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Background: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common encephalopathy syndrome among Japanese children. We report, for the first time, a case of AESD, in which magnetic resonance imaging (MRI) showed no diffusion abnormalities, but hyperperfusion was detected by arterial spin labelling (ASL)., Case Report: A previously healthy Japanese 1-year and 5-month-old boy was transferred to our hospital due to a consciousness disorder after >60 min of status epilepticus on the first day of fever. Brain MRI on the first day revealed no abnormal findings. On the fourth day, focal seizures of the left upper and lower limbs were observed. Thereafter, the patient's condition progressed without seizures. Diffusion-weighted imaging (DWI) on day 6 showed no abnormal findings, including a bright tree appearance. However, ASL showed hyperperfusion in the frontoparietal lobes. MRI scans on days 19 and 39 revealed that the hyperperfusion lesions on day 6 had transitioned to hypoperfusion on ASL and displayed high signal intensity on T2-weighted and fluid-attenuated inversion recovery imaging. Cerebral atrophy was also observed. Based on the clinical course and imaging findings during the chronic phase, a diagnosis of AESD was made., Conclusion: ASL may be more sensitive than DWI for detecting AESD lesions and should be performed in children with suspected AESD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Short-chain enoyl-CoA hydratase, encoded by ECHS1, plays a major role in the valine catabolic pathway and mitochondrial fatty acid β-oxidation. Deficiency of this enzyme causes Leigh syndrome. Herein, we report a case of ECHS1 -related Leigh syndrome with a prominent ketone body spectrum on magnetic resonance spectroscopy during acute exacerbation. A 6-month-old boy with mild motor developmental delay presented with disturbances of consciousness and hypercapnia without prior infection or feeding failure. Upon admission, investigations revealed prominent ketosis and elevated 2,3-dihydroxy-2-methylbutyric acid excretion. Brain magnetic resonance imaging revealed symmetrical T2 prolongation with restricted diffusion in the basal ganglia. Magnetic resonance spectroscopy showed a prominent ketone body spectrum in the cerebral white matter, and prominent ketone bodies, elevated lactate and markedly decreased N-acetylaspartate levels in the basal ganglia. Genetic analysis identified compound heterozygous variants of ECHS1 . Short-chain enoyl-CoA hydratase deficiency is a disease for which a valine-restricted diet is reported to be beneficial, and early diagnosis is desirable. Severe ketosis and the ketone body magnetic resonance spectroscopy spectrum during acute exacerbation may aid in the diagnosis of this disease., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: Infantile traumatic brain injury (TBI) with a biphasic clinical course and late reduced diffusion (TBIRD) has recently been reported as a distinct type of TBI in infancy. However, the pathological and prognostic factors of TBIRD remain unknown. We aimed to compare patients with and without TBIRD and evaluate the pathomechanism of TBIRD using magnetic resonance spectroscopy (MRS)., Methods: Ten Japanese patients with TBI were admitted to our hospital and underwent MRS between September 2015 and September 2022 (age range, 3-15 months; median age, 8.5 months). TBIRD was diagnosed in six patients. MRS data were compared among patients with TBIRD, patients without TBIRD, and controls. Neurological prognosis was classified into grades 1 (normal) to 3 (severe)., Results: In patients with TBIRD, MRS revealed an increase in the glutamine (Gln) level on days 3-29, which subsequently became close to normal. The degree of Gln elevation in the non-TBIRD group was smaller (117-158 % of controls) than that in the TBIRD group (210-337 %) within 14 days. MRS in the TBIRD group showed decreased N-acetyl aspartate (NAA) concentrations. The degree of NAA decrease was more prominent in grade 3 than in grades 1 and 2. NAA levels in the non-TBIRD group were almost normal., Conclusions: Patients with TBI and markedly elevated Gln levels on MRS may develop TBIRD. Neuro-excitotoxicity is a possible pathological mechanism of TBIRD. Decreased NAA levels may be useful for predicting the prognosis of patients with TBIRD., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gold nanorods (GNR) produce heat upon irradiation with near-infrared light, enabling a tumor-targeted photothermal therapy. In this study, we prepared GNR coated with sulfated hyaluronic acid (sHA) with a binding affinity for CD44 via electrostatic interactions to deliver GNR to tumors efficiently and stably, and evaluated their usefulness for photothermal therapy. Cationic GNR modified with trimethylammonium groups electrostatically interacted with native HA or sHA with varying degrees of sulfation to form complexes. While GNR/HA was unstable in saline, GNR/sHA maintained the absorbance peak in the near-infrared region, particularly for GNR/sHA with higher degrees of sulfation. GNR/sHA exhibited an intense photothermal effect upon irradiation with near-infrared light. Furthermore, in vitro and in vivo studies revealed that GNR coated with sHA containing approximately 1.2 sulfated groups per HA unit could accumulate in CD44-positive tumors via an HA-specific pathway. These findings indicate the effectiveness of GNR/sHA as a tumor-targeted photothermal therapeutic agent., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Infantile traumatic brain injury (TBI) with a biphasic clinical course and late reduced diffusion (TBIRD) has been reported as a type of TBI. However, it remains uncertain which pediatric patients with TBI develop TBIRD., Methods: Patients with TBI who were admitted to our hospital and underwent magnetic resonance imaging (MRI) between December 2006 and October 2022 were included in this study. A diagnosis of TBIRD was made in patients with or suspected TBI, with initial symptoms being convulsions or disturbance of consciousness and late-onset subcortical reduced diffusion, the so-called bright tree appearance. Clinical features, neuroimaging (computed tomography (CT) and MRI) findings, laboratory data, and Tada score were retrospectively compared between TBIRD and non-TBIRD patients. Neurological prognosis was assessed using the Pediatric Cerebral Performance Category scale., Results: Of 21 patients who met the inclusion criteria, a diagnosis of TBIRD was made in 7 patients (median age: 8 months). The factors contributing to TBIRD development were seizures lasting over 30 min as the initial symptom (5/7 in TBIRD vs. 0/14 in non-TBIRD), tracheal intubation during initial treatment (5/7 vs. 0/14), and brain parenchymal lesions on CT (3/7 vs. 0/14), suggesting that severe TBI may progress to TBIRD. The Tada score was more positive in patients with TBIRD (6/7) than in those without (0/14)., Conclusions: It is important to monitor infant patients with severe TBI for the development of TBIRD. The Tada score can be a useful tool for TBIRD prediction., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Some Capsicum synthesize a unique pungent alkaloid called capsaicin in their fruits. In the synthetic pathway of capsaicin, vanillylamine is produced from vanillin in a reaction catalyzed by a putative aminotransferase (pAMT). Therefore, the capsaicinoids content in the fruits is thought to partially depend on the characteristics of pAMT. Comparing Yume-matsuri (yume), C. annuum variety, and red habanero (RH), C. chinense variety, the vanillylamine synthesis activity of the placental extract was higher in yume than in RH. When each recombinant pAMT (rpAMT) was generated using the Escherichia coli expression system and their activities were compared, yume rpAMT synthesized 14-fold more vanillylamine than RH rpAMT. The amino acid sequence of yume and RH pAMT deduced from the cDNAs revealed that only 7 of 459 residues differed. When a single amino acid residue-substituted rpAMT was generated in which the 56th amino acid was swapped with one other, the amount of vanillylamine synthesis of yume and RH rpAMTs was inverted. Furthermore, it was suggested that the 56th amino acid contributed to the affinity for the coenzyme pyridoxal phosphate. Differences in the vanillylamine synthesis activity of pAMT may also lead to differences in the amount of capsaicin synthesis that accumulates in the fruit. Since capsaicin is a compound with commercial value, this finding may provide new insights into the creation of a variety that can synthesize more capsaicin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Macrophage infiltration is a characteristic feature of atherosclerotic plaque progression. Since liposomes containing 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG) are efficiently phagocytosed by macrophages, we deduced that radiolabeled liposomes containing DSPG could potentially be used for nuclear imaging of vulnerable atherosclerotic plaques. Indium-111 ( 111 In)-labeled liposomes containing different ratios of DSPG were developed with a high labeling efficiency. 111 In-labeled liposomes with higher DSPG content showed higher uptake by macrophage-like RAW264 cells. A biodistribution study demonstrated rapid blood clearance and selective accumulation in the liver and spleen, especially in normal mice injected with 111 In-labeled liposomes with higher DSPG content. Accumulation in atherosclerotic plaques was evaluated using 111 In-labeled DSPG liposomes, which had the highest DSPG content among the studied liposomes. 111 In-labeled DSPG liposomes accumulated in the plaques and the radioactive regions were mostly consistent with the distribution of macrophages. The target-to-non-target ratio of 111 In-labeled DSPG liposomes was higher than that of 111 In-labeled control liposomes without DSPG. These results suggest that 111 In-labeled liposomes containing DSPG are useful for nuclear medical diagnosis of atherosclerotic plaques., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Oligomannose-type glycans on glycoproteins are important signaling molecules in the glycoprotein quality control system in the endoplasmic reticulum. Recently, free oligomannose-type glycans generated by the hydrolysis of glycoproteins or dolichol pyrophosphate-linked oligosaccharides were recognized as important signals for immunogenicity. Hence, there is a high demand for pure oligomannose-type glycans for biochemical experiments; however, the chemical synthesis of glycans to achieve high-concentration products is laborious. In this study, we demonstrate a simple and efficient synthetic strategy for oligomannose-type glycans. Sequential regioselective α-mannosylation at the C-3 and C-6 positions of 2,3,4,6-unprotected galactose residues in galactosylchitobiose derivatives was demonstrated. Subsequently, the inversion of the configuration of the two hydroxy groups at the C-2 and C-4 positions of the galactose moiety was successfully carried out. This synthetic route reduces the number of the protection-deprotection reactions and is suitable for constructing different branching patterns of oligomannose-type glycans, such as M9, M5A, and M5B., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A fluorescence-quenching-based assay system to determine the hydrolytic activity of endo-β-N-acetylglucosaminidases (ENGases), which act on the innermost N-acetylglucosamine (GlcNAc) residue of the chitobiose segment of core-fucosylated N-glycans, was constructed using a dual-labeled fluorescent probe with a hexasaccharide structure. The fluorogenic probe was evaluated using a variety of ENGases, including Endo-M W251N mutant, Endo-F3, and Endo-S, which recognize core fucosylated N-glycans. The occurrence of a hydrolysis reaction was detected by observing an increased fluorescence intensity, ultimately allowing the ENGase activities to be easily and quantitatively evaluated, with the exception of Endo-S. The obtained results clearly indicated the substrate specificities of the examined ENGases., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A part of this study was conducted by the collaborative research with Daiichi Sankyo Co., Ltd. Hiroshi Muto is an employee of Daiichi Sankyo Co., Ltd. A part of this study was also financially supported by Gunma university for the promotion of scientific research, and Organization to Promote Research and University-Industry Collaboration, Gunma University. Other authors declare that they have no other known competing financial interests or personal relationships that could have influenced the work reported in this study., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aims: The acetabular morphology varies greatly among individuals, and hypoplasia is more common in Asia than in Europe. Dislocation after bipolar hip arthroplasty (BHA) for femoral neck fracture occurs at a constant rate, and is affected by the acetabular morphology. This study aimed to clarify individual differences in the acetabula of Asian patients with displaced femoral neck fractures., Patients and Methods: Fifty patients with displaced femoral neck fractures were assessed (50 fractured hips, 50 non-fractured hips). On CT corrected by the anterior pelvic plane, the 100 hips were assessed regarding acetabular coverage (six parameters), acetabular depth (two parameters), and acetabular opening angle (four parameters). Additional parameters related to the fracture and sex were examined. The percentile of each parameter was shown for all hips., Results: There was no patient with hip dysplasia defined as superior acetabular sector angle (SASA) less than 110° Compared with men, women had a significantly smaller anterior acetabular sector angle (AASA) (p = 0.016), and significantly larger acetabular inclination angle (p = 0.006) and acetabular index angle (p = 0.034). In the group with a normal SASA, seven hips (7.3%) had an anterior wall defect (AASA<50°) and five hips (5.2%) had a posterior wall defect (posterior acetabular sector angle<90°)., Conclusion: Older adults with femoral neck fractures can have anterior wall and posterior wall defects, even if their SASA is normal. Hidden acetabular dysplasia may be related to post-BHA dislocation. So, our results suggest that is important to accurately evaluate the acetabulum of patients with femoral neck fracture before surgery., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: In acute myocardial infarction (MI), the prognosis has been improved, and the length of hospital stay has been shortened. In the present study, we aimed to evaluate the potential of identifying low-risk patients for early discharge after acute MI using the GRACE and CADILLAC risk scores., Methods: This bi-center registry included 797 patients with acute MI undergoing primary percutaneous coronary intervention. Patients were divided into 3 groups according to the tertiles and pre-defined thresholds of the GRACE and CADILLAC scores. The primary endpoint was a composite of in-hospital major adverse events (all-cause death, sustained ventricular arrhythmia, recurrent MI, heart failure requiring intravenous treatment, stroke, and major bleeding events)., Results: Of 797 patients, 271 (34.0%) and 316 (39.7%) had low GRACE and CADILLAC risk scores. During the hospitalization, 251 (31.5%) patients had major adverse events. Higher GRACE and CADILLAC scores were associated with longer length of stay and higher in-hospital adverse event rates. In patients with low GRACE and/or CADILLAC risk scores, 16 (5.9%) and 16 (5.1%) had in-hospital adverse events, most of which occurred within 3 days. Only 1 (0.4% and 0.3%) patient had major adverse events on day 4 or later in the low GRACE and CADILLAC risk score groups., Conclusion: In patients with acute MI with low GRACE and/or CADILLAC risk scores who were free from acute events within 3 days, early discharge after primary percutaneous coronary intervention may be feasible and safe., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Ltd.)

Objectives: Sarcopenia is defined as a combination of low skeletal muscle mass index (SMI), weak muscle strength, and reduced physical function. Recently, many studies have reported that the creatinine/cystatin C ratio (Cr/CysC) is useful for evaluating muscle mass. We designed a cross-sectional study with separate model development and validation groups to develop a prediction equation to estimate bioimpedance analysis (BIA)-measured SMI with Cr/CysC., Design: The current study was a retrospective cross-sectional study., Setting and Participants: The model development group included 908 subjects (288 men and 620 women) from the Frail Elderly in the Sasayama-Tamba Area (FESTA) study, and the validation group included 263 subjects (112 men and 151 women) from participants in the medical checkup program at the Anti-Aging Center in Ehime Prefecture., Measures: Multivariate regression analysis indicated that age, hemoglobin (Hb), body weight (BW), and Cr/CysC were independently associated with SMI in both men and women. The SMI prediction equation was developed as follows: Men:4.17-0.012×Age+1.24×(Cr/CysC)-0.0513×Hb+0.0598×BW Women:3.55-0.00765×Age+0.852×(Cr/CysC)-0.0627×Hb+0.0614×BW RESULTS: The SMI prediction equation was applied to the validation group and strong correlations were observed between the BIA-measured and predicted SMI (pSMI) in men and women. According to the receiver operator characteristic (ROC) analysis, the areas under the curve were 0.93 (specificity 89.0%, sensitivity 87.2%) among men and 0.88 (specificity 83.6%, sensitivity 79.6%) among women for using pSMI to identify low SMI in the model development group. The pSMI also indicated high accuracy in ROC analysis for low SMI in the validation group. The Bland-Altman plot regression showed good agreement between BIA-measured and pSMI., Conclusions and Implications: Our new prediction equation to estimate SMI is easy to calculate in daily clinical practice and would be useful for diagnosing sarcopenia., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Recent guidelines recommend risk stratification using objective scoring systems in patients with acute coronary syndrome. In this context, the CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) and GRACE (Global Registry of Acute Coronary Events) risk scores were both originally established to predict short-term mortality. However, their impact on short- and long-term clinical outcomes in a contemporary cohort of patients with acute myocardial infarction (MI) is unclear., Methods: This bi-center registry included 809 patients with acute MI undergoing primary percutaneous coronary intervention. Patients were divided into three groups according to the pre-defined thresholds and tertiles of the CADILLAC and GRACE scores. The study endpoints included all-cause death and major adverse cardiovascular events (MACE) during the index hospitalization and after discharge., Results: Of 809 patients, 323 (39.9%) and 255 (31.5%) had high CADILLAC and GRACE risk scores. During the index hospitalization, 61 (7.5%) patients died and 262 (32.4%) had MACE. Both CADILLAC and GRACE risk scores were associated with in-hospital mortality and MACE rates. After discharge, out of 683 patients with available follow-up information who survived to discharge, 42 (6.1%) died and 123 (18.0%) had MACE during the median follow-up period of 632 days. Significantly higher incidence of MACE in higher CADILLAC and GRACE risk scores was observed in a stepwise manner., Conclusion: Both CADILLAC and GRACE risk scores were predictive for short- and long-term mortality and MACE rates in a contemporary cohort of acute MI patients undergoing primary percutaneous coronary intervention., (Copyright © 2021. Published by Elsevier Ltd.)

Background: The application of gold nanorods (GNRs) in photothermal therapy is a promising avenue for cancer treatment. The aim of this study was to develop a GNR-based targeted photothermal therapy for melanoma., Methods: We utilized the electrostatic interaction between cationic GNRs and an anionic polymer chondroitin sulfate A (CSA), which has an affinity for binding to melanoma cells, to construct an anionic binary GNR-CSA complex (GNR-CS) at an optimal theoretical charge ratio of the trimethylammonium groups of GNR: carboxyl and sulfate groups of CSA = 1:2.5. The cytotoxicity to normal cells and erythrocyte agglutination activity of GNR-CS were evaluated. After the cellular uptake of GNR-CS by melanoma cells (B16-F10) was investigated, the photothermal performance of GNR-CS against B16-F10 cells was evaluated in vitro., Results: The particle size and zeta potential of GNR-CS were approximately 35 nm and -20 mV, respectively. GNR-CS showed little cytotoxicity to normal cells and low erythrocyte agglutination activity, indicating good biocompatibility. Compared with negatively-charged GNR, GNR-CS was highly taken up by B16-F10 cells even if it was negatively charged. Cellular uptake was significantly suppressed upon treatment with excess CSA, suggesting the involvement of a CSA-specific uptake pathway. Furthermore, irradiation of the GNR-CS solution with near-infrared (NIR) light increased its temperature in light-intensity and GNR-concentration dependent manners. GNR-CS exhibited significant and GNR-dose dependent cytotoxicity in melanoma cells in combination with NIR light irradiation., Conclusion: GNRs coated with CSA have the potential as a medicine in targeted photothermal therapy for melanoma., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Information on the effectiveness of personal protective equipment (PPE) for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers (HCWs), especially among HCWs with frequent contact with patients with SARS-CoV-2, is limited., Methods: We conducted a prospective cohort study on 49 HCWs who worked in close contact with patients with SARS-CoV-2 infection. HCWs had blood samples taken every 2 weeks to test for SARS-CoV-2 antibodies using two different types of assay., Results: Forty-nine participants (31 nurses, 15 doctors, 3 other workers) were enrolled. In total, 112 blood samples are obtained from participants. The median work days in 2 weeks was 9 (interquartile range (IQR): 5-10) days. In a single work day, 30 of the 49 participants (61.5%) had contact with patients with suspected or conformed SARS-CoV-2 at least 8 times, and approximately 60% of participants had more than 10 min of contact with a single patient. The median self-reported compliance to PPE was 90% (IQR: 80-100%). Seven participants tested positive for SARS-CoV-2 antibody using enzyme-linked immunosorbent assay (ELISA); however, none were seropositive for SARS-CoV-2 neutralizing antibody, so the positive ELISA results were assumed to be false-positive., Conclusions: The study provides evidence that appropriate PPE is sufficient to prevent infection amongHCWs. It is necessary to establish a system that provides a stable supply of PPE for HCWs to perform their duties., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Prion diseases are fatal neurodegenerative disorders caused by the deposition of abnormal prion protein aggregates (PrP Sc ) in the central nervous system. This study aimed to evaluate the use of iodinated pyridyl benzofuran (IPBF) derivatives as single-photon emission computed tomography (SPECT) probes for the detection of cerebral PrP Sc deposits., Methods: In vitro binding assays of IPBF derivatives were carried out in the recombinant mouse prion protein (rMoPrP) and brain sections of mouse-adapted bovine spongiform encephalopathy (mBSE)-infected mice. SPECT imaging of 5-(5-[ 123 I]iodobenzofuran-2-yl)-N-methylpyridin-2-amine ([ 123 I]IPBF-NHMe) was performed on mBSE-infected and mock-infected mice., Results: Fluorescence microscopy results showed that fluorescence signals of IPBF derivatives corresponded to the thioflavin-T positive amyloid deposits of PrP Sc in the brain sections of mouse-adapted bovine spongiform encephalopathy (mBSE)-infected mice. Among the IPBF derivatives, 5-(5-iodobenzofuran-2-yl)-N-methylpyridin-2-amine (IPBF-NHMe) exhibited the highest binding affinity to the recombinant mouse prion protein (rMoPrP) aggregates with a K i of 14.3 nM. SPECT/computed tomography (CT) imaging and ex vivo autoradiography demonstrated that the [ 123 I]IPBF-NHMe distribution in brain tissues of mBSE-infected mice co-localized with PrP Sc deposits., Conclusion: [ 123 I]IPBF-NHMe appears to be a prospective SPECT tracer for monitoring prion deposits in living brain tissues., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In order to completely remove tumors in surgeries, probes are needed both preoperatively and intraoperatively. For tumor diagnosis, magnetic resonance imaging (MRI) has been widely used as a precise preoperative method, and photoacoustic imaging (PAI) is a recently emerged intraoperative (or preoperative) method, which detects ultrasonic waves thermoelastically induced by optical absorbers irradiated by laser. Iron oxide nanoparticles (IONPs) can be used as both MR and PA imaging probes. In order to improve the sensitivity of IONPs as MR/PA imaging probes, we newly prepared liposomes encapsulated with a number of IONPs (Lipo-IONPs). Interestingly, Lipo-IONPs showed 2.6 and 3.8-times higher PA and MR signals, respectively, compared to dispersed IONPs at the same concentration. Furthermore, trastuzumab (Tra) (anti-human epidermal growth factor receptor 2 (EGFR2; HER2) monoclonal antibody) was introduced onto the surface of liposomes for detection of HER2 related to tumor malignancy. In an cellular uptake study, Tra-Lipo-IONPs were taken up by HER2-positive tumor cells and HER2-specific MR/PA dual imaging was achieved. Finally, a biodistribution study using radiolabeled Tra-Lipo-IONPs showed HER2-specific tumor accumulation. In conclusion, we demonstrated the usefulness of Lipo-IONPs as platforms for sensitive MR/PA dual imaging and the possibility of HER2-specific tumor MR/PA imaging using Tra-Lipo-IONPs., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

An α(1,2)-linked oligomannoside derivative having a free C-2 hydroxyl group and a C-3 pivaloyl group was synthesized from a thiophenyl mannose derivative 1 using a one-pot self-condensation and applying a α-stereoselective procedure. The mannosylation exclusively generated α-mannoside linkages. The observed α-directing effect was rationalized by the remote participation of the pivaloyl group in C-3 position. The polymerization degree was controlled by the promoter amount providing the mannobiose derivative as a major product. Applying this method eliminated many synthetic steps. The α(1,2)-linked oligomannoside derivatives, which are key intermediates for the synthesis of oligomannose type N-glycans for glycoproteins, were easily prepared., Competing Interests: Declaration of competing interest To the best of our knowledge, the named authors have no conflict of interest, financial or otherwise., (Copyright © 2020. Published by Elsevier Ltd.)

Oral antibiotic therapy is routinely administered when a third molar (M3) is extracted to prevent infectious complications after surgery. Oral third-generation cephalosporins are frequently used after M3 extraction in Japan but at the expense of an increased risk of antimicrobial resistance. Therefore, the infection control team (ICT) at our institution recommended a reduction in use of these agents after M3 extraction. In this study, we compared the types of antibiotic agents prescribed for patients undergoing M3 extraction before and after this recommendation. We investigated the relationship between type of antibiotic used and the likelihood of infectious complications as well as cost savings in patients who underwent M3 extraction in the 6 months before and after the ICT recommendation in July 2018. There was a marked reduction in use of oral third-generation cephalosporins after M3 extraction (P < 0.0001) and increased use of oral penicillins and first-generation cephalosporins after the ICT recommendation. Moreover, surgical site infection (SSIs) were significantly less common after the ICT recommendation (P = 0.0099); however, the SSI rate was higher in patients who received a third-generation cephalosporin than in those who received penicillin (8.8% vs 0.5%). There was also a significant saving in per-patient antibiotic costs after the ICT recommendation (269.5 ± 282.0 JPY vs 454.7 ± 376.6 JPY; P < 0.0001). These findings suggest that collaboration with an ICT promotes appropriate antibiotic use, decreases the risk of an SSI, and improves the cost-benefit ratio in patients undergoing M3 extraction., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: Acute excitotoxic encephalopathy is the most common encephalopathy syndrome in Japan, and consists of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and mild encephalopathy associated with excitotoxicity (MEEX). Neurological sequelae remain in approximately 70% of patients with AESD, however, it is difficult to predict the prognosis early in the course. We evaluated the brain metabolites observed on MRS as to whether they can predict the neurological outcome., Methods: 16 previously healthy Japanese patients with excitotoxic encephalopathy (8 with AESD and 8 with MEEX) were included in this study. MR spectroscopy (MRS) was acquired from the fronto-parietal white matter (TR/TE = 5000/30 msec) with a 3.0 T scanner. Quantification of metabolites was performed using an LCModel. Neurological outcome was assessed with the Pediatric Cerebral Performance Category score, score 1 being classified as G1 (normal), scores 2 and 3 as G2 (mild to moderate), and scores 4-6 as G3 (severe)., Results: MRS data which predict a poor neurological outcome (G2 and 3) include the following: decreased N-acetyl aspartate (NAA) (sensitivity 88%, specificity 100%), decreased creatine (47%, 100%), increased lactate (47%, 100%), and decreased glutamate (sensitivity 35%, specificity 100%). Limited to the acute stage within seven days of onset, those for a poor prognosis are as follows, decreased NAA (88%, 100%), decreased creatine (38%, 100%), and increased lactate (38%, 100%)., Conclusion: MRS is useful for prognosis prediction of acute excitotoxic encephalopathy. Decreased NAA will be the most effective metabolite for neurological prognosis prediction., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Recently, the topical application of tranexamic acid has become widespread, and it is effective in reducing postoperative blood loss and transfusion rate in total hip arthroplasty. There is no consensus on the optimal dose of topical tranexamic acid. This study aimed to assess the efficacy and safety of topical tranexamic acid on postoperative blood loss and determine the optimal topical dose for primary total hip arthroplasty., Methods: This prospective cohort study with a robust protocol enrolled 79 patients who received either 1 or 2 g of topical tranexamic acid in 30 mL normal saline solution or an equivalent volume of normal saline at the end of surgery. The primary outcomes were postoperative drain blood loss and hemoglobin decrease on postoperative day 7. The secondary outcomes were transfusion rate, d-dimer level on postoperative day 7, symptomatic deep vein thrombosis rate, and duration of hospital stay., Results: Both 1 and 2 g tranexamic acid significantly reduced postoperative drain blood loss (p < 0.001). These doses also reduced the hemoglobin concentration decrease on postoperative day 7, but not significantly. Furthermore, 1 and 2 g doses of tranexamic acid had similar effects on postoperative blood loss and hemoglobin concentration decrease. There was no difference in the transfusion rate, d-dimer level, symptomatic deep vein thrombosis rate, and length of hospital stay., Conclusions: The use of topical tranexamic acid at the end of surgery is effective and safe for reducing postoperative blood loss in primary total hip arthroplasty. Topical tranexamic acid at a dose of 1 g may be sufficient and cost-effective, with fewer side effects than the higher dose., (Copyright © 2018 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

MRI of a female patient with xeroderma pigmentosum group A (XP-A) showed progressive cerebral atrophy, but no disease-specific lesion. MR spectroscopy with short TE sequences in the bilateral white matter revealed decreased N-acetyl aspartate (neuro-axonal marker) and increased myo-inositol (astroglial marker) with a normal concentration of choline (membrane marker), which are compatible with the neuropathology of XP-A, consisting of a reduced number of neurons, and fibrillary astrogliosis with preservation of myelinated fibers. MR spectroscopy reveals neurochemical derangement in XP-A, which cannot be observed on conventional MRI, and will be useful to monitor the neurochemical derangements of XP-A., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Purpose: The Hybrid Assistive Limb® (HAL®, CYBERDYNE) is a wearable robot that provides assistance to a patient while they are walking, standing, and performing leg movements based on the wearer's intended movement. The effect of robot-assisted training using HAL® for cerebral palsy (CP) is unknown. Therefore, we assessed the effect of robot-assisted training using HAL® on patients with CP, and compared walking and gross motor abilities between pre-intervention and post-intervention., Methods: Six subjects with CP were included (mean age: 16.8 years; range: 13-24 years; Gross Motor Function Classification System levels II-IV: n = 1, 4, 1). Robot-assisted training using HAL® were performed 2-4 sessions per week, 20 min per session, within a 4 weeks period, 12 times in total. Outcome measures included gait speed, step length, cadence, single-leg support per gait cycle, hip and knee joint angle in stance, and swing phase per gait cycle, 6-minute walking distance (6 MD), physiological cost index (PCI), knee-extension strength, and Gross Motor Function Measure (GMFM)., Results: There were significant increases in self-selected walking speed (SWS), cadence during SWS and maximum walking speed (MWS), single-leg support per gait cycle, hip joint angle in the swing phase, 6 MD, and GMFM. In contrast, gait speed during MWS, step length during SWS and MWS, hip and knee joint angle in the stance phase, knee joint angle in the swing phase, PCI, and knee-extension strength generally improved, but not significantly., Conclusion: Robot-assisted training using HAL® may improve walking and gross motor abilities of patients with CP., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Macrophages are key factors in the formation of unstable atherosclerotic plaques, which may be identified through macrophage imaging. We tested whether activatable fluorescence probes of iron oxide nanoparticles (IONPs) conjugated with indocyanine green (ICG) (IONP-ICG), consisting of biocompatible reagents, can visualize macrophages present in atherosclerotic plaques., Methods: IONP-based probes conjugated with different numbers of ICG molecules were synthesized. Six-week-old spontaneously hyperlipidemic (SHL) mice were fed either a Western or normal diet for 14 weeks, and were intravenously injected with IONP-ICG (55.8 mg Fe/kg). Aortas were harvested 48 h later, and aortas containing atherosclerotic plaques were imaged., Results: Phantom imaging studies using IONP-ICG solution demonstrated that the addition of surfactants to IONP-ICG solutions yielded fluorescence activation. Incubation of macrophages with IONP-ICG led to internalization of IONP-ICG and near infrared fluorescence (NIRF) activation. In NIRF imaging studies, intense fluorescence signals were clearly visible primarily at the margins of atherosclerotic plaques, and relatively weak signals were evident inside the plaques, demonstrating the feasibility of detection of NIRF signals at atherosclerotic plaques. In the quantitative evaluation of NIRF, administration of a probe conjugated with more ICG molecules led to a significant increase in the NIRF signal, indicating that probes with greater numbers of ICG molecules are effective for sensitive NIRF detection. SHL mice given a low-cholesterol normal diet showed a significantly lower NIRF signal compared with mice given the Western diet. Histologically, NIRF signals in atherosclerotic plaques strongly correlated with the location of macrophages, suggesting the possibility of NIRF macrophage imaging using IONP-ICG., Conclusions: Localization of macrophages in atherosclerotic plaques may be achieved using the activatable NIRF probe, IONP-ICG., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Adult T-cell leukemia-lymphoma (ATL) is a refractory T-cell malignancy caused by infection of human T-cell leukemia virus type I (HTLV-I). Although the pathogenesis of ATL remains unclear, HTLV-1 oncoprotein Tax plays an important role in pathogenesis (Matsuoka, 2003; Jeang et al., 2004). Chemotherapy resistance of ATL leads the poor prognosis of this disease. In order to understand the pathogenesis and establish an animal model useful for therapy attempts, we have generated HTLV-1 Tax transgenic mice using the Lck proximal promoter to restrict the Tax expression in T-cells. The HTLV-1 Tax transgenic mice developed diffuse large-cell lymphomas and leukemia with the similar features of a clinical, pathological and immunological characteristic of acute ATL. The fulminant disease also developed rapidly in SCID mice after engraftment of mouse ATL cells derived from the transgenic mice. In this review, we introduce the therapeutic attempts using this animal model and discuss the possible signaling pathway for a therapeutic target., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The Elite-Plus stem has two shape variations: roundback and flanged. The correlation between the radiographic results and stem geometry has not been previously investigated. The objective of this study was to evaluate the long-term primary total hip arthroplasty results using Elite-Plus stems, and the effect of stem geometry on radiographic distal femoral cortical hypertrophy., Methods: We retrospectively evaluated, radiographically, 156 patients (173 hips) who underwent total hip arthroplasty between April 1998 and November 2005, and were followed up for >5 years, postoperatively. Radiographic factors affecting distal femoral cortical hypertrophy were analysed using multivariable logistic regression analysis., Results: The mean follow-up period was 11.6 (5-17.8) years. During follow-up, femoral components were revised in 7 hips; one was revised due to aseptic loosening. Another femoral component was loosened and waiting for revision. The 10- and 15-year survival rates for aseptic stem loosening were 100% and 98.1% (95% CI: 92.5-99.5), respectively. Distal femoral cortical hypertrophy occurred in 23 hips (14.8%), and more often with roundback type (34.1%) than with flanged type (7.2%). Distal femoral cortical hypertrophy was observed in 34.8% of hips with valgus alignment, 11.3% with neutral alignment, and 12.5% with varus alignment. Multivariable logistic regression analysis showed that roundback stem shape and valgus stem alignment significantly affected the occurrence of distal femoral cortical hypertrophy., Conclusions: The Elite-Plus stem has excellent long-term clinical and radiographic results in Japanese patients. The occurrence of distal femoral cortical hypertrophy significantly depends on the shape and alignment of Elite-Plus stems., (Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

We herein report on two middle-aged men with TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis or renal failure, and organomegaly) syndrome, a unique clinicopathological variant of multicentric Castleman׳s disease recently proposed in Japan. Strikingly similar anterior mediastinal fat swellings with soft tissue density were observed in the patients on chest computed tomography. In TAFRO syndrome, bilateral pleural effusion and slight lymph node swelling are common in the thoracic region; however, anterior mediastinal lesions have not been previously observed. Although the mechanisms of anterior mediastinal lesions have not been defined, these lesions seem to have a close relationship with TAFRO syndrome., (Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Exosomes are cell-derived extracellular vesicles that function as intercellular delivery carriers. Our previous study demonstrated that macrophages in the liver contributed to the rapid clearance of intravenously administered B16BL6-derived exosomes from the systemic circulation in mice. Phosphatidylserine (PS) may be responsible for this clearance because it is exposed on the surface of exosomes and is recognized by macrophages. In this study, the role of PS exposed on the membranes of exosomes in the uptake of B16BL6-derived exosomes by macrophages was investigated. Negatively charged PS- or phosphatidylglycerol-loaded liposomes suppressed the cellular uptake of PKH67-labeled exosomes by macrophages, whereas phosphatidylcholine-containing liposome did not affect uptake. Subsequently, for the in vivo analysis, exosomes were labeled with Gaussia luciferase, a reporter protein, or (3- 125 I-iodobenzoyl)norbiotinamide using exosome-tropic fusion proteins comprising the exosome-tropic protein lactadherin. The blood clearance of Gaussia luciferase-labeled exosomes after intravenous injection into mice was significantly delayed by the preinjection of PS- or phosphatidylglycerol-containing liposomes. Moreover, the accumulation of (3- 125 I-iodobenzoyl)norbiotinamide-labeled exosomes in the liver was decreased by the preinjection of PS-containing liposomes. These results indicate that the negative charge of PS in exosomal membranes is involved in the recognition and clearance of intravenously injected exosomes by macrophages., (Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Wide resection is the generally recommended surgical treatment for dedifferentiated liposarcoma (DDLPS) in the extremities. However, it may be appropriate to distinguish the surgical margin of low-grade atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLPS) area from the high-grade dedifferentiated area, because the low- and high-grade areas can be clearly separated, both radiologically and histologically. This study re-evaluated the details of surgical margin of DDLPS in the extremities, and aimed to investigate the optimal surgical margin and the usefulness of adjuvant therapy for DDLPS in the extremities., Methods: Seven patients diagnosed with DDLPS in the extremities and treated between 1995 and 2013 were analyzed. The use of adjuvant therapy before and after surgery was assessed, and the surgical margins for the ALT/WDLPS and dedifferentiated areas were re-evaluated by using the specimens resected at surgery. Subsequently, the recurrence rates, metastatic rates, and oncological outcomes were examined., Results: Four and three patients had wide (adequate wide margin, n = 3; inadequate wide margin, n = 1) and marginal margins for the dedifferentiated area, respectively, while three and four patients had wide (adequate wide margin, n = 2; inadequate wide margin, n = 1) and marginal margins for the ALT/WDLPS area, respectively. Postoperative radiotherapy was performed in three patients with an inadequate wide margin or a marginal margin for the dedifferentiated area. No patient had local recurrence. Distant metastases occurred in two patients. These patients died of their disease. The other five patients were disease-free., Conclusion: The ALT/WDLPS and dedifferentiated areas in the tumor margin may be better to be considered separately in determining the appropriate resection extent for DDLPS in the extremities. Postoperative radiotherapy may provide good local control for cases with a narrow surgical margin., (Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: It has been reported that recombinant human soluble thrombomodulin (rhsTM) has a high-mobility group box (HMGB)1 inhibitory effect. Some investigators reported that HMGB1 is associated with ischemic stroke. However, there have been no previous studies to determine whether rhsTM can ameliorate cerebral ischemic injury through its HMGB1 inhibitory mechanism in ischemic stroke. We investigated the effects of rhsTM on cerebral ischemic injury in a 4-h middle cerebral artery occlusion (MCAO) murine model., Methods: rhsTM (1 or 5mg/kg, i.v.) was administered immediately after 4-h MCAO. Infarct volume, motor coordination, plasma HMGB1 level, and hemorrhage volume were evaluated 24h after 4-h MCAO., Results: The infarct volume (P<0.05) was reduced by rhsTM in mice subjected to 4-h MCAO in a dose-dependent manner. Moreover, rhsTM (5mg/kg) significantly improved motor coordination determined by the rotarod test (P<0.05), and significantly decreased plasma HMGB1 level compared with vehicle-treated controls (P<0.001). In addition, there was no difference in hemorrhage volume between vehicle-treated controls and the rhsTM treatment group., Conclusions: This represents the first report that rhsTM ameliorates cerebral ischemic injury through an HMGB1 inhibitory mechanism without hemorrhagic complications in mice. Taken together, these observations indicate a palliative effect of rhsTM and suggest new therapeutic possibilities for treatment of ischemic stroke via inhibition of HMGB1., (Copyright © 2016 Elsevier B.V. All rights reserved.)