Comparison of a coupling system and the suture method in end-to-side microvascular anastomosis in head and neck reconstruction.

BACKGROUND: Use of coupling devices in microvascular anastomosis continues to increase, but it is not yet actively used in end-to-side (ETS) anastomosis because there is no standard method. Therefore, we propose an easy and time-saving ETS micro-anastomosis method using coupling devices in head and neck reconstruction and compare it with the conventional suture method. MATERIALS AND METHODS: We retrospectively reviewed 30 consecutive cases (43 anastomoses) of ETS anastomosis in head and neck reconstruction from 2018 to 2022. Patient characteristics, operative details, and anastomosis time were evaluated. When using the coupling device, a cross incision was created in the recipient vessel to form vascular flaps. By pulling the flaps out of the ring, the intact vessel lining was fixed. Other procedures were the same as for a traditional anastomosis. RESULTS: The mean anastomosis time was 12.81 min (range, 6.7-24.87) for the suture and 4.96 min (range, 2.02-9.4) for the coupling device, a statistically significant difference (p-value <.00005). There was no venous insufficiency or flap failure with either method. CONCLUSIONS: ETS venous anastomosis using the coupling device is an easy-to-use, safe, and timesaving procedure for head and neck reconstruction.

Transverse division of the rectus abdominis muscle in deep inferior epigastric perforator flap elevation: A rescue technique to include more than one perforator.

BACKGROUND: It is important to include as many perforators as possible in order to enhance the vascularity of a deep inferior epigastric perforator (DIEP) flap. However, the rectus muscle must be transected transversely, which prevents suturing and can cause a defect along the same line as the muscle-sparing procedure. When harvesting the DIEP flap, no specific method was suggested to solve these muscle defects. We found that by transecting the rectus muscle transversely, the muscle could be sutured in the tendinous area more easily while maintaining muscle function. The purpose of this study is to confirm the long-term recovery of the rectus abdominis muscle through the volume change after DIEP flap using this tendinous transection and suture method. PATIENTS AND METHODS: A retrospective review of 28 patients who underwent unilateral breast reconstruction using a DIEP flap and the tendinous transection method for multiple perforators between May 2018 and April 2020 was conducted. The preoperative and postoperative volumes of the rectus abdominis muscle were estimated both the harvest and opposite sides. RESULTS: The preoperative and postoperative muscle volumes from the harvest side were 50.08 ± 8.71 cm3 and 48.56 ± 8.61 cm3, respectively. The volume difference was 1.522 cm3 decrease, which was not statistically significant (p = .070). The preoperative and postoperative muscle volumes from the opposite side were 50.50 ± 8.15 cm3 and 50.08 ± 8.18 cm3, respectively. The volume difference was 0.434 cm3 increase and was not statistically significant (p = .064). Postoperative volume changes in the rectus muscle were not statistically significant on either side. CONCLUSION: The tendinous transection method in the DIEP flap procedure did not significantly affect postoperative rectus muscle volume. Therefore, we expect this harvest method to allow DIEP flap reconstruction that includes multiple perforators and complete donor muscle recovery.

SARS-CoV-2 spike protein promotes inflammatory cytokine activation and aggravates rheumatoid arthritis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) induces inflammation, autoantibody production, and thrombosis, which are common symptoms of autoimmune diseases, including rheumatoid arthritis (RA). However, the effect of COVID-19 on autoimmune disease is not yet fully understood. METHODS: This study was performed to investigate the effects of COVID-19 on the development and progression of RA using a collagen-induced arthritis (CIA) animal model. Human fibroblast-like synoviocytes (FLS) were transduced with lentivirus carrying the SARS-CoV-2 spike protein gene in vitro, and the levels of inflammatory cytokine and chemokine expression were measured. For in vivo experiments, CIA mice were injected with the gene encoding SARS-CoV-2 spike protein, and disease severity, levels of autoantibodies, thrombotic factors, and inflammatory cytokine and chemokine expression were assessed. In the in vitro experiments, the levels of inflammatory cytokine and chemokine expression were significantly increased by overexpression of SARS-CoV-2 spike protein in human FLS. RESULTS: The incidence and severity of RA in CIA mice were slightly increased by SARS-CoV-2 spike protein in vivo. In addition, the levels of autoantibodies and thrombotic factors, such as anti-CXC chemokine ligand 4 (CXCL4, also called PF4) antibodies and anti-phospholipid antibodies were significantly increased by SARS-CoV-2 spike protein. Furthermore, tissue destruction and inflammatory cytokine level in joint tissue were markedly increased in CIA mice by SARS-CoV-2 spike protein. CONCLUSIONS: The results of the present study suggested that COVID-19 accelerates the development and progression of RA by increasing inflammation, autoantibody production, and thrombosis. Video Abstract.

Proximal peroneal perforator flap, cadaveric study, and clinical applications for shallow defect reconstructions.

PURPOSE: Peroneal artery perforator offers a versatile range of microvascular tissue transfer methods from local flaps to vascularized osteocutaneous fibula flaps. It is one of the few flaps that can cover shallow defects that require thin and pliable skin paddles, such as in hands and feet (Han et al., 2018). The proximal region of the lower leg offers such flexible and thin flap compared to the middle and distal lower leg (Winters & de Jongh, 1999). However, the anatomy of the proximal peroneal artery perforator is relatively unknown in literature and its proximity to the common peroneal nerve (CPN) has not yet been studied. This study conducted a cadaveric study and put it in application into clinical settings. METHODS: Twenty lower leg specimens were dissected according to the methods of clinical proximal peroneal artery perforator flap harvest. Perforators arising in the proximal lower leg area of between 20 and 40 percentile of fibular length were inspected. Perforator length, location from fibular head, course, and location of CPN were recorded. Clinical reconstruction cases using the proximal lateral lower leg were analyzed. Six patients between the ages of thirty and seventy were included. Five cases were due to trauma, and one from mass excision, but all required thin and pliable flaps for reconstructions in hands or feet. Flaps were designed concentrical oval shapes, and harvest was done similarly to cadaveric perforator dissection, but perforator dissection was done only up to the required pedicle length. Perforator length, flap size, thickness, and long-term complications were recorded. RESULTS: Among 20 specimens, a total of 20 perforators were found in 18 cadavers (90%). Two specimens showed no perforators while two specimens showed multiple perforators. The perforators were located at an average of 101 mm from fibular head, with an average length of 55 mm ranging from 20 to 153 mm. The average size of perforator at origin was 2.0 mm, ranging from 1.0 to 3.6 mm. 45% showed septocutaneous course and 55% intramuscular course. Two out of 20 perforators were shown to arise from source vessels other than the peroneal artery. All clinical cases were successful without complications or debulking for contour shaping. Flap sizes ranged from 15 to 40 cm2 . Largest flap width was 5 cm, and all donor sites were primarily closed without complications. One year of follow-up showed no complications. CONCLUSION: Proximal peroneal artery perforator flap provides a reliable pedicle for a versatile tissue transfer. This study shows that the perforators of the proximal lateral lower leg often arise from vessels other than the peroneal artery, such as the anterior tibial artery or popliteal artery, as had been previously reported (Winters & de Jongh, 1999). Although the source vessel varies, perforator anatomy is at a safe distance from CPN. This variation of source vessels suggests a change in nomenclature to "proximal peroneal perforator flap." The clinical applications of this flap showed that it can be effectively used for reconstructions of shallow defects, such as in the hands and feet without secondary procedures for debulking.

Correction of Temporal Hollowing With the Superior Gluteal Artery Perforator Free Flap.

ABSTRACT: Temporal hollowing is most frequently an acquired deformity and can be caused by volume defects of bone, soft tissue, or both. Recently, surgical reconstruction with autogenous fat or allografts has been introduced, but these materials can be resorbed over time and may also lead to infection. Herein, the authors present 2 cases demonstrating the treatment of temporal hollowing with a superior gluteal artery perforator (SGAP) free flap. Both patients had a history of traffic accidents and subsequent craniectomy because of subdural hemorrhage, followed by cranioplasty. An SGAP free flap was selected to reconstruct the soft tissue temporal defect in both patients. Pre-operatively, computed tomography (CT) angiography was used to locate the superior temporal artery (STA). A preauricular incision provided surgical access to the STA, and a subcutaneous pocket was created. The STA and SGAP artery and vein anastomoses were performed. Before flap insetting, it was de-epithelized, and its volume and shape trimmed to fit into the temporal defect. The patients' post-operative courses were without complications, and facial symmetry was achieved. This is the first case report describing the microvascular reconstruction of temporal hollowing with an SGAP free flap. The SGAP free flap is permanent and highly vascularized with no risk of infection. These case reports illustrate a unique reconstruction technique that resulted in a satisfactory outcome for the patients.

Microscale droplets covered by amphiphilic gold nanoparticles with various ligand ratios and concentrations.

We describe a simple and reliable route for forming microscale droplets covered with amphiphilic gold nanoparticles (AuNPs) functionalized with mixed hydrophilic and hydrophobic ligands on the AuNP surface. When an aqueous solution of amphiphilic AuNPs was mixed with hexane, the hexane (or water) droplets covered with amphiphilic AuNPs in the water (or hexane) phase were created, in which amphiphilic AuNPs in water phase migrated to the hexane-water interface. The extent of AuNP migration to the interface could be tuned by the ratio of the hydrophobic to hydrophilic ligands on the AuNP surface and the overall concentration of AuNPs. Importantly, the extent of the AuNP migration to the interface depending on the AuNP concentration followed the Langmuir isotherm model well. The equilibrium constant and maximum uptake of AuNPs at the interface were estimated using the Langmuir isotherm model. To the best of our knowledge, this is the first report of the equilibrium constant determination of amphiphilic AuNPs at the liquid-liquid interface. Based on the maximum uptake of AuNPs at the hexane-water interface, we demonstrated that the AuNPs could be closely packed at the interface.

The cover of an ear thermometer probe as a split-thickness skin graft mold in external auditory canal reconstruction.

Maintaining the patency of the external auditory canal (EAC) during reconstruction is important because of its physiological role in hearing and immunological protective functions. The curved shape of the EAC presents a challenge when performing a skin graft. One of the key points for a successful skin graft is to ensure compression on the wound bed, and many novel methods, including prefabricated ear molds, have been reported for this purpose. In this study, we present a case of a skin graft performed to reconstruct a skin defect following excision of actinic keratosis in the EAC, using the cover of an ear thermometer probe as a mold for the graft to match the curvature of the EAC. This is an economical and practical method for secure compression dressing of a skin graft in the EAC.

Vessel-Derived Decellularized Extracellular Matrices (VdECM): Novel Bio-Engineered Materials for the Wound Healing.

BACKGROUND: Decellularized extracellular matrix (dECM) is a non-cellular scaffold with various functions in tissue engineering and regenerative medicine. Elastin is related to tissue elasticity and scarless wound healing, abundantly found in lung and blood vessel tissues. We studied the characteristics of blood vessel-derived dECM (VdECM) and its effect in wound healing. METHODS: VdECM was prepared from porcine blood vessel tissue. Weight percentages of elastin of VdECM and atelocollagen were analyzed. Migratory potential of VdECM was tested by scratch assay. VdECM in hydrogel form was microscopically examined, tested for fibroblast proliferation, and examined for L/D staining. Cytokine array of various growth factors in adipocyte-derived mesenchymal stem cell (ASC) media with VdECM was done. Animal wound model showed the wound healing effect of VdECM hydrogel in comparison to other topical agents. RESULTS: VdECM contained 6.7 times more elastin than atelocollagen per unit weight. Microscopic view of 0.35% VdECM hydrogel showed consistent distribution. Compared to 3% atelocollagen, 0.35% VdECM showed superior results in fibroblast migration. Fluorescent microscopic findings of L/D assay had highest percentage of cell survival in 1% VdECM compared to atelocollagen. Growth factor expression was drastically amplified when VdECM was added to ASC media. In the animal study model, epithelialization rate in the VdECM group was higher than that of control, oxytetracycline, and epidermal growth factor ointments. CONCLUSION: VdECM contains a high ratio of elastin to collagen and amplifies expressions of many growth factors. It promotes fibroblast migration, proliferation, and survival, and epithelialization comparable to other topical agents.

Anterolateral Thigh Chimeric Flap: An Alternative Reconstructive Option to Free Flaps for Large Soft Tissue Defects.

The anterolateral thigh (ALT) skin flap provides abundant, thin, pliable skin coverage with adequate pedicle length and calibre, and tolerable donor site morbidity. However, coverage of relatively large defects using the ALT flap alone is limited. We present our experience of using the ALT flap coupled with the vastus lateralis (VL) flap supplied by the same pedicle for large defect reconstruction. Between 2016 and 2020, ten patients with extensive lower-extremity or trunk defects were treated using the ALT/VL chimeric flap. The ALT portion was used to cover the cutaneous and joint defect while the VL part was used to resurface remnant defects, and a skin graft was performed. All flaps were based on the common descending pedicle, and branches to separate the components were individually dissected. All defects were successfully reconstructed using the ALT/VL chimeric flap. No surgery-related acute complications were observed, and the patients had no clinical issues with ambulation or running activities during the long-term follow-up period. With the separate components supplied by a common vascular pedicle, the ALT/VL chimeric flap allows us to reconstruct extensive defects with joint involvement or posterior trunk lesions. Thus, the ALT/VL chimeric flap may be a suitable alternative for extensive tissue defect reconstruction.

IL-17 Induces Autophagy Dysfunction to Promote Inflammatory Cell Death and Fibrosis in Keloid Fibroblasts via the STAT3 and HIF-1α Dependent Signaling Pathways.

Keloid is an abnormal fibrotic disease after cutaneous injury characterized by exaggerated scar tissue formation, which often extends beyond the boundaries of the original wound. Although chronic inflammation is known to be associated with the excessive inflammation in keloid tissue, there are few studies on the role of autophagy in the pathogenesis of keloid. In this study, we evaluated the pattern of autophagy in keloid fibroblasts (KF) and normal fibroblasts (NF). Expression of HIF-1α, STAT3 and autophagic flux markers were evaluated in KF and NF. Defective autophagy caused by IL-17 was evaluated, and the relationship between defective autophagy and necroptosis was also examined. The expression of IL-17, HIF-1α and STAT3 was significantly increased in keloid tissue, and autophagosome-to autophagolysosome conversion was defective in KF. IL-17 treatment significantly elevated the expression of STAT3 and HIF-1α in NF and caused defective autophagy, which was reversed by HIF-1α inhibitor. In addition, the defective autophagy was associated with the increased necroptosis and fibrosis. In keloid tissue, the elevated necroptosis marker was confirmed, and with the HIF-1α inhibitor, the defective autophagy, necroptosis and fibrosis was decreased in KF. In conclusion, autophagy was defective in keloid tissue, which was associated with increased necroptosis and fibrosis. The IL-17-STAT3-HIF-1α axis was involved in defective autophagy in KF, and this suggests that targeting the axis could alleviate chronic inflammation in keloid disease.

Two-team-approached free flap reconstruction for plantar malignant melanoma: An observational (STROBE-compliant) trial.

Reconstructive treatments of heel defects usually involve regional flap techniques such as medial plantar flap procedures due to the limited availability of adjacent soft tissues. Although free flaps have advantages in terms of function and aesthetics, they remain challenging due to the longer operation time required than for regional flaps. Thus, we introduce an appropriate 2-team surgical protocol to reconstruct plantar defects after wide excision of malignant melanoma using free flap coverage. From 2015 to 2020, a retrospective study was performed including 21 patients who underwent free flap surgeries to reconstruct defects due to plantar malignant melanoma. Lymphoscintigraphy was performed to localize sentinel lymph nodes, and the procedure was carried out by 2 teams working together, a tumor-ablative team and a reconstructive team. The present study is adhered to the STROBE guidelines for cohort studies. The average operation time was 241.4 minutes and was not significantly different even in cases with inguinal dissection (P value: 0.641). All flaps survived after 2 cases of venous insufficiency and 1 case of hematoma were resolved by immediate revision surgery. The 2-team approach to surgically reconstruct heel defects after wide excision of malignant melanoma using free flap coverage offers favorable results and lower morbidity than regional flap approaches.

A novel cytokine consisting of the p40 and EBI3 subunits suppresses experimental autoimmune arthritis via reciprocal regulation of Th17 and Treg cells.

OBJECTIVE: The interleukin (IL)-12 cytokine family is closely related to the development of T helper cells, which are responsible for autoimmune disease enhancement or suppression. IL-12 family members are generally heterodimers and share three α-subunits (p35, p19, and p28) and two ß-subunits (p40 and EBI3). However, a ß-sheet p40 homodimer has been shown to exist and antagonize IL-12 and IL-23 signaling 1. Therefore, we assumed the existence of a p40-EBI3 heterodimer in nature and sought to investigate its role in immune regulation. METHODS: The presence of the p40-EBI3 heterodimer was confirmed by ELISA, immunoprecipitation, and western blotting. A p40-EBI3 vector and p40-EBI3-Fc protein were synthesized to confirm the immunological role of this protein in mice with collagen-induced arthritis (CIA). The anti-inflammatory effects of p40-EBI3 were analyzed with regard to clinical, histological, and immune cell-regulating features in mice with CIA. RESULTS: Clinical arthritis scores and the expression levels of proinflammatory cytokines (e.g., IL-17, IL-1ß, IL-6, and TNF-α) were significantly attenuated in p40-EBI3-overexpressing and p40-EBI3-Fc-treated mice with CIA compared to vehicle-treated mice with CIA. Structural joint damage and vessel formation-related gene expression were also reduced by p40-EBI3 heterodimer treatment. In vitro, the p40-EBI3-Fc protein significantly suppressed the differentiation of Th17 cells and reciprocally induced CD4+CD25+Foxp3+ (regulatory T) cells. p40-EBI3 also inhibited osteoclast formation in a concentration-dependent manner. CONCLUSION: In this study, p40-EBI3 ameliorated proinflammatory conditions both in vivo and in vitro. We propose that p40-EBI3 is a novel anti-inflammatory cytokine involved in suppressing the immune response through the expansion of Treg cells and suppression of Th17 cells and osteoclastogenesis.

Expanded IL-22+ Group 3 Innate Lymphoid Cells and Role of Oxidized LDL-C in the Pathogenesis of Axial Spondyloarthritis with Dyslipidaemia.

Group 3 innate lymphoid cells (ILC3), which express IL-22 and IL-17A, has been introduced as one of pathologic cells in axial spondyloarthritis (axSpA). Dyslipidaemia should be managed in axSpA patients to reduce cardiovascular disease, and dyslipidaemia promotes inflammation. This study aimed to reveal the role of circulating ILC3 in axSpA and the impact of dyslipidaemia on axSpA pathogenesis. AxSpA patients with or without dyslipidaemia and healthy control were recruited. Peripheral blood samples were collected, and flow cytometry analysis of circulating ILC3 and CD4+ T cells was performed. The correlation between Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP) and circulating immune cells was evaluated. The effect of oxidized low-density lipoprotein cholesterol (oxLDL-C) on immune cell differentiation was confirmed. AxSpA human monocytes were cultured with with oxLDL-C, IL-22, or oxLDL-C plus IL-22 to evaluate osteoclastogenesis using tartrate-resistant acid phosphatase (TRAP) staining and real-time quantitative PCR of osteoclast-related gene expression. Total of 34 axSpA patients (13 with dyslipidaemia and 21 without) were included in the analysis. Circulating IL-22+ ILC3 and Th17 were significantly elevated in axSpA patients with dyslipidaemia (p=0.001 and p=0.034, respectively), and circulating IL-22+ ILC3 significantly correlated with ASDAS-CRP (Rho=0.4198 and p=0.0367). Stimulation with oxLDL-C significantly increased IL-22+ ILC3, NKp44- ILC3, and Th17 cells, and these were reversed by CD36 blocking agent. IL-22 and oxLDL-C increased TRAP+ cells and osteoclast-related gene expression. This study suggested potential role of circulating IL-22+ ILC3 as biomarker in axSpA. Furthermore, dyslipidaemia augmented IL-22+ ILC3 differentiation, and oxLDL-C and IL-22 markedly increased osteoclastogenesis of axSpA.

The Lower-Risk Cannabis Use Guidelines' (LRCUG) recommendations: How are Canadian cannabis users complying?

Canada, alongside other jurisdictions, implemented non-medical cannabis legalization in 2018, partly towards improving public health. Evidence-based 'Lower-Risk Cannabis Use Guidelines' (LRCUG), including recommendations for cannabis users on how to decrease risk-behaviors for harms, have been developed and widely disseminated in Canada since 2017. However, knowledge on users' compliance with the LRCUG is limited. We identified four major Canadian (three national, one provincial) population surveys presenting key data on cannabis-related behaviors: the National Cannabis Survey, Canadian Cannabis Survey, Canadian Tobacco, Alcohol & Drugs Survey, and CAMH Monitor. We scanned each survey for indicator data mapping onto either of the LRCUG's recommendations for the years 2017 to 2019. Relevant indicator data, albeit with varying operationalizations, were found for six of the ten LRCUG's recommendation clusters in at least some of the surveys, and were extracted and summarized. For results, substantial -- but declining -- majorities of users consumed cannabis by smoking, yet with shifts towards other use modes. Between one- to two-in-five users engaged in the risk-behaviors of using high-potency cannabis products, frequent cannabis use and cannabis-impaired driving, respectively. A small proportion of pregnant or breastfeeding women continued cannabis use during the study period. The data identified found suggested a heterogeneous picture regarding cannabis users' compliance with the LRCUG's recommendations. Non-compliance is highest for recommendations regarding modes-of-use, and applies to minorities of users for other risks factors. These sub-groups are at elevated risk for acute (e.g., accidents) or long-term (e.g., dependence) cannabis-related harms contributing to the public health burden. Appropriate targeted interventions in these areas require improvement.

Optimal Condition of Isolation from an Adipose Tissue-Derived Stromal Vascular Fraction for the Development of Automated Systems.

BACKGROUND: The stromal vascular fraction (SVF) isolated from adipose tissue, which contains stem cells as well as other cell types, has been applied in various research fields. Although different enzymatic concentrations and treatment durations have been applied to isolate the SVF, optimal conditions have not been established. Thus, we aimed to establish the optimal conditions for isolation of the SVF from adipose tissue by automated systems. METHODS: The SVF was collected from removed adipose tissues of five donors during surgery. The SVF was treated with 0.1% or 0.2% collagenase type I for 20, 40, or 60 min. Then, colony forming unit (CFU) assays and flow cytometry were performed to characterize the adipose stem cells (ASCs). A cytokine array was used to investigate the correlation between colony-formation ability and the secretion of isolated ASCs. RESULTS: Treatment with 0.1% collagenase type I for 60 min resulted in a higher SVF yield, whereas treatment with 0.1% collagenase for 40 min resulted in higher CFU values. In addition, expression of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 in the SVF was higher in the high-CFU group than in the low-CFU group. CONCLUSION: The optimal conditions for isolation of the SVF from adipose tissue were treatment with 0.1% collagenase type I for 40 min. We identified the conditions required for efficient SVF isolation based on high CFU values, and our results will facilitate the development of automated systems.

Robot-assisted laparoscopic myomectomy for deep intramural myomas.

BACKGROUND: To evaluate the efficacy of robot-assisted laparoscopic myomectomy for deep intramural myomas. METHODS: We have conducted a retrospective study for 170 patients who underwent robot-assisted laparoscopic myomectomy by a single operator of tertiary university hospital. RESULTS: There were 100 cases of robot-assisted laparoscopic myomectomy for deep intramural myomas. The patients had 3.8±3.5 myomas on average, and the mean size of the largest myoma of each patient was 7.5±2.1 centimeters in diameter. Mean operative time was 276.4±97.1 minutes, and mean console time was 146.0±62.7 minutes. Thirty two patients had surgeries for other gynecologic conditions such as pelvic endometriosis or endometrial polyps along with myomectomy at the same time. All the patients recovered without any major complication. After the surgery, nine(75.0 %) of the 12 women pursuing a pregnancy became pregnant. CONCLUSION: Robot-assisted laparoscopic myomectomy for deep intramural myomas could be a minimal invasive surgical option for women who wish preserve fertility. Copyright © 2016 John Wiley & Sons, Ltd.

Three cases of complications after high-intensity focused ultrasound treatment in unmarried women.

High-intensity focused ultrasound (HIFU) has been regarded as a non-surgical, minimally invasive therapeutic option for patients who prioritize uterus-conservation. Although many studies have shown that HIFU therapy is a safe and effective treatment of uterine fibroid, not all fibroids are suitable for HIFU due to risks of serious complications. We experienced three cases of complications after the HIFU ablation for huge uterine fibroids, including two cases of rapid myoma enlargement and one case of heavy vaginal bleeding.