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 and Objectives: The number of people with heart failure (HF) is increasing worldwide, and the social burden is increasing as HF has high mortality and morbidity. We aimed to provide updated trends on the epidemiology of HF in Korea to shape future social measures against HF. Methods: We used the National Health Information Database of the National Health Insurance Service to determine the prevalence, incidence, hospitalization rate, mortality rate, comorbidities, in-hospital mortality, and healthcare cost of patients with HF from 2002 to 2020 in Korea. Results: The prevalence of HF in the total Korean population rose from 0.77% in 2002 to 2.58% (1,326,886 people) in 2020. Although the age-standardized incidence of HF decreased over the past 18 years, the age-standardized prevalence increased. In 2020, the hospitalization rate for any cause in patients with HF was 1,166 per 100,000 persons, with a steady increase from 2002. In 2002, the HF mortality was 3.0 per 100,000 persons, which rose to 15.6 per 100,000 persons in 2020. While hospitalization rates and in-hospital mortality for patients with HF increased, the mortality rate for patients with HF did not (5.8% in 2020), and the one-year survival rate from the first diagnosis of HF improved. The total healthcare costs for patients with HF were approximately $2.4 billion in 2020, a 16-fold increase over the $0.15 billion in 2002. Conclusions The study’s results underscore the growing socioeconomic burden of HF in Korea, driven by an aging population and increasing HF prevalence.

Background and Objectives: Optimal anticoagulation in very elderly patients is challenging due to the high risk of anticoagulant-induced bleeding. The aim of this study was to assess outcomes of on-label reduced-dose edoxaban (30 mg) in very elderly patients who had additional risk factors for bleeding. Methods: This was a multi-center, prospective, non-interventional observational study to evaluate the efficacy and safety of on-label reduced-dose edoxaban in atrial fibrillation (AF) patients 80 years of age or older and who had more than 1 risk factor for bleeding. Results: A total of 2448 patients (mean age 75.0±8.3 years, 801 [32.7%] males) was included in the present study, and 586 (23.9%) were 80 years of age or older with additional risk factors for bleeding. Major bleeding events occurred frequently among very elderly AF patients who had additional bleeding risk factors compared to other patients (unadjusted hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.16–4.02); however, there were no significant differences in stroke incidence (HR, 1.86; 95% CI, 0.98–3.55). There were no significant differences for either factor after adjusting for age and sex (adjusted HR, 1.65; 95% CI, 0.75–3.62 for major bleeding; adjusted HR, 1.13; 95% CI, 0.51–2.50 for stroke). Conclusions In very elderly AF patients with comorbidities associated with greater risk of bleeding, the incidence of major bleeding events was significantly increased. In addition, risk of stroke showed tendency to increase in same population. Effective anticoagulation therapy might be important in these high-risk population, and close observation of bleeding events might also be required.

Background and Objectives: Accumulating evidence shows that sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce adverse cardiovascular outcomes. However, whether SGLT2i, compared with other antidiabetic drugs, reduce the new development of atrial fibrillation (AF) is unclear. In this study, we compared SGLT2i with dipeptidyl peptidase-4 inhibitors (DPP-4is) in terms of reduction in the risk of AF in individuals with type 2 diabetes. Methods: We included 42,786 propensity score-matched pairs of SGLT2i and DPP-4i users without previous AF diagnosis using the Korean National Health Insurance Service database between May 1, 2016, and December 31, 2018. Results: During a median follow-up of 1.3 years, SGLT2i users had a lower incidence of AF than DPP-4i users (1.95 vs. 2.65 per 1,000 person-years; hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55–0.97; p=0.028]). In individuals without heart failure, SGLT2i users was associated with a decreased risk of AF incidence (HR, 0.70; 95% CI, 0.52–0.94; p=0.019) compared to DPP-4i users. However, individuals with heart failure, SGLT2i users was not significantly associated with a change in risk (HR, 1.04; 95% CI, 0.44–2.44; p=0.936). Conclusions In this nationwide cohort study of individuals with type 2 diabetes, treatment with SGLT2i was associated with a lower risk of AF compared with treatment with DPP-4i.

Background: Epinephrine (EPI) or norepinephrine (NOR) is widely used to treat cardiovascular collapse during lipid emulsion (LE) resuscitation for drug toxicity. However, the effect of LE on the vasoconstriction caused by EPI or NOR remains unknown. The purpose of this study was to examine the effect of an LE (Intralipid) on the vasoconstriction caused by EPI and NOR in isolated rat aorta. Methods: The effect of LE on the vasoconstriction caused by EPI or NOR in isolated rat aorta was examined. Additionally, the effect of LE on the calcium increase caused by EPI or NOR was investigated. The distribution constant (KD: lipid to aqueous phase) of EPI or NOR between a LE (1%) and an aqueous phase was determined. Results: LE (1 and 2%) did not significantly alter vasoconstriction caused by EPI or NOR in isolated endothelium-intact aorta. Moreover, the LE did not significantly alter the increased calcium level caused by EPI or NOR. The log KD of EPI in the LE (1%) was −0.71, −0.99, and −1.00 at 20, 50, and 100 mM ionic strength, respectively. The log KD of NOR in the LE (1%) was −1.22, −1.25, and −0.96 at 20, 50, and 100 mM ionic strength, respectively. Conclusions Taken together, the Intralipid emulsion did not alter vasoconstriction induced by EPI or NOR that seems to be due to the hydrophilicity of EPI or NOR, leading to sustained hemodynamic support produced by EPI or NOR used during LE resuscitation.

OBJECTIVES: Long-term care facilities (LTCFs) are communal environments for patients with chronic diseases or older adults, making them particularly susceptible to significant harm during infectious disease outbreaks. Nonetheless, LTCFs have historically been subject to less stringent infection prevention and control (IPC) mandates. This study aimed to assess the current state of LTCFs and to develop an IPC system tailored for these facilities following the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted an online survey of 11,366 LTCFs in Korea from December 30, 2022 to January 20, 2023, to evaluate the components of IPC in LTCFs. The infectious diseases targeted for IPC included COVID-19, influenza, and scabies. Additionally, we compared institution-based and home-based long-term care insurance facilities. RESULTS: Overall, 3,537 (31.1%) LTCFs responded to the survey, comprising 1,819 (51.4%) institution-based and 1,718 (48.6%) home-based facilities. A majority (87.4%, 2,376/2,720) of these facilities experienced COVID-19 outbreaks. However, only 42.2% of home-based facilities, in contrast to 90.6% of institution-based facilities, were equipped to manage concurrent COVID-19 cases. Similarly, while 92.1% of institution-based facilities were capable of managing influenza, only 50.5% of home-based facilities could do the same. The incidence of scabies was significantly higher in institution-based facilities than in home-based ones (26.1 vs. 4.3%). Additionally, 88.7% of institution-based facilities managed scabies cases effectively, compared to only 42.1% of home-based facilities. CONCLUSIONS Approximately half of the LTCFs had a basic capacity to respond to infectious diseases. However, there were differences in response capabilities between institution-based facilities and home-based facilities.

Myosin heavy chain 9 (MYH9) related diseases are autosomal dominant diseases characterized by macrothrombocytopenia and inclusion bodies in leukocyte, which can be accompanied by extra-hematologic symptoms such as sensorineural hearing loss, renal dysfunction, and cataract. They are often diagnosed incidentally in adulthood or misdiagnosed as idiopathic thrombocytopenic purpura (ITP), leading to unnecessary treatment with intravenous high-dose gamma-globulin, steroids, or splenectomy. Here, we report the case of a brother and sister confirmed to have a MYH9 gene mutation during follow-up. An 8-year-old boy was confirmed to have thrombocytopenia at birth and treated with intravenous gamma-globulin under suspicion of ITP or sepsis. He was discharged after showing an increase in platelet count. Subsequently, during outpatient workup, he exhibited thrombocytopenia, large platelets, and neutrophilic inclusion bodies. His 10-year-old sister also presented with the same findings. In 2021, DNA analysis revealed that they share a mutation (c.4270G> A, p. Asp1424Asn), a pathogenic variant associated with MYH9-related disorder.

OBJECTIVES: Long-term care facilities (LTCFs) are communal environments for patients with chronic diseases or older adults, making them particularly susceptible to significant harm during infectious disease outbreaks. Nonetheless, LTCFs have historically been subject to less stringent infection prevention and control (IPC) mandates. This study aimed to assess the current state of LTCFs and to develop an IPC system tailored for these facilities following the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted an online survey of 11,366 LTCFs in Korea from December 30, 2022 to January 20, 2023, to evaluate the components of IPC in LTCFs. The infectious diseases targeted for IPC included COVID-19, influenza, and scabies. Additionally, we compared institution-based and home-based long-term care insurance facilities. RESULTS: Overall, 3,537 (31.1%) LTCFs responded to the survey, comprising 1,819 (51.4%) institution-based and 1,718 (48.6%) home-based facilities. A majority (87.4%, 2,376/2,720) of these facilities experienced COVID-19 outbreaks. However, only 42.2% of home-based facilities, in contrast to 90.6% of institution-based facilities, were equipped to manage concurrent COVID-19 cases. Similarly, while 92.1% of institution-based facilities were capable of managing influenza, only 50.5% of home-based facilities could do the same. The incidence of scabies was significantly higher in institution-based facilities than in home-based ones (26.1 vs. 4.3%). Additionally, 88.7% of institution-based facilities managed scabies cases effectively, compared to only 42.1% of home-based facilities. CONCLUSIONS Approximately half of the LTCFs had a basic capacity to respond to infectious diseases. However, there were differences in response capabilities between institution-based facilities and home-based facilities.

OBJECTIVES: Long-term care facilities (LTCFs) are communal environments for patients with chronic diseases or older adults, making them particularly susceptible to significant harm during infectious disease outbreaks. Nonetheless, LTCFs have historically been subject to less stringent infection prevention and control (IPC) mandates. This study aimed to assess the current state of LTCFs and to develop an IPC system tailored for these facilities following the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted an online survey of 11,366 LTCFs in Korea from December 30, 2022 to January 20, 2023, to evaluate the components of IPC in LTCFs. The infectious diseases targeted for IPC included COVID-19, influenza, and scabies. Additionally, we compared institution-based and home-based long-term care insurance facilities. RESULTS: Overall, 3,537 (31.1%) LTCFs responded to the survey, comprising 1,819 (51.4%) institution-based and 1,718 (48.6%) home-based facilities. A majority (87.4%, 2,376/2,720) of these facilities experienced COVID-19 outbreaks. However, only 42.2% of home-based facilities, in contrast to 90.6% of institution-based facilities, were equipped to manage concurrent COVID-19 cases. Similarly, while 92.1% of institution-based facilities were capable of managing influenza, only 50.5% of home-based facilities could do the same. The incidence of scabies was significantly higher in institution-based facilities than in home-based ones (26.1 vs. 4.3%). Additionally, 88.7% of institution-based facilities managed scabies cases effectively, compared to only 42.1% of home-based facilities. CONCLUSIONS Approximately half of the LTCFs had a basic capacity to respond to infectious diseases. However, there were differences in response capabilities between institution-based facilities and home-based facilities.

There are limited data on outcomes after implantation of everolimus-eluting stents (EES) in East Asian patients with small vessel coronary lesions. A total of 1,600 patients treated with XIENCE EES (Abbott Vascular, CA, USA) were divided into the small vessel group treated with one ≤2.5 mm stent (n=119) and the non-small vessel group treated with one ≥2.75 mm stent (n=933). The primary end point was a patient-oriented composite outcome (POCO), a composite of all-cause death, myocardial infarction (MI), and any repeat revascularization at 12 months. The key secondary end point was a device-oriented composite outcome (DOCO), a composite of cardiovascular death, target-vessel MI, and target lesion revascularization at 12 months. The small vessel group was more often female, hypertensive, less likely to present with ST-elevation MI, and more often treated for the left circumflex artery, whereas the non-small vessel group more often had type B2/C lesions, underwent intravascular ultrasound, and received unfractionated heparin. In the propensity matched cohort, the mean stent diameter was 2.5±0.0 mm and 3.1±0.4 mm in the small and non-small vessel groups, respectively. Propensity-adjusted POCO at 12 months was 6.0% in the small vessel group and 4.3% in the non-small vessel group (p=0.558). There was no significant difference in DOCO at 12 months (small vessel group: 4.3% and non-small vessel group: 1.7%, p=0.270).Outcomes of XIENCE EES for small vessel disease were comparable to those for non-small vessel disease at 12-month clinical follow-up in real-world Korean patients.