Ethnic differences in craniofacial and upper spine morphology in children with skeletal Class II malocclusion

OBJECTIVES: To analyze differences in upper cervical spine and craniofacial morphology, including posterior cranial fossa and growth prediction signs, between Danish and South Korean pre-orthodontic skeletal Class II children and to analyze associations between upper cervical spine morphology and craniofacial characteristics. MATERIALS AND METHODS: One hundred forty-six skeletal Class II children—93 Danes (54 boys and 39 girls, mean age 12.2 years) and 53 Koreans (27 boys and 26 girls, mean age 10.8 years)—were included. Upper spine morphology, Atlas dimensions, and craniofacial morphology, including posterior cranial fossa and growth prediction signs, were assessed on lateral cephalograms. Differences and associations were analyzed by multiple linear and logistic regression analyses adjusted for age and gender. RESULTS: Significant differences between the ethnic groups were found in the sagittal and vertical craniofacial dimensions (P < .001), mandibular shape (P < .01), dental relationship (P < .01), posterior cranial fossa (P < .05), and growth prediction signs (P < .001). No significant differences were found in upper spine morphology and Atlas dimensions between the groups. Upper spine morphology/dimensions were significantly associated with the cranial base angle (P < .01), sagittal craniofacial dimensions (P < .001), posterior cranial fossa (P < .001), and growth prediction signs (P < .05). CONCLUSIONS: Upper spine morphology/dimensions may be valuable as predictive factors in treatment planning for growing Class II children

FK506-binding protein-like and FK506-binding protein 8 regulate dual leucine zipper kinase degradation and neuronal responses to axon injury

The dual leucine zipper kinase (DLK) is a key regulator of axon regeneration and degeneration in response to neuronal injury; however, regulatory mechanisms of the DLK function via its interacting proteins are largely unknown. To better understand the molecular mechanism of DLK function, we performed yeast two-hybrid screening analysis and identified FK506-binding protein-like (FKBPL, also known as WAF-1/CIP1 stabilizing protein 39) as a DLK-binding protein. FKBPL binds to the kinase domain of DLK and inhibits its kinase activity. In addition, FKBPL induces DLK protein degradation through ubiquitin-dependent pathways. We further assessed other members in the FKBP protein family and found that FK506-binding protein 8 (FKBP8) also induced DLK degradation. We identified the lysine 271 residue in the kinase domain as a major site of DLK ubiquitination and SUMO3 conjugation and was thus responsible for regulating FKBP8-mediated proteasomal degradation that was inhibited by the substitution of the lysine 271 to arginine. FKBP8-mediated degradation of DLK is mediated by autophagy pathway because knockdown of Atg5 inhibited DLK destabilization. We show that in vivo overexpression of FKBP8 delayed the progression of axon degeneration and suppressed neuronal death after axotomy in sciatic and optic nerves. Taken together, this study identified FKBPL and FKBP8 as novel DLK-interacting proteins that regulate DLK stability via the ubiquitin-proteasome and lysosomal protein degradation pathways

Revisiting roles of mast cells and neural cells in keloid: exploring their connection to disease activity

BackgroundMast cells (MCs) and neural cells (NCs) are important in a keloid microenvironment. They might contribute to fibrosis and pain sensation within the keloid. However, their involvement in pathological excessive scarring has not been adequately explored.ObjectivesTo elucidate roles of MCs and NCs in keloid pathogenesis and their correlation with disease activity.MethodsKeloid samples from chest and back regions were analyzed. Single-cell RNA sequencing (scRNA-seq) was conducted for six active keloids (AK) samples, four inactive keloids (IK) samples, and three mature scar (MS) samples from patients with keloids.ResultsThe scRNA-seq analysis demonstrated notable enrichment of MCs, lymphocytes, and macrophages in AKs, which exhibited continuous growth at the excision site when compared to IK and MS samples (P = 0.042). Expression levels of marker genes associated with activated and degranulated MCs, including FCER1G, BTK, and GATA2, were specifically elevated in keloid lesions. Notably, MCs within AK lesions exhibited elevated expression of genes such as NTRK1, S1PR1, and S1PR2 associated with neuropeptide receptors. Neural progenitor cell and non-myelinating Schwann cell (nmSC) genes were highly expressed in keloids, whereas myelinating Schwann cell (mSC) genes were specific to MS samples.ConclusionsscRNA-seq analyses of AK, IK, and MS samples unveiled substantial microenvironmental heterogeneity. Such heterogeneity might be linked to disease activity. These findings suggest the potential contribution of MCs and NCs to keloid pathogenesis. Histopathological and molecular features observed in AK and IK samples provide valuable insights into the mechanisms underlying pain and pruritus in keloid lesions

The Effect of Intravenous Dexamethasone and Dexmedetomidine on Analgesia Duration of Supraclavicular Brachial Plexus Block: A Randomized, Four-Arm, Triple-Blinded, Placebo-Controlled Trial

Intravenous dexamethasone and dexmedetomidine, in conjunction with peripheral nerve blockade, have each been reported to prolong the duration of analgesia. This study tested whether combined use further prolongs analgesia duration after supraclavicular brachial plexus block (BPB) in patients undergoing orthopedic upper extremity surgery. One hundred twenty patients were randomized 1:1:1:1 to Control (saline bolus and midazolam infusion [0.05 mg/kg loading, 20 &micro;g/kg/h thereafter]); DMED (saline bolus and dexmedetomidine infusion [1 &mu;g/kg loading, 0.4 &mu;g/kg/h thereafter]); DEXA (dexamethasone [10 mg] bolus and midazolam infusion); and DMED-DEXA (dexmedetomidine infusion and dexamethasone bolus) groups. The primary outcome was the duration of postoperative analgesia, defined as the time from the end of the BPB to the first dose of analgesia via a patient-controlled device. Median (interquartile range) times to first dose of analgesia in the Control, DMED, DEXA, and DMED-DEXA groups were 8.1 (6.2&ndash;11.6), 9.0 (8.1&ndash;11.3), 10.7 (8.1&ndash;20.5), and 13.2 (11.5&ndash;19.1) hours, respectively (p &lt; 0.001). Pairwise comparisons showed significant prolongation of analgesia in the DEXA included groups compared with the non-DEXA included groups (DEXA vs. control, p = 0.045; DEXA vs. DMED, p = 0.045; DMED-DEXA vs. control, p &lt; 0.001; DMED-DEXA vs. DMED, p &lt; 0.001). A mixed effect model showed that dexamethasone was the only significant factor for the prolongation of analgesia (p &lt; 0.001). Intravenous dexamethasone prolonged the analgesia duration of supraclavicular BPB after orthopedic upper extremity surgery. The concurrent use of mild to moderate sedation dose of intravenous dexmedetomidine in addition to intravenous dexamethasone showed no additional benefit to the prolongation of analgesia

Contributions of Ammonia to High Concentrations of PM_2.5 in an Urban Area

Atmospheric ammonia (NH3) plays a critical role in PM2.5 pollution. Data on atmospheric NH3 are scanty; thus, the role of NH3 in the formation of ammonium ions (NH4+) in various environments is understudied. Herein, we measured concentrations of NH3, PM2.5, and its water-soluble SO42−, NO3−, and NH4+ ions (SNA) at an urban site in Jeonju, South Korea from May 2019 to April 2020. During the measurement period, the average concentrations of NH3 and PM2.5 were 10.5 ± 4.8 ppb and 24.0 ± 12.8 μg/m3, respectively, and SNA amounted to 4.3 ± 3.1, 4.4 ± 4.9, and 1.6 ± 1.8 μg/m3, respectively. A three-dimensional photochemical model analysis revealed that a major portion of NH3, more than 88%, originated from Korea. The enhancement of the ammonium-to-total ratio of NH3, NHX (NHR = [NH4+]/[NH4+] + [NH3]) was observed up to ~0.61 during the increase of PM2.5 concentration (PM2.5 ≥ 25 μg/m3) under low temperature and high relative humidity conditions, particularly in winter. The PM2.5 and SNA concentrations increased exponentially as NHR increased, indicating that NH3 contributed significantly to SNA formation by gas-to-particle conversion. Our study provided experimental evidence that atmospheric NH3 in the urban area significantly contributed to SNA formation through gas-to-particle conversion during PM2.5 pollution episodes

Contributions of Ammonia to High Concentrations of PM2.5 in an Urban Area

Atmospheric ammonia (NH3) plays a critical role in PM2.5 pollution. Data on atmospheric NH3 are scanty; thus, the role of NH3 in the formation of ammonium ions (NH4+) in various environments is understudied. Herein, we measured concentrations of NH3, PM2.5, and its water-soluble SO42&minus;, NO3&minus;, and NH4+ ions (SNA) at an urban site in Jeonju, South Korea from May 2019 to April 2020. During the measurement period, the average concentrations of NH3 and PM2.5 were 10.5 &plusmn; 4.8 ppb and 24.0 &plusmn; 12.8 &mu;g/m3, respectively, and SNA amounted to 4.3 &plusmn; 3.1, 4.4 &plusmn; 4.9, and 1.6 &plusmn; 1.8 &mu;g/m3, respectively. A three-dimensional photochemical model analysis revealed that a major portion of NH3, more than 88%, originated from Korea. The enhancement of the ammonium-to-total ratio of NH3, NHX (NHR = [NH4+]/[NH4+] + [NH3]) was observed up to ~0.61 during the increase of PM2.5 concentration (PM2.5 &ge; 25 &mu;g/m3) under low temperature and high relative humidity conditions, particularly in winter. The PM2.5 and SNA concentrations increased exponentially as NHR increased, indicating that NH3 contributed significantly to SNA formation by gas-to-particle conversion. Our study provided experimental evidence that atmospheric NH3 in the urban area significantly contributed to SNA formation through gas-to-particle conversion during PM2.5 pollution episodes