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Abstract Background Interstitial pneumonia with autoimmune features (IPAF), which does not meet any of the criteria for connective tissue diseases (CTD), has been attracting an attention in patients with idiopathic interstitial pneumonia (IIP). However, the biomarkers that reflect the clinical course of these patients have not been fully elucidated. Objective To identify useful serum biomarkers reflecting CTD-related features and favorable prognoses in patients with IIP. Methods This was a post hoc analysis of a prospective and multicenter cohort study between 2015 and 2020. Newly diagnosed patients with IIP were consecutively enrolled, and 74 autoimmune features and autoantibodies were comprehensively checked during IIP diagnosis. Serum levels of CXCL10, CXCL1, CCL2, BAFF, angiopoietin-2, and leptin were evaluated at the time of IIP diagnosis. Results Two hundred twenty-two patients (159 men and 63 women) with IIP were enrolled. The median observation duration was 36 months. The median age was 71 years old, and median %forced vital capacity (FVC) was 84.1% at the time of IIP diagnosis. The proportion of patients who met the classification criteria for IPAF was 11.7%. In patients with high serum CXCL10, changes in both %FVC and %diffusion lung capacity for carbon monoxide at one year were significantly higher than those in patients with low CXCL10 (p = 0.014 and p = 0.009, respectively), whereas these changes were not significant for other chemokines and cytokines. High CXCL10 levels were associated with acute/subacute onset (p

Category: Ankle Arthritis; Ankle Introduction/Purpose: Distal tibial oblique osteotomy for ankle osteoarthritis is an effective procedure with joint preserving. However, there is the risk of nonunion due to open wedge osteotomy and complication associated with autogenous bone harvesting. We performed distal tibial rotational osteotomy (DTRO) for ankle osteoarthritis, which modified osteotomy design is expected to reduce the risk of nonunion without autologous bone grafting and soft tissue complications. We evaluated the clinical and radiographical outcome of DTRO. Methods: A total of 23 feet (4 males and 19 females) who underwent DTRO for ankle osteoarthritis in our institutions between 2016 and 2022 was included. All patients required a minimum of one year follow-up. As a surgical procedure, tri-plane osteotomy was performed using anteromedial approach. Then, the distal tibial fragment was rotated distally in the 3D plane until ankle stability was achieved, and the prominence of the medial tibia was resection after the correction. A medial tibial locking plate was applied for stabilization after filling opening gap with synthetic bone blocks. We evaluated demographic data, radiographical measurements, classification of arthritis severity, and the rate of nonunion, wound complications and reoperation. In addition, JSSF scale (Japanese Society for Surgery of the Foot ankle) and SAFE- Q (Self-Administered Foot Evaluation Questionnaire) were assessed preoperatively and at the latest follow-up. Results: Subjects had an average age of 64 years, an average follow-up period of 42 months, and were classified as stage 2/3a/3b in 1/19/2 feet preoperatively. The average of tibial anterior surface angle changed from 83.7° to 93.5°, and the tibial lateral surface angle changed from 81.0° to 81.9° in pre- and postoperative radiography. The JSSF scale significantly improved from 49.1 to 88.2 (p< 0.01) and the SAFE-Q showed significant improvement in all subscales at the latest follow-up. Bone union was obtained within 3 months in all cases, and no nonunion was observed. Delayed wound healing was observed in 1 case (4.4%). Ankle arthrodesis was needed in 1 case of deep infection and in 1 case of arthritis progression stage 3b to 4. Conclusion: In general, the distal tibia has poor soft tissue and blood flow that may lead the nonunion and soft tissue complications for distal tibial osteotomy. The advantage of DTRO was to maintain tibial bone contact after the osteotomy which may be favorable for bone stability and union, and to resect the medial bone prominence which reduce the tension of soft tissue. In this study, bone union was obtained in all cases without harvesting autogenous bone, and wound complications were low at 4.4%. Good intermediate-term outcomes were obtained, and DTRO can be a favorable surgical procedure for ankle osteoarthritis.

Introduction: Increased greenhouse gas emissions since the industrial age have led to higher global temperatures and frequency and severity of climate events, such as heat waves, wildfires, floods, and storms. These changes are adversely affecting human health and increasing disease risk, including risk of allergic diseases. Further understanding of the environmental factors and the cellular and molecular mechanisms mediating these increases can assist in developing strategies to adapt to and mitigate climate change. Materials and Methods: We conducted a scoping review of the literature from 2010 through 2024 using PubMed and Scopus. Results: Thunderstorms, dust storms, wildfires, and other climate change factors increase allergies both directly and indirectly through increases in particulate matter, pollen, migration of disease vectors and decreases in biodiversity. The epithelial barrier, hygiene, “old friends,” and biodiversity hypotheses have been put forward to explain the underlying mechanism mediating these increases. Conclusion: There is an urgent need to reduce the use of fossil fuels to mitigate climate change and protect planetary and human health. While international accords such as the 2015 Paris Agreement have been signed with the aim of lowering greenhouse gases and limiting future global temperature increases, it is clear that increased efforts are needed to meet these goals. Evidence-based solutions for adapting to the increased prevalence of allergic diseases and cost-benefit analysis of current mitigation strategies for lowering allergic diseases are also needed.

ABSTRACT Background Radiotherapy is considered an alternative treatment for unresectable or pharmacologically resistant desmoid‐type fibromatosis. While it results in relatively good local control, the risk of secondary malignancy remains a concern. Case We present a case of secondary osteosarcoma after carbon‐ion radiation therapy (CIRT). A 31‐year‐old male patient presented with left thigh pain. The tumor was located between the left gluteus maximus and gluteus medius and extended to the vastus lateralis and biceps femoris. It was diagnosed as desmoid‐type fibromatosis after needle biopsy. The patient was treated with several medications, including a cyclooxygenase 2 inhibitor and tamoxifen; however, his left thigh pain did not improve. He was treated with CIRT 1 year after diagnosis (67.2 Gy [relative biological effectiveness] 16fr/4wks). He developed osteosarcoma of the left femur 8 years later. He underwent chemotherapy and tumor excision with disarticulation of the left hip. Pulmonary metastasis was detected 6 and 17 months after the definitive surgery and excised using metastasectomy. However, he died due to the recurrence of multiple pulmonary metastases 29 months after the definitive surgery. Conclusions In this case, we believe that the low radiation dose to the femur may have caused secondary malignancy.

Recently, arthroscopic anterior talofibular ligament (ATFL) repair has become popular, and favorable outcomes have been reported. In general, ATFL injuries are often caused by fibular attachment, and there are no reports of arthroscopic ligament repair of talar attachment injuries. We present a surgical technique for arthroscopic ligament repair via the anterolateral portal, accessory anterolateral portal, and far accessory anterolateral portal for ATFL injuries on the talar side. Ligament plication is performed using a suture anchor at the talar footprint of the ATFL after the small bone fragments are removed under arthroscopy. Arthroscopic surgery may lead to less postoperative swelling and pain than open surgery, allowing for early exercise and return to activity.

Abstract We previously reported that enhanced corticotropin-releasing factor (CRF) signaling in the bed nucleus of the stria terminalis (BNST) caused the aversive responses during acute pain and suppressed the brain reward system during chronic pain. However, it remains to be examined whether chronic pain alters the excitability of CRF neurons in the BNST. In this study we investigated the chronic pain-induced changes in excitability of CRF-expressing neurons in the oval part of the BNST (ovBNSTCRF neurons) by whole-cell patch-clamp electrophysiology. CRF-Cre; Ai14 mice were used to visualize CRF neurons by tdTomato. Electrophysiological recordings from brain slices prepared from a mouse model of neuropathic pain revealed that rheobase and firing threshold were significantly decreased in the chronic pain group compared with the sham-operated control group. Firing rate of the chronic pain group was higher than that of the control group. These data indicate that chronic pain elevated neuronal excitability of ovBNSTCRF neurons.

Background Dual antiplatelet therapy plays a crucial role in preventing thrombosis in the perioperative period of carotid artery stenting (CAS); however, it has been associated with a risk of hemorrhagic complications. A standard regimen for the duration and combination of antiplatelet therapy is yet to be established. Angioscopy enables direct visualization of neointimal coverage and might help determine the optimal duration of dual antiplatelet therapy through the assessment of post‐CAS neointimal coverage. Methods This prospective study enrolled 20 patients who were scheduled to undergo CAS at the Osaka Police Hospital. A 2‐month post‐CAS period was chosen for angioscopic neointima evaluation on the basis of previous evidence of reliable neointimal coverage 2 months following coronary artety stenting. Furthermore, antiplatelet therapy was initiated 1 week before CAS and continued until angioscopic examination. Angioscopic evaluation categorized the degree of neointimal coverage and was supplemented with carotid ultrasonography and biplane angiography. Results Coincidentally, a dual‐layer stent was used in all cases. The stent lumen was observed in 19 of the 20 cases. One case was difficult to evaluate owing to poor visibility. Angioscopy showed complete neointimal coverage in 18 of 19 cases and partial coverage in 1 case. Ultrasonography could detect neointima in 9 of 20 cases, and angiography showed a radiolucent gap suggestive of neointima in all cases in which neointima was confirmed via angioscopy. No post‐CAS or procedural complications occurred. Conclusion Angioscopy performed 2 months following CAS revealed large neointimal coverage, suggesting that a 2‐month duration of dual antiplatelet therapy is generally sufficient. However, as a limitation, this study was performed using the same dual‐layer stent; thus, additional studies with other stents are required.

Abstract Thermal switches that switch the thermal conductivity (κ) of the active layers are attracting increasing attention as thermal management devices. For electrochemical thermal switches, several transition metal oxides (TMOs) are proposed as active layers. After electrochemical redox treatment, the crystal structure of the TMO is modulated, which results in the κ switching. However, the κ switching width is still small (

Objectives: Detailed superiority of CAD EYE (Fujifilm, Tokyo, Japan), an artificial intelligence for polyp detection/diagnosis, compared to endoscopists is not well examined. We examined endoscopist's ability using movie sets of colorectal lesions which were detected and diagnosed by CAD EYE accurately. Methods: Consecutive lesions of 10 mm were examined live by CAD EYE from March-June 2022 in our institution. Short unique movie sets of each lesion with and without CAD EYE were recorded simultaneously using two recorders for detection under white light imaging (WLI) and linked color imaging (LCI) and diagnosis under blue laser/light imaging (BLI). Excluding inappropriate movies, 100 lesions detected and diagnosed with CAD EYE accurately were evaluated. Movies without CAD EYE were evaluated first by three trainees and three experts. Subsequently, movies with CAD EYE were examined. The rates of accurate detection and diagnosis were evaluated for both movie sets. Results: Among 100 lesions (mean size: 4.7±2.6 mm; 67 neoplastic/33 hyperplastic), mean accurate detection rates of movies without or with CAD EYE were 78.7%/96.7% under WLI (p

Summary: Quantification of cytokine secretion has facilitated advances in the field of immunology, yet the dynamic and varied secretion profiles of individual cells, particularly those obtained from limited human samples, remain obscure. Herein, we introduce a technology for quantitative live-cell imaging of secretion activity (qLCI-S) that enables high-throughput and dual-color monitoring of secretion activity at the single-cell level over several days, followed by transcriptome analysis of individual cells based on their phenotype. The efficacy of qLCI-S was demonstrated by visualizing the characteristic temporal pattern of cytokine secretion of group 2 innate lymphoid cells, which constitute less than 0.01% of human peripheral blood mononuclear cells, and by revealing minor subpopulations with enhanced cytokine production. The underlying mechanism of this feature was linked to the gene expression of stimuli receptors. This technology paves the way for exploring gene expression signatures linked to the spatiotemporal dynamic nature of various secretory functions.

Fifth generation (5G) mobile communication systems have been deployed in the millimeter wave (mmWave) band. Since electromagnetic (EM) waves in this band exhibit high propagation loss and antennas are highly directive, the performance of wireless communications is largely degraded in a non-line-of-sight (NLOS) area, resulting in a limited coverage area. To improve the performance and increase the coverage area, a metamaterial-based electromagnetic scattering sheet (EMSS) with broad scattering characteristics is proposed in this paper. We also introduce fast design and optimization methods using equivalent circuits of metamaterials, antenna array theory, and the genetic algorithm (GA). The diffusion coefficient is used as a fitness value to evaluate the scattering characteristics of the EMSS generated by GA. The broad scattering characteristics of the designed EMSS are experimentally confirmed. We clarified that the optimized EMSS has a higher diffusion coefficient than a metal plate of the same size. Finally, we demonstrated improved wireless communication performance in an NLOS area by diffusing the incoming EM fields using our designed EMSS.

Abstract Pulmonary fibrosis (PF), a condition characterized by inflammation and collagen deposition in the alveolar interstitium, causes dyspnea and fatal outcomes. Although the bleomycin-induced PF mouse model has improved our understanding of exogenous factor-induced fibrosis, the mechanism governing endogenous factor-induced fibrosis remains unknown. Here, we find that Ifngr1 -/- Rag2 -/- mice, which lack the critical suppression factor for group 2 innate lymphoid cells (ILC2), develop PF spontaneously. The onset phase of fibrosis includes ILC2 subpopulations with a high Il1rl1 (IL-33 receptor) expression, and fibrosis does not develop in ILC-deficient or IL-33-deficient mice. Although ILC2s are normally localized near bronchioles and blood vessels, ILC2s are increased in fibrotic areas along with IL-33 positive fibroblasts during fibrosis. Co-culture analysis shows that activated-ILC2s directly induce collagen production from fibroblasts. Furthermore, increased IL1RL1 and decreased IFNGR1 expressions are confirmed in ILC2s from individuals with idiopathic PF, highlighting the applicability of Ifngr1 -/- Rag2 -/- mice as a mouse model for fibrosis research.

At the beginning of the 21st century, a reform of the judicial system was carried out, essentially aimed at increasing the number of lawyers and opening public participation. In this context, a new class action legislation was promulgated in the field of consumer law to prevent instances of commercial malpractice and as a mechanism to recover damages from professionals in cases involving large numbers of consumers. This article examines how and the extent to which the new class action system contributes to the expansion of the judicial function. It also examines the potential for wider acceptance of this type of legal action within Japanese society.

Abstract Background Diabetes is associated with an increased risk of deleterious changes in muscle mass and function or sarcopenia, leading to physical inactivity and worsening glycaemic control. Given the negative energy balance during sodium–glucose cotransporter‐2 (SGLT2) inhibition, whether SGLT2 inhibitors affect skeletal muscle mass and function is a matter of concern. However, how SGLT2 inhibition affects the skeletal muscle function in patients with diabetes remains insufficiently explored. We aimed to explore the effects of canagliflozin (CANA), an SGLT2 inhibitor, on skeletal muscles in genetically diabetic db/db mice focusing on the differential responses of oxidative and glycolytic muscles. Methods Db/db mice were treated with CANA for 4 weeks. We measured running distance and handgrip strength to assess skeletal muscle function during CANA treatment. At the end of the experiment, we performed a targeted metabolome analysis of the skeletal muscles. Results CANA treatment improved the reduced endurance capacity, as revealed by running distance in db/db mice (414.9 ± 52.8 vs. 88.7 ± 22.7 m, P

ABSTRACT Aim/Introduction This study aimed to investigate the clinical utility of 3 Screen ICA ELISA in identifying immune‐mediated type 1 diabetes in Japanese subjects. Methods We compared the positivity of 3 Screen ICA were compared with autoantibodies against GAD, IA‐2, and ZnT8 in 638 patients with type 1 diabetes and 159 healthy control subjects. Results With a cut‐off value of 20.0 index, 67.4% of acute‐onset type 1 diabetic patients, 71.8% of slowly progressive type 1 diabetic (SPIDDM) patients, and none of the fulminant type 1 diabetic patients showed 3 Screen ICA levels above this threshold. The prevalence of 3 Screen ICA was 14.2% higher in acute‐onset type 1 diabetes and 1.6% higher in SPIDDM than in GADA. 3 Screen ICA‐positive cases were found in 4.8% of cases of individual autoantibody‐negative acute‐onset type 1 diabetes and 3.8% of SPIDDM, indicating improved diagnostic sensitivity with the 3 Screen ICA. Among individual autoantibody‐negative patients, the sum of each autoantibody level was significantly lower in fulminant type 1 diabetes than in acute onset type 1 diabetes and in SPIDDM (P

Abstract The decision of whether cells are activated or not is controlled through dynamic intracellular molecular networks. However, the low population of cells during the transition state of activation renders the analysis of the transcriptome of this state technically challenging. To address this issue, we have developed the Time-Dependent Cell-State Selection (TDCSS) technique, which employs live-cell imaging of secretion activity to detect an index of the transition state, followed by the simultaneous recovery of indexed cells for subsequent transcriptome analysis. In this study, we used the TDCSS technique to investigate the transition state of group 2 innate lymphoid cells (ILC2s) activation, which is indexed by the onset of interleukin (IL)-13 secretion. The TDCSS approach allowed us to identify time-dependent genes, including transiently induced genes (TIGs). Our findings of IL4 and MIR155HG as TIGs have shown a regulatory function in ILC2s activation.

Global warming and climate change have increased the pollen burden and the frequency and intensity of wildfires, sand and dust storms, thunderstorms, and heatwaves—with concomitant increases in air pollution, heat stress, and flooding. These environmental stressors alter the human exposome and trigger complex immune responses. In parallel, pollutants, allergens, and other environmental factors increase the risks of skin and mucosal barrier disruption and microbial dysbiosis, while a loss of biodiversity and reduced exposure to microbial diversity impairs tolerogenic immune development. The resulting immune dysregulation is contributing to an increase in immune-mediated diseases such as asthma and other allergic diseases, autoimmune diseases, and cancer. It is now abundantly clear that multisectoral, multidisciplinary, and transborder efforts based on Planetary Health and One Health approaches (which consider the dependence of human health on the environment and natural ecosystems) are urgently needed to adapt to and mitigate the effects of climate change. Key actions include reducing emissions and improving air quality (through reduced fossil fuel use), providing safe housing (e.g., improving weatherization), improving diets (i.e., quality and diversity) and agricultural practices, and increasing environmental biodiversity and green spaces. There is also a pressing need for collaborative, multidisciplinary research to better understand the pathophysiology of immune diseases in the context of climate change. New data science techniques, biomarkers, and economic models should be used to measure the impact of climate change on immune health and disease, to inform mitigation and adaptation efforts, and to evaluate their effectiveness. Justice, equity, diversity, and inclusion (JEDI) considerations should be integral to these efforts to address disparities in the impact of climate change.

ABSTRACT Aims/Introduction Although the association between dipeptidyl peptidase‐4 (DPP‐4) inhibitors and bullous pemphigoid (BP) has begun to be established, some studies have suggested there are risk differences among DPP‐4 inhibitors. We conducted a population‐based cohort study to examine the risk differences. Materials and Methods Using the claims databases of the Fukuoka Prefecture Wide‐Area Association of Latter‐Stage Elderly Healthcare between April 1, 2013 and March 31, 2017, we conducted a retrospective cohort study to compare patients receiving one DPP‐4 inhibitor with those who were prescribed another antidiabetic drug. The primary outcome was an adjusted hazard ratio (HR) of the development of bullous pemphigoid during a 3‐year follow‐up. The secondary outcome was the development of BP requiring systemic steroids immediately after the diagnosis. These were estimated using Cox proportional hazards regression models. Results The study comprised 33,241 patients, of which 0.26% (n = 88) developed bullous pemphigoid during follow‐up. The percentages of patients with bullous pemphigoid who required immediate systemic steroid treatment was 0.11% (n = 37). We analyzed four DPP‐4 inhibitors: sitagliptin, vildagliptin, alogliptin, and linagliptin. Vildagliptin and linagliptin raised the risk of BP significantly (primary outcome, vildagliptin, HR 2.411 [95% confidence interval (CI) 1.325–4.387], linagliptin, HR 2.550 [95% CI 1.266–5.136], secondary outcome, vildagliptin HR 3.616 [95% CI 1.495–8.745], linagliptin HR 3.556 [95% CI 1.262–10.024]). A statistically significant risk elevation was not observed with sitagliptin and alogliptin (primary outcome, sitagliptin, HR 0.911 [95% CI 0.508–1.635], alogliptin, HR 1.600 [95% CI 0.714–3.584], secondary outcome, sitagliptin, HR 1.192 [95% CI 0.475–2.992], alogliptin, HR 2.007 [95% CI 0.571–7.053]). Conclusions Not all the DPP‐4 inhibitors could induce bullous pemphigoid significantly. Therefore, the association warrants further investigations before generalization.

Abstract Excessive TGF-β signaling and mitochondrial dysfunction fuel chronic kidney disease (CKD) progression. However, inhibiting TGF-β failed to impede CKD in humans. The proximal tubule (PT), the most vulnerable renal segment, is packed with giant mitochondria and injured PT is pivotal in CKD progression. How TGF-β signaling affects PT mitochondria in CKD remained unknown. Here, we combine spatial transcriptomics and bulk RNAseq with biochemical analyses to depict the role of TGF-β signaling on PT mitochondrial homeostasis and tubulo-interstitial interactions in CKD. Male mice carrying specific deletion of Tgfbr2 in the PT have increased mitochondrial injury and exacerbated Th1 immune response in the aristolochic acid model of CKD, partly, through impaired complex I expression and mitochondrial quality control associated with a metabolic rewiring toward aerobic glycolysis in the PT cells. Injured S3T2 PT cells are identified as the main mediators of the maladaptive macrophage/dendritic cell activation in the absence of Tgfbr2. snRNAseq database analyses confirm decreased TGF-β receptors and a metabolic deregulation in the PT of CKD patients. This study describes the role of TGF-β signaling in PT mitochondrial homeostasis and inflammation in CKD, suggesting potential therapeutic targets that might be used to mitigate CKD progression.

Abstract Background and Aim A hemostatic gel, PuraStat (3‐D Matrix, Tokyo, Japan), is used for various gastrointestinal hemostasis. In this study, we analyzed the efficacy of PuraStat for perioperative bleeding (POB) and prevention of delayed bleeding (DB) to colorectal cold snare polypectomy (CSP) with continuous anticoagulant. Methods This was a single‐center, retrospective study. Subjects were lesions of 2–9 mm under continuous anticoagulant from 2021 to 2023 and treated with PuraStat for POB. The definition of POB was bleeding which did not stop spontaneously by 1.0–1.5 min after resection and needed hemostasis. Successful hemostasis was defined as cessation of bleeding within 1.0–1.5 min after spraying PuraStat and the rate of it and risk factors of POB were analyzed. For comparison, cases receiving previous CSP without PuraStat were extracted from all cases with CSP (2018‐2021), and POB and DB rate (DBR) were analyzed after propensity score matching. Results One hundred twenty‐two lesions (91: direct oral anticoagulant (DOAC), 31: warfarin) with anticoagulant were analyzed and the rate of successful hemostasis with PuraStat was 92.6% (DOAC/warfarin: 93.4%/80.6%, P = 0.01). The rate of DB was 0.0%. Multivariate analysis showed that significant risk factors about unsuccessful hemostasis for POB with PuraStat were lesion size 8–9 mm (P

[This corrects the article DOI: 10.1371/journal.pone.0296006.].

Objectives. Diagnostic ability of sessile serrated lesions (SSL) and SSL with dysplasia (SSLD) using blue laser/light imaging (BLI) has not been well examined. We analyzed the diagnostic accuracy of BLI for SSL and SSLD using several endoscopic findings compared to those of narrow band imaging (NBI). Materials and Methods. This was a subgroup analysis of prospective studies. 476 suspiciously serrated lesions of ≥2 mm on the proximal colon showing serrated change with magnified NBI or BLI in our institution between 2014 and 2021 were examined histopathologically. After propensity score matching, we evaluated the diagnostic ability of SSL and SSLD of the NBI and BLI groups regarding various endoscopic findings. For WLI findings, granule, depression, and reddish were examined for diagnosing SSLD. For NBI/BLI findings, expanded crypt opening (ECO) or thick and branched vessels (TBV) were examined for diagnosing SSL. Network vessels (NV) and white dendritic change (WDC) defined originally were examined for diagnosing SSLD. Results. Among matched 176 lesions, the sensitivity of lesions with either ECO or TBV for SSL in the NBI/BLI group was 97.5%/98.5% (p=0.668). Those with either WDC or NV for diagnosing SSLD in the groups were 81.0%/88.9% (p=0.667). Regarding the rates of endoscopic findings among 30 SSLD and 290 SSL, there were significant differences in WDC (66.4% vs. 8.6%, p

Category: Trauma; Sports Introduction/Purpose: Surgical technique to treatment syndesmosis injury is controversial. Additional suture-tape (ST) augmentation of anterior inferior tibiofibular ligament (AITFL) has been reported to improve syndesmotic stability compared with only suture-button (SB) fixation. ST fixation on the fibula is mainly performed with suture anchors, but suture holes with fibular plates can also be used. However, there is no biomechanical study about syndesmotic injury treated with ST augmentation using fibular plate. The aim of this study is to evaluate the stability of the syndesmosis injury model treated with ST augmentation using fibular plate. Our hypothesis is that ST augmentation using fibular plate can provide equivalent syndesmotic stability compared with ST augmentation using suture anchor. Methods: 8 normal fresh-frozen cadaver legs (4 males and 4 females) were used. The mean age at the time of death was 84.3 (70- 101). The specimens were tested while applied traction and rotational forces to represent dorsiflexion and external rotation of ankle joint. The fibular rotational angle related to the tibia (FRA) and anterior tibiofibular diastasis(aTFD) were measured using the magnetic tracking system while each load was applied. Intact, injured, SB + ST augmentation using suture anchor (anchor model), SB + ST augmentation fixation using fibular plate (plate model) models made, and loaded forces and measured FRA and aTFD with each model. One-way ANOVA was used to evaluate the relationship of the angles or the diastasis among each model. Post-hoc analysis for differences among the models were checked using Dunnett’s test. P value of 0.05 was chosen as the level of significance. Results: With dorsiflexion forces, in the injured model, both FRA and aTFD were significantly increased compared with intact model. In the anchor and plate model, both FRA and aTFD were not significantly different compared with intact model. With external rotation forces, in the injured model, both FRA and aTFD were significantly increased compared with intact model. In the anchor and plate model, both FRA and aTFD were not significantly different compared with intact model. Conclusion: The result of this study presented that ST augmentation using fibular plate provide syndesmotic stability similarly with ST augmentation using suture anchor. This technique was considered to be useful in cases of syndesmosis injury with lateral malleolar fracture. Particularly, it is difficult to use suture anchor for ST fixation to the fibula when there is a comminuted fracture near the AITFL attachment of the fibula. Using plate allows for stable ST fixation to the fibula without worrying about it.

Abstract Optogenetics is a powerful tool for manipulating neuronal activity by light illumination with high temporal and spatial resolution. Anion-channelrhodopsins (ACRs) are light-gated anion channels that allow researchers to efficiently inhibit neuronal activity. A blue light-sensitive ACR2 has recently been used in several in vivo studies; however, the reporter mouse strain expressing ACR2 has not yet been reported. Here, we generated a new reporter mouse strain, LSL-ACR2, in which ACR2 is expressed under the control of Cre recombinase. We crossed this strain with a noradrenergic neuron-specific driver mouse (NAT-Cre) to generate NAT-ACR2 mice. We confirmed Cre-dependent expression and function of ACR2 in the targeted neurons by immunohistochemistry and electrophysiological recordings in vitro, and confirmed physiological function using an in vivo behavioral experiment. Our results show that the LSL-ACR2 mouse strain can be applied for optogenetic inhibition of targeted neurons, particularly for long-lasting continuous inhibition, upon crossing with Cre-driver mouse strains. The LSL-ACR2 strain can be used to prepare transgenic mice with homogenous expression of ACR2 in targeted neurons with a high penetration ratio, good reproducibility, and no tissue invasion.

Abstract Background The manual traditional anterior drawer test (ADT) is essential for deciding the treatment for chronic ankle instability, but it has been shown to have a comparatively low reproducibility and accuracy, especially in less experienced hands. To clarify the inter-examiner reproducibility, we compared the actual distance of anterior translation between junior and senior examiners in ADT. We also evaluated the diagnostic abilities of traditional ADT, and a novel modified ADT (supported ADT). Methods Thirty ankles were included in this study, and ankle instability was defined using stress radiography. All subjects underwent two methods of manual ADT by junior and senior examiners, and ankle instability was judged in a blinded fashion. The anterior drawer distance was calculated from the lengthening measured using a capacitance-type sensor device. Results The degree of anterior translation determined by the junior examiner was significantly lower than that determined by the senior examiner when traditional ADT was performed (3.3 vs. 4.5 mm, P = 0.016), but there was no significant difference in anterior translation between the two examiners when supported ADT was performed (4.6 vs. 4.1 mm, P = 0.168). The inter-examiner reliability of supported ADT was higher than that of traditional ADT. For the junior examiner, the diagnostic accuracy of supported ADT was higher than that of traditional ADT (sensitivity, 0.40 vs. 0.80; specificity, 0.75 vs. 0.80). Conclusion Supported ADT may have the advantage of being a simple manual test of ankle instability with less error between examiners.

Abstract Background Total pancreatectomy (TP) is often selected for treatment of various pancreatic diseases. However, the resultant lack of autoregulation of glycometabolism necessitates careful postoperative management. Case presentation A 77-year-old man who had undergone right nephrectomy for renal cell carcinoma 11 years previously presented with multiple histologically diagnosed pancreatic metastases. The patient had no notable comorbidities, including diabetes. Because no extrapancreatic organ metastasis was identified, he underwent TP as a curative treatment. He awoke from anesthesia and was extubated without any problems in the operating room. However, 15 min after entering the intensive care unit, he suddenly lost consciousness and became apneic, resulting in reintubation. Blood gas analysis revealed an increased glucose concentration (302 mg/dL) and mixed acid–base disorder (pH of 7.21) due to insulin insufficiency and fentanyl administration. After induction of continuous intravenous insulin infusion and termination of fentanyl, the glucose concentration and pH gradually improved. He regained clear consciousness and spontaneous ventilation and was extubated the next day with no difficulties or complications. Conclusion This case highlights the importance of active monitoring of the glycemic state and pH after TP because of the possibility of deterioration due to TP itself as well as the lingering effects of anesthesia.

The oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are important processes for various energy devices, including polymer electrolyte fuel cells, rechargeable metal–air batteries, and water electrolyzers. We herein report the preparation of a rare metal-free and highly efficient ORR/OER electrocatalyst by calcination of a mixture of blood meal and ascidian-derived cellulose nanofibers. The obtained carbon alloys showed high ORR/OER performances and proved to be promising electrocatalysts. The carbon alloys synthesized entirely from biomass resources not only lead to a new electrocatalyst fabrication process but also contribute to CO2 reduction and the realization of a good life-cycle assessment value in fabrication of a sustainable energy device.

Abstract Background Tenosynovial giant cell tumor (TSGCT) is a benign fibrohistiocytic tumor that affects the synovium of joints, bursa, and tendon sheaths and is categorized into localized TSGCT (LTSGCT) and diffuse TSGCT (DTSGCT). LTSGCT and DTSGCT are characterized by recurrent fusions involving the colony-stimulating factor 1 (CSF1) gene and its translocation partner collagen type VI alpha 3 chain. The fusion gene induces intratumoral overexpression of CSF1 mRNA and CSF1 protein. CSF1 expression is a characteristic finding of TSGCT and detection of CSF1 mRNA and CSF1 protein may be useful for the pathological diagnosis. Although there have been no effective anti-CSF1 antibodies to date, in situ hybridization (ISH) for CSF1 mRNA has been performed to detect CSF1 expression in TSGCT. We performed CSF1 immunohistochemistry (IHC) using anti-CSF1 antibody (clone 2D10) in cases of TSGCT, giant cell-rich tumor (GCRT), and GCRT-like lesion and verified its utility for the pathological diagnosis of TSGCT. Methods We performed CSF1 IHC in 110 cases including 44 LTSGCTs, 20 DTSGCTs, 1 malignant TSGCT (MTSGCT), 10 giant cell tumors of bone, 2 giant cell reparative granulomas, 3 aneurysmal bone cysts, 10 undifferentiated pleomorphic sarcomas, 10 leiomyosarcomas, and 10 myxofibrosarcomas. We performed fluorescence ISH (FISH) for CSF1 rearrangement to confirm CSF1 expression on IHC in TSGCTs. We considered the specimens to have CSF1 rearrangement if a split signal was observed in greater than 2% of the tumor cells. Results Overall, 50 of 65 TSGCT cases, including 35 of the 44 LTSGCTs and 15 of the 20 DTSGCTs, showed distinct scattered expression of CSF1 in the majority of mononuclear tumor cells. MTSGCT showed no CSF1 expression. Non-TSGCT cases were negative for CSF1. FISH revealed CSF1 rearrangement in 6 of 7 CSF1-positive cases on IHC. On the other hand, FISH detected no CSF1 rearrangement in all CSF1-negative cases on IHC. Thus, the results of IHC corresponded to those of FISH. Conclusion We revealed characteristic CSF1 expression on IHC in cases of TSGCT, whereas the cases of non-TSGCT exhibited no CSF1 expression. CSF1 IHC may be useful for differentiating TSGCTs from histologically mimicking GCRTs and GCRT-like lesions.

We report a case in which neointima was confirmed by angioscopy and antiplatelet drug administration was reduced 2 months after carotid artery stenting (CAS). A patient in their 80s was scheduled to undergo resection for renal cancer; however, he also had right cervical internal carotid artery stenosis. Because this was a risk for general anesthesia, CAS was performed after first starting dual antiplatelet therapy. Urologically, early reduction of antiplatelet drugs was necessary for a nephrectomy. Although no obvious neointima could be identified on ultrasound 2 months after CAS, thin neointima was observed using angioscopy. Based on the above results, we reduced the antiplatelet drug administration, and then the nephrectomy was performed. Ultimately, no cerebral infarction occurred in the perioperative or postoperative periods. Angioscopy allows for visual confirmation of thin neointima. If sufficient neointima can be confirmed, antiplatelet drug reduction can be performed more safely and reliably.

Case presentation A 78‐year‐old man with a mobile lesion was diagnosed with thrombus using carotid ultrasonography, but the lesion was not completely resolved with dual antiplatelet and anticoagulation therapy. Direct visualization by angioscopy showed a white mobile plaque. The carotid artery was stented with a double‐layered stent, as the plaque persisted despite continuing the medical treatment and was linked to an increased risk of cerebral embolism. The plaque was attached to the arterial wall, and it subsequently disappeared. The patient recovered well and no further emboli were observed. Conclusions Angioscopy is effective for identifying lesions under direct vision. The characteristics and dynamics of plaques may be viewed via angioscopy, which aids in making treatment‐related decisions, particularly in the case of carotid artery plaques.

Abstract Background Acute exacerbation (AE) of systemic autoimmune disease-related interstitial lung diseases (SAID-ILD) is less common than AE of idiopathic pulmonary fibrosis (IPF) and the details of AE-SAID-ILD have not been elucidated, but the prognosis is similarly devastating. This study was undertaken to determine the incidences of AE-ILD in each SAID and to elucidate the proportion of progressive fibrosing (PF)-ILD in AE-SAID-ILD. Methods We retrospectively analysed data for patients with SAID-ILD who were diagnosed and observed at our hospital between 1999 and 2020. Results Two hundred and thirty-two patients with SAID-ILD were enrolled, with a mean observation period of 100.2 months. AE-SAID-ILD was found in 25 patients (10.78%), mainly in patients with RA (17 patients, 68%) and elderly male patients with a smoking history. The overall incidence of AE-SAID-ILD was 1.29%/person-year, and the incidence for each SAID was as follows: RA 2.193, microscopic polyarteritis (MPA) 3.203, systemic sclerosis (SSc) 2.277, primary Sjögren syndrome 0.426, and polymyositis/dermatomyositis 0.222. The incidence of AE of RA/MPA/SSc-ILD was significantly higher than that of other AE-SAID-ILD (p

Abstract Background The aim of the present study was to evaluate the prevalence of non-ossifying fibroma (NOF) and fibrous cortical defect (FCD) in a Japanese pediatric population and the association between the lesion size and pain. Methods This retrospective study, conducted across 10 Japanese institutions, included patients aged 5–15 years who had undergone standard antero-posterior and lateral view radiography of the knee. Using these radiographs, we diagnosed the lesion as a NOF or FCD. Patient demographics, including age, sex, the size and location of the NOF, and chief complaint were recorded. The lesion size was determined using radiographs. Student’s t-test was used to compare the associations between the lesion size and spontaneous pain. Results A total of 6222 subjects (3567 boys and 2455 girls) were included in this study. The number of NOF and FCD cases was 143 and 437, respectively, and the prevalence of NOF and FCD was 2.3% and 7.0%, respectively. The average size of NOF and FCD was 22.1 mm (range: 4–102 mm) and 13.2 mm (range: 5–21 mm), respectively. Three patients (2.1%) had pathological fractures due to NOF. Of the 140 NOFs and 437 FCDs, we obtained complaints from the medical records of 126 and 393 patients, respectively. The number of patients with spontaneous pain or other problems with NOF was 68 (54%) and 58 (46%), respectively, that of patients with FCD was 195 (50%) and 198 (50%) patients, respectively. The lesion size was not associated with spontaneous pain in either lesion (p = 0.67 and p = 0.27, respectively). Conclusion The prevalence of NOF and FCD around the knee was lower than that reported in previous studies. The prevalence of NOF increased and that of FCD decreased with advancing age. In both lesions, the lesion size may not be associated with pain.

Abstract Background Ultrasound examinations for syndesmosis injury might be useful for the quantitative evaluation of syndesmotic instability. The purpose of this study was to evaluate the efficacy of ultrasound assessment by measuring the tibiofibular distance of syndesmosis injuries in various ligament-injured models and stress load conditions. Methods Five normal ankles from Thiel-embalmed cadavers were used. Ultrasound assessment was performed by placing a probe in parallel with the ligament running just above the anterior inferior tibiofibular ligament (AITFL). The distance between the anterior border of the tibia and the fibula was measured in the intact condition. Next, Bassett’s ligament was cut arthroscopically to reduce damage to soft tissues as much as possible and measurement was performed in the same way. After that, the AITFL, interosseous membrane (IOM), deltoid ligament, and posterior inferior tibiofibular ligament (PITFL) were macroscopically cut and measured in that order. Ankle positions were without stress (natural plantar flexion without applying stress to the ankle joint), dorsiflexion stress, inversion stress, and external rotation stress. All stress to the ankle joint was carried out manually to the maximum extent. Results As with the without-stress condition, significant increases in tibiofibular distances after AITFL dissection were seen compared with the intact state under all stress conditions (intact: 4.9 ± 1.0 mm without stress, 5.6 ± 1.2 mm with dorsiflexion, 5.9 ± 1.0 mm with inversion, and 6.7 ± 1.3 mm with external rotation; AITFL dissection: 6.7 ± 1.5 mm without stress, 7.3 ± 1.2 mm with dorsiflexion, 7.5 ± 1.4 mm with inversion, and 8.7 ± 1.6 mm with external rotation). AITFL dissection with external rotation stress significantly increased the tibiofibular distance compared to without stress. Conclusion Changes in tibiofibular distance with the severity of syndesmosis injury were measured by ultrasound using cadavers. No significant change was seen with Bassett’s ligament injury, but tibiofibular distance increased significantly with injuries of equal to or greater severity than AITFL injury. Results were similar not only for external rotation stress, but also for dorsiflexion stress and inversion stress, and even in unloaded states, significant tibiofibular widening was confirmed with injuries of equal to or greater severity than AITFL injury.

Although there are some reports highlighting the applicability of double plates in distal femoral fractures, there is no standard approach or fixation method for supracondylar fractures combined with posterior coronal shear fractures. We report a case of distal femoral fracture treated with a lateral locking plate and posterior buttress plate using anterolateral and posterolateral approaches from one incision.A 70-year-old man was hit by a motorcycle and had an intra-articular distal femoral fracture involving a long medial proximal spike and a single lateral condyle fragment, with the lateral condyle fragment posteriorly displaced. A 12-cm lateral skin incision was made, and the joint was developed using a para-patellar approach from the anterior to iliotibial band. Posterior buttress plate fixation was successfully performed from behind the iliotibial band using a posterolateral approach, followed by cannulated cancellous screw and lateral locking plate fixation from the anterolateral window.Combined anterolateral and posterolateral approaches from one incision enable intra-articular exposure and fixation based on fixation principles for lateral condyle fragments combined with supracondylar fracture.

Abstract Aims/Introduction Diagnosis of diabetic peripheral neuropathy (DPN) depends on subjective findings, certain investigations for DPN risks have not been performed enough. Bilirubin protects against vascular complications by reducing oxidative stress in diabetes, but is not fully tested for DPN. This study aimed to evaluate sural nerve conduction impairments (SNCI) as an objective DPN marker and the contribution of bilirubin to SNCI. Materials and methods Using DPN‐Check®, SNCI was defined as a decline of amplitude potential or conduction velocity below the normal limit in 150 inpatients with diabetes. The correlations between SNCI and conventional DPN diagnosis criteria, the incidence of diabetic retinopathy/nephropathy, biomarkers for atherosclerosis, cardiac function by ultrasonic cardiogram, and bilirubin were statistically tested, followed by the comparison of logistic regression models for SNCI to find confounders with bilirubin. Results The incidence of SNCI was 72.0%. The sensitivity and specificity of SNCI for DPN prediagnosis by simplified criteria were 54.6 and 90.5%, respectively, and similarly corresponded with diabetic retinopathy and nephropathy (sensitivity 57.4 and 50.0%, respectively). SNCI significantly related to diabetes duration, declined estimated glomerular filtration rate, albuminuria and total bilirubin. SNCI incidence was attenuated in the higher bilirubin tertiles (89.8/65.3/54.8%, P

A 75-year-old woman was admitted to our hospital with progressive dyspnea 7 months after second-line treatment with pembrolizumab for advanced non-small cell lung cancer. Chest radiography revealed hyperinflation in both lung fields, and pulmonary function tests revealed severe obstructive dysfunction without bronchodilator reversibility. There were no identifiable causes such as infections or autoimmune diseases. Therefore, bronchiolitis obliterans syndrome associated with immune checkpoint inhibitors was clinically diagnosed. Pembrolizumab was discontinued, but the respiratory dysfunction was irreversible and resulted in death. Bronchiolitis obliterans syndrome is an extremely rare but potentially severe adverse event associated with immune checkpoint inhibitor-related lung disease.

The Cre-loxP strategy for tissue-specific gene inactivation has become a widely employed tool in several research studies. Conversely, inadequate breeding and genotyping without considering the potential for non-specific Cre-recombinase expression may lead to misinterpretations of results. Nestin-Cre transgenic mice, widely used for the selective deletion of genes in neurons, have been observed to have an incidence of Cre-line germline recombination. In this study, we attempted to generate neuron-specific Glucagon-like peptide 1 receptor (Glp1r) knock-out mice by crossing mice harboring the Nestin-Cre transgene with mice harboring the Glp1r gene modified with loxP insertion, in order to elucidate the role of Glp1r signaling in the nervous system. Surprisingly, during this breeding process, we discovered that the null allele emerged in the offspring irrespective of the presence or absence of the Nestin-Cre transgene, with a high probability of occurrence (93.6%). To elucidate the cause of this null allele, we conducted breeding experiments between mice carrying the heterozygous Glp1r null allele but lacking the Nestin-Cre transgene. We confirmed that the null allele was inherited by the offspring independently of the Nestin-Cre transgene. Furthermore, we assessed the gene expression, protein expression, and phenotype of mice carrying the homozygous Glp1r null allele generated from the aforementioned breeding, thereby confirming that the null allele indeed caused a global knock-out of Glp1r. These findings suggest that the null allele in the NestinCre-Glp1r floxed breeding arose due to germline recombination. Moreover, we demonstrated the possibility that germline recombination may occur not only during the spermatogenesis at testis but also during epididymal sperm maturation. The striking frequency of germline recombination in the Nestin-Cre driver underscores the necessity for caution when implementing precise breeding strategies and employing suitable genotyping methods.

Objectives. Oral sulfate solution (OSS) is used for bowel preparation (BP) during colonoscopy. The way of taking this agent can be used a same-day regimen (only on the day of colonoscopy) and split regimen (the day before and on the day of colonoscopy) for receiving it. In this study, we analyzed the efficacy of a same-day regimen of 480 ml OSS for insufficient bowel preparation (BP) with high-concentrated polyethylene glycol (H-PEG). Materials and Methods. This multicenter retrospective study was conducted from December 2021 to December 2022 at three related institutions on patients aged≥20 years with a fair or poor Aronchick score of BP with 1 l H-PEG in previous colonoscopy. All patients received a low-residual diet and 10 ml of 0.75% picosulfate sodium a day before the colonoscopy and 480 ml of OSS and ≥1 l of water 3 hours before the colonoscopy. We analyzed the rate of improvement with OSS compared to H-PEG and other efficacies, and adverse events (AE). Results. We evaluated 125 cases (77 males) with an average age of 72.1±8.8 years. The completion rate of 480 ml of OSS was 97.6% (122/125). The improvement rate of BP showing good or excellent score with OSS was 70.4% (88/125). Compared OSS with previous H-PEG, the insertion time (min) was 7.0±4.8 vs. 8.1±6.0 (p=0.01), and the adenoma detection rates were 67.2% vs. 63.2% (p=0.05). The cleansing time (min) was 131±46 vs. 165±53 (p

Category: Ankle Introduction/Purpose: The manual traditional anterior drawer test (ADT) is essential for the treatment decision of chronic ankle instability, but have been pointed out of comparatively low reproducibility and accuracy, especially in less experienced hands. To clarify the inter-examiner reproducibility, we compared the actual distance of anterior translation between the junior and senior examiner in the ADT. We also evaluate the diagnostic abilities of the traditional ADT and a novel modified ADT, fixed ADT. Methods: Thirty ankles were included in this study and the ankle instability was defined by the stress radiography. All subjects were performed two methods of manual ADT by junior and senior examiner, and judged the ankle instability in a blinded fashion. The anterior drawer distance was calculated from the lengthening measured by the capacitance-type sensor device. Results: The amount of anterior translation of junior examiner was significantly lower than senior examiner in the traditional ADT (3.3 vs. 4.5 mm, p=0.016), while, there was no significant difference between two examiners in the fixed ADT (4.6 vs. 4.1 mm, p=0.168). The inter-examiner reliability of fixed ADT was higher than traditional ADT. In the junior examiner, the diagnostic accuracy of the fixed ADT was higher than that of traditional ADT (sensitivity, 0.40 vs. 0.80; specificity, 0.75 vs. 0.80, respectively). Conclusion: Fixed ADT may have advantage for a simple manual test of ankle instability as a method with less error between examiners.

As part of ongoing efforts to realize a low‐carbon and hydrogen‐based society, there is an increasing demand for high‐performance electrocatalysts, which are key materials for fuel cells and water electrolysis systems. Although platinum group metals exhibit high catalytic activity, increasing production costs due to resource constraints, limited countries of production, and geopolitical supply issues are threatening their use. Therefore, it is crucial to make substantial changes in resource utilization for the sustainable production of electrochemical catalysts. Herein, the preparation of trifunctional biomass‐derived electrocatalysts for the oxygen reduction reaction and oxygen/hydrogen evolution reactions by the pyrolysis of cellulose nanofibers from ascidian tunicates, dried blood meal, and cyanocobalamin is reported. The combination of N, P, FeN4, and CoN4 structures incorporated in the carbon network leads to high electrochemical performance comparable with rare‐metal‐based electrocatalysts and other carbon alloy electrocatalysts. This work provides a possible strategy for fabricating high‐capacity energy storage devices from biomass resources such as industrial waste without the need for rare metals or other harmful heavy metals.

Category: Arthroscopy; Ankle; Sports Introduction/Purpose: Although the minimal invasiveness of arthroscopic ankle lateral ligament repair (ALLR) means that an early return to sporting activities can be anticipated, many reports have described postoperative cast immobilization and the avoidance of weight-bearing for a certain period of time. Accelerated rehabilitation (AR), in which the period of immobilization is kept to a minimum and early weight-bearing exercises are actively introduced, may be helpful for an early return to sport. The purpose of this study was to investigate the therapeutic outcomes of ALLR with AR including the minimum duration of postoperative ankle immobilization and proactive early weight-bearing. Methods: A total of 23 ankles of 22 patients (11 men, 11 women; mean age 38.7 years) who underwent ALLR for chronic lateral ankle instability were investigated. Postoperative management included the avoidance of weight-bearing until postoperative day (POD) 3, after which full weight-bearing walking with a brace was permitted. The objective was to return to competitive sport 8 weeks after surgery. Preoperative and postoperative major symptoms, ankle range of motion (ROM), stress X-ray assessment, anterior translation (AT) measured with a capacitance-type strain sensor, the Japanese Society for Surgery of the Foot (JSSF) ankle-hindfoot scale, and the Self-Administered Foot Evaluation Questionnaire (SAFE-Q) were evaluated. Results: Postoperatively, instability and pain resolved or improved in all patients. There was no significant postoperative change in ROM. There were significant improvements in the mean talar tilt angle (from 12° to 5.6°), in the mean anterior drawer distance (from 8.2 mm to 4.4 mm) on stress X-rays, and in the mean AT (from 10.5 mm to 4.6 mm). The JSSF scale improved significantly (from 68.8 to 96.8), and the SAFE-Q improved significantly on all subscales. Complete return to sport was achieved by 75% of the patients at 8 weeks after surgery. Conclusion: When AR with proactive weight-bearing exercises was implemented from POD 3 without ankle immobilization after ALLR, there were significant improvements in both objective assessments of ankle stability and clinical scores, and as many as 75% of the patients were able to make a complete return to sport within 8 weeks.

Category: Basic Sciences/Biologics; Trauma Introduction/Purpose: Severe ankle syndesmotic injuries can cause not only anterior inferior tibiofibular ligament (AITFL) injury but also posterior inferior tibiofibular ligament (PITFL) injury. However, the biomechanical stability and the best surgical treatment method for PITFL injuries are unknown. This study aimed to evaluate the stability of AITFL and PITFL injury models and the treatment models with suture-button (SB) fixation, AITFL augmentation with suture-tape (aST), and PITFL augmentation with suture-tape (pST). We hypothesized that PITFL injury causes posterior instability of syndesmosis and that this can be stabilized with pST fixation Methods: This study was approved by our institution's ethics review board. Ten normal fresh-frozen cadaver legs (4 males and 6 females) that were donated to our university's department of anatomy were used. The specimens were tested with the application of traction and rotational forces for dorsiflexion and external and internal rotation of the ankle joint. The fibular rotational angle related to the tibia (FRA), anterior tibiofibular diastasis (aTFD), and posterior tibiofibular diastasis (pTFD) were measured using the magnetic tracking system. Intact, injured (AITFL, PITFL and IOM resection), SB fixation, SB + aST fixation, and SB + aST + pST fixation models were made and loaded with forces. One-way ANOVA was used to evaluate the relationship between the models. Post-hoc analysis of the differences between the models was performed using Dunnett's test. A p value of 0.05 was chosen as the level of significance. Results: In the injured model, both FRA and TFD were significantly increased compared with those of the intact model in all directions. In the SB fixation model, only FRA with an external rotation force was significantly increased compared with that of the intact model. In the SB+aST model, both FRA and aTFD were not significantly different from those in the intact model. Conclusion: The results of this study showed that there was external and internal rotational instability in the AITFL and PITFL injury models, while there was stability in the SB + aST model. SB fixation alone did not reduce FRA with an external rotation force and there was no significantly different FRA with an internal rotation force. With SB fixation alone, anterior instability was found to be greater than posterior stability, while aST fixation was associated with anterior stability. In this study, the change in syndesmosis stability after pST fixation was found to be restrictive.

Abstract Background No case definition of Type 1 diabetes (T1D) for the claims data has been proposed in Japan yet. This study aimed to evaluate the performance of candidate case definitions for T1D using Electronic health care records (EHR) and claims data in a University Hospital in Japan. Methods The EHR and claims data for all the visiting patients in a University Hospital were used. As the candidate case definitions for claims data, we constructed 11 definitions by combinations of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. (ICD 10) code of T1D, the claims code of insulin needles for T1D patients, basal insulin, and syringe pump for continuous subcutaneous insulin infusion (CSII). We constructed a predictive model for T1D patients using disease names, medical practices, and medications as explanatory variables. The predictive model was applied to patients of test group (validation data), and performances of candidate case definitions were evaluated. Results As a result of performance evaluation, the sensitivity of the confirmed disease name of T1D was 32.9 (95% CI: 28.4, 37.2), and positive predictive value (PPV) was 33.3 (95% CI: 38.0, 38.4). By using the case definition of both the confirmed diagnosis of T1D and either of the claims code of the two insulin treatment methods (i.e., syringe pump for CSII and insulin needles), PPV improved to 90.2 (95% CI: 85.2, 94.4). Conclusions We have established a case definition with high PPV, and the case definition can be used for precisely detecting T1D patients from claims data in Japan.

A 79-year-old man presented with high fever, marked eosinophilia, altered biochemical liver function tests (LFT) with predominance of biliary enzymes, and severe wall thickening of the gallbladder. Magnetic resonance cholangiopancreatography (MRCP) suggested cholecystitis, without signs of biliary strictures. Laparoscopic cholecystectomy and exploratory liver excision revealed eosinophilic cholangitis and cholecystitis, complicated with hepatitis and portal phlebitis. Prednisolone monotherapy rapidly improved peripheral eosinophilia, but not LFT. Liver biopsy showed that infiltrating eosinophils were replaced by lymphocytes and plasma cells. Treatment with ursodeoxycholic acid improved LFT abnormalities. Nevertheless, after 2 months, transaminase-dominant LFT abnormalities appeared. Transient prednisolone dose increase improved LFT, but biliary enzymes’ levels re-elevated and jaundice progressed. The second and third MRCP within a 7-month interval showed rapid progression of biliary stricture. The repeated liver biopsy showed lymphocytic, not eosinophilic, peribiliary infiltration and hepatocellular reaction to cholestasis. Eighteen months after the first visit, the patient died of hepatic failure. Autopsy specimen of the liver showed lymphocyte-dominant peribiliary infiltration and bridging fibrosis due to cholestasis. Though eosinophil-induced biliary damage was an initial trigger, repeated biopsy suggested that lymphocytes played a key role in progression of the disease. Further studies are needed to elucidate the relationship between eosinophils and lymphocytes in eosinophilic cholangitis.

GABAergic neurons in the ventral tegmental area (VTA) have brain-wide projections and are involved in multiple behavioral and physiological functions. Here, we revealed the responsiveness of Gad67+ neurons in VTA (VTAGad67+) to various neurotransmitters involved in the regulation of sleep/wakefulness by slice patch clamp recording. Among the substances tested, a cholinergic agonist activated, but serotonin, dopamine and histamine inhibited these neurons. Dense VTAGad67+ neuronal projections were observed in brain areas regulating sleep/wakefulness, including the central amygdala (CeA), dorsal raphe nucleus (DRN), and locus coeruleus (LC). Using a combination of electrophysiology and optogenetic studies, we showed that VTAGad67+ neurons inhibited all neurons recorded in the DRN, but did not inhibit randomly recorded neurons in the CeA and LC. Further examination revealed that the serotonergic neurons in the DRN (DRN5–HT) were monosynaptically innervated and inhibited by VTAGad67+ neurons. All recorded DRN5–HT neurons received inhibitory input from VTAGad67+ neurons, while only one quarter of them received inhibitory input from local GABAergic neurons. Gad67+ neurons in the DRN (DRNGad67+) also received monosynaptic inhibitory input from VTAGad67+ neurons. Taken together, we found that VTAGad67+ neurons were integrated in many inputs, and their output inhibits DRN5–HT neurons, which may regulate physiological functions including sleep/wakefulness.

Abstract The stress response is a physiological system for adapting to various internal and external stimuli. Corticotropin-releasing factor-producing neurons in the paraventricular nucleus of the hypothalamus (PVN-CRF neurons) are known to play an important role in the stress response as initiators of the hypothalamic–pituitary–adrenal axis. However, the mechanism by which activity of PVN-CRF neurons is regulated by other neurons and bioactive substances remains unclear. Here, we developed a screening method using calcium imaging to identify how physiological substances directly affect the activity of PVN-CRF neurons. We used acute brain slices expressing a genetically encoded calcium indicator in PVN-CRF neurons using CRF-Cre recombinase mice and an adeno-associated viral vector under Cre control. PVN-CRF neurons were divided into ventral and dorsal portions. Bath application of candidate substances revealed 12 substances that increased and 3 that decreased intracellular calcium concentrations. Among these substances, angiotensin II and histamine mainly increased calcium in the ventral portion of the PVN-CRF neurons via AT1 and H1 receptors, respectively. Conversely, carbachol mainly increased calcium in the dorsal portion of the PVN-CRF neurons via both nicotinic and muscarinic acetylcholine receptors. Our method provides a precise and reliable means of evaluating the effect of a substance on PVN-CRF neuronal activity.

Abstract Background Morphologically, osteofibrous dysplasia-like adamantinoma is thought to be intermediate between osteofibrous dysplasia and adamantinoma. Its treatment is not well established owing to its rarity. Case presentation We report about of a 10-year-old girl with osteofibrous dysplasia-like adamantinoma initially diagnosed as osteofibrous dysplasia and treated via intercalary segmental resection with partial cortex preservation using a pedicled vascularized fibula graft for reconstruction. Bone union was observed 9 weeks after surgery. Twenty-two months after the definitive surgery, no recurrence was observed. Conclusion This case illustrates the upgrade from osteofibrous dysplasia to osteofibrous dysplasia-like adamantinoma. The surgical method may aid the treatment of osteofibrous dysplasia-like adamantinoma with incomplete cortex involvement of the tumor.

Interleukin (IL)-24 is a member of the IL-20 family of cytokines and is produced by various types of cells, such as CD4+ T cells, NK cells, mast cells, keratinocytes, bronchial epithelial cells, and myofibroblasts. Previous studies suggest that IL-24 plays an essential role in the pathogenesis of pro-inflammatory autoimmune disorders such as psoriasis, arthritis, and inflammatory bowel diseases. However, the role of IL-24 in the pathogenesis of allergic diseases has been elusive. It has already been reported that IL-24 is involved in the pathogenesis of allergic lung and skin diseases. Moreover, we have recently revealed for the first time the pivotal functions of IL-24 in IL-13–mediated skin barrier dysfunction in atopic dermatitis (AD), which is known to be a characteristic of AD caused by Th2 cytokines such as IL-4 or IL-13. In this review, we show recent advances in the basic characteristics of IL-24 and its novel functions in the pathogenesis of allergic skin inflammation, focusing on AD. A better understanding of the role of IL-24 in allergic diseases can lead to the development of new therapeutic options.