No Association Between First Exposure to General Anaesthesia and Atopic Dermatitis in the Paediatric Population.

General anaesthesia could affect various immune responses, including Th1 and Th2 immunity, which might also affect cells that play an important role in the pathogenesis of atopic dermatitis. However, the relationship between general anaesthesia exposure and atopic dermatitis remains unknown. The aim of this study was to investigate the risk of developing atopic dermatitis after first exposure to general anaesthesia in the paediatric population (18 years or under). A retrospective cohort study, including those exposed (n = 7,681) and unexposed (n = 38,405; control participants) to general anaesthesia (1:5 ratio), was conducted using national sample cohort data from 2002 to 2015. All participants were followed up for 2 years after cohort entry. The 2-year cumulative incidences of atopic dermatitis in the exposed and unexposed groups were 2.3% and 2.2%, respectively. In the subgroup analysis by age, the cumulative incidence was not significantly different between these cohorts. The risks of atopic dermatitis were not significant in the exposed group in the univariate model (hazard ratio 1.05; confidence interval 0.88-1.24) and in the multivariate model, wherein all covariates were adjusted (adjusted hazard ratio, 1.03; 95% confidence interval 0.87-1.23). The results suggest that children's exposure to general anaesthesia was not associated with increased or decreased risk of atopic dermatitis.

Study for Cephalometrics of Facial Bone by Computerized Tomography Images.

Authors tried to investigate the maxillomandibular morphology of Korean nationality with computerized tomography images and establish a series of cephalometric values which should be considered in orthognathic plastic surgery in Korea.The computerized tomography images of 200 patients were retrospectively reviewed with the computer workstation in Sanggye Paik Hospital, Inje University College of Medicine from 2016 to 2017.The mean distance between nasion to point A (NA) line and the maxillary central incisor was 5.07 cm. The mean distance from nasion to point B (NB) line to the mandibular central incisor was 7.11 cm. The mean angle between NA line and the long axis of the maxillary central incisor was 20.58 degree. The mean angle between NB line and the long axis of the mandibular central incisor was 26.47 degree. The mean angle between SN (sella to nasion) line and NA line was 83.18 degree. The mean angle between SN line and NB line was 78.83 degree. The mean angle between NA line and NB line was 4.35 degree. There were no any statistically significant differences between age groups. But there were statistically significant difference in the mean of angle between NB line and the long axis of the mandibular central incisor (P = 0.025, between sex groups) and in the mean of angle between NA line and the long axis of the maxillary central incisor between sex groups in the 51 to 60 age group (P = 0.045).The maxillomandibular profile of Korean adults was established which can be applied for orthognathic surgery of Korean patients.

Falcarindiol inhibits LPS-induced inflammation via attenuating MAPK and JAK-STAT signaling pathways in murine macrophage RAW 264.7 cells.

Falcarindiol (FAD) is a natural polyacetylene compound found rich in many plants of the Umbelliferae family. Previously, we isolated FAD from the rhizome of Cnidium officinale Makino, which belongs to the Umbelliferae family and found it to have a significant inhibitory effect on lipopolysaccharide (LPS)-induced production of nitric oxide, a pro-inflammatory molecule in murine macrophage RAW 264.7 cells. In this study, we investigated its effect on the expression of other major pro-inflammatory molecules as well as the mechanism underlying these effects. Pre-treatment of RAW 264.7 cells with FAD suppressed LPS-stimulated mRNA expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and interleukin-1 beta (IL-1ß) and thereby reduced the respective protein levels. Mechanistic studies demonstrated that FAD attenuated the LPS-induced activation of JNK, ERK, STAT1, and STAT3 signaling molecules. Moreover, we found that FAD did not influence LPS-induced activation of p38 and NFκB signaling pathways. Collectively, this study provides evidence that FAD inhibits the production of major pro-inflammatory molecules in LPS-challenged murine macrophages via suppression of JNK, ERK, and STAT signaling pathways.

Anti-inflammatory activity of Ternstroemia gymnanthera stem bark extracts in bacterial lipopolysaccharide-stimulated RAW264.7 murine macrophage cells.

CONTEXT: Ternstroemia gymnanthera Sprague (Theaceae) possesses various known pharmacological properties. However, its anti-inflammatory activity has not been reported. OBJECTIVE: The anti-inflammatory activity of Ternstroemia gymnanthera stem bark aqueous extract (TGSBE) was evaluated using LPS-stimulated RAW264.7 macrophages. MATERIALS AND METHODS: Cytotoxicity was assessed by MTT assay after 24 h with TGSBE (25-200 µg/mL). Further testing used TGSBE at 100 and 200 µg/mL. Griess and ELISA methods after 24 h with TGSBE determined NO and cytokine levels, respectively; then, mRNA levels (iNOS & cytokines) were analyzed by Quantitative-PCR after 12 h. NF-κB and MAPK were assessed by immunoblotting after TGSBE treatment for 12 h, followed by LPS for 30 min. Immunofluorescence assay was also performed for NF-κB. ROS and MMP, after 12 h with TGSBE, were determined by flow cytometry. The antioxidant potential of TGSBE was analyzed by ABTS assay. The Folin-Ciocalteu method determined the total phenolic content of TGSBE. LPS concentration was 0.5 µg/mL. RESULTS: TGSBE at 200 µg/mL showed about 96.2% viability while suppressing the production of NO (88.99%), TNFα (24.38%), IL-6 (61.70%) and IL-1ß (55.12%) and gene expression by 67.88, 45.24, 65.84, and 70.48%, respectively. TGSBE decreased ROS (79.26%) and improved MMP (48.01%); it inhibited translocation of NF-κB and MAPK activation. Radical scavenging activity was 50% at 402.17 µg/mL (ascorbic acid standard: 88.8 µg/mL). Total phenolic content was 240.9 mg GAE/g. DISCUSSION AND CONCLUSION: TGSBE suppresses the inflammatory response by inhibiting the NF-κB and MAPK cascades exhibiting therapeutic potential to treat inflammatory diseases associated with increased activation of macrophages.

Pinus radiata bark extract induces caspase-independent apoptosis-like cell death in MCF-7 human breast cancer cells.

In the present study, we investigated the anticancer activity of Pinus radiata bark extract (PRE) against MCF-7 human breast cancer cells. First, we observed that PRE induces potent cytotoxic effects in MCF-7 cells. The cell death had features of cytoplasmic vacuolation, plasma membrane permeabilization, chromatin condensation, phosphatidylserine externalization, absence of executioner caspase activation, insensitivity to z-VAD-fmk (caspase inhibitor), increased accumulation of autophagic markers, and lysosomal membrane permeabilization (LMP). Both the inhibition of early stage autophagy flux and lysosomal cathepsins did not improve cell viability. The antioxidant, n-acetylcysteine, and the iron chelator, deferoxamine, failed to restore the lysosomal integrity indicating that PRE-induced LMP is independent of oxidative stress. This was corroborated with the absence of enhanced ROS production in PRE-treated cells. Chelation of both intracellular calcium and zinc promotes PRE-induced LMP. Geranylgeranylacetone, an inducer of Hsp70 expression, also had no significant protective effect on PRE-induced LMP. Moreover, we found that PRE induces endoplasmic reticulum (ER) stress and mitochondrial membrane depolarization in MCF-7 cells. The ER stress inhibitor, 4-PBA, did not restore the mitochondrial membrane integrity, whereas cathepsin inhibitors demonstrated significant protective effects. Collectively, our results suggest that PRE induces an autophagic block, LMP, ER stress, and mitochondrial dysfunction in MCF-7 cells. However, further studies are clearly warranted to explore the exact mechanism behind the anticancer activity of PRE in MCF-7 human breast cancer cells.

The composite anterolateral thigh flap for knee extensor and skin reconstruction.

The simultaneous reconstruction of a skin defect and lost extensor mechanism of the knee joint is difficult. We present a 31-year-old male who lost the patella and had a 9 × 10 cm skin defect after a total patellectomy for an infected open patellar fracture. A composite anterolateral thigh (ALT) flap including vascularized skin and fascia lata (FL) was elevated. The FL was folded and sutured to the remaining patellar tendon. The skin flap covered the skin defect. The wound healed uneventfully. Thirty months later, the active range of motion of the knee joint was 0°-120° and the extension strength of the knee joint was normal. He could stand on his right leg and walk without assistance. The composite ALT flap is a valuable option in knee reconstruction after a total patellectomy.

Association between the first exposure to general anesthesia and alopecia areata.

Alopecia areata (AA) is an autoimmune cutaneous disorder reported to be related to various immunologic diseases and psychiatric disorders. Some AA patients report the onset of patchy hair loss after surgeries under general anesthesia (GA). However, no large-scale studies have been conducted on the relationship between AA and GA. Thus, we aimed to evaluate whether exposure to GA is associated with an increased risk of AA. In this retrospective study, we analyzed a population exposed to GA. These individuals were compared to unexposed controls, matched by age, sex, income level, and comorbidities (propensity score matching, 1:2 ratio), from the national sample cohort from January 1, 2002, to December 31, 2015. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for the risk of AA associated with GA using Cox proportional hazard regression. As a result, the risk of AA occurrence was significantly higher in the GA-exposed group after adjusting confounding factors (adjusted HR 1.22, 95% CI 1.07-1.43, P = 0.005). The cumulative incidence of AA was higher in the GA-exposed group (log-rank P = 0.005). The risk of AA increased with GA exposure time. However, the type of surgery and the method of anesthesia did not impact the risk of developing AA. Thus, in conclusion, exposure to GA was associated with a higher risk of developing AA.

A multicenter, randomized, double-blind, comparative study of a multiphasic hyaluronic acid filler and existing hyaluronic acid fillers for temporary restoration of the midface volume of Asian individuals.

BACKGROUND: Giselleligne is the world's first multiphasic gel product that evenly surrounds particles. In the current study, Giselleligne was compared with other existing fillers to evaluate their clinical use, safety, and ability to improve midface volume deficits of Asian individuals. METHODS: A comparative experiment was conducted to gain an understanding of the physical properties of Giselleligne, which is a multilayered hyaluronic acid filler, and to compare its properties with those of existing hyaluronic acid fillers. The primary outcome of this study was a Midface Volume Deficit Scale (MFVDS) score improvement at 24 weeks after the procedure. The secondary outcomes were as follows: MFVDS score improvement after the procedure; MFVDS score changes after the procedure; Global Esthetic Improvement Scale (GAIS) scores as evaluated by the operator after the procedure; the operator's satisfaction with the product; evaluation of the GAIS scores by the patient after the procedure; and pain level of the patient on the day of the procedure. RESULTS: Giselleligne exhibited properties that are expected to result in significantly superior clinical outcomes compared to existing products. Giselleligne was superior not only to the existing products but also in terms of global esthetic improvement, effect duration, and operator satisfaction. Furthermore, Giselleligne was found significantly safer than the existing products. CONCLUSION: Giselleligne is a safer, more user-friendly, and more effective alternative to existing products for improving the midfacial volume.

Fracture of the anterior nasal spine.

A 24-year-old man was assaulted and complained of vague discomfort with tenderness on the nose. Physical examination manifested pain over the nasolabial angle region aggravated by upper lip closure. Computed tomography with three-dimensional reconstruction of the facial bone revealed a fracture of the anterior nasal spine accompanying the overt displacement. The patient underwent open reduction and internal fixation. Clinical symptoms were completely resolved after the surgery. Regular diet was recommenced in 2 weeks without any complications. The purpose of this study was to emphasize the awareness of the clinical feature and the modality of treatment in case of anterior nasal spine fracture with displacement.

Atypical traumatic subperiosteal orbital hematoma treated by surgical evacuation.

Subperiosteal orbital hematoma occurs rarely after blunt trauma. However, this is of importance, as this condition may cause ocular symptoms. The major characteristics of subperiosteal orbital hematomas are painful proptosis, downward displacement of the globe, absence of lid ecchymosis, chemosis without subconjunctival hemorrhage, and motility impairment. Visual impairment is known as a rarely presenting symptom. A 22-year-old male patient presented with right periorbital ecchymosis, swelling, and diplopia with upper lateral gaze limitation. Besides, the patient complained of lower visual field disturbance. Radiologic evaluation revealed traumatic subperiosteal orbital hematoma. The hematoma was evacuated through a lacerated wound on the right lateral eyebrow with additional incision. After the hematoma evacuation, the orbital symptoms are restored. Postoperative computed tomographic scans showed normally restored orbital space without any evidence of remnant hematoma or rebleeding. In case of subperiosteal hematoma, early detection and complete surgical evacuation is crucial for preventing possible complications and sequelae.

Improvement of compliance to the Portland intensive insulin therapy during liver transplantation after introducing an application software: a retrospective single center cohort study.

BACKGROUND: The Portland intensive insulin therapy effectively controls acute hyperglycemic change after graft reperfusion during liver transplantation. However, the time-consuming sophistication acts as a barrier leading to misinterpretation and decreasing compliance to the protocol; thus, we newly introduced an application software "Insulin protocol calculator" which automatically calculates therapeutic bolus/continuous insulin doses based on the Portland protocol. METHODS: Of 144 patients who underwent liver transplantation, 74 patients were treated before the introduction of "Insulin protocol calculator" by using a paper manual, and 70 patients were treated by using the application. Compliance was defined as the proportion of patients treated with exact bolus/continuous insulin dose according to the Portland protocol. RESULTS: Compliance was significantly greater in app group than in paper group regarding bolus dose (94.5% and 86.9%, P < 0.001), continuous dose (88.9% and 77.3%, P = 0.001), and both doses (86.6% and 73.8%, P < 0.001). Blood glucose concentration was significantly lower in app group at 3 h (125 ± 17 mg/dl vs. 136 ± 19 mg/dl, P = 0.014) and 4 h (135 ± 22 mg/dl vs. 115 ± 15 mg/dl, P = 0.029) after graft reperfusion. Acute hyperglycemic change during 30 min was more prominent in app group while hyperglycemia incidence was 71.4% vs. 54.1% (P = 0.031). However, hyperglycemia risk was comparable at 2 h (31.4% vs. 31.1%, P = 0.964), and even insignificantly lower in app group at 3 h (7.1% vs. 19.5%, P = 0.184). CONCLUSIONS: Compliance to the Portland protocol was significantly improved after introducing the application software; post-reperfusion hyperglycemia was better controlled. "Insulin protocol calculator" is cost-effective and time-saving with potential clinical benefits.

Components of rhizome extract of Cnidium officinale Makino and their in vitro biological effects.

The anti-inflammatory and anticancer activities of a methanol extract of the rhizome of Cnidium officinale were investigated. Four compounds, namely falcarindiol (1), 6-hydroxy-7-methoxy-dihydroligustilide (2), ligustilidiol (3), and senkyunolide H (4) were isolated from the extract of the rhizome of Cnidium officinale and their structures were elucidated by analysis of their spectroscopic data and by comparison with previously reported data. These compounds showed anti-inflammatory activities, measured as inhibition of nitric oxide (NO) release in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells, with IC(50) values of 4.31 ± 5.22, 152.95 ± 4.23, 72.78 ± 5.13, and 173.42 ± 3.22 µM, respectively. They also inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expression induced by LPS. Among these compounds, falcarindiol (1) was found to have anti-proliferative effect against MCF-7 human breast cancer cells by induction of a G(0)/G(1) cell cycle block of the cells, with an IC(50) value of 35.67 µM. Typical apoptotic effects were observed by phase contrast microscopy and were also exhibited in fluorescence microscopy with Hoechst 33342 staining. In addition, falcarindiol induced apoptosis through strongly increased mRNA expression of Bax and p53, and slightly reduced Bcl-2 mRNA levels in a dose dependent manner. This study suggested that C. officinale extract and its components would be valuable candidates in therapeutic applications for anti-inflammatory and anti-cancer agents.

Compounds from Viburnum sargentii Koehne and evaluation of their cytotoxic effects on human cancer cell lines.

Compounds were isolated from a methanol extract of the dried stem barks of Viburnum sargentii Koehne. The structures of the compounds, namely 9'-O-methylvibsanol (3), furcatoside A (4) and lareciresinol (5) were elucidated by analysis of spectroscopic data and comparison with values for previously known analogues. In addition, (+)-catechin (1), (+)-epicatechin (2) were also isolated. This work also examined the cytotoxic effects of three compounds 3-5 (25-100 microM) in MCF-7 and A549 cells after 24, 48 and 72 h of exposure. Our results showed that 9'-O-methylvibsanol (3) exhibited strong concentration-dependent anticancer effects according to the MTT assay and produced morphological changes consistent with apoptosis, as confirmed by Ho3342 staining analysis revealed that more apoptotic cells were observed after 9'-Omethylvibsanol (3) treatment.

Scalp reconstruction: A 10-year experience.

BACKGROUND: The scalp is an important functional and aesthetic structure that protects the cranial bone. Due to its inelastic characteristics, soft-tissue defects of the scalp make reconstruction surgery difficult. This study aims to provide an improved scalp reconstruction decision making algorithm for surgeons. METHODS: This study examined patients who underwent scalp reconstruction within the last 10 years. The study evaluated several factors that surgeons use to select a given reconstruction method such as etiology, defect location, size, depth, and complications. An algorithmic approach was then suggested based on an analysis of these factors. RESULTS: Ninety-four patients were selected in total and 98 cases, including revision surgery, were performed for scalp reconstruction. Scalp reconstruction was performed by primary closure (36.73%), skin graft (27.55%), local flap (17.34%), pedicled regional flap (15.30%), and free flap (3.06%). The ratio of primary closure to more complex procedure on loose scalps (51.11%) was significantly higher than on tight scalps (24.52%) (p= 0.011). The choice of scalp reconstruction method was affected significantly by the defect size (R = 0.479, p< 0.001) and depth (p< 0.001). There were five major complications which were three cases of flap necrosis and two cases of skin necrosis. Hematoma was the most common of the 29 minor complications reported, followed by skin necrosis. CONCLUSION: There are multiple factors affecting the choice of scalp reconstruction method. We suggest an algorithm based on 10 years of experience that will help surgeons establish successful surgical management for their patients.

Impact of Different Extraction Solvents on Phenolic Content and Antioxidant Potential of Pinus densiflora Bark Extract.

It is well established that various extraction factors, including the method, temperature, time, and solvent system, significantly influence the antioxidant quality of plant-derived products. Previously, we observed that extraction of Pinus densiflora bark (PDB) by the most common traditional Soxhlet method using water at two different temperature conditions 60°C and 100°C for 6-15 h noticeably altered their antioxidant quality. In this study, we examined the impact of different extraction solvents such as ethanol, methanol, isopropanol, acetonitrile, and acetone at a different percentage with water (vol/vol) on antioxidant efficiency as well as the total phenolic content (TPC) of PDB extracts. Among the fourteen different PDB extracts, the extracts obtained from 20% ethanol (E20), 40% ethanol (E40), and 20% acetonitrile (ACN20) showed more significant antioxidant potential, as well as high total phenol content (TPC). Extracts from other aqueous mixtures of organic solvents such as isopropanol, acetone, and methanol, as well as water, showed lesser antioxidant capacity and also had less TPC compared to these three most active extracts, E20, E40, and ACN20. Moreover, using ethanol at 100% for extraction significantly decreased the TPC and antioxidant capacity of PDB extracts. Data are implicating that an increased phenolic content in PDB extracts proportionally increases their antioxidant efficiency.

Effect of an extraction solvent on the antioxidant quality of Pinus densiflora needle extract.

Pinus densiflora needle extract (PDNE) is widely reported to have many pharmacological activities including antioxidant potential. However, the solvent system used for extraction greatly affects its antioxidant quality. Hence, in the present study, we investigated the effect of a different ratio (vol/vol) of ethanol to water (0-100%) in the extraction of PDNE with potent antioxidant capacity. The chemical assays, 2,2-diphenyl-1 picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), were conducted to assess the antioxidant potential of PDNE. Subsequently, the cytoprotective effect of PDNE was determined using tert-butyl hydroperoxide (TBHP)-challenged HepG2 cellular model. The needle extracts from 40% ethanol (PDNE-40) showed greater radical scavenging activity followed by 60%, 20%, 80%, 0% and 100% ethanol extracts. EC50 value of the most active extract, PDNE-40, was 8.56 ±â€¯0.51 µg/mL, relative to 1.34 ±â€¯0.28 µg/mL of the standard trolox (for ABTS radical), and 75.96 ±â€¯11.60 µg/mL, relative to 4.83 ±â€¯0.26 µg/mL of the standard trolox (for DPPH radical). Either PDNE-20 or PDNE-40 pretreatment remarkably decreased the levels of reactive oxygen species (ROS), lipid peroxides and protein carbonyls in TBHP-challenged HepG2 cells. In addition, both PDNE-20 and PDNE-40 significantly reversed the decreased ratio of reduced (GSH) to oxidized (GSSG) glutathione. Moreover, these two extracts showed a significant inhibitory effect on TBHP-induced nuclear damage and loss of cell viability. In summary, the inclusion of 40% ethanol in water for extraction of Pinus densiflora needle greatly increases the antioxidant quality of the extract.

Pinus densiflora needle supercritical fluid extract suppresses the expression of pro-inflammatory mediators iNOS, IL-6 and IL-1ß, and activation of inflammatory STAT1 and STAT3 signaling proteins in bacterial lipopolysaccharide-challenged murine macrophages.

BACKGROUND: Regulation of a persistently-activated inflammatory response in macrophages is an important target for treatment of various chronic diseases. Pine needle extracts are well known to have potent immunomodulatory effects. The current study was designed to evaluate the effects of Pinus densiflora needle supercritical fluid extract (PDN-SCFE) on bacterial lipopolysaccharide (LPS)-induced inflammatory response in RAW 264.7 murine macrophages. METHODS: Cytotoxic effect of PDN-SCFE was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The levels of nitric oxide (NO) and the corresponding enzyme, inducible nitric oxide synthase (iNOS), were quantified by Griess and immunoblotting methods, respectively. The levels of cytokines were quantified using commercial ELISA kits. Quantitative real-time PCR (qRT-PCR) analysis was performed to assess the mRNA expression of iNOS and cytokines. To elucidate the mechanism of action, the involvement of nuclear transcription factor-kappa B (NFκB), mitogen activated protein kinases (MAPKs) and Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathways were examined by an immunoblotting method. In addition, the cellular localization of NFκB was analyzed by immunofluorescence staining. RESULTS: MTT assay results indicated that PDN-SCFE is non-toxic to RAW 264.7 cells up to a maximum assayed concentration of 40 µg/mL. The PDN-SCFE exhibited a concentration-dependent inhibitory effect on LPS-induced NO production by down regulating the expression of iNOS. In addition, the extract suppressed the LPS-induced expression of interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) but not tumour necrosis factor-α (TNFα). Mechanistic studies revealed that PDN-SCFE does not influence the NFκB and MAPK pathways. However, it showed a significant inhibitory effect on LPS-induced activation of STAT1 and STAT3 proteins in macrophages. CONCLUSION: The present findings revealed that the anti-inflammatory activity of PDN-SCFE in LPS-challenged RAW 264.7 macrophages is probably caused by the suppression of the JAK-STAT signaling pathway.