Complications of Costal Cartilage Asian Rhinoplasty and Their Management.

The abundance, biocompatibility, and versatility of autologous costal cartilage allow rhinoplasty surgeons to perform an array of maneuvers needed to successfully manage cases that require an ample source of grafting materials. Hence, there has been a steady increase in the use of costal cartilage in Asian rhinoplasty. Despite its many advantages, autologous costal cartilage rhinoplasty is also associated with complications, which include warping, infection, and displacement, as well as donor-site morbidity issues such as pneumothorax, pain, and chest scars. Many of these can be minimized by adhering to the recommended techniques. In this review, operative techniques that focus on the prevention and management of complications associated with the use of autologous costal cartilage are presented.

Minimally Invasive Technique to Reduce the Isolated Anterior Wall Fracture of the Frontal Sinus.

Conventional open reduction and internal fixation of frontal sinus anterior wall fractures are associated with risks of visible scarring and limited access to the nasofrontal duct. The goal of this study was to report the minimally invasive surgical techniques and their results in cases with frontal sinus anterior wall fractures. A retrospective study was performed on 20 consecutive cases of isolated anterior wall fractures of the frontal sinus between July, 2008 and February, 2017. Causes of injury, interval between the injury and operation, and operation time were reviewed. The fractures were reduced using the minimally invasive techniques of endoscopic endonasal reduction or reduction through a small trephination. Anatomical and aesthetic outcomes were evaluated, and postoperative complications were reviewed. The fractures were reduced with endoscopic endonasal techniques in 11 patients and through a small trephination with a minimal incision in the forehead in 9 patients. The fractures were successfully reduced in all cases. The mean follow-up period was 21.2 months, and no postoperative complications were observed. For isolated anterior wall fractures of the frontal sinus, minimally invasive techniques, such as endonasal endoscopic reduction or reduction through a small trephination, are safe and effective options.

Use of Mastoid Periosteum Graft in Primary and Revision Rhinoplasty.

BACKGROUND: The authors initiated the use of a mastoid periosteum graft to augment or camouflage the dorsum and radix. This report describes the techniques and treatment outcomes of mastoid periosteum grafts in primary and revision rhinoplasty. MATERIALS AND METHODS: Medical records of 62 patients who underwent rhinoplasty with mastoid periosteum were reviewed retrospectively. Of these, 21 patients who participated in follow-up for more than 6 months were analyzed through a comparison of pre- and postoperative photographs. Aesthetic results were scored on a scale of 0 to 4 (0 = poor, 1 = fair, 2 = moderate, 3 = good, 4 = excellent) with photographic evaluation by two independent surgeons. RESULTS: A mastoid periosteum graft was used in 32 primary and 30 revision cases. The graft was used to augment the radix (28 cases), dorsum (15 cases), and both radix and dorsum (19 cases). Cartilage underlay was combined with mastoid periosteum grafts in 38 patients (61.3%, 17 in radix graft, 8 in dorsal graft, and 13 in both). The aesthetic outcome score assessed in 21 patients was 2.8 on average (3.2 in primary and 2.4 in revision cases). Cartilage combined cases showed better aesthetic outcome than free graft cases (3.1 vs. 2.5, respectively). Three cases of partial graft resorption were found, but there were no major complications. CONCLUSIONS: Mastoid periosteum grafting is a safe and effective method to augment the radix or dorsum in primary and revision rhinoplasty. Long-term partial resorption cannot be completely excluded, which necessitates further study. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The role of interleukin-33 in chronic rhinosinusitis.

RATIONALE: Interleukin (IL)-33, a new member of the IL-1 family, is constitutively expressed in epithelial tissues and lymphoid organs and plays an important role in the pathogenesis of allergic disease. However, the role of IL-33 in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. OBJECTIVE: To investigate the role of IL-33 in the pathophysiology of CRSwNP. METHODS: We investigated IL-33 expression and its cellular origins in the nasal polyps (NPs) of human subjects by immunohistochemistry (IHC), quantitative reverse transcription PCR (qRT-PCR), and multiplex cytokine assays. Correlations between IL-33 expression and other inflammatory markers were also explored. To investigate the role of IL-33 in CRSwNP, anti-IL-33 antibody was used in a murine model of CRS. RESULTS: Uncinate process tissues from control (19), CRSsNP (61), CRSwNP (69) and NP tissues (71) were used in this study. Increased expression of IL-33 mRNA and protein in patients with CRSwNP compared with controls was observed. The concentration of IL-33 protein in CRSwNP was positively correlated with the number of neutrophils and the expression of several Th1 and Th17 inflammatory markers, including interferon (IFN)-γ, IL-1ß, tumour necrosis factor (TNF)-α, IL-17A, IL-22, and various markers for neutrophil recruitment. However, protein levels of IL-5 and quantity of eosinophils were inversely correlated with levels of IL-33. The expression of tissue inhibitor of metalloproteinase (TIMP)-1 was negatively correlated with IL-33 protein levels, while the expression of matrix metalloproteinase (MMP)-2 and MMP-9 was positively correlated with IL-33 protein levels. In animal studies, IL-33 expression was upregulated in the CRSwNP group compared with controls. Anti-IL-33 treatment reduced the thickness of oedematous mucosa, subepithelial collagen deposition, and infiltration of neutrophils, but infiltration of eosinophils was not reduced. This treatment also inhibited the expression of neutrophilic inflammatory cytokines, but not IL-4. In addition, the expression of intracellular adhesion molecule 1, vascular adhesion molecule 1 and CXCL-2 in the nasal mucosa was suppressed in mice treated with anti-IL-33 antibody. CONCLUSIONS: Our data suggest a role for IL-33 in the pathogenesis of CRSwNP via neutrophil recruitment. Therefore, anti-IL-33 may provide a new treatment strategy to target infiltrating neutrophils in CRSwNP.

Chronic anosmia induces depressive behavior and reduced anxiety via dysregulation of glucocorticoid receptor and corticotropin-releasing hormone in a mouse model.

BACKGROUND: Olfactory loss is highly prevalent, and comorbid mood disorders are common. Considering olfactory input is highly interconnected with the limbic system, and that the limbic system manages mood, it is predictable that impairments in the sense of smell may result in mood changes. METHODOLOGY: Chronic olfactory deficits were induced by repeated intranasal irrigation of ZnSO4 for 12 weeks in BALB/c mice. H&E staining, OMP staining, and potato chip finding test were performed to confirm olfactory loss. Tail suspension, forced swim, and splash tests were performed to evaluate depression, as well as open field, elevated plus maze tests were applied to assess anxiety. The mRNA levels of glucocorticoid receptor (GR) and corticotropin releasing hormone (CRH) were measured by real-time PCR to confirm relevant molecular changes. RESULTS: Disruption of the olfactory epithelium and olfactory loss was confirmed in histological studies and potato chip finding test. Behavioral tests show that the chronic anosmic state caused increased depression and reduced anxiety. PCR data showed that mRNA levels of GR in the hypothalamus and CRH in the amygdala were significantly decreased. CONCLUSIONS: These results propose that ZnSO4-induced chronic anosmia can cause a depressive and anxiolytic state via decreased hypothalamic GR and amygdalar CRH.

IL-25 as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps (NPs) in Western populations is associated with TH2 cytokine polarization. IL-25, an IL-17 family cytokine, was recently reported to induce TH2-type immune responses and to contribute to several allergic diseases, such as atopic dermatitis and asthma. However, the role of IL-25 in Asian patients with nasal polyposis remains unclear. OBJECTIVE: We sought to determine the role of IL-25 in Asian patients with nasal polyposis and CRS. METHODS: We investigated IL-25 expression and its cellular origins in NPs of human subjects using immunohistochemistry (IHC), quantitative RT-PCR, and ELISA of NP tissues. Correlations between IL-25 expression and expression of other inflammatory markers in NP tissues were also explored. Anti-IL-25 neutralizing antibody was administered in an ovalbumin- and staphylococcal enterotoxin B-induced murine NP model to confirm the function of IL-25 during nasal polypogenesis. RESULTS: IL-25 expression was upregulated in NP mucosa from patients with CRS with NPs compared with uncinate process tissue from control subjects and those with CRS without NPs. Overexpression of epithelial IL-25 was confirmed by using IHC, and double IHC staining showed that tryptase-positive cells were one of the main sources of IL-25 among immune cells. Furthermore, IL-17 receptor B levels were also increased in immune cells of patients with NPs compared with those in control subjects. In NPs IL-25 mRNA expression positively correlated with the expression of several inflammatory markers, including T-box transcription factor, RAR-related orphan receptor C, GATA3, eosinophil cationic protein, TGF-ß1, and TGF-ß2. IL-25 was more abundant in the murine NP model compared with control mice, and similar correlations between IL-25 and inflammatory markers were observed in murine models. Anti-IL-25 treatment reduced the number of polyps, mucosal edema thickness, collagen deposition, and infiltration of inflammatory cells, such as eosinophils and neutrophils. This treatment also inhibited expression of local inflammatory cytokines, such as IL-4 and IFN-γ. Furthermore, expression of CCL11, CXCL2, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in the nasal mucosa was suppressed in the anti-IL-25-treated group. CONCLUSION: Our results suggest that IL-25 secreted from the sinonasal epithelia and infiltrating mast cells plays a crucial role in the pathogenesis of CRS with NPs in Asian patients. In addition, our results suggest the novel possibility of treating nasal polyposis with anti-IL-25 therapy.

Diced Cartilage in Fascia for Major Nasal Dorsal Augmentation in Asians: A Review of 15 Consecutive Cases.

BACKGROUND: Warping remains a primary issue in the use of autologous costal cartilage for nasal augmentation. To mitigate such issues, diced cartilage in fascia (DCIF) has been proposed as an alternative for use in rhinoplasty. The objective of this study was to assess the efficacy of DCIF in nasal dorsal augmentation for Asian patients, with particular focus on the strengths and weaknesses of this material. MATERIALS AND METHODS: Fifteen patients who underwent major dorsal augmentation with DCIF during the last 2 years were retrospectively reviewed. Diced cartilage wrapped in deep temporal fascia was used. RESULTS: Costal cartilage was used as the dicing material in 11 cases, while a mixture of septal and conchal cartilage was used in the other four cases. In the majority of cases, DCIF was inserted from the radix to the supratip. In 10 of the 15 cases, acceptable aesthetic and functional results were obtained; at a mean follow-up of 13.3 months, no complications were observed in these patients. In the remaining five cases, complications such as mild deviation, mild supratip depression, irregularities of the nasal dorsum, considerable resorption, and hair loss at the fascial harvesting site were observed. CONCLUSIONS: This study suggests that DCIF is useful in major nasal dorsal augmentation; however, it involves certain complications. Although obvious warping can be avoided, irregularity and mild deviation may still occur, potentially requiring technical refinement. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Dorsal Preservation Rhinoplasty in Asian Hump Noses.

SUMMARY: Dorsal preservation rhinoplasty, which preserves the bony-cartilaginous junction and the keystone area, has been gaining popularity in Western countries for hump nose correction. The authors aimed to report the feasibility, surgical outcome, and technical considerations of dorsal preservation rhinoplasty in Asian hump nose correction. A retrospective case series study was performed on nine patients who had undergone primary dorsal preservation rhinoplasty for hump nose correction. Rhinoplasty was performed by the senior author (H.R.J.) from March of 2019 to December of 2021. Clinical charts, graphic operation records, and standardized photographs of the patients were retrospectively reviewed and analyzed. Operations were performed using an open approach in all patients. Either the push-down technique ( n = 3) or the let-down technique ( n = 6) was used for dorsal preservation. All patients underwent tip modification, with or without radix grafting, together with dorsal preservation rhinoplasty. Bony step-off camouflage at the transverse osteotomy site was required in three patients. After surgery, both the nasofacial and rhinion angles exhibited significant changes ( P = 0.008). In all cases, hump reduction was successful, without recurrence or saddle nose, and no major complications occurred. All patients were satisfied with the aesthetic and functional results. Dorsal preservation rhinoplasty seems to be a viable option for correcting Asian hump noses. Technical considerations include a preference for the open approach; camouflage of bony step-off deformity; and strategic management of the septal cartilage, in consideration of tip modification.

Gossypiboma in the nasal septum after septorhinoplasty: a case study.

This report describes a case of gossypiboma in the septum. A 31-year-old woman presented with nasal obstruction and crusting that started 2 years previously after she underwent rhinoseptoplasty in another private clinic. Physical examination disclosed remaining posterior septal deviation to the left side with septal mucosal erosion on the left side. Under general anesthesia, the septal flap was elevated on the left side of the nasal cavity. A gossypiboma was found around the perpendicular ethmoid plate and between the septal flaps. The perpendicular ethmoid plate was resected and the gossypiboma was removed under endoscopy. Because of severe adhesion between the gossypiboma and the septal mucosa, removal of the gossypiboma resulted in a defect on the left mucoperichondrial flap. Right inferior turbinate mucosa was harvested and grafted on the mucosal defect of the left side. Five months after the operation, the nasal cavity showed a straight septum with a well-healed mucosa without any nasal symptoms. This case is a reminder of the fundamental importance of absolute care at every step of rhinologic surgery.

The effect of septorhinoplasty on quality of life and nasal function in Asians.

This is the first study that aimed to assess the effects of septorhinoplasty on quality of life (QOL) in an Asian population. The study consisted of 2 parts. First, the Derriford Appearance Scale 59 (DAS-59) was translated into Korean, and the reliability and validity were assessed by administering the Korean version of Derriford Appearance Scale 59 (DAS-59K) and 36-item short-form health survey to 88 inpatients scheduled for operations. Then, a prospective study was conducted which included 31 patients who underwent primary septorhinoplasty from October 2008 through May 2009. The changes in QOL and nasal symptoms were evaluated by comparing the preoperative and postoperative 3 month DAS-59K and nasal obstruction symptom evaluation scales. Principal component analysis of the DAS-59K showed an optimum 5-factor and the Cronbach α for each factor was greater than 0.7. Significant correlation was found between the DAS-59K and 36-item short-form health survey. Objective evaluation showed at least an improvement in every patient. After septorhinoplasty, there was improvement at scores related to general self-consciousness, negative self-concept, and physical stress (P < 0.05). The pattern of improvement differed by sex, age, and the presence of external nose deviation. Mean nasal obstruction symptom evaluation scores decreased significantly after surgery. The DAS-59K is a reliable and valid test, which can be a useful tool to assess individual response to living with problems of appearance. Septorhinoplasty improves both QOL and nasal function which should be taken into consideration in future counseling of individual patients expecting septorhinoplasty.

Nuances with the Asian tip.

Rhinoplasty among Asians includes peculiarities that distinguish the procedure from its Caucasian counterpart. These peculiarities can be perceived as nuances to surgeons unfamiliar to Asian rhinoplasty. Characteristics of the Asian tip surgery will be addressed with emphasis on surgical techniques commonly used to obtain reliable results.

Feminization of the forehead in a transgender: frontal sinus reshaping combined with brow lift and hairline lowering.

UNLABELLED: The case of a 39-year-old male-to-female transgender patient who underwent feminization of his masculine forehead is presented. Surgical techniques to feminize his forehead were as follows. The outer table of the frontal sinus was removed and divided into four pieces with an oscillation saw. These pieces were reshaped, regrafted, and fixed back along with two microplates. The bilateral supraorbital ridges were shaved with a surgical bur. Brow lifting and lowering of the frontolateral hairline were performed simultaneously. There were no complications during the 1-year follow-up. The patient is satisfied with the more feminine forehead. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article.

Presentation Patterns and Surgical Management of the Complications of Thread Rhinoplasty.

OBJECTIVES: Nonsurgical rhinoplasty using threads has gained popularity in recent years. While the benefits of this procedure have been emphasized, possible complications and their management are not well-known. This study aimed to present the surgical management and results of the complications of thread rhinoplasty. METHODS: We retrospectively reviewed the medical records of seven patients who underwent revision rhinoplasty due to the complications of thread rhinoplasty from January 2018 to May 2021. The presentation of complications, detailed surgical procedures, and outcomes of revision rhinoplasty were reviewed. RESULTS: Visible or extruded threads at the tip were the most common complication, followed by dorsum irregularity. All the threads were unabsorbed and intact in shape, even several years after insertion. Thread removal necessitated careful tissue dissection, resulting in the loss of tip support and dorsal irregularity. To restore the tip support and camouflage the dorsum shape, an autologous tissue graft was needed. CONCLUSION: Removal of threads at the tip and dorsum was accompanied by structural weakening and partial tissue loss, which required tip support restoration and dorsum camouflage.

Genetic Variants and Clinical Phenotypes in Korean Patients With Hereditary Hemorrhagic Telangiectasia.

OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by recurrent epistaxis, telangiectasia, and visceral arteriovenous malformations (AVMs). Activin A receptor-like type 1 (ACVRL1/ALK1) and endoglin (ENG) are the principal genes whose mutations cause HHT. No multicenter study has yet investigated correlations between genetic variations and clinical outcomes in Korean HHT patients. METHODS: Seventy-two members from 40 families suspected to have HHT based on symptoms were genetically screened for pathogenic variants of ACVRL1 and ENG. Patients with genetically diagnosed HHT were also evaluated. RESULTS: In the HHT genetic screening, 42 patients from 24 of the 40 families had genetic variants that met the pathogenic criteria (pathogenic very strong, pathogenic strong, pathogenic moderate, or pathogenic supporting) based on the American College of Medical Genetics and Genomics Standards and Guidelines for either ENG or ACVRL1: 26 from 12 families (50%) for ENG, and 16 from 12 families (50%) for ACVRL1. Diagnostic screening of 42 genetically positive HHT patients based on the Curaçao criteria revealed that 24 patients (57%) were classified as having definite HHT, 17 (41%) as having probable HHT, and 1 (2%) as unlikely to have HHT. Epistaxis was the most common clinical presentation (38/42, 90%), followed by visceral AVMs (24/42, 57%) and telangiectasia (21/42, 50%). Five patients (12%) did not have a family history of HHT clinical symptoms. CONCLUSION: Only approximately half of patients with ACVRL1 or ENG genetic variants could be clinically diagnosed as having definite HHT, suggesting that genetic screening is important to confirm the diagnosis.

Revision rhinoplasty in asians.

Revision rhinoplasty is increasing in the Asian population. We present causes of revision rhinoplasty in Asians, introduce operative techniques, report surgical results, and make implications for ways to assist in their prevention. During a period of 3 years, 52 patients (among 623 rhinoplasties) who had undergone revision rhinoplasty with at least 1 year follow-up were included in this study. A retrospective review was performed using chart review, graphic operation records, pre- and postoperative photographs. Outcome was determined by subjective assessment of 2 blinded rhinoplasty surgeons. The patients were classified into 2 groups; revision because of alloplastic implant-related problems (33 cases) and revision unrelated to alloplastic implants (19 cases). The most common reason for revision in the alloplastic implant-related group was deviation of the implant, followed by implant extrusion, foreign body reaction, and infection. Reasons for revision in the alloplastic implant-unrelated group included upper two-thirds problems in 12 cases, and tip problems in 7. Autologous cartilage was used in the majority of revision cases. Subjective evaluation of postoperative results were good in 29 (69%), fair in 10 (24%), and poor in 3 (7%). Revision rhinoplasty in Asians was most commonly associated with alloplastic implants. Proper and judicious use of alloplastic implants is important to reduce the chances for revision surgery in Asians.

Nasal tip augmentation in Asians using autogenous cartilage.

OBJECTIVES: To present surgical techniques and results of nasal tip augmentation in Asian noses and suggest a surgical algorithm for a successful outcome. STUDY DESIGN: A case series at a tertiary hospital. SUBJECTS AND METHODS: One hundred and seven patients who had undergone nasal tip augmentation using autogenous cartilages from January 2005 to December 2006 were enrolled in the study. Medical records, graphic operation records, and standardized patient photographs were retrospectively reviewed. Initial diagnoses, techniques for tip augmentation, combined tip surgery techniques, surgical results, and complications were analyzed. RESULTS: Initial diagnoses included deviated nose, hump nose, saddle nose, low-profile nose, and short nose. An external approach was used in 74 percent and intranasal approach in 26 percent. For augmentation of the tip projection, onlay grafts with or without columellar strut (59%) and septal extension grafts with or without onlay grafts (25%) were the most commonly used techniques. Ninety-three percent of the patients were satisfied with the results. Complications included tip deviation and visible tip graft. CONCLUSION: Augmentation of nasal tip projection in Asians can be effectively performed using autogenous cartilage. Onlay graft and septal extension graft are two important techniques for a successful outcome.

Computed tomography versus nasal endoscopy for the measurement of the internal nasal valve angle in Asians.

CONCLUSIONS: The internal nasal valve (INV) angle in Asians is 21.6 degrees +/-4.5 degrees and it is significantly larger than that of Caucasians. The reconstructed CT method has better reproducibility than the endoscopic method in measuring the INV angle. OBJECTIVES: The INV is an area of interest for nasal surgeons due to its functional significance in rhinoplasty and septoplasty. This study was designed to evaluate the size of the INV angle in an Asian population by measuring the angle through reconstructed CT scans and nasal endoscopy. PATIENTS AND METHODS: Thirty-eight ostiomeatal unit CTs and 24 endoscopic photos of patients who had minimal or no sinonasal problems were analyzed. CT images that had been reconstructed perpendicular to the acoustic axis and endoscopic photos were used to measure the INV angle. Each method was verified as to reproducibility and the angles measured by the two methods were compared. RESULTS: The INV angle of the Asians measured by CT scan was 21.6 degrees +/-4.5 degrees . This value was significantly larger than that of the Caucasians, which has been reported to be 11.4 degrees +/-2.6 degrees (p<0.001). The INV angle measured endoscopically was 19.3 degrees +/-3.6 degrees . Reproducibility of the reconstructed CT method was good (p<0.001), while the reproducibility of the endoscopic method was poor (p=0.093). The correlation between the two methods was also poor (p=0.107).

Nasal cavity paraganglioma with malignant transformation: a case report.

BACKGROUND: In this report, we describe a young woman with a nasal cavity paraganglioma with malignant transformation. METHODS AND RESULTS: A 23-year-old woman presented with frequent right-sided epistaxis. Physical examination revealed a pedunculated mass originating from the right superior turbinate and filling the posterior nasal cavity. The endoscopically removed mass was composed of a reddish anterior portion and a white, flesh-looking posterior portion, the latter comprising the majority of the tumor. Histologically, the anterior portion showed a paraganglioma and the posterior portion showed a separate malignant lesion simulating Ewing's sarcoma/PNET. She underwent wide endoscopic excision including the site of tumor origin and has been followed up for 3 years without any evidence of disease recurrence. CONCLUSION: This is a rare case of nasal cavity paraganglioma that had transformed into a malignant tumor.

Common Sites, Etiology, and Solutions of Persistent Septal Deviation in Revision Septoplasty.

OBJECTIVES: To investigate the common causes of persistent septal deviation in revision septoplasty and to report the surgical techniques and results to correct them. METHODS: A total of 100 consecutive patients (86 males) who had revision septoplasty due to persistent septal deviation from 2008 and 2014 were included in the study. Their mean age was 35.6 years and the mean follow-up duration was 9.1 months. Presenting symptoms, sites of persistent septal deviation, techniques used to correct the deviation, and surgical results were reviewed. RESULTS: The mean interval between primary and revision surgery was 6.2 years. Forty-eight patients received revision septoplasty and 52 received revision septoplasty combined with rhinoplasty. Nasal obstruction was the most presenting symptom in almost all patients. The most common site of persistent septal deviation was middle septum (58%) followed by caudal septum (31%). Correcting techniques included further chondrotomy and excision of deviated portion in 76% and caudal batten graft in 39%. Rhinoscopic and endoscopic exams showed straight septum in 97% and 92 patients had subjective symptom improvement postoperatively. CONCLUSION: Middle septum and caudal septum were common sites of persistent deviation. Proper chondrotomy with excision of deviated middle septum and correction of the caudal deviation with batten graft are key maneuvers to treat persistent deviation.