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: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). Materials and Methods: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). Results: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

In the fracture operation of pan facial fracture, there are many cases where the shape and position of the occlusal and oral structures are abnormally changed because the index for repositioning to the original position is insufficient. And trismus and gag reflex in patients with pan facial fractures increase the difficulty of dental treatment, and the difference in the position of the jaw bone makes it difficult to restore aesthetically and functionally. In this case, digital workflows for minimal intraoral work could be selected to reduce patient discomfort and the difficulty of dental treatment. This case is using a digital workflow from implant planning to final prosthesis production in a patient with acquired skeletal grade III, trismus, and gag reflex due to pan facial fracture 15 years ago. In this case report, the use of digital workflow in a patient who has difficulty in dental treatment was able to minimize patient discomfort and obtain esthetic and functionally appropriate results.

Purpose: Nutritional status and support in critically ill patients are important factors in determining patient recovery and prognosis.The aim of this study was to analyze the early nutritional status and the methods of nutritional support in critically ill patients with acute poisoning and to evaluate the effect of nutritional status on prognosis. Methods: A retrospective study was conducted in tertiary care teaching hospital from January 2018 to December 2020. in an emergency department of university hospital, 220 patients who were stayed more than 2 days of poisoning in intensive care unit were enrolled. Results: 155 (70.5%) of patients with acute poisoning had low-risk in nutritional risk screening (NRS). Patients with malignancy had higher NRS (low risk 5.2%, moderate risk 18.5%, high risk 13.2%, p=0.024). Patients of 91.4% supplied nutrition via oral route or enteral route. Parenteral route for starting method of nutritional support were higher in patients with acute poisoning of herbicide or pesticide (medicine 3.2%, herbicide 13.8%, pesticide 22.2%, p=0.000). In multivariate logistic regression analysis, herbicide or pesticide intoxication, higher risk in NRS and sequential organ failure assessment over 4.5 were affecting factor on poor recovery at discharge. Conclusion NRS in patients intoxicated with herbicide or pesticide were higher than that in patients intoxicated with medicine intoxication. Enteral nutrition in patients intoxicated with herbicide or pesticide was less common. Initial NRS was correlated with recovery at discharge in patient with intoxication. It is expected to be helpful in finding patients with high-risk nutritional status in acute poisoning patients and establishing a treatment plan that can actively implement nutritional support.

Stress severely disturbs physiological and mental homeostasis which includes adult neurogenesis in hippocampus. Neurogenesis in hippocampus is a key feature to adapt to environmental changes and highly regulated by multiple cellular signaling pathways. The primary cilium is a cellular organelle, which acts as a signaling center during development and neurogenesis in adult mice. However, it is not clear how the primary cilia are involved in the process of restraint (RST) stress response. Using a mouse model, we examined the role of primary cilia in repeated and acute RST stress response. Interestingly, RST stress increased the number of ciliated cells in the adult hippocampal dentate gyrus (DG). In our RST model, cell proliferation in the DG also increased in a time-dependent manner. Moreover, the analysis of ciliated cells in the hippocampal DG with cell type markers indicated that cells that were ciliated in response to acute RST stress are neurons. Taken together, these findings suggest that RST stress response is closely associated with an increase in the number of ciliated neurons and leads to an increase in cell proliferation.
Adult ; Animals ; Cell Proliferation ; Cilia ; Dentate Gyrus ; Hippocampus ; Homeostasis ; Humans ; Mice* ; Neurogenesis ; Neurons* ; Organelles

Despite advancements in treating ruptured cerebral aneurysms, an aneurysmal subarachnoid hemorrhage (aSAH) is still a grave cerebrovascular disease associated with a high rate of morbidity and mortality. Based on the literature published to date, worldwide academic and governmental committees have developed clinical practice guidelines (CPGs) to propose standards for disease management in order to achieve the best treatment outcomes for aSAHs. In 2013, the Korean Society of Cerebrovascular Surgeons issued a Korean version of the CPGs for aSAHs. The group researched all articles and major foreign CPGs published in English until December 2015 using several search engines. Based on these articles, levels of evidence and grades of recommendations were determined by our society as well as by other related Quality Control Committees from neurointervention, neurology and rehabilitation medicine. The Korean version of the CPGs for aSAHs includes risk factors, diagnosis, initial management, medical and surgical management to prevent rebleeding, management of delayed cerebral ischemia and vasospasm, treatment of hydrocephalus, treatment of medical complications and early rehabilitation. The CPGs are not the absolute standard but are the present reference as the evidence is still incomplete, each environment of clinical practice is different, and there is a high probability of variation in the current recommendations. The CPGs will be useful in the fields of clinical practice and research.
Aneurysm ; Brain Ischemia ; Cerebrovascular Disorders ; Diagnosis ; Disease Management ; Hydrocephalus ; Intracranial Aneurysm ; Mortality ; Neurology ; Quality Control ; Rehabilitation ; Risk Factors ; Search Engine ; Subarachnoid Hemorrhage ; Surgeons

BACKGROUND: The National Health Insurance Service (NHIS) recently signed an agreement to provide limited open access to the databases within the Korean Diabetes Association for the benefit of Korean subjects with diabetes. Here, we present the history, structure, contents, and way to use data procurement in the Korean National Health Insurance (NHI) system for the benefit of Korean researchers. METHODS: The NHIS in Korea is a single-payer program and is mandatory for all residents in Korea. The three main healthcare programs of the NHI, Medical Aid, and long-term care insurance (LTCI) provide 100% coverage for the Korean population. The NHIS in Korea has adopted a fee-for-service system to pay health providers. Researchers can obtain health information from the four databases of the insured that contain data on health insurance claims, health check-ups and LTCI. RESULTS: Metabolic disease as chronic disease is increasing with aging society. NHIS data is based on mandatory, serial population data, so, this might show the time course of disease and predict some disease progress, and also be used in primary and secondary prevention of disease after data mining. CONCLUSION: The NHIS database represents the entire Korean population and can be used as a population-based database. The integrated information technology of the NHIS database makes it a world-leading population-based epidemiology and disease research platform.
Aging ; Chronic Disease ; Data Mining ; Delivery of Health Care ; Epidemiology ; Insurance, Health ; Insurance, Long-Term Care ; Korea ; Metabolic Diseases ; National Health Programs* ; Secondary Prevention

Aspergilloma and Allergic Bronchopulmonary Aspergillosis (ABPA) are different types of spectrum of pulmonary aspergillosis. ABPA results from hypersensitivity reaction to Aspergillus species and is known to be usually associated with bronchial asthma and cystic fibrosis. Aspergilloma results from simple colonization of this fungus within cavitary lung lesion or bronchiectasis. But rarely some patients can present together with ABPA and aspergilloma. We experienced a case of ABPA associated with aspergilloma in a 38 year-old male. The diagnosis was confirmed by asthma, immediate cutaneous reactivity to A. fumigatus, IgG antibody to A. fumigatus, elevated total and specific IgE antibodies to A. fumigatus, central bronchiectasis and peripheral eosinophilia coincident with radiographic infiltrates. During follow-up management with steroid, left pneumonectomy was done because of spontaneous pneumothorax with persistent air-leak and multidrug resistance pulmonary tuberculosis in association with aspergilloma. His respiratory symptoms and ABPA activity was much more improved after removal of aspergilloma. These findings suggest that surgical resection of aspergilloma can be considered to reduce antigenic source of colonized fungi in ABPA patients when associated with aspergilloma.
Adult ; Antibodies ; Aspergillosis, Allergic Bronchopulmonary* ; Aspergillus ; Asthma ; Bronchiectasis ; Colon ; Cystic Fibrosis ; Diagnosis ; Drug Resistance, Multiple ; Eosinophilia ; Follow-Up Studies ; Fungi ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunoglobulin G ; Lung ; Male ; Pneumonectomy ; Pneumothorax ; Pulmonary Aspergillosis ; Tuberculosis ; Tuberculosis, Pulmonary

Juvenile rheumatoid arthritis (JRA) can develop the extra-articular manifestations, which are growth retardation, osteopenia, chronic uveitis, and rarely pleuropulmonary involvement. Approximately 30% of patients with JRA show abnormal pulmonary function test without pulmonary symptoms, in which the frequent abnormality is in carbon monoxide diffusing capacity, but clinically evident pulmonary parenchymal disease in JRA is extremely uncommon. We describe a 23-years-old female with JRA who presented with dyspnea due to interstitial lung disease and pulmonary hypertension. She had suffered from polyarthralgia and dyspnea since 8 years old.
Arthralgia ; Arthritis, Juvenile* ; Bone Diseases, Metabolic ; Carbon Monoxide ; Child ; Dyspnea ; Female ; Humans ; Hypertension, Pulmonary ; Lung Diseases, Interstitial* ; Respiratory Function Tests ; Uveitis

A 42 year-old male with a history of multidrug-resistant pulmonary tuberculosis suddenly developed massive hemoptysis. Embolization of a bronchial artery branch and the collateral systemic arteries did not resolve the recurrent bleeding. Spiral computerized tomography(spiral CT) of the chest showed contrast enhanced nodules within a large cavity at the left lower lobe in the arterial phase suggesting a Rasmussen aneurysm. A pulmonary angiogram showed abnormal vascular nodules at that site. Coils were deployed at both the proximal and distal vessels of this aneurysmal sac for embolization. Transcatheter arterial embolization is a safe and effective means of controlling bleeding from this pulmonary arterial pseudoaneurysm. Here we report a case of a Rasmussen aneurysm diagnosed by spiral CT, which was successfully treated by pulmonary arterial embolization with a coil.
Aneurysm* ; Aneurysm, False ; Arteries ; Bronchial Arteries ; Embolization, Therapeutic ; Hemoptysis ; Hemorrhage ; Humans ; Male ; Respiratory Insufficiency ; Thorax ; Tomography, Spiral Computed ; Tuberculosis, Pulmonary