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1.
Article in English | MEDLINE | ID: mdl-39175268

ABSTRACT

BACKGROUND: Health literacy, influenced by sociodemographic characteristics such as ethnicity, economic means and societal factors, affects the ways in which pregnant women maintain their health; this in turn may increase risk of adverse pregnancy outcomes. OBJECTIVE: To explore what is known about the impact of personal health literacy on prevention of stillbirth and related adverse outcomes in pregnant women of low socioeconomic status or from ethnic minority backgrounds. SEARCH STRATEGY: MEDLINE, CINAHL, PsychINFO, and CENTRAL were searched as well as reference lists of included studies and gray literature. SELECTION CRITERIA: Included studies focused on personal health literacy and stillbirth prevention in women from low socioeconomic or ethnic minority backgrounds in the perinatal period. DATA COLLECTION AND ANALYSIS: A meta-summary approach was adopted for qualitative, observational, descriptive, and audit studies. Findings of intervention studies were extracted, and meta-analyses were conducted where possible. The primary outcome was stillbirth; maternal mortality and neonatal mortality were secondary outcomes. MAIN RESULTS: Forty-one studies were included from diverse geographical settings. The meta-summary synthesized five abstracted statements. These recognized lower personal health literacy and greater difficulty interacting with healthcare services in the studied populations, primarily as the result of limited health knowledge, lack of positive perception towards health services, language barriers, illiteracy, and relying on friends or family members for health information. Meta-analysis of intervention studies revealed no association between current interventions that aimed to increase personal health literacy and the risk of stillbirth (relative risk [RR] 1.04, 95% confidence interval [CI] 0.96-1.12), neonatal mortality (RR 0.88, 95% CI 0.75-1.03), and maternal mortality (RR 0.87, 95% CI 0.63-1.22). CONCLUSIONS: Various factors suggest lower personal health literacy in women of low socioeconomic status or ethnic minority, which can increase the risk of stillbirth. However, this review identified no significant impact of current health education interventions on the risk of stillbirth, or neonatal or maternal mortality. Although not directly measured, the health education interventions were anticipated to increase personal health literacy. Further research on the topic of this scoping review is warranted, particularly in lower-resource settings and regarding the potential role of e-literacy and organizational health literacy to improve pregnancy outcomes. To address deficits in health literacy, efforts must be made to provide pregnant women with health information in novel, accessible ways.

2.
Circ Cardiovasc Imaging ; 17(8): e016852, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39163376

ABSTRACT

BACKGROUND: Right ventricular (RV) dysfunction is known to impact prognosis, but its determinants in coronary artery disease are poorly understood. Stress cardiac magnetic resonance (CMR) has been used to assess ischemia and infarction in relation to the left ventricle (LV); the impact of myocardial tissue properties on RV function is unknown. METHODS: Vasodilator stress CMR was performed in patients with known coronary artery disease at 7 sites between May 2005 and October 2018. Myocardial infarction was identified on late gadolinium enhancement-CMR, and infarct transmurality was graded on a per-segment basis. Ischemia was assessed on stress CMR based on first-pass perfusion and localized by using segment partitions corresponding to cine and late gadolinium enhancement analyses. RV function was evaluated by CMR-feature tracking for primary analysis with a global longitudinal strain threshold of 20% used to define impaired RV strain (RVIS); secondary functional analysis via RV ejection fraction was also performed. RESULTS: A total of 2604 patients were studied, among whom RVIS was present in 461 patients (18%). The presence and magnitude of RVIS were strongly associated with LV dysfunction, irrespective of whether measured by LV ejection fraction or wall motion score (P<0.001 for all). Regarding tissue substrate, regions of ischemic and dysfunctional myocardium (ie, hibernating myocardium) and infarct size were each independently associated with RVIS (both P<0.001). During follow-up (median, 4.62 [interquartile range, 2.15-7.67] years), 555 deaths (21%) occurred. Kaplan-Meier analysis for patients stratified by presence and magnitude of RV dysfunction by global longitudinal strain and RV ejection fraction each demonstrated strong prognostic utility for all-cause mortality (P<0.001). RVIS conferred increased mortality risk (hazard ratio, 1.35 [95% CI, 1.11-1.66]; P=0.003) even after controlling for LV function, infarction, and ischemia. CONCLUSIONS: RVIS in patients with known coronary artery disease is associated with potentially reversible LV processes, including LV functional impairment due to ischemic and predominantly viable myocardium, which confers increased mortality risk independent of LV function and tissue substrate.


Subject(s)
Coronary Artery Disease , Magnetic Resonance Imaging, Cine , Myocardial Perfusion Imaging , Ventricular Dysfunction, Right , Ventricular Function, Right , Humans , Male , Female , Coronary Artery Disease/physiopathology , Coronary Artery Disease/complications , Coronary Artery Disease/diagnostic imaging , Middle Aged , Aged , Magnetic Resonance Imaging, Cine/methods , Ventricular Dysfunction, Right/physiopathology , Ventricular Dysfunction, Right/etiology , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Function, Right/physiology , Myocardial Perfusion Imaging/methods , Predictive Value of Tests , Stroke Volume/physiology , Ventricular Function, Left/physiology , Prognosis , United States/epidemiology
3.
Cancer Res Treat ; 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39118525

ABSTRACT

Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non-small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of TCGA and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in disease control rate per the TP53 mutation status (p=0.503); however, female patients with TP53 mutated (MT) had a significantly prolonged median progression-free survival (PFS) compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). PD-L1 high (≥50%) expression was significantly enriched in female patients with TP53 MT (p=0.001). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p<0.001). In TCGA analysis, expression of immune-related genes, and TMB score in TP53 MT females were higher than in males without TP53 MT. Conclusion: Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

4.
Article in English | MEDLINE | ID: mdl-39162101

ABSTRACT

OBJECTIVES: To evaluate the treatment outcomes in patients with advanced-stage olfactory neuroblastoma (ONB) who received induction chemotherapy (IC). MATERIALS AND METHODS: The clinical data of 38 patients with advanced-stage ONB who received initial IC were retrospectively analyzed. The response was defined using the Response Evaluation Criteria in Solid Tumors version 1.1. Patients with complete remission or partial remission were defined as responders. RESULTS: Seventeen (44.7%) patients responded to IC. The response rate was higher in patients with high Hyams grade tumor (III/IV) compared to those with low-grade tumors (I/II) (60% vs. 22.2%, p = 0.038). Overall, the 5-year cancer-specific survival (CSS) rate was 76.0%. Among nonresponders to IC, a significant difference in 5-year CSS rates was observed between surgery with adjuvant radiotherapy (RT) (100%) versus definitive RT or chemoradiotherapy (CRT) (68.6%) (log-rank p = 0.006). However, for responders, there was no significant difference in 5-year CSS rates between surgery with adjuvant therapy (75%) and definitive RT or CRT (51.1%) (log-rank p = 0.536). When only high-grade tumors were considered among responders, the 5-year CSS rate was significantly higher in patients who received RT or CRT (51.4%) compared to those who underwent surgery with adjuvant therapy (0%) (log-rank p = 0.008). CONCLUSION: In advanced-stage ONB, RT or CRT may be preferable for high-grade tumor responding to IC. Higher response rate and a potential role for induction IC in determining the optimal definitive treatment modality suggest a positive role for advanced-stage high-grade ONB.

5.
Mol Cancer ; 23(1): 155, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39095793

ABSTRACT

BACKGROUND: Immune checkpoint therapy (ICT) provides durable responses in select cancer patients, yet resistance remains a significant challenge, prompting the exploration of underlying molecular mechanisms. Tyrosylprotein sulfotransferase-2 (TPST2), known for its role in protein tyrosine O-sulfation, has been suggested to modulate the extracellular protein-protein interactions, but its specific role in cancer immunity remains largely unexplored. METHODS: To explore tumor cell-intrinsic factors influencing anti-PD1 responsiveness, we conducted a pooled loss-of-function genetic screen in humanized mice engrafted with human immune cells. The responsiveness of cancer cells to interferon-γ (IFNγ) was estimated by evaluating IFNγ-mediated induction of target genes, STAT1 phosphorylation, HLA expression, and cell growth suppression. The sulfotyrosine-modified target gene of TPST2 was identified by co-immunoprecipitation and mass spectrometry. The in vivo effects of TPST2 inhibition were evaluated using mouse syngeneic tumor models and corroborated by bulk and single-cell RNA sequencing analyses. RESULTS: Through in vivo genome-wide CRISPR screening, TPST2 loss-of-function emerged as a potential enhancer of anti-PD1 treatment efficacy. TPST2 suppressed IFNγ signaling by sulfating IFNγ receptor 1 at Y397 residue, while its downregulation boosted IFNγ-mediated signaling and antigen presentation. Depletion of TPST2 in cancer cells augmented anti-PD1 antibody efficacy in syngeneic mouse tumor models by enhancing tumor-infiltrating lymphocytes. RNA sequencing data revealed TPST2's inverse correlation with antigen presentation, and increased TPST2 expression is associated with poor prognosis and altered cancer immunity across cancer types. CONCLUSIONS: We propose TPST2's novel role as a suppressor of cancer immunity and advocate for its consideration as a therapeutic target in ICT-based treatments.


Subject(s)
Programmed Cell Death 1 Receptor , Sulfotransferases , Animals , Humans , Mice , Sulfotransferases/genetics , Sulfotransferases/metabolism , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/metabolism , Cell Line, Tumor , Interferon-gamma/metabolism , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , CRISPR-Cas Systems , Xenograft Model Antitumor Assays , Neoplasms/genetics , Neoplasms/drug therapy , Neoplasms/immunology , Neoplasms/pathology , Neoplasms/metabolism , Disease Models, Animal
6.
Heliyon ; 10(14): e34749, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39130470

ABSTRACT

Climate change is an imminent threat, particularly affecting agricultural productivity, which relies heavily on weather conditions. Understanding the specific impacts of climate change on key crops is crucial for developing effective adaptation strategies to ensure food security. The growth patterns of onions and garlic were observed at over ten different locations in South Korea, and the yield data from the past 40 years were analyzed. The yield was significantly correlated with temperature and strongly affected by the frequent and unexpected patterns of precipitation. The increase in mean temperature during winter and the spatial and temporal concentration of precipitation are expected to be the most influential factors for Allium crop production in the future. In addition, the yields of onions and garlic can serve as good indicators for predicting the impacts of weather on agricultural productivity, given their extended cultivation periods and significant correlations with temperature and precipitation. As climate change scenarios become available, the results of this study can serve as a basis for predicting changes in agricultural production in the future and identifying opportunities to adapt cultivation systems for food security.

7.
Pharmaceuticals (Basel) ; 17(7)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-39065733

ABSTRACT

Objective: The pleiotropic effect of hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) is responsible for potent defense against inflammatory response. This study evaluated the inhibitory effects of HMG-CoA reductase inhibitors on the monosodium urate (MSU)-induced inflammatory response through the regulation of interleukin-37 (IL-37) expression. Methods: Serum was collected from patients with gout (n = 40) and from healthy controls (n = 30). The mRNA and protein expression of the target molecules IL-1ß, IL-37, caspase-1, and Smad3 were measured in THP-1 macrophages stimulated with MSU, atorvastatin, or rosuvastatin using a real-time quantitative polymerase chain reaction and Western blot assay. Transfection with IL-1ß or Smad3 siRNA in THP-1 macrophages was used to verify the pharmaceutical effect of statins in uric-acid-induced inflammation. Results: Serum IL-37 levels in gout patients were significantly higher than in controls (p < 0.001) and was associated with the serum uric acid level (r = 0.382, p = 0.008). THP-1 cells stimulated with MSU markedly induced IL-37 mRNA expression and the transition of IL-37 from the cytoplasm to the nucleus. Recombinant IL-37 treatment dose-dependently inhibited activation of caspase-1 and IL-1ß in MSU-induced inflammation. Atorvastatin and rosuvastatin attenuated caspase-1 activation and mature IL-1ß expression but augmented translocation of IL-37 from the cytoplasm to the nucleus. Atorvastatin and rosuvastatin induced phosphorylation of Smad3 in THP-1 cells treated with MSU crystals. Statins potently attenuated translocation of IL-37 from the cytoplasm to the nucleus in THP-1 macrophages transfected with Smad3 siRNA compared to cells with negative control siRNA. Conclusions: This study revealed that statins inhibit the MSU-induced inflammatory response through phosphorylated Smad3-mediated IL-37 expression in THP-1 macrophages.

8.
Article in English | MEDLINE | ID: mdl-39003647

ABSTRACT

BACKGROUND: Wheat allergy is one of the most prevalent allergens in Korea, decreasing quality of life and causing nutritional repercussions. OBJECTIVE: We aimed to investigate the efficacy and safety of the home-based wheat oral immunotherapy (OIT) using wheat noodles in children with a wheat allergy. METHODS: We conducted a retrospective study involving 72 children aged 3 to 17 years diagnosed with a wheat allergy. Patients received wheat OIT using wheat noodles (n = 50) and were compared with a historical control group (n = 22). Baseline characteristics, adverse events, and immunological changes were assessed. Predictors of successful desensitization were identified using logistic regression analysis. RESULTS: Among 50 patients completing the up-dosing phase, 82.0% achieved desensitization to 2,400 mg of wheat protein, compared to 4.5% in the control group (p < 0.001). During the up-dosing period, the median number of adverse reactions per person was 2, and anaphylaxis occurred in 30.0% (15/50). However, there were no life-threatening adverse events. In multivariable analysis, the presence of asthma (adjusted odds ratio [aOR], 8.88; 95% confidence interval [CI], 1.10-71.97; p = 0.041) and a higher ratio of specific IgE (sIgE) to ω-5-gliadin and total IgE (aOR 19.09, 95%CI 1.21-300.80, p = 0.036) were significantly associated with treatment outcomes of wheat OIT. CONCLUSION: Our study showed the safety and efficacy of home-based wheat OIT using boiled noodles in Korean children with wheat allergies. Careful consideration is warranted for patients with elevated baseline sIgE to ω-5-gliadin to total IgE ratio and a history of asthma.

9.
Circ Heart Fail ; 17(7): e011123, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38979607

ABSTRACT

BACKGROUND: Systemic hemodynamics and specific ventilator settings have been shown to predict survival during venoarterial extracorporeal membrane oxygenation (ECMO). How the right heart (the right ventricle and pulmonary artery) affect survival during venoarterial ECMO is unknown. We aimed to identify the relationship between right heart function with mortality and the duration of ECMO support. METHODS: Cardiac ECMO runs in adults from the Extracorporeal Life Support Organization Registry between 2010 and 2022 were queried. Right heart function was quantified via pulmonary artery pulse pressure (PAPP) for pre-ECMO and on-ECMO periods. A multivariable model was adjusted for modified Society for Cardiovascular Angiography and Interventions stage, age, sex, and concurrent clinical data (ie, pulmonary vasodilators and systemic pulse pressure). The primary outcome was in-hospital mortality. RESULTS: A total of 4442 ECMO runs met inclusion criteria and had documentation of hemodynamic and illness severity variables. The mortality rate was 55%; nonsurvivors were more likely to be older, have a worse Society for Cardiovascular Angiography and Interventions stage, and have longer pre-ECMO endotracheal intubation times (P<0.05 for all) than survivors. Increasing PAPP from pre-ECMO to on-ECMO time (ΔPAPP) was associated with reduced mortality per 2 mm Hg increase (odds ratio, 0.98 [95% CI, 0.97-0.99]; P=0.002). Higher on-ECMO PAPP was associated with mortality reduction across quartiles with the greatest reduction in the third PAPP quartile (odds ratio, 0.75 [95% CI, 0.63-0.90]; P=0.002) and longer time on ECMO per 10 mm Hg (beta, 15 [95% CI, 7.7-21]; P<0.001). CONCLUSIONS: Early on-ECMO right heart function and interval improvement from pre-ECMO values were associated with mortality reduction during cardiac ECMO. Incorporation of right heart metrics into risk prediction models should be considered.


Subject(s)
Extracorporeal Membrane Oxygenation , Hospital Mortality , Pulmonary Artery , Registries , Humans , Extracorporeal Membrane Oxygenation/mortality , Extracorporeal Membrane Oxygenation/methods , Male , Female , Middle Aged , Pulmonary Artery/physiopathology , Aged , Adult , Heart Failure/mortality , Heart Failure/therapy , Heart Failure/physiopathology , Ventricular Function, Right/physiology , United States/epidemiology , Risk Factors , Time Factors
10.
Angew Chem Int Ed Engl ; : e202409655, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967990

ABSTRACT

5,18-Dimesitylorangarin and its BF2 complex were synthesized by double SNAr reaction of 3,5-dibromo-BODIPY with 2-pyrrolydipyrrin as the first examples of meso-aryl-substituted orangarin. These orangarins, delineated as [20]pentaphyrin(1.0.1.0.0), are strongly antiaromatic but rather stable. The free base orangarin was coupled by oxidation with MnO2 to give a 11,11'-linked dimer, a cyclooctatetraene(COT)-centered trimer, and a spiro-trimer. Fused COT-centered 3H-orangarin dimer was oxidized to the corresponding 2H-orangarin dimer, which was further coupled to give a triply COT-centered 2H-orangarin tetramer. 3H-Orangarin oligomers are all antiaromatic as evinced by extremely low-field-shifted 1H NMR signals of the inner NH and ill-defined absorption spectra with broad tails. In contrast, COT-centered 2H-orangarin dimer and tetramer show moderately low-field-shifted NH signals and intense NIR absorbance over 900 nm, suggesting effective π-conjugation through the COT bridge and almost non-antiaromatic character. These orangarin oligomers exhibit many reversible redox potentials owing to the intramolecular electronic interactions. Regardless of the different aromatic characters, all the orangarin monomers and oligomers exhibit very rapid excited-state decays.

11.
Materials (Basel) ; 17(13)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38998216

ABSTRACT

Recent advances in the leisure boat industry have spurred demand for improved materials for propeller manufacturing, particularly high-strength aluminum alloys. While traditional Al-Si alloys like A356 are commonly used due to their excellent castability, they have limited mechanical properties. In contrast, 7xxx series alloys (Al-Zn-Mg-Cu based) offer superior mechanical characteristics but present significant casting challenges, including hot-tearing susceptibility (HTS). This study investigates the optimization of 7xxx series aluminum alloys for low-pressure die-casting (LPDC) processes to enhance propeller performance and durability. Using a constrained rod-casting (CRC) method and finite element simulations, we evaluated the HTS of various alloy compositions. The results indicate that increasing Zn and Cu contents generally increase HTS, while a sufficient Mg content of 2 wt.% mitigates this effect. Two optimized quaternary Al-Zn-Mg-Cu alloys with relatively low HTS were selected for LPDC propeller production. Simulation and experimental results demonstrated the effectiveness of the proposed alloy compositions, highlighting the need for further process optimization to prevent hot tearing in high Mg and Cu content alloys.

12.
J Speech Lang Hear Res ; 67(8): 2638-2652, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39024517

ABSTRACT

PURPOSE: Developmental language disorder (DLD) is a neurodevelopmental disorder that impacts approximately 7% of the population and is characterized by unexplained deficits in expressive and/or receptive components of language. A common procedural learning task, serial reaction time (SRT), has been used to develop models of the basis of DLD. However, paradigms involve differing levels of implicit and explicit learning during this task, muddying interpretations of the data. Here, we tested adults with DLD on implicit and explicit SRT tasks to better understand implicit and explicit procedural learning in this population. We hypothesized that adults with DLD would demonstrate reduced learning on only the implicit SRT task, as alternate explicit neural mechanisms could lead to equivalent performance on the explicit task. METHOD: Fifty participants (25 with DLD and 25 with typical language) completed implicit and explicit SRT tasks, measuring their ability to learn visually presented 10-element sequences. Group differences were evaluated on sequence learning, error rates, and explicit recall of the sequence after learning. RESULTS: Sequence learning was the same between the groups on both tasks. However, individuals with DLD showed increased errors and significantly worse recall of the explicitly learned sequence. CONCLUSIONS: Results suggest that sequence learning may be intact in this population, while aspects of explicit learning and motoric responses are impaired. Results are interpreted in light of a neurobiological model of DLD. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.26210651.


Subject(s)
Language Development Disorders , Reaction Time , Serial Learning , Humans , Male , Female , Adult , Language Development Disorders/psychology , Language Development Disorders/physiopathology , Young Adult , Serial Learning/physiology , Mental Recall , Learning , Language Tests , Adolescent
13.
Nat Commun ; 15(1): 6127, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39033208

ABSTRACT

The anisotropic water interfaces provide an environment to drive various chemical reactions not seen in bulk solutions. However, catalytic reactions by the aqueous interfaces are still in their infancy, with the emphasis being on the reaction rate acceleration on water. Here, we report that the oil-water interface activates and oxidizes C(sp3)-H bonds in toluene, yielding benzaldehyde with high selectivity (>99%) and conversion (>99%) under mild, catalyst-free conditions. Collision at the interface between oil-dissolved toluene and hydroxyl radicals spontaneously generated near the water-side interfaces is responsible for the unexpectedly high selectivity. Protrusion of free OH groups from interfacial water destabilizes the transition state of the OH-addition by forming π-hydrogen bonds with toluene, while the H-abstraction remains unchanged to effectively activate C(sp3)-H bonds. Moreover, the exposed free OH groups form hydrogen bonds with the produced benzaldehyde, suppressing it from being overoxidized. Our investigation shows that the oil-water interface has considerable promise for chemoselective redox reactions on water without any catalysts.

14.
Clin Exp Med ; 24(1): 133, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38900301

ABSTRACT

This study aimed to investigate the serum and expression levels of C-X-C motif chemokine ligand 9 (CXCL9), CXCL10, CXCL11, and CXC receptor 3 (CXCR3) in minor salivary glands (MSGs) of patients with primary Sjögren's syndrome (pSS), and to explore their correlations with clinical parameters. Serum samples from 49 patients diagnosed with pSS, 33 patients with rheumatoid arthritis (RA), and 30 healthy controls (HCs) were collected for measurements of CXCL9, CXCL10, CXCL11, and CXCR3. Additionally, CXCL levels in the MSG tissues were measured in 41 patients who underwent MSG biopsy. Correlations between CXCL and CXCL/CXCR levels in serum/MSG tissues and clinical factors/salivary scintigraphy parameters were analyzed. Serum CXCL11 and CXCR3 showed statistically significant differences among patients with pSS and RA and HCs (serum CXCL11, pSS:RA:HC = 235.6 ± 500.1 pg/mL:90.0 ± 200.3 pg/mL:45.9 ± 53.6 pg/mL; p = 0.041, serum CXCR3, pSS:RA:HC = 3.27 ± 1.32 ng/mL:3.29 ± 1.17 ng/mL:2.00 ± 1.12 ng/mL; p < 0.001). Serum CXCL10 showed a statistically significant difference between pSS (64.5 ± 54.2 pg/mL) and HCs (18.6 ± 18.1 pg/mL, p < 0.001), while serum CXCL9 did not exhibit a significant difference among the groups. Correlation analysis of clinical factors revealed that serum CXCL10 and CXCL11 levels positively correlated with erythrocyte sedimentation rate (r = 0.524, p < 0.001 and r = 0.707, p < 0.001, respectively), total protein (r = 0.375, p = 0.008 and r = 0.535, p < 0.001, respectively), globulin (r = 0.539, p < 0.001 and r = 0.639, p < 0.001, respectively), and European Alliance of Associations for Rheumatology SS Disease Activity Index (r = 0.305, p = 0.033 and r = 0.321, p = 0.025). Additionally, serum CXCL10 negatively correlated with the Schirmer test score (r = - 0.354, p = 0.05), while serum CXCL11 positively correlated with the biopsy focus score (r = 0.612, p = 0.02). In the MSG tissue, the percentage of infiltrating CXCL9-positive cells was highest (75.5%), followed by CXCL10 (29.1%) and CXCL11 (27.9%). In the correlation analysis, CXCL11-expressing cells were inversely related to the mean washout percentage on salivary gland scintigraphy (r = - 0.448, p = 0.007). Our study highlights distinct serum and tissue chemokine patterns in pSS, emphasizing CXCL9's potential for early diagnosis. This suggests that CXCL10 and CXCL11 are indicators of disease progression, warranting further investigation into their roles in autoimmune disorders beyond pSS.


Subject(s)
Chemokine CXCL10 , Chemokine CXCL11 , Receptors, CXCR3 , Sjogren's Syndrome , Humans , Sjogren's Syndrome/pathology , Sjogren's Syndrome/blood , Sjogren's Syndrome/metabolism , Female , Middle Aged , Male , Receptors, CXCR3/metabolism , Adult , Chemokine CXCL11/blood , Chemokine CXCL10/blood , Aged , Salivary Glands, Minor/pathology , Salivary Glands, Minor/metabolism , Chemokine CXCL9/blood , Serum/chemistry , Serum/metabolism
15.
J Korean Med Sci ; 39(22): e175, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38859738

ABSTRACT

BACKGROUND: Multiple myeloma (MM) patients are at risk of skeletal-related events (SREs) like spinal cord compression, pathologic fractures, bone surgery, and radiation to bone. Real-world data regarding SREs in MM are limited. METHODS: We conducted a large, retrospective, nationwide cohort study using the Korean Health Insurance Review and Assessment Service (HIRA) database from 2007 to 2018. RESULTS: Over a 12-year study period, we identified 6,717 patients who developed symptomatic MM. After a median follow-up of 35.1 months (interquartile range [IQR], 20.8-58.2 months), 43.6% of these patients experienced SREs, and 39.6% had four or more SREs. One in five patients (20.0%) experienced pathologic fractures within the first year of follow-up. The median time to first SRE was 9.6 months (IQR, 1.2-25.8 months), with 3.0 months in the group with prior SREs and 19.8 months in the group without prior SREs. During follow-up, 78.5% of patients received bisphosphonates. Multiple logistic regression analysis revealed several factors associated with an increased risk of SREs, including being female (odds ratio [OR], 1.44), aged 50 or older (OR, 1.87), having cerebrovascular disease (OR, 1.34), undergoing first-line chemotherapy regimens not containing bortezomib or lenalidomide (OR, 1.49), and being in the group with prior SREs and bisphosphonate use (OR, 5.63), compared to the group without prior SREs and without bisphosphonate use. CONCLUSION: This population-based study is the first to report the incidence and risk factors of SREs in Korean MM patients, which can be used to assess their bone health.


Subject(s)
Multiple Myeloma , Humans , Multiple Myeloma/epidemiology , Multiple Myeloma/pathology , Multiple Myeloma/diagnosis , Multiple Myeloma/complications , Female , Male , Retrospective Studies , Middle Aged , Aged , Diphosphonates/therapeutic use , Risk Factors , Databases, Factual , Republic of Korea/epidemiology , Bone Density Conservation Agents/therapeutic use , Odds Ratio , Fractures, Spontaneous/etiology , Fractures, Spontaneous/epidemiology , Spinal Cord Compression/etiology , Adult , Logistic Models
16.
Int J Mol Sci ; 25(12)2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38928513

ABSTRACT

Arterial macrophage cholesterol accumulation and impaired cholesterol efflux lead to foam cell formation and the development of atherosclerosis. Modified lipoproteins interact with toll-like receptors (TLR), causing an increased inflammatory response and altered cholesterol homeostasis. We aimed to determine the effects of TLR antagonists on cholesterol efflux and foam cell formation in human macrophages. Stimulated monocytes were treated with TLR antagonists (MIP2), and the cholesterol efflux transporter expression and foam cell formation were analyzed. The administration of MIP2 attenuated the foam cell formation induced by lipopolysaccharides (LPS) and oxidized low-density lipoproteins (ox-LDL) in stimulated THP-1 cells (p < 0.001). The expression of ATP-binding cassette transporters A (ABCA)-1, ABCG-1, scavenger receptor (SR)-B1, liver X receptor (LXR)-α, and peroxisome proliferator-activated receptor (PPAR)-γ mRNA and proteins were increased (p < 0.001) following MIP2 administration. A concentration-dependent decrease in the phosphorylation of p65, p38, and JNK was also observed following MIP2 administration. Moreover, an inhibition of p65 phosphorylation enhanced the expression of ABCA1, ABCG1, SR-B1, and LXR-α. TLR inhibition promoted the cholesterol efflux pathway by increasing the expression of ABCA-1, ABCG-1, and SR-B1, thereby reducing foam cell formation. Our results suggest a potential role of the p65/NF-kB/LXR-α/ABCA1 axis in TLR-mediated cholesterol homeostasis.


Subject(s)
ATP Binding Cassette Transporter 1 , Cholesterol , Foam Cells , Lipoproteins, LDL , Liver X Receptors , Toll-Like Receptors , Humans , Foam Cells/metabolism , Foam Cells/drug effects , Cholesterol/metabolism , Liver X Receptors/metabolism , Toll-Like Receptors/metabolism , ATP Binding Cassette Transporter 1/metabolism , ATP Binding Cassette Transporter 1/genetics , Lipoproteins, LDL/metabolism , Lipoproteins, LDL/pharmacology , PPAR gamma/metabolism , THP-1 Cells , Macrophages/metabolism , Macrophages/drug effects , ATP Binding Cassette Transporter, Subfamily G, Member 1/metabolism , ATP Binding Cassette Transporter, Subfamily G, Member 1/genetics , Lipopolysaccharides/pharmacology , Scavenger Receptors, Class B/metabolism , Scavenger Receptors, Class B/genetics
17.
Front Immunol ; 15: 1369385, 2024.
Article in English | MEDLINE | ID: mdl-38915417

ABSTRACT

Introduction: This study aimed to demonstrate the potential of activated leukocyte cell adhesion molecule (ALCAM), hemopexin (HPX), and peroxiredoxin 6 (PRDX6) as urine biomarkers for systemic lupus erythematosus (SLE). Methods: Urine samples were collected from 138 Korean patients with SLE from the Ajou Lupus Cohort and 39 healthy controls (HC). The concentrations of urine biomarkers were analyzed using enzyme-linked immunosorbent assay kits specific for ALCAM, HPX, and PRDX6, respectively. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic utility, and Pearson's correlation analysis was conducted to assess the relationships between the disease activity and urine biomarkers. Results: Patients with SLE and patients with lupus nephritis (LN) showed significantly elevated ALCAM, HPX, and PRDX6 levels compared with HCs. ALCAM, HPX, and PRDX6 showed significant diagnostic values, especially for lupus nephritis (LN), with areas under the receiver operating characteristic curve for LN was 0.850 for ALCAM (95% CI, 0.778-0.921), 0.781 for HPX (95% CI, 0.695-0.867), and 0.714 for PRDX6 (95% CI, 0.617-0.812). Correlation analysis revealed that all proteins were significantly associated with anti-double stranded DNA antibody (ALCAM, r = 0.350, p < 0.001; HPX, r = 0.346, p < 0.001; PRDX6, r = 0.191, p = 0.026) and SLEDAI (ALCAM, r = 0.526, p < 0.001; HPX, r = 0.479, p < 0.001; PRDX6, r = 0.262, p = 0.002). Results from the follow-up of the three biomarker levels in these patients revealed a significant decrease, showing a positive correlation with changes in SLEDAI-2k scores (ALCAM, r = 0.502, p < 0.001; HPX, r = 0.475, p < 0.001; PRDX6, r = 0.245, p = 0.026), indicating their potential as indicators for tracking disease activity. Discussions: Urinary ALCAM, HPX, and PRDX6 levels have diagnostic value and reflect disease activity in Korean patients with SLE, emphasizing their potential for non-invasive monitoring and treatment response evaluation.


Subject(s)
Biomarkers , Lupus Erythematosus, Systemic , Peroxiredoxin VI , Humans , Female , Male , Biomarkers/urine , Adult , Lupus Erythematosus, Systemic/urine , Lupus Erythematosus, Systemic/diagnosis , Republic of Korea , Peroxiredoxin VI/urine , Middle Aged , Fetal Proteins/urine , Longitudinal Studies , Severity of Illness Index , Young Adult , Antigens, CD/urine , ROC Curve , Cell Adhesion Molecules, Neuronal/urine , Case-Control Studies , Lupus Nephritis/urine , Lupus Nephritis/diagnosis , Activated-Leukocyte Cell Adhesion Molecule
18.
Technol Health Care ; 32(S1): 361-369, 2024.
Article in English | MEDLINE | ID: mdl-38759061

ABSTRACT

BACKGROUND: Studies investigating postural balance during various infant care postures have not been reported yet. OBJECTIVE: The aim of this study was to measure static postural balance when holding an infant dummy in-arms and carrying an infant dummy on back according to different infant dummy weights. METHODS: Sixteen healthy young subjects participated in a balance test. Infant dummies with weights of 4.6 kg (1-month) and 9.8 kg (12-month) were used in this study. All subjects were asked to naturally stand on a force platform in two infant care postures (holding an infant in-arms and carrying an infant on one's back). Center of pressure (COP) was measured from the force platform. Quantitative variables were derived from the COP. Two-way repeated measure analysis of variance (ANOVA) was performed to determine main effects of infant care postures, infant weight, and their interactions on COP variables. RESULTS: Back carrying a 12-month infant dummy had the greatest amplitude in all COP variables. Back carrying posture showed significantly greater mean distance and peak power, faster mean velocity, and wider COP area compared to holding posture (P< 0.05). There were significant weight effects of most COP variables mainly in AP direction (P< 0.01). CONCLUSIONS: Our results could contribute to the prevention of musculoskeletal diseases or prevention of fall due to various infant care activities by developing an assisting device to improve postural balance.


Subject(s)
Body Weight , Postural Balance , Posture , Humans , Postural Balance/physiology , Male , Posture/physiology , Infant , Female , Body Weight/physiology , Infant Care/methods , Young Adult
19.
Radiol Cardiothorac Imaging ; 6(3): e230177, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38722232

ABSTRACT

Purpose To develop a deep learning model for increasing cardiac cine frame rate while maintaining spatial resolution and scan time. Materials and Methods A transformer-based model was trained and tested on a retrospective sample of cine images from 5840 patients (mean age, 55 years ± 19 [SD]; 3527 male patients) referred for clinical cardiac MRI from 2003 to 2021 at nine centers; images were acquired using 1.5- and 3-T scanners from three vendors. Data from three centers were used for training and testing (4:1 ratio). The remaining data were used for external testing. Cines with downsampled frame rates were restored using linear, bicubic, and model-based interpolation. The root mean square error between interpolated and original cine images was modeled using ordinary least squares regression. In a prospective study of 49 participants referred for clinical cardiac MRI (mean age, 56 years ± 13; 25 male participants) and 12 healthy participants (mean age, 51 years ± 16; eight male participants), the model was applied to cines acquired at 25 frames per second (fps), thereby doubling the frame rate, and these interpolated cines were compared with actual 50-fps cines. The preference of two readers based on perceived temporal smoothness and image quality was evaluated using a noninferiority margin of 10%. Results The model generated artifact-free interpolated images. Ordinary least squares regression analysis accounting for vendor and field strength showed lower error (P < .001) with model-based interpolation compared with linear and bicubic interpolation in internal and external test sets. The highest proportion of reader choices was "no preference" (84 of 122) between actual and interpolated 50-fps cines. The 90% CI for the difference between reader proportions favoring collected (15 of 122) and interpolated (23 of 122) high-frame-rate cines was -0.01 to 0.14, indicating noninferiority. Conclusion A transformer-based deep learning model increased cardiac cine frame rates while preserving both spatial resolution and scan time, resulting in images with quality comparable to that of images obtained at actual high frame rates. Keywords: Functional MRI, Heart, Cardiac, Deep Learning, High Frame Rate Supplemental material is available for this article. © RSNA, 2024.


Subject(s)
Deep Learning , Magnetic Resonance Imaging, Cine , Humans , Male , Magnetic Resonance Imaging, Cine/methods , Middle Aged , Female , Prospective Studies , Retrospective Studies , Heart/diagnostic imaging , Image Interpretation, Computer-Assisted/methods
20.
Circ Cardiovasc Imaging ; 17(5): e016420, 2024 May.
Article in English | MEDLINE | ID: mdl-38716661

ABSTRACT

BACKGROUND: Echocardiographic (2-dimensional echocardiography) thresholds indicating disease or impaired functional status compared with normal physiological aging in individuals aged ≥65 years are not clearly defined. In the present study, we sought to establish standard values for 2-dimensional echocardiography parameters related to chamber size and function in older adults without cardiopulmonary or cardiometabolic conditions. METHODS: In this cross-sectional study of 3032 individuals who underwent 2-dimensional echocardiography at exam 6 in the MESA (Multi-Ethnic Study of Atherosclerosis), 608 participants fulfilled our inclusion criteria of healthy aging, with normative values defined as the mean ± 1.96 standard deviation and compared across sex and race and ethnicity. Functional status measures included NT-proBNP (N-terminal pro-B-type natriuretic peptide), 6-minute walk distance, and Kansas City Cardiomyopathy Questionnaire. Prognostic performance using MESA cutoffs was compared with established guideline cutoffs using time-to-event analysis. RESULTS: The normative aging cohort (69.5±7.0 years, 46.2% male, 47.5% White) had lower NT-proBNP, higher 6-minute walk distance, and higher (better) Kansas City Cardiomyopathy Questionnaire summary values. Women had significantly smaller chamber sizes and better biventricular systolic function. White participants had the largest chamber dimensions, whereas Chinese participants had the smallest, even after adjustment for body size. Current guidelines identified 81.6% of healthy older adults in MESA as having cardiac abnormalities. CONCLUSIONS: Among a large, diverse group of healthy older adults, we found significant differences in cardiac structure and function by sex and race/ethnicity, which may signal sex-specific cardiac remodeling with advancing age. It is crucial for existing guidelines to consider the observed and clinically significant differences in cardiac structure and function associated with healthy aging. Our study highlights that existing guidelines, which grade abnormalities in echocardiographic cardiac chamber size and function based on younger individuals, may not adequately address the anticipated changes associated with normal aging.


Subject(s)
Peptide Fragments , Humans , Female , Male , Aged , Cross-Sectional Studies , Aged, 80 and over , Peptide Fragments/blood , Ventricular Function, Left/physiology , Natriuretic Peptide, Brain/blood , Reference Values , United States/epidemiology , Atherosclerosis/ethnology , Atherosclerosis/physiopathology , Atherosclerosis/diagnostic imaging , Age Factors , Echocardiography/methods , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Ventricular Function, Right/physiology , Walk Test , Predictive Value of Tests , Healthy Aging/ethnology , Middle Aged
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