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

Purpose: To report five cases of macular hole (MH) coexisting with uveal melanoma (UM) and review the literature. Methods: Seventeen patients (5 new and 12 from previous reports) with coexisting MH and UM were reviewed. The patients were divided into two groups based on whether the MH was diagnosed before or after tumor treatment. The clinical features, pathogenesis, management options, and clinical outcomes were reviewed. Results: Of 505 patients with UM in our institution, 5 (1.0%) had a concurrent MH in the ipsilateral eye. The 17 patients reviewed had a mean age of 63.9 years at the time of MH diagnosis. Of 16 patients with available data on sex, 11 (64.7%) were female. There were no major differences in the demographic or clinical data of the groups. Of the 15 known tumor locations, 6 (35.3%) were juxtapapillary or macular. In patients who developed MH after UM treatment, the durations from tumor treatment (radiotherapy or transpupillary thermotherapy) to MH diagnosis were 3 to 56 months (median, 8.5 months). MH surgery was performed in nine eyes, and hole closure was achieved in seven eyes with postoperative data. The mean visual acuity showed a tendency of improvement after surgery. No intraocular or extraocular tumor dissemination associated with surgery was observed. Conclusions MH is observed in approximately 1% of patients with UM, either before or after tumor treatment. Of patients with coexisting MH and UM, MH surgery appears to be safe and effective in those with stable tumors and visual potential.

Purpose: To investigate the outcomes of brolucizumab reinjection after intraocular inflammation (IOI) development. Methods: This retrospective study analyzed patients with brolucizumab injections from April 2021 to January 2024. Patients who developed IOI after brolucizumab were included and categorized into subgroups depending on reinjection, discontinuation, and further IOI development. Results: A total of 472 eyes of 432 patients received brolucizumab injections. Thirty-eight cases developed IOI at least once, and 25 continued brolucizumab. Sixteen cases had no more IOI events, and nine experienced a second or more IOI events. Among the nine cases, three maintained brolucizumab injections despite IOI recurrence. The incidence of IOI was 8.1% based on the number of eyes (38 of 472 eyes) and 2.0% based on the number of brolucizumab injections (50 of 2,468 injections). The incidence of occlusive retinal vasculitis was 0.2% (1 of 472 eyes). The recurrence rate was 23.7% (9 of 38 eyes). The average number of injections between the first brolucizumab injection and the injection date on which IOI first developed was 2.15 times in the no-reinjection group, 3.44 times in the no-IOI-recurrence group, and 2.0 times in the second-IOI-episode group. Time to IOI occurrence in cases with first IOI episode was 18.60 ± 16.73 days, with 15 cases developing IOI within 1 week. Conclusions This study elucidates the real-world incidence of brolucizumab associated IOIs, with a description of information related to reinjections after the IOI episodes. A comprehensive understanding of brolucizumab reinjection is essential for its optimal utilization.

Objective: This study evaluated the effect of an accelerated three-dimensional (3D) T1-weighted pediatric brain MRI protocol using a deep learning (DL)-based reconstruction algorithm on scan time and image quality. Materials and Methods: This retrospective study included 46 pediatric patients who underwent conventional and accelerated, pre- and post-contrast, 3D T1-weighted brain MRI using a 3T scanner (SIGNA Premier; GE HealthCare) at a single tertiary referral center between March 1, 2023, and April 30, 2023. Conventional scans were reconstructed using intensity Filter A (Conv), whereas accelerated scans were reconstructed using intensity Filter A (Fast_A) and a DL-based algorithm (Fast_DL).Image quality was assessed quantitatively based on the coefficient of variation, relative contrast, apparent signal-to-noise ratio (aSNR), and apparent contrast-to-noise ratio (aCNR) and qualitatively according to radiologists’ ratings of overall image quality, artifacts, noisiness, gray-white matter differentiation, and lesion conspicuity. Results: The acquisition times for the pre- and post-contrast scans were 191 and 135 seconds, respectively, for the conventional scan. With the accelerated protocol, these were reduced to 135 and 80 seconds, achieving time reductions of 29.3% and 40.7%, respectively. DL-based reconstruction significantly reduced the coefficient of variation, improved the aSNR, aCNR, and overall image quality, and reduced the number of artifacts compared with the conventional acquisition method (all P < 0.05). However, the lesion conspicuity remained similar between the two protocols. Conclusion Utilizing a DL-based reconstruction algorithm in accelerated 3D T1-weighted pediatric brain MRI can significantly shorten the acquisition time, enhance image quality, and reduce artifacts, making it a viable option for pediatric imaging.

Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules, recurrent thyroid cancers (RTCs), and primary thyroid microcarcinomas. The Korean Society of Thyroid Radiology (KSThR) initially developed recommendations for the optimal use of RFA for thyroid tumors in 2009 and revised them in 2012 and 2017. As new meaningful evidence has accumulated since 2017 and in response to a growing global interest in the use of RFA for treating malignant thyroid lesions, the task force committee members of the KSThR decided to update the guidelines on the use of RFA for the management of RTCs based on a comprehensive analysis of current literature and expert consensus.

Endoscopic spine surgery (ESS) is growing in popularity worldwide. An expanding body of literature demonstrates rapid functional recovery with reduced morbidity compared to open techniques. Both full endoscopic spine surgery, or uniportal endoscopy, and unilateral biportal endoscopy (UBE) can be employed in conjunction with various navigation and enabling technologies for assistance with localization of anatomic orientation and assessment of the intraoperative target spinal pathology. This review article describes various navigation technologies in ESS, including 2-dimensional (2D) fluoroscopic imaging, 2D fluoroscopic navigation, 3-dimensional C-arm navigation, augmented reality, and spinal robotics. Employment of enabling navigation and emerging technology with the registration of patient-specific anatomy enables clear delineation of anatomic landmarks and facilitation of a successful procedure. Additionally, avoidance of common pitfalls during use of navigation systems in ESS is discussed in this review.

BACKGROUND/OBJECTIVES: Rosa hybrida has been demonstrated to exert biological effects on several cell types. This study investigated the efficacy of the edible ethanol extract of R.hybrida (EERH) against human colorectal carcinoma cell line (HCT116) cells.MATERIALS/METHODS: HCT116 cells were cultured with different concentrations of EERH (0, 400, 600, 800, and 1,000 µg/mL) in Dulbecco’s modified Eagle medium. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide and viable cell counting assays. Cell cycle pattern was observed by flow cytometry analysis. The wound-healing migration assay, invasion assay, and zymography were used to determine the migratory and invasive level of HCT116 cells treated with EERH. The protein expression and binding ability level of HCT116 cells following EERH treatment were analyzed via immunoblotting and the electrophoretic mobility shift assay. RESULTS: EERH suppressed HCT116 cell proliferation, thus arresting the G1-phase cell cycle.It also reduced cyclin-dependent kinases and cyclins, which are associated with p27KIP1 expression. Additionally, EERH differentially regulated the phosphorylation of extracellular signal-regulated kinase 1/2, c-Jun NH2-terminal kinase, p38, and protein kinase B. Moreover, EERH treatment inhibited the enzymatic activity of matrix metalloproteinase-9 (MMP-9) and MMP-2, resulting in HCT116 cell migration and invasion. The EERH-induced inhibition of MMP-9 and MMP-2 was attributed to the reduced transcriptional binding of activator protein-1, specificity protein-1, and nuclear factor-κB motifs in HCT116 cells. Kaempferol was identified as the main compound contributing to EERH's antitumor activity. CONCLUSION EERH inhibits HCT116 cell proliferation and metastatic potential. Therefore, it is potentially useful as a preventive and curative nutraceutical agent against colorectal cancer.

Objective: Since coronavirus disease 2019 (COVID-19) vaccination began, abnormal uterine bleeding (AUB) has occurred at a high rate. This study assessed the association between COVID-19 vaccination and AUB. Methods: In this retrospective cohort study, we analyzed mobile application data on menstrual cycles to investigate differences in the prevalence, duration, and amount of intermenstrual bleeding (IMB) after COVID-19 vaccination. We also analyzed the duration of menstruation, menstrual cycle length, and associated symptoms after the COVID-19 vaccination. Additionally, we investigated the prevalence of IMB according to the vaccine type. Results: After vaccination, IMB prevalence increased to 3.35% (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.46-1.76; p<0.0001) and IMB duration increased by 0.43 days (95% CI, 0.25-0.60; p<0.0001). The proportion of respondents whose amount of IMB was heavier than regular menstruation increased (OR, 2.96; 95% CI, 1.47-5.93; p=0.002). Menstrual duration decreased by -0.01 days (95% CI, -0.023 to 0.003; p=0.114), and menstrual cycle length increased by 1.39 days (95% CI, 1.30-1.48; p<0.0001). The proportion of participants who answered that there was a difference in menstruation amount increased (OR, 1.52; 95% CI, 1.41-1.64; p<0.0001). The prevalence of IMB increased regardless of the vaccine type. Conclusion There were statistically significant differences in the prevalence, duration and amount of IMB, menstrual duration, menstrual cycle length, and menstrual amount after COVID-19 vaccination. However, these values were not clinically meaningful and could be regarded as within the normal menstruation range.

Objective: Previous studies have reported an association between cancer-related symptoms and perceived social support (PSS). The objective of this study was to analyze whether Chemotherapy-Induced Peripheral Neuropathy (CIPN), a prevalent side effect of chemotherapy, varies according to PSS level using a validated tool for CIPN at prospective follow-up. Methods: A total of 39 breast cancer patients were evaluated for PSS using the Multidimensional Scale of Perceived Social Support (MSPSS) prior to chemotherapy and were subsequently grouped into one of two categories for each subscale: low-to-moderate PSS and high PSS. CIPN was prospectively evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20) at five time points. A linear mixed-effects model with square root transformation was employed to investigate whether the CIPN20 scales varied by PSS level and time point. Results: Statistical analysis of the MSPSS total scale and subscales revealed a significant effect of the friends subscale group and time point on the CIPN20 sensory scale. The sensory scale score of CIPN20 was found to be lower in participants with high PSS from friends in comparison to those with low-to-moderate PSS at 1 month post-chemotherapy (p=0.010). Conclusion This is the first study to prospectively follow the long-term effect of pre-treatment PSS from friends on CIPN. Further studies based on larger samples are required to analyze the effects of PSS on the pathophysiology of CIPN.