The comprehensive in vitro proarrhythmia assay (CiPA) initiative, led by the U.S. Food and Drug Administration (FDA), provides a framework for predicting drug-induced arrhythmia risk. To support domestic CiPA implementation, we evaluated the proarrhythmic risk of sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor. Sildenafil has been misused recreationally, with reports of highdose non-medical intake. To simulate misuse, in vitro assays were conducted using concentrations up to 100× the maximum therapeutic plasma concentration (Cmax). The assessment followed the three core components of the CiPA paradigm. Patch clamp assays were conducted in Human Embryonic Kidney 293 (HEK293) and Chinese hamster ovary (CHO) cells transiently expressing Nav1.5, Cav1.2, and hERG ion channels. In silico modeling was performed using the CiPAORdv1.0 model based on IC₅₀ and Hill coefficient values. Functional evaluation included multi-electrode array (MEA) recordings in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), and in vivo electrocardiography (ECG) analysis in rats was performed to observe QT interval prolongation. Sildenafil significantly inhibited hERG currents by 40.5% at 100× Cmax. In silico modeling predicted a low Torsades de Pointes (TdP) risk based on qNet biomarkers. In contrast, MEA recordings showed a concentration-dependent prolongation of corrected field potential duration (FPDc), with a significant 13.3% increase at 100× Cmax. The TdP risk estimated from MEA modeling was 64%. In vivo ECG analysis revealed significant QT prolongation at 50× Cmax. Despite low in silico TdP predictions, functional assays suggest that high concentrations of sildenafil as in misuse may pose a clinically relevant risk of QT prolongation and arrhythmia.

Purpose: Many breast cancer patients experience genitourinary syndrome of menopause (GSM) symptoms. Concerns about systemic absorption limit the use of local estrogen therapy, and clinicians are often hesitant to prescribe it to breast cancer survivors.Therefore, other treatment options are essential. The aim of this study was to examine the safety and effectiveness of fractional CO2 laser treatment in breast cancer survivors experiencing GSM. Materials and Methods: Each woman received three fractional CO2 treatments at 4-week intervals between sessions: baseline (V1), 4-week follow-up (V2), 8-week follow-up (V3), and a final follow-up at 12 weeks (V4). Breast cancer survivors who had one or more symptoms related to GSM qualified for inclusion in this study. Severity of symptoms was assessed with a visual analog scale (VAS) at baseline and every follow-up visit. We also measured GSM objectively using the vaginal health index score (VHIS) at every visit. At V4, patients evaluated their satisfaction with laser therapy using a 5-point Likert scale. Results: Twenty-four women were included in the study. Almost all symptoms showed improvement based on mean VAS score after treatment. Vaginal dryness and urgency improved after the second treatment. After completion of all treatments, all symptoms except frequency showed improvement. VHIS increased significantly after completion of laser treatment (8.5±3.1 at baseline vs. 16.2±2.9 at V4; p<0.001). Conclusion Fractional CO2 laser treatment appears to be an effective and safe method in breast cancer survivors with GSM.

This study aimed to investigate changes in candidemia incidence, species distribution, antifungal susceptibility, initial antifungal use, and mortality trends in Korea before and during the COVID-19 pandemic. A retrospective analysis was conducted on candidemia cases from two tertiary care hospitals in Korea between 2017 and 2022. Data were compared between the pre-pandemic (2017-2019) and pandemic (2020-2022) periods. Statistical methods included incidence rate ratios (IRRs) and multivariate Cox regression to assess 30-day mortality risk factors. A total of 470 candidemia cases were identified, with 48.7% occurring pre-pandemic and 51.3% during the pandemic. While the overall incidence of candidemia remained similar across the two periods (IRR 1.15;p=0.13), the incidence in intensive care units (ICUs) significantly increased during the pandemic (IRR 1.50; p<0.01). The distribution of Candida species did not differ significantly between the two periods. Fluconazole non-susceptibility in C. albicans markedly decreased (10.0% vs. 0.9%, p<0.01), whereas C. glabrata exhibited a significant rise in caspofungin non-susceptibility during the pandemic (0% vs. 22.4%, p<0.01).Echinocandin use increased (21.8% vs. 34.4%; p<0.01), while fluconazole use declined (48.0% vs. 32.8%; p<0.01). Although the 30-day mortality rate was higher during the pandemic (60.2% vs. 57.2%), the difference was not statistically significant (p=0.57).The findings highlight the need for region-specific surveillance and tailored management strategies to improve candidemia outcomes, especially during healthcare disruptions like the COVID-19 pandemic.

Background: Though accumulating evidence suggests an association between childhood trauma and anhedonia, further analysis is needed to consider specific traumatic dimensions, both traits and state anhedonia, and the role of circulating proteins. Therefore, this study investigated the association between different types of childhood traumas and their influence on anhedonia-related symptoms, and to evaluate the influence of anhedonia traits and plasma proteins as mediators. Methods: This study included 170 patients with schizophrenia, bipolar disorder, major depressive disorder, and healthy controls aged 19–65 years. Multiple reaction monitoring was performed to quantify plasma proteins, and 464 proteins were analyzed. The association between childhood trauma dimensions, anhedonic traits, and related symptoms was analyzed with linear regression. A series of mediation analyses was performed to determine whether anhedonic traits and plasma proteins mediated the association between childhood trauma and anhedonia-related symptoms. Results: Childhood emotional neglect was significantly associated with anhedonic traits and anhedonia-related symptoms. Mediation analysis revealed that the indirect effect of anhedonic traits for childhood emotional neglect on anhedonia-related symptoms (effect = 0.037; bias-corrected CI, 0.009 to 0.070) was statistically significant. The indirect effect of plasma TNR5 for anhedonic traits on anhedonia-related symptoms was statistically significant (effect = −0.011; bias-corrected CI, −0.026 to −0.002). Serial mediation analysis revealed that the indirect effect of childhood emotional neglect on anhedonia-related symptoms via anhedonic traits and TNR5 was statistically significant (effect = 0.007; biascorrected CI, 0.001 to 0.017). Conclusion Anhedonic traits and plasma TNR5 protein levels serially mediated the association between childhood emotional neglect and anhedonia-related symptoms.The study highlights the importance of considering both psychopathological traits and biological correlates when investigating the association between childhood trauma and psychopathological symptoms.

The rapid advancement of digital dentistry has enabled the integration of digital technologies into full-mouth rehabilitation, improving communication between clinicians and dental technicians while greatly enhancing treatment efficiency.This case report details the treatment of a patient with severe tooth erosion and wear, where full-mouth rehabilitation with an increase in vertical dimension was planned. Four digital tools‒an intraoral scanner, facial scanner, T-scan, and Jaw Motion Analyzer‒were used to collect and integrate data, which were then utilized to create a virtual patient through CAD software for the design and fabrication of the prosthesis. The effective use of these digital technologies supported the achievement of a stable occlusion and resulted in both functional and esthetic outcomes. This case demonstrates the effectiveness of a digital workflow in enhancing the accuracy and efficiency of the treatment process, producing clinically satisfactory results.

This study aimed to investigate changes in candidemia incidence, species distribution, antifungal susceptibility, initial antifungal use, and mortality trends in Korea before and during the COVID-19 pandemic. A retrospective analysis was conducted on candidemia cases from two tertiary care hospitals in Korea between 2017 and 2022. Data were compared between the pre-pandemic (2017-2019) and pandemic (2020-2022) periods. Statistical methods included incidence rate ratios (IRRs) and multivariate Cox regression to assess 30-day mortality risk factors. A total of 470 candidemia cases were identified, with 48.7% occurring pre-pandemic and 51.3% during the pandemic. While the overall incidence of candidemia remained similar across the two periods (IRR 1.15;p=0.13), the incidence in intensive care units (ICUs) significantly increased during the pandemic (IRR 1.50; p<0.01). The distribution of Candida species did not differ significantly between the two periods. Fluconazole non-susceptibility in C. albicans markedly decreased (10.0% vs. 0.9%, p<0.01), whereas C. glabrata exhibited a significant rise in caspofungin non-susceptibility during the pandemic (0% vs. 22.4%, p<0.01).Echinocandin use increased (21.8% vs. 34.4%; p<0.01), while fluconazole use declined (48.0% vs. 32.8%; p<0.01). Although the 30-day mortality rate was higher during the pandemic (60.2% vs. 57.2%), the difference was not statistically significant (p=0.57).The findings highlight the need for region-specific surveillance and tailored management strategies to improve candidemia outcomes, especially during healthcare disruptions like the COVID-19 pandemic.

Background: Though accumulating evidence suggests an association between childhood trauma and anhedonia, further analysis is needed to consider specific traumatic dimensions, both traits and state anhedonia, and the role of circulating proteins. Therefore, this study investigated the association between different types of childhood traumas and their influence on anhedonia-related symptoms, and to evaluate the influence of anhedonia traits and plasma proteins as mediators. Methods: This study included 170 patients with schizophrenia, bipolar disorder, major depressive disorder, and healthy controls aged 19–65 years. Multiple reaction monitoring was performed to quantify plasma proteins, and 464 proteins were analyzed. The association between childhood trauma dimensions, anhedonic traits, and related symptoms was analyzed with linear regression. A series of mediation analyses was performed to determine whether anhedonic traits and plasma proteins mediated the association between childhood trauma and anhedonia-related symptoms. Results: Childhood emotional neglect was significantly associated with anhedonic traits and anhedonia-related symptoms. Mediation analysis revealed that the indirect effect of anhedonic traits for childhood emotional neglect on anhedonia-related symptoms (effect = 0.037; bias-corrected CI, 0.009 to 0.070) was statistically significant. The indirect effect of plasma TNR5 for anhedonic traits on anhedonia-related symptoms was statistically significant (effect = −0.011; bias-corrected CI, −0.026 to −0.002). Serial mediation analysis revealed that the indirect effect of childhood emotional neglect on anhedonia-related symptoms via anhedonic traits and TNR5 was statistically significant (effect = 0.007; biascorrected CI, 0.001 to 0.017). Conclusion Anhedonic traits and plasma TNR5 protein levels serially mediated the association between childhood emotional neglect and anhedonia-related symptoms.The study highlights the importance of considering both psychopathological traits and biological correlates when investigating the association between childhood trauma and psychopathological symptoms.

The rapid advancement of digital dentistry has enabled the integration of digital technologies into full-mouth rehabilitation, improving communication between clinicians and dental technicians while greatly enhancing treatment efficiency.This case report details the treatment of a patient with severe tooth erosion and wear, where full-mouth rehabilitation with an increase in vertical dimension was planned. Four digital tools‒an intraoral scanner, facial scanner, T-scan, and Jaw Motion Analyzer‒were used to collect and integrate data, which were then utilized to create a virtual patient through CAD software for the design and fabrication of the prosthesis. The effective use of these digital technologies supported the achievement of a stable occlusion and resulted in both functional and esthetic outcomes. This case demonstrates the effectiveness of a digital workflow in enhancing the accuracy and efficiency of the treatment process, producing clinically satisfactory results.

The rapid advancement of digital dentistry has enabled the integration of digital technologies into full-mouth rehabilitation, improving communication between clinicians and dental technicians while greatly enhancing treatment efficiency.This case report details the treatment of a patient with severe tooth erosion and wear, where full-mouth rehabilitation with an increase in vertical dimension was planned. Four digital tools‒an intraoral scanner, facial scanner, T-scan, and Jaw Motion Analyzer‒were used to collect and integrate data, which were then utilized to create a virtual patient through CAD software for the design and fabrication of the prosthesis. The effective use of these digital technologies supported the achievement of a stable occlusion and resulted in both functional and esthetic outcomes. This case demonstrates the effectiveness of a digital workflow in enhancing the accuracy and efficiency of the treatment process, producing clinically satisfactory results.

The rapid advancement of digital dentistry has enabled the integration of digital technologies into full-mouth rehabilitation, improving communication between clinicians and dental technicians while greatly enhancing treatment efficiency.This case report details the treatment of a patient with severe tooth erosion and wear, where full-mouth rehabilitation with an increase in vertical dimension was planned. Four digital tools‒an intraoral scanner, facial scanner, T-scan, and Jaw Motion Analyzer‒were used to collect and integrate data, which were then utilized to create a virtual patient through CAD software for the design and fabrication of the prosthesis. The effective use of these digital technologies supported the achievement of a stable occlusion and resulted in both functional and esthetic outcomes. This case demonstrates the effectiveness of a digital workflow in enhancing the accuracy and efficiency of the treatment process, producing clinically satisfactory results.