Purpose: In this study, we investigated the effect of bisphenol-A (BPA) and its major analogs, bisphenol-F (BPF), and bisphenol-S (BPS), on spermatogonial stem cells (SSCs) populations using in vitro SSC culture and in vivo transplantation models. Materials and Methods: SSCs enriched from 6- to 8-day-old C57BL/6-eGFP+ male mice testes were treated with varying concentrations of bisphenols for 7 days to examine bisphenol-derived cytotoxicity and changes in SSC characteristics. We utilized flow cytometry, immunocytochemistry, real-time quantitative reverse transcription-PCR, and western blot analysis. The functional alteration of SSCs was further investigated by examining donor SSC-derived spermatogenesis evaluation through in vivo transplantation and subsequent testis analysis. Results: BPF exhibited a similar inhibitory effect on SSCs as BPA, demonstrating a significant decrease in SSC survival, inhibition of proliferation, and induction of apoptosis. On the other hand, while BPS was comparatively weaker than BPA and BPF, it still showed significant SSC cytotoxicity. Importantly, SSCs exposed to BPA, BPF, and BPS exhibited a significant reduction in donor SSC-derived germ cell colonies per total number of cultured cells, indicating that, like BPA, BPF, and BPS can induce a comparable reduction in functional SSCs in the recipient animals. However, the progress of spermatogenesis, as evidenced by histochemistry and the expressions of PCNA and SSC specific markers, collectively indicates that BPA, BPF, and BPS may not adversely affect the spermatogenesis. Conclusions Our findings indicate that the major BPA substitutes, BPF and BPS, have significant cytotoxic effects on SSCs, similar to BPA. These effects may lead to a reduction in the functional self-renewal stem cell population and potential impacts on male fertility.

BACKGROUND: Bone defects are commonly encountered due to accidents, diseases, or aging, and the demand for effective bone regeneration, particularly for dental implants, is increasing in our aging society. Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapies; however, obtaining sufficient quantities of these cells for clinical applications remains challenging. DW-MSCs, derived from embryonic stem cells and developed by Daewoong Pharmaceutical, exhibit a robust proliferative capacity even after extensive culture. METHODS: This study explores the therapeutic potential of DW-MSCs in various animal models of bone defects. DWMSCs were expanded for over 13 passages for in vivo use in rat and canine models of bone defects and osteomyelitis. The research focused on the in vivo osteogenic differentiation of DW-MSCs, the establishment of a fibrin-based system for bone regeneration, the assessment of bone repair following treatment in animal models, and comparisons with commercially available bone grafts. RESULTS: Results showed that DW-MSCs exhibited superior osteogenic differentiation compared to other materials, and the fibrinization process not only preserved but enhanced their proliferation and differentiation capabilities through a 3D culture effect. In both bone defect models, DW-MSCs facilitated significant bone regeneration, reduced inflammatory responses in osteomyelitis, and achieved effective bone healing. The therapeutic outcomes of DW-MSCs were comparable to those of commercial bone grafts but demonstrated qualitatively superior bone tissue restructuring. CONCLUSION Our findings suggest that DW-MSCs offer a promising approach for bone regeneration therapies due to their high efficacy and anti-inflammatory properties.

BACKGROUND: Embryo-endometrium cross-talk is one of the critical processes for implantation, and unsuccessful cross-talk leads to infertility. We established an endometrium-embryo (or embryoid bodies, hEBs) in vitro model in 2D and 3D conditions and assessed its potential through the fusion of embryos and the expression of specific markers. METHODS: C57BL/6 mouse embryos and human embryoid body (hEB) derived from embryonic stem cells were prepared as embryo models. Mouse endometrium (EM) and human endometrium cell line, HEC-1-A, were prepared, and 2D or 3D EMs were generated. The viability of the 3D endometrium was analyzed, and the optimal ratio of the gelation was revealed. The invasion of the embryos or hEBs was examined by immunostaining and 3D image rendering. RESULTS: The embryos and the alternative hEBs were effectively fused into 2D or 3D vitro EM models in both mouse and human models. The fused embryos and hEBs exhibited migration and further development. Notably, the established in vitro model expressed Oct4 and E-Cadherin, markers for early embryonic development; human CG Receptor and Progesterone Receptor, critical for implantation and pregnancy maintenance; and TSH Receptor, Epiregulin, and Prolactin, indicators of endometrial receptivity and embryo implantation. CONCLUSION This study marks a significant advancement in the field, as we have successfully established a novel in vitro model for studying embryo-endometrium cross-talk. This model, a crucial tool for understanding fertility and the causes of miscarriage due to failed implantation, provides a unique platform for investigating the complex processes of successful implantation and pregnancy, underscoring its potential impact on reproductive health.

High-flow nasal cannula (HFNC) is a noninvasive respiratory support system that delivers air that is heated at 31°C−38°C, humidified 100%, and oxygen-enriched at a constant high flow rate of 15−60 L/min. Because of its numerous physiological benefits, convenience, and minimal side effects, HFNC has been increasingly used over the past decade in patients with acute hypoxemic respiratory failure, yet the clinical benefits of long-term HFNC remain uncertain. Several studies have suggested its potential use as an alternative home oxygen therapy for patients with chronic stable lung diseases, such as chronic obstructive pulmonary disease (COPD), interstitial lung disease, and bronchiectasis. The use of long-term home HFNC in patients with chronic respiratory failure is an emerging area with promising potential. Despite limited clinical research, this review aims to describe the physiology of HFNC use and summarize the current evidence on its long-term application, to provide healthcare providers with insights and perspectives on the potential role of long-term home HFNC.

Background: Lung ultrasound (LUS) has proven valuable in the initial assessment of coronavirus disease 2019 (COVID-19), but its role in detecting pulmonary fibrosis following intensive care remains unclear. This study aims to assess the presence of pulmonary sequelae and fibrosis-like changes using LUS in survivors of severe COVID-19 pneumonia one month after discharge. Methods: We prospectively enrolled patients with severe COVID-19 who required mechanical ventilation in the intensive care unit (ICU) and conducted LUS assessments from admission to the outpatient visit after discharge. We tracked changes in key LUS findings and applied our proprietary LUS scoring system. To evaluate LUS accuracy, we correlated measured LUS values with computed tomography scores. Results: We evaluated B-line presence, pleural thickness, and consolidation in 14 eligible patients. The LUS scores exhibited minimal changes, with values of 19.1, 19.2, and 17.5 at admission, discharge, and the outpatient visit, respectively. Notably, the number of B-lines decreased significantly, from 1.92 at admission to 0.56 at the outpatient visit (p<0.05), while pleural thickness increased significantly, from 2.05 at admission to 2.48 at the outpatient visit (p≤0.05). Conclusion This study demonstrates that LUS can track changes in lung abnormalities in severe COVID-19 patients from ICU admission through to outpatient follow-up. While pleural thickening and B-line patterns showed significant changes, no correlation was found between LUS and high-resolution computed tomography fibrosis scores. These findings suggest that LUS may serve as a supplementary tool for assessing pulmonary recovery in severe COVID-19 cases.

Background: The development of frailty at hospital discharge affects the clinical outcomes in severe coronavirus disease 2019 (COVID-19) survivors who had no frailty before hospitalization. We aimed to describe the prevalence of new frailty using the clinical frailty scale (CFS) and evaluate its associated factors in patients with severe COVID-19 without pre-existing frailty before hospitalization. Methods: We performed a secondary analysis of clinical data from a nationwide retrospective cohort collected from 22 hospitals between January 1, 2020 and August 31, 2021. The patients were at least 19 years old and survived until discharge after admission to the intensive care unit (ICU) because of severe COVID-19. Development of new frailty was defined as a CFS score ≥5 at hospital discharge. Results: Among 669 severe COVID-19 survivors without pre-existing frailty admitted to the ICU, the mean age was 65.2±12.8 years, 62.5% were male, and 50.2% received mechanical ventilation (MV). The mean CFS score at admission was 2.4±0.9, and new frailty developed in 27.8% (186/483). In multivariate analysis, older age, cardiovascular disease, CFS score of 3–4 before hospitalization, increased C-reactive protein level, longer duration of corticosteroid treatment, and use of MV and extracorporeal membrane oxygenation were identified as factors associated with new-onset frailty. Conclusion Our study suggests that new frailty is not uncommon and is associated with diverse factors in survivors of severe COVID-19 without pre-existing frailty.

Purpose: Emphysematous pyelonephritis (EPN) is a life-threatening disease requiring immediate treatment. This multicenter retrospective cohort study aimed to analyze the mortality rate and risk factors associated with EPN. Materials and Methods: Between January 2011 and February 2021, 217 patients diagnosed with EPN via computed tomography who visited 14 teaching hospitals were retrospectively analyzed. Clinical data, including age, sex, comorbidities, Huang and Tseng classification, hydronephrosis, acute kidney injury, blood and urine tests, surgical interventions, percutaneous drainage, and conservative treatments, were compared between the survival and death groups. Risk factors for mortality due to EPN were analyzed using univariate and multivariate methods. Results: The mean age of survivors and deceased patients was 67.8 and 69.0 years, respectively (p=0.136). The sex distribution (male/female) was 48/146 and 8/15, respectively (p=0.298). Of the 217 patients, 23 died, resulting in a mortality rate of 10.6%. In univariate analysis, the Huang and Tseng classification (p=0.004), platelet count (p=0.005), and acute kidney injury (p=0.007) were significantly associated with mortality from EPN. In multivariate analysis, only the Huang and Tseng classification (p=0.029) was identified as a risk factor. Mortality rates according to the Huang and Tseng classification were as follows: class I (5.88%), class II (7.50%), class IIIa (14.28%), class IIIb (25.00%), and class IV (23.07%). Conclusions EPN is associated with a high mortality rate. Among various clinical factors, the Huang and Tseng classification was the most significant indicator for predicting mortality.

Purpose: Point-of-care ultrasound (POCUS) is widely used for heart function evaluation in emergency departments (EDs), but requires specific equipment and skilled operators. This study evaluates the diagnostic accuracy of a mobile application for estimating left ventricular (LV) systolic dysfunction [left ventricular ejection fraction (LVEF) <40%] using electrocardiography (ECG) and tests its non-inferiority to POCUS. Materials and Methods: Patients (aged ≥20 years) were included if they had both a POCUS-based EF evaluation and an ECG within 24 hours of their ED visit between January and May 2022, along with formal echocardiography within 2 weeks before or after the visit. A mobile app (ECG Buddy, EB) estimated LVEF (EF from EB) and the risk of LV dysfunction (LV-Dysfunction score) from ECG waveforms, which were compared to NT-proBNP levels and POCUS-evaluated LVEF (EF from POCUS). A non-inferiority margin was set at an area under the curve (AUC) difference of 0.05. Results: Of the 181 patients included, 37 (20.4%) exhibited LV dysfunction. The AUCs for screening LV dysfunction using POCUS and NT-proBNP were 0.885 and 0.822, respectively. EF from EB and LV-Dysfunction score outperformed NT-proBNP, with AUCs of 0.893 and 0.884, respectively (p=0.017 and p=0.030, respectively). EF from EB was non-inferior to EF from POCUS, while LV-Dysfunction score narrowly missed the mark. A subgroup analysis of sinus-origin rhythm ECGs supported the non-inferiority of both EF from EB and LV-Dysfunction score to EF from POCUS. Conclusion A smartphone application that analyzes ECG image can screen for LV dysfunction with a level of accuracy comparable to that of POCUS.

Background: s/Aims: Radiofrequency ablation (RFA) is widely employed for managing recurrent hepatocellular carcinoma (HCC) following transarterial chemoembolization (TACE). However, local tumor progression (LTP) after treatment remains a significant challenge. This study evaluates the efficacy of saline-perfused bipolar RFA using twin internally cooled-perfusion (TICP) electrodes in managing recurrent HCC post-TACE. Methods: Between September 2017 and January 2019, 100 patients with 105 nodules (mean diameter, 1.6±0.5 cm) were prospectively enrolled. Bipolar RFA with TICP electrodes was performed under ultrasound-computed tomography/magnetic resonance fusion guidance. The primary outcome was the 2-year cumulative incidence of LTP. Results: The technical success and technique efficacy rates were 100% and 97%, respectively. During a median follow-up period of 34.0 months (range, 3-41), the estimated LTP rates were 13.3% at 1 year and 17.7% at 2 years. Progression-free survival rates were 37.8% and 27.7% at 1 year and 2 years, respectively. Conclusions Saline-perfused bipolar RFA using TICP electrodes demonstrates promising results for recurrent HCC after TACE, achieving high technical success and effective local tumor control rates.