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

Objectives: To compare the vital sign stability and cost of two commonly used sedatives, midazolam (MDZ) and dexmedetomidine (DEX). Patients and Methods: This retrospective study targeted patients who underwent mandibular third molar extractions under intravenous sedation using MDZ or DEX. The predictor variable was the type of sedative used. The primary outcome variables were vital signs (heart rate and blood pres-sure), vital sign outliers, and cost of the sedatives. A vital sign outlier was defined as a 30% or more change in vital signs during sedation; the fewer changes, the higher the vital sign stability. The secondary outcome variables included the observer’s assessment of alertness/sedation scale, level of amnesia, patient satisfaction, and bispectral index score. Covariates were sex, age, body mass index, sleeping time, dental anxiety score, and Pederson scale. Descriptive statistics were computed including propensity score matching (PSM). The P-value was set at 0.05. Results: The study enrolled 185 patients, 103 in the MDZ group and 82 in the DEX group. Based on the data after PSM, the two samples had simi-lar baseline covariates. The sedative effect of both agents was satisfactory. Heart rate outliers were more common with MDZ than with DEX (49.3% vs 22.7%, P=0.001). Heart rate was higher with MDZ (P=0.000). The cost was higher for DEX than for MDZ (29.27±0.00 USD vs 0.37±0.04 USD, P=0.000). Conclusion DEX showed more vital sign stability, while MDZ was more economical. These results could be used as a reference to guide clinicians during sedative selection.

OBJECTIVES: The aims of this study were to determine the effectiveness of local compression in patients presenting to the emergency room with intraoral bleeding and to identify when complex haemostatic measures may be required. MATERIALS AND METHODS: Five hundred forty patients who had experienced intraoral haemorrhage were retrospectively reviewed. The outcome variable was the haemostasis method used, i.e., simple (local compression with gauze) or complex (an alternative method after local compression has failed). Predictor variables were sex, age, American Society of Anesthesiologists (ASA) class, hepatic cirrhosis, bleeding disorder, use of antithrombotic agents, and site/cause of haemorrhage. RESULTS: The mean patient age was 48.9±23.9 years, 53.5% were male, 42.8% were ASA class II or higher, and 23.7% were taking antithrombotic agents. Local compression was used most often (68.1%), followed by local haemostatic agents, sutures, systemic tranexamic acid or blood products, and electrocautery. The most common site of bleeding was the gingiva (91.7%), and the most common cause was tooth extraction (45.7%). Risk factors for needing a complex haemostasis method were use of antithrombotic agents (odds ratio 2.047, P=0.009) and minor oral surgery (excluding extraction and implant procedures; odds ratio 6.081, P=0.001). CONCLUSION A haemostasis method other than local compression may be needed in patients taking antithrombotic agents or having undergone minor oral surgery.

OBJECTIVES: The aims of this study were to determine the effectiveness of local compression in patients presenting to the emergency room with intraoral bleeding and to identify when complex haemostatic measures may be required.MATERIALS AND METHODS: Five hundred forty patients who had experienced intraoral haemorrhage were retrospectively reviewed. The outcome variable was the haemostasis method used, i.e., simple (local compression with gauze) or complex (an alternative method after local compression has failed). Predictor variables were sex, age, American Society of Anesthesiologists (ASA) class, hepatic cirrhosis, bleeding disorder, use of antithrombotic agents, and site/cause of haemorrhage.RESULTS: The mean patient age was 48.9±23.9 years, 53.5% were male, 42.8% were ASA class II or higher, and 23.7% were taking antithrombotic agents. Local compression was used most often (68.1%), followed by local haemostatic agents, sutures, systemic tranexamic acid or blood products, and electrocautery. The most common site of bleeding was the gingiva (91.7%), and the most common cause was tooth extraction (45.7%). Risk factors for needing a complex haemostasis method were use of antithrombotic agents (odds ratio 2.047, P=0.009) and minor oral surgery (excluding extraction and implant procedures; odds ratio 6.081, P=0.001).CONCLUSION: A haemostasis method other than local compression may be needed in patients taking antithrombotic agents or having undergone minor oral surgery.
Anticoagulants ; Electrocoagulation ; Emergency Service, Hospital ; Emergency Treatment ; Fibrinolytic Agents ; Gingiva ; Hemorrhage ; Humans ; Liver Cirrhosis ; Male ; Methods ; Odds Ratio ; Retrospective Studies ; Risk Factors ; Surgery, Oral ; Sutures ; Tooth Extraction ; Tranexamic Acid

BACKGROUND: For proper recovery from craniofacial fracture, it is necessary to establish guidelines based on trends. This study aimed to analyze the patterns and causes of craniofacial fractures. METHODS: This retrospective study analyzed patients who underwent surgery for craniofacial fractures between 2010 and 2017 at a single center. Several parameters, including time of injury, region and cause of fracture, alcohol intoxication, time from injury to surgery, hospitalization period, and postoperative complications, were evaluated. RESULTS: This study analyzed 2708 fracture lesions of 2076 patients, among whom males aged 10 to 39 years were the most numerous. The number of patients was significantly higher in the middle of a month. The most common fractures were a nasal bone fracture. The most common causes of fracture were ground accidents and personal assault, which tended to frequently cause more nasal bone fracture than other fractures. Traffic accidents and high falls tended to cause zygomatic arch and maxillary wall fractures more frequently. Postoperative complications—observed in 126 patients—had a significant relationship with the end of a month, mandible or panfacial fracture, and traffic accidents. CONCLUSIONS: The present findings on long-term craniofacial fracture trends should be considered by clinicians dealing with fractures and could be useful for policy decisions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40902-018-0168-y) contains supplementary material, which is available to authorized users.
Accidental Falls ; Accidents, Traffic ; Hospitalization ; Humans ; Incidence ; Male ; Mandible ; Nasal Bone ; Postoperative Complications ; Retrospective Studies ; Zygoma

T-helper (Th)17 cell responses are important for the development of neutrophilic inflammatory disease. Recently, we found that acetyl salicylic acid (ASA) inhibited Th17 airway inflammation in an asthma mouse model induced by sensitization with lipopolysaccharide (LPS)-containing allergens. To investigate the mechanism(s) of the inhibitory effect of ASA on the development of Th17 airway inflammation, a neutrophilic asthma mouse model was generated by intranasal sensitization with LPS plus ovalbumin (OVA) and then challenged with OVA alone. Immunologic parameters and airway inflammation were evaluated 6 and 48 h after the last OVA challenge. ASA inhibited the production of interleukin (IL)-17 from lung T cells as well as in vitro Th17 polarization induced by IL-6. Additionally, ASA, but not salicylic acid, suppressed Th17 airway inflammation, which was associated with decreased expression of acetyl-STAT3 (downstream signaling of IL-6) in the lung. Moreover, the production of IL-6 from inflammatory cells, induced by IL-17, was abolished by treatment with ASA, whereas that induced by LPS was not. Altogether, ASA, likely via its acetyl moiety, inhibits Th17 airway inflammation by blockade of IL-6 and IL-17 positive feedback.
Animals ; Aspirin/pharmacology/*therapeutic use ; Cell Polarity/drug effects/immunology ; Feedback, Physiological/*drug effects ; Interferon-gamma/deficiency/metabolism ; Interleukin-17/*metabolism/pharmacology ; Interleukin-6/biosynthesis/*metabolism ; Lipopolysaccharides/pharmacology ; Lung/drug effects/metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Pneumonia/*drug therapy/*immunology/pathology ; Th17 Cells/drug effects/*immunology/pathology ; Transforming Growth Factor beta1/pharmacology

The current study evaluated DSM-IV psychiatric diagnoses and investigated the psychological characteristics of sexual offenders by using the Hypersexual Behavior Inventory(HBI), Sexual Addiction Screening Test (SAST), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Fifty male sexual offenders and 36 male healthy controls completed the psychiatric diagnosis and 30 of the 50 male sexual offenders completed the psychological tests listed above. Thirty-two of the 50 sexual offenders were patients with paraphilias, these sexual offenders had been admitted by the Ministry of Justice to the Institute for Forensic Psychiatry in Gongjui-si due to sexual violence. Participants displayed high lifetime rates of psychiatric disorders: 32 (64%) had paraphilias, 16 (32%) had depressive disorders, 10 (20%) had anxiety disorders, 9 (18%) had impulse control disorders, 6 (12%) had schizophrenia, 2 (4%) had bipolar disorders, and 16 (32%) had personality disorders or some other Axis II disorder. Scores for the sexual offenders were significantly higher both on the HBI and the SAST than the comparison group. Scores for the sexual offenders were also higher for the BDI and the BAI as compared to the control group, but this difference was not statistically significant. Results indicate that sexual offenders may have sexual addictions and be hypersexual. In addition to depressive and anxious psychopathologies, they also seem to have sexual psychopathologies. These results suggested that the psychopathology of sexual offenders may be different than that of a control group.
Anxiety ; Anxiety Disorders ; Axis, Cervical Vertebra ; Bipolar Disorder ; Criminals ; Depression ; Depressive Disorder ; Diagnostic and Statistical Manual of Mental Disorders ; Forensic Psychiatry ; Humans ; Disruptive, Impulse Control, and Conduct Disorders ; Male ; Mass Screening ; Mental Disorders ; Paraphilic Disorders ; Personality Disorders ; Psychological Tests ; Psychopathology ; Schizophrenia ; Sex Offenses ; Social Justice

PURPOSE: Transcatheter closure has become an effective therapy in most patients with patent ductus arteriosus (PDA). However, there are difficulties in transcatheter closure of PDA in small children. We reviewed clinical outcomes of transcatheter closure of PDA in children weighing less than 10 kg in a single center. METHODS: Between January 2003 and December 2009, 314 patients with PDA underwent transcatheter closure in our institute. Among them, 115 weighed less than 10 kg. All of these patients underwent transcatheter closure of PDA using either COOK Detachable Coil(R), PFM Nit-Occlud(R), or Amplatzer duct occluder(R). A retrospective review of the treatment results and complications was performed. RESULTS: The mean age of patients was 9.1+/-5.9 months (median, 8 months), and mean weight was 7.6+/-1.8 kg (median, 7.8 kg). The mean diameter of PDA was 3.2+/-1.4 mm (median, 3 mm). Complete occlusion occurred in 113 patients (98%). One patient was sent to surgery because of a failed attempt at device closure, and another patient had a small residual shunt after device placement. The average mean length of hospital stay was 3.0+/-3.3 days, and mean follow-up duration was 21.0+/-19.6 months. There were no major complications in any of the patients. CONCLUSION: Transcatheter closure of PDA is considered safe and efficacious in infants weighing less than 10 kg. With sufficient experience and further effort, transcatheter closure of PDA can be accepted as the gold standard of treatment for this group of patients.
Catheterization ; Child ; Ductus Arteriosus, Patent ; Follow-Up Studies ; Humans ; Infant ; Length of Stay ; Retrospective Studies

Theophylline is commonly used to treat severe asthma and chronic obstructive pulmonary disease (COPD) characterized by non-eosinophilic inflammation. Acetyl salicylic acid (ASA) is one of the most widely used medications worldwide, but up to 20% of patients with asthma experience aggravated respiratory symptoms after taking ASA. Here we evaluated the adverse effect of ASA on the therapeutic effect of theophylline in mice with non-eosinophilic asthma. A non-eosinophilic asthma mouse model was induced by airway sensitization with lipopolysaccharide-containing allergen and then challenged with allergen alone. Therapeutic intervention was performed during allergen challenge. Theophylline inhibited lung inflammation partly induced by Th1 immune response. ASA attenuated the beneficial effects of theophylline. However, co-administration of the ASA metabolite salicylic acid (SA) showed no attenuating effect on theophylline treatment. The therapeutic effect of theophylline was associated with increase in cAMP levels, which was blocked by co-treatment of theophylline and ASA. ASA co-treatment also attenuated the anti-inflammatory effects of a specific phosphodiesterase 4 inhibitor. These results demonstrate that ASA reverses anti-inflammatory effects of theophylline, and that ASA exerts its adverse effects through the inhibition of cAMP production. Our data suggest that ASA reverses lung inflammation in patients taking theophylline, although clinical evidence will be needed.
Animals ; Anti-Inflammatory Agents/*therapeutic use ; Aspirin/*therapeutic use ; Asthma/*drug therapy/*metabolism ; Blotting, Western ; Bronchoalveolar Lavage Fluid ; Cyclic AMP/*metabolism ; Enzyme-Linked Immunosorbent Assay ; Immunoprecipitation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pulmonary Eosinophilia/*drug therapy/metabolism ; Theophylline/*therapeutic use

BACKGROUND: Excessive daytime sleepiness (EDS) is a common symptom in patients with habitual snoring, including obstructive sleep apnea (OSA). However, there had been no studies for the prevalence and related factors of EDS in patients with habitual snoring in Korea. So we studied the prevalence and related factors of EDS in patients with habitual snoring. METHODS: Sixty two patients with habitual snoring were selected from our sleep center from February 2004 to January 2007. All patients were given an overnight polysomnography and then took the multiple sleep latency tests the following day. They were classified into two groups: EDS (mean sleep latency, MSL<10 minutes) and no EDS (MSL> or =10 minutes). We studied the prevalence of EDS in patients with habitual snoring and compared two groups about the demographic data and polysomnographic characteristics. RESULTS: Most (72.6%) patients with habitual snoring demonstrated EDS. There were significant different parameters between the EDS group and the no EDS group, such as total sleep time, percent of slow wave sleep, snoring index, arousal index, and number of desaturation. Among these, the logistic regression analysis identified total sleep time as a significant predictive factor for daytime sleepiness. MSL correlated significantly with the percent of slow wave sleep and number of desaturation. CONCLUSIONS: Our results showed the high prevalence of EDS in patients with habitual snoring in Korea. Long total sleep time in polysomnography seems to predict EDS.
Arousal ; Humans ; Korea ; Logistic Models ; Polysomnography ; Prevalence* ; Sleep Apnea, Obstructive ; Snoring*