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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]

Introduction: Randomised controlled trials (RCTs) of early childhood home-visiting interventions led by nurses have been conducted mainly in Western countries, whereas such trials have been limited in non-Western cultures, including Asia. In South Korea, a national nurse home visit programme (Korea Early Childhood Home-visiting Intervention (KECHI)) was developed in 2020 and launched throughout the country. We designed a pragmatic RCT to evaluate the effectiveness of KECHI on child health and development and maternal health., Methods and Analysis: Eligible participants will be pregnant women at <37 weeks of gestation with risk factor scores of 2 or over, who are sufficiently fluent in Korean to read and answer the questionnaire written in Korean and live in districts where the KECHI services are available. Eight hundred participants will be recruited from the general community and through the District Public Health Centres. The participants will be randomised 1:1 to KECHI plus usual care or usual care. KECHI encompasses 25-29 home visits, group activities and community service linkage. Participants will complete assessments at baseline (<37 weeks gestation), 6 weeks, 6 months, 12 months, 18 months and 24 months post partum. The six primary outcomes will be (1) home environment (assessed by Infant/Toddler Home Observation for Measurement of the Environment), (2) emergency department visits due to injuries, (3) child development (assessed using Korean Bayley Scales of Infant and Toddler Development-III), (4) breastfeeding duration, (5) maternal self-rated health and (6) community service linkage., Ethics and Dissemination: This trial has received full ethical approval from the Institutional Review Board of the Seoul National University Hospital. Written consent will be obtained from the participants. The results will be reported at conferences, disseminated through peer-reviewed publications and used by the Korean government to expand the KECHI services., Trial Registration Number: NCT04749888., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study aimed to evaluate the agreement of disease status collected through a survey of the Korean Atomic Bomb Survivor Cohort (K-ABC), compared with medical claim records from the Korean National Health Insurance Service (NHIS) database and the Korean Central Cancer Registry (KCCR)., Methods: Data on the lifetime physician-diagnosed morbidities of 1,215 K-ABC participants were collected through an interviewer-administered questionnaire between 2020 and 2022. Survey data were linked to the NHIS and KCCR databases. Eleven diseases were included for validation. We evaluated the following indicators: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, the area under the curve (AUC), and the kappa coefficient., Results: The mean (standard deviation) age was 62.1 (18.7) years, and 42.6% of the participants were aged ≥70 years. Hypertension and cataracts showed the highest prevalence rates (33.8% and 28.8%, respectively). Hypertension, diabetes, and cancer demonstrated high sensitivity (>0.8) and specificity (>0.9), whereas diabetes, cancer, myocardial infarction, angina pectoris, and asthma exhibited high accuracy (>0.9). In contrast, arthritis, allergic rhinitis, and asthma showed low sensitivity (<0.4) and kappa values (<0.3). In the participants aged ≥70 years, the kappa value was ≥0.4 for all diseases except arthritis, allergic rhinitis, and asthma., Conclusion: The results from this initial analysis showed relatively high agreement between the survey and NHIS/KCCR databases, especially for hypertension, diabetes, and cancer. Our findings suggest that the information on morbidities collected through the questionnaires in this cohort was valid for both younger and older individuals.