👤 M Okayama

Hospitalization-associated disability (HAD) is linked to poor post-discharge outcomes in older individuals with heart failure (HF). We investigated whether HAD could be predicted by physical activity measured using a wearable device. We retrospectively analyzed data from 104 older individuals with HF whose physical activity was recorded for 3 consecutive days after initiating cardiac rehabilitation. Physical activity was categorized as sedentary behavior (≤1.5 metabolic equivalents [METs]), light-intensity physical activity (LPA; 1.6-2.9 METs), and moderate-to-vigorous physical activity (≥3.0 METs). HAD was observed in 31 (29.8%) individuals. LPA duration was significantly shorter in the HAD than non-HAD group (mean [±SD] 45.7±24.9 vs. 121.2±67.4 min/day; P<0.0001). In receiver operating characteristic curve analysis, the optimal LPA cut-off was 68 min/day, with 87.1% sensitivity and 80.8% specificity (area under the curve=0.888; P<0.0001). Physical activity measured using a wearable device may be useful in predicting HAD in older individuals with HF. Show less

Cyclic adenosine monophosphate-response element-binding protein-1-regulated transcription coactivator-1 (CRTC1), a cytoplasmic coactivator that translocates to the nucleus in response to cAMP, is associated with obesity. We previously reported that Show less

Complete endoscopic mucosal healing is defined as a Mayo endoscopic subscore of 0. Some patients diagnosed with a Mayo endoscopic subscore 0 may present with subsequent clinical relapse. Here, we aimed to demonstrate mucosal cytokine profile as a predictor of clinical relapse in ulcerative colitis patients with a Mayo endoscopic subscore of 0 as a marker of mucosal healing. We conducted prospective observational pilot study to examine the relationship between mucosal cytokine expression and subsequent relapse of UC patients diagnosed with a Mayo endoscopic subscore of 0. We enrolled 55 patients, and expression of cytokines tumor necrosis factor-α, interferon γ, interleukin-1β, interleukin-2, interleukin-4, interleukin-5, interleukin-6, interleukin-7, interleukin-8, interleukin-9, interleukin-10, interleukin-12, interleukin-13, interleukin-15, interleukin-17A, interleukin-17F, interleukin-18, interleukin-21, interleukin-22, interleukin-23, interleukin-27, and interleukin-33 was measured by quantitative real-time PCR using rectal mucosa biopsy materials. Cytokine expression levels were compared between patients who relapsed between March 1, 2016, and March 30, 2020, of the study period and those who remained in remission. Ten cytokines, including interleukin-2, interleukin-4, interleukin-8, interleukin-10, interleukin-12, interleukin-15, interleukin-17A, interleukin-21, interleukin-23, and interleukin-33, were significantly elevated in patients with subsequent relapse compared with those who remained in remission. Interleukin-8 expression was the most useful predictor. In the rectal mucosa of ulcerative colitis patients with Mayo endoscopic subscore 0, levels of several cytokines were elevated in cases of subsequent relapse. Among these, interleukin-8 expression was the most useful for predicting relapse. Show less

The activation of liver X receptor (LXR) α or LXRβ negatively regulates the expression of pro-inflammatory genes in mammalian cells. We recently reported that 25-hydroxycholesterol, a representative LXR-activating oxysterol, suppresses IL-6 production in mouse mast cells (MCs) following its engagement of the high-affinity IgE receptor (FcεRI). This finding suggests that murine MCs express functional LXRs; however, the mechanisms underlying the LXR-dependent repression of the MC-mediated production of pro-inflammatory cytokines, including IL-6, are poorly understood. Therefore, we employed the synthetic LXR ligand GW3965 to examine the functions of LXRα and LXRβ in the production of pro-inflammatory cytokines by murine bone marrow-derived MCs (BMMCs). We prepared BMMCs from wild-type (WT), LXRα(-/-), and LXRα/β(-/-) mice. Each group of BMMCs was pretreated with GW3965 and then stimulated with IgE+antigen (Ag) or lipopolysaccharide (LPS). Cytokine production was then analyzed using specific ELISA kits. The activation of LXRs by GW3965 significantly attenuated the production of IL-1α and IL-1β, but not of IL-6, in the WT and LXRα(-/-) BMMCs stimulated with IgE+Ag. However, GW3965 treatment decreased the production of IL-1α, IL-1β, and IL-6 in WT and LXRα(-/-) BMMCs upon stimulation with LPS, while the GW3965-mediated suppression of cytokine production was nearly absent from the LXRα/β(-/-) BMMCs. These findings demonstrate, for the first time, that the activation of LXRs by GW3965 attenuates the antigen- or LPS-induced production of pro-inflammatory cytokines, such as IL-1α and IL-1β, in murine MCs and that LXRβ plays an important role in the LXR-mediated repression of cytokine production. Show less

Recent genome wide association studies discovered seven novel loci that influence plasma concentrations of triglycerides, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol in Europeans. To date, large scale replication studies using populations with known differences in genome-wide linkage disequilibrium (LD) pattern have not been undertaken. To address this issue, we tested associations between single nucleotide polymorphisms (SNPs) within the seven novel loci and plasma lipid profiles in 21 010 Japanese individuals. Multiple linear regression analyses showed that the rs3812316 in MLXIPL was strongly associated with triglyceride concentrations (p approximately 3.0x10(-11), 7.1 mg/dl decrease per minor C allele) and that rs599839 in CELSR2/PSRC1/SORT1 was strongly associated with LDL cholesterol concentrations (p approximately 3.1x10(-11), 4.7 mg/dl decrease per minor G allele) in the Japanese population. SNPs near ANGPTL3, TRIB1 and GALNT2 showed evidence for associations with triglyceride concentrations (3.6x10(-6)Show less