Surgical approach and orthodontic treatment of mandibular condylar osteochondroma / 대한치과교정학회지

Osteochondroma is a common benign tumor of bones, but it is rare in the mandibular condyle. With its outgrowth it manifests clinically as deviation of the mandible limitation of mouth opening, and facial asymmetry. After the tumor is diagnosed on the basis of clinical symptoms and radiographic examination including cone-beam computed tomography (CBCT) analysis, an appropriate surgery and treatment plan should be formulated. Herein, we present the case of a 44-year-old female patient who visited our dental hospital because her chin point had been deviating to the left side slowly but progressively over the last 3 years and she had difficulty masticating. Based on CBCT, she was diagnosed with skeletal Class III malocclusion accompanied by osteochondroma of the right mandibular condyle. Maxillary occlusal cant with the right side down was observed, but it was confirmed to be an extrusion of the molars associated with dental compensation. Therefore, after intrusion of the right molars with the use of temporary anchorage devices, sagittal split ramus osteotomy was used to remove the tumor and perform orthognathic surgery simultaneously. During 6 months after the surgery, continuous bone resorption and remodeling were observed in the condyle of the affected side, which led to a change in occlusion. During the postoperative orthodontic treatment, intrusive force and buccal torque were applied to the molars on the affected side, and a proper buccal overjet was created. After 18 months, CBCT revealed that the rate of bone absorption was continuously reduced, bone corticalization appeared, and good occlusion and a satisfying facial profile were achieved.

Growth observation and orthodontic treatment of a hemifacial microsomia patient treated with distraction osteogenesis / 대한치과교정학회지

Hemifacial microsomia (HFM) patients may experience emotional withdrawal during their growth period due to their abnormal facial appearance. Distraction osteogenesis at an early age to improve their appearance can encourage these patients. Some abnormalities of the affected side can be overcome by distraction osteogenesis at an early age. However, differences in the growth rate between the affected and unaffected sides during the rest of the growth period are inevitable due to the characteristics of HFM. Therefore, re-evaluation should be performed after completion of growth in order to achieve stable occlusion through either orthognathic surgery or camouflage orthodontic treatment. An eight-year-old patient visited the clinic exhibiting features of HFM with slight mandibular involvement. He received phase I treatment with distraction osteogenesis and a functional appliance. Distraction osteogenesis was performed at the right ramus, which resulted in an open bite at the right posterior dentition. After distraction osteogenesis, a functional appliance and partial fixed appliance were used to achieve extrusion of the affected posterior dentition and settlement of the occlusion adjustment on the unaffected posterior dentition. The patient visited the clinic regularly for follow-up assessments, and at the age of 20 years, he showed facial asymmetry of the mandible, which had deviated to the right side. He received orthodontic treatment to improve the occlusion of his posterior dentition after the growth period. Without orthognathic surgery, stable occlusion and a satisfactory facial appearance were obtained through camouflage orthodontic treatment.

Resveratrol Inhibits Hypoxia-Induced Vascular Endothelial Growth Factor Expression and Pathological Neovascularization

PURPOSE: To investigate the effects of resveratrol on the expression of hypoxia-inducible factor 1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in human adult retinal pigment epithelial (ARPE-19) cells, and on experimental choroidal neovascularization (CNV) in mice. MATERIALS AND METHODS: ARPE-19 cells were treated with different concentrations of resveratrol and then incubated under hypoxic conditions with subsequent evaluation of cell viability, expression of HIF-1alpha, and expression of VEGF. The effects of resveratrol on the synthesis and degradation of hypoxia-induced HIF-1alpha were evaluated using inhibitors of the PI3K/Akt/mTOR and the ubiquitin proteasome pathways. In animal studies, CNV lesions were induced in C57BL/6 mice by laser photocoagulation. After 7 days of oral administration of resveratrol or vehicle, which began one day after CNV induction, image analysis was used to measure CNV areas on choroidal flat mounts stained with isolectin IB4. RESULTS: In ARPE-19 cells, resveratrol significantly inhibited HIF-1alpha and VEGF in a dose-dependent manner, by blocking the PI3K/Akt/mTOR signaling pathway and by promoting proteasomal HIF-1alpha degradation. In mice experiments, orally administered resveratrol significantly inhibited CNV growth in a dose-dependent manner. CONCLUSION: Resveratrol may have therapeutic value in the management of diseases involving pathological neovascularization.

Concomitant Acute Transverse Myelitis and Sensory Motor Axonal Polyneuropathy in Two Children: Two Case Reports

Acute transverse myelitis (ATM) is an upper motor neuron disease of the spinal cord, and concomitant association of peripheral polyneuropathy, particularly the axonal type, is rarely reported in children. Our cases presented with ATM complicated with axonal type polyneuropathy. Axonal type polyneuropathy may be caused by acute motor-sensory axonal neuropathy (AMSAN) or critical illness polyneuropathy and myopathy (CIPNM). These cases emphasize the need for nerve and muscle biopsies to make the differential diagnosis between AMSAN and CIPNM in patients with ATM complicated with axonal polyneuropathy.

Arnold-Chiari Malformation Type III With Meningoencephalocele: A Case Report

Arnold-Chiari malformation type III (CM III) is an extremely rare anomaly with poor prognosis. An encephalocele with brain anomalies as seen in CM II, and herniation of posterior fossa contents like the cerebellum are found in CM III. The female infant was a twin, born at 33 weeks, weighing 1.7 kg with a huge hydrocele on the craniocervical junction. After operations were performed, she was referred to the department of rehabilitation medicine for poor motor development, swallowing dysfunction, and poor eye fixation at 22 months. The child was managed with neurodevelopmental treatment, oromotor facilitation, and light perception training. After 14 months, improvement of gross motor function was observed, including more stable head control, rolling, and improvement of visual perception. CM III has been known as a condition with poor prognosis. However, with the improvement in operative techniques and intensive rehabilitations, the prognosis is more promising than ever before. Therefore, more attention must be paid to the rehabilitation issues concerning patients with CM III.

Protective Effect of Survivin in Doxorubicin-Induced Cell Death in H9c2 Cardiac Myocytes

BACKGROUND AND OBJECTIVES: Apoptosis has been known to be an important mechanism of doxorubicin-induced cardiotoxicity. Survivin, which belongs to the inhibitor of apoptosis protein family, is associated with apoptosis and alteration of the cardiac myocyte molecular pathways. Therefore, we investigated the anti-apoptotic effect and cellular mechanisms of survivin using a protein delivery system in a doxorubicin-induced cardiac myocyte injury model. MATERIALS AND METHODS: We constructed a recombinant survivin which was fused to the protein transduction domain derived from HIV-TAT protein. In cultured H9c2 cardiac myocytes, TAT-survivin (1 microM) was added for 1 hour prior to doxorubicin (1 microM) treatment for 24 hours. Cell viability and apoptosis were evaluated by 2-(4,5-dimethyltriazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, caspase-3 activity, and terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay. We measured the expression levels of several apoptosis-related signal proteins. RESULTS: The survivin level was significantly reduced in a dose dependent manner up to 1 microM of doxorubicin in concentration. Purified recombinant TAT-survivin protein was efficiently delivered to H9c2 cardiac myocytes, and its transduction showed an anti-apoptotic effect, demonstrated by reduced caspase-3 activity and the apoptotic index, concomitantly with increased cell viability against doxorubicin injury. The phosphorylation of p38 mitogen-activated protein (MAP) kinase and the release of Smac from mitochondria were suppressed and the expression levels of Bcl-2 and cAMP response element-binding protein (CREB), the transcription factor of Bcl-2, were recovered following TAT-survivin transduction, indicating that survivin had an anti-apoptotic effect against doxorubicin injury. CONCLUSION: Our results suggest that survivin has a potentially cytoprotective effect against doxorubicin-induced cardiac myocyte apoptosis through mechanisms that involve a decrease in the phosphorylation of p38 MAP kinase, mitochondrial Smac release, and increased expression of Bcl-2 and CREB.

Antiplaque and antigingivitis effects of a mouthrinse containing cetylpyridinium chloride, triclosan and dipotassium glycyrrhizinate

PURPOSE: The goal of this study was to evaluate the clinical anitplaque and antigingivitis effects of a mouthrinse containing cetylpyridinium chloride (CPC), triclosan and dipotassium glycyrrhizinate (DPZ) in patients with gingivitis and mild periodontitis. METHODS: Thirty-two subjects were randomized into 2 groups. The test group used a mouthrinse containing 0.05% CPC, 0.02% triclosan and 0.02% DPZ, while the control group used a placebo mouthrinse. At baseline, 2 weeks and 4 weeks, the papillary bleeding index (PBI), Turesky-Quigley-Hein plaque index (PI) and Loe-Silness gingival index (GI) were assessed. During the experimental period, the patients used the mouthrinse for 30 seconds, 4 to 5 times/day (10 mL/time) within 30 minutes after toothbrushing. RESULTS: No adverse effects appeared in either the experimental or the control group. Regarding PBI, PI and GI values, statistical significance was detected between values at baseline and 2 weeks for both groups (P<0.05). In the experimental group, statistically significantly lower values were detected at 4 weeks compared to at 2 weeks. However, in the control group, no statistically significant difference was detected between the values at 2 weeks and 4 weeks. Additionally, the mean value after 4 weeks for the control group was slightly higher than the mean value after 2 weeks for the control group. CONCLUSIONS: This study for 4 weeks demonstrated that mouthrinses containing CPC, triclosan and DPZ may contribute to the reduction of supragingival plaque and gingivitis.

Antiplaque and antigingivitis effects of a mouthrinse containing cetylpyridinium chloride, triclosan and dipotassium glycyrrhizinate

PURPOSE: The goal of this study was to evaluate the clinical anitplaque and antigingivitis effects of a mouthrinse containing cetylpyridinium chloride (CPC), triclosan and dipotassium glycyrrhizinate (DPZ) in patients with gingivitis and mild periodontitis. METHODS: Thirty-two subjects were randomized into 2 groups. The test group used a mouthrinse containing 0.05% CPC, 0.02% triclosan and 0.02% DPZ, while the control group used a placebo mouthrinse. At baseline, 2 weeks and 4 weeks, the papillary bleeding index (PBI), Turesky-Quigley-Hein plaque index (PI) and Loe-Silness gingival index (GI) were assessed. During the experimental period, the patients used the mouthrinse for 30 seconds, 4 to 5 times/day (10 mL/time) within 30 minutes after toothbrushing. RESULTS: No adverse effects appeared in either the experimental or the control group. Regarding PBI, PI and GI values, statistical significance was detected between values at baseline and 2 weeks for both groups (P<0.05). In the experimental group, statistically significantly lower values were detected at 4 weeks compared to at 2 weeks. However, in the control group, no statistically significant difference was detected between the values at 2 weeks and 4 weeks. Additionally, the mean value after 4 weeks for the control group was slightly higher than the mean value after 2 weeks for the control group. CONCLUSIONS: This study for 4 weeks demonstrated that mouthrinses containing CPC, triclosan and DPZ may contribute to the reduction of supragingival plaque and gingivitis.

Cathepsin L derived from skeletal muscle cells transfected with bFGF promotes endothelial cell migration

Gene transfer of basic fibroblast growth factor (bFGF) has been shown to induce significant endothelial migration and angiogenesis in ischemic disease models. Here, we investigate what factors are secreted from skeletal muscle cells (SkMCs) transfected with bFGF gene and whether they participate in endothelial cell migration. We constructed replication-defective adenovirus vectors containing the human bFGF gene (Ad/bFGF) or a control LacZ gene (Ad/LacZ) and obtained conditioned media, bFGF-CM and LacZ-CM, from SkMCs infected by Ad/bFGF or Ad/LacZ, respectively. Cell migration significantly increased in HUVECs incubated with bFGF-CM compared to cells incubated with LacZ-CM. Interestingly, HUVEC migration in response to bFGF-CM was only partially blocked by the addition of bFGF-neutralizing antibody, suggesting that bFGF-CM contains other factors that stimulate endothelial cell migration. Several proteins, matrix metalloproteinase-1 (MMP-1), plasminogen activator inhibitor-1 (PAI-1), and cathepsin L, increased in bFGF-CM compared to LacZ-CM; based on 1-dimensional gel electrophoresis and mass spectrometry. Their increased mRNA and protein levels were confirmed by RT-PCR and immunoblot analysis. The recombinant human bFGF protein induced MMP-1, PAI-1, and cathepsin L expression in SkMCs. Endothelial cell migration was reduced in groups treated with bFGF-CM containing neutralizing antibodies against MMP-1 or PAI-1. In particular, HUVECs treated with bFGF-CM containing cell-impermeable cathepsin L inhibitor showed the most significant decrease in cell migration. Cathepsin L protein directly promotes endothelial cell migration through the JNK pathway. These results indicate that cathepsin L released from SkMCs transfected with the bFGF gene can promote endothelial cell migration.

Analysis of the Clinicopathologic Features of Eosinophilic Esophagitis: Comparative Study with Nonobstructive Dysphagia / 대한소화기내시경학회지

BACKGROUND/AIMS: Eosinophilic esophagitis (EoE) has emerged as one of the most common causes of dysphagia and esophageal food impactions. However, it is doubtful that gastroenterologists and pathologists make the correct diagnosis of EoE because of the insufficient recognition of EoE based on the endoscopic and pathological findings. This study was performed to investigate the symptoms and the endoscopic and pathologic findings of EoE as compared with those of nonobstructive dysphagia (NOD). METHODS: We retrospectively reviewed the medical records and the endoscopic and pathologic findings from 12 patients who were diagnosed with EoE based on an eosinophil count of > or =20 per high-power field (HPF) and 13 patients diagnosed with NOD, and these patients were treated at our hospital from June 2006 till October 2010. RESULTS: The endoscopic findings of EoE included rings (41.7%), furrows (75.0%), exudates (33.3%), mucosal friability (8.3%) and multi-findings (6.7%). Furrows and multi-findings were identified more frequently in EoE as comparison to that in NOD. The pathologic findings revealed that the maximal eosinophil counts/HPF were 87.2 (range 20~232) and 2.2 (0~1) in EoE and NOD, respectively. Moreover, eosinophil microabscess (58.3%), degranulation (100%) and spongiosis (91.7%) were more significantly observed in EoE compared with that in NOD. CONCLUSIONS: EoE had specific endoscopic and clinicopathologic features that distinguish it from NOD. For patients with dysphagia, the endoscopic and pathologic findings of EoE should be kept in mind.

A Case of Successful Colonoscopic Treatment of Acute Appendiceal Bleeding by Endoclips

Lower gastrointestinal bleeding is a common disease among elderly patients. The common sources of lower gastrointestinal bleeding include vascular disease, Crohn's disease, neoplasm, inflammatory bowel disease, hemorrhoid, and ischemic colitis. However, bleeding from the appendix has been reported very rarely in patients with lower gastrointestinal tract bleeding. In general, after a colonoscopic diagnosis of appendiceal bleeding, a laparoscopic or surgical appendectomy would be recommended. We report a case of successful colonoscopic treatment of appendiceal bleeding without complications by endoclips. This report suggests that colonoscopic clipping is a safe and effective means to treat bleeding from appendiceal lesions. Further study is needed to evaluate procedure-related complications and to confirm the procedure's safety and efficacy.

A radiographical study on the changes in height of grafting materials after sinus lift: a comparison between two types of xenogenic materials

PURPOSE: The performance of implant surgery in the posterior maxilla often poses a challenge due to insufficient available bone. Sinus floor elevation was developed to increase the needed vertical height to overcome this problem. However, grafting materials used for the sinus lift technique eventually show resorption. The present study radiographically compared and evaluated the changes in height of the grafting materials after carrying out maxillary sinus elevation with a window opening procedure. This study also evaluated the difference between two xenogenic bone materials when being used for the sinus lifting procedure. METHODS: Twenty-one patients were recruited for this study and underwent a sinus lift procedure. All sites were treated with either bovine bone (Bio-Oss(R)) with platelet-rich plasma (PRP) or bovine bone (OCS-B(R))/PRP. A total of 69 implants were placed equally 6-8 months after the sinus lift. All sites were clinically and radiographically evaluated right after the implant surgery, 7-12 months, 13-24 months, and 25-48 months after their prosthetic loading. RESULTS: Changes of implant length/bone length with time showed a statistically significant decreasing tendency (P 0.05). In contrast, the OCS-B(R) group showed a significant decrease with time (P 0.05). CONCLUSIONS: The results showed that there was significant reduction in comparison with data right after placement, after 7 to 12 months, 13 to 24 months, and over 25 months; however, reduction rates between each period have shown to be without significance. No significant difference in height change was observed between the Bio-Oss(R) and the OCS-B(R) groups.

Heat shock protein 90 regulates IkappaB kinase complex and NF-kappaB activation in angiotensin II-induced cardiac cell hypertrophy

Heat shock protein 90 (HSP90), one of the most abundant proteins in the cardiac cells is essential for cell survival. Previous studies have shown that angiotensin II induces cardiac cell hypertrophy. However, the role of HSP90 in the angiotensin II-induced cardiac hypertrophy is unclear. In this study, we showed that HSP90 regulated angiotensin II-induced hypertrophy via maintenance of the IkappaB kinase (IKK) complex stability in cardiac cells. An HSP90 inhibitor, geldanamycin (GA), significantly suppressed angiotensin II-induced [3H]leucine incorporation and atrial natriuretic factor expression in cardiac cells. GA also inhibited the NF-kappaB activation induced by angiotensin II. Importantly, treatment with GA caused a degradation of IKKalpha/beta; on the other hand, a proteasome-specific inhibitor restored the level of IKKalpha/beta. We also found that GA prevented HSP90-IKKs complex induced by angiotensin II in cardiac cells. The small interfering RNA (siRNA)-mediated knockdown of HSP90 expression significantly inhibited angiotensin II-induced cell hypertrophy and NF-kappaB activation. These results suggest that angiotensin II-induced cardiac hypertrophy requires HSP90 that regulates the stability and complex of IKK.

Corneal Melting and Descemetocele Resulting From Noninfectious Keratitis Related to the Cosmetic Contact Lenses

PURPOSE:To report 2 cases of corneal melting and corneal melting with descemetocele that occurred in users of cosmetic contact lenses. CASE SUMMARY: A-12-year-old and a 13-year-old female who used cosmetic contact lenses were referred to our clinic under the preliminary diagnosis of keratitis and corneal melting. The patients had purchased the lenses from an optician and had worn the lenses for approximately 1 month without being educated on their proper use. The signs and symptoms improved after 2 weeks of treatment with oral steroid and 1% topical prednisolone acetate. However, descemetocele occurred in the 12-year-old patient. Reepithelization of the cornea had been completed within the treatment period. However, corneal thinning with mild opacity remained in the lesions, and the best corrected visual acuities on the Snellen chart were 20/30 in both patients.

Comparison of implant survival rate by sinus lifting technique in implantation with sinus lift / 대한치주과학회지

PURPOSE: The purpose of this study was comparison of survival rate of implant as two sinus elevation techniques and when window opening procedure had done it was comparison of survival rate of implant between the procedure of implantation after 6 month of sinus elevation to allow healing period and that of implantation with sinus elevation simultaneously. MATERIAL AND METHODS: All 79 of patients treated at DanKook University Dental Hospital Dept. of Periodontics for 164 implantation of maxillary posterior edentulous area with sinus elevation. Sinus elevation technique was divided of the technique : Osteotome technique and window opening technique. RESULT: 14 implants among 96 implants was failed implants of using osteotome for sinus elevation whereas one implant of 68 implants was failed of using window opening technique. CONCLUSION: Window opening technique had higher survival rate than osteotome technique. In case of window opening, there was no significant difference of immediate implantation and delayed implantation.

A study on the biological characteristics of modified titanium surface / 대한치주과학회지

PURPOSE: The purpose of this research is to study about initial adhesion, proliferation and activation of osteoblast to titanium surface treated with machined, hydroxyapatite coating, resorbable blast material blasting and anodizing method. MATERIAL AND METHODS: After treating the titanium surface of each block with machined, impurities were removed and sterilized. The number of cells attached from cultured osteoblast of respective experimental groups were measured at 1, 4, 7, and 14day and alkaline phosphatase, calcium, and inorganic phosphate concentration of cultured solution was measured. RESULT: Anodizing group showed the highest rate of cell attachment and proliferation activity. RBM treated group showed the highest increasing on their alkaline phosphatase activity, on the calcium apposition, on inorganic phosphate apposition of 1 and 4 days in cultured osteoblast to compare with other groups. CONCLUSION: On the basis of these findings, we conclude that surface modification of titanium was profoundly effected on the attachment, proliferation and activation of osteoblast in initial stage osseointegration.

A compare research of machined implant and RBM surface implant / 대한치주과학회지

PURPOSE: To evaluate RBM surface implant which has its good character like that good initial stability, early bone formation. MATERIAL AND METHODS: In this study fixures have divided in 2 group: Machined(Group I), RBM(Group II). Total 10 fixtures were implanted on rabbit which sacrificed on week 2 and week 4 for the histological specimens. By these specimens polarized microscopic view, micro CT view, ISQ value were measured, compared and analysed by each group to figure out the evidence that clinical use of RBM implant. RESULT: ISQ value had no significance differences between 2 groups, However in each group 4, 8 weeks had higher ISQ value than 2 weeks. In polarized microscope, calcification level was following : Group II, Group I. In micro CT, formation of cancellous bone level was following : Group II, Group I. CONCLUSION: RBM implant was the most excellent on the early bone formation and good initial stability.

A comparative study for guided bone regeneration of silk fibroin nanomembrane(NanoGide-S(TM)) / 대한치주과학회지

PURPOSE: To evaluate the safety and efficiency of bone regenerative abilities of silk fibroin nanomembrane(Nanoguide-S) MATERIAL AND METHODS: The objects were 38 patients who had large defect at extraction sockets caused by chronic periodontitis and silk fibroin nano matrix were used on experimental group(N=19) and PLA/PLGA matrix were used on control group(N=19). The width, height, and length by crown-apical direction(socket depth) of defects were measured with the occlusal plane as a reference plane, and tooth axis direction, perpendicular to tooth axis direction were measured on radiographs at 3 months pre-operative, 3 months post-operative. RESULT: Tissue response to silk fibroin nano matrix and Biomesh were clinically satisfactory and complications such as swelling, exudation, ulceration and vesicles were not found except the ordinary discomfort of operated portion. 3 months later, the width, height, and length by crown-apical direction (socket depth) of defects were clinically improved in both groups with no significant difference. 3 months later radiolucency of tooth axis direction and perpendicular to tooth axis direction were all increased in both groups with no significant difference. CONCLUSION: By these results biodegradadable silk fibroin nano matrix was efficient in GBR on alveolar bone resorption caused by periodontitis compared to Biomesh.

A Comparison of Clinical Effect for Root Coverage / 대한치주과학회지

PURPOSE: The purpose of this study was to compare clinical effect of the Langer & Langer technique , the modified Langer & Langer technique and Bruno technique. MATERIAL AND METHODS: 30 patients who have gingiva recession(Miller class I or class II) were carried root coverage. Langer & Langer technique(14 patients/32 tooth), modified Langer & Langer technique(5 patients/10 tooth) and Bruno technique(11 patients/18 tooth) was carried. At baseline and average 3 months after operation, it was estimated clinical index(Pocket depth, gingiva recession, clinical attachment level, keratinized gingiva, scar tissue, root coverage rate) by Williams style probe. RESULT: Root coverage rate is indicated Langer & Langer technique(85%), Modified Langer & Langer technique(86%) and Bruno technique(90%). CONCLUSION: All three of the procedures were effective in gingival recession and improved clinical parameters.

The comparative study: the regenerative effect depends on size of bone graft material in bone loss site around dental implant / 대한치주과학회지

PURPOSE: The purpose of this study is to investigate on the regenerative capacity by using different size of graft materials around bony defect around implant. MATERIAL AND METHODS: Dental implant fixtures(Bio-TIS, Korea) were placed into the tibia of 8 rabbits. After placement of implant, artificial defects were created for each group, and the size of bone graft materials were used according to each designated group. 4 weeks after surgery, 8 rabbits were sacrificed. The histologic and histomorphometrical study were done for comparison of the regenerative capacity using 80-90micrometer and 200~1000micrometer size of grafting materials of OCS-B(R). RESULT: Matured bone formation was significantly increased more in Group E1(80-90micrometer) than in Group E2(200~1000micrometer). Group E1(80-90micrometer) showed more significant augmentation in marginal length of graft material per unit area than Group E2(200~1000micrometer). Group E1(80-90micrometer) showed more interspace in graft material than Group E2(200~1000micrometer). Control group showed no new bone formation around and inside of implanted fixture. CONCLUSION: Small grafting material size has great influence on bone regeneration.