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Aims/Introduction: To investigate whether sarcopenic obesity is associated with the progression of atherosclerotic lesions in older patients with diabetes and to identify the obesity components of sarcopenic obesity that best reflect atherosclerosis. Materials and Methods: In 118 inpatients aged ≥75 years with diabetes mellitus, sarcopenia defined as a low skeletal muscle mass and low grip strength was assessed, and sarcopenia coexisting with a high body‐fat percentage or visceral fat area was defined as sarcopenic obesity. Correlations between the obesity components and atherosclerotic markers, including the carotid intima‐media thickness, were analyzed; the intima‐media thickness was analyzed in four groups with and without obesity and sarcopenia, and a multiple linear regression analysis adjusted for covariates was conducted to investigate whether sarcopenic obesity was independently associated with the intima‐media thickness. Results: The visceral fat area and intima‐media thickness showed positive correlations in the overall patients (P = 0.032) and the sarcopenia (P = 0.016) group but showed no associations in participants without sarcopenia. The intima‐media thickness in the group showing sarcopenia with a high visceral fat area was significantly higher than that in the control group (P = 0.012). Sarcopenic obesity defined by a high body‐fat percentage and high visceral fat area was independently associated with the intima‐media thickness even after adjusting for age, sex, and atherogenic risk factors. However, sarcopenic obesity defined by a high visceral fat area was more strongly associated with the intima‐media thickness (β = 0.384, P = 0.002) than that defined by the high body‐fat percentage (β = 0.237, P = 0.068). Conclusions: Sarcopenic obesity, especially that defined by visceral fat accumulation, reflected the risk of atherosclerotic lesion progression in older patients with diabetes. [ABSTRACT FROM AUTHOR]

Aim: This longitudinal study aimed to determine whether categorization by the Dementia Assessment Sheet for Community‐based Integrated Care System 8‐items (DASC‐8) is associated with risk of frailty onset, disability, and mortality. Methods: We analyzed longitudinal data from outpatients aged 65 years and older evaluated for the DASC‐8 at the Frailty Clinic. The outcomes during the 3‐year follow‐up period were (Study A) frailty onset (Kihon Checklist ≥8) and (Study B) disability (new certification of nursing care needs) or mortality. Multivariate Cox regression analyses were performed to examine independent associations between the DASC‐8 category and outcomes, and hazard ratios and 95% confidence intervals (CIs) were calculated after adjustment for age, sex, and the presence or absence of diabetes, hypertension, and dyslipidemia. Results: (Study A) Out of the 216 patients without frailty in Categories I or II at baseline, 40 (20.4%) and 11 (55.0%) developed frailty, respectively. The adjusted hazard ratio was 3.62 (95% CI: 1.69–7.76, P < 0.001). (Study B) Out of the 350 patients who did not require long‐term care at baseline, disability or death occurred for 20 (7.3%) in Category I, 14 (23.0%) in Category II, and 9 (56.3%) in Category III. The adjusted hazard ratios were 2.40 (Category I vs. II; 95% CI: 1.13–5.11, P = 0.023) and 5.43 (Category I vs. III; 95% CI: 2.23–13.3, P < 0.001). Conclusion: Categorization according to DASC‐8 is associated with the risk of frailty, disability, and mortality in older patients. Geriatr Gerontol Int 2024; 24: 150–155. [ABSTRACT FROM AUTHOR]

The document is a response to comments on a study about the coexistence of high visceral fat area, sarcopenia, and atherosclerotic markers in older patients with diabetes. The authors address concerns about the measurement of carotid intima-media thickness (cIMT) and the use of electrocardiographic (ECG) synchronization. They defend their measurement protocol for cIMT, emphasizing the importance of accurate measurement protocols in clinical research. The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Tokyo Metropolitan Geriatric Hospital. [Extracted from the article]

Adenosine causes the anti-inflammatory effect of MTX; however, the contributions of synoviocyte adenosine receptors (AdoRs) are unknown, and matrix metalloproteinase 3 (MMP-3) is released by fibroblast-like synoviocytes in response to inflammatory signaling. To understand the mechanism of the clinical observation that the matrix proteinase-3 concentration of patients with rheumatoid arthritis treated successfully with methotrexate does not usually normalize, we investigated the effects of A2A AdoR activation and inhibition on tumor necrosis factor-alpha (TNFα)-induced MMP-3 release by MH7A human rheumatoid synovial cells. MH7A cells constitutively expressed membrane-associated A2A AdoRs, and HENECA enhanced intracellular cAMP. Stimulation with TNFα markedly enhanced release of MMP-3 from MH7A cells, whereas HENECA partially and dose-dependently inhibited TNFα-evoked MMP-3 release. Similarly, dbcAMP partially inhibited TNFα-induced MMP-3 release. Pretreatment with ZM241385 reversed the inhibitory effects of HENECA. Further, TNFα induced p38 MAPK and ATF-2 phosphorylation, whereas HENECA suppressed p38 MAPK and ATF-2 phosphorylation. We concluded that adenosine signaling via A2A AdoRs, adenylyl cyclase, and cAMP reduces TNFα-induced MMP-3 production by interfering with p38 MAPK/ATF-2 activity. Activation of A2A AdoR signaling alone using HENECA did not reduce TNFα-induced MMP-3 production to the basal levels, which may explain why MTX usually decreases but does not eliminate serum MMP-3. [ABSTRACT FROM AUTHOR]

[Purpose] This study aimed to verify muscle activity patterns during posterior gait assistance with a knee-ankle-foot orthosis (KAFO) in patients with severe acute stroke hemiplegia and clarify its relationships with physical therapy parameters. [Participants and Methods] We measured activity in the rectus femoris, biceps femoris, tibialis anterior, and gastrocnemius muscles in 30 patients with acute stroke during KAFO posterior gait assistance and examined their muscle activity patterns using the Japan Coma Scale (JCS), Brunnstrom Recovery Stage (BRS), Berg Balance Scale (BBS), Functional Movement Screen (FMS), and Functional Independence Measure (FIM). We divided lower extremity muscle activity into first and second half of the stance phase, compared muscle activity during the first half of the stance phase and the second half of the stance phase. In addition, the relationship between muscle activity during gaiting and each parameter was analyzed. [Results] All four muscles showed significantly higher values in the first half of the stance phase than in the second half of the stance phase. Rectus femoris first half of the stance phase muscle activity showed a moderate correlation with the BRS, BBS, and FMS scores. [Conclusion] The amount of gastrocnemius muscle activity when KAFO assists walking from behind increases in the latter half of stance in healthy individuals. However, in patients with stroke, the activity was lower and deviated from the gastrocnemius muscle activity during walking in healthy individuals., Competing Interests: The authors declares that there is no conflict of interest., (2023©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Glycosylation is involved in various pathophysiological conditions. N-Acetylglucosaminyltransferase V (GnT-V), catalyzing β1-6 branching in asparagine-linked oligosaccharides, is one of the most important glycosyltransferases involved in cancer and the immune system. Recent findings indicate that aberrant N-glycan structure can modify lipid metabolism. In this study, we investigated the effects of aberrant glycosylation by GnT-V on high-density lipoprotein cholesterol (HDL) assembly. We used GnT-V transgenic (Tg) mice and GnT-V Hep3B cell (human hepatoma cell line) transfectants. The study also included 96 patients who underwent medical health check-ups. Total serum cholesterol levels, particularly HDL-cholesterol (HDL-C) levels, were significantly increased in Tg vs. wild-type (WT) mice. Hepatic expression of apolipoprotein AI (ApoAI) and ATP-binding cassette subfamily A member 1 (ABCA1), two important factors in HDL assembly, were higher in Tg mice compared with WT mice. ApoAI and ABCA1 were also significantly elevated in GnT-V transfectants compared with mock-transfected cells. Moreover, ApoAI protein in the cultured media of GnT-V transfectants was significantly increased. Finally, we found a strong correlation between serum GnT-V activity and HDL-C concentration in human subjects. Multivariate logistic analyses demonstrated that GnT-V activity was an independent and significant determinant for serum HDL-C levels even adjusted with age and gender differences. Further analyses represented that serum GnT-V activity had strong correlation especially with the large-size HDL particle concentration. These findings indicate that enhanced hepatic GnT-V activity accelerated HDL assembly and could be a novel mechanism for HDL synthesis., (Copyright © 2016 the American Physiological Society.)

Purpose: Mac-2 binding protein (Mac-2 bp) is one of the major fucosylated glycoproteins, which we identified with glycol-proteomic analyses. We previously reported that fucosylated glycoproteins are secreted into bile, but scarcely secreted into sera in normal liver and hypothesized that the fucosylation-based sorting machinery would be disrupted in ballooning hepatocytes due to the loss of cellular polarity. In the present study, we investigated the availability of Mac-2 bp for differential diagnosis of nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD) as a biomarker., Experimental Design: Serum Mac-2 bp levels were determined with our developed ELISA kit. Our cohort of 127 patients with NAFLD had liver biopsy to make a histological diagnosis of NASH and simple fatty liver., Results: Mac-2 bp levels were significantly elevated in NASH patients compared with non-NASH (simple steatosis) patients (2.132 ± 1.237 vs. 1.103 ± 0.500 μg/mL, p < 0.01). The area under the receiver-operating characteristic curve for predicting NASH by Mac-2 bp was 0.816. Moreover, multivariate logistic regression analyses showed Mac-2 bp levels could predict the fibrosis stage and the presence of ballooning hepatocytes in NAFLD patients., Conclusions and Clinical Relevance: These results support the potential usefulness of measuring Mac-2 bp levels in clinical practice as a biomarker for NASH., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)