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Nuclear factor of activated T-cells 5 (NFAT5), an osmo-sensitive transcription factor, can be activated by isotonic stimuli, such as infection. It remains unclear, however, whether NFAT5 is required for damage-associated molecular pattern- triggered (DAMP-triggered) inflammation and immunity. Here, we found that several DAMPs increased NFAT5 expression in macrophages. In particular, serum amyloid A (SAA), primarily generated by the liver, substantially upregulated NFAT5 expression and activity through TLR2/4-JNK signalling pathway. Moreover, the SAA-TLR2/4-NFAT5 axis promoted migration and chemotaxis of macrophages in an IL-6- and chemokine ligand 2-dependent (CCL2-dependent) manner in vitro. Intraarticular injection of SAA markedly accelerated macrophage infiltration and arthritis progression in mice. By contrast, genetic ablation of NFAT5 or TLR2/4 rescued the pathology induced by SAA, confirming the SAA-TLR2/4-NFAT5 axis in vivo. Myeloid-specific depletion of NFAT5 also attenuated SAA-accelerated arthritis. Of note, inflammatory arthritis in mice strikingly induced SAA overexpression in the liver. Conversely, forced overexpression of the SAA gene in the liver accelerated joint damage, indicating that the liver contributes to bolstering chronic inflammation at remote sites by secreting SAA. Collectively, this study underscores the importance of the SAA-TLR2/4-NFAT5 axis in innate immunity, suggesting that acute phase reactant SAA mediates mutual interactions between liver and joints and ultimately aggravates chronic arthritis by enhancing macrophage activation., Introduction Macrophages play a pivotal role in the pathogenesis of chronic inflammatory diseases, such as rheumatoid arthritis (RA), with broad proinflammatory, destructive, and remodeling capabilities (1, 2). Similar to other [...]

Objective We aimed to evaluate the correlation and agreement of interleukin (IL)-8 and matrix metalloproteinases (MMP-9) levels between cervicovaginal (CVF) and amniotic fluids (AF) in women with preterm labor (PTL) and to determine the clinical values of these proteins in CVF compared with those in AF. Study Design We designed a retrospective cohort study of 85 singleton pregnant women with PTL at 23 to 34 weeks, who underwent amniocentesis. The AF was cultured, and CVF samples were collected at the time of amniocentesis. Paired AF and CVF samples were assayed for IL-8 and MMP-9 by enzyme-linked immunoassay (ELISA) in duplicate on a single plate, using similar dilution ratios. Results A significant but weak correlation was found for IL-8 levels between AF and CVF (r = 0.333), while no correlation was found for MMP-9 levels between AF and CVF (r = −0.039). Intra-class correlation coefficient for the agreement of IL-8 levels between CVF and AF was 0.4335 and −0.279 for MMP-9, indicating a poor-to-fair level of agreement between the two measured values, respectively. IL-8 and MMP-9 levels in CVF were not associated with the risk of either microbial invasion of the amniotic cavity (MIAC) or spontaneous preterm delivery (SPTD) within 7 days, whereas those in AF provided good-to-excellent predictive values for these two outcomes (area under the curve [AUCs]: 0.82–0.95). AUCs for IL-8 and MMP-9 were significantly larger using AF rather than using CVF for the prediction of MIAC and SPTD. Conclusion In women with PTL, IL-8 and MMP-9 levels in CVF do not precisely reflect the levels of the corresponding proteins in AF. IL-8 and MMP-9 levels in CVF had poor predictive values for the risk of MIAC and SPTD and were significantly inferior to those in AF. Key Points IL-8 and MMP-9 levels in CVF do not precisely reflect levels of the corresponding proteins in AF. Diagnostic accuracy of IL-8 and MMP-9 in CVF alone is not sufficient to predict MIAC and SPTD. IL-8 and MMP-9 levels in AF provide good-to-excellent predictive values for these two outcomes. [ABSTRACT FROM AUTHOR]

(1) Background and Methods: This study evaluated characteristics of South Korean patients necessitating home-based primary care (HBPC) from 2018 to 2022, distinguishing between homebound individuals with chronic conditions and those with registered disabilities. (2) Result: Among 171 HBPC recipients, 56.1% were homebound, predominantly older with a median age of 81 years (interquartile range (IQR 68.5–86.0)), while 43.9% were disabled, generally younger with a median age of 39 years (IQR, 28–64). Activities of daily living were assessed, revealing a median score of 14 (IQR, 10–19), indicative of high care dependency. The most common conditions among homebound patients were dementia (27.1%) and physical mobility difficulties (21.9%), whereas mental disabilities (53.3%) and mobility issues (36.0%) prevailed in disabled patients. The primary HBPC needs for homebound patients included management of acute medical conditions (27.1%) and sores (17.7%). Conversely, regular health check-ups (46.7%) and management of neuropsychiatric symptoms (26.7%) were prevalent among the disabled group. (3) Conclusion: Notably, over 90% of HBPC patients required assistance with daily activities, highlighting significant differences in the needs and characteristics between older, homebound individuals with multiple comorbidities and younger, disabled patients receiving medical aid. These insights emphasize the necessity to develop customized HBPC programs to adequately cater to the diverse patient needs within South Korea. [ABSTRACT FROM AUTHOR]

Objective We sought to determine whether the levels of complement and other inflammatory and angiogenic mediators in cervicovaginal fluid (CVF) are independently associated with intra-amniotic infection and/or inflammation (IAI) and imminent spontaneous preterm birth (SPTB, £48 hours of sampling) in women with preterm premature rupture of membranes (PPROM). Study Design This was a retrospective study consisting of 85 singleton pregnant women with PPROM at 20 0/7 to 33 6/7 weeks. Amniotic fluid (AF) obtained via amniocentesis was cultured and assayed for interleukin-6. CVF samples collected at the time of amniocentesis were assayed for complement C3a, C4a, and C5a, HSP70 (heat shock protein 70), M-CSF (macrophage colony-stimulating factor), M-CSF-R (macrophage colony-stimulating factor-receptor), S100 A8, S100 A9, thrombospondin-2, VEGF (vascular endothelial growth factor-receptor), and VEGFR-1 (vascular endothelial growth factor-receptor 1) by enzyme-linked immunosorbent assay. Results Multivariate logistic regression analyses revealed that elevated CVF concentrations of complement C3a, 4a, and 5a were significantly associated with an increased risk of IAI and imminent SPTB, whereas those of M-CSF were associated with IAI, but not imminent SPTB (p = 0.063), after adjustment for baseline covariates (e.g., gestational age at sampling). However, univariate, and multivariate analyses showed that the CVF concentrations of angiogenic (thrombospondin-2, VEGF, and VEGFR-1) and inflammatory (HSP70, M-CSF-R, S100 A8, and S100 A9) proteins were not associated with either IAI or imminent SPTB. Conclusion In women with PPROM, elevated CVF concentrations of complement C3a, C4a, and C5a are independently related to an increased risk of IAI and imminent SPTB. These findings suggest that complement activation in CVF is significantly involved in mechanisms underlying preterm birth and in the host response to IAI in the context of PPROM. Key Points Elevated CVF levels of C3a, 4a and 5a are associated with IAI and SPTB. CVF C3a, 4a and 5a have better predictability for SPTB, compared to AF WBC. Elevated CVF levels of M-CSF were associated with IAI, but not SPTB. [ABSTRACT FROM AUTHOR]

Background: To examine the independent and combined association between relative quadriceps strength and the prevalence of type 2 diabetes mellitus (T2DM) in older adults. Methods: Among 1441 Korean older adults aged ≥65 years (71 [4.7] y) recruited between 2007 and 2016, 1055 older adults with no history of myocardial infarction, stroke, or cancer were included in the analysis. Cases of T2DM were identified by self-reported physician diagnosis, use antihyperglycemic medication or insulin, or fasting blood glucose ≥126 mg/dL. Logistic regression was used to calculate the odds ratios and 95% confidence intervals of T2DM by quartiles of relative quadriceps strength. Results: There were 162 T2DM cases (15%). Compared with the lowest quartile (weakest), the odds ratios (95% confidence intervals) of T2DM were 0.56 (0.34–0.90), 0.60 (0.37–0.96), and 0.47 (0.28–0.80) in the second, third, and fourth quartiles, respectively, after adjusting for possible confounders, including body mass index. In the joint analysis, compared with the "weak and overweight/obese" group, the odds (odds ratios [95% confidence intervals]) of T2DM was only lower in the "strong and normal weight" group (0.36 [0.22–0.60]) after adjusting for possible confounders. Conclusions: Greater relative quadriceps strength is associated with reduced odds of T2DM in older adults after adjusting for potential confounders including body mass index. [ABSTRACT FROM AUTHOR]