Purpose: Pediatric papillary thyroid cancer (PTC) is recommended to perform aggressive surgery to reduce the risk of recurrence.This study was designed to evaluate the concurrent association between multifocality, bilaterality, and the risk of recurrence in pediatric PTC. Materials and Methods: This retrospective cohort study included pediatric patients (age <19 years) who underwent total thyroidectomy for PTC between 1996 and 2014 in a single tertiary center. Clinicopathological parameters were analyzed to evaluate the prevalence of multifocality, bilaterality, recurrence, and their association. Results: We analyzed 58 pediatric patients with PTC. There was no factor related to the presence of multifocality or bilaterality in multivariate analysis. Also, in univariate analysis, multifocality and bilaterality were not independent risk factors of each other’s presentation (p=0.061 and p=0.061, respectively). Recurrence was observed in 19 (32.8%) patients. In multivariate analysis of recurrence, clear cell subtype, multifocality, and gross extrathyroidal extension (ETE) were independent risk factors (p=0.027, p=0.035, and p=0.038, respectively). Most recurrences (68.4%) happened during the first 4 years of follow-up after the initial thyroidectomy. Conclusion Multifocality and bilaterality were not independent risk factors of each other’s presentation; however, multifocality was the risk factor for recurrence in pediatric PTC. For pediatric PTC, close monitoring for recurrence within the initial 4 years is recommended, particularly in patients with clear cell subtype, multifocality, and gross ETE.

Purpose: Improvement of left ventricular (LV) diastolic dysfunction (DD) is known to be a good prognostic factor in patients with heart failure with reduced ejection fraction (EF). In the present study, we investigated the predisposing risk factors affecting the reversibility of LV diastolic filling pattern (DFP) in patients with preserved EF. Materials and Methods: A total of 600 patients with pseudonormal LVDFP and preserved EF who underwent follow-up echocardiography were enrolled between 2011 and 2020. We compared their index and follow-up echocardiography findings and determined the predisposing risk factor affecting the reversibility of LVDFP. Results: Comparing the index and follow-up echocardiography findings showed that 379 (63%) patients had improved to normal or impaired relaxation LVDFP (improved group) and 221 (37%) patients had maintained or worsened LVDFP (unimproved group).The incidence of paroxysmal atrial fibrillation (PAF) was significantly higher in the unimproved group than in the improved group (4.7% vs. 9.5%, p=0.026). After adjustment for relevant clinical risk factors of diastolic dysfunction, PAF was determined to be an independent predisposing risk factor for the unimproved LVDFP (odds ratio: 2.10, 95% confidence interval: 1.06–4.15, p=0.033).Among the parameters of diastolic dysfunction in follow-up echocardiography, the left atrial volume index, mean E/A ratio, and E/e' were significantly improved in patients without PAF but remained in patients with PAF. Conclusion We identified that PAF was an independent predisposing risk factor of the unimproved LVDFP in patients with pseudonormal LVDFP and preserved EF. Therefore, early detection and management of PAF might be required in patients with LVDD and preserved EF to prevent adverse cardiovascular events.

Purpose: To investigate the association between soluble suppressor of tumorigenicity 2 (sST2) levels and cardiovascular disease predictors in patients with gout. Materials and Methods: We retrospectively reviewed the medical records of patients with gout who were tested for sST2 but did not receive uric acid-lowering therapy. These patients were classified into elevated and normal sST2 groups using a cut-off of >49.6 ng/mL and >35.4 ng/mL in males and females, respectively. Correlations between clinical and laboratory variables, sST2 levels, and elevated sST2 level predictors were assessed using linear and logistic regression analyses. Results: Notably, 27 (11.3%) and 211 (88.7%) of the 238 identified patients had elevated and normal sST2 levels, respectively. Linear regression analysis revealed that male sex (β=-0.190, p=0.002), body mass index (BMI) (β=-0.184, p=0.002), white blood cell count (β=0.231, p<0.001), C-reactive protein (β=0.135, p=0.031), and fasting blood glucose (β=0.210, p<0.001) were independently associated with sST2 levels. In multivariate logistic regression analysis, male sex [odds ratio (OR) 0.112, p=0.001], BMI (OR 0.836, p=0.008), creatinine (OR 5.730, p=0.024), and fasting blood glucose (OR 1.042, p=0.002) predicted elevated sST2 levels. Patients with increased sST2 levels had a significantly higher atherosclerotic cardiovascular disease risk score and a greater proportion of high-risk Framingham Risk Score compared to the normal sST2 group (p=0.002 and p<0.001). Conclusion Patients with gout and elevated sST2 levels have a higher risk of future cardiovascular disorders, which may provide insights into risk stratification and the implementation of intervention strategies.

Objective: Using finite element method (FEM) analysis of a clear aligner (CA), this study aimed to investigate the effects of varying the edentulous space on canine distal bodily movement during space closure following maxillary first premolar extraction. Methods: FEM analysis was used to simulate distal canine bodily movement following maxillary first premolar extraction using CAs. Four CA designs for edentulous spaces were compared: no-pontic, full-pontic, halfpontic, and beam. Three-dimensional models of the tooth components and CA were created. The target was set at a 0.25-mm distal canine movement. Long-term tooth movement was simulated using an iterative calculation method. Results: All the groups initially showed crown displacement, distal tipping, and distal rotation.Over time, the movement patterns differed in relation to the design. The no-pontic design exhibited the greatest displacement and tipping. The beam design exhibited the largest initial displacement but showed the lowest displacement and tipping thereafter. Full- and half-pontic designs yielded intermediate results. Significant force reduction was observed immediately after CA application, and was followed by a gradual decrease. The mean tooth-movement achievement rate was approximately 76.7%. Conclusions The edentulous space design of the CA substantially affected tooth-movement behavior. An iterative simulation is necessary to evaluate longterm tooth-movement patterns. The beam design demonstrated optimal suitability for bodily movement with minimal tipping. For optimal results, additional setup or overcorrection may be necessary.

Background: Chronic pain significantly affects daily activities, mental health, and the interpersonal relationships of patients. Consequently, physicians use various treatments to manage pain. This study investigated the perceptions of treatment, accompanying symptoms, and other problems in patients with chronic pain. Methods: The authors enrolled patients with chronic pain from 19 university hospitals in South Korea. Data was collected on age, gender, diagnosis, disease duration, severity of pain, perception of pain treatment, and accompanying symptoms or problems using an anonymous survey comprising 19 questions. Results: In total, 833 patients with chronic pain completed the survey, and 257 (31.0%) and 537 (64.5%) patientsexpressed concerns about the potential adverse effects of medication and opioid addiction, respectively. Personalitychanges such as irritability or anger were the most frequent accompanying symptoms in 507 (63.8%) patients, followed by depression and sleep disturbance in 462 (58.1%) and 450 (54.5%) patients, respectively. Depression (P = 0.001) and anxiety (P = 0.029) were more common among women, whereas divorce (P = 0.016), family conflict (P < 0.001), unemployment (P < 0.001), suicide attempts (P < 0.001), and restrictions on economic activity (P < 0.001) were more common among men. The frequency of accompanying symptoms, except for suicidal ideation,was higher in the younger patients aged ≤ 40 years than in the older patients aged > 40 years. Conclusions Many patients with chronic pain had concerns about adverse effects or medication tolerance and experienced anxiety, depression, or sleep disturbances. The prevalence of accompanying problems varies according to age and gender.

Echinochrome A (Ech A) isolated from marine organisms is a therapeutic effector for various cardiovascular diseases, but its precise mechanisms are unclear.This study identified the role and mechanisms mediating the effects of Ech A on the migration of vascular smooth muscle cells (VSMCs) induced by high-mobility group box 1 (HMGB1). Compared to the control cells, the migration of VSMCs stimulated with HMGB1 (100 ng/ml) was markedly increased, which was significantly attenuated in cells pretreated with MPIIIB10 (100 ng/ml), a neutralizing monoclonal antibody for osteopontin (OPN). In VSMCs stimulated with HMGB1, the increased expression of OPN mRNA and protein was accompanied by an increased OPN promoter activity. In reporter gene assays using OPN promoter-luciferase constructs, the promoter region 538-234 bp of the transcription start site containing the binding sites for activator protein 1 (AP-1) was shown to be responsible for the increased transcriptional activity by HMGB1. In addition, the binding activity of AP-1 was increased in HMGB1-stimulated cells, highlighting the pivotal role of AP-1 on OPN expression in HMGB1-stimulated VSMCs. An examination of the vascular effects of Ech A showed that the increased AP-1 binding/promoter activities and OPN expression induced by HMGB1 were attenuated in cells pretreated with Ech A (3 or 10 μM). Similarly, Ech A inhibited HMGB1-induced VSMC migration in a concentration-dependent manner. These findings suggest that Ech A inhibits VSMC migration by suppressing OPN expression.Hence, Ech A is suggested as a potential therapeutic strategy for vascular remodeling in the injured vasculatures.

Renal cell carcinoma (RCC) presents significant clinical challenges, highlighting the importance of understanding its molecular mechanisms. While store-operated Ca2+ entry (SOCE) is known to play an essential role in tumorigenesis and metastasis, its specific implications across various RCC subtypes remain underexplored.This study analyzed SOCE-related mRNA profiles from the KIRC and KIRP projects in The Cancer Genome Atlas (TCGA) database, focusing on differential gene expression and overall survival outcomes. Functional studies in clear cell RCC (Caki-1) and papillary RCC cell lines (pRCC, Caki-2) revealed increased expression of Orai1 and Orai3, along with STIM1, exhibited in both subtypes, with decreased STIM2 and increased Orai2 expression in pRCC. Notably, Orai3 expression had a gender-specific impact on survival, particularly in females with pRCC, where it inversely correlated with STIM2 expression. Functional assays showed Orai3 dominance in Caki-2 and Orai1 in Caki-1. Interestingly, 2-APB inhibited SOCE in Caki-1 but enhanced it in Caki-2, suggesting Orai3 as the primary SOCE channel in pRCC. Knockdown of Orai1 and Orai3 reduced cell migration and proliferation via regulating focal adhesion kinase (FAK) and Cyclin D1 in both cell lines. These findings highlight the critical roles of Orai1 and Orai3 in RCC metastasis, with Orai3 linked to poorer prognosis in females with pRCC. This study offers valuable insights into RCC diagnostics and potential therapeutic strategies targeting ORAI channels and STIM proteins.

Purpose: Pediatric papillary thyroid cancer (PTC) is recommended to perform aggressive surgery to reduce the risk of recurrence.This study was designed to evaluate the concurrent association between multifocality, bilaterality, and the risk of recurrence in pediatric PTC. Materials and Methods: This retrospective cohort study included pediatric patients (age <19 years) who underwent total thyroidectomy for PTC between 1996 and 2014 in a single tertiary center. Clinicopathological parameters were analyzed to evaluate the prevalence of multifocality, bilaterality, recurrence, and their association. Results: We analyzed 58 pediatric patients with PTC. There was no factor related to the presence of multifocality or bilaterality in multivariate analysis. Also, in univariate analysis, multifocality and bilaterality were not independent risk factors of each other’s presentation (p=0.061 and p=0.061, respectively). Recurrence was observed in 19 (32.8%) patients. In multivariate analysis of recurrence, clear cell subtype, multifocality, and gross extrathyroidal extension (ETE) were independent risk factors (p=0.027, p=0.035, and p=0.038, respectively). Most recurrences (68.4%) happened during the first 4 years of follow-up after the initial thyroidectomy. Conclusion Multifocality and bilaterality were not independent risk factors of each other’s presentation; however, multifocality was the risk factor for recurrence in pediatric PTC. For pediatric PTC, close monitoring for recurrence within the initial 4 years is recommended, particularly in patients with clear cell subtype, multifocality, and gross ETE.

Purpose: Improvement of left ventricular (LV) diastolic dysfunction (DD) is known to be a good prognostic factor in patients with heart failure with reduced ejection fraction (EF). In the present study, we investigated the predisposing risk factors affecting the reversibility of LV diastolic filling pattern (DFP) in patients with preserved EF. Materials and Methods: A total of 600 patients with pseudonormal LVDFP and preserved EF who underwent follow-up echocardiography were enrolled between 2011 and 2020. We compared their index and follow-up echocardiography findings and determined the predisposing risk factor affecting the reversibility of LVDFP. Results: Comparing the index and follow-up echocardiography findings showed that 379 (63%) patients had improved to normal or impaired relaxation LVDFP (improved group) and 221 (37%) patients had maintained or worsened LVDFP (unimproved group).The incidence of paroxysmal atrial fibrillation (PAF) was significantly higher in the unimproved group than in the improved group (4.7% vs. 9.5%, p=0.026). After adjustment for relevant clinical risk factors of diastolic dysfunction, PAF was determined to be an independent predisposing risk factor for the unimproved LVDFP (odds ratio: 2.10, 95% confidence interval: 1.06–4.15, p=0.033).Among the parameters of diastolic dysfunction in follow-up echocardiography, the left atrial volume index, mean E/A ratio, and E/e' were significantly improved in patients without PAF but remained in patients with PAF. Conclusion We identified that PAF was an independent predisposing risk factor of the unimproved LVDFP in patients with pseudonormal LVDFP and preserved EF. Therefore, early detection and management of PAF might be required in patients with LVDD and preserved EF to prevent adverse cardiovascular events.

Purpose: To investigate the association between soluble suppressor of tumorigenicity 2 (sST2) levels and cardiovascular disease predictors in patients with gout. Materials and Methods: We retrospectively reviewed the medical records of patients with gout who were tested for sST2 but did not receive uric acid-lowering therapy. These patients were classified into elevated and normal sST2 groups using a cut-off of >49.6 ng/mL and >35.4 ng/mL in males and females, respectively. Correlations between clinical and laboratory variables, sST2 levels, and elevated sST2 level predictors were assessed using linear and logistic regression analyses. Results: Notably, 27 (11.3%) and 211 (88.7%) of the 238 identified patients had elevated and normal sST2 levels, respectively. Linear regression analysis revealed that male sex (β=-0.190, p=0.002), body mass index (BMI) (β=-0.184, p=0.002), white blood cell count (β=0.231, p<0.001), C-reactive protein (β=0.135, p=0.031), and fasting blood glucose (β=0.210, p<0.001) were independently associated with sST2 levels. In multivariate logistic regression analysis, male sex [odds ratio (OR) 0.112, p=0.001], BMI (OR 0.836, p=0.008), creatinine (OR 5.730, p=0.024), and fasting blood glucose (OR 1.042, p=0.002) predicted elevated sST2 levels. Patients with increased sST2 levels had a significantly higher atherosclerotic cardiovascular disease risk score and a greater proportion of high-risk Framingham Risk Score compared to the normal sST2 group (p=0.002 and p<0.001). Conclusion Patients with gout and elevated sST2 levels have a higher risk of future cardiovascular disorders, which may provide insights into risk stratification and the implementation of intervention strategies.