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A case of esophageal lymphangioma in a 75-year-old man who complained of worsening dysphagia is presented. Endoscopic ultrasound showed an echogenic pattern of honeycomb or grid-like multiple microcysts within the submucosa. The sagittal image of computed tomography showed a thickened esophageal wall and fluid retention in the proximal esophageal lumen. Magnetic resonance imaging showed a high signal intensity mass with a septate-like internal structure on T2-weighted imaging and short tau inversion recovery. The tumor was completely resected by endoscopic submucosal dissection. Esophageal lymphangioma is a rare submucosal tumor that can be precisely diagnosed by CT and/or MRI.

Abstract Background Several cognitive functions are related to sex. However, the relationship between auditory attention and sex remains unclear. The present study aimed to explore sex differences in auditory saliency judgments, with a particular focus on bottom-up type auditory attention. Methods Forty-five typical adults (mean age: 21.5 ± 0.64 years) with no known hearing deficits, intelligence abnormalities, or attention deficits were enrolled in this study. They were tasked with annotating attention capturing sounds from five audio clips played in a soundproof room. Each stimulus contained ten salient sounds randomly placed within a 1-min natural soundscape. We conducted a generalized linear mixed model (GLMM) analysis using the number of responses to salient sounds as the dependent variable, sex as the between-subjects factor, duration, maximum loudness, and maximum spectrum of each sound as the within-subjects factor, and each sound event and participant as the variable effect. Results No significant differences were found between male and female groups in age, hearing threshold, intellectual function, and attention function (all p > 0.05). Analysis confirmed 77 distinct sound events, with individual response rates of 4.0–100%. In a GLMM analysis, the main effect of sex was not statistically significant (p = 0.458). Duration and spectrum had a significant effect on response rate (p = 0.006 and p

Abstract Background Minimally invasive posterior fixation surgery for pyogenic spondylitis is known to reduce invasiveness and complication rates; however, the outcomes of concomitant insertion of pedicle screws (PS) into the infected vertebrae via the posterior approach are undetermined. This study aimed to assess the safety and efficacy of PS insertion into infected vertebrae in minimally invasive posterior fixation for thoracolumbar pyogenic spondylitis. Methods This multicenter retrospective cohort study included 70 patients undergoing minimally invasive posterior fixation for thoracolumbar pyogenic spondylitis across nine institutions. Patients were categorized into insertion and skip groups based on PS insertion into infected vertebrae, and surgical data and postoperative outcomes, particularly unplanned reoperations due to complications, were compared. Results The mean age of the 70 patients was 72.8 years. The insertion group (n = 36) had shorter operative times (146 versus 195 min, p = 0.032) and a reduced range of fixation (5.4 versus 6.9 vertebrae, p = 0.0009) compared to the skip group (n = 34). Unplanned reoperations occurred in 24% (n = 17) due to surgical site infections (SSI) or implant failure; the incidence was comparable between the groups. Poor infection control necessitating additional anterior surgery was reported in four patients in the skip group. Conclusions PS insertion into infected vertebrae during minimally invasive posterior fixation reduces the operative time and range of fixation without increasing the occurrence of unplanned reoperations due to SSI or implant failure. Judicious PS insertion in patients with minimal bone destruction in thoracolumbar pyogenic spondylitis can minimize surgical invasiveness.

Background Some people use illicit drugs to relieve stress. However, these drugs cause serious damage not only to individuals but also to society as a whole. Stress caused by the COVID-19 pandemic is considerable, as the number of illicit drug users continues to increase, despite a decrease in the availability of drugs and opportunities to leave the house during the pandemic. Fear of COVID-19 causes stress; however, its association with illicit drug use is not yet understood. In this study, we examined whether the fear of COVID-19 affects the subsequent use of illicit drugs. Methods We conducted a retrospective longitudinal case-control study using data from an Internet survey performed annually between 2020–2022, with the 2020 survey as the baseline survey and the 2021 and 2022 surveys as follow-up surveys. Those who were illicit drug use-free at the baseline survey but had a history of drug use upon follow-up were defined as the outcome group, whereas those who remained illicit drug use-free at follow-up were defined as the no-outcome group. Logistic regression analysis was conducted between the two groups, using “the fear of COVID-19” as the explanatory variable and adjusting for the effects of confounding factors. The same analysis was conducted by dividing illicit drugs into cannabis and non-cannabis groups, then setting their use as a secondary outcome. Results The study included 17,800 subjects, 837 of whom used illicit drugs at follow-up and 16,963 who did not use illicit drugs at follow-up. Logistic regression analysis revealed that higher levels of fear over COVID-19 correlated with higher illicit drug use among the participants. However, our analysis of cannabis-only outcomes showed no significant differences. Conclusions We found that fear of COVID-19 was a contributing factor to illicit drug use. Although the exact mechanism through which fear influences illicit drug use remains unknown, previous studies have shown that fear of certain targets increases illicit drug use, and our study adds to this evidence. However, in this study, we were unable to show a statistically significant causal relationship between fear of COVID-19 and the use of cannabis alone. Further research on the relationship between fear and the use of cannabis or other drugs, for varying focuses of fear, may broaden our knowledge of the different reasons individuals have for using different drugs.

Abstract The aggregated alpha-synuclein (αsyn) in oligodendrocytes (OLGs) is one of the pathological hallmarks in multiple system atrophy (MSA). We have previously reported that αsyn accumulates not only in neurons but also in OLGs long after the administration of αsyn preformed fibrils (PFFs) in mice. However, detailed spatial and temporal analysis of oligodendroglial αsyn aggregates was technically difficult due to the background neuronal αsyn aggregates. The aim of this study is to create a novel mouse that easily enables sensitive and specific detection of αsyn aggregates in OLGs and the comparable analysis of the cellular tropism of αsyn aggregates in MSA brains. To this end, we generated transgenic (Tg) mice expressing human αsyn-green fluorescent protein (GFP) fusion proteins in OLGs under the control of the 2’, 3’-cyclic nucleotide 3’-phosphodiesterase (CNP) promoter (CNP-SNCAGFP Tg mice). Injection of αsyn PFFs in these mice induced distinct GFP-positive aggregates in the processes of OLGs as early as one month post-inoculation (mpi), and their number and size increased in a centripetal manner. Moreover, MSA-brain homogenates (BH) induced significantly more oligodendroglial αsyn aggregates than neuronal αsyn aggregates compared to DLB-BH in CNP-SNCAGFP Tg mice, suggestive of their potential tropism of αsyn seeds for OLGs. In conclusion, CNP-SNCAGFP Tg mice are useful for studying the development and tropism of αsyn aggregates in OLGs and could contribute to the development of therapeutics targeting αsyn aggregates in OLGs.

Hereditary spastic paraplegia (HSP) is a heterogeneous group of neurological disorders that are characterized by progressive spasticity and weakness in the lower limbs. SPG26 is a complicated form of HSP, which includes not only weakness in the lower limbs, but also cognitive impairment, developmental delay, cerebellar ataxia, dysarthria, and peripheral neuropathy, and is caused by biallelic mutations in the B4GALNT1 (beta-1,4-N-acetylgalactosaminyltransferase 1) gene. The B4GALNT1 gene encodes ganglioside GM2/GD2 synthase (GM2S), which catalyzes the transfer of N-acetylgalactosamine to lactosylceramide, GM3, and GD3 to generate GA2, GM2, and GD2, respectively. The present study attempted to characterize a novel B4GALNT1 variant (NM_001478.5:c.937G>A p.Asp313Asn) detected in a patient with progressive multi-system neurodegeneration as well as deleterious variants found in the general population in Japan. Peripheral blood T cells from our patient lacked the ability for activation-induced ganglioside expression assessed by cell surface cholera toxin binding. Structural predictions suggested that the amino acid substitution, p.Asp313Asn, impaired binding to the donor substrate UDP-GalNAc. An in vitro enzyme assay demonstrated that the variant protein did not exhibit GM2S activity, leading to the diagnosis of HSP26. This is the first case diagnosed with SPG26 in Japan. We then extracted 10 novel missense variants of B4GALNT1 from the whole-genome reference panel jMorp (8.3KJPN) of the Tohoku medical megabank organization, which were predicted to be deleterious by Polyphen-2 and SIFT programs. We performed a functional evaluation of these variants and demonstrated that many showed perturbed subcellular localization. Five of these variants exhibited no or significantly decreased GM2S activity with less than 10% activity of the wild-type protein, indicating that they are carrier variants for HSP26. These results provide the basis for molecular analyses of B4GALNT1 variants present in the Japanese population and will help improve the molecular diagnosis of patients suspected of having HSP.

Introduction: The smiley face rod method is an effective treatment for symptomatic terminal-stage spondylolysis. However, the risk factors for treatment failure are unknown. We investigated the association of pars defect type with the treatment outcomes of this method. Methods: We retrospectively examined data from 34 patients (18.0±6.7 years) with terminal-stage spondylolysis who underwent surgery using the smiley face rod method. The mean follow-up period was 44.9±21.4 months. The patients were divided into 2 groups: pars defect without bone atrophy or sclerosis (group A; 18 patients), and with bone atrophy and sclerosis (group B; 16 patients). We evaluated and compared the visual analog scale (VAS) score for back pain, bone union rate, and time to return to preinjury athletics level between the groups. Fisher exact and paired t tests were used to compare the variables between groups. The VAS score between the groups was compared using a 2-factor repeated-measures analysis of variance. Results: Within groups, the VAS score was significantly different over time (p

Abstract Background Endoscopic biliary stenting is a standard treatment for biliary strictures after liver transplantation. Plastic stents are often replaced before stent dysfunction to prevent the development of cholangitis and jaundice. Therefore, the precise duration of stent patency is unclear. Methods We compared retrospectively the stent patency period and stent dysfunction rate between inside stents (IS) and conventional plastic stents (PS) in 48 patients with post‐transplant strictures, distinguishing endoscopic biliary stenting with and without stent dysfunction at stent replacement. Results In observations focused on the first treatment, the median patency periods were 369 days for IS (n = 18) and 154 days for PS (n = 30; p = 0.01), significantly longer for IS. The 1‐year cholangitis incidence rate was lower for IS (20% vs. 43%, p = 0.04). Additionally, no stent dislocation was observed for IS, but this occurred for 33.3% of PS (p = 0.004). Comparing all endoscopic biliary stenting, including second and subsequent procedures, IS again had a longer patency period than PS (356 days, n = 89, vs. 196 days, n = 127, p = 0.009). Conclusions IS had a significantly longer patency period than PS, suggesting that IS replacement could be reduced to once per year for patients who prefer less frequent stent replacement.

Abstract Lysinuric protein intolerance (LPI), caused by pathogenic variants of SLC7A7, is characterized by protein aversion, failure to thrive, hyperammonemia, and hepatomegaly. Recent studies have reported that LPI can cause multiple organ dysfunctions, including kidney disease, autoimmune deficiency, pulmonary alveolar proteinosis, and osteoporosis. We report the case of a 47‐year‐old Japanese woman who was initially diagnosed with renal tubular acidosis (RTA), Fanconi syndrome, and rickets. At the age of 3 years, she demonstrated a failure to thrive. Urinary amino acid analysis revealed elevated lysine and arginine levels, which were masked by pan‐amino aciduria. She was subsequently diagnosed with rickets at 5 years of age and RTA/Fanconi syndrome at 15 years of age. She was continuously treated with supplementation of vitamin D3, phosphate, and bicarbonate. A renal biopsy at 18 years of age demonstrated diffuse proximal and distal tubular damage with endocytosis‐lysosome pathway abnormalities. Distinctive symptoms of LPI, such as protein aversion and postprandial hyperammonemia were not observed throughout the patient's clinical course. The patient underwent a panel‐based comprehensive genetic testing and was diagnosed with LPI. As the complications of LPI involve many organs, patients lacking distinctive symptoms may develop various diseases, including RTA/Fanconi syndrome. Our case indicates that proximal and distal tubular damages are notable findings in patients with LPI. The possibility of LPI should be carefully considered in the management of RTA/Fanconi syndrome and/or incomprehensible pathological tubular damage, even in the absence of distinctive symptoms; furthermore, a comprehensive genetic analysis is useful for diagnosing LPI.

Abstract Background Epilepsy is a common neurological disorder. Lacosamide is a third-generation antiepileptic drug used to treat partial-onset seizures. Limited information is currently available on the transfer of lacosamide to breast milk. To facilitate studies on the safety of lacosamide use during breastfeeding, we aimed to develop a method to quantify lacosamide in human breast milk and plasma using ultra-performance liquid chromatography/tandem mass spectrometry. Methods Fifty microliters of breast milk or plasma was used, and samples were prepared by protein precipitation using methanol containing lacosamide-d3 as an internal standard (IS). Chromatography was performed using an ACQUITY HSS T3 column with an isocratic flow of 10 mM ammonium acetate solution/methanol (70:30, v/v). Lacosamide and IS were detected by multiple reaction monitoring in positive ion electrospray mode. The run time was 3.5 min. Results Calibration curves were linear and in the range of 0.5 to 100 ng/mL both in breast milk and plasma. The validation assessment indicated that precision, accuracy, matrix effects, selectivity, dilution integrity, and stability were acceptable. The developed method was successfully applied to quantify lacosamide in breast milk and plasma obtained from a volunteer who had been orally administered lacosamide twice a day (100 mg × 2). Relative infant dose of lacosamide was estimated to be 14.6% in breast milk at five time points. Conclusions We developed a simple and robust method to quantify of lacosamide in human breast milk and plasma. This method could be useful for in future studies investigating the safety of lacosamide use during breastfeeding.

Acoustic emission tomography (“AET”) is used to visualize internal structural damage. In this study, we aimed to improve the accuracy of the identified elastic wave velocity distribution when including errors in the observed arrival time, which is used as the observation value in AET. Weights were assigned to the potential excitation times used in location determination and elastic wave velocity distribution according to the magnitude of the potential excitation time and the wave line length. As a result, 100 instances of observation errors were generated for each observation error ratio via truncated normal distribution. The analysis results showed that the normalization error of the elastic wave velocity distribution increased in about 85%, 90%, and 95% of the cases for observation error ratios of 5%, 10%, and 15%, respectively. In conclusion, the weights used for the potential excitation time were effective in identifying elastic wave velocity distribution.

Introduction: Lumbar spondylolysis is a common fatigue fracture of the pars interarticularis of the lamina of the lumbar spine in adolescent athletes presenting with pars clefts. Some pseudarthrotic lumbar spondylolysis causes low back pain or radiculopathy. This study presents a case of pseudarthrotic lumbar spondylolysis that was successfully treated using a modified smiley face rod technique. Technical Note: We developed a modified smiley face rod technique, which places pedicle screws in the lateral edge of the pedicle to preserve the erector spinae muscles and inserts a U-shaped rod between the spinous processes to preserve the supraspinous ligament. When a U-shaped rod penetrates the interspinous ligament subcutaneously, the resection of the supraspinous ligaments can be avoided. When the screw head is positioned more anterolaterally, a compression force is applied perpendicular to the surface of the pars cleft by rod clamping. This intrasegmental fusion technique preserves the mobile segment and simultaneously repairs the pars cleft. It is less invasive and more appropriate than interbody fusion for young athletes to avoid the possibility of future adjacent segment disorders. Conclusions: This is a minimally invasive procedure that can easily achieve bone fusion and should be introduced for patients who are suffering from the symptoms of pseudarthrotic lumbar spondylolysis.

Abstract Background Lumbar spondylolysis, a common identifiable cause of low back pain in young athletes, reportedly has a higher incidence rate in males. However, the reason for its higher incidence in males is not clear. This study aimed to investigate the epidemiological differences between the sexes in adolescent patients with lumbar spondylolysis. Methods A retrospective study was conducted in 197 males and 64 females diagnosed with lumbar spondylolysis. These patients visited our institution from April 2014 to March 2020 with their main complaint being low back pain, and they were followed-up until the end of their treatment. We investigated associations between lumbar spondylosis, their background factors, and characteristics of the lesions and analyzed their treatment results. Results Males had a higher prevalence of spina bifida occulta (SBO) (p = 0.0026), more lesions with bone marrow edema (p = 0.0097), and more lesions in the L5 vertebrae (p = 0.021) than females. The popular sports disciplines were baseball, soccer, and track and field in males, and volleyball, basketball, softball in females. The dropout rate, age at diagnosis, bone union rate, and treatment period did not differ between the sexes. Conclusion Lumbar spondylolysis was more common in males than in females. SBO, bone marrow edema, and L5 lesions were more frequent in males, and sports discipline varied between the sexes.

Abstract Ultraviolet (UV) irradiation offers an effective and convenient method for the disinfection of pathogenic microorganisms. However, UV irradiation causes protein and/or DNA damage; therefore, further insight into the performance of different UV wavelengths and their applications is needed to reduce risks to the human body. In this paper, we determined the efficacy of UV inactivation of the SARS-CoV-2 omicron BA.2 and BA.5 variants in a liquid suspension at various UV wavelengths by the 50% tissue culture infection dose (TCID50) method and quantitative polymerase chain reaction (qPCR) assay. The inactivation efficacy of 220 nm light, which is considered safe for the human body, was approximately the same as that of health hazardous 260 nm light for both BA.2 and BA.5. Based on the inactivation rate constants determined by the TCID50 and qPCR methods versus the UV wavelength, the action spectra were determined, and BA.2 and BA.5 showed almost the same spectra. This result suggests that both variants have the same UV inactivation characteristics.

Abstract Background Various neurological manifestations associated with coronavirus disease 2019 have been increasingly reported. Herein, we report a rare case of anterior interosseous nerve syndrome, which occurred 5 days after the onset of coronavirus disease 2019. Case presentation A 62-year-old Asian woman with a history of coronavirus disease 2019 who developed a complete motor deficit in the left flexor pollicis longus and pronator quadratus without sensory deficits. The symptoms appeared as a sudden onset fatigue and severe pain of the left arm, 5 days after the onset of coronavirus disease 2019. She noticed paralysis of the left thumb at 2 weeks after the onset of coronavirus disease 2019. Electromyography assessment of the anterior interosseous nerve-dominated muscles revealed neurogenic changes such as positive sharp wave and fibrillation in flexor pollicis longus and pronator quadratus, confirming the diagnosis of anterior interosseous nerve syndrome. There were no other diseases that could have resulted in peripheral nerve palsy. We performed a functional reconstruction surgery of the thumb by tendon transfer from the extensor carpi radialis longus to the flexor pollicis longus. The patient reported a good patient-reported outcome (2.27 points in QuickDASH Disability/Symptom scoring and 5 points in Hand20 scoring) at final follow-up (1 year after the surgery). Conclusion This case highlights the need for vigilance regarding the possible development of anterior interosseous nerve syndrome in patients with coronavirus disease 2019. Tendon transfer from extensor carpi radialis longus to flexor pollicis longus can provide good functional recovery for unrecovered motor paralysis after anterior interosseous nerve syndrome.

ObjectivesCompared to conventional disease-modifying antirheumatic drugs (DMARDs), biological DMARDs demonstrate superior efficacy but come with higher costs and increased infection risks. The ability to stop and resume biological DMARD treatment while maintaining remission would significantly alleviate these barriers and anxieties. The objective of this study was to identify biomarkers that can predict an imminent relapse, hopefully enabling the timely resumption of biological DMARDs before relapse occurs.MethodsForty patients with rheumatoid arthritis who had been in remission for more than 12 months were included in the study. The patients discontinued their biological DMARD treatment and were monitored monthly for the next 24 months. Out of the 40 patients, 14 (35%) remained in remission at the end of the 24-month period, while 26 (65%) experienced relapses at different time points. Among the relapse cases, 13 patients experienced early relapse within 6 months, and another 13 patients had late relapse between 6 months and 24 months. Seventy-three cytokines in the sera collected longitudinally from the 13 patients with late relapse were measured by multiplex immunoassay. Using cytokines at two time points, immediately after withdrawal and just before relapse, volcano plot and area under the receiver operating characteristic curves (AUC) were drawn to select cytokines that distinguished imminent relapse. Univariate and multivariate logistic regression analyses were used for the imminent relapse prediction model.ResultsIL-6, IL-29, MMP-3, and thymic stromal lymphopoietin (TSLP) were selected as potential biomarkers for imminent relapse prediction. All four cytokines were upregulated at imminent relapse time point. Univariate and multivariate logistic regression showed that a combination model with IL-6, MMP-3, and TSLP yielded an AUC of 0.828 as top predictors of imminent relapse.ConclusionsThis methodology allows for the prediction of imminent relapse while patients are in remission, potentially enabling the implementation of on- and off-treatments while maintaining remission. It also helps alleviate patient anxiety regarding the high cost and infection risks associated with biological DMARDs, which are the main obstacles to benefiting from their superb efficacy.

Abstract Background & Aims Relationships of serum C‐C motif chemokine ligand 5 (CCL5) and C‐X‐C motif chemokine ligand 10 (CXCL10) levels with hot immune features have been reported in patients with hepatocellular carcinoma (HCC). Therefore, we examined the utility of their levels for predicting the efficacy of atezolizumab plus bevacizumab (Atez/Bev) in patients with HCC. Design In total, 98 patients with HCC treated with Atez/Bev were enrolled, and their initial responses were evaluated at least once via dynamic computed tomography or magnetic resonance imaging. Serum CCL5 and CXCL10 levels were assessed by enzyme‐linked immunosorbent assay before treatment and at the start of the second course of Atez/Bev therapy, and their relationships with treatment efficacy were determined. Results No analyzed factor was associated with the initial therapeutic response. Among the 56 patients with Barcelona Clinic Liver Cancer (BCLC) stage C, serum CXCL10 levels at the beginning of course two (CXCL10‐2c) tended to be higher in responders than in non‐responders in the initial evaluation, and its optimal cutoff level of 690 pg/mL could be used to stratify patients regarding overall survival (OS; high vs. low: not reached vs. 17.6 months, p = 0.034) and progression‐free survival (high vs. low: 13.6 vs. 5.1 months, p = 0.014). In multivariate analysis, high CXCL10 levels and neutrophil‐to‐lymphocyte ratios at the start of course two and Child–Pugh stage A at baseline were independent predictive factors of improved OS. Conclusions Serum CXCL10‐2c levels were predictive of Atez/Bev efficacy in patients with BCLC stage C HCC.

Abstract Background Pyogenic spondylitis by methicillin-resistant Staphylococcus aureus (MRSA) is known to be intractable. In the past, the insertion of an implant into infected vertebra was considered contraindicated in affected patients because it may exacerbate the infection, but there are increasing numbers of reports indicating the usefulness of posterior fixation to correct instability and alleviate infection. Bone grafting is often required to repair large bone defect due to infection, but free grafts can exacerbate infection and are controversial. Case presentation We present the case of a 58-year-old Asian man with intractable pyogenic spondylitis who had repeated septic shocks due to MRSA. Back pain from repeated pyogenic spondylitis caused by a huge bone defect in L1–2 rendered him unable to sit. Posterior fixation by percutaneous pedicle screws (PPSs) without bone transplantation improved spinal stability and regenerated bone in the huge vertebral defect. He regained his activities of daily living, had no reoccurrence of pyogenic spondylitis nor bacteremia, and was completely cured of the infection without antibiotics after removal of all screws. Conclusions For intractable MRSA pyogenic spondylitis with instability accompanied by a huge bone defect, posterior fixation using PPSs and administration of antibacterial agents stopped the infection, allowed the bone to regenerate, and recovered the patient’s activities of daily living.

Introduction: Variants in the galactosidase alpha (GLA) gene cause Fabry disease (FD), an X-linked lysosomal storage disorder caused by α-galactosidase A (α-GAL) deficiency. Recently, disease-modifying therapies have been developed, and simple diagnostic biomarkers for FD are required to initiate these therapies in the early stages of the disease. Detection of urinary mulberry bodies and cells (MBs/MCs) is beneficial for diagnosing FD. However, few studies have evaluated the diagnostic accuracy of urinary MBs/MCs in FD. Herein, we retrospectively evaluated the diagnostic ability of urinary MBs/MCs for FD. Methods: We analyzed the medical records of 189 consecutive patients (125 males and 64 females) who underwent MBs/MCs testing. Out of these, two female patients had already been diagnosed with FD at the time of testing, and the remaining 187 patients were suspected of having FD and underwent both GLA gene sequencing and/or α-GalA enzymatic testing. Results: Genetic testing did not confirm the diagnosis in 50 females (26.5%); hence, they were excluded from the evaluation. Two patients were previously diagnosed with FD, and sixteen were newly diagnosed. Among these 18 patients, 15, including two who had already developed HCM at diagnosis, remained undiagnosed until targeted genetic screening of at-risk family members of patients with FD was performed. The accuracy of urinary MBs/MCs testing exhibited a sensitivity of 0.944, specificity of 1, positive predictive value of 1, and negative predictive value of 0.992. Conclusions: MBs/MCs testing is highly accurate in diagnosing FD and should be considered during the initial evaluation prior to genetic testing, particularly in female patients.

Abstract Metabolic reprogramming of cancer cells is a potential target for cancer therapy. It is also known that a hypoxic environment, one of the tumor microenvironments, can alter the energy metabolism from oxidative phosphorylation to glycolysis. However, the relationship between hypoxia and drug sensitivity, which targets energy metabolism, is not well known. In this study, A549 cells, a cell line derived from lung adenocarcinoma, were evaluated under normoxia and hypoxia for the sensitivity of reagents targeting oxidative phosphorylation (metformin) and glycolysis (α-cyano-4-hydroxycinnamic acid [CHC]). The results showed that a hypoxic environment increased the expression levels of monocarboxylate transporter (MCT) 4 and hypoxia-induced factor-1α (HIF-1α), whereas MCT1 and MCT2 expression did not vary between normoxia and hypoxia. Furthermore, the evaluation of the ATP production ratio indicated that glycolysis was enhanced under hypoxic conditions. It was then found that the sensitivity to metformin decreased while that to CHC increased under hypoxia. To elucidate this mechanism, MCT4 and HIF-1α were knocked down and the expression level of MCT4 was significantly decreased under both conditions. In contrast, the expression of HIF-1α was decreased by HIF-1α knockdown and increased by MCT4 knockdown. In addition, changes in metformin and CHC sensitivity under hypoxia were eliminated by the knockdown of MCT4 and HIF-1α, suggesting that MCT4 is involved in the phenomenon described above. In conclusion, it was shown that the sensitivity of reagents targeting energy metabolism is dependent on their microenvironment. As MCT4 is involved in some of these mechanisms, we hypothesized that MCT4 could be an important target molecule for cancer therapy.

Anti-metabotropic glutamate receptor 1 (mGluR1) encephalitis is a rare autoimmune disorder manifesting with cerebellar syndrome. Patients with mGluR1 encephalitis have been treated with immunomodulatory therapies; however, little is known about the efficacy of this therapy. A 58-year-old Japanese woman presented with dizziness when walking and standing up. Symptoms persisted and the patient gradually deteriorated. The neurological examination revealed a broad-based gait, horizontal and slightly gaze-evoked nystagmus, noticeable head titubation, and truncal ataxia without limb ataxia. Magnetic resonance imaging was normal. The 123I-isopropyl-iodoamphetamine single-photon emission-computed tomography scans showed normal cerebellar perfusion. Based on a positive antibody test for anti-mGluR1, the patient was diagnosed with anti-mGluR1 encephalitis. She was treated with intravenous methylprednisolone and intravenous immunoglobulin (IVIg). Symptoms gradually improved over 1 month and almost disappeared after additional IVIg therapy. Anti-mGluR1 encephalitis is a rare disease, and effective treatment is unclear. In this case, a favorable outcome was obtained with immunomodulatory therapy, even though the neurological disability of the disease course is worse. We emphasize the importance of early diagnosis and therapeutic intervention, suspecting the disease on the basis of its characteristic symptoms.

Abstract Since the advent of biological disease modifying anti-rheumatic drugs (bDMARDs) in the treatment of rheumatoid arthritis (RA), most RA patients receiving such drugs have achieved remission at the expense of cost and infection risk. After bDMARDs are withdrawn, a substantial proportion of patients would have relapses even if they were in complete remission. In our previous report, relapse prediction could be made at the time of bDMARD withdrawal by measuring the serum levels of five cytokines. We report herein that, among 73 cytokines examined, serum levels of only interferon β (IFNβ) at the time of bDMARD withdrawal could predict early relapse (within 5 months) in patients who were categorized to relapse by the five cytokines in our previous report, with a cut-off value of 3.38 in log2 and AUC of 0.833. High serum levels of IFNβ in the early-relapse group remained high until actual relapse occurred. Therefore, patients who relapse early might be biochemically different from those who relapse late or do not relapse at all. We recommend that patients who are predicted to relapse early continue bDMARDs even if they are in complete remission. This finding contributes to shared decision-making regarding how and when bDMARDs should be discontinued.

Abstract The pathological hallmarks of Parkinson’s disease (PD) are α-synuclein (αSYN)-positive inclusions referred to as Lewy bodies and Lewy neurites, collectively referred to as Lewy-related pathology (LRP). LRP is thought to propagate in an ascending manner throughout the brain as the disease progresses. LRP is visible with histologic methods and is thought to represent a later stage of the disease process, while αSYN oligomers, which are not visible with routine histologic methods, are considered earlier. There is increasing evidence to suggest that αSYN oligomers may be more toxic than visible LRP. Detecting αSYN oligomers requires special techniques, and their distribution and association with clinical features are important research objectives. In this report, we describe the distribution of αSYN oligomers in multiple cortical and subcortical regions of PD using a proximity ligation assay (PLA). We observe widespread distribution of αSYN oligomers with PLA and more restricted distribution of LRP with αSYN immunohistochemistry. The distribution of αSYN oligomers differed from LRP in that αSYN oligomer burden was significantly greater in the neocortex, while LRP was greater in vulnerable subcortical regions, including the brainstem. We also found that cognitive impairment was associated with αSYN oligomers in the hippocampus. These results suggest that αSYN oligomers may be widely distributed in PD early in the disease process and that they may contribute to cognitive impairment in PD.

Abstract Background Lumbar spondylolisthesis is reported to present with a familiar pattern, with the dysplastic type of spondylolysis being minor but more hereditary than the isthmic type. Siblings presenting during adolescence with neurological symptoms owing to high-grade dysplastic-type spondylolisthesis are rare. Case presentation The older brother suffered from left leg pain and numbness and dysesthesia of the right posterior thigh and calf and could not walk without a crutch at the age of 15 years. He had canal stenosis with disc bulging and dysplastic bilateral facet joint at L5/S1. The L5 vertebral body was slipped anterior downward to S1, with a round-shaped S1 cranial endplate. We diagnosed dysplastic-type spondylolisthesis and performed posterior lumbar interbody fusion at L5/S with mild reduction and sublaminar wiring at L4/5. The younger brother had no neurological symptoms at age 14 years but suffered from bilateral lower leg numbness at age 18 years. He had canal stenosis with disc bulging at L4/5 and L5/S1 and dysplastic bilateral facet joint at L5/S1 with right pars defect. The L5 vertebral body was vertically displaced anterior to the S1 vertebral body, with an S1 round-shaped cranial endplate. We diagnosed dysplastic-type spondylolisthesis, and posterior lumbar interbody fusion at L4/5 and L5/S with reduction was performed. Their neurological symptoms of the lower legs disappeared, and interbody bone fusion was obtained. Conclusions The surgical technique for high-grade dysplastic spondylolisthesis remains controversial in terms of in situ fusion versus reduction. We recommend that surgery be performed promptly at the end of bone maturation because neurological symptoms often appear at the end of bone maturation. Because high-grade slips are rare but siblings may be present, the sibling should also be screened when dysplastic spondylolisthesis is detected.

Introduction: Fatty acids are a major nutrient in dietary fat, some of which are ligands of long-chain fatty acid receptors, including G-protein-coupled receptor (GPR) 40 and GPR120. Pretreatment with GPR40 agonists enhanced the secretion of insulin in response to elevating blood glucose levels after glucose load in a diabetes model, but pretreatment with GPR120 agonist did not ameliorate postprandial hyperglycemia. This study examined whether oral administration of linoleic acid (LA), a GPR40 and GPR120 agonist, immediately before glucose load would affect the elevation of postprandial blood glucose levels in rats.Methods: Male rats and rats with type 1 diabetes administered streptozocin were orally administered LA, trilinolein, α-linolenic acid (α-LA), oleic acid, TAK-875, or TUG-891 immediately before glucose load. Blood glucose levels were measured before, then 15, 30, 60 and 120 min after glucose load. CACO-2 cells were used to measure the uptake of [14C] α-MDG for 30 min with or without LA. Gastric content from rats administered LA was collected 15 and 30 min after glucose load, and blood samples were collected for measurement of glucagon-like peptide 1 (GLP-1) and cholecystokinin concentrations.Results: The elevation of postprandial blood glucose levels was slowed by LA but not by trilinolein in rats without promotion of insulin secretion, and this effect was also observed in rats with type 1 diabetes. The uptake of α-MDG, an SGLT-specific substrate, was, however, not inhibited by LA. Gastric emptying was slowed by LA 15 min after glucose load, and GLP-1, but not cholecystokinin, level was elevated by LA 15 min after glucose load. TUG-891, a GPR120 agonist, ameliorated postprandial hyperglycemia but TAK-875, a GPR40 agonist, did not. Pretreatment with AH7614, a GPR120 antagonist, partially canceled the improvement of postprandial hyperglycemia induced by LA. α-LA, which has high affinity with GPR120 as well as LA, slowed the elevation of postprandial blood glucose levels, but oleic acid, which has lower affinity with GPR120 than LA, did not.Conclusion: Oral administration of LA immediately after glucose load ameliorated postprandial hyperglycemia due to slowing of gastric emptying via promotion of GLP-1 secretion. The mechanisms may be associated with GPR120 pathway.

Background There is no global consensus on whether pandemic-related factors are related to child abuse. How the pandemic reinforces the risk factors of child abuse might depend largely on individuals’ current and past lifestyles in each country. Some changes of lifestyles continue after the pandemic, and it is important to understand which factors are strongly associated with child abuse. We analyzed the pandemic-related characteristics of offenders and non-offenders of self-reported child physical abuse from Internet survey data in Japan and discussed how the pandemic affected physical child abuse and what caused the difference by gender. Methods We conducted a cross-sectional study on physical child abuse by caregivers based on the Internet survey conducted from September to October 2021. We divided the participants who were living with their child aged less than 14 years into offenders and non-offenders based on the answer to the question about physical child abuse. The population distribution of the sample was compared to that of caregivers under the same conditions in a large Japanese dataset. The association between their characteristics and physical child abuse was analyzed by univariable and multivariable analysis. Results The caregivers analyzed in the cohort had similar population distributions to those in the large Japanese dataset. As risk factors of male offenders, “work from home 4–7 days/week,” “decreased work,” “normal relationships with household members (compared to good relationships),” “COVID-19 infected, both themselves and household members, within a year,” “unwillingness to receive COVID-19 vaccination because the license process of the vaccine is doubtful,” “high levels of benevolent sexism,” and “history of child abuse” were observed. As risk factors of female offenders, “bad relationships with household members (compared to good relationships),” “fear of COVID-19,” “COVID-19 infected, both themselves and household members, within a year,” “feelings of discrimination related to COVID-19 in the past two months,” and “history of child verbal abuse” were observed. Conclusions Among male offenders, a significant relationship was observed regarding work-related changes, which may have been reinforced by the pandemic. Furthermore, the extent of the influence and fear of losing jobs caused by these changes may have varied according to the strength of gender roles and financial support in each country. Among female offenders, a significant relationship was observed regarding fear of infection itself, which is consistent with the findings of other studies. In terms of factors related to dissatisfaction with families, in some countries with prominent stereotyped gender roles, men are thought to experience difficulties adapting to work-related changes induced by crises, while women are thought to experience intense fear of the infection itself.

Advanced hepatocellular carcinoma (HCC) remains a highly lethal malignancy, although several systemic therapeutic options are available, including sorafenib (SFN), which has been one of the standard treatment agents for almost a decade. As early prediction of response to SFN remains challenging, biomarkers that enable early prediction using a clinically feasible method are needed. Here, we report that the serum secretory form of clusterin (sCLU) protein and its related predictive index are potential beneficial biomarkers for early prediction of SFN response. Using high‐throughput screening and subsequent multivariate analysis in the derivation cohort, we found that changes in the concentrations of CLU, vascular cell adhesion molecule‐1 (VCAM1), and α‐fetoprotein were significantly associated with response to SFN. Furthermore, we confirmed that an increase in CLU serum level 1 month after treatment initiation was significantly associated with shorter progression‐free survival. In addition, “NR‐index,” which comprises these proteins, was evaluated as a tool for accurately predicting the efficacy of SFN and confirmed in the validation cohort. We also established SFN‐resistant HepG2 cells (HepG2‐SR) and found that sCLU significantly increased in HepG2‐SR cells compared with normal HepG2 cells, and confirmed that HepG2‐SR cells treated with SFN were resistant to apoptosis. The mechanism underlying activation of sCLU expression in acquired SFN resistance involves aberrant signaling and expression of Akt, mammalian target of rapamycin (mTOR), and a nutrient‐related transcription factor, sterol regulatory element binding protein 1c (SREBP‐1c). Furthermore, the PI3K and mTOR inhibitor BEZ235 markedly decreased sCLU expression in HepG2‐SR cells. Conclusion: These results suggest that measurement of sCLU serum levels and the sCLU‐related NR‐index are promising clinical tools for the early prediction of SFN response in HCC. Additionally, sCLU‐overexpressing HCC might be susceptible to mTOR inhibition.

Abstract Background In general, the diagnosis of pedicle screw (PS) loosening is evaluated qualitatively based on the presence of a radiolucent area around the implant wider than 1 mm on plain radiographs and computed tomography (CT). Digital tomosynthesis is a novel imaging technology that can acquire reconstructed tomographic images of patients in different postures with relatively low radiation. In this study, PS loosening is evaluated quantitatively by measuring the PS displacement angle in the vertebrae using digital tomosynthesis. Methods We evaluated 41 patients who underwent posterior spinal fusion surgery using PS. The 72 pedicle screws at the cranial end of the fused segments were evaluated. The patients were divided in two groups, one with PS loosening (7 patients, 12 screws) and the other without PS loosening (34 patients, 60 screws), based on conventional CT findings. All patients underwent tomosynthesis in two different postures during a single CT session. Results The displacement angles of the PS in patients in a lying position and in a standing position were measured using selected slices of the same cross-sectional view from digital tomosynthesis. The displacement angle was significantly greater in the PS loosening group (5.7°) than in the group without PS loosening (0.6°) (p

Background/objective: It is important to assess the atrophy of the rotator cuff to better understand shoulder function and pain. Previously, magnetic resonance imaging has been used for the evaluation of atrophy of rotator cuff muscles, which is time consuming. Therefore, a measurement tool requiring little time and easy accessibility is clinically desirable to be used frequently in rehabilitation. Recently, rotator cuff muscles have been evaluated using ultrasonography. However, little is known about the agreement of evaluation in rotator cuff muscles between magnetic resonance imaging and ultrasonography. The purpose of this study was to demonstrate the agreement between the muscle thickness measurements of supraspinatus, infraspinatus, and teres minor muscles by ultrasonography and the cross-sectional area measured by magnetic resonance imaging in the patient with rotator cuff tears. Methods: A total of 47 patients with rotator cuff tears were enrolled. There were the 37 small tears, four medium tears, and six large tears, and the involved rotator cuff muscles were the supraspinatus in 37 shoulders, and the supraspinatus and infraspinatus in 10 shoulders. The measuring variables were muscle thickness and cross-sectional area of supraspinatus, infraspinatus, and teres minor muscles by using magnetic resonance imaging. Further, the muscle thickness of the rotator cuff were assessed using ultrasonography. A single regression model was used for demonstrating the agreement between the cross-sectional area measurement by magnetic resonance imaging and the muscle thickness measured using ultrasonography and magnetic resonance imaging of rotator cuff muscles. Additionally, the Bland-Altman plots between magnetic resonance imaging and ultrasonography was analyzed. Results: The cross-sectional area were correlated with the muscle thickness measurement of rotator cuff muscles by magnetic resonance imaging, significantly (supraspinatus: r = 0.84, infraspinatus: ρ = 0.63, teres minor: ρ = 0.61, all p

Abstract Occasionally lumbar spondylolysis in adolescents will recur after conservative treatment. The goal of this study was to retrospectively review the conditions in which recurrence transpired in a subset of adolescent patients diagnosed with acute lumbar spondylolysis. A retrospective survey was conducted in 141 patients who had been treated for spondylolysis and had obtained bone union. Twenty subjects were selected who had recurrent lumbar spondylolysis after returning to sports activity following the initial spondylolysis treatment. There were 18 males and two females with an average age at the time of initial visit of 13.3 years and 14.1 years at the time of recurrence. The average period of initial treatment was 101 days, and the average time to recurrence after healing was 149 days. There were three cases at L3, two cases at L4 and 15 cases at L5. At recurrence, 18 patients had unilateral involvement and two patients presented with bilateral occurrence. Four cases did not achieve bony union. In this study, the recurrence rate was 13.2%. Eighty percent of cases had recurrence within six months after healing. After recurrence, 20% of the cases reached pseudoarthrosis. It is useful to take regular MRI images to detect recurrence within six months after returning to sports.

Background The existence of social withdrawal (Hikikomori), which meets the conditions “not attending school”, “not working”, and “isolated at home for more than 6 months”, is gradually being discovered by the world, and their mental health and healing is being highlighted. However, there are very few Hikikomori-related surveys searching their physical health, as it is generally believed that most Hikikomori are adolescents. Middle-aged Hikikomori are also found outside Japan, and their physical health is more important, because Hikikomori have difficulty managing their health due to the socially isolated circumstances and lack of sociability. Although “isolated at home for more than 6 months” could not be used, we extracted a group with low social independence with reference to Hikikomori-related surveys. We estimate that people with low social independence have similar characteristics and problems to Hikikomori, because they share many causes for the problem of difficulty in managing their own health. People with low social independence were identified, and their physical health, such as smoking and drinking status, consultation rates of various diseases, and how often they attend cancer screenings, was analyzed. Methods We extracted middle-aged people with low social independence and a control group from the national survey in Japan and stratified them by sex and age. Their health risks were assessed by univariate analysis. Criteria for the experimental group were set with reference to Hikikomori-related surveys. Criteria for the control group included “aged 40–69”, “living with parents”, “not receiving care for disabilities”, and ”working”. Results Low-social-independent men had higher consultation rates for diabetes, stroke or cerebral hemorrhage, myocardial infarction or angina, gastric and duodenum diseases, kidney disease, anemia, and depression, while lower consultation rates for dyslipidemia and hypertension. The tendency of non-smoking and non-drinking was found among them. They seldom attended cancer screenings. Low-social-independent women had higher consultation rates for liver and gallbladder diseases, other digestive diseases, kidney diseases, anemia, osteoporosis, and depression. The tendency of non-drinking was the same as men. More heavy smokers were found among those aged 40–49 years, with no significant differences in other age groups. They seldom attended cancer screenings, as well as men. Conclusions In terms of current physical health, low-social-independent men have more fatal diseases. Both sexes with low social independence seldom attend cancer screenings and have an increased risk of developing progressive cancer in the future. At least in terms of non-smoking and non-drinking, they live healthier lives than the control group, and what makes low-social-independent men have various fatal diseases is still unclear.

Background: Thymic stromal lymphopoietin (TSLP) has been shown to be able to amplify Tregs. Thus, TSLP induction has the potential to induce endogenous Tregs and control autoimmunity. In the previous research, we found that a new compound named 02F04 can induce TSLP production while simultaneously activating the liver X receptor (LXR). Because LXR activation leads to a decrease in Treg, we attempted to find a 02F04-derivative, druggable lead compound with a basic skeleton that induces TSLP production without activating LXR. As the results, we found HA-7 and HA-19 and, in this study, examined the molecular mechanisms in TSLP production. Methods: A murine keratinocyte cell line PAM 212 was stimulated with HA-7 and HA-19, and then the expressions of cytokines were examined via ELISA and real-time fluorescence quantitative PCR. Results: HA-7 and HA-19 induced TSLP production but almost not the expression of TNF-α, IL-13, IL-25, and IL-33 in PAM212 cells. These compounds inhibited LXR activities. The TSLP expression induced by HA-7 and HA-19 was inhibited by the Gq/11 inhibitor YM-254890, ROCK inhibitor Y-27632, and ERK inhibitor U0126. HA-7 and HA-19 also induced the formation of stress fiber and ERK phosphorylation, which were inhibited by YM-254890 and Y-27632. Conclusions: Our findings indicated that HA-7 and HA-19 selectively induced TSLP production in PAM212 via Gq/11, Rho/ROCK and ERK pathways. Our findings also indicated that TSLP expression was differentially regulated from other cytokines, and the selective expression could be induced with low-molecular-weight compounds such as HA-7 and HA-19.

Abstract Biological disease modifying anti-rheumatic drugs (bDMARDs) show dramatic treatment efficacy in rheumatoid arthritis (RA). Long-term use of bDMARDs, however, has disadvantages such as high costs and infection risk. Therefore, a methodology is needed to predict any future RA relapse. Herein, we report a novel multi-biomarker combination which predicts relapse after bDMARDs-withdrawal in patients in remission. Forty patients with RA in remission for more than 12 months were enrolled. bDMARDs were withdrawn and they were followed monthly for the next 24 months. Fourteen patients (35%) of 40 in the cohort remained in remission at 24 months, whereas 26 (65%) relapsed at various time-points. Serum samples obtained longitudinally from patients in remission were assessed for the relapse-prediction biomarkers and index from 73 cytokines by the exploratory multivariate ROC analysis. The relapse-prediction index calculated from the 5 cytokines, IL-34, CCL1, IL-1β, IL-2 and IL-19, strongly discriminated between patients who relapsed and those who stayed in remission. These findings could contribute to clinical decision-making as to the timing of when to discontinue bDMARDs in RA treatment.

Recent clinical studies indicate that dry eye is closely associated with psychiatric disorders such as depression and anxiety. Here, we investigated whether two types of mouse dry eye models showed depressive-like behavior in forced swim and sucrose preference tests, and whether voluntary wheel-running helped ameliorate depressive states. To reproduce the dry eye models, the exorbital lacrimal glands (ELG) or exorbital and intraorbital lacrimal glands (ELG+ILG) were bilaterally excised from male C57BL/6J mice. Tear volume was persistently reduced in both models, but the ELG+ILG excision mice exhibited more severe corneal damage than the ELG excision mice. In the forced swim and sucrose preference tests, the gland excision mice showed longer immobility and shorter climbing times, and lower sucrose preference than sham-operated mice, respectively, which appeared earlier in the ELG+ILG excision mice. Wheel-running activities were significantly lower in the ELG+ILG excision mice, but not in the ELG excision mice. After short-period wheel-running, the longer immobility times and the shorter climbing times in the forced swim completely disappeared in both models. Our results suggest that dry eyes might directly cause a depressive disorder that depends on the severity and duration of the ocular surface damage, and that voluntary motor activity could help recovery from a depressive state induced by dry eye.

We report a rare case of KIT-negative extra-gastrointestinal stromal tumor, in a 40-year-old woman. Contrast-enhanced computed tomography and magnetic resonance imaging revealed a >15-cm mass of multiple cystic lesions in the greater omentum. Histopathological findings after surgery showed a sheet-like growth of stellate tumor cells from epithelial cells, cystic degeneration, and mucus-like stroma. Immunohistochemistry was positive for discovered on GIST-1 (DOG1) but negative for CD117 (c-kit).

Abstract Ossification of the posterior longitudinal ligament (OPLL) is a progressive disease. The bridging of ossified lesions to the vertebral body gradually increases, thereby decreasing the mobility of the cervical spine; thus, cervical spine function may decrease over time. However, cervical spine function in patients with cervical OPLL has not been evaluated in large prospective studies. Therefore, we conducted a prospective multicenter study to clarify whether ossification spread can influence cervical spine function and quality of life (QOL) in patients with cervical OPLL. In total, 238 patients (162 men, 76 women; mean age, 63.9 years) were enrolled from 16 institutions. Each patient underwent whole spine computed tomography and was evaluated for cervical spine function and QOL using the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). In the multivariate regression analysis, a higher neck VAS score and a larger number of bridge formations of OPLL in the whole spine were significant predictors of adverse outcomes related to cervical spine function. This is the first prospective multicenter study to reveal the impact of ossification spread on cervical spine function. These findings are important to understand the natural course of OPLL and can serve as controls when evaluating postoperative cervical spine function.

Abstract Background Breast cancer patients are known to develop brain metastasis at a relatively high frequency. However, imaging findings of brain metastases vary, and it is sometimes very difficult to distinguish these from other tumorous lesions and non-neoplastic lesions, such as cerebral hemorrhage. Meanwhile, there are various causes of cerebral hemorrhage; a major one is cerebral amyloid angiopathy (CAA). With the advancement of imaging technology, CAA-related cerebral hemorrhage can be more precisely diagnosed with magnetic resonance imaging (MRI), but definitive diagnosis of CAA can only be made based on pathological assessment. Herein, we report a case of consciousness disorder appearing during adjuvant therapy for breast cancer. We initially considered that the patient’s cerebral hemorrhage was due to a metastatic tumor, but based on excisional biopsy, she was diagnosed with CAA. Case presentation A 73-year-old Japanese woman underwent curative surgery for left breast cancer. Her disease was hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-positive invasive ductal carcinoma (pStage IIB). While receiving adjuvant treatment, she developed disorientation, and emergent imaging revealed multiple cerebral hemorrhages. There was no apparent enhancement in the cerebral parenchyma on MRI, and differential diagnosis included hemorrhage due to a metastatic tumor, intravascular large B-cell lymphoma, CAA and thrombotic intracranial bleeding. After hospitalization, the bleeding lesion enlarged, resulting in cerebral hernia, and she needed emergency drainage surgery. The tissue surrounding the hemorrhage was pathologically assessed, and she was diagnosed with CAA. Although we initially suspected the lesion to be a metastatic tumor from breast cancer, there were no tumorous cells. Conclusion Atypical MRI findings made diagnosis difficult in this case, but it should be considered for differential diagnosis when multiple cerebral hemorrhages in elderly patients are observed, especially in cases with symptoms such as transient multifocal neurological deficits and dementia.

Abstract Sarcopenia is an adverse prognostic factor for diffuse large B‐cell lymphoma. A case of diffuse large B‐cell lymphoma whose diagnosis, severity, and therapeutic effect of sarcopenia were difficult to determine owing to lymphoma cell infiltration into the psoas major and femoral bone marrow is reported. At presentation, the cross‐sectional area of left psoas major at L3 was enlarged owing to lymphoma cell infiltration; thus, sarcopenia evaluation was impossible by L3 skeletal muscle index. The patient was bedridden; thus, sarcopenia evaluation was impossible by the Asian Working Group for Sarcopenia 2019 consensus diagnostic criteria at presentation. At the terminal stage, she could not walk due to bilateral anterior thigh pain caused by lymphoma infiltration into femoral marrow; thus, sarcopenia evaluation was impossible by the Asian Working Group for Sarcopenia 2019 consensus diagnostic criteria. Although the L3 skeletal muscle index and the Asian Working Group for Sarcopenia 2019 consensus diagnostic criteria are representative sarcopenia evaluation systems, they cannot be used to evaluate sarcopenia in some diffuse large B‐cell lymphoma patients.

Abstract Three types of sacral alar fatigue fractures are elderly, postnatal, and sport-related. They are most prevalent in athletes during adulthood; there are few reports of sacral alar fatigue fractures in young athletes. The purpose of this study was to analyze sacral alar fatigue fractures in adolescent athletes. Of the 920 patients hospitalized with low back pain, 13 were diagnosed with sacral alar fatigue fractures with magnetic resonance imaging (MRI) abnormalities. We investigated age, sex, sports discipline, span from symptom onset to consultation, laterality, complication with spondylolysis, computed tomography (CT) findings, and treatment span. The average age was 14.5 years old (8-men and 5-women). The most frequent discipline was basketball. The span to consultation was 13.2 days. The number of right-side cases was 9. Seven cases were complicated by bilateral spondylolysis. MRI abnormalities were observed in all the cases. Only two patients showed abnormal findings on CT. Averagely 67 days after treatment, participants returned to their sports. Sacral alar fatigue fractures suggest that the span from onset to consultation is short. Fracture lines are often unclear on CT, and MRI is useful for diagnosis. More than half of the cases in this study were complicated by lumbar spondylolysis.

Spinal instrumentation surgery for older patients with osteoporosis is increasing. Implant loosening may occur due to inappropriate fixation in osteoporotic bone. Developing implants that achieve stable surgical results, even in osteoporotic bone, can reduce re-operation, lower medical costs, and maintain the physical status of older patients. Fibroblast growth factor-2 (FGF-2) promotes bone formation; thus, coating pedicle screws with an FGF-2–calcium phosphate (FGF-CP) composite layer is hypothesized to enhance osteointegration in spinal implants. We designed a long-term implantation pilot study that estimated the safety and bone-forming efficacy of pedicle screws coated with an FGF-CP composite layer in cynomolgus monkeys. Titanium alloy screws, either uncoated (controls) or aseptically coated with an FGF-CP composite layer, were implanted in the vertebral bodies of six female adult cynomolgus monkeys (three monkeys per group) for 85 days. Physiological, histological, and radiographic investigations were performed. There were no serious adverse events, and no radiolucent areas were observed around the screws in either group. The bone apposition rate in the intraosseous region was significantly higher in the FGF-CP group than in the controls. Moreover, as analyzed by Weibull plots, the bone formation rate of the FGF-CP group exhibited a significantly higher regression line slope than the control group. These results demonstrated that there was significantly less risk of impaired osteointegration in the FGF-CP group. Our pilot study suggests that FGF-CP-coated implants could promote osteointegration, be safe, and reduce the probability of screw loosening.

Acoustic emission (AE) source localization has been used to visualize progress failures generated in a wide variety of materials. In the conventional approaches, AE source localization algorithms assume that the AE signal is propagated as a straight line. However, it is supposed that progress failures form heterogeneity of elastic wave velocity distributions. Hence, with the conventional source localization, it is expected that the localization accuracy is reduced in heterogeneous materials since diffraction and refraction waves are generated. Thus, if the straight propagation waves are classified, conventional source localizations are performed in the heterogeneous materials. The self-organizing map (SOM) is one of the unsupervised learning methods, and the SOM has potential to classify straight propagation waves for the source localizations. However, the application of classified AE signals in source localization is not popular. If classified AE signals are applied to the time difference of arrival (TDOA) method, which is the popular localization method, it is expected that number of visualized sources are decreased because the algorithm does not consider the selection of the propagated wave. Although ray tracing has potential to localize a larger number of sources than the TDOA method, it is expected that the localized sources are less accurate in comparison with results of the TDOA method. In this study, classified waves were applied to two of the source localizations, and model tests based on pencil-lead breaks (PLBs) generating artificial AE sources were conducted to validate the performance of the source localizations with classified waves. The results of the validation confirmed that the maximum error in the TDOA method is larger in comparison with ray tracing conducted with 20 mm intervals of source candidates. Moreover, ray tracing localizes the same number of sources as the number of PLB tests. Therefore, ray tracing is expected to more practically localize AE sources than the TDOA method if classified waves are applied.

Study Design Prospective experimental study in humans. Purpose To determine whether the hybrid assistive limb (HAL) for Care Support can reduce lumbar load during a patient transfer. Overview of Literature The prevalence of work-related low back pain (LBP) among nurses is high. In particular, transferring patients poses a high risk for LBP due to the large lumbar load. Attempts to reduce the lumbar load are crucial to avoid the risk of LBP. Therefore, we investigated the effects of the HAL for Care Support. Methods Nineteen volunteers (16 men, three women) lifted a 60-kg doll from a seated position to a standing position. The first transfer was performed without the HAL for Care Support, and the second was performed with the HAL for Care Support assistive robot. We evaluated transfer performance, the visual analog scale (VAS) score for lumbar fatigue, and electromyogram analyses of the trunk and hip. Results Four participants (two men, two women) succeeded with the HAL for Care Support even though they were unable to perform the task without it. The mean lumbar fatigue VAS score for all participants without the HAL for Care Support was 62 mm, while that with it was 43 mm. With lumbar assistance from the HAL for Care Support, subjective lumbar fatigue during the transfer decreased significantly. A power analysis indicated adequate statistical power to detect a difference in the VAS score for lumbar fatigue (0.99). The activity of the left gluteus maximus alone increased significantly during transfers with the HAL for Care Support. No adverse events occurred during use of the HAL for Care Support for transfers. Conclusions The HAL for Care Support was able to reduce lumbar load in a simulated patient transfer.

The slow kinetics of the oxygen exchange reaction at the surface of air electrodes for solid oxide fuel cells must be improved to reduce their operating temperature. In this study, we use first-principles computation, based on the density functional theory, to investigate the surface morphology and oxygen vacancy formation energies of perovskite-type LaCoO3 and La0.5Sr0.5Co0.5Fe0.5O3 (LSCF5555) compounds. The cationic arrangement is optimized energetically for LSCF5555 using a genetic algorithm approach. We confirm that Sr and Co condensation occurs near the LSCF5555 surface. Significant lowering of the oxygen vacancy formation energies at the perovskite surface is indicated for both the compounds. In addition, several surface O sites in LSCF5555 exhibit lower oxygen vacancy formation energies than those in LaCoO3, which may improve the kinetics of the surface charge-transfer reaction in the LSCF-related compounds.

Abstract Background If bone union is expected, conservative treatment is generally selected for lumbar spondylolysis. However, sometimes conservative treatments are unsuccessful. We sought to determine the factors associated with failure of bony union in acute unilateral lumbar spondylolysis with bone marrow edema including contralateral pseudarthrosis. Methods This study targeted unilateral lumbar spondylolysis treated conservatively in high school or younger students. Conservative therapy was continued until the bone marrow edema disappeared on MRI and bone union was investigated by CT. We conducted a univariate analysis of sex, age, pathological stage, lesion level complicating the contralateral bone defect, lesion level, and intercurrent spina bifida occulta, and variables with p

Background: The pathogenesis of articular- and bursal-sided partial-thickness rotator cuff tears (PTRCTs) is considered to be different, and associated lesions with PTRCTs need to be examined. Methods: The current study consisted of 76 shoulders of 73 patients (27 men, 46 women, 64.0 ± 8.3 years old) who underwent mini-open repair after conversion to full-thickness tears for either articular side (group A; n = 56) or bursal side (group B; n = 20) PTRCT with at least a 2-year follow-up. Clinical outcomes and their images were compared between the groups. Plain radiographs were used with the arm passively elevated in maximum elevation to assess restriction of glenohumeral motion. Results: The retear rate was not significantly different between the groups. Both groups showed significant improvement in functional scores at the final follow-up. Patients in group A showed a higher incidence of preoperative fibrosis in the rotator interval (69.6% vs. 35.0%, respectively; P = .006) and a lower incidence of an acromial spur (7.1% vs. 35.0%, respectively; P = .008) compared with group B. Plain radiographs with arm elevation showed restriction of glenohumeral movement in 49 of 76 shoulders (64.5%) preoperatively, including 36 of the 46 shoulders with fibrosis and 13 of the other 30 shoulders. Conclusion: Both articular- and bursal-sided PTRCTs showed significant functional improvements after surgery. The articular-sided tears had a lower incidence of an acromial spur, but had a higher incidence of fibrosis in the rotator interval, which led to a limitation in glenohumeral motion.

Abstract Background Sarcopenia is a syndrome characterized by progressive and systemic decreases in skeletal muscle mass and muscle strength. The influence or prognosis of various liver diseases in this condition have been widely investigated, but little is known about whether sarcopenia and/or muscle mass loss are related to minimal hepatic encephalopathy (MHE). Methods To clarify the relationship between MHE and sarcopenia and/or muscle mass loss in patients with liver cirrhosis. Methods Ninety-nine patients with liver cirrhosis were enrolled. MHE was diagnosed by a neuropsychiatric test. Skeletal mass index (SMI) and Psoas muscle index (PMI) were calculated by dividing skeletal muscle area and psoas muscle area at the third lumbar vertebra by the square of height in meters, respectively, to evaluate muscle volume. Results This study enrolled 99 patients (61 males, 38 females). MHE was detected in 48 cases (48.5%) and sarcopenia in 6 cases (6.1%). Patients were divided into two groups, with or without MHE. Comparing groups, no significant differences were seen in serum ammonia concentration or rate of sarcopenia. SMI was smaller in patients with MHE (46.4 cm2/m2) than in those without (51.2 cm2/m2, P = 0.027). Similarly, PMI was smaller in patients with MHE (4.24 cm2/m2) than in those without (5.53 cm2/m2, P = 0.003). Skeletal muscle volume, which is represented by SMI or PMI was a predictive factor related to MHE (SMI ≥ 50 cm2/m2; odds ratio 0.300, P = 0.002, PMI ≥ 4.3 cm2/m2; odds ratio 0.192, P = 0.001). Conclusions Muscle mass loss was related to minimal hepatic encephalopathy, although sarcopenia was not. Measurement of muscle mass loss might be useful to predict MHE.

Background: Non-alcoholic liver disease is of increased concern and contributing to economic burdens not only in developing countries but in developed countries as well. Identifying the biomarker of early diagnosis and early intervention approaches for non-alcoholic liver disease is unmet and required further investigation. Although the alpha-ketoglutarate (α-KG) is recently proposed to be a potential biomarker in differentiating patients with obesity from those with non-alcoholic liver disease, how α-ketoglutatate is involved in the fatty liver progression is not clear. Methods: A high-fat diet (HFD) feeding animal model, liver functional assays, and molecular approaches were adopted to clarify the impact of α-KG in fatty liver progression. Results: In the current study, it was found that dietary α-KG would inhibit weight gain in male and female mice fed with a normal chew or HFD. HFD feeding caused fatty liver in male mice, but α-KG treatment could substantially inhibit hepatic steatosis progression. Biochemical studies revealed the possible linkage of α-KG protective functions to lipid metabolism. Further analysis identified the important role of peroxisome proliferator-activated receptors in beneficial α-KG-mediated effects on fatty liver progression. Conclusions: The current study demonstrates the therapeutic potential of α-KG and how it may be used, via dietary supplementation, as a preventive intervention for non-alcoholic liver disease in obese patients.

Background: Resistance to endocrine therapy has been a major obstacle in the management of hormone receptor (HR)-positive metastatic breast cancer (MBC). Meanwhile, a number of treatments are available to such patients, and physicians often encounter difficulties in choosing the most appropriate treatments for individual patients. The combination of CDK 4/6 inhibitors (CDKi) and endocrine therapy has now become a standard treatment for HR-positive and human epidermal growth factor receptor 2 (HER2)-negative MBC. However, no predictive markers for CDKi-based treatments have been established. Considering their side effects and the financial burden on patients, identifying such markers is crucial. Methods: Clinicopathological features of 107 patients with HR-positive HER2-negative MBC, who received CDKi-based treatments at our institution were retrospectively investigated. HR status in distant metastatic lesions and immunocompetent cells in peripheral blood were also studied. Results: Progression-free survival (PFS) was significantly shorter in patients whose primary tumour was high grade ( P = 0.016) or high neutrophil-to-lymphocyte ratio (NLR) at baseline ( P = 0.017). Meanwhile, there were no differences in other factors, such as expression levels of hormone receptors. Patients whose metastatic lesions were of low tumour grade or high Ki67 labelling index had longer PFS, and such trends were more obvious than primary lesions. Conclusion: Our data indicate that tumour grade in primary lesion and NLR are potential predictive factors for CDKi-based treatments. Moreover, pathological assessment of metastatic lesions might also be useful.