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With the topical focus on the prevention of and countermeasures for frailty, scattered studies have subdivided its social elements and aspects as "social frailty." While the concepts and definition of "social frailty" are yet to be established, the purpose of using the term is to capture the attention of professionals using the social aspects of frailty to support older adults. The goal is to increase healthy life expectancy by recognizing that social factors are unlikely to pose a risk of functional decline in isolation, but may increase such a decline when combined with other factors. At feasible scopes of intervention, ways to address these factors should be pursued. Although social aspects are often expressed by frail people, or social factors with complex processes that can cause functional decline, there is no unified definition or indicator of social frailty. Further research and discussion are needed to clarify its academic significance and usefulness for disability prevention. Recognizing this, when the Japanese Socio-Gerontological Society's Study Committee on "Social Frailty" published its recommendations, it suggested that when using the term "social frailty" we should specify the significance of its use; consider the comprehensiveness of frailty; be mindful of the interrelationship of social activities and other social aspects; and consider environmental conditions such as a person's values, preferences and life course, social norms, systems, and government policies. High-risk individuals may need multidisciplinary approaches delivered by various professionals, including clinicians, in realizing a life in line with their unique values and preferences. In such cases, it is necessary to understand the background and process that led to frailty, from physical, psychological, and social perspectives, referring to the abovementioned four points. The introduction of social aspects as one of the assessment frameworks can significantly bridge the gap between medical care and the community. Geriatr Gerontol Int 2022; 22: 991-996.

We aimed to verify antitumor effects of zinc acetate on hepatocellular carcinoma (HCC) in vitro. Five HCC cell lines (HepG2, Hep3B, Huh7, HLE and Alex) were used to evaluate the antitumor effects of zinc acetate. Cell viability was determined by the Cell Counting Kit-8 assay. The cell-cycle alteration was evaluated by a flow cytometric analysis and the detection of cell cycle-related proteins. Apoptosis was determined based on the caspase-cleaved cytokeratin 18 (cCK18) levels. The microRNAs (miRNAs) related to an antitumor effect of zinc acetate were identified using microarrays. Zinc acetate significantly inhibited the proliferation of HCC cells in a dose-dependent manner. The treatment with zinc acetate resulted in significantly increased cCK18 levels in the supernatant and enhanced the expression of heme oxygenase-1 (HO-1) in HCC cells. The flow cytometric analysis revealed an increase of HCC cells in the S and G

Although fasciculation on muscle ultrasonography (MUS) is useful in diagnosing amyotrophic lateral sclerosis (ALS), its applicability to early diagnosis remains unclear. We aimed to develop and validate diagnostic models especially beneficial to early-stage ALS via machine learning.We investigated 100 patients with ALS, including 50 with early-stage ALS within 9 months from onset, and 100 without ALS. Fifteen muscles were bilaterally observed for 10 s each and the presence of fasciculations was recorded. Hierarchical clustering and nominal logistic regression, neural network, or ensemble learning were applied to the training cohort comprising the early-stage ALS to develop MUS-based diagnostic models, and they were tested in the validation cohort comprising the later-stage ALS.Fasciculations on MUS in the brainstem or thoracic region had high specificity but limited sensitivities and predictive profiles for diagnosis of ALS. A machine learning-based model comprising eight muscles in the four body regions had a high sensitivity (recall), specificity, and positive predictive value (precision) for both early- and later-stage ALS patients.We developed and validated MUS-fasciculation-based diagnostic models for early- and later-stage ALS.Fasciculation detected in relevant muscles on MUS can contribute to the diagnosis of ALS from the early stage.

To measure the neuromagnetic fields of carpal tunnel syndrome patients after electrical digital nerve stimulation and evaluate median nerve function with high spatial resolution.A superconducting quantum interference device magnetometer system was used to record neuromagnetic fields at the carpal tunnel after electrical stimulation of the middle digital nerve in 10 hands of nine patients with carpal tunnel syndrome. The patients were diagnosed based on symptoms (numbness, tingling, and pain) supported by a positive Phalen or Tinel sign. A novel technique was applied to remove stimulus-induced artifacts, and current distributions were calculated using a spatial filter algorithm and superimposed on X-ray.In 6 of the 10 hands, the amplitude of the inward current waveform attenuated to70% or the nerve conduction velocity was40 m/s. The results of conventional nerve conduction studies were normal for two of these six hands. All four hands that could not be diagnosed by magnetoneurography had severe carpal tunnel syndrome superimposed on peripheral neuropathy secondary to comorbidities.Technical improvements enabled magnetoneurography to noninvasively visualize the electrophysiological nerve activity in carpal tunnel syndrome patients.Magnetoneurography may have the potential to contribute to the detailed diagnosis of various peripheral nerve disorders.

To improve the clinical results of lateral ulnar collateral ligament (LUCL) reconstruction of the elbow joint, better understanding of the anatomy of the aponeuroses and joint capsule could be relevant. This study considers the previously described anatomy of the LUCL in relation to the related aponeuroses and joint capsule rather than as a discrete ligament. We hypothesized that the deep aponeuroses of the superficial extensor muscles and supinator form a relevant portion of the joint capsule previously defined as the LUCL.Twenty-four elbows (12 right) from 21 embalmed cadavers (age at the time of death, 54 to 99 years) were included in the study. Twenty elbows were studied macroscopically and 4, histologically. The joint capsule was detached from the bones, and local thickness was quantitatively analyzed using micro-computed tomography (micro-CT).The supinator aponeurosis and joint capsule intermingled to form a thick membrane (mean and standard deviation, 4.8 ± 1.2 mm), which we termed "the capsulo-aponeurotic membrane." It was thicker than the anterior (1.3 ± 0.4 mm) and posterior (2.5 ± 0.9 mm) parts of the capsule of the humeroradial joint (p0.001). The capsulo-aponeurotic membrane had a wide attachment on the distal part of the extensor digitorum communis and extensor digiti minimi (EDC/EDM) origin of the humerus, the lateral part of the coronoid process, and the posterior part of the radial notch of the ulna. The humeral attachment had a fibrocartilaginous structure. The deep aponeuroses of the EDC and extensor carpi ulnaris (ECU) were connected to the capsulo-aponeurotic membrane.The capsulo-aponeurotic membrane was composed of the supinator aponeurosis and joint capsule and was attached to the lateral epicondyle of the humerus, radial side of the coronoid process, and posterior part of the radial notch on the ulna. The entire structure appeared identical to the commonly defined lateral collateral ligament. The most posterior part was connected to the EDC and ECU aponeuroses, which is commonly labeled the LUCL but does not exist as a discrete ligament.Consideration of the accurate anatomy of the extensive attachment of the capsulo-aponeurotic membrane could provide useful clues for improvement in techniques of LUCL reconstruction and lateral epicondylitis pathology.

Drug resistance to molecular targeted agents, such as lenvatinib, is an important issue. The aim of this study was to explore the mechanism of lenvatinib resistance and to investigate potential drugs that may improve the treatment of lenvatinib-resistant (LR) hepatocellular carcinoma (HCC).LR cells were developed by long-term culture under lenvatinib exposure. We analyzed the biological characteristics of LR cells in vitro, and investigated the antitumor effects and endogenous mechanisms of cisplatin in LR cells.The proliferative potential of LR cells was enhanced by activation of ERK signaling and changes in several miRNAs. Cisplatin inhibited cell proliferation of LR cells and induced G2/M cell cycle arrest. Furthermore, cisplatin triggered the DNA damage response, via the ATM/ATR-Chk1/Chk2 signaling pathway.Proliferation of LR cells was induced upon ERK signaling activation. Cisplatin exerted antitumor effects in LR cells and was involved in the regulation of miRNAs associated with drug resistance.

L-type neutral amino acid transporter 1 (LAT1) is a heterodimeric membrane transport protein involved in neutral amino acid transport. LAT1 is highly expressed in various malignant solid tumors and plays an essential role in cell proliferation. However, its role in malignant lymphoma remains unknown. Here, we evaluated LAT1 expression level in tissues from 138 patients with Non-Hodgkin lymphoma (NHL). Overexpression of LAT1 was confirmed in all types of NHL and we found that there is a significant correlation between the level of LAT1 expression and lymphoma grade. The LAT1 expression was higher in aggressive types of lymphomas when compared with static types of lymphomas, suggesting that active tumor proliferation requires nutrient uptake via LAT1. The expression level of LAT1 was inversely correlated with patients’ survival span. Furthermore, pharmacological inhibition of LAT1 by a specific inhibitor JPH203 inhibits lymphoma cell growth. In conclusion, our study demonstrated that LAT1 expression can be used as a prognostic marker for patients with NHL and targeting LAT1 by JPH203 can be a novel therapeutic modality for NHL.

Background Cervical myelopathy is a progressive disease, and early detection and treatment contribute to prognosis. Evaluation of cervical intervertebral instability by simple X-ray is used in clinical setting and the information about instability is important to understand the cause of myelopathy, but evaluation of the intervertebral instability by X-ray is complicated. To reduce the burden of clinicians, a system that automatically measures the range of motion was developed by comparing the flexed and extended positions in the lateral view of a simple X-ray of the cervical spine. The accuracy of the system was verified by comparison with spine surgeons and residents to determine whether the system could withstand actual use. Methods An algorithm was created to recognize the four corners of the vertebral bodies in a lateral cervical spine X-ray image, and a system was constructed to automatically measure the range of motion between each vertebra by comparing X-ray images of the cervical spine in extension and flexion. Two experienced spine surgeons and two residents performed the study on the remaining 23 cases. Cervical spine range of motion was measured manually on X-ray images and compared with automatic measurement by this system. Results Of a total of 322 cervical vertebrae in 46 images, 313 (97%) were successfully estimated by our learning model. The mean intersection over union value for all the 46-test data was 0.85. The results of measuring the CRoM angle with the proposed cervical spine motion angle measurement system showed that the mean error from the true value was 3.5° and the standard deviation was 2.8°. The average standard deviations for each measurement by specialist and residents are 2.9° and 3.2°. Conclusions A system for measuring cervical spine range of motion on X-ray images was constructed and showed accuracy comparable to that of spine surgeons. This system will be effective in reducing the burden on and saving time of orthopedic surgeons by avoiding manually measuring X-ray images. Trial registration Retrospectively registered with opt-out agreement.

AIM The homebound status is associated with unhealthy factors and physical disability. However, the prevalence of those who may be at an earlier stage of the homebound status ("semi-homebound") is unclear. This study thus examines the prevalence of semi-homebound individuals and identifies the associated physical, psychological, and social factors. METHODS A cross-sectional study invited 1,157 participants aged 65 years and more in rural Japan. The mean age was 74.7 ± 6.8. The survey questionnaire accounted for different parameters, such as age, sex, homebound status, morbidity, instrumental activities of daily living (IADL), and mental health. Ordinal regression analysis examined participants' homebound status; socio-demographic characteristics; and physical, psychological, and social variables. RESULTS The prevalence of the homebound status was 0.11 (95%CI = 0.99-0.13), and the semi-homebound status was 0.30 (95%CI = 0.28-0.33). In the multivariable analysis, the homebound status was negatively associated with IADL (p

Study design Cross-sectional study. Objective To develop a binary classification model for cervical myelopathy (CM) screening based on a machine learning algorithm using Leap Motion (Leap Motion, San Francisco, CA, USA), a novel non-contact sensor device. Summary of background data Progress of CM symptoms are gradual and cannot be easily identified by the patients themselves. Therefore, screening methods should be developed for patients of CM before deterioration of myelopathy. Although some studies have been conducted to objectively evaluate hand movements specific to myelopathy using cameras or wearable sensors, their methods are unsuitable for simple screening outside hospitals because of the difficulty in obtaining and installing their equipment and the long examination time. Methods In total, 50 and 28 participants in the CM and control groups were recruited, respectively. The diagnosis of CM was made by spine surgeons. We developed a desktop system using Leap Motion that recorded 35 parameters of fingertip movements while participants gripped and released their fingers as rapidly as possible. A support vector machine was used to develop the binary classification model, and a multiple linear regression analysis was performed to create regression models to estimate the total Japanese Orthopaedic Association (JOA) score and the JOA score of the motor function of the upper extremity (MU-JOA score). Results The binary classification model indexes were as follows: sensitivity, 84.0%; specificity, 60.7%; accuracy, 75.6%; area under the curve, 0.85. The Spearman's rank correlation coefficient between the estimated score and the total JOA score was 0.44 and that between the estimated score and the MU-JOA score was 0.51. Conclusion Our binary classification model using a machine learning algorithm and Leap Motion could classify CM with high sensitivity and would be useful for CM screening in daily life before consulting doctors and telemedicine.Level of Evidence: 3.

Human language is a multi-componential function comprising several sub-functions each of which may have evolved in other species independently of language. Among them, two sub-functions, or modules, have been claimed to be truly unique to the humans, namely hierarchical syntax (known as “Merge” in linguistics) and the “lexicon.” This kind of species-specificity stands as a hindrance to our natural understanding of human language evolution. Here we challenge this issue and advance our hypotheses on how human syntax and lexicon may have evolved from pre-existing cognitive capacities in our ancestors and other species including but not limited to nonhuman primates. Specifically, we argue that Merge evolved from motor action planning, and that the human lexicon with the distinction between lexical and functional categories evolved from its predecessors found in animal cognition through a process we call “disintegration.” We build our arguments on recent developments in generative grammar but crucially depart from some of its core ideas by borrowing insights from other relevant disciplines. Most importantly, we maintain that every sub-function of human language keeps evolutionary continuity with other species’ cognitive capacities and reject a saltational emergence of language in favor of its gradual evolution. By doing so, we aim to offer a firm theoretical background on which a promising scenario of language evolution can be constructed.

Anti-inflammatory drugs, such as aspirin, have attracted attention as anticancer agents that can be applied to standard chemotherapy for pancreatic cancer. This study aimed to examine the antitumour effects and possible fundamental mechanisms of aspirin in pancreatic cancer cells.We appraised the antitumour effects of aspirin on cell proliferation and tumour growth, cell cycle distribution, apoptosis, signalling pathways, angiogenesis-related proteins, and phosphorylated receptor tyrosine kinases (p-RTKs) and identify miRNAs associated with its antitumour effects.Aspirin inhibited cell proliferation in pancreatic cancer cell lines and induced GAspirin inhibited the proliferation of pancreatic cancer cells and induced cell cycle arrest. Aspirin also inactivated GSK-3β but not the p38 MAPK pathway. Thus, aspirin may be used in combination with chemotherapeutic agents for pancreatic cancer.

Dyslipidemia is considered an essential component of the pathological process of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disease. Although TAR DNA Binding Protein 43 kDa (TDP-43) links both familial and sporadic forms of ALS and cytoplasmic aggregates are a hallmark of most cases of ALS, the molecular mechanism and the in vivo relation of ALS dyslipidemia with TDP-43 have been unclear. To analyze the dyslipidemia-related gene expression by TDP-43, we performed expression microarray and RNA deep sequencing (RNA-Seq) using cell lines expressing high levels of TDP-43 and identified 434 significantly altered genes including sterol regulatory element-binding protein 2 (SREBP2), a master regulator of cholesterol homeostasis and its downstream genes. Elevated TDP-43 impaired SREBP2 transcriptional activity, leading to inhibition of cholesterol biosynthesis. The amount of cholesterol was significantly decreased in the spinal cords of TDP-43-overexpressed ALS model mice and in the cerebrospinal fluids of ALS patients. These results suggested that TDP-43 could play an essential role in cholesterol biosynthesis in relation to ALS dyslipidemia., 筋萎縮性側索硬化症（ALS）病因タンパク質TDP-43は コレステロール合成を制御する --ALSにおける脂質代謝異常と栄養療法の分子メカニズム探索--. 京都大学プレスリリース. 2022-05-16., ALS-related protein TDP-43 regulates cholesterol synthesis --Insight for molecular mechanisms of lipid metabolism and nutritional therapy in ALS--. 京都大学プレスリリース. 2022-05-20.

Hepatitis B virus (HBV) infection is a major public health problem worldwide. The study aimed to evaluate the efficacy of pegylated interferon (Peg-IFN) alfa-2a treatment for seroclearance of HBs antigen (HBsAg) in HBe antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. This retrospective study investigated 16 HBeAg-negative CHB patients who received Peg-IFN alfa-2a weekly for 48 weeks. Thereafter, the patients were followed-up for 48 weeks after the end of therapy. The following criteria were also used for inclusion: HBV-DNA

The management of postoperative bleeding, after gastric endoscopic submucosal dissection (ESD), has become particularly important because of the recent increase in antithrombotic use. Endoscopic shielding with polyglycolic acid (PGA) sheets has been shown to be effective. However, shrinkage and early displacement of the sheet remain challenges. This study aimed to determine the efficacy and safety of our developed method, named wafer paper and ring-mounted PGA sheet (WaRP).Twenty-four patients with antithrombotic uptake who underwent the WaRP method following gastric ESD were retrospectively examined. This involved the delivery of a PGA sheet wrapped in wafer paper with ring-thread, and its fixation on the gastric floor using hemoclips. The primary outcome was the technical success rate of the WaRP, and several secondary outcomes were evaluated.The technical success rate of WaRP was 100%. The procedure lasted a mean of 10.5 min (SD 6.7 min). The prevalence of complete retention at follow-up endoscopy was 83.3% (20/24). There were no WaRP-associated complications, but post-ESD hemorrhage occurred in two patients undergoing hemodialysis (8.3%).The WaRP method is a simple and reliable means of PGA sheet delivery and placement that reduces the incidence of post-ESD hemorrhage.

Aim To maintain the frequency of going out and to improve homebound status among older adults, specific barriers need to be identified. Hence, this study developed a scale to measure barriers to going out. Methods A preliminary study was carried out to collect items for the scale. We conducted semi-structured interviews with five homebound older adults, and created 14 items as a draft barrier scale. The main study included 2273 older adults and their cohabitating family members in rural Japan. For older adults, the questions included demographic characteristics, responses to the draft scale and variables to examine its validity. For family members, the questions included demographic characteristics, their relationship with the older adult and their assessment of their older relative's willingness to go out. We used data from 892 pairs for our analysis. Results We selected nine items through the criterion group strategy, and confirmed the unidimensional structure of the scale through factor analysis. The results showed significant relationships between the scale and older adults' self-efficacy about going out, their health locus of control, the frequency of going out and their reluctance to go out as assessed by family members. We carried out a receiver operating characteristic analysis to determine the scale's cut-off point. Our multivariate analysis showed that the scale had a significantly stronger association with homebound status than with other variables. Conclusion We developed a highly reliable and valid scale on barriers to going out among community-dwelling older adults and confirmed its usability. Geriatr Gerontol Int 2021; 21: 238-244.

Cholangiocarcinoma is the most common biliary duct malignancy and the second most common primary liver cancer, accounting for 10‑20% of hepatic malignancies. With high mortality and poor prognosis, the 5‑year survival rate of cholangiocarcinoma is only 10%. A previous study demonstrated a significant association between aspirin use and a decreased risk of cholangiocarcinoma. However, the effect of aspirin on cholangiocarcinoma remains unknown. Therefore, the aim of the present study was to investigate the effects of aspirin on cholangiocarcinoma in vitro and in vivo. Three cholangiocarcinoma cell lines were used to analyze the effect of aspirin on cell proliferation, cell cycle progression, apoptosis, and the regulation of microRNAs. MicroRNAs are known to regulate the development and progression of various types of cancer. An HuCCT‑1 xenograft model was used for the in vivo study. It was determined that aspirin inhibited the proliferation of human cholangiocarcinoma cells (except TKKK cells). Aspirin induced cell cycle arrest in the G0/G1 phase and regulated cell‑cycle related proteins in cholangiocarcinoma cells (HuCCT‑1 cells) but did not induce apoptosis. The expression of miR‑340‑5p was significantly upregulated after treatment, and overexpression of miR‑340‑5p inhibited the proliferation of HuCCT‑1 cells and decreased the levels of cyclin D1. TKKK cells had low miR‑340‑5p expression, which may explain why aspirin had no effect on their proliferation. In vivo, aspirin reduced the growth of xenografted tumors. In conclusion, the present study indicated that aspirin partially inhibited cholangiocarcinoma cell proliferation and tumor growth by inducing G0/G1 phase cell cycle arrest, potentially through the miR‑340‑5p/cyclin D1 axis.

Background and aim Direct-acting antiviral (DAA) therapies have been proven to be highly effective for the eradication of hepatitis C virus (HCV) without resistance-associated substitutions (RASs). However, even in cases with no detected RASs, treatment sometimes fails, suggestive of the existence of some host-related factors involved in HCV eradication by DAAs. To explore such factors, we analyzed the serum microRNAs (miRNAs) of patients who received DAA treatment. Methods The serum miRNA expression levels of 39 patients with chronic HCV infection without any detectable RASs, who achieved sustained virological response with asunaprevir/daclatasvir or grazoprevir/elbasvir therapy, were investigated cyclopedically, using oligonucleotide microarrays. The effects of specific miRNAs on the replication of HCV were measured in the HCV genomic replicon containing Huh-7 hepatoma cells. Results Along with the disappearance of HCV, the expression quantiles of 16 miRNAs in the asunaprevir/daclatasvir group and 18 miRNAs in the grazoprevir/elbasvir group showed a tendency to increase or decrease. Among these molecules, adjustments for multiple testing yielded a significant differential expression at a false discovery rate of less than 5% for only one molecule, hsa-miR-762. Its expression quantile increased after HCV exclusion in all patients who had achieved sustained virological response. Quantitative polymerase chain reaction analysis validated a significant increase in the serum hsa-miR-762 after disappearance of HCV. On the contrary, hsa-miR-762 was decreased in the relapse and breakthrough of HCV in DAA failures. Transfection of hsa-miR-762 into cultured HCV-infected hepatocytes significantly decreased HCV-RNA replication. Conclusion These data suggest that hsa-miR-762 is one of the host factors participating in HCV exclusion by DAA therapy.

AIM The aim of this study was to determine whether oral L-carnitine administration reduces the blood ammonia concentration and number of hospital admissions for hepatic encephalopathy in patients with advanced cirrhosis. METHODS Of 68 patients with hepatic encephalopathy treated with oral L-carnitine supplementation from April 2013 to March 2016, we enrolled 19 patients who had received full standard treatment. We analyzed blood ammonia concentration, number of hospital admissions, and prognosis to determine how effective L-carnitine was in achieving mid-term to long-term suppression of recurrent hepatic encephalopathy. RESULTS Median blood ammonia concentrations at the start, 1 week, 12 weeks, 24 weeks, and 48 weeks were 159, 79, 75, and 82 μg/dL, respectively. Blood ammonia concentrations 12 week, 24 weeks, and 48 weeks after L-carnitine administration were significantly lower than those at the start (P

A 65-year-old woman with spinocerebellar ataxia presented with generalized seizures due to subcortical hemorrhaging. Magnetic resonance imaging (MRI) revealed obstruction of the superior sagittal sinus. Despite treatment, she became comatose. MRI newly revealed subdural fluid collection and descent of the brainstem. Her history indicated a recent fall, prompting additional studies, which revealed lumbar fracture and cerebrospinal fluid (CSF) leaks. We performed an epidural blood patch, and her consciousness was fully restored in one month. This is the first report of cerebral venous thrombosis with CSF leaks in the lumbar region due to a fall injury.

The radioulnar ligaments are the major stabilizers of the distal radioulnar joint under dynamic loading; however, anatomical detail regarding their attachment on the middle and distal thirds of the styloid process of the ulna remains unclear. Because previous anatomical studies included only old cadavers, their anatomical findings might not reflect the morphological features of younger and healthy specimens. This study investigated the anatomical features of the distal ulna, particularly the styloid process, to determine the attachment of the radioulnar ligaments to the styloid process and verified their direction and attachment to the styloid process in younger and healthy donors using magnetic resonance imaging (MRI). We investigated the morphological features of the distal ulna of 12 cadaveric wrists using micro‐computed tomography (micro‐CT). We also visualized and measured the distribution of the cortical bone thickness. We histologically analyzed three specimens in the axial plane and macroscopically analyzed seven specimens to examine the attachment of the radioulnar ligaments to the styloid process. In addition, we evaluated five wrists from living volunteers using 3.0 Tesla MRI. The distal ulna has a ridge on the dorsoradial aspect of the styloid process that corresponds to the attachment of the radioulnar ligaments. Micro‐CT images after data processing revealed that the cortical thickness of the dorsoradial quadrant was thicker than that of the other quadrant at the proximal slice of the styloid process (p, We observed that the styloid process of the distal ulna had a ridge on its dorsoradial aspect, corresponding to the chondral‐apophyseal entheses of the radioulnar ligaments. The directions of the radioulnar ligaments were sterically intersected, which may better satisfy both slipping stability and rotational mobility.

Background Postmenopausal women are at risk of fall and fracture with the physical decline. Distal radius fracture (DRF) is considered as the primary fragility fracture, and women with this fracture showed poor results in the usual Timed Up-and-Go (TUG) test, indicating a decline in balance and physical ability. The detailed physical characteristics of female DRF patients have not been extensively examined. Research question Is the novel laser TUG system able to detect and analyze the detailed gait characteristics in patients with DRF whose physical ability has tended to decline? Methods In this cross-sectional case control study, the gait characteristics of 32 female patients with DRF who had undergone surgery were evaluated at 2 weeks postoperatively with a laser TUG system to analyze the detailed leg motion during normal TUG test. Forty-three age- and sex-matched non-fractured women were evaluated by the laser TUG system as controls. Lifestyle and present illness were corrected at the time of TUG measurement. Detailed data during laser TUG in both groups were compared statistically, and odds ratio and thread shod of the fracture was elucidated through a logistic regression analysis. Results DRF patients showed slower speed and had to do more steps to complete the TUG test. Furthermore, asymmetric trajectory and significantly further distance from the marker were observed. Thirteen steps to complete the TUG test was the thread shod of DRF. Significance Detailed gait characteristics of patients with DRF were detected by the laser TUG system. The gait decline and abnormality could be one of the reasons of consecutive fragility fracture. To prevent secondary fragility fractures, this system can be useful for screening.

Background and Aims: Endoscopic submucosal dissection (ESD) seems to be a reasonable option for gastrointestinal subepithelial lesions (SELs) localized within the submucosa. Indications for ESD include small neuroendocrine tumors (NETs) and indeterminate SELs. However, the prospective data regarding ESD and surveillance remain unclear. This study was performed to prospectively investigate the outcomes of ESD, including organ-specific outcomes and the mid-term prognosis. Methods: This prospective multicenter study included 57 patients who underwent ESD for SELs localized within the submucosa [definite NETs (n = 42) and indeterminate SELs (n = 15)]. The efficacy and safety of ESD were evaluated in the whole cohort and in subgroups (NETs and indeterminate SELs). All patients were followed up. Results: The rates of en bloc resection, curative resection, and complications were 98.2%, 66.7%, and 7.7% for the overall population (n=57); 100%, 61.9%, and 2.4% for NETs (n=42); and 93.3%, 80.0%, and 20.0% for indeterminate SELs (n=15), respectively. The rates of curative resection for NETs were poorer in the stomach (20%, n=5) and duodenum (33%, n=3) than in the rectum (71%, n=34). Including 11 of 16 patients with NETs who underwent a conservative approach resulting in non-curative resection, no patients developed tumor recurrence during the follow-up period (median, 24.5 months; range, 1–60 months). ESD followed by surveillance demonstrated acceptable mid-term outcomes for non-curative NETs. Conclusions: ESD can be an efficient therapy for SELs localized within the submucosa. However, gastric and duodenal ESD for NETs may be limited in terms of its curative and technical aspects. Clinicians should be aware of the potential complications of ESD for indeterminate SELs.

Hepatitis B virus (HBV)-related hepatocarcinogenesis is not necessarily associated with the liver fibrotic stage and is occasionally seen at early fibrotic stages. MicroRNAs (miRNAs) are essentially 18- to 22-nucleotide-long endogenous noncoding RNAs. Aberrant miRNA expression is a common feature of various human cancers. The aberrant expression of specific miRNAs has been shown in hepatocellular carcinoma (HCC) tissue compared with nontumor tissue. Thus, we examined targetable miRNAs as a potential new biomarker related to the high risk of HBV-related hepatocarcinogenesis, toward the prevention of cancer-related deaths. HCC tissue samples from 29 patients who underwent hepatectomy at our hospital in 2002–2013 were obtained. We extracted the total RNA and analyzed it by microRNA array, real-time RT-PCR, and three comparisons: 1) HBV-related HCC and adjacent nontumor tissue, 2) HCV-related HCC and adjacent nontumor tissue, and 3) non-HBV-, non-HCV-related HCC and adjacent nontumor tissue. We also performed a functional analysis of miRNAs specific for HBV-related HCC by using HBV-positive HCC cell lines. MiR-210-3p expression was significantly increased only in the HBV-related HCC tissue samples. MiR-210-3p expression was upregulated, and the levels of its target genes were reduced in the HBV-positive HCC cells. The inhibition of miR-210-3p enhanced its target gene expression in the HBV-positive HCC cells. In addition, miR-210-3p regulated the HBx expression in HBV-infected Huh7/NTCP cells. The enhanced expression of miR-210-3p was detected specifically in HBV-related HCC and regulated various target genes, including HBx in the HBV-positive HCC cells. MiR-210-3p might, thus, be a new biomarker for the risk of HBV-related HCC. NEW & NOTEWORTHY Our present study demonstrated that miR-210-3p is the only microRNA with enhanced expression in HBV-related HCC, and the enhanced expression of miR-210-3p upregulates HBx expression. Therefore, miR-210-3p might be a pivotal biomarker of HBV-related hepatocarcinogenesis, and the inhibition of miR-210-3p could prevent inducing hepatocarcinogenesis related to HBV infection.

This study aims to identify and validate a gray matter volume network in patients with Alzheimer's disease (AD).To identify a disease-related network, a principal component analysis-based algorithm, Scaled Subprofile Model, was applied to gray matter volume data derived from structural T1-weighted magnetic resonance imaging of the training sample that consisted of nine patients with AD (women, four; dementia, seven; mild cognitive impairment, two; age, 66.7 ± 8.8 [mean ± SD] years) with positiveA significant network from the training sample, for which subject expression differed between the groups (permutation test, P = 0.006; sensitivity and specificity, 100%; area under the curve, 1), was identified. This network was represented by the principal components 1, 2, and 3 and showed a relative decrease in the inferior parietal lobule including angular gyrus, inferior temporal gyrus, premotor cortex, amygdala, hippocampus, and precuneus. It significantly differed between the groups with a sensitivity, specificity, and area under the curve of 83%, 91%, and 0.85, respectively, in the validation sample (P = 0.003).An AD-related gray matter volume network that captured relevant regions was identified in amyloid positron emission tomography-positive patients and validated in an independent sample.

To determine the pathogenesis of trapeziometacarpal (TMC) joint instability, which leads to osteoarthritis, we investigated the anatomical relationships among the surrounding ligaments, muscles (first dorsal interosseous [FDI] and opponens pollicis [OPP]), and joint capsule. We examined the bone morphology and cortical bone thickening in 25 cadaveric thumbs using micro-computed tomography and performed macroscopic and histological analyses. The dorsal trapezium had a tubercle with cortical bone thickening, corresponding to the attachment of the FDI aponeurosis intermingled with the joint capsule. Radially, the thin joint capsule was observed to underlie the muscular part of the OPP. Therefore, the dorsal ligaments, which have been previously considered static stabilizers, could be interpreted as parts of the capsuloaponeurotic complex consisting of the FDI aponeurosis and joint capsule. In the radial aspect, muscular OPP activation may be essential for TMC joint stabilization. Our findings may contribute to the appropriate management of TMC osteoarthritis.

We examined the association between serum miRNA (-192-5p, -122-3p, -320a and -6126-5p) levels and the efficacy of pegylated interferon (Peg-IFN) monotherapy for chronic hepatitis B (CHB) patients. We enrolled 61 CHB patients treated with Peg-IFNα-2a weekly for 48 weeks, of whom 12 had a virological response (VR) and 49 did not VR (non-VR). A VR was defined as HBV DNA < 2,000 IU/ml, hepatitis B e antigen (HBeAg)-negative, and nucleos(t)ide analogue free at 48 weeks after the end of treatment. The non-VR group showed a significantly higher HBeAg-positivity rate, ALT, HBV DNA, and serum miR-192-5p levels at baseline (P = 0.024, P = 0.020, P = 0.007, P = 0.021, respectively). Serum miR-192-5p levels at 24-weeks after the start of treatment were also significantly higher in the non-VR than the VR group (P = 0.011). Multivariate logistic regression analysis for predicting VR showed that miR-192-5p level at baseline was an independent factor (Odds 4.5, P = 0.041). Serum miR-192-5p levels were significantly correlated with the levels of HBV DNA, hepatitis B core-related antigen, and hepatitis B surface antigen (r = 0.484, 0.384 and 0.759, respectively). The serum miR-192-5p level was useful as a biomarker for the therapeutic efficacy of Peg-IFN in CHB treatment.

Comparative research on language, music, and action in cognitive neuroscience keeps finding evidence for both shared and non-shared components of cognitive systems. The discussions, then, tend to quickly fall into the sterile dichotomy between domain-specific versus domain-general options. In this position paper, we take issue with this dichotomy and argue for an alternative account based on neural reuse theories to understand findings on the relationship between language, music, and action. We argue that the differences between those cognitive systems can be explained in terms of the specialization of the same brain mechanism(s) for each domain, which emerges in the course of development and/or evolution.

Background This retrospective study was conducted to assess the clinical outcome and complications between tension band wiring (TBW) with eyelet wire and locking plate fixation used for the treatment of displaced olecranon fractures. Methods A total of 58 patients (36 males and 22 females; mean age: 63 years) were reviewed between April 2014 and September 2020. TBW with Ring Pin (RP group) was applied in 24 patients, including 15 Mayo type ⅡA and 9 Mayo type ⅡB patients. Anatomical locking plate (ALP group) was used in 34 patients, including 22 Mayo type ⅡA and 12 Mayo type ⅡB patients. Clinical outcome was evaluated using the Mayo Elbow Performance Score (MEPS), and active range of motion of the elbow and forearm and postoperative complications were reviewed. Results General characteristic of the patients and the fracture type were similar in the two groups. The mean MEPS values were 96.5 ± 7.3 in the RP group and 94.9 ± 9.4 in the ALP group. The mean elbow flexion arc was 127°±11 in the RP group. The mean elbow flexion arc was 122°±18 in the ALP group. No significant differences in clinical outcomes were observed between the two groups. Complication rates were significantly higher in the ALP group (19/34: 56%) than in the RP group (6/24: 25%). Conclusion Although there were no statistically significant differences in clinical outcomes between the two groups, the ALP group had a higher proportion of any complication than the RP group.

Study design Cross-sectional study. Objective This study aimed to objectively evaluate spastic gait and reveal its novel characteristics via analysis of gait in patients with cervical myelopathy (CM) using the Timed Up and Go (TUG) test with a laser range sensor. Summary of background data Among patients with CM, spastic gait is a common diagnostic symptom; thus, objective assessments of spastic gait would be useful for the diagnosis of CM and recognition of disease status. Although spastic gait has been objectively evaluated in previous studies, the methods employed in those studies are not suitable for clinical settings. Methods In total, 37 and 24 participants were recruited for a control group and CM group, respectively. CM was diagnosed by spine surgeons. We developed a laser TUG test, in which the position and velocity of both the legs were captured. The parameter values for both groups were statistically compared, and odds ratios were calculated using logistic regression analyses. Results The total TUG test time, time to stand up, time to first step, number of steps, and trajectory error for the CM group were significantly higher than those for the control group, whereas the average velocity and average stride length for the CM group were significantly lower than those for the control group. There was a significant independent association between the total TUG test time and CM. The optimal cutoff point of the total test time for CM risk was approximately 9 seconds. Conclusion Through the use of the laser TUG test, we were able to identify characteristics of spastic gait, which leads to difficulty in standing and taking the first step, wobbling while walking, and an increased risk of falling. We found that the risk of CM was higher if the individual took longer than 9 seconds to complete the TUG test.Level of Evidence: 4.

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related deaths worldwide. Sorafenib has been used as a first-line systemic treatment for over a decade. However, resistance to sorafenib limits patient response and presents a major hurdle during HCC treatment. Lenvatinib has been approved as a first-line systemic treatment for advanced HCC and is the first agent to achieve non-inferiority against sorafenib. Therefore, in the present study, we evaluated the inhibition efficacy of lenvatinib in sorafenib-resistant HCC cells. Only a few studies have been conducted on this topic. Two human HCC cell lines, Huh-7 and Hep-3B, were used to establish sorafenib resistance, and in vitro and in vivo studies were employed. Lenvatinib suppressed sorafenib-resistant HCC cell proliferation mainly by inducing G1 cell cycle arrest through ERK signaling. Hep-3B sorafenib-resistant cells showed partial cross-resistance to lenvatinib, possibly due to the contribution of poor autophagic responsiveness. Overall, the findings suggest that the underlying mechanism of lenvatinib in overcoming sorafenib resistance in HCC involves FGFR4-ERK signaling. Lenvatinib may be a suitable second-line therapy for unresectable HCC patients who have developed sorafenib resistance and express FGFR4.

Purpose To clarify the clinical and microbial characteristics of polymicrobial bacteremia (PMB) to contribute to improvements in clinical diagnosis and effective early treatment. Methods This retrospective multicenter study used data from three acute-care hospitals in Okayama Prefecture, Japan, collected between January 2014 and March 2019. We reviewed the demographics, comorbidities, organisms isolated, infectious focus, and 30-day mortality of patients with PMB. Results Of the 7233 positive blood cultures, 808 (11.2%) were positive for more than one organism. Of the patients with bacteremia, 507 (7.0%) had PMB, of whom 65.3% were male. Infectious foci were identified in 78.3% of the cases, of which intra-abdominal infections accounted for 47.1%. A combination of Gram-positive cocci (GPC) (chain form) and Gram-negative rods (GNR) accounted for 32.9% of the cases, and GPC/GNR and GNR/GNR patterns were significantly associated with intra-abdominal infections. The 30-day mortality rate of patients with PMB was 18.1%, with a median of 7.5 days from diagnosis to death. The mortality in patients with an infectious focus identified was significantly lower than that in patients with an unknown focus (16.3% vs. 24.5%; p = 0.031). Conclusions Intra-abdominal infections were the most common source of PMB, and were strongly associated with a Gram-staining combination pattern of GPC (chain form)/GNR. PMB cases with an unknown focus had a poorer prognosis, highlighting the importance of early diagnosis and appropriate treatment.

Significance Human breast cancer develops after a long period of latency under premalignant conditions. Strategies to target the premalignant conditions have yet to materialize since the molecular mechanisms remain obscure. Here, we discovered that FRS2β, expressed in a subset of mammary epithelial cells, directly activates nuclear factor–κB (NF-κB) and drives the initiation and promotion of the stroma-rich premalignant conditions. The FRS2β-triggered activation of NF-κB takes place in the early endosomes, the organelles, which have not been believed to be a major place for NF-κB signaling. The endosome signaling should be a novel focus for targeting therapy for prevention of breast cancer. This work paves a new way to develop preventive strategies of breast tumor development., Although it is held that proinflammatory changes precede the onset of breast cancer, the underlying mechanisms remain obscure. Here, we demonstrate that FRS2β, an adaptor protein expressed in a small subset of epithelial cells, triggers the proinflammatory changes that induce stroma in premalignant mammary tissues and is responsible for the disease onset. FRS2β deficiency in mouse mammary tumor virus (MMTV)–ErbB2 mice markedly attenuated tumorigenesis. Importantly, tumor cells derived from MMTV-ErbB2 mice failed to generate tumors when grafted in the FRS2β-deficient premalignant tissues. We found that colocalization of FRS2β and the NEMO subunit of the IκB kinase complex in early endosomes led to activation of nuclear factor–κB (NF-κB), a master regulator of inflammation. Moreover, inhibition of the activities of the NF-κB–induced cytokines, CXC chemokine ligand 12 and insulin-like growth factor 1, abrogated tumorigenesis. Human breast cancer tissues that express higher levels of FRS2β contain more stroma. The elucidation of the FRS2β–NF-κB axis uncovers a molecular link between the proinflammatory changes and the disease onset.

Study design Retrospective observational study of consecutive patients. Objective We sought to: (1) clarify the key factors predominantly associated with the insertional torque of pedicle screws; (2) compare the optimal factors for pedicle screw insertion to obtain rigid screw fixation in patients with adult spinal deformity (ASD) and in those with adolescent idiopathic scoliosis (AIS); (3) determine the optimal screw/pedicle ratio (S/P) to obtain rigid pedicle screw fixation. Summary of background data Rigid pedicle screw fixation is mandatory to perform corrections for spinal deformities properly and to allow successful fusion after surgery. The fixation depends mainly on screw position accuracy and patient bone quality. Traditionally, spinal surgeons have decided the screw size, trajectory, and tapping size based on their intuition. Insertional torque has been indicated as useful to predict screw fixation strength, and is correlated with screw pullout strength and frequency of postoperative screw loosening. Methods We compared insertion torque at L1-L3 levels of 324 screws in 68 patients with ASD and 58 screws in 32 patients with AIS. We assessed the association between screw/pedicle ratio and insertion torque by constructing a spline curve. Results Pedicle and screw diameter correlated positively with insertion torque in patients with either ASD or AIS. The optimal screw/pedicle ratio to obtain rigid pedicle screw fixation in patients with ASD was close to, but less than one, and, by contrast, was about 1 to 1.25 in patients with AIS. Conclusion We propose the concept of an optimal S/P ratio for obtaining rigid pedicle screw fixation during spinal corrective surgery, which is different for patients with ASD and patients with AIS. The S/P ratio is useful for deciding the appropriate diameter screw for each case in preoperative planning.Level of Evidence: 4.

Previous studies showed that microRNA-29b (miR-29b) inhibits renal fibrosis. Therefore, miR-29b replacement therapy represents a promising approach for treating renal fibrosis. However, an efficient method of kidney-targeted miRNA delivery has yet to be established. Recombinant adeno-associated virus (rAAV) vectors have great potential for clinical application. For kidney-targeted gene delivery, the most suitable AAV serotype has yet to be established. Here, we identified the most suitable AAV serotype for kidney-targeted gene delivery and determined that AAV-mediated miR-29b delivery can suppress renal fibrosis in vivo. To determine which AAV serotype is suitable for kidney cells, GFP-positive cells were identified by flow cytometry after the infection of rAAV serotype 1–9 vectors containing the EGFP gene. Next, we injected rAAV vectors into the renal pelvis to determine transduction efficiency in vivo. GFP expression was measured seven days after injecting rAAV serotype 1–9 vectors carrying the EGFP gene. Finally, we investigated whether rAAV6-mediated miR-29b delivery can suppress renal fibrosis in UUO mouse model. We found that rAAV6 vector is the most suitable for targeting kidney cells regardless of animal species in vitro and rAAV6 is the most suitable vector for kidney-targeted in vivo gene delivery in mice. Intra-renal pelvic injection of rAAV vectors can transduce genes into kidney TECs. Furthermore, rAAV6-mediated miR-29b delivery attenuated renal fibrosis in UUO model by suppressing Snail1 expression. Our study has revealed that rAAV6 is the most suitable serotype for kidney-targeted gene delivery and rAAV6-mediated miR-29b delivery into kidney TECs can suppress established renal fibrosis.

The Kapandji score is used widely to record thumb opposition and is the only alternative to angular measurements. We aimed to verify the extent to which the Kapandji score reflects the angle of pronation. We recruited volunteers with unaffected upper limbs (33 hands) and patients with carpal tunnel syndrome (20 hands). We attached a small gyroscope to the thumb metacarpal and measured the pronation and palmar abduction angles at each position of the Kapandji score in both groups. The Kapandji score showed a strong ceiling effect, and the increase in angle size at each Kapandji score levelled off around a score of 6 in both groups. A Kapandji score greater than 6 does not necessarily reflect thumb opposition. Level of Evidence: III

Background Carpal tunnel syndrome (CTS) is common among patients receiving hemodialysis and deeply influences their daily life. Amyloid deposits are considered the main reason for median nerve compression, but its prevalence is unclear. Therefore, to determine the main region of amyloid deposition inside the carpal tunnel, we measured the cross-sectional area (CSA) of each component of the carpal tunnel in preoperative magnetic resonance imaging (MRI). Methods Thirty-five hemodialysis patients (HD group) and age- and sex-matched 35 non-hemodialysis patients (non-HD group), who underwent the first surgery for CTS in registered hospitals from 2005 to 2015, were retrospectively enrolled. CTS was diagnosed from clinical and electromyographic (EMG) findings. The CSA of carpal tunnel, each of the flexor tendons, and the median nerve at the level of the hook of hamate were measured in T1-weighted axial images in preoperative MRI, by using Synapse OP-A software. Statistical analysis was performed using the Student’s t test and Pearson’s chi-squared test. Results The mean age of the HD group was 65.9 years and the dialysis duration was 21.9 (11–35) years. The mean age of the non-HD group was 65.3 years. The CSA of carpal tunnel (p = 0.006), flexor tendon (p = 0.03), and flexor digitorum profundus (FDP) tendon (p = 0.04) were bigger in the HD group. However, the median nerve, the flexor digitorum superficialis (FDS) tendon, and the flexor pollicis longus tendon (FPL) were not significantly different between the two groups. The dialysis duration or age at surgery did not show any strong correlation to each CSA. Conclusions We confirmed that hemodialysis caused expansion of the carpal tunnel due to amyloid deposition as previously described. Hemodialysis also caused expansion of the CSA of the flexor tendon, especially the FDP, possibly because of amyloid deposition inside the tendon. Furthermore, the duration of dialysis or age did not correlate with any CSA, which could be due to the good progress of the beta 2-microglobulin removal technique. Based on our results, FDS excision could be considered in case severe deposition of amyloid in FDP is observed during surgery.

Objectives: This study aimed to compare Takayasu arteritis (TAK) with giant cell arteritis (GCA) through immunohistochemistry principally of inflammatory cells; these two disorders may be o...

A 71-year-old man who had undergone total gastrectomy, partial pancreatectomy, and splenectomy with Roux-en-Y reconstruction for gastric cancer was referred for a possible pancreatic tail tumor. Contrast-enhanced computed tomography showed mold-like, poor contrast lesion in the dilated main pancreatic duct in the pancreatic tail. Endoscopic ultrasonography revealed a slightly hyperechoic solid lesion that occupied the lumen of the main pancreatic duct. Linear calcification was observed in the lesions on both computed tomography and endoscopic ultrasonography, and endoscopic ultrasound-guided fine-needle biopsy was performed. Histopathology revealed sulfur grains and inflammatory infiltrates with no malignant findings. We also performed an anaerobic culture using fine-needle biopsy specimens, and Actinomyces meyeri was detected in the culture results. After confirming susceptibility, oral administration of amoxicillin was initiated. After 8 months of treatment, the size of the lesion slightly decreased, and the antibiotics treatment is still ongoing. This shows that such cases could be diagnosed based on histological findings and anaerobic culture using a fine-needle biopsy specimen, and unnecessary surgery may be avoided. In the case of tumors developed in the residual pancreas without typical malignant imaging findings, pancreatic actinomycosis should be considered as a differential diagnosis.

Small knee flexion motion is a characteristic of gait in individuals with knee osteoarthritis. This study examined the relationship between knee flexion excursion in loading response and knee self-perception in individuals with knee osteoarthritis. Twenty-one individuals with knee osteoarthritis participated in this study. Knee flexion excursions in loading response while walking at a comfortable and a fast-walking speed were measured using an inertial measurement unit-based motion capture system. The degree of knee perceptual impairment was evaluated using the Fremantle Knee Awareness Questionnaire (FreKAQ). The relationships between the FreKAQ score and gait variables and knee function were evaluated by calculating the correlation coefficient. The unique contributions of knee self-perception and muscle strength to knee flexion excursion in loading response were analyzed using hierarchical linear regression. Knee self-perception was significantly correlated with pain during walking, muscle strength and knee flexion excursion at fast speed. In the fast speed condition only, impaired knee self-perception was inversely proportional to knee flexion excursion and accounted for 21.8% of the variance in knee flexion excursion. This result suggests that impaired self-perception of the knee may help to explain the decrease in the knee flexion excursion in the loading response in individuals with knee osteoarthritis.

BRCA1 is a well-studied tumor suppressor involved in the homologous repair of DNA damage, whereas PINK1, a mitochondrial serine/threonine kinase, is known to be involved in mitochondrial quality control. Genetic mutations of PINK1 and Parkin cause autosomal recessive early-onset Parkinson’s disease. We found that in breast cancer cells, the mitochondrial targeting reagents, which all induce mitochondrial depolarization along with PINK1 upregulation, induced proteasomal BRCA1 degradation. This BRCA1 degradation was dependent on PINK1, and BRCA1 downregulation upon mitochondrial damage caused DNA double-strand breaks. BRCA1 degradation was mediated through the direct interaction with the E3 ligase Parkin. Strikingly, BRCA1 and PINK1/Parkin expression were inversely correlated in cancerous mammary glands from breast cancer patients. BRCA1 knockdown repressed cancer cell growth, and high BRCA1 expression predicted poor relapse-free survival in breast cancer patients. These observations indicate a novel mechanism by which mitochondrial damage is transmitted to the nucleus, leading to BRCA1 degradation.

Colon cancer is the second leading cause of cancer-related mortality worldwide, and the prognosis of advanced colon cancer has remained poor in recent years. Galectin-9 (Gal-9) is a tandem-repeat type galectin that has recently been shown to exert antiproliferative effects on various types of cancer cells. The present study aimed to assess the effects of Gal-9 on human colon and colorectal cancer cells in vitro and in vivo, as well as to evaluate the microRNAs (miRNAs/miRs) associated with the antitumor effects of Gal-9. We examined the ability of Gal-9 to inhibit cell proliferation via apoptosis, and the effects of Gal-9 on cell cycle-related molecules in various human colon and colorectal cancer cell lines. In addition, Gal-9-mediated changes in activated tyrosine kinase receptors and angiogenic molecules were assessed using protein array chips in colon and colorectal cancer cells. Moreover, miRNA array analysis was performed to examine Gal-9-induced miRNA expression profiles. We also elucidated if Gal-9 inhibited tumor growth in a murine in vivo model. We found that Gal-9 suppressed the cell proliferation of colon cancer cell lines in vitro and in vivo. Our data further revealed that Gal-9 increased caspase-cleaved keratin 18 levels in Gal-9-treated colon cancer cells. In addition, Gal-9 enhanced the phosphorylation of ALK, DDR1, and EphA10 proteins. Furthermore, the miRNA expression levels, such as miR-1246, miR-15b-5p, and miR-1237, were markedly altered by Gal-9 treatment in vitro and in vivo. In conclusion, Gal-9 suppresses the cell proliferation of human colon cancer by inducing apoptosis, and these findings suggest that Gal-9 can be a potential therapeutic target in the treatment of colon cancer.

The liver is well recognized as a non-immunological visceral organ that is involved in various metabolic activities, nutrient storage, and detoxification. Recently, many studies have demonstrated that resident immune cells in the liver drive various immunological reactions by means of several molecular modulators. Understanding the mechanistic details of interactions between hepatic host immune cells, including Kupffer cells and lymphocytes, and various hepatic pathogens, especially viruses, bacteria, and parasites, is necessary. MicroRNAs (miRNAs), over 2600 of which have been discovered, are small, endogenous, interfering, noncoding RNAs that are predicted to regulate more than 15,000 genes by degrading specific messenger RNAs. Several recent studies have demonstrated that some miRNAs are associated with the immune response to pathogens in the liver. However, the details of the underlying mechanisms of miRNA interference in hepatic host–pathogen interactions still remain elusive. In this review, we summarize the relationship between the immunological interactions of various pathogens and hepatic resident immune cells, as well as the role of miRNAs in the maintenance of liver immunity against pathogens.

Background Carpal tunnel syndrome (CTS) is a medical condition caused by compression of the median nerve in the carpal tunnel due to aging or overuse of the hand. The symptoms include numbness of the fingers and atrophy of the thenar muscle. Thenar atrophy recovers slowly postoperatively; therefore, early diagnosis and surgery are important. While physical examinations and nerve conduction studies are used to diagnose CTS, problems with the diagnostic ability and equipment, respectively, exist. Despite research on a CTS-screening app that uses a tablet and machine learning, problems with the usage rate of tablets and data collection for machine learning remain. Objective To make data collection for machine learning easier and more available, we developed a screening app for CTS using a smartphone and an anomaly detection algorithm, aiming to examine our system as a useful screening tool for CTS. Methods In total, 36 participants were recruited, comprising 36 hands with CTS and 27 hands without CTS. Participants controlled the character in our app using their thumbs. We recorded the position of the thumbs and time; generated screening models that classified CTS and non-CTS using anomaly detection and an autoencoder; and calculated the sensitivity, specificity, and area under the curve (AUC). Results Participants with and without CTS were classified with 94% sensitivity, 67% specificity, and an AUC of 0.86. When dividing the data by direction, the model with data in the same direction as the thumb opposition had the highest AUC of 0.99, 92% sensitivity, and 100% specificity. Conclusions Our app could reveal the difficulty of thumb opposition for patients with CTS and screen for CTS with high sensitivity and specificity. The app is highly accessible because of the use of smartphones and can be easily enhanced by anomaly detection.

Objectives To clarify the longitudinal changes in patients with preoperative Stage-3 locomotive syndrome (LS) according to different types of surgeries, we investigated the changes in the LS stage in patients who underwent surgery for degenerative musculoskeletal diseases. Methods A prospective cohort study was conducted on 168 patients with degenerative diseases [46 spinal deformities treated with thoracolumbar interbody fusion (T/LIF), 86 hips with osteoarthritis treated with total hip arthroplasty (THA), and 36 knees with osteoarthritis treated with total knee arthroplasty (TKA)]. The results for the LS stage, stand-up test, two-step test, and 25-question Geriatric Locomotive Function Scale (GLFS-25) were evaluated preoperatively and at 6 months, 1 year, and 2 years postoperatively. Results Preoperatively, most patients had Stage-3 LS (89.1, 90.8, and 80.6% in the T/LIF, THA, and TKA groups, respectively). At 2 years postoperatively, the Stage-3 LS improved in 41.5, 75.6, and 55.2% of patients in the T/LIF, THA, and TKA groups, respectively. All groups showed similar improvements in the two-step test. The THA group showed the best result in the GLFS-25. Conclusions LS stage improved in different patterns over 2 years postoperatively and the LS risk test revealed differences in postoperative movement ability according to the type of surgery.

We treated a 51-year-old Japanese man with chronic hepatitis B (viral load 7.6 LC/mL, genotype C). Hepatitis B virus DNA and HBe antigen were undetectable during the administration of the nucleic acid analogs (NUCs) lamivudine and adefovir, although the concentration of HBs antigen (HBsAg) was 851.2 IU/mL. The HBsAg levels were reduced 150-fold when pegylated-interferon (Peg-IFN) α-2a was administered weekly for 48 weeks and did not increase during the rest period. Therefore, Peg-IFNα-2a was administered twice each week. During this time, HBsAg reached undetectable concentrations, and HBs antibody was detected and continued to be detectable during the three-year follow-up. These unprecedented findings suggest that IFN may contribute to the seroclearance of HBsAg in patients treated with NUCs.

The Over-The-Scope Clip (OTSC) can effectively treat refractory gastrointestinal diseases. However, most reports have focused on short-term effectiveness. We examined clinical outcomes of the deployed clips and long-term characteristics.Of 47 patients with OTSC treatment, 35 with follow-up periods of ≥3 months were retrospectively examined. The indications were 11 bleedings, 17 perforations, and seven fistulas. The observation period was defined as medium-term (3 to12 months) or long-term (≥12 months). The primary outcome was the clinical success rate without disease recurrence. The secondary outcomes were the complication rate, survival duration, and clip retention rate.The medium- and long-term clinical success rates were 100% during the observation period (median, 44 months; range, 3-78 months). The complication rate was 2.9% (Regardless of clip detachment, the OTSC can be effective in long-term.

To visualize the neural activity of the ulnar nerve at the elbow using magnetoneurography (MNG).Subjects were asymptomatic volunteers (eight men and one woman; age, 26-53 years) and a male patient with cubital tunnel syndrome (age, 54 years). The ulnar nerve was electrically stimulated at the left wrist and evoked magnetic fields were recorded by a 132-channel biomagnetometer system with a superconducting quantum interference device at the elbow. Evoked potentials were also recorded and their correspondence to the evoked magnetic fields was evaluated in healthy participants.Evoked magnetic fields were successfully recorded by MNG, and computationally reconstructed currents were able to visualize the neural activity of the ulnar nerve at the elbow. In the affected arm of the patient, reconstructed intra-axonal and inflow currents attenuated and decelerated around the elbow. Latencies of reconstructed currents and evoked potentials were correspondent within an error of 0.4 ms in asymptomatic participants.Neural activity in the ulnar nerve can be visualized by MNG, which may be a novel functional imaging technique for ulnar neuropathy at the elbow, including cubital tunnel syndrome.MNG permits visualization of evoked currents in the ulnar nerve at the cubital tunnel.

Background Previous studies have shown that posttraumatic cubitus varus deformity in children is somehow related to subsequent humeral lateral condyle fracture. Moreover, we had previously encountered an exactly similar case. In this study, we aim to understand whether there is a morphological difference between pediatric supracondylar and lateral condyle fracture of the humerus by comparing Baumann's angle of the unaffected elbow. Methods We conducted a retrospective evaluation of 40 cases of supracondylar fractures (36 boys, 4 girls) and 20 cases of lateral condyle fractures (16 boys, 4 girls) at a single facility between January 2014 and December 2018. The unaffected Baumann's angles and lateral capitellohumeral angles of both groups were measured by two orthopedic surgeons and analyzed using Welch's t-test. The effect size was also calculated using Cohen's d, and intraclass correlation coefficients were applied for intra-rater and inter-rater reliability. Results The average age of patients in the supracondylar fracture group was 6.78 years and that in the lateral condyle fracture group was 5.70 years. No significant differences were observed between gender and fracture type, between laterality and fracture type, and in the lateral capitellohumeral angles between the groups. Baumann's angle was significantly less in the lateral condyle fracture group (17.27° ± 4.68°) than in the supracondylar fracture group (20.28° ± 3.10°) as analyzed by Welch's t-test (p = 0.015). The effect size was 0.76. Each of the intra-rater reliabilities were 0.97 and 0.96, whereas the inter-rater reliability was 0.75. Conclusions A significant morphological difference was found between the supracondylar fracture group and the lateral condyle fracture group. The loss of Baumann's angle which tends to occur after the healing of supracondylar fracture may increase the susceptibility to lateral condyle fracture. Orthopedic surgeons should repair and fix supracondylar fractures appropriately to avoid an ipsilateral second fracture, such as lateral condyle fracture.

Background Locomotive syndrome (LS) was proposed by the Japanese Orthopedic Association and refers to a scenario in which imminent future nursing care services will be required by elderly adults to manage the functional deterioration of their locomotive organs. It is a social imperative to clarify the risk factors and treatment strategy for LS. However, the relationship between LS and adult spinal deformity (ASD) in those who are treated with spinal corrective surgery remains largely unknown. Methods Forty consecutive patients who had ASD and underwent spinal surgery for their disorder were included in this study. Locomotive dysfunction was evaluated using the 25-item Geriatric Locomotive Function Scale-25 (GLFS-25) questionnaire and physical performance tests including the one-legged standing test, the two-step test, the stand-up test, the handgrip strength, and gait speed test which were measured preoperatively, 6 months after surgery, and 1 year after surgery. Results Of the patients with ASD treated surgically, 95% of them had LS preoperatively and LS prevalence decreased significantly 1 year after surgery by 67.5% compared with the preoperative rate. Among physical performance tests, the walking stride and one-legged standing test improved significantly after spinal corrective surgery. The GLFS-25 items for the domains of pain, mobility, and domestic life improved overall postoperatively, whereas items in the self-care domain did not and the item for difficulty in putting on and taking off trousers and pants worsened. Conclusions Spinal corrective surgery significantly improved physical performance tests as well as the frequency and severity of LS in patients with ASD. However, some GLFS-25 items can worsen after surgery and require attention.