To address the limitations of animal testing, scientific research is increasingly focused on developing alternative testing methods. These alternative tests utilize cells or tissues derived from animals or humans for in vitro testing, as well as artificial tissues and organoids. In western countries, animal testing for cosmetics has been banned, leading to the adoption of artificial skin for toxicity evaluation, such as skin corrosion and irritation assessments. Standard guidelines for skin organoid technology becomes necessary to ensure consistent data and evaluation in replacing animal testing with in vitro methods. These guidelines encompass aspects such as cell sourcing, culture techniques, quality requirements and assessment, storage and preservation, and organoid-based assays.

Background/Aims: To compare the effects of abatacept and conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the progression and development of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Methods: This multi-center retrospective study included RA patients receiving abatacept or csDMARDs who underwent at least two pulmonary function tests and/or chest high-resolution computed tomography (HRCT). We compared the following outcomes between the groups: progression of RA-ILD, development of new ILD in RA patients without ILD at baseline, 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR), and safety. Longitudinal changes were compared between the groups by using a generalized estimating equation. Results: The study included 123 patients who were treated with abatacept (n = 59) or csDMARDs (n = 64). Nineteen (32.2%) and 38 (59.4%) patients treated with abatacept and csDMARDs, respectively, presented with RA-ILD at baseline. Newly developed ILD occurred in one patient receiving triple csDMARDs for 32 months. Among patients with RA-ILD at baseline, ILD progressed in 21.1% of cases treated with abatacept and 34.2% of cases treated with csDMARDs during a median 21-month follow-up. Longitudinal changes in forced vital capacity and diffusing capacity for carbon monoxide were comparable between the two groups. However, the abatacept group showed a more significant decrease in DAS28-ESR and glucocorticoid doses than csDMARDs group during the follow-up. The safety of both regimens was comparable. Conclusions Abatacept and csDMARDs showed comparable effects on the development and stabilization of RA-ILD. Nevertheless, compared to csDMARDs, abatacept demonstrated a significant improvement in disease activity and led to reduced glucocorticoid use.

Purpose: This study examined the effects of a paraffin treatment with exercise on the muscle strength and fatigue of the hand according to the use of smartphones. Methods: The measurement subjects were 30 healthy males in their 20s who were divided randomly into the control and paraffin treatment groups. A typing exercise using a smartphone was performed. The pinch grip force was measured to evaluate the muscle strength of the thumb, and muscle fatigue analysis using electromyography was performed to analyze muscle fatigue. Results: The functional changes to the arm and the fatigue of the hand through the use of a smartphone were examined to determine the effects of the paraffin treatment. The dominant hand-pinch grip force test did not show a significant difference, but the non-dominant hand-pinch grip force test showed a significant difference between the groups (p=0.030). In the dominant hand fatigue test, there was a significant difference between the groups (p=0.037). In the non-dominant hand, there was a significant difference between time (p=0.012) and the groups (p<0.001). Conclusion The effects of paraffin intervention on the hand muscle strength and fatigue due to repeated use of the smartphone were confirmed. These results can be used as a basis for clinical use and can be a guide for the correct use of smartphones, which are essential in modern life.

Background and Objectives: The relationship between the hospital percutaneous coronary intervention (PCI) volumes and the in-hospital clinical outcomes of patients with acute myocardial infarction (AMI) remains the subject of debate. This study aimed to determine whether the in-hospital clinical outcomes of patients with AMI in Korea are significantly associated with hospital PCI volumes. Methods: We selected and analyzed 17,121 cases of AMI, that is, 8,839 cases of non-ST-segment elevation myocardial infarction and 8,282 cases of ST-segment elevation myocardial infarction, enrolled in the 2014 Korean percutaneous coronary intervention (K-PCI) registry. Patients were divided into 2 groups according to hospital annual PCI volume, that is, to a high-volume group (≥400/year) or a low-volume group (<400/year). Major adverse cardiovascular and cerebrovascular events (MACCEs) were defined as composites of death, cardiac death, non-fatal myocardial infarction (MI), stent thrombosis, stroke, and need for urgent PCI during index admission after PCI. Results: Rates of MACCE and non-fatal MI were higher in the low-volume group than in the high-volume group (MACCE: 10.9% vs. 8.6%, p=0.001; non-fatal MI: 4.8% vs. 2.6%, p=0.001, respectively). Multivariate regression analysis showed PCI volume did not independently predict MACCE. Conclusions Hospital PCI volume was not found to be an independent predictor of in-hospital clinical outcomes in patients with AMI included in the 2014 K-PCI registry.

Purpose: This study examined the effects of a paraffin treatment with exercise on the muscle strength and fatigue of the hand according to the use of smartphones. Methods: The measurement subjects were 30 healthy males in their 20s who were divided randomly into the control and paraffin treatment groups. A typing exercise using a smartphone was performed. The pinch grip force was measured to evaluate the muscle strength of the thumb, and muscle fatigue analysis using electromyography was performed to analyze muscle fatigue. Results: The functional changes to the arm and the fatigue of the hand through the use of a smartphone were examined to determine the effects of the paraffin treatment. The dominant hand-pinch grip force test did not show a significant difference, but the non-dominant hand-pinch grip force test showed a significant difference between the groups (p=0.030). In the dominant hand fatigue test, there was a significant difference between the groups (p=0.037). In the non-dominant hand, there was a significant difference between time (p=0.012) and the groups (p<0.001). Conclusion The effects of paraffin intervention on the hand muscle strength and fatigue due to repeated use of the smartphone were confirmed. These results can be used as a basis for clinical use and can be a guide for the correct use of smartphones, which are essential in modern life.

OBJECTIVE: The biological rhythm is closely related to mood symptoms. The purpose of this study was to assess the differences in biological rhythms among subjects with mood disorder [bipolar I disorder (BD I), bipolar II disorder (BD II), major depressive disorder (MDD)] and healthy control subjects.METHODS: A total of 462 early-onset mood disorder subjects were recruited from nine hospitals. The controls subjects were recruited from the general population of South Korea. Subject groups and control subject were evaluated for the Korean language version of Biological Rhythms Interview of Assessment in Neuropsychiatry (K-BRIAN) at the initial evaluation.RESULTS: The mean K-BRIAN scores were 35.59 [standard deviation (SD)=13.37] for BD I, 43.05 (SD=11.85) for BD II, 43.55 (SD=12.22) for MDD, and 29.1 (SD=8.15) for the control group. In the case of mood disorders, biological rhythm disturbances were greater than that in the control group (p<0.05). A significant difference existed between BD I and BD II (BD I Bipolar Disorder ; Cohort Studies ; Depression ; Depressive Disorder, Major ; Korea ; Mood Disorders ; Neuropsychiatry ; Periodicity

OBJECTIVE: Contrast-induced nephropathy (CIN) frequently occurs after percutaneous intervention. Objective of this study was to investigate the usefulness of serum cystatin C, neutrophil gelatinase-associated lipocalcin (NGAL), urinary kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) as early predictors for CIN after percutaneous coronary intervention (PCI). METHODS: In 53 patients who underwent PCI were enrolled. Serum creatinine and cystatin C level were measured immediately before, and 24 hours and 48 hours after catheterization. Serum NGAL, urinary KIM-1, and IL-18 were measured immediately before, and 4 hours, 24 hours, and 48 hours after catheterization. CIN was defined as a rise in creatinine 0.5 mg/dL or 25% above baseline. RESULTS: CIN occurred in four patients (7.5%). Serum cystatin C levels were higher at 24 hours and 48 hours in CIN patients than in those without CIN (P<0.05). Serum NGAL levels were higher at 48 hours in CIN patients than in those without CIN. Urinary KIM-1 levels were higher at 48 hours in CIN patients than in those without CIN. There were no significant markers of CIN on multi-variate analysis. CONCLUSION: In this study, the occurrence of CIN after PCI was 7.5%. Although there were some time-course changes in serum cystatin C and urinary KIM-1 after PCI, there was no significant predictor for CIN after PCI.
Catheterization ; Catheters ; Contrast Media ; Creatinine ; Cystatin C ; Humans ; Interleukin-18 ; Kidney ; Neutrophils ; Percutaneous Coronary Intervention*

Periodontal disease is one of the most prevalent chronic disorders worldwide. It is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss. Here, we focused on the role of adipokines, which are locally expressed by periodontal tissues, in the regulation of catabolic gene expression leading to periodontal inflammation. The expression of the nicotinamide phosphoribosyltransferase (NAMPT) adipokine was dramatically increased in inflamed human and mouse gingival tissues. NAMPT expression was also increased in lipopolysaccharide- and proinflammatory cytokine-stimulated primary cultured human gingival fibroblasts (GF). Adenovirus-mediated NAMPT (Ad-Nampt) overexpression upregulated the expression and activity of COX-2, MMP1 and MMP3 in human GF. The upregulation of IL-1β- or Ad-Nampt-induced catabolic factors was significantly abrogated by the intracellular NAMPT (iNAMPT) inhibitor, FK866 or by the sirtuin (SIRT) inhibitor, nicotinamide (NIC). Recombinant NAMPT protein or extracellular NAMPT (eNAMPT) inhibition using a blocking antibody did not alter NAMPT target gene expression levels. Moreover, intragingival Ad-Nampt injection mediated periodontitis-like phenotypes including alveolar bone loss in mice. SIRT2, a part of the SIRT family, was positively associated with NAMPT actions in human GF. Furthermore, in vivo inhibition of the NAMPT-NAD⁺-SIRT axis by NIC injection in mice ameliorated the periodontal inflammation and alveolar bone erosion caused by intragingival injection of Ad-Nampt. Our findings indicate that NAMPT is highly upregulated in human GF, while its enzymatic activity acts as a crucial mediator of periodontal inflammation and alveolar bone destruction via regulation of COX-2, MMP1, and MMP3 levels.
Adipokines ; Alveolar Bone Loss ; Animals ; Fibroblasts* ; Gene Expression* ; Gingiva ; Humans ; Inflammation ; Mice ; Niacinamide ; Nicotinamide Phosphoribosyltransferase ; Periodontal Diseases ; Periodontitis* ; Phenotype ; Up-Regulation

Radial artery perforation is one of the major complications of transradial percutaneous coronary intervention (PCI). Previous reports have suggested that sealing the perforation with a smaller guiding catheter may be possible. In one such study, the perforated segment was sealed with a 0.014- or 0.021-inch guidewire, and PCI was successfully completed. In this study, we describe a radial artery perforation that occurred after diagnostic coronary angiography and during insertion of a 6 French (FR) guiding catheter. PCI and the perforation were successfully managed through the use of a 5 Fr guiding catheter and a 0.035-inch guidewire.
Catheters ; Coronary Angiography ; Percutaneous Coronary Intervention* ; Radial Artery*

OBJECTIVE: Longstanding hypertension lead to left ventricular diastolic dysfunction with a development of a left atrial enlargement (LAE) which may result in vulnerability to atrial fibrillation (AF). Paroxysmal AF is usually unrevealed in the acute period of ischemic stroke, but is crucial for anticoagulation to prevent recurrent stroke. This study was aimed to investigate the frequency of LAE and the predictors of paroxysmal AF during the hospitalization of acute ischemic stroke. METHODS: A total 1,643 consecutive patients with acute ischemic stroke were registered in between January 2005 and December 2014. The subjects who had AF before index stroke or at admission were excluded. The clinical and echocardiographic findings of all patients were reviewed. Paroxysmal AF were detected on electrocardiography of Holter monitoring during hospitalization. LAE were defined as LA diameter larger than 44 mm in echocardiography. We compared the frequency of LAE between the patients with or without AF. Logistic regression analysis were performed to determine the echocardiographic parameters for prediction of paroxysmal AF. RESULTS: The mean age was 67.3 and the male was 55.6%. AF were detected in 123 (11.4%) of LAE(-) group but were detected in 102 (49.0%) in LAE(+) group. In logistic regression analysis, LAE significantly predicted for newly detected AF during hospitalization after adjusting covariates (odds ratio, 5.698; 95% confidence interval, 3.799-8.546; P<0.001). CONCLUSION: LAE was an independent predictor for AF during hospitalization in patients with acute ischemic stroke. Prolonged electrocardiography monitoring should be meticulously indicated for acute ischemic stroke with LAE to detect paroxysmal AF.
Atrial Fibrillation* ; Atrial Function, Left ; Echocardiography* ; Electrocardiography ; Electrocardiography, Ambulatory ; Hospitalization ; Humans ; Hypertension ; Logistic Models ; Male ; Stroke*