Primary cilia function as critical sensory organelles that mediate multiple signaling pathways, including the Hedgehog (Hh) pathway, which is essential for organ patterning and morphogenesis. Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice. Cilk1, a highly conserved serine/threonine-protein kinase localized within primary cilia, plays a critical role in ciliary transport. Loss of Cilk1 results in severe ciliopathy phenotypes, including polydactyly, edema, and cleft palate. However, the role of Cilk1 in tooth development remains unexplored. In this study, we investigated the role of Cilk1 in tooth development. Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars. Cilk1 deficiency resulted in altered ciliary dynamics, characterized by reduced frequency and increased length, accompanied by downregulation of Hh target genes, such as Ptch1 and Sostdc1, leading to the formation of diastemal supernumerary teeth. Furthermore, in Cilk1^-/-;PCS1-MRCS1^△/△ mice, which exhibit a compounded suppression of Hh signaling, we uncovered a novel phenomenon: diastemal supernumerary teeth can be larger than first molars. Based on these findings, we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning: initially inducing diastemal supernumerary teeth, then enlarging them, and ultimately leading to molar fusion. This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.
Animals ; Hedgehog Proteins/physiology* ; Mice ; Signal Transduction/physiology* ; Tooth, Supernumerary ; Molar ; Cilia/physiology* ; Odontogenesis/physiology* ; Patched-1 Receptor ; Protein Serine-Threonine Kinases/physiology* ; Mice, Knockout ; Adaptor Proteins, Signal Transducing

Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE –/–mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.

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.

Purpose: This study aimed to define an optimal age cutoff for early-onset gastric cancer (EOGC) and compare its characteristics with those of late-onset gastric cancer (LOGC) using nationwide survey data. Methods: Using data from a nationwide survey, this comprehensive population-based study analyzed data spanning 3 years (2009, 2014, and 2019). The joinpoint analysis and interrupted time series (ITS) methodology were employed to identify age cutoffs for EOGC based on the sex ratio and tumor histology. Clinicopathologic characteristics and surgical outcomes were compared between the EOGC and LOGC groups. Results: The age cutoff for defining EOGC was suggested to be 50 years, supported by joinpoint and ITS analyses. Early gastric cancer was predominantly present in the EOGC and LOGC groups. Patients with EOGC comprised 20.3% of the total study cohort and demonstrated a more advanced disease stage compared to patients with LOGC. However, patients with EOGC underwent more minimally invasive surgeries, experienced shorter hospital stays, and had lower postoperative morbidity and mortality rates. Conclusion This study proposes an age of ≤50 years as a criterion for defining EOGC and highlights its features compared to LOGC. Further research using this criterion should guide tailored treatment strategies and improve outcomes for young patients with gastric cancer.

Purpose: Multidisciplinary treatment (MDT) in gastric cancer is an effective approach for establishing treatment plans.However, the appropriateness of using “ratio of MDT” as an item for evaluating the adequacy of gastric cancer treatment in Korea has not been previously researched. The purpose of this study is to verify whether the “ratio of MDT” is appropriate as an item for gastric cancer adequacy evaluation from the surgeon’s perspective. Methods: This study involved 142 patients who received MDT at our hospital between December 2015 and January 2023.Patients were divided into 2 groups based on the date when gastric cancer adequacy evaluation was implemented; there were 71 patients before and after the evaluation was conducted, respectively. Based on electronic medical records, the initial plan prepared before the MDT clinic and the final plan prepared after the clinic were compared to determine whether the plan was changed. Results: The average age of patients who received MDT before and after the evaluation was 64.8 and 62.2 years, respectively. Overall, 50 and 21 patients were male (70.4%) and female (29.6%), respectively, in both groups. Before the evaluation, 26 patients (36.6%) who received MDT changed their treatment plans after visiting the clinic, and 15 patients (21.1%) who received MDT after the evaluation had their treatment plans modified. Groups who received MDT and changes in treatment plans were significantly correlated (P = 0.042). Conclusion Our findings suggest that including the “ratio of MDT” as an item of gastric cancer adequacy evaluation needs reassessment.

The application area of biportal endoscopic spine surgery (BESS) is gradually expanding. Compared with conventional fusion surgery, transforaminal interbody fusion (TLIF) using BESS (BESS-TLIF) has the advantages of less bleeding, minimal postoperative pain, and faster recovery. This technical note highlights its application in managing complex conditions such as scar tissue adhesion, altered anatomy, and implant removal, common in reoperations. The method focuses on precise dissection, endoscopic visualization, and careful tissue handling to ensure effective decompression and stabilization. Three representative cases, including reoperations for recurrent disc herniation, adjacent segment disease (ASD) following prior fusion, and ASD with nonunion of the prior fusion site requiring fusion extension, were described. All three cases exhibited clinical improvement following surgery. BESS is an effective and safe method for spinal revision surgery not only in simple decompression surgery but also in cases that required fusion surgery. As BESS is advancing, its role in complex spinal surgeries is expected to expand, potentially setting new standards in minimally invasive spine surgery.

Recent technological advancements and environmental changes are leading to an increase in various diseases such as obesity, fibrosis, metabolic disorders, and degenerative diseases associated with aging. Additionally, micro- and nanoplastics are emerging as as potential contributors to many of these conditions, posing a serious threat to human health. This special issue aims to explore new directions and opportunities for future drug development through recent review articles published in the issue, focusing on these key medical topics.