Divergent Actions of Renal Tubular and Endothelial Type 1 IL-1 Receptor Signaling in Toxin-Induced AKI.

SIGNIFICANCE STATEMENT: Activation of the type 1 IL-1 receptor (IL-1R1) triggers a critical innate immune signaling cascade that contributes to the pathogenesis of AKI. However, blockade of IL-1 signaling in AKI has not consistently demonstrated kidney protection. The current murine experiments show that IL-1R1 activation in the proximal tubule exacerbates toxin-induced AKI and cell death through local suppression of apolipoprotein M. By contrast, IL-1R1 activation in endothelial cells ameliorates AKI by restoring VEGFA-dependent endothelial cell viability. Using this information, future delivery strategies can maximize the protective effects of blocking IL-1R1 while mitigating unwanted actions of IL-1R1 manipulation. BACKGROUND: Activation of the type 1 IL-1 receptor (IL-1R1) triggers a critical innate immune signaling cascade that contributes to the pathogenesis of AKI. IL-1R1 is expressed on some myeloid cell populations and on multiple kidney cell lineages, including tubular and endothelial cells. Pharmacological inhibition of the IL-1R1 does not consistently protect the kidney from injury, suggesting there may be complex, cell-specific effects of IL-1R1 stimulation in AKI. METHODS: To examine expression of IL-1 and IL-1R1 in intrinsic renal versus infiltrating immune cell populations during AKI, we analyzed single-cell RNA sequencing (scRNA-seq) data from kidney tissues of humans with AKI and mice with acute aristolochic acid exposure. We then investigated cell-specific contributions of renal IL-1R1 signaling to AKI using scRNA-seq, RNA microarray, and pharmacological interventions in mice with IL-1R1 deletion restricted to the proximal tubule or endothelium. RESULTS: scRNA-seq analyses demonstrated robust IL-1 expression in myeloid cell populations and low-level IL-1R1 expression in kidney parenchymal cells during toxin-induced AKI. Our genetic studies showed that IL-1R1 activation in the proximal tubule exacerbated toxin-induced AKI and cell death through local suppression of apolipoprotein M. By contrast, IL-1R1 activation in endothelial cells ameliorated aristolochic acid-induced AKI by restoring VEGFA-dependent endothelial cell viability and density. CONCLUSIONS: These data highlight opposing cell-specific effects of IL-1 receptor signaling on AKI after toxin exposure. Disrupting pathways activated by IL-1R1 in the tubule, while preserving those triggered by IL-1R1 activation on endothelial cells, may afford renoprotection exceeding that of global IL-1R1 inhibition while mitigating unwanted actions of IL-1R1 blockade.

Mapping the Japanese orthopedic association national registry (JOANR) to the international classification of health interventions (ICHI).

BACKGROUND: The Japanese Orthopedic Association launched the Japanese Orthopedic Association National Registry (JOANR), Japan's first large-scale nationwide musculoskeletal disease registry, in 2020. The World Health Organization released the International Classification of Health Interventions (ICHI) Beta-3 version in the same year. This concurrence served as an impetus to examine the relationship between domestic and international classification for orthopedic interventions. Our objective was to evaluate the possibility of utilizing JOANR for international comparison and the potential usage of ICHI in the domestic medical fee reimbursement system. This study is a novel attempt at mapping a domestic orthopedic scheme to the ICHI. METHODS: We mapped 149 codes out of 581 orthopedic surgical codes, on JOANR's registration form, to the ICHI, and then classified the nature of JOANR codes' relationship, to both ICHI single stem codes and stem codes accompanied by other additional stem codes, extension codes, and International Classification of Diseases for Mortality and Morbidity Statistics (ICD) codes, into five categories: Equivalent (exact match), Narrower (compared to ICHI; can be smoothly incorporated into ICHI), Broader (compared to ICHI), Slipped (combination of both Narrower and Broader), and None (no appropriate code). Finally, debatable issues that arose during the mapping operation were noted. RESULTS: The domestic codes' relationship to ICHI single stem code by category were Equivalent: 27 (18.1%) and Narrower: 65 (43.6%), respectively. Further, the rate of Equivalent rose to 120 (80.5%) on adding other stem codes, extension codes, and ICD codes. Additionally, certain domestic titles, which were unsuitable for classification as they included diagnostic information, and arthroscopic surgeries without corresponding ICHI codes, were recoded. CONCLUSIONS: JOANR can be converted to an international comparison standard via ICHI to a certain extent, and ICHI accompanied by ICD codes has potential for deployment in the domestic medical fee reimbursement system.

Asymmetric Synthesis of α-Spiro-γ-lactones and α-Substituted γ-Lactones via Chiral Bifunctional Sulfide-Catalyzed Bromolactonizations.

An efficient enantioselective synthesis of γ-chiral α-spiro-γ-lactones, which are important building blocks for pharmaceuticals, was achieved via BINOL-derived chiral bifunctional sulfide-catalyzed bromolactonizations of α-allyl carboxylic acids containing either hetero- or carbocyclic structures. Transformations of the resultant α-spiro-type bromolactonization product were examined to obtain optically active γ-functionalized α-spiro-γ-lactones. The utility of this catalytic system was also demonstrated in the asymmetric synthesis of α,α-diaryl- and dialkyl-substituted γ-lactones.

Evaluation of Serum Albumin and Globulin in Combination With C-Reactive Protein Improves Serum Diagnostic Accuracy for Low-Grade Periprosthetic Joint Infection.

BACKGROUND: Serum immune markers can be useful in the diagnosis of periprosthetic joint infection (PJI) by detecting long-lasting abnormal immunological conditions. The purpose of this study was to examine whether serum immune markers can improve the diagnostic accuracy of PJI. METHODS: We enrolled 51 PJI, 45 aseptic loosening, and 334 osteoarthritis patients for assessment of the discriminatory accuracy of serum markers including white blood cell count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and D-dimer, total protein, albumin (Alb), globulin (Glb), neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, platelet-lymphocyte ratio, albumin-globulin ratio (AGR), CRP-albumin ratio (CAR), and CRP-AGR ratio (CAGR). These diagnostic accuracies for low-grade PJI were also calculated in patients who had serum CRP levels < 10 mg/L. RESULTS: Among serum markers, Alb, Glb, AGR, CRP, ESR, CAR, and CAGR had highly accurate diagnostic accuracy for PJI, with area under the curve of 0.92, 0.90, 0.96, 0.97, 0.92, 0.97, and 0.98, respectively. In low-grade PJI patients, area under the curve of CRP, ESR, CAR, and CAGR (0.69, 0.80, 0.65, and 0.82, respectively) was decreased but that of Alb, Glb, and AGR (0.90, 0.88, and 0.95, respectively) remained high, indicating the diagnostic utility of these immune markers. The sensitivity and specificity of AGR with cutoff value of 1.1 were demonstrated as 0.92 and 0.89, respectively, and with cutoff value of 1.2, 1.00, and 0.79, respectively, in the diagnosis of low-grade infection. CONCLUSION: Our results demonstrate the potential value of Alb, Glb, AGR, and combination indices of these immune makers with CRP in improving preoperative serum diagnosis for PJI, especially in low-grade PJI. LEVEL OF EVIDENCE: Diagnostic- Level II.

Deaths caused by osteoporotic fractures in Japan: An epidemiological study.

BACKGROUND: Osteoporosis is a global issue with a worldwide prevalence of 18.3%, and the presence of coexisting fragility fractures can reduce the survival rate by approximately 20%. In Japan, the prevalence of osteoporosis is estimated to be 12.8 million, and the annual occurrence of hip fractures is approximately 193,400. Remarkably, coexisting hip or spinal fragility fractures caused by slight external force meet the Japanese diagnostic criterion for osteoporosis regardless of bone mineral density. However, only 191 deaths due to osteoporosis were published in 2021 in Japan. With the concern that some cases of hip and spinal fragility fractures were assigned an underlying cause of death of traumatic fracture instead of osteoporosis, this study aimed to elucidate the actual number of deaths due to osteoporosis in Japan. METHODS: We used the data from Japan in 2018. First, the number of deaths due to osteoporosis and hip or spinal fractures was reviewed using published vital statistics. Second, we calculated the number of elderly deaths (age ≥80 years) resulting from hip or spinal fractures caused by falls on the same level using data from approximately 1.4 million annual individual death certificates. Combining the above data, the actual number of deaths due to osteoporosis was estimated. RESULTS: Only 190 deaths due to osteoporosis were reported in the published data. The individual certificate data revealed 3437 elderly deaths due to hip or spinal fractures caused by falls on the same level, which could meet the criteria of osteoporotic fragility fractures. Accordingly, the estimated number of deaths caused by osteoporosis was calculated as 3,627, approximately 19 times the published value. CONCLUSIONS: After researching the individual death certificate data focusing on the coexisting hip or spinal fragility fracture, it was implied that osteoporosis may have a higher mortality rate in Japan than what is published.

Efficient methods for the synthesis of chiral 2-oxazolidinones as pharmaceutical building blocks.

Although the wide variety of heterocyclic compounds is common knowledge, chiral 2-oxazolidinones are recognized as some of the most important heterocycles in medicinal chemistry. Many important pharmaceutical molecules have been constructed based on the chiral 2-oxazolidinone backbone. Therefore, the development of even more efficient catalytic methods for the synthesis of chiral 2-oxazolidinones remains a very important pursuit in the field of synthetic organic chemistry. This review summarizes the coupling reactions of epoxides and isocyanates for the preparation of 2-oxazolidinones. Both metal catalysts and organocatalysts promote these reactions. Optically pure 2-oxazolidinones are prepared from optically pure epoxide substrates via these catalytic methods. A synthetic example of a commercially available pharmaceutical compound utilizing this method is also introduced.

Assessment of locomotive syndrome in patients with visceral cancer, the comparison with non-cancer patients using propensity score matching.

BACKGROUND: When treating cancer patients, the progression of symptoms is accompanied by the deterioration of systemic conditions and motor function. From a risk-benefit perspective, a certain level of physical function must be maintained to continue cancer treatment. Recently, outpatient cancer treatment has become more common. Motor function is important to determine the feasibility of continuing cancer treatment. The study aimed to evaluate the motor function of patients with visceral cancer using locomo tests established by Japanese Orthopaedic Association. METHODS: Locomo tests were performed, and the results were compared with data from non-cancer individuals. Background data were matched by propensity score matching. Data from 53 cancer patients (group C) were compared with that of 75 non-cancer patients (group N). RESULTS: The average score in the two-step test of group C was lower than that of group N (1.27: 1.37, p = 0.004). The average function in the stand-up test of group C was worse than that of group N (p = 0.001). The average score in the 25-question geriatric locomotive function scale (GLFS) of group C was significantly higher than that of group N (19.92: 5.29, SE 2.21, p < 0.001). Higher 25-question GLFS scores indicate reduced mobility. The proportion of the locomo stage 2 in group C was significantly higher than in group N (51%: 13%, p < 0.001). The results of the two field tests revealed a clinically minimal difference between the two groups, but a statistically significant difference. Locomo tests may be detect potential motor dysfunction in outpatient cancer patients with apparently maintained motor function. CONCLUSIONS: Even in cancer patients who attend outpatient clinics, their motor functions could be potentially impaired. Therapeutic interventions to maintain and enhance motor function for cancer patients could be useful for continuing cancer treatment, and furthermore, improving prognosis.

Activation of the angiotensin II receptor promotes autophagy in renal proximal tubular cells and affords protection from ischemia/reperfusion injury.

Roles of the renin-angiotensin system in autophagy and ischemia/reperfusion (I/R) injury in the kidney have not been fully characterized. Here we examined the hypothesis that modest activation of the angiotensin II (Ang II) receptor upregulates autophagy and increases renal tolerance to I/R injury. Sprague-Dawley rats were assigned to treatment with a vehicle or a non-pressor dose of Ang II (200 ng/kg/min) for 72 h before 30-min renal I/R. LC3-immunohistochemistry showed that Ang II treatment increased autophagosomes in proximal tubular cells by 2.7 fold. In Ang II-pretreated rats, autophagosomes were increased by 2.5 fold compared to those in vehicle-treated rats at 4 h after I/R, when phosphorylation of Akt and S6 was suppressed and ULK1-Ser555 phosphorylation was increased. Serum creatinine and urea nitrogen levels, incidence of oliguria, and histological score of tubular necrosis at 24 h after I/R were attenuated by Ang II-pretreatment. In NRK-52E cells, Ang II induced LC3-II upregulation, which was inhibited by losartan but not by A779. The results indicate that a non-pressor dose of Ang-II promotes autophagy via ULK1-mediated signaling in renal tubular cells and attenuates renal I/R injury. The AT1 receptor, but not the Mas receptor, contributes to Ang-II-induced autophagy and presumably also to the renoprotection.

Incidence and risk factors of acute kidney injury, and its effect on mortality among Japanese patients receiving immune check point inhibitors: a single-center observational study.

BACKGROUND: Immune checkpoint inhibitors (ICPis) are associated with multi-organ immune-related adverse effects. Here, we examined the incidence rate, recovery rate, and risk factors of acute kidney injury complicated with ICPis (ICPi-AKI) and evaluted the association between ICPi-AKI and mortality in Japanese patients. METHODS: We analyzed 152 consecutive patients receiving ICPis between 2015 and 2019. A logistic regression analysis was performed to identify risk factors for ICPi-AKI incidence and Cox regression analysis was performed to evaluate the association between ICPi-AKI and mortality. RESULTS: The mean patient age was 67 ± 10 years, with the median baseline serum creatinine level of 0.78 mg/dL. Twenty-seven patients (18%) developed ICPi-AKI, and 19 (73%) of them recovered. Pembrolizumab use and liver diseases were significant risk factors for the ICPi-AKI incidence. During the follow-up, 85 patients (59%) died, 17 patients (63%) with ICPi-AKI and 68 (54%) patients without ICPi-AKI, respectively. The ICPi-AKI incidence was not independently associated with mortality (adjusted hazard ratio, 0.85; 95% confidence intervals, 0.46-1.61). CONCLUSIONS: Our finding suggest that pembrolizumab use and liver diseases are associated with a higher risk of ICPi-AKI development, but ICPi-AKI did not affect mortality. Future multi-center studies are needed to develop optimal management and prevention strategies for this complication in patients receiving ICPis.

Impact of atrial fibrillation on the risk of ischemic stroke in patients on hemodialysis: BOREAS-HD3 Study.

BACKGROUND: Atrial fibrillation (AF) is an established risk factor for ischemic stroke in a general population. However, its impact in patients on hemodialysis (HD), a group with a high risk for stroke, is still controversial. Here we examined this issue in a Japanese cohort. METHODS: This study was designed as a multicenter cohort study. HD patients (n = 1,067) were enrolled from 22 institutes in January 2009 and followed up for 3 years. Patients with missing data (n = 196) or kidney transplantation (n = 4) were excluded, and 867 patients contributed to the analysis of the risk of new-onset of ischemic stroke. RESULTS: At baseline, AF was observed in 123 patients (14.2%, AF group) and not in the others (n = 744: 85.8%, non-AF group). During a follow-up period of 31.3 months, the cumulative incidence rate for ischemic stroke was significantly higher in the AF group than in the non-AF group (6.5% vs. 2.9%, p < 0.05). In Cox regression analysis, AF was a significant independent risk factor for new-onset of ischemic stroke after adjustment for age, sex, prior history of ischemic stroke, use of warfarin, dialysis vintage, comorbidity of diabetic nephropathy, and interdialytic weight gain (hazard ratio 2.17-2.68). CONCLUSION: Present analyses using comprehensive adjustment for multiple confounders, including prior history of ischemic stroke, indicated that AF independently increases the risk of new-onset of ischemic stroke by more than twofold in Japanese HD patients.

Effect of Ultrasound-Guided Hydrorelease of the Multifidus Muscle on Acute Low Back Pain.

OBJECTIVES: To examine improvement in acute low back pain (LBP) using ultrasound-guided hydrorelease of the multifidus muscle. METHODS: This prognostic cohort study was conducted in a private clinic on samples of 75 patients with acute LBP diagnosed based on physical and imaging findings. Hydrorelease of the multifidus muscle was performed at the L4/5 level. The LBP visual analog scale (VAS) scores (cm) before and 5 minutes after hydrorelease were statistically evaluated. We defined improvement rate (%) as {LBP VAS scores (cm) immediately before hydrorelease - LBP VAS scores (cm) 5 minutes after hydrorelease} × 100 / LBP VAS scores (cm) immediately before hydrorelease and examined the correlation of the Heckmatt score and average age with the improvement rate. RESULTS: LBP VAS scores (cm) before and 5 minutes after hydrorelease were 7.19 ± 1.01 (mean ± SD) and 2.85 ± 1.25, respectively (p < 0.05). No significant correlations were noted between the LBP improvement rate and the Heckmatt score or age. There were no gender variations in the improvement rate. CONCLUSIONS: Ultrasound-guided hydrorelease of the multifidus muscle led to considerable LBP VAS score improvement at the outpatient level. The improvement rate showed no correlations with the Heckmatt score or age, and there were no significant gender variations in the improvement rate. Therefore, fatty degeneration of muscles and change in muscle echogenicity due to age and gender may not be associated with muscular LBP. These findings suggest that multifidus muscle hydrorelease could be useful in the diagnosis and treatment of acute LBP.

Association between Functional Independence Measure and mortality in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: A single-center observational study.

OBJECTIVES: Previous studies have identified several predictors of mortality in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). However, functional dependence as a predictor of mortality has never been reported. In this study, we investigated whether Functional Independence Measure (FIM) was associated with mortality in AAV patients. METHODS: We analyzed 52 adults with biopsy-proven AAV in Teine Keijinkai Medical Center between January 2000 and March 2019. Adjusted Cox regression analyses were conducted to evaluate the association between three FIM-based groups and all-cause mortality. Estimates were calculated as hazard ratios with 95% confidence intervals (95% CIs). RESULTS: During a median follow-up of 2.3 years (interquartile range, 0.7-4.6 years), death occurred in 15 patients (29%). Compared to the highest-FIM group (91-126 points), the adjusted hazard ratios for the intermediate- (55-90 points) and lowest-FIM (18-54 points) groups were 3.59 (95% CIs, 0.40-32.0) and 15.7 (95% CIs, 2.07-119) for all-cause mortality, respectively. In addition, the lower-FIM groups were associated with higher mortality (p=.0179). CONCLUSION: This study suggested that the FIM score is a predictor of all-cause mortality in AAV patients. Future studies will have to investigate whether FIM assessment leads to better outcomes.

Advanced glycation end products are associated with sarcopenia in older women: aging marker dynamics.

The aim of this study was to determine whether advanced glycation end products (AGEs) revealed by skin autofluorescence (SAF), serum and urine pentosidine level, and serum homocysteine level can serve as a biomarker for sarcopenia in older women. The participants were 70 elderly women. The AGEs pentosidine, homocysteine, and SAF were measured as aging markers. This study shows that among the biomarkers for aging, serum pentosidine correlates with a loss of appendicular lean mass and can serve as a biomarker for sarcopenia. Moreover, SAF and homocysteine values exhibited a positive correlation with age and correlated with each other.Abbreviations: AGEs: advanced glycation end products; BIA: bioelectrical impedance analyzer; BMD: bone mineral density; DLS: degenerative lumbar scoliosis; DXA: dual-energy X-ray absorptiometry; ELISA: enzyme-linked immunoassay; HHcy: hyperhomocysteinemia; RIA: radioimmunoassay; SAF: skin autofluorescence; SMI: skeletal muscle mass index; T2DM: type 2 diabetes patients.

Objective evaluation of postoperative changes in real-life activity levels in the postoperative course of lumbar spinal surgery using wearable trackers.

BACKGROUND: Lumbar spinal disease causes disabilities in performing daily activities. Operative treatments are aimed at pain relief and rapid return to routine activity. Patient-based outcome measures are used to evaluate pathologies and therapeutic effects associated with lumbar spinal disease. Nevertheless, it remains unknown as to how much such treatment improves activity levels. The purpose of the current study was to measure changes in activity levels before and after lumbar spinal surgery using a wearable activity tracker and to analyze the differences between results and patient-based outcomes. METHODS: Sixty patients who underwent lumbar surgery were studied. The physical activity of participants was objectively evaluated using a wearable Micro-Motion logger system (Actigraph). We measured the amount of activity before and at 1, 3, 6, and 12 months after the surgery to evaluate postoperative changes. The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, Oswestry Disability Index, Roland-Morris Disability Questionnaire and visual analog scale were used to assess patient-based outcomes of pain and activities of daily living-related scores; we analyzed the relationships between scores and actual activity levels. RESULTS: The amount of actual activity decreased significantly 1 month after the surgery compared to that during the preoperative period, which then improved after 3 months postoperatively (p < 0.01). Furthermore, there was a significant improvement 6 months after the surgery compared to that during the preoperative period (p < 0.05). The changes in activity for each period were strongly correlated, regardless of the period. In contrast, a significant improvement was observed at 1 month after the surgery in almost all items of the patient-based questionnaires (p < 0.05). CONCLUSIONS: The objective activity tracker demonstrated that lumbar surgery results in the amount of activity decreasing 1 month just after surgery followed by gradual postoperative recovery within 3 months. By contrast, patient-based outcomes showed improvement in 1 month that was significantly different from the change in actual activity, indicating a gap between patient-oriented clinical scores and their actual activities.

Empagliflozin, an SGLT2 Inhibitor, Reduced the Mortality Rate after Acute Myocardial Infarction with Modification of Cardiac Metabolomes and Antioxidants in Diabetic Rats.

The mechanism by which SGLT2 inhibitors reduce cardiac events in diabetic patients remains unclear. Here, we examined the effects of an SGLT2 inhibitor on the acute survival rate after myocardial infarction (MI) in an animal model of type 2 diabetes mellitus (DM) and the possible involvement of modification of cardiac metabolomes and antioxidative proteins. MI was induced in DM Otsuka Long-Evans Tokushima Fatty (OLETF) rats and Long-Evans Tokushima Otsuka (LETO) control rats. Treatment with empagliflozin (10 mg/kg per day, 14 days) before MI reduced blood glucose and increased blood and myocardial ß-hydroxybutyrate (ßOHB) levels in OLETF. Survival rate at 48 hours after MI was significantly lower in OLETF rats than in LETO rats (40% vs. 84%), and empagliflozin significantly improved the survival rate in OLETF rats to 70%, although the sizes of MI were comparable. Patterns of metabolomes and gene expression in the noninfarcted myocardium of OLETF rats were consistent with increased fatty acid oxidation and decreased glucose oxidation. The patterns were modified by empagliflozin, suggesting both increased glucose oxidation and ketone utilization in OLETF rats. Empagliflozin prevented reduction of ATP level in the noninfarcted myocardium after MI and significantly increased myocardial levels of Sirt3 and superoxide dismutase 2 in OLETF rats. Administration of ßOHB partially mimicked the effects of empagliflozin in OLETF rats. The results suggest that empagliflozin prevents DM-induced increase in post-MI mortality, possibly by protective modification of cardiac energy metabolism and antioxidant proteins.

Analysis of skeletal muscle mass in women over 40 with degenerative lumbar scoliosis.

PURPOSE: We investigated the involvement of sarcopenia in middle-aged and elderly women with degenerative lumbar scoliosis (DLS). METHODS: A total of 971 women (mean age 70.4 years) were included in our study. These included 87 cases of DLS (mean 73.8 years) and 884 controls (69.8). Lumbar and femur BMD was measured for all participants using dual-energy X-ray absorptiometry. We used a bioelectrical impedance analyzer to analyze body composition, including appendicular skeletal muscle mass index (SMI; appendicular lean mass (kg)/(height (m))2. We determined bone density and skeletal muscle mass in both groups and determined the prevalence of sarcopenia. We examined the correlation between bone density and appendicular muscle mass in both groups. We also examined factors related to scoliosis using logistic regression analysis. RESULTS: The DLS group showed significantly higher lumbar BMD, lower femur BMD, lower lean mass arm, and lower lean mass leg, and lower lean mass trunk (p < 0.05). Sarcopenia prevalence (SMI < 5.75) was 59.8% in DLS subjects and 42.8% in controls, revealing a high prevalence in DLS (p < 0.05). In both groups, lumbar and femur BMD were positively correlated with appendicular muscle mass. By logistic regression analysis, trunk muscle mass was detected as a risk factor for DLS independent of age (p < 0.05). CONCLUSIONS: In middle-aged and elderly women, prevalence of sarcopenia was 59.8% in DLS cases and 42.8% in controls, which revealed a high prevalence in DLS. A decrease in trunk muscle was a significant risk factor for DLS that was independent of age. These slides can be retrieved under Electronic Supplementary Material.

Relationship between patient-based scoring systems and the activity level of patients measured by wearable activity trackers in lumbar spine disease.

PURPOSES: To evaluate whether a relationship exists between patient-based scoring systems and the activity level of patients with low back pain (LBP) by using wearable activity trackers, and to determine whether activity level was affected by patient factors. METHODS: The subjects were 66 patients with LBP. The physical activity of participants was objectively evaluated using the Micro-Motion logger (Actigraph). The activity level was analyzed with the mean active count of the proportional-integrating mode (PMAC) and zero-crossing mode. Clinical symptoms were evaluated using the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Roland-Morris Disability Questionnaire, the Oswestry Disability Index, and visual analog scale (VAS). The relationships between each item of the patient-based questionnaire and activity level, and the influence of individual factors (age, sex, body mass index [BMI], low back pain, and muscle mass) on the activity level were evaluated. RESULTS: In each domain of the JOABPEQ, lumbar spine dysfunction and social life dysfunction were correlated with PMAC (r = 0.327 and 0.321, respectively). The low back pain VAS scores were correlated with PMAC (r = - 0.246). Multiple regression analysis shows that individual factors affecting the activity level of patients with LBP were sex, BMI, low back pain, and muscle mass in PMAC (p < 0.01). CONCLUSIONS: Some domains of the questionnaires were correlated with activity level, but others were not. Additionally, the activity level of patients with LBP was affected by sex, BMI, LBP, and skeletal muscle mass index. These slides can be retrieved under Electronic Supplementary Material.

Translational regulation by miR-301b upregulates AMP deaminase in diabetic hearts.

AMP deaminase (AMPD) plays a crucial role in adenine nucleotide metabolism. Recently we found that upregulated AMPD activity is associated with ATP depletion and contractile dysfunction under the condition of pressure overloading in the heart of a rat model of type 2 diabetes mellitus (T2DM), OLETF. Here we examined the mechanism of AMPD upregulation by T2DM. The protein level of 90-kDa full-length AMPD3 was increased in whole myocardial lysates by 55% in OLETF compared to those in LETO, a non-diabetic control. In contrast, the mRNA levels of AMPD3 in the myocardium were similar in OLETF and LETO. AMPD3 was comparably ubiquitinated in OLETF and LETO, and its degradation ex vivo was more sensitive to MG-132, a proteasome inhibitor, in OLETF than in LETO. MicroRNA array analysis revealed downregulation (>50%) of 57 microRNAs in OLETF compared to those in LETO, among which miR-301b was predicted to interact with the 3'UTR of AMPD3 mRNA. AMPD3 protein level was significantly increased by a miR-301b inhibitor and was decreased by a miR-301b mimetic in H9c2 cells. A luciferase reporter assay confirmed binding of miR-301b to the 3'UTR of AMPD3 mRNA. Transfection of neonatal rat cardiomyocytes with a miR-301b inhibitor increased 90-kDa AMPD3 and reduced ATP level. The results indicate that translational regulation by miR-301b mediates upregulated expression of cardiac AMPD3 protein in OLETF, which potentially reduces the adenine nucleotide pool at the time of increased work load. The miR-301b-AMPD3 axis may be a novel therapeutic target for intervening enegy metabolism in diabetic hearts.

Pentosidine concentration is associated with degenerative lumbar scoliosis in older women: preliminary results.

PURPOSE: Advanced glycation end products (AGEs) have been implicated in the pathogenesis of sarcopenia. The objective of the study was to investigate the prevalence of sarcopenia in degenerative lumbar scoliosis (DLS), and the relationship between biochemical markers including major AGEs, pentosidine, and DLS in older women. METHODS: Our study participants were 20 elderly women with idiopathic DLS (mean age 76.4 years, range 56-88). Nineteen age- and sex-matched volunteers (mean age 74.0 years, range 62-86) served as controls. Spinal and femoral BMD of all participants was measured using dual-energy X-ray absorptiometry. We used a bioelectrical impedance analyzer to analyze body composition, including appendicular skeletal muscle mass index [SMI; appendicular lean mass (kg)/(height (m)]2. SMI < 5.75 was considered diagnostic for sarcopenia. Coronal and sagittal spinal alignments were measured. The following biochemical markers were measured: serum and urinary pentosidine, serum homocysteine, 1,25(OA)2D, and 25(OH)D. The level of each variable was compared between DLS and controls. The relationship between biochemical markers including pentosidine and DLS was examined. RESULTS: Sarcopenia was observed at a high prevalence in participants with DLS: 50% compared with 15.8% of healthy controls. Height, weight, femoral BMI, appendicular lean mass, total lean mass, and SMI all had significantly lower values in the DLS group. Serum pentosidine was significantly higher for the DLS group compared with controls. Correlations with serum pentosidine revealed a significant positive correlation between lumbar scoliosis, pelvic tilt, and pelvic incidence-lumbar lordosis mismatch, and a significantly negative correlation between thoracic kyphosis (P < 0.05). CONCLUSIONS: We found that sarcopenia was involved in DLS, and high serum pentosidine levels are associated with severity of coronal and sagittal malalignment in older women, suggesting that high levels of AGEs are a potential biomarker for the progression of lumbar scoliosis and kyphotic deformity. Further studies are needed to clarify the pathogenesis of DLS.

Successful Transcatheter Diagnosis and Medical Treatment of Right Atrial Involvement in IgG4-related Disease.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder characterized by lymphoplasmacytic infiltration of numerous IgG4-positive plasma cells, leading to fibrous thickening in the affected tissue. Typical cardiovascular manifestations of IgG4-RD are periaortitis, coronary arteritis, and pericarditis. Rare cases of myocardial involvement in IgG4-RD have been reported, but surgical resection or open biopsy was required for the diagnosis in those cases. Here, we report a case in which percutaneous transcatheter biopsy under the guidance of intracardiac echocardiography was useful for diagnosis of IgG4-RD manifested as an intracavitary right atrial mass, extending into the superior vena cava. Successful transcatheter diagnosis of myocardial involvement of IgG4-RD led to immediate favorable response to steroid therapy. Including the present case, previous IgG4-RD cases with myocardial involvement are reviewed to delineate its clinical characteristics.