LIGHT regulated gene expression in rheumatoid synovial fibroblasts.

BACKGROUND: Synovial hyperplasia caused by rheumatoid arthritis (RA), an autoimmune inflammatory disease, leads to the destruction of the articular cartilage and bone. A member of the tumor necrosis factor superfamily, Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpes virus entry mediator on T cells (LIGHT) has been shown to correlate with the pathogenesis of RA. METHODS: We used cDNA microarray analysis to compare the expression of genes in rheumatoid fibroblast-like synoviocytes with and without LIGHT stimulation. RESULTS: Significant changes in gene expression (P-values < 0.05 and fold change ≥ 2.0) were associated mainly with biological function categories of glycoprotein, glycosylation site as N-linked, plasma membrane part, integral to plasma membrane, intrinsic to plasma membrane, signal, plasma membrane, signal peptide, alternative splicing, and topological domain as extracellular. CONCLUSIONS: Our results indicate that LIGHT may regulate the expression in RA-FLS of genes which are important in the differentiation of several cell types and in cellular functions.

The impact of diabetic polyneuropathy on toe grip strength in patients with type 2 diabetes mellitus: a cross-sectional study.

Purpose: Type 2 diabetes mellitus (T2DM) and concomitant diabetic polyneuropathy (DPN) induce muscle weakness. Muscle weakness in the foot is associated with foot deformities and falls. However, factors affecting toe grip strength (TGS) are not well known. Therefore, the present study investigated factors related to TGS in patients with T2DM. Methods: This was a cross-sectional study involving 100 patients with T2DM who were hospitalized for the treatment of T2DM and 50 healthy adults. The subjects were divided into three groups: a group of healthy subjects, a group of T2DM patients without DPN, and a group of T2DM patients with DPN. Hierarchical multiple regression analysis was performed with TGS and the TGS-to-weight ratio (TGS/Wt%) as dependent variables and with age, the presence of T2DM, and DPN as independent variables, and sex and BMI as confounders. Results: There were no significant differences in age or sex among the three groups. In the final regression analysis, age and presence of T2DM and DPN were associated in both models with TGS and TGS/Wt% as dependent variables. Conclusion: DPN, T2DM, and age were found to be related to TGS. The findings of this study could contribute to healthcare providers developing foot care and rehabilitation programs for diabetic patients. Trial registration: This study was registered with UMIN-CTR (UMIN000034320) on 1 November 2018.

Demographic, Physical, and Psychological Determinants of Patient Experience with Subcutaneous Self-Injection in Patients with Rheumatoid Arthritis: Structural Equation Modeling Approach.

Purpose: To achieve a better patient experience with self-injection, an assessment of potential demographic, physical, and psychological barriers is necessary. The aim of this study was to examine the demographic, physical, and psychological characteristics associated with the experiences of self-injection in patients with rheumatoid arthritis (RA). Patients and Methods: In this study, overall patient experience with subcutaneous self-injection was assessed using the Self-Injection Assessment Questionnaire. Upper limb function was assessed using the three domains of the Health Assessment Questionnaire associated with upper extremity disability (dressing and grooming, eating, and grip). Structural equation modeling was used to estimate the association between the demographic and clinical characteristics of patients with RA and their experiences with self-injection in the theoretical model. Results: Data from 83 patients with RA were analyzed. Compared with younger patients, elderly patients were more likely to experience lower self-confidence, self-image, and ease of use. Female patients had lower ease of use than male patients. In terms of upper limb function, patients with more difficulty in performing activities of daily living were more likely to have a lower self-image. Self-injection perceptions before learning the method of injection, such as fear of needles and anxiety about self-injection, were associated with post-injection feelings, injection site reactions, self-confidence, and ease of use. Conclusion: To optimize patients' experiences with self-injection, healthcare workers should assess each patient's age, sex, upper limb function, and pre-self-injection perceptions as demographic, physical, and psychological barriers.

A screening method for visual attention disabilities in cerebral palsy with periventricular leukomalacia.

PURPOSE: Patients with periventricular leukomalacia (PVL) have been reported to have a variety of complications; however, whether these involve impaired visual attention disabilities remains unclear. Therefore, this study aimed to investigate the presence or absence and degree of visual attention disabilities in patients with PVL and propose a screening test that would allow anyone to check for visual attention disabilities easily. METHODS: The study participants were 14 patients with PVL and seven controls with dyskinetic cerebral palsy. All participants performed three types of visual attention tasks: spatial attention tasks, feature-based attention tasks, and object-based attention tasks. The participants also performed counting tasks to determine how many squares of the same size and color could be counted (up to nine). Receiver operating characteristic analysis was used to calculate cutoff values, with disability as the objective variable and the value of the counting task as the explanatory variable. RESULTS: The results revealed that patients with PVL often had visual attention disabilities, as indicated by a significant reduction in tasks requiring divided attention. Visual attention disabilities could be detected by a score of ≤8 in the square counting task. CONCLUSIONS: These findings suggest that family members and teachers of patients with PVL can easily screen for visual attention disabilities at home and school to improve mobility precautions in patients with this disability.

Factors related to indoor prosthetic use in individuals with unilateral lower limb amputation.

BACKGROUND: The rate of indoor prosthetic use in people with lower limb amputation (LLA) is lower than that of outdoor use. Very few studies of indoor prosthetic use have been conducted, and no studies have focused on the perspective of instrumental activities of daily living (IADLs). OBJECTIVES: To assess the indoor prosthetic use of individuals with unilateral LLA from the perspective of IADLs. STUDY DESIGN: Cross-sectional study. METHODS: A total of 162 people with LLA participated in this study. Based on the information obtained from a questionnaire and medical records, the relationships between each outcome and indoor prosthetic use were assessed by univariate analysis and multivariate logistic regression analysis. RESULTS: Of the 110 respondents (72.8%), 6 participants did not use the prosthesis or used it for cosmesis. With respect to the prosthetic users (n = 104), 74 (71.2%) used their prosthesis indoors and outdoors and 30 (28.8%) used it only outdoors, but none used it indoors only. On univariate analysis, five items were identified: household size, amputation level, domestic chores and outdoor activities of the Frenchay Activities Index, and difficulty donning/doffing the prosthesis. Small household, transtibial amputation, and a high score on the domestic chores of the Frenchay Activities Index (cutoff value 9.0 points) were independently associated with indoor prosthetic use. CONCLUSIONS: Training of motions that are desirable to use the prosthesis and participation in domestic chores frequently based on IADLs before hospitalization may increase the frequency of prosthesis use in people with transfemoral amputation who use their prosthesis outdoors.

Expression profiling of genes in rheumatoid fibroblast-like synoviocytes regulated by Fas ligand via cDNA microarray analysis.

Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation in synovial tissues. Hyperplasia of synovial tissues leads to the formation of pannus that invades the joint cartilage and bone, resulting in joint destruction. Fas ligand (FasL), which is a member of the tumor necrosis factor superfamily, contributes to the pathogenesis of autoimmune diseases, including RA. The current study attempted to identify genes whose expressions in rheumatoid fibroblast-like synoviocytes (RA-FLS) were regulated by FasL, using cDNA microarray. A total of four individual lines of primary cultured RA-FLS were incubated either with recombinant human FasL protein or PBS as an unstimulated control for 12 h. Gene expression was detected using a microarray assay. The results revealed the expression profiles of genes in RA-FLS regulated by Fas and investigated the functions of the genes that were regulated. Among the genes in this profile, the mRNA expression changes of the following genes were indicated to be of note using RT-qPCR: Dual specificity phosphatase 6, epiregulin, interleukin 11, angiopoietin-like 7, protein inhibitor of activated STAT 2 and growth differentiation factor 5. These genes may affect the pathogenesis of RA by affecting apoptosis, proliferation, cytokine production, cytokine-induced inflammation, intracellular signaling, angiogenesis, bone destruction and chondrogenesis. To the best of our knowledge, the current study is the first study to reveal the expression profile of genes in RA-FLS regulated by FasL. The data demonstrated that FasL may regulate the expression of a number of key molecules in RA-FLS, thus affecting RA pathogenesis. Further studies of the genes detected may improve the understanding of RA pathogenesis and provide novel treatment targets for RA.

Clinical Comparison of Unilateral Biportal Endoscopic Laminectomy versus Microendoscopic Laminectomy for Single-Level Laminectomy: A Single-Center, Retrospective Analysis.

BACKGROUND: The purpose of this study was to compare clinical results of microendoscopic laminectomy (MEL) with those of unilateral biportal endoscopic laminectomy (UBEL) in patients with single-level lumbar spinal canal stenosis. METHODS: The subjects consisted of 181 patients who underwent MEL (139 cases) and UBEL (42 cases) who were followed up for at least 6 months. All patients had lumber canal stenosis for 1 level. Outcomes of the patients were assessed with the duration of surgery, the bone resection area in 3-dimensional computed tomography, the facet preservation rates in computed tomography axial imagery, Visual Analog Scale (VAS) for low back pain, the Oswestry Disability Index, and the EuroQol 5-Dimensions questionnaire. RESULTS: The bone resection area in 3-dimensional computed tomography was 1.5 for MEL versus 1.0 cm2 for UBEL (P < 0.05). The facet preservation rates on the advancing side and the opposite side were 78% versus 86% (advancing side: MEL vs. UBEL) and 85% versus 94% (opposite side) (P < 0.05). The VAS (low back pain) score, VAS (leg pain), Oswestry Disability Index, and EuroQol 5-Dimension questionnaire significantly dropped in both groups at the final period (P < 0.05), however, exhibiting no difference between the 2 groups at each period. MEL resulted in greater numbers of complications, including 5 cases of hematoma paralysis, 8 cases of dura injury, 2 cases of reoperation, as opposed to zero cases of hematoma paralysis and only 2 cases of dura injury resulting from UBEL. CONCLUSIONS: The UBEL method is a more useful technique than the MEL method as it requires a smaller bone resection area and produces fewer complications.

Postoperative Outcomes After Transsacral Epiduroscopic Laser Decompression in Japanese Patients: Denervation Therapy for Discogenic Low-Back Pain.

Background: Transsacral epiduroscopic laser decompression (SELD) is a very noninvasive surgery, so it is effective for elderly patients and athletes and is a new and minimally invasive therapeutic technique that may be useful in many patients with discogenic low-back pain (LBP) having high signal intensity zone (HIZ) in magnetic resonance imaging (MRI). We investigated the clinical outcomes of SELD in Japanese patients with discogenic LBP having HIZ as a first trial. Methods: The subjects consisted of 52 patients who underwent SELD and were followed up for at least 6 months. All patients with LBP with HIZ were operative using the SELD technique. Outcomes of the patients were assessed with visual analogue scale (VAS) for LBP, the Oswestry disability index (ODI), and the EuroQol 5 dimension (EQ-5D). Statistical analyses were carried out using a paired t-test. A p-value of <0.05 was considered significant. For statistical analysis, we used the SPSS software program. Results: At 12 months after the procedure, the average VAS score for LBP fell to 1.2 from 5.6 (p-value <0.05). The ODI score also dropped from the preoperative level of 22.3 to 8.8. The EQ-5D score also significantly increased from the preoperative level of 0.865 (SD 0.10) to 0.950 (SD 0.05). Eight cases of intraoperative cervical pain were observed as complications with no cases of hematomas, infections, and postoperative neurosis was observed. Conclusions: SELD provides a novel minimally invasive technique capable of performing multilevel intervertebral surgery. We believe that SELD is an effective method of treating discogenic LBP due to HIZs.

Do Sociodemographic Factors Relate to Walking Ability in Individuals Who Underwent Total Knee Arthroplasty?

BACKGROUND AND PURPOSE: Knee osteoarthritis is one of the most common health problems in older adults and total knee arthroplasty (TKA) is able to improve walking ability in these individuals. There have been few studies investigating whether sociodemographic factors influence walking ability after TKA. The aim of this study was to examine which sociodemographic factors relate to walking ability in Japanese older adults following TKA during the acute stage of recovery. METHODS: This prospective cohort study included 388 participants, from a multicenter database, who underwent TKA. The Timed Up and Go test 2 weeks after TKA was the dependent variable. Sociodemographic factors including age, sex, body mass index, marital status, and academic qualification were independent variables. In addition, type of surgery and severity of osteoarthritis were measured as confounding variables. A hierarchical multiple regression analysis was used to predict the factors that have the greatest influence on walking ability. Models were examined with and without confounding factors. RESULTS AND DISCUSSION: In the final regression model, older age, conventional TKA approaches, increased severity of Kellgren-Lawrence grade, and women were associated with longer Timed Up and Go time. Academic qualification and marital status were not related to walking ability. CONCLUSIONS: Our results suggest that age, type of surgery, severity of osteoarthritis, and sex are related to Timed Up and Go time during the acute stage following TKA and need to be assessed.

Denosumab Treatment Improved Health-Related Quality of Life in Osteoporosis: A Prospective Cohort Study.

Improving patient health-related quality of life (HRQOL) and prevention of bone fracture are important components of the treatment of osteoporosis. Our aim in this study was to evaluate the effect of denosumab treatment in improving HRQOL among patients with osteoporosis. Our analysis was based on 332 patients with osteoporosis, followed for 24 months. All patients received denosumab (60 mg) subcutaneously every 6 months. Bone mineral density (BMD) was assessed at the distal radius, with serum concentration of calcium, phosphate, P1NP, and TRACP5b also measured. HRQOL assessment included pain (visual analogue scale [VAS]) and the EQ-5D questionnaire. A multivariate analysis was performed to identify the possible confounders associated with deterioration in the EQ-5D utility score in response to denosumab treatment. Denosumab treatment yielded a 3.4% increase in BMD at 24 months. Serum levels of TRACP5b and P1NP decreased significantly, from baseline, at 6 months, with no effect on calcium and phosphate levels. Pain VAS and EQ-5D utility score improved significantly, from baseline, at 6 months, with the EQ-5D utility score correlating with the BMD at all time points of measurement over the 24-month period of observation. Knee osteoarthritis and multiple comorbidities were significantly associated with a worse HRQOL in response to denosumab treatment. Denosumab treatment increased BMD, with improvements in BMD correlating with improved HRQOL, supporting a possible benefit of using denosumab for the treatment of osteoporosis. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Conditional Upregulation of IFN-α Alone Is Sufficient to Induce Systemic Lupus Erythematosus.

The cause of systemic lupus erythematosus (SLE) is unknown. IFN-α has been suggested as a causative agent of SLE; however, it was not proven, and to what extent and how IFN-α contributes to the disease is unknown. We studied the contribution of IFN-α to SLE by generating inducible IFN-α transgenic mice and directly show that conditional upregulation of IFN-α alone induces a typical manifestation of SLE in the mice not prone to autoimmunity, such as serum immune complex, autoantibody against dsDNA (anti-dsDNA Ab), and the organ manifestations classical to SLE, such as immune complex-deposited glomerulonephritis, classical splenic onion-skin lesion, alopecia, epidermal liquefaction, and positive lupus band test of the skin. In the spleen of mice, activated effector CD4 T cells, IFN-γ-producing CD8 T cells, B220+CD86+ cells, and CD11c+CD86+ cells were increased, and the T cells produced increased amounts of IL-4, IL-6, IL-17, and IFN-γ and decreased IL-2. In particular, activated CD3+CD4-CD8- double-negative T cells positive for TCRαß, B220, CD1d-teteramer, PD-1, and Helios (that produced increased amounts of IFN-γ, IL-4, IL-17, and TNF-α) were significantly expanded. They infiltrated into kidney and induced de novo glomerulonephritis and alopecia when transferred into naive recipients. Thus, sole upregulation of IFN-α is sufficient to induce SLE, and the double-negative T cells expanded by IFN-α are directly responsible for the organ manifestations, such as lupus skin disease or nephritis.

Expression profiling of genes in rheumatoid fibroblast-like synoviocytes regulated by tumor necrosis factor-like ligand 1A using cDNA microarray analysis.

Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation in synovial tissues. Hyperplasia of synovial tissue leads to the formation of pannus, which invades joint cartilage and bone resulting in joint destruction. Tumor necrosis factor-like ligand 1A (TL1A), a member of the tumor necrosis factor superfamily (TNFSF15), contributes to the pathogenesis of autoimmune diseases, including RA. In the present study, a cDNA microarray was used to search for genes whose expression in rheumatoid fibroblast-like synoviocytes (RA-FLS) were regulated by TL1A. Four individual lines of primary cultured RA-FLS were incubated either with recombinant human TL1A protein or phosphate-buffered saline, as an unstimulated control, for 12 h. Gene expression was then detected through the microarray assay. The results revealed the expression profiles of genes in RA-FLS regulated by TL1A. The present study also demonstrated the functions of those genes whose expression in RA-FLS was regulated by TL1A. Among the genes in this profile, the present study focused on the following genes: Spectrin repeat-containing nuclear envelope 1, Fc receptor-like 2, PYD (pyrin domain)-containing 1, cell division cycle 45 homolog, signal transducer and activator of transcription 5B, and interferon regulatory factor 4. These genes may affect the pathogenesis of RA, including proliferation, regulation of B cells and T cells, inflammation, and cytokine processing. The present study revealed for the first time, to the best of our knowledge, the expression profile of genes in RA-FLS regulated by TL1A. The data indicate that TL1A may regulate the gene expression of various key molecules in RA-FLS, thus affecting the pathogenesis of RA. Further investigations of the genes detected in the current profiles may provide a deeper understanding of the pathogenesis and a novel target for the treatment of RA.

The relationship between balance ability and walking ability using the Berg Balance Scale in people with transfemoral amputation.

BACKGROUND: Few reports have examined the relationship between balance ability and walking ability in people with transfemoral amputation using the Berg Balance Scale. OBJECTIVES: To assess the construct validity (known groups discrimination, convergent validity, and floor/ceiling effects) of Berg Balance Scale for people with transfemoral amputation. STUDY DESIGN: Cross-sectional study. METHODS: Thirty people with transfemoral amputation participated (age: 54 ± 19 years; range: 18-78 years). Outcome measures (Berg Balance Scale, Timed Up & Go test, Six-Minute Walk Test, and use of ambulatory aids) were compared between the groups requiring and not requiring ambulatory aids by the Mann-Whitney U test, Student's t-test or Welch's t-test. Correlations were assessed using Spearman's rank correlation coefficients and age-corrected Spearman's partial rank correlation coefficients. RESULTS: The group using ambulatory aids had a significantly lower Berg Balance Scale score (41 ± 5 vs 52 ± 3). Berg Balance Scale score was correlated with Timed Up & Go test, use of aids, and Six-Minute Walk Test using Spearman's rank correlation coefficients (r =-0.85, p < 0.0001; r =-0.82, p < 0.0001; r = 0.81, p < 0.0001) and age-corrected partial rank correlation coefficients (r =-0.66, p < 0.0001; r =-0.56, p = 0.0017; r = 0.57, p = 0.0012). No ceiling effect of Berg Balance Scale was observed. CONCLUSIONS: Balance ability in people with transfemoral amputation could be evaluated using Berg Balance Scale and is correlated with walking ability. CLINICAL RELEVANCE: In clinical practice, using Berg Balance Scale for people with transfemoral amputation may adequately enable us to discriminate different groups based on walking ability from the perspective of balance ability. When walking ability is evaluated as low, the improvement of walking ability may be evaluated by Berg Balance Scale improvement during rehabilitation.

Step-by-Step Sublaminar Approach With a Newly-Designed Spinal Endoscope for Unilateral-Approach Bilateral Decompression in Spinal Stenosis.

OBJECTIVE: Spinal stenosis is increasingly common due to population aging. In elderly patients with lumbar central canal stenosis (LCCS), minimizing muscle damage and bone resection is particularly important. We performed a step-by-step operation with a newly designed spinal endoscope to obtain adequate decompression in patients with spinal stenosis. METHODS: From April 2015 to August 2016, 78 patients (48 males, 30 females) with LCCS (91 segments) underwent endoscopic decompression using a newly designed endoscope system. The inclusion criteria were: (1) neurogenic intermittent claudication with or without radiculopathy, (2) LCCS, and (3) having exhausted conservative treatment (>3 months). The exclusion criteria were: (1) >10° of instability, (2) spondylolisthesis grade II or greater according to the Meyerding criteria, (3) foraminal stenosis, (4) vascular intermittent claudication, (5) infection, and (6) stenosis combined with malignancy. We performed a step-by-step procedure using a newly designed endoscope system for unilateral-approach bilateral decompression. We used the same incision for 2-3 segments, only moving the skin. RESULTS: The mean follow-up was 2.3±1.3 years. Excellent or good results were found according to the MacNab criteria in 85.9% of cases (67 of 78). The visual analogue scale, Japanese Orthopedic Association score, and Oswestry Disability Index showed significant decreases at 1 month, persisting until the 2-year follow-up. Dural tear occurred in 4 cases (5.1%), and patch repair was performed under endoscopy. No patients experienced aggravated instability requiring surgery. CONCLUSION: We obtained good results with endoscopic decompression surgery using a newly designed instrument that minimized muscle and bone damage in elderly patients with spinal stenosis.

Efficient functional cyst formation of biliary epithelial cells using microwells for potential bile duct organisation in vitro.

Establishing a bile duct in vitro is valuable to obtain relevant hepatic tissue culture systems for cell-based assays in chemical and drug metabolism analyses. The cyst constitutes the initial morphogenesis for bile duct formation from biliary epithelial cells (BECs) and serves the main building block of bile duct network morphogenesis from the ductal plate during embryogenesis in rodents. Cysts have been commonly cultured via Matrigel-embedded culture, which does not allow structural organisation and restricts the productivity and homogeneity of cysts. In this study, we propose a new method utilising oxygen permeable honeycomb microwells for efficient cyst establishment. Primary mouse BECs were seeded on four sizes of honeycomb microwell (46, 76, 126, and 326 µm-size in diameter). Matrigel in various concentrations was added to assist in cyst formation. The dimension accommodated by microwells was shown to play an important role in effective cyst formation. Cytological morphology, bile acid transportation, and gene expression of the cysts confirmed the favourable basic bile duct function compared to that obtained using Matrigel-embedded culture. Our method is expected to contribute to engineered in vitro liver tissue formation for cell-based assays.

Differential expression of Lutheran/BCAM regulates biliary tissue remodeling in ductular reaction during liver regeneration.

Under chronic or severe liver injury, liver progenitor cells (LPCs) of biliary origin are known to expand and contribute to the regeneration of hepatocytes and cholangiocytes. This regeneration process is called ductular reaction (DR), which is accompanied by dynamic remodeling of biliary tissue. Although the DR shows apparently distinct mode of biliary extension depending on the type of liver injury, the key regulatory mechanism remains poorly understood. Here, we show that Lutheran (Lu)/Basal cell adhesion molecule (BCAM) regulates the morphogenesis of DR depending on liver disease models. Lu+ and Lu- biliary cells isolated from injured liver exhibit opposite phenotypes in cell motility and duct formation capacities in vitro. By overexpression of Lu, Lu- biliary cells acquire the phenotype of Lu+ biliary cells. Lu-deficient mice showed severe defects in DR. Our findings reveal a critical role of Lu in the control of phenotypic heterogeneity of DR in distinct liver disease models.

Impact of Sarcopenia on Unplanned Readmission and Survival After Esophagectomy in Patients with Esophageal Cancer.

BACKGROUND: Although sarcopenia increases postoperative complications following esophagectomy, its effects on prognosis remain unclear. This study was performed to identify the effect of sarcopenia on 90-day unplanned readmission and overall survival (OS) after esophagectomy. METHODS: Ninety-eight patients with esophageal cancer who underwent esophagectomy were enrolled in this study. Unplanned readmission was defined as any emergent hospitalization within 90 days after discharge. Sarcopenia, defined as low muscle mass plus low muscle strength and/or low physical performance according to the Asian consensus definition, was assessed prior to esophagectomy. Multivariate logistic regression analysis was performed to identify factors that contributed to 90-day unplanned readmission. OS was estimated using the Kaplan-Meier method, and a Cox proportional hazards model was used to assess the relationship between sarcopenia and OS. RESULTS: Thirty-one patients (31.6%) were diagnosed with sarcopenia. The 90-day unplanned readmission rate was significantly higher in patients with sarcopenia than those without (42.9% vs. 16.4%, respectively; p = 0.01). Multivariable logistic regression analysis showed that sarcopenia was an independent predictor of 90-day unplanned readmission [odds ratio 3.71, 95% confidence interval (CI) 1.29-11.05; p = 0.02], and the log-rank test showed that sarcopenia was associated with OS (p = 0.01). Moreover, sarcopenia was a significant predictor of OS after adjustment for age, sex, and pathological stage (hazard ratio 2.35, 95% CI 1.21-4.54; p = 0.01). CONCLUSIONS: Sarcopenia is a risk factor for 90-day unplanned readmission and OS following esophagectomy. Assessment of sarcopenia could help to identify patients at higher risk of a poor prognosis after esophagectomy.

Decoy receptor 3 down-regulates centrosomal protein 70 kDa specifically in rheumatoid synovial fibroblasts.

OBJECTIVES: Decoy receptor 3 (DcR3) competitively binds to Fas ligand, lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpes virus entry mediator on T cells (LIGHT) and TNF-like ligand 1A (TL1A), thereby preventing their effects. Using a microarray assay, we previously newly identified centrosomal protein 70 kDa (CEP70) as one of the genes whose expression in fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA-FLS) is reduced by DcR3. Here, we investigated the significance of DcR3 regulation of CEP70 for RA-FLS. METHODS: Synovial samples were obtained from RA patients who had never been treated with biologics and from osteoarthritis (OA) patients. CEP70 mRNA expression was quantified using RT-qPCR analysis. CEP70 protein expression was assessed using immunohistochemical and western blot analyses. RESULTS: CEP70 was expressed predominantly in the superficial lining layer in RA synovial tissue. CEP70 expression was dose-dependently downregulated by DcR3-Fc in RA-FLS but was not downregulated in OA-FLS. TL1A antibody prevented the DcR3-Fc inhibitory effects on CEP70 expression in RA-FLS. CONCLUSIONS: These results indicated that DcR3 reduces CEP70 expression in RA-FLS by binding to membrane-bound TL1A and may suppress RA-FLS proliferation. The reduction in CEP70 expression by DcR3/TL1A signaling may control the hyperplasia of RA synovium.

Mechanical Stress by Spasticity Accelerates Fracture Healing After Spinal Cord Injury.

Accelerated fracture healing in patients with spinal cord injuries (SCI) is often encountered in clinical practice. However, there is no distinct evidence in the accelerated fracture healing, and the mechanisms of accelerated fracture healing in SCI are poorly understood. We aimed to determine whether SCI accelerated fracture healing in morphology and strength, to characterize the healing process with SCI, and to clarify the factors responsible for accelerated fracture healing. In total, 39 male Wistar rats were randomly divided into healthy control without intervention, SCI only, fracture with SCI, botulinum toxin (BTX) A-treated fracture with SCI, and propranolol-treated fracture with SCI groups. These rats were assessed with computed microtomography, histological, histomorphological, immunohistological, and biomechanical analyses. Both computed microtomography and histological analyses revealed the acceleration of a bony union in animals with SCI. The strength of the healed fractures after SCI recovered to the same level as that of intact bones after SCI, while the healed bones were weaker than the intact bones. Immunohistology revealed that SCI fracture healing was characterized by formation of callus with predominant intramembranous ossification and promoting endochondral ossification. The accelerated fracture healing after SCI was attenuated by BTX injection, but did not change by propranolol. We demonstrated that SCI accelerate fracture healing in both morphology and strength. The accelerated fracture healing with SCI may be due to predominant intramembranous ossification and promoting endochondral ossification. In addition, our results also suggest that muscle contraction by spasticity accelerates fracture healing after SCI.

Expression and localization of sterile alpha motif domain containing 5 is associated with cell type and malignancy of biliary tree.

Cholangiocarcinoma (CC) is a type of relatively rare neoplasm in adenocarcinoma. The characteristics of CCs as well as biliary epithelial cells are heterogeneous at the different portion of the biliary tree. There are two candidate stem/progenitor cells of the biliary tree, i.e., biliary tree stem/progenitor cell (BTSC) at the peribiliary gland (PBG) of large bile ducts and liver stem/progenitor cell (LPC) at the canals of Hering of peripheral small bile duct. Although previous reports suggest that intrahepatic CC (ICC) can arise from such stem/progenitor cells, the characteristic difference between BTSC and LPC in pathological process needs further investigation, and the etiology of CC remains poorly understood. Here we show that Sterile alpha motif domain containing 5 (SAMD5) is exclusively expressed in PBGs of large bile ducts in normal mice. Using a mouse model of cholestatic liver disease, we demonstrated that SAMD5 expression was upregulated in the large bile duct at the hepatic hilum, the extrahepatic bile duct and PBGs, but not in proliferating intrahepatic ductules, suggesting that SAMD5 is expressed in BTSC but not LPC. Intriguingly, human ICCs and extrahepatic CCs exhibited striking nuclear localization of SAMD5 while the normal hilar large bile duct displayed slight-to-moderate expression in cytoplasm. In vitro experiments using siRNA for SAMD5 revealed that SAMD5 expression was associated with the cell cycle regulation of CC cell lines. CONCLUSION: SAMD5 is a novel marker for PBG but not LPC in mice. In humans, the expression and location of SAMD5 could become a promising diagnostic marker for the cell type as well as malignancy of bile ducts and CCs.