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Abstract Background This study aimed to examine whether the non-weight-bearing tunnel view X-ray is effective for short-term evaluation of medial meniscus posterior root tear (MMPRT) by assessing the X-ray characteristics at the initial and follow-up visits. Methods This was a retrospective longitudinal study of 26 enrolled knees diagnosed with MMPRT on magnetic resonance imaging. The distance between the medial tibial eminence and medial femoral condyle (MTE–MFC distance) and medial tibiofemoral joint (MTFJ) width were measured by obtaining non-weight-bearing tunnel view and frontal view X-ray radiographs. The initial and follow-up values at a median interval of 17 days were compared. Additionally, the correlations between the MTE–MFC distance increase rate and body mass index (BMI), age, femorotibial angle (FTA), and posterior tibial slope (PTS) were evaluated using linear regression analysis. Results The tunnel view images of the initial and follow-up X-rays showed a significant increase in the MTE–MFC distance and a significant decrease in the MTFJ width. Furthermore, a moderate correlation was observed between the change in the MTE–MFC distance and the time interval between X-rays. However, no substantial correlation was observed for the change in the MTFJ width over time. Moreover, no significant correlation was observed between the change in the MTE–MFC distance in the non-weight-bearing tunnel view and BMI, age, FTA, and PTS. Conclusions The non-weight-bearing tunnel view is highly beneficial for evaluating MMPRT progression in the short term.

As an alternative to conventional plastic dishes, the interface between water-immiscible hydrophobic fluids, such as perfluorocarbons and silicones, permits cell adhesion and growth. Thus, it is expected to replace the petroleum-derived products in a sustainable society. However, most hydrophobic fluids are cytotoxic, which limits the range of mechanical and chemical cues exposed to the cells. Using a data-driven approach, this study aimed to identify non-cytotoxic ionic liquids (ILs) as fluid culture platforms to take advantage of their ‘designer’ nature for broadening the possible physicochemical ranges exposed to cells and their repeated use owing to their high heat stability before their biological applications. The new candidates within the readily synthesized ammonium-type ILs were identified through the active cycle of regression and a limited number of cytotoxicity tests. Structure – cytotoxicity analysis indicated that the presence of multiple long alkyl branches was critical for low cytotoxicity. Particularly, we successfully cultured human mesenchymal stem cells (hMSCs) at the trihexylethylammonium trifluoromethylsulfonylimide interface and repeated their use after solvent extraction and heat sterilization. This study identified non-cytotoxic ILs that fulfill plastics’ 3 R (Reduce, Recycle, and Replace) requirements and opens new avenues for hMSC fate manipulation through mechanotransduction.

Collective cell migration is an essential biological process. Migration behaviors of multiple cellular units depend on the mechanical and chemical properties of their scaffolds and the geometry of the cells. However, the mechanisms by which these properties synergistically regulate the collective cell characteristics remain unknown. A robust method is required to analyze collective cell migration. Therefore, in this study, we developed a new method for collective cell migration analysis using defined chemical, mechanical, and geometrical properties. Our method is based on a poly(acrylic acid) hydrogel, whose surface is functionalized with photocleavable poly(ethylene glycol) and a cell-adhesive peptide. By controlling the UV irradiation of the photoactivatable hydrogel, we created geometrically controlled cellular clusters and induced collective migration. Furthermore, chemical and mechanical cues exposed to cell clusters were manipulated depending on the surface density of the cell-adhesive peptide and crosslinking density of the hydrogel. As a proof of concept, we also demonstrated that the collective migration of epithelial cells was synergistically regulated by the chemical and mechanical properties of the scaffold. Our results suggest the new photoactivatable substrate as a promising tool for advanced molecular and mechanobiological analyses of collective cell migration.

Polycystic ovary syndrome (PCOS) is associated with an increased risk of psychological distress as well as enhanced responses to psychosocial stress. Recently, it was hypothesized that PCOS patients may be at high risk of novel COVID-19 infections and worse clinical presentations during such infections. Here, we evaluated the effects of PCOS on stress responses to bacterial and viral mimetics using dihydrotestosterone-induced PCOS model rats. Lipopolysaccharide (LPS; a bacterial mimetic) or polyinosinic-polycytidylic acid (Poly-IC; a viral mimetic) was injected into PCOS model rats (PCOS) and non-PCOS rats (control), and the rats' stress responses were evaluated. In the PCOS group, the rats’ anorectic and febrile responses to LPS injection were enhanced, whereas their anorectic and febrile responses to Poly-IC injection were unaltered. The PCOS group also exhibited greater changes in peripheral cytokine levels in response to LPS, but not Poly-IC. On the contrary, after the injection of Poly-IC depressed locomotor activity was more evident in the PCOS group, whereas no such changes were observed after LPS injection. These findings indicate that although the stress responses of PCOS model rats to infection may be enhanced, the patterns of change in stress responses and their underlying mechanisms may differ between bacterial and viral infections.

Activin A promotes the development of endometriotic lesions in a murine model of endometriosis, and the immunohistochemical localization of phosphorylated suppressor of mothers against decapentaplegic homolog 2/3 (pSMAD2/3) complex in endometriotic lesions has been reported. Activin may therefore be involved in the development and proliferation of endometriotic cells via the SMAD signaling pathway. However, few detailed reports exist on SMAD7 expression in endometriosis. The purpose of this study was to investigate the expression of pSMAD2/3 or pSMAD3 and SMAD7 in the orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine model and the effect of activin A on pSMAD2/3 and SMAD7 expression. We established an endometriosis murine model via the intraperitoneal administration of endometrial tissue and blood from donor mice. Activin A was intraperitoneally administered to the activin group. We immunohistochemically evaluated orthotopic endometria, ovarian endometriotic tissues, and endometriotic lesions in the murine model followed by western blotting. We found that pSMAD3 and SMAD7 were expressed in ovarian endometriosis and orthotopic endometria from patients with and without endometriosis. In the murine model, endometriotic lesions expressed pSMAD2/3 and SMAD7 in the activin and control groups, and higher SMAD7 expression was found in the activin group. To the best of our knowledge, this study is the first to show that SMAD7 expression is upregulated in endometriosis. In conclusion, these results suggest that activin A activates the SMAD signaling pathway and promotes the development of endometriotic lesions, thus identifying SMAD7 as a potential therapeutic target for endometriosis.

Abstract Microglia are resident macrophages in the central nervous system (CNS) that play various roles during brain development and in the pathogenesis of CNS diseases. Recently, reprogramming of cellular energetic metabolism in microglia has drawn attention as a crucial mechanism for diversification of microglial functionality. Lipids are highly diverse materials and crucial components of cell membranes in every cell. Accumulating evidence has shown that lipid and its metabolism are tightly involved in microglial biology. In this review, we summarize the current knowledge about microglial lipid metabolism in health and disease.

Abstract Introduction Hypoxic pulmonary vasoconstriction optimises oxygenation in the lung by matching the local‐blood perfusion to local‐ventilation ratio upon exposure to alveolar hypoxia. It plays an important role in various pulmonary diseases, but few imaging evaluations of this phenomenon in humans. This study aimed to determine whether chest digital dynamic radiography could detect hypoxic pulmonary vasoconstriction as changes in pulmonary blood flow in healthy individuals. Methods Five Asian men underwent chest digital dynamic radiography before and after 60 sec breath‐holding at the maximal inspiratory level in upright and supine positions. Alveolar partial pressure of oxygen and atmospheric pressure were calculated using the blood gas test and digital dynamic radiography imaging, respectively. To evaluate the blood flow, the correlation rate of temporal change in each pixel value between the lung fields and left cardiac ventricles was analysed. Results Sixty seconds of breath‐holding caused a mean reduction of 26.7 ± 6.4 mmHg in alveolar partial pressure of oxygen. The mean correlation rate of blood flow in the whole lung was significantly lower after than before breath‐holding (before, upright 51.5%, supine 52.2%; after, upright 45.5%, supine 46.1%; both P

ABSTRACTDespite considerable interest in the impact of space travel on human health, the influence of the gravity vector on collective cell migration remains unclear. This is primarily because of the difficulty in inducing collective migration, where cell clusters appear in an inverted position against gravity, without cellular damage. In this study, photoactivatable surfaces were used to overcome this challenge. Photoactivatable surfaces enable the formation of geometry-controlled cellular clusters and the remote induction of cellular migration via photoirradiation, thereby maintaining the cells in the inverted position. Substrate inversion preserved the circularity of cellular clusters compared to cells in the normal upright position, with less leader cell appearance. Furthermore, the inversion of cells against the gravity vector resulted in the remodeling of the cytoskeletal system via the strengthening of external actin bundles. Within the 3D cluster architecture, enhanced accumulation of active myosin was observed in the upper cell-cell junction, with a flattened apical surface. Depending on the gravity vector, attenuating actomyosin activity correlates with an increase in the number of leader cells, indicating the importance of cell contractility in collective migration phenotypes and cytoskeletal remodeling.

Abstract The current study aimed to test whether the ratio of T1-weighted to T2-weighted signal intensity (T1W/T2W ratio: rT1/T2) derived from conventional MRI could act as a surrogate relaxation time predictive of IDH mutation status in histologically lower-grade gliomas. Strong exponential correlations were found between rT1/T2 and each of T1- and T2-relaxation times in eight subjects (rT1/T2 = 1.63exp−0.0005T1-relax + 0.30 and rT1/T2 = 1.27exp−0.0081T2-relax + 0.48; R2 = 0.64 and 0.59, respectively). In a test cohort of 25 patients, mean rT1/T2 (mrT1/T2) was significantly higher in IDHwt tumors than in IDHmt tumors (p

Abstract The best available evidence and the predictive value of computed tomography (CT) findings for prognosis in patients with acute respiratory distress syndrome (ARDS) are unknown. We systematically searched three electronic databases (MEDLINE, CENTRAL, and ClinicalTrials.gov). A total of 410 patients from six observational studies were included in this systematic review. Of these, 143 patients (34.9%) died due to ARDS in short-term. As for CT grade, the CTs used ranged from 4- to 320-row. The index test included diffuse attenuations in one study, affected lung in one study, well-aerated lung region/predicted total lung capacity in one study, CT score in one study and high-resolution CT score in two studies. Considering the CT findings, pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 62% (95% confidence interval [CI] 30–88%), 76% (95% CI 57–89%), 2.58 (95% CI 2.05–2.73), 0.50 (95% CI 0.21–0.79), and 5.16 (95% CI 2.59–3.46), respectively. This systematic review revealed that there were major differences in the definitions of CT findings, and that the integration of CT findings might not be adequate for predicting short-term mortality in ARDS. Standardisation of CT findings and accumulation of further studies by CT with unified standards are warranted.

In this study, intracranial EEG recordings show that neural representations of imagined images can still be present in humans even when they are shown conflicting images.

Introduction Left renal vein thrombus complicating nutcracker syndrome is relatively rare. To the best of our knowledge, there have been only four previous case reports. Furthermore, there have been no reports of pulmonary thromboembolism caused by nutcracker syndrome. Herein, we report a rare case of pulmonary thromboembolism caused by nutcracker syndrome and its clinical management. Case presentation A 40‐year‐old man was admitted to our hospital with acute left flank pain. Computed tomography angiography revealed compression of the left renal vein between the aorta and the superior mesenteric artery with a left renal vein thrombus. Furthermore, computed tomography revealed bilateral pulmonary thromboembolism. Rivaroxaban was administered as an anticoagulant. Twenty days after initiation, computed tomography revealed complete resolution of pulmonary thromboembolism and left renal vein thrombus, and repeated computed tomography showed no recurrence. Conclusion This case report highlights nutcracker syndrome as a likely cause of pulmonary thromboembolism.

Previous research has shown that simulated child sexual abuse (CSA) interview training using avatars paired with feedback and modeling improves interview quality. However, to make this approach scalable, the classification of interviewer questions needs to be automated. We tested an automated question classification system for these avatar interviews while also providing automated interventions (feedback and modeling) to improve interview quality. Forty-two professionals conducted two simulated CSA interviews online and were randomly provided with no intervention, feedback, or modeling after the first interview. Feedback consisted of the outcome of the alleged case and comments on the quality of the interviewer’s questions. Modeling consisted of learning points and videos illustrating good and bad questioning methods. The total percentage of agreement in question coding between human operators and the automated classification was 72% for the main categories (recommended vs. not recommended) and 52% when 11 subcategories were considered. The intervention groups improved from first to second interview while this was not the case in the no intervention group (intervention x time: p = 0.007, ηp2 = 0.28). Automated question classification worked well for classifying the interviewers’ questions allowing interventions to improve interview quality.

β3-Adrenoceptor (AR) agonists are used to treat patients with an overactive bladder (OAB). Clinical proof-of-concept data have been obtained for the β3-AR agonists vibegron, mirabegron, solabegron, and ritobegron; however, the selectivities of these agents have not been compared directly under the same experimental conditions. Moreover, the bladders of some patients express lower β3-AR densities than those of healthy individuals, and the β3-AR density might be expected to affect agonist activity. This study assessed the β3-AR selectivities of four β3-AR agonists and examined the effects of β-AR density on their pharmacological profiles. Functional cellular assays were performed using Chinese hamster ovary-K1 cells expressing three human β-AR subtypes transfected with different amounts of plasmid DNA (0.1, 0.05, 0.025 μg/well). The half-maximal effective concentration values, intrinsic activities (IAs), and β3-AR selectivities of vibegron, mirabegron, solabegron, and ritobegron were calculated to assess their pharmacological profiles. The β3-AR selectivities of vibegron, mirabegron, solabegron, and ritobegron were >7937-, 517-, 21.3-, and >124-fold higher than for β1-ARs, and >7937-, 496-, >362- and 28.1-fold higher than for β2-ARs, respectively, under the same experimental conditions. The IAs of mirabegron, solabegron, and ritobegron decreased in line with decreasing receptor density, while the IA of vibegron was maintained at the same level as that of the full agonist isoproterenol at various β3-AR densities. Vibegron has high β3-AR selectivity and exhibits full agonist activity, regardless of the β3-AR density. These results suggest that vibegron is a highly effective and safe drug for treating OAB.

Oxaliplatin is a key drug used in the management of solid tumors, such as colorectal cancer; however, it causes peripheral neuropathy. In this study, we investigated the effect of ibudilast, a phosphodiesterase inhibitor, on oxaliplatin-induced mechanical allodynia and histological changes in rats. Ibudilast (7.5 mg/kg, i.p., 5 times per week) reduced mechanical allodynia and histological changes induced by oxaliplatin (4 mg/kg, i.p., twice a week). In contrast, ibudilast (0.01–10 μM) had no effect on oxaliplatin-induced tumor cytotoxicity in murine colon adenocarcinoma 26 cells. These findings suggest that ibudilast could be useful for preventing oxaliplatin-induced peripheral neuropathy in clinical settings.

Computed tomography (CT) -guided bone biopsy is a diagnostic procedure performed on the musculoskeletal system with a high diagnostic yield and low complications. However, CT-guided bone biopsy has the disadvantage that it is difficult to confirm the presence of tumor cells during the biopsy procedure. Recently, the clinical benefits of dual-energy CT (DECT) over single-energy CT have been revealed. DECT can provide material decomposition images including calcium suppression images, and effective atomic number (Zeff) and electron density (ED) maps. ED maps have been reported to indicate cellularity. A 61-year-old woman with a history of breast cancer surgery was admitted to our hospital and underwent a CT-guided bone biopsy of the right ilium using ED maps. As a result, she was diagnosed with breast cancer metastases of intertrabecular bone. A comparison of ED maps with a pathological specimen revealed that high ED values occurred exclusively in the tumor area with high cellularity. This study indicates that ED maps produced using DECT may have potential utility in the accurate identification of metastases with high cellularity in bone lesions.

Abstract Background Pancreatic acinar cell carcinoma is rare; it accounts for 1% of all malignant pancreatic exocrine tumors. Although surgical resection is an option for curative treatment, the safety and efficacy of conversion surgery in patients with pancreatic acinar cell carcinoma with metastasis remain unknown. Case A 67‐year‐old man with epigastric pain and a pancreatic tumor was referred to our hospital. Computed tomography revealed a large tumor with a maximum diameter of 67 mm at the pancreatic head and a 23‐mm mass in the left upper abdominal cavity. Because a definitive diagnosis could not be made based on endoscopic ultrasonography‐guided fine needle aspiration biopsy findings, a diagnostic laparoscopy was performed. The tumor in the greater omentum at the left upper abdomen, resected under laparoscopy, was histopathologically diagnosed as pancreatic acinar cell carcinoma. Therefore, the pancreatic tumor was diagnosed as an unresectable pancreatic acinar cell carcinoma with a solitary peritoneal dissemination. The size of the main pancreatic tumor decreased to 15 mm after 18 courses of FOLFIRINOX (5‐fluorouracil, leucovorin, irinotecan, and oxaliplatin). Subsequently, the patient underwent conversion surgery, and the initial diagnosis of pancreatic acinar cell carcinoma was confirmed on pathological examination. The patient was discharged 31 days postoperatively, following which he received adjuvant chemotherapy with S‐1. No sign of recurrence has been observed for 32 months after surgical resection. Conclusion FOLFIRINOX may be effective in patients with pancreatic acinar cell carcinoma, and conversion surgery after FOLFIRINOX may be applicable to selective patients.

Peripheral nerve injury (PNI) induces neuronal hyperexcitability, which underlies neuropathic pain. The emergence of RNA sequencing technologies has enabled profiling of transcriptional changes in pathological conditions. However, these approaches do not provide information regarding metabolites such as lipids that are not directly encoded by genes. Fatty acids (FAs) are some of the essential lipids in mammalian organisms and are mainly stored as membrane phospholipids. In response to various biological stimuli, FAs are rapidly released and converted into several mediators, such as eicosanoids and docosanoids. FAs themselves or their metabolites play important roles in physiology and pathology. In this study, using a comprehensive lipidomic analysis of FA metabolites, 152 species were measured in the dorsal root ganglia of mice at multiple time points after PNI. We found that PNI increased the ω-6 FA metabolites produced by cyclooxygenases but not those produced by lipoxygenases or cytochrome P450 enzymes in the dorsal root ganglia. In contrast, ω-3 FA metabolites biosynthesized by any enzyme transiently increased after nerve injury. Overall, these findings provide a new resource and valuable insights into PNI pathologies, including pain and nerve regeneration.

Abstract This paper discusses the outline and the conditions of the phenomenon known as the “merged temple,” a composite building consisting of the extension of a “sub‐building” covering or wrapping an existing Hindu temple, or “main temple.” These are frequently observed in the Old City of Varanasi (Uttar Pradesh, India). Their number and distribution, morphological variations, forming process, and other properties were investigated through a field survey and interviews with their residents. Merged temples of various shapes and degrees are generated through a combination of extrinsic development pressure and intrinsic characteristics of Hindu temples, their continuity, and their immobility, in the urban space which has historically accumulated numerous temples. In its formative process, the “moderate” plasticity of the Hindu temple building works effectively as a medium, and covering the top of the temple with new construction is carefully avoided.

Abstract Background To evaluate the efficacy and safety of transcatheter arterial embolization for renal angiomyolipoma using a 1.8-French tip microballoon catheter and a mixture of ethanol and Lipiodol. Methods Seven consecutive patients with total of eight angiomyolipomas underwent this procedure between June 2014 and June 2017. A 1.8-French tip microballoon catheter was advanced to the feeding artery of the angiomyolipoma, and transcatheter arterial embolization was performed with a mixture of ethanol and Lipiodol under microballoon inflation. We retrospectively evaluated the characteristics of angiomyolipomas, technical success rate, clinical success rate, renal function, and adverse events. Technical success and clinical success were defined as complete embolization of all feeding arteries and reduction of tumor size, respectively. Results The median size of the angiomyolipomas was 46 mm (range, 40–64 mm). Transcatheter arterial embolization was successful in all eight angiomyolipomas. The median volume of the mixture of ethanol and Lipiodol was 6.0 ml (range, 2.0–14 ml). The median ratio of ethanol to Lipiodol was 71% (range, 71–75%). All eight angiomyolipomas shrank with a median shrinkage rate of 34% in diameter (range, 9–63%) and 77% in volume (range, 48–94%). The median follow-up period was 13 months (range, 9–54 months). Clinical success was achieved in all cases. Serum creatinine concentrations and the pre- and post-procedural estimated glomerular filtration rates did not change notably, and there were no major complications. Conclusion Transcatheter arterial embolization for renal angiomyolipoma using a 1.8-French tip microballoon catheter with a mixture of ethanol and Lipiodol is effective and safe.

Abstract Background Approximately 30% of patients on dialysis received combination therapy for their phosphate binder prescription; however, few studies for combined effects of phosphate binders are reported. For the purpose of evaluating the efficacy of combination therapy, we compared the efficacy of sucroferric oxyhydroxide (PA21) combined with calcium carbonate with that of lanthanum carbonate hydrate, sevelamer hydrochloride, and ferric citrate hydrate combined with calcium carbonate. Methods For in vitro studies, calcium carbonate and the other phosphate binders alone or in combination were stirred in phosphate solution at pH 2–8 for 2 h. After centrifuging the suspension, the phosphorus level in the supernatant was determined. For in vivo studies, rats were orally administered calcium carbonate and the other phosphate binders (except for sevelamer hydrochloride) alone or in combination, followed by oral administration of phosphate solution adjusted to pH 2 or 7. Serum samples were collected from the rats at predetermined timepoints and the serum phosphorus levels were determined and analyzed using a two-way analysis of variance. Results In the in vitro study, the measured phosphate-binding capacity of combining sevelamer hydrochloride, PA21, and lanthanum carbonate hydrate with calcium carbonate was approximately equal to or greater than the theoretical values under most conditions. Furthermore, these combined effects were insensitive to pH in that order. The measured phosphate-binding capacity of ferric citrate hydrate combined with calcium carbonate was smaller than the theoretical values, and the combination did not exhibit efficacy under any of the tested conditions. In the in vivo study, the combined effect of PA21 and calcium carbonate at both pH values and that of lanthanum carbonate hydrate and calcium carbonate at pH 2 were additive. In contrast, the combined effect of lanthanum carbonate hydrate and calcium carbonate at pH 7 and that of ferric citrate hydrate and calcium carbonate at pH 2 were antagonistic. Conclusions These results suggest that coadministration of PA21 and calcium carbonate showed good and relatively stable efficacy throughout the range of the gastrointestinal pH and that combining lanthanum carbonate hydrate and ferric citrate hydrate with calcium carbonate may not produce the expected efficacy under certain conditions.

Abstract Introduction Bronchial thermoplasty (BT) is a bronchoscopic procedure that involves the delivery of thermal radiofrequency energy to the bronchial wall for treating severe asthma. It has been suggested that too many radiofrequency activations could induce serious adverse events (SAEs) at an early stage. We aimed to examine the number of radiofrequency activations at each session and early lung function changes from baseline to determine whether these are related to SAEs. Methods We retrospectively investigated 13 consecutive patients who underwent three sessions each of BT for severe asthma from February 2015 to January 2016. Lung function tests were performed on the day before and after each BT procedure. Since we compared the number of activations and lung function changes from baseline after each session, a total of 39 sessions were reviewed. The relationship between the number of radiofrequency activations and each lung function change from baseline was also examined by linear regression analysis. Results A total of 10 SAEs (4 of pneumonia, 3 of atelectasis, 2 of bronchial asthma exacerbation and 1 of hemoptysis) were observed following the 39 BT sessions. When we compared sessions with and without SAEs, there were no differences in the number of activations (mean ± SD, 71.5 ± 28.6 times in sessions with SAEs; 66.5 ± 25.1 times in sessions without SAEs; p = 0.772) and lung function changes (mean changes in FVC/%FVC/FEV1/%FEV1/%PEF from baseline; − 0.49 l/− 14.2%/− 0.36 l/− 11.7%/− 9.6% in sessions with SAEs; − 0.43 l/− 13.3%/− 0.34 l/− 12.1%/− 9.4% in sessions without SAEs; p > 0.05 for all the above). Increase in the number of activations correlated with decreased FEV1 (R 2 = 0.17, p = 0.0088) and %FEV1 (R 2 = 0.11, p = 0.0357). Conclusions Increase in the number of radiofrequency activations during BT is related to a decrease in FEV1 and %FEV1 from baseline. The number of radiofrequency activations, however, is not associated with SAEs after BT.

Key message Chest digital dynamic radiography (DDR) is a novel method for evaluating pulmonary perfusion and ventilation. It could depict ventilation–perfusion mismatch in a pulmonary artery sarcoma with severe stenosis in the right pulmonary artery. This report is the first demonstration of ventilation–perfusion mismatch in a malignant neoplasm using DDR.

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe adverse effect observed in most patients treated with neurotoxic anti-cancer drugs. Currently, there are no therapeutic options available for the prevention of CIPN. Furthermore, few drugs are recommended for the treatment of existing neuropathies because the mechanisms of CIPN remain unclear. Each chemotherapeutic drug induces neuropathy by distinct mechanisms, and thus we need to understand the characteristics of CIPN specific to individual drugs. Here, we review the known pathogenic mechanisms of oxaliplatin- and paclitaxel-induced CIPN, highlighting recent findings. Cancer chemotherapy is performed in a planned manner; therefore, preventive strategies can be planned for CIPN. Drug repositioning studies, which identify the unexpected actions of already approved drugs, have increased in recent years. We have also focused on drug repositioning studies, especially for prevention, because they should be rapidly translated to patients suffering from CIPN.

Although previous research has confirmed the effectiveness of simulated child sexual abuse interviews with feedback, its validation is limited to Western contexts and face-to-face settings. The present study aims to extend this research to non-Western and online/remote training conditions. Thirty-two Japanese undergraduate students were randomly assigned to a control or feedback group. The feedback group conducted a set of six online simulated child sexual abuse interviews while receiving feedback after each interview in an attempt to improve the quality of their questioning style. The feedback consisted of the outcome of the alleged cases and the quality of the questions asked in the interviews. The control group conducted the interviews without feedback. The feedback (vs. control) increased the proportion of recommended questions (first interview: 45%; last interview: 65% vs. first: 43%; last: 42%, respectively) by using fewer not-recommended questions and eliciting fewer incorrect details. Furthermore, only participants in the feedback group (7 out of 17) demonstrated a reliable change in the proportion of recommended questions. The present study explores the efficacy of simulated interview training with avatars in a different cultural setting and in the context of remote administration. The differences between the present study and previous research are discussed in light of cultural and logistical aspects.

Primary lung cancer (PLC) presents with various symptoms. However, there have been no reports of PLC causing haemothorax and haemoptysis simultaneously. We present an unusual case of massive haemothorax and haemoptysis caused by a PLC, in which haemostasis was secured with interventional radiology. A 58‐year‐old woman was hospitalized for a right secondary pneumothorax associated with emphysema. Chest computed tomography showed a mass shadow at the right lower lobe and on the right parietal pleura. Three days after air drainage, about 2000 mL of bloody pleural effusion accompanied by massive haemoptysis was observed. Haemoglobin concentration decreased to 4.9 g/dL and the patient was treated with selective embolization of the bronchial artery and the intercostal arteries. A diagnosis of PLC was made based on pleural fluid cytology. The patient was transferred to the palliative care hospital three months later without recurrence of haemothorax and haemoptysis.

Pulmonary arteriovenous malformations (PAVMs) are rare vascular structures providing direct capillary-free communications between pulmonary arteries and veins. Embolotherapy is indicated as a front-line therapy. We report an unusual long-term complication of coil embolization for a 44-year-old woman with hereditary hemorrhagic telangiectasia (HHT) who had repeatedly undergone the procedures for her PAVMs. She expectorated the coil which had been placed 12 years earlier and migrated to the bronchus according to the chest radiogram and bronchoscopy. Histology of the resected lung segment suggested the cavity communicating with the bronchus was the consequence of abscess formation around the coils. Even after technically successful embolization to PAVMs, long term follow-up should be necessary paying attention to the symptoms and imaging to avoid massive hemoptysis and subsequent emergency surgery.

One of the challenges in glioblastoma (GBM) imaging is to visualize non-enhancing tumor (NET) lesions. The ratio of T1- and T2-weighted images (rT1/T2) is reported as a helpful imaging surrogate of microstructures of the brain. This research study investigated the possibility of using rT1/T2 as a surrogate for the T1- and T2-relaxation time of GBM to visualize NET effectively. The data of thirty-four histologically confirmed GBM patients whose T1-, T2- and contrast-enhanced T1-weighted MRI and 11C-methionine positron emission tomography (Met-PET) were available were collected for analysis. Two of them also underwent MR relaxometry with rT1/T2 reconstructed for all cases. Met-PET was used as ground truth with T2-FLAIR hyperintense lesion, with >1.5 in tumor-to-normal tissue ratio being NET. rT1/T2 values were compared with MR relaxometry and Met-PET. rT1/T2 values significantly correlated with both T1- and T2-relaxation times in a logarithmic manner (p < 0.05 for both cases). The distributions of rT1/T2 from Met-PET high and low T2-FLAIR hyperintense lesions were different and a novel metric named Likeliness of Methionine PET high (LMPH) deriving from rT1/T2 was statistically significant for detecting Met-PET high T2-FLAIR hyperintense lesions (mean AUC = 0.556 ± 0.117; p = 0.01). In conclusion, this research study supported the hypothesis that rT1/T2 could be a promising imaging marker for NET identification.

Oxaliplatin causes acute cold hypersensitivity in most patients. We previously reported oxalate derived from oxaliplatin induced cold allodynia via overexpression of transient receptor potential melastatin 8 (TRPM8) in the dorsal root ganglion (DRG) in rats. In this study, we examined the effect of riluzole on oxaliplatin-induced cold allodynia. In cultured DRG neurons, riluzole suppressed oxalate-induced increase of the number of menthol (TRPM8 agonist)-sensitive cells. Moreover, riluzole prevented cold allodynia and increase in levels of TRPM8 mRNA in oxaliplatin-treated rats. These results suggest that riluzole prevents oxaliplatin-induced cold allodynia via inhibition of TRPM8 overexpression in the DRG. Keywords: Oxaliplatin-induced cold allodynia, Riluzole, TRPM8

In the present study, we investigated the effect of a Kampo medicine Goshajinkigan (GJG) on the bortezomib-induced mechanical allodynia in von Frey test in rats. The single administration of tramadol (10 mg/kg), GJG (1.0 g/kg) and its component processed Aconiti tuber (0.1 g/kg) significantly reversed the reduction in withdrawal threshold by bortezomib. These effects were abolished by the intrathecal injection of nor-binaltorphimine (10 μg/body), kappa opioid receptor antagonist. These findings suggest that kappa opioid receptor is involved in the effect of GJG on the bortezomib-induced mechanical allodynia.

Bortezomib, an effective anticancer drug for multiple myeloma, often causes peripheral neuropathy which is mainly characterized by numbness and painful paresthesia. Nevertheless, there is no effective strategy to escape or treat bortezomib-induced peripheral neuropathy (BIPN), because we have understood few mechanism of this side effect. In this study, we evaluated behavioral and pathological characteristics of BIPN, and investigated pharmacological efficacy of various analgesic drugs and adjuvants on mechanical allodynia induced by bortezomib treatment in rats. The repeated administration of bortezomib induced mechanical and cold allodynia. There was axonal degeneration of sciatic nerve behind these neuropathic symptoms. Furthermore, the exposure to bortezomib shortened neurite length in PC12 cells. Finally, the result of evaluation of anti-allodynic potency, oral administration of tramadol (10 mg/kg), pregabalin (3 mg/kg), duloxetine (30 mg/kg) or mexiletine (100 mg/kg), but not amitriptyline or diclofenac, transiently relieved the mechanical allodynia induced by bortezomib. These results suggest that axonal degeneration of the sciatic nerve is involved in BIPN and that some analgesic drugs and adjuvants are effective in the relief of painful neuropathy.

In this study, the structure-function relationships of a series of polymersomes composed of well-defined amphiphilic diblock copolymers were investigated. The building blocks were synthesized by clicking hydrophobic polymers, synthesized beforehand, and commercially available poly(ethylene glycol) with photocleavable 2-nitrobenzyl compounds bearing alkyne and maleimide functionalities. All of the tested polymersomes preserved their hollow structures even after sufficient photoirradiation. Nevertheless, the release rate of an entrapped anionic fluorophore was highly dependent on the molecular weight and the type of hydrophobic polymer, as well as on the presence or absence of the charged end groups. Moreover, the polymersomes with a 2-nitrosobenzyl photolysis residue within the hydrophobic shells exhibited photo-induced payload release after complete photolysis. It was concluded that the payload release was mediated by photo-induced permeability changes of the hydrophobic shells rather than the decomposition of their overall structures.

Atom transfer radical polyaddition (ATRPA) was utilized herein to synthesize a specific functional polyester. We conducted ATRPA of 4-vinylbenzyl 2-bromo-2-phenylacetate (VBBPA) inimer and successfully obtained a linear type poly(VBBPA) (PVBBPA) polyester with benzylic bromides along the backbone. To obtain a novel amphiphilic polymer bottlebrush, however, the lateral ATRP chain extension of PVBBPA with N-vinyl pyrrolidone (NVP) met the problem of quantitative dimerization. By replacing the bromides to xanthate moieties efficiently, we thus observed a pseudo linear first order reversible addition−fragmentation chain transfer (RAFT) polymerization to obtain novel poly(4-vinylbenzyl-2-phenylacetate)-g-poly(NVP) (PVBPA-g-PNVP) amphiphilic polymer bottlebrushes. The critical micelle concentration (CMC) and particle size of the amphiphilic polymer bottlebrushes were characterized by fluorescence spectroscopy, dynamic light scattering (DLS), and scanning electron microscopy (SEM) (CMCs < 0.5 mg/mL; particle sizes = ca. 100 nm). Toward drug delivery application, we examined release profiles using a model drug of Nile red at different pH environments (3, 5, and 7). Eventually, low cytotoxicity and well cell uptake of the Madin-Darby Canine Kidney Epithelial (MDCK) for the polymer bottlebrush micelles were demonstrated.

P2X4 receptors (P2X4R) are a family of ATP-gated non-selective cation channels. We previously demonstrated that activation of P2X4R in spinal microglia is crucial for neuropathic pain, a highly debilitating chronic pain condition, suggesting that P2X4R is a potential therapeutic target for treating neuropathic pain. Thus, the identification of a compound that has a potent inhibitory effect on P2X4R is an important clinical challenge. In the present study, we screened a chemical library of clinically approved drugs and show for the first time that duloxetine, a serotonin and noradrenaline reuptake inhibitor, has an inhibitory effect on rodent and human P2X4R. In primary cultured microglial cells, duloxetine also inhibited P2X4R-, but not P2X7R-, mediated responses. Moreover, intrathecal administration of duloxetine in a model of neuropathic pain produced a reversal of nerve injury-induced mechanical allodynia, a cardinal symptom of neuropathic pain. In rats that were pretreated with a serotonin-depleting agent and a noradrenaline neurotoxin, the antiallodynic effect of duloxetine was reduced, but still remained. Based on these results, we suggest that, in addition to duloxetine's primary inhibitory action on serotonin and noradrenaline transporters, an inhibitory effect on P2X4R may be involved at least in part in an antiallodynic effect of intrathecal duloxetine in a model of neuropathic pain.

We developed a method for pattern recognition of baby's emotions (discomfortable, hungry, or sleepy) expressed in the baby's cries. A 32-dimensional fast Fourier transform is performed for sound form clips, detected by our reported method and used as training data. The power of the sound form judged as a silent region is subtracted from each power of the frequency element. The power of each frequency element after the subtraction is treated as one of the elements of the feature vector. We perform principal component analysis (PCA) for the feature vectors of the training data. The emotion of the baby is recognized by the nearest neighbor criterion applied to the feature vector obtained from the test data of sound form clips after projecting the feature vector on the PCA space from the training data. Then, the emotion with the highest frequency among the recognition results for a sound form clip is judged as the emotion expressed by the baby's cry. We successfully applied the proposed method to pattern recognition of baby's emotions. The present investigation concerns the first stage of the development of a robotics baby caregiver that has the ability to detect baby's emotions. In this first stage, we have developed a method for detecting baby's emotions. We expect that the proposed method could be used in robots that can help take care of babies.