately 1%., Conclusions: The incidence and prevalence of lymphangioleiomyomatosis were higher in women than those reported previously. Although the incidence did not change during the 6-year period, the prevalence gradually increased. Moreover, lymphangioleiomyomatosis was observed to be rare in men. The practice of treating patients with lymphangioleiomyomatosis changed across the six years while mortality remained low, at approximately 1%., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Medial meniscus posterior root tear (MMPRT) is a common medial meniscus injury among elderly patients and often necessitates repair. Although the clinical outcomes of MMPRT repair have demonstrated improvements, subsequent second-look arthroscopy shows poor healing postrepair. Consequently, numerous repair techniques have been reported. Herein, we introduce a simple locking-suture method, the "delta-grip" stitch, for MMPRT repair. This technique exhibited sufficient pullout strength compared with conventional suturing methods, offering promising prospects for enhancing the outcomes of MMPRT repair., Competing Interests: The authors (Y.I., E.S., Y.K., T.T.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Diaphyseal forearm fractures are common traumatic injuries among children. There has been much debate on the use of intramedullary nailing (IMN) or plate fixation in the adolescent population (10-16 years of age). Furthermore, as ultrasound technology has advanced, the safety and efficacy of ultrasound-guided axillary brachial plexus block for children has dramatically improved. Therefore, anesthesia options for adolescent patients have increased in recent years. This study aimed to investigate recent surgical and regional anesthesia trends of diaphyseal forearm fractures in patients 10 to 16 years of age in Japan through a multicenter epidemiological survey from 2011 to 2020., Methods: This retrospective, multicenter study included 226 pediatric patients with diaphyseal forearm fracture aged 10-16 years treated from January 2011 to December 2020. We divided the patients into four groups according to the period in which they were treated: early (2011-2013), middle (2014-2016), late (2017-2019), and COVID-19 (2020). Information from medical records was used to investigate the number of surgeries, types of anesthesia administered, and internal fixation methods used for diaphyseal forearm fracture in adolescent patients during each period., Results: The number of surgeries was generally constant in each period but decreased during the COVID-19 period. In the early, middle, late, and COVID-19 periods, the percentages of surgeries performed under regional anesthesia were 67.7, 85.5, 87.0, and 100% respectively (p = 0.003). During the same periods, the percentages of patients receiving IMN were 41.5, 49.3, 58.0, and 66.7%, respectively (p = 0.033)., Conclusion: The use of IMN and regional anesthesia to treat diaphyseal forearm fracture in patients 10 to 16 years of age steadily increased during the study period from 2011 to 2020. These results indicate that regional anesthesia is safe, effective, and well-tolerated by adolescent patients. The treatment strategy for diaphyseal forearm fractures in adolescents using regional anesthesia in combination with IMN worked well and was effective during COVID-19. Our evidence suggests this trend will continue. We anticipate that our findings can be extrapolated for upper extremity fractures in adolescent patients beyond the Tokai region of Japan where the study was based., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Mechanical compression of cardiac conduction system by transcatheter heart valves leads to complete atrioventricular block (CAVB) after transcatheter aortic valve replacement (TAVR). Bulging of ventricular septum in the left ventricular outflow tract (LVOT) may be associated with greater compression of conduction system, leading to irreversible CAVB., Objective: This study aimed to investigate the association of ventricular septal bulging with TAVR-related CAVB and permanent pacemaker implantation (PPI)., Methods: Among 294 consecutive patients with severe aortic stenosis who underwent TAVR between July 2017 and February 2023, 271 were included in the analysis. As a quantitative evaluation of bulging of the ventricular septum, the ratio of LVOT area to aortic annulus area (L/A ratio) was measured at the systolic phase of computed tomography images., Results: TAVR-related CAVB occurred in 64 patients (23.6%). Twenty-eight patients (10.3%) required PPI. The optimal thresholds of L/A ratio for predicting TAVR-related CAVB and PPI were 1.0181 and 0.985, respectively. Patients with less than the cut-off values had higher rate of TAVR-related CAVB and PPI than those above (28.3% vs 13.1%, p = 0.0063; 14.7% vs 4.4%, p = 0.0077, respectively). A multivariate analysis showed that L/A ratio < 1.0181 was an independent predictor of TAVR-related CAVB (odds ratio [OR] 2.65, p = 0.011), in addition to prior right bundle branch block (OR 3.76, p = 0.0005), use of a self-expanding valve (OR 1.99, p = 0.030), and short membranous septum length (OR 0.96, p = 0.037). Only L/A ratio < 0.985 was independently associated with PPI (OR 3.70, p = 0.011)., Conclusion: Low L/A ratio is a predictor of TAVR-related CAVB and PPI., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Phospholipid-protein interactions play important roles in regulating the function and morphology of photosynthetic membranes in purple phototrophic bacteria. Here, we characterize the phospholipid composition of intracytoplasmic membrane (ICM) from Rhodobacter (Rba.) sphaeroides that has been genetically altered to selectively express light-harvesting (LH) complexes. In the mutant strain (DP2) that lacks a peripheral light-harvesting (LH2) complex, the phospholipid composition was significantly different from that of the wild-type strain; strain DP2 showed a marked decrease in phosphatidylglycerol (PG) and large increases in cardiolipin (CL) and phosphatidylcholine (PC) indicating preferential interactions between the complexes and specific phospholipids. Substitution of the core light-harvesting (LH1) complex of Rba. sphaeroides strain DP2 with that from the purple sulfur bacterium Thermochromatium tepidum further altered the phospholipid composition, with substantial increases in PG and PE and decreases in CL and PC, indicating that the phospholipids incorporated into the ICM depend on the nature of the LH1 complex expressed. Purified LH1-reaction center core complexes (LH1-RC) from the selectively expressing strains also contained different phospholipid compositions than did core complexes from their corresponding wild-type strains, suggesting different patterns of phospholipid association between the selectively expressed LH1-RC complexes and those purified from native strains. Effects of carotenoids on the phospholipid composition were also investigated using carotenoid-suppressed cells and carotenoid-deficient species. The findings are discussed in relation to ICM morphology and specific LH complex-phospholipid interactions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Glial activation is central to the pathogenesis of Alzheimer's disease (AD). However, researchers have not demonstrated its relationship to longitudinal cognitive deterioration. We aimed to compare the prognostic effects of baseline positron emission tomography (PET) imaging of glial activation and amyloid/tau pathology on the successive annual cognitive decline in patients with AD., Methods: We selected 17 patients diagnosed with mild cognitive impairment or AD. We assessed the annual changes in global cognition and memory. Furthermore, we assessed the predictive effects of baseline amyloid and tau pathology indicated by cerebrospinal fluid (CSF) concentrations and PET imaging of glial activation ( 11 C-DPA-713-binding potential in the area of Braak 1-3 [ 11 C-DPA-713-BP ND ]) on global cognition and memory using a stepwise regression analysis., Results: The final multiple regression model of annual changes in global cognition and memory scores included 11 C-DPA-713-BP ND as the predictor. The CSF Aβ42/40 ratios and p-tau concentrations were removed from the final model. In stepwise Bayesian regression analysis, the Bayes factor-based model comparison suggested that the best model included 11 C-DPA-713-BP ND as the predictor of decline in global cognition and memory., Conclusions: Translocator protein-PET imaging of glial activation is a stronger predictor of AD clinical progression than the amount of amyloid/tau pathology measured using CSF concentrations. Glial activation is the primary cause of tau-induced neuronal toxicity and cognitive deterioration, thereby highlighting the potential of blocking maladaptive microglial responses as a therapeutic strategy for AD treatment., 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. Published by Elsevier Inc.)

This report documents the pathological features of primary cardiac myxoid tumour (MT) in 11 dogs. Macroscopically, all the tumours were located in the tricuspid valve (TV), its septal leaflet being predominantly affected. Therefore, it appears that the TV is the most common site of occurrence for cardiac MT in dogs. Two gross anatomical types of canine valvular MT were evident. Seven of the 11 tumours were round or oval with a smooth or gently lobulated and glistening surface, while the other four were gelatinous, multilobulated and polypoid, with an irregular surface. Microscopically, in nine cases the tumours had an abundant myxoid matrix within which elongated spindle-shaped cells with no remarkable cytological atypia were sparsely embedded, suggesting a benign character (ie, myxoma). In the other two cases the tumours consisted of variably dense, haphazardly arranged, interlacing streams of anaplastic spindle-shaped or polygonal cells containing many mitotic figures, indicative of a malignant form of myxoma (ie, myxosarcoma). Isolated or clustered collections of myxoma cells (eg, cords, rings, syncytia) characteristic of human atrial myxoma were only rarely evident or lacking in all 11 cases, indicating that rarity or absence of such structural features may be specific to valvular MTs. Immunohistochemical findings were indicative of smooth muscle differentiation of the neoplastic cells. Tumour embolization to the intrapulmonary arteries and/or tumour implantation on the endocardium of the right heart chambers was evident only in the four cases of irregular-surfaced MT., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Although the microgravity (μ-g) environment that astronauts encounter during spaceflight can cause severe acute bone loss, the molecular mechanism of this bone loss remains unclear. To investigate the gravity-response proteins involved in bone metabolism, it is important to comprehensively determine which proteins exhibit differential abundance associated with mechanical stimuli. However, comprehensive proteomic analysis using small bone samples is difficult because protein extraction in mineralized bone tissue is inefficient. Here, we established a high-sensitivity analysis system for mouse bone proteins using data-independent acquisition mass spectrometry. This system successfully detected 40 proteins in the femoral diaphysis showing differential abundance between mice raised in a μ-g environment, where the bone mass was reduced by gravity unloading, and mice raised in an artificial 1-gravity environment on the International Space Station. Additionally, 22 proteins, including noncollagenous bone matrix proteins, showed similar abundance between the two groups in the mandible, where bone mass was unaltered due to mastication stimuli, suggesting that these proteins are responsive to mechanical stimuli. One of these proteins, SPARCL1, is suggested to promote osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand. We expect these findings to lead to new insights into the mechanisms of bone metabolism induced by mechanical stimuli. SIGNIFICANCE: We aimed to investigate the gravity-response proteins involved in bone metabolism. To this end, we established a comprehensive analysis system for mouse bone proteins using data-independent acquisition mass spectrometry, which is particularly useful in comprehensively analyzing the bone proteome using small sample volumes. In addition, a comprehensive proteomic analysis of the femoral diaphysis and mandible, which exhibit different degrees of bone loss in mice raised on the International Space Station, identified proteins that respond to mechanical stimuli. SPARCL1, a mechanical stimulus-responsive protein, was consequently suggested to be involved in osteoclast differentiation associated with bone remodeling. Our findings represent an important step toward elucidating the molecular mechanism of bone metabolism induced by mechanical stimuli., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: A relationship between body mass index and functional recovery in older survivors of stroke is unclear. Therefore, this study aimed to investigate the association of body mass index with post-stroke functional recovery in older Japanese stroke survivors undergoing hospital rehabilitation., Methods: This was a multicenter retrospective observational study of 757 older survivors of stroke, from six convalescent rehabilitation hospitals in Japan. The participants were classified into seven categories according to body mass index at admission. The measurements included outcomes of the absolute gain in the motor subscale of the Functional Independence Measure. Poor functional recovery was defined as gain < 17 points. Multivariate logistic regression analysis was performed to examine the impact of these body mass index categories on poor functional recovery., Results: The mean motor gains were highest in the 23.5-25.4 kg/m 2 group (28.1 points), and lowest in the < 17.5 kg/m 2 group (2 2 0.0 points). The results of the multivariate regression analyses (reference; 23.5-25.4 kg/m 2 group) showed that the < 17.5 kg/m 2 group (odds ratios 4.30; 95 % confidence intervals 2.09-8.87), the 17.5-19.4 kg/m 2 group (1.99; 1.03-3.87), the 19.5-21.4 kg/m 2 group (1.93; 1.05-3.54), and the ≥ 27.5 kg/m 2 group (3.34; 1.33-8.4 2 ) were significantly associated with poor functional recovery, but not in the other groups., Conclusions: Older survivors of stroke with high-normal weight had the most favorable functional recovery among the seven groups. Meanwhile, both low and extremely high body mass indexes were associated with poor functional recovery., Competing Interests: Declaration of Competing Interest We declare that we have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)