Neurosteroids play an important role as endogenous neuromodulators that are locally produced in the central nervous system and rapidly change the excitability of neurons and the activation of microglial cells and astrocytes. Here we review the mechanisms of synthesis, metabolism, and actions of neurosteroids in the central nervous system. Neurosteroids are able to play a variety of roles in the central nervous system under physiological conditions by binding to membrane ion channels and receptors such as gamma-aminobutyric acid type A receptors, Nmethyl-D-aspartate receptors, L- and T-type calcium channels, and sigma-1 receptors. In addition, numerous neurological disorders, including persistent neuropathic pain, multiple sclerosis, and seizures, have altered the levels of neurosteroids in the central nervous system. Thus, we review how local synthesis and metabolism of neurosteroids are modulated in the central nervous system and describe the role of neurosteroids under pathological conditions. Furthermore, we discuss whether neurosteroids may play a role as a new therapeutic for the treatment of neurological disorders.

Purpose: Several types of dermal fillers have been recently introduced and used for penile augmentation (PA). However, few studies have compared outcomes after the injection of different fillers. This study aimed to compare the clinical outcomes of hyaluronic acid (HLA), polylactic acid (PLA), and polymethyl methacrylate (PMA) filler injections, which are the most commonly used for aesthetic purposes. Materials and Methods: This prospective study was conducted for 24 weeks after a filler injection by a surgeon between March 2017 and December 2021. Healthy adult men complaining of small penis were enrolled. Penile girth, satisfaction, and injection-associated adverse events (AEs) were assessed at baseline and 4, 12, and 24 weeks after injection. Results: Of the 301 men who received filler injections, 125, 134, and 42 received HLA, PLA, and PMA fillers, respectively. The augmentation effect was in the order of PMA, HLA, and PLA, respectively, at 24 weeks (PMA vs. HLA, p<0.001; HLA vs. PLA, p=0.006). Satisfaction levels increased significantly at 24 weeks in all groups (each with p<0.001). However, the increase in satisfaction levels was smaller in the PMA group (PMA vs. HLA or PLA, p<0.05, for both penile appearance and sexual life). No serious or systemic AEs were recorded. Filler injection-associated local AEs in the HLA, PLA, and PMA groups occurred in 9 (7.2%), 16 (11.9%), and 6 (14.3%) men, respectively. There was no significant difference in AEs among the groups (p=0.299). Conclusions The augmentative effect was greater in the PMA group than in the HLA and PLA groups, whereas the increase in satisfaction levels was smaller in the PMA group. Our study demonstrated the clinical course of different types of fillers and suggests that the filler type should be selected after detailed counseling considering individual characteristics and preferences.

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.

Purpose: We investigated the results of endoscopic fenestration for deeply located intracranial cysts (DLICs), risk factors for reoperation, and symptom improvement. Materials and Methods: We included 51 patients with DLICs who underwent endoscopic fenestration between November 2006 and October 2022. The median age was 5±20 years (6 days–67 years), and 36 (70.6%) patients were aged <20 years. The male-tofemale ratio was 1.3:1. The ventriculoscope was used to fenestrate the cysts, which had diameters under 4.5 mm. The volume of DLICs was measured separately on serial magnetic resonance imaging, and the patients were followed up for 32±40 months. Results: The mean preoperative volume of DLICs was 63.5±87.4 cm, 3 , which decreased to 23.7±56.2 cm 3postoperatively, with a 45.4%±32.1% decrease rate in 32 months. All DLICs were approached appropriately, avoiding the eloquent areas. Overall, 39 (76.5%) patients showed symptom improvement after a single operation, which was preserved without recurrence, whereas 12 (23.5%) underwent a second operation [shunting (17.6%) or repeating the endoscopic fenestration (5.9%)] owing to symptom aggravation and recurrent cysts. Patients aged <12 months showed 7.4 times more re-operation rate (p>0.046) and 7.4 times less symptom improvement (p=0.038) compared to those with older age. Females showed 6.5 times more re-operation rate (p=0.037) and 7.1 times less symptom improvement (p=0.027) than males. No patients experienced complications such as cerebrospinal fluid leakage, postoperative hemorrhage, or infection. Conclusion Endoscopic surgery is feasible for the treatment of DLICs. Female sex and age <12 months are risk factors for re-operation and less symptom improvement.

Purpose: To evaluate the relationship between distal fusion level in correction and fusion surgery for adolescent idiopathic scoliosis (AIS) and radiologic changes in the sacroiliac (SI) joint. Materials and Methods: This retrospective cohort study evaluated patients who underwent correction and fusion for AIS between 2005 and 2017 with at least 5 years of follow-up. We categorized patients into two groups: Group 1 (distal fusion above L2, 74 patients) and Group 2 (distal fusion at L3 and below, 52 patients). Radiologic parameters and SI joint changes were evaluated on plain radiographs obtained from preoperative to 5 years postoperatively. We also investigated other risk factors for SI joint change. Results: Analysis of demographic factors revealed no significant difference between the two groups. There was a significant difference in the incidence of SI joint change between Group 1 (5 patients, 6.75%) and Group 2 (18 patients, 34.61%), with Group 2 showing a faster increase in incidence according to the Kaplan-Meier method (p<0.0001). Preoperative lumbar lordosis (LL) and ΔLL had a significant relationship with SI joint changes [preoperative LL, hazard ratio (HR)=0.77, 95% confidence interval (CI)=0.64– 0.93, p=0.008; ΔLL, HR=0.79, 95% CI=0.67–0.95, p=0.01). Conclusion After AIS surgery, patients who had fusion to the lower lumbar vertebrae (L3 or L4) experienced a higher incidence and faster progression of degenerative changes in the SI joint. Low preoperative LL and inadequate correction of LL during the operation were also risk factors for SI joint degeneration.

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.

Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from Serratula coronata, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. In vivo administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.

Microplastics (MP) are pervasive environmental pollutants with potential adverse effects on human health, particularly concerning neurotoxicity. This study investigates the accumulation and neurotoxic effects of MP in cerebral organoids and mouse brains. Utilizing in vitro cerebral organoids and in vivo mouse models, we examined the penetration of MP, revealing that smaller MP (50 nm) infiltrated deeper into the organoids compared to larger ones (100 nm). Exposure to 50 nm MP resulted in a significant reduction in organoid viability. Furthermore, total RNA sequencing indicated substantial alterations in neurotoxicity-related gene expression.In vivo, MP-treated mice exhibited notable DNA fragmentation in the hippocampus and cortex, alongside elevated levels of inflammatory markers and neurotoxic metabolites, such as kynurenine (KYN) and 3-hydroxykynurenine (3-HK). Our findings suggest that MP may promote neurotoxicity through the kynurenine pathway, leading to heightened levels of neurotoxic compounds like quinolinic acid. This research highlights the potential for MP to induce neuroinflammatory responses and disrupt normal brain function, underscoring the need for further investigation into the long-term effects of MP exposure on neurological health.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.