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

This case report details a rare presentation of multifocal osteomyelitis with bilateral femoral pathologic fractures caused by Klebsiella pneumoniae sepsis in a 54-year-old female patient. In the initial evaluation, the patient presented with swelling and pain in the left lower limb. Imaging revealed multiple liver abscesses and deep vein thrombosis. Further bone scan assessments confirmed extensive osteolytic lesions in the femurs and left tibias, which is consistent with multifocal osteomyelitis. Initial management involved broad-spectrum antibiotics and debridement. On the other hand, temporary circular wiring and intramedullary nailing were required for stabilization as fractures developed in both femurs, including additional fixation for a fracture at the curettage site on the contralateral femur. Infected tibial lesions were treated with antibiotic-loaded cement beads after abscess drainage to control local infection. Despite the complexities, the patient ultimately achieved bone union after a year-long recovery, including dynamic conversion of femoral fixation. This paper reports a rare experience in treating multiple osteomyelitis and introduces the emergence of a highly pathogenic hypervirulent K. pneumoniae strain (hvKP), causing invasive infections, including metastatic and severe infections (e.g., osteomyelitis). Furthermore, the authors emphasize that early identification of hvKP and coordinated treatment strategies are crucial for improving the outcomes in severe hvKP-related infections.

This case report details a rare presentation of multifocal osteomyelitis with bilateral femoral pathologic fractures caused by Klebsiella pneumoniae sepsis in a 54-year-old female patient. In the initial evaluation, the patient presented with swelling and pain in the left lower limb. Imaging revealed multiple liver abscesses and deep vein thrombosis. Further bone scan assessments confirmed extensive osteolytic lesions in the femurs and left tibias, which is consistent with multifocal osteomyelitis. Initial management involved broad-spectrum antibiotics and debridement. On the other hand, temporary circular wiring and intramedullary nailing were required for stabilization as fractures developed in both femurs, including additional fixation for a fracture at the curettage site on the contralateral femur. Infected tibial lesions were treated with antibiotic-loaded cement beads after abscess drainage to control local infection. Despite the complexities, the patient ultimately achieved bone union after a year-long recovery, including dynamic conversion of femoral fixation. This paper reports a rare experience in treating multiple osteomyelitis and introduces the emergence of a highly pathogenic hypervirulent K. pneumoniae strain (hvKP), causing invasive infections, including metastatic and severe infections (e.g., osteomyelitis). Furthermore, the authors emphasize that early identification of hvKP and coordinated treatment strategies are crucial for improving the outcomes in severe hvKP-related infections.

This case report details a rare presentation of multifocal osteomyelitis with bilateral femoral pathologic fractures caused by Klebsiella pneumoniae sepsis in a 54-year-old female patient. In the initial evaluation, the patient presented with swelling and pain in the left lower limb. Imaging revealed multiple liver abscesses and deep vein thrombosis. Further bone scan assessments confirmed extensive osteolytic lesions in the femurs and left tibias, which is consistent with multifocal osteomyelitis. Initial management involved broad-spectrum antibiotics and debridement. On the other hand, temporary circular wiring and intramedullary nailing were required for stabilization as fractures developed in both femurs, including additional fixation for a fracture at the curettage site on the contralateral femur. Infected tibial lesions were treated with antibiotic-loaded cement beads after abscess drainage to control local infection. Despite the complexities, the patient ultimately achieved bone union after a year-long recovery, including dynamic conversion of femoral fixation. This paper reports a rare experience in treating multiple osteomyelitis and introduces the emergence of a highly pathogenic hypervirulent K. pneumoniae strain (hvKP), causing invasive infections, including metastatic and severe infections (e.g., osteomyelitis). Furthermore, the authors emphasize that early identification of hvKP and coordinated treatment strategies are crucial for improving the outcomes in severe hvKP-related infections.

This case report details a rare presentation of multifocal osteomyelitis with bilateral femoral pathologic fractures caused by Klebsiella pneumoniae sepsis in a 54-year-old female patient. In the initial evaluation, the patient presented with swelling and pain in the left lower limb. Imaging revealed multiple liver abscesses and deep vein thrombosis. Further bone scan assessments confirmed extensive osteolytic lesions in the femurs and left tibias, which is consistent with multifocal osteomyelitis. Initial management involved broad-spectrum antibiotics and debridement. On the other hand, temporary circular wiring and intramedullary nailing were required for stabilization as fractures developed in both femurs, including additional fixation for a fracture at the curettage site on the contralateral femur. Infected tibial lesions were treated with antibiotic-loaded cement beads after abscess drainage to control local infection. Despite the complexities, the patient ultimately achieved bone union after a year-long recovery, including dynamic conversion of femoral fixation. This paper reports a rare experience in treating multiple osteomyelitis and introduces the emergence of a highly pathogenic hypervirulent K. pneumoniae strain (hvKP), causing invasive infections, including metastatic and severe infections (e.g., osteomyelitis). Furthermore, the authors emphasize that early identification of hvKP and coordinated treatment strategies are crucial for improving the outcomes in severe hvKP-related infections.

Purpose: Patients with cancer have a high risk of depression. However, a few studies have assessed differences in the incidence of depression among patients with prostate cancer (PC) based on whether they received radiotherapy (RTx) or surgical treatment. Materials and Methods: We analyzed data from the National Health Insurance Sharing Service database regarding the entire Korean adult population with PC (n=210,924) between 2007 and 2017. The adjusted hazard ratios (HRs) of depression associated with treatment were estimated using propensity score-matched Cox proportional hazards models and Kaplan–Meier survival analyses. Results: Our final cohort comprised 9,456 patients with PC; of which, 8,050 men underwent surgery. During a mean follow-up duration of 7.1 years, 503 (5.3%) patients were newly diagnosed with depression. A significant difference in the incidence of depression was noted between the RTx and surgery groups (RTx vs. surgery: 5.55% vs. 5.28%; p=0.011) in the unmatched cohort. In the matched cohort, older age (≥70 years, HR: 1.596, p<0.001) and poor Charlson comorbidity index scores (HR: 1.232, p=0.039) were correlated with the risk of depression. In addition, the adjusted HR for depression in the surgery group was 0.843 (p=0.221) compared with that in the RTx group. Kaplan–Meier analyses revealed that no significant difference in the cumulative probability of persistent depression was detected between the RTx and surgery groups in matched cohort (p=0.3386). Conclusions In this nationwide population-based study, no significant differences in the risk of depression were observed between the surgical and RTx groups.

Objectives: ：Depressive disorder and anxiety disorder frequently co-occur, even at sub-threshold level. This study aims to identify network structure of co-morbid depression and anxiety at symptom level in nonclinical population and to reveal the central symptoms and bridge symptoms of the co-morbidity. Methods: ：This study was based on 2022 Asan Youth Mental Health Screening. Patient health questionnaire (PHQ-9) and Generalized anxiety disorder scale (GAD-7) were used to assess depressive and anxiety symptoms of 810 young adult participants from community sample. Network structure of co-morbid depressive and anxiety symptoms was estimated by Isingfit model. Results: ：Depressed mood, Restlessness and Nervousness were the most central symptoms in the network. Bridge symptoms between anxiety and depression were Restlessness and Irritability. Conclusions ：This study revealed key central symptoms and bridge symptoms of co-morbid depression and anxiety in nonclinical population and provided potential insight for treatment targets to reduce co-morbidity.

Methods: We retrospectively collected the medical records of 2,134 patients with end-stage renal disease who were dependent on hemodialysis and underwent surgery under general anesthesia between January 2018 and December 2019. Propensity score matching was used. The primary outcome was the 30-day mortality rate, and secondary outcomes were the 1-year mortality rate and causes of death. Results: A total of 2,039 patients were included in the study. Sugammadex was administered as a reversal agent for rocuronium in 806 (39.5%) patients; the remaining 1,233 (60.5%) patients did not receive sugammadex. After matching, 1,594 patients were analyzed; 28 (3.5%) of the 797 patients administered sugammadex, and 28 (3.5%) of the 797 patients without sugammadex, died within 30 days after surgery (P > 0.99); 38 (4.8%) of the 797 patients administered sugammadex, and 45 (5.7%) of the 797 patients without sugammadex, died within 1 year after surgery (P = 0.499). No significant differences in the causes of 30-day mortality were observed between the two groups after matching (P = 0.860). Conclusions In this retrospective study, sugammadex did not increase the 30-day and 1-year mortality rate after surgery in end-stage renal disease patients.

Background: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. Methods: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. Results: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI;additionally, age (65–74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. Conclusions Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.

Purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis and a lack of targeted therapy. Overexpression of FRAT1 is thought to be associated with this aggressive subtype of cancer. Here, we performed a comprehensive analysis and assessed the association between overexpression of FRAT1 and TNBC. Methods: First, using different web-based bioinformatics platforms (TIMER 2.0, UALCAN, and GEPIA 2), the expression of FRAT1 was assessed. Then, the expression of the FRAT1 protein and hormone receptors and HER2 status were assessed by immunohistochemical analysis. For samples of tumors with equivocal immunoreactivity, we performed silver in situ hybridization of the HER2 gene to determine an accurate HER2 status. Next, we used the R package and bc-GenExMiner 4.8 to analyze the relationship between FRAT1 expression and clinicopathological parameters in breast cancer patients.Finally, we determined the relationship between FRAT1 overexpression and prognosis in patients. Results: The expression of FRAT1 in breast cancer tissues is significantly higher than in normal tissue. FRAT1 expression was significantly related to worse overall survival (P < 0.05) and was correlated with these clinicopathological features:T stage, N stage, age, high histologic grade, estrogen receptor status, progesterone receptor status, Her-2 status, TNBC status, basal-like status, CK5/6 status, and Ki67 status. Conclusion FRAT1 was overexpressed in breast cancer compared to normal tissue, and it may be involved in the progression of breast cancer malignancy. This study provides suggestive evidence of the prognostic role of FRAT1 in breast cancer and the therapeutic target for TNBC.