[Association between depressive tendencies and oral diadochokinesis in the older adults in private residential nursing home].

AIM: This study aimed to investigate the relationship between depressive tendencies and oral diadochokinesis (ODK) in 24 older adults living in a private residential nursing home. ODK is an indicator of the oral function. METHODS: Depressive tendencies were assessed using the Geriatric Depression Scale 5, with scores of two or higher indicating probable depression. ODK was measured across four syllable tasks (/pa/, /ta/, /ka/, and /pataka/), which were evaluated using coefficient of variation (CV) values. Low CV values indicate superior performance. Potential confounders, including the cognitive function, sleep status, body mass index, instrumental activities of daily living, and physical function, were controlled. RESULTS: Five participants (20.8%) experienced depression. Individuals with depressive tendencies demonstrated significantly poor ODK performance (higher CV) in the /ta/ task and a marginally significant difference in the /ka/ task. No significant differences were observed between /pa/ and /pataka/. CONCLUSIONS: These findings suggest a link between depressive tendencies and reduced proficiency in specific ODK tasks among older nursing home residents. This finding implies that a decline in the oral function in articulating /ta/ and /ka/ syllables may precede other common depressive symptoms. Furthermore, depression monitoring could be a valuable tool for early detection of the oral function in this population, enabling timely interventions.

Theoretical analysis of efficacy of biological agent for rheumatoid arthritis based on target molecular binding occupancy.

Recently, biological agents have been used for treatment of rheumatoid arthritis (RA), though the standard therapeutic doses vary among the agents utilized. To investigate the mechanisms related to those differences, we theoretically analyzed the target molecular binding occupancies of 4 biological agents: tocilizumab, infliximab, adalimumab, and etanercept. The average binding occupancy to the target molecule (Φss) was estimated to be 99.50 ± 0.44 % in a steady state after administration of the standard therapeutic dose of each agent. Furthermore, achieved American College of Rheumatology (ACR) 20, used as an index of clinical efficacy, increased in correlation with the value for Φss. These results suggest that clinical effects are achieved with a high value of target molecular binding occupancy. Thus, we considered that all of the agents examined in this study are antagonists and elicit clinical efficacy by inhibiting the signaling of biologically active substances that are not necessary for life maintenance and are secreted or released specifically in pathological conditions. In addition, target molecular binding occupancy can be used as an appropriate index for evaluating the standard therapeutic dose of biological agent for RA.

Immunosuppressants Tacrolimus and Sirolimus revert the cardiac antifibrotic properties of p38-MAPK inhibition in 3D-multicellular human iPSC-heart organoids.

Cardiac reactive fibrosis is a fibroblast-derived maladaptive process to tissue injury that exacerbates an uncontrolled deposition of large amounts of extracellular matrix (ECM) around cardiomyocytes and vascular cells, being recognized as a pathological entity of morbidity and mortality. Cardiac fibrosis is partially controlled through the sustained activation of TGF-ß1 through IL-11 in fibroblasts. Yet, preclinical studies on fibrosis treatment require human physiological approaches due to the multicellular crosstalk between cells and tissues in the heart. Here, we leveraged an iPSC-derived multi-lineage human heart organoid (hHO) platform composed of different cardiac cell types to set the basis of a preclinical model for evaluating drug cardiotoxicity and assessing cardiac fibrosis phenotypes. We found that the inhibition of the p38-MAPK pathway significantly reduces COL1A1 depositions. Yet, concomitant treatment with organ-rejection immunosuppressant drugs Tacrolimus or Sirolimus reverts this effect, opening new questions on the clinical considerations of combined therapies in reducing fibrosis after organ transplantation.