Chronic Recurrent Multifocal Osteomyelitis Associated With Inflammatory Bowel Disease Successfully Treated With Infliximab

Chronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory bone disorder presenting with sterile osteomyelitis, most often presenting in childhood. Although the etiology is understood incompletely, its association with other auto-inflammatory diseases including inflammatory bowel disease (IBD); psoriasis; Wegener’s disease; arthritis; and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome suggests that dysregulated innate immunity may play an important role in the pathogenesis. We report a case of a 13-year-old boy with CRMO associated with Crohn’s disease (CD) successfully treated with infliximab after failure of non-steroidal anti-inflammatory drug (NSAID) treatment. He initially was diagnosed with CRMO based on symmetric and aseptic bone lesions with no fever, lack of response to antibiotic treatment, vertebral involvement, and normal blood cell counts. Despite five months of NSAID treatment, his musculoskeletal symptoms were aggravated, and he developed gastrointestinal symptoms. Finally, he was diagnosed with CRMO associated with CD. Due to the severity of symptoms, infliximab was initiated and produced symptom improvement. This case supports infliximab as another choice for treatment of bowel symptoms in addition to the bone and joint symptoms of CRMO when other first-line treatments are ineffective.

Characterization of the Onychomatricodermis Containing Onychofibroblasts of the Nail Unit :Histology, Immunohistochemistry, and Electron Microscopic Study

Background@#We recently discovered the presence of specialized nail mesenchyme below the nail matrix and designated it as onychomatricodermis. @*Objective@#We did further research to characterize the histologic, histochemical, immunohistochemical and ultrastructural features of the onychomatricodermis containing onychofibroblasts in the nail unit. @*Methods@#Ten polydactyly nail unit specimens and 8 nail matrix biopsies were included. H&E-stained slides were reviewed. We did Alcian blue staining and Masson Trichrome staining, as well as immunohistochemical staining for type Ⅰ collagen, CD10, CD13 and CD34. In addition, polydactyly nail units were examined by transmission electron microscopy. @*Results@#In H&E staining, the specialized mesenchyme called onychomatricodermis was observed to be slightly distant from the undersurface of the nail matrix and be less eosinophilic area. Onychomatricodermal onychofibroblasts showed light purple abundant cytoplasm.Masson Trichrome staining revealed fewer collagen fibers within the onychomatricodermis. In Alcian blue staining the onychomatricodermis showed mucin deposition within the onychofibroblasts and around them. Immunohistochemically, type Ⅰ collagen was expressed much less in the onychomatricodermis while it was strongly expressed elsewhere in the nail unit. In nail matrix biopsy specimens onychomatricodermal onychofibroblasts expressed CD10 and CD13 strongly, and expressed CD34 as well. Ultrastructurally, collagen fibrils were found sparsely within the onychomatricodermis, whereas collagen fibrils were densely distributed in the dermis of other parts of the nail unit. @*Conclusion@#We demonstrated that there was less collagen expression in the onychomatricodermis containing onychofibroblasts. In addition, we found morphological and immunohistochemical features of onychomatricodermal onychofibroblasts (onychofibroblasts of Dongyoun). These findings support the presence of onychomatricodermis containing onychofibroblasts in the nail unit.

Secondary Cervicothoracic Scoliosis in Congenital Muscular Torticollis

BACKGROUND: Although secondary cervicothoracic scoliosis frequently occurs in patients with congenital muscular torticollis (CMT), the relationship between scoliosis and CMT has not been evaluated. This study aims to evaluate the effects of surgical release of sternocleidomastoid (SCM) muscle on secondary cervicothoracic scoliosis in patients with CMT and determine factors affecting the improvement of scoliosis after surgical release of SCM muscle. METHODS: Eighty-seven of the 106 patients, confirmed as having secondary cervicothoracic scoliosis with CMT with a minimum 1-year follow-up, were included in this study. Preoperative and last follow-up radiologic outcomes were assessed for the cervicomandibular angle (CMA), Cobb angle of the cervicothoracic scoliosis, and direction of convexity in the scoliosis curve. Patients were divided into two groups to assess the improvement of Cobb angle according to residual growth potential; age ≤ 15 years and > 15 years. The improvement of Cobb angle after surgical release was compared in the two groups. Correlation analysis and multivariable regression analysis were performed to determine the factors affecting the improvement of scoliosis. RESULTS: All the radiologic parameters, such as the Cobb angle and CMA, improved significantly after surgical release (p 15 years (p < 0.001). The improvement of Cobb angle was significantly correlated with age (r = −0.474, p < 0.001) and the preoperative Cobb angle (r = 0.221, p = 0.036). In multivariable regression analysis, age and preoperative Cobb angle were shown to be predisposing factors affecting the improvement of scoliosis. CONCLUSIONS: The results showed that SCM release can be a beneficial treatment for secondary cervicothoracic scoliosis. The improvement of scoliosis was greater when the SCM release was performed before the patient reached the end of growth.

Surgical Results of Limb Lengthening at the Femur, Tibia, and Humerus in Patients with Achondroplasia

BACKGROUND: Results of limb lengthening in patients with achondroplasia were previously reported in many studies. However, the reports of comparison among the three long bones (femur, tibia, and humerus) are rare, especially for the results of crossed lengthening (lengthening of one femur and contralateral tibia followed by that of the opposite side) for the lower limbs. The purpose of this study was to report the surgical results of a series of limb lengthening in achondroplastic or hypochondroplasia patients at our institution. METHODS: Fifteen patients (14 with achondroplasia and 1 with hypochondroplasia) underwent lower limb lengthening of the femur (n = 32) and tibia (n = 28), and 12 of them underwent crossed lengthening. Humeral lengthening was performed in 14 patients (n = 28). The mean age at the first operation was 11.7 years, and the mean follow-up duration was 66.7 months. The healing index, consolidation period index (duration of consolidation period/gained length), and other radiographic indices were analyzed. Limb length discrepancy and hip-knee-ankle alignment in lower limbs, and the occurrence of difficulties were assessed. RESULTS: The average gain in length for the femur, tibia, and humerus was 8.3 cm, 8.5 cm, and 7.4 cm, respectively. The mean healing index was 29.6 days/cm for the femur, 29.0 days/cm for the tibia, and 27.2 days/cm for the humerus. The mean consolidation period index was 14.7 days/cm for the humerus, which was significantly lower than that in the lower limb (17.3 days/cm for the femur and 17.8 days/cm for the tibia). Of the 12 who underwent crossed lengthening, five showed limb length discrepancy ≥ 1.0 cm. Among their 24 lower limbs, three showed valgus alignment ≥ 5° and one showed varus alignment ≥ 5°. Thirty-two pin site infections and three fractures were conservatively managed. Three femoral fractures, eight equinus deformities, and four cases with premature consolidation of the fibula were surgically treated. Obstacle and true complication related to humeral lengthening were not observed. CONCLUSIONS: Humeral lengthening was relatively effective and safe. Careful attention will be needed to avoid the occurrence of limb length discrepancy or malalignment in crossed lengthening.

The Concept of Onychodermis (Specialized Nail Mesenchyme) Is Applicable in Normal Adult Nail Unit

No abstract available.

Recurrence of a Unicameral Bone Cyst in the Femoral Diaphysis

Diaphyseal unicameral bone cysts of the long bone are generally known to originate near the growth plate and migrate from the metaphysis to the diaphysis during skeletal growth. In the case of unicameral bone cysts of diaphyseal origin, recurrence at the same location is extremely rare. We report a case of recurrence of a unicameral bone cyst in the diaphysis of the femur that developed 8 years after treatment with curettage and bone grafting. We performed bone grafting and lengthening of the affected femur with an application of the Ilizarov apparatus over an intramedullary nail to treat the cystic lesion and limb length discrepancy simultaneously.

The Efficacy of Percutaneous Lateral Hemiepiphysiodesis on Angular Correction in Idiopathic Adolescent Genu Varum

BACKGROUND: Percutaneous lateral hemiepiphysiodesis of the lower extremity is a simple and excellent method to correct the angular and length problems cosmetically. However, the efficacy of percutaneous lateral hemiepiphysiodesis is not well established in the literature. The purpose of this study was to evaluate the efficacy of percutaneous lateral hemiepiphysiodesis for angular corrections in adolescent idiopathic genu varum patients with proximal tibia vara and identify the factors affecting the amount of deformity correction of the lower limb in the coronal plane. METHODS: We retrospectively reviewed 20 patients (40 lower limbs) who had percutaneous lateral hemiepiphysiodesis on the proximal lateral tibia between 1997 and 2010. Radiographic evaluations were made using (1) the hip-knee-ankle angle and (2) the length of the tibia. Furthermore, the intercondylar distance was evaluated at the level of the knee joint. Preoperative factors (gender, age, body mass index, intercondylar distance, preoperative hip-knee-ankle angle, remaining growth of tibia, and calculated correctable angle) were analyzed, as well as their correlation with the degree of the actual correction angle. RESULTS: The amount of coronal deformity of the lower limb was improved from its preoperative state. The median average of hip-knee-ankle angle improved from 8.0degrees (interquartile range [IQR], 7.0degrees to 10.0degrees) preoperatively to 3.0degrees (IQR, 2.5degrees to 4.0degrees) at the final follow-up (p < 0.001). The median percent ratio of the angular correction was 60% (IQR, 50% to 71.3%). The correlation coefficients were -0.537, 0.832, 0.791, and 0.685 for the bone age, preoperative hip-knee-ankle angle, the remaining growth of tibia, and calculated correctable angle, respectively. CONCLUSIONS: Despite the excellent cosmetic outcome of percutaneous lateral hemiepiphysiodesis on the proximal lateral tibia in adolescent idiopathic genu varum, the effect was limited in most cases. For optimum results, surgery a few months earlier is recommended, rather than at the calculated operation time.

Outcomes of Combined Shelf Acetabuloplasty with Femoral Varus Osteotomy in Severe Legg-Calve-Perthes (LCP) Disease: Advanced Containment Method for Severe LCP Disease

BACKGROUND: Standard treatments may provide adequate containment in mild to moderate Legg-Calve-Perthes disease (LCPD), but they can be problematic in more severe cases. The purpose of this study was to report the results of combined shelf acetabuloplasty with femoral varus osteotomy in severe LCPD. METHODS: We reviewed 12 patients who had undergone combined shelf acetabuloplasty with femoral varus osteotomy. The indications for this type of operation were: (1) above 8 years of age at clinical onset; (2) massive femoral epiphysis involvement (Catterall group 4, lateral pillar C); (3) femoral head lateral subluxation on the anteroposterior radiograph; and (4) impending hinged abduction on preoperative magnetic resonance imaging or arthrography. The mean age was 9.3 years (range, 8 to 10.8 years). The patients were clinically evaluated with Iowa hip score and leg length discrepancy at the final follow-up. Radiographic outcome was assessed using the Stulberg classification to evaluate femoral head sphericity. The presence of osteoarthritis was evaluated by the Tonnis classification. Correlation analysis was conducted to analyze the preoperative factors that were strongly associated with patients' outcomes. RESULTS: The mean follow-up period was 10.1 years (range, 7.1 to 13.2 years). Functional grade was excellent in all patients at last follow-up (mean, 92; range, 82 to 99). The mean leg length discrepancy after skeletal maturity was 0.9 cm (range, 0 to 1.7 cm). There were no significant complications or need for additional surgery. Radiographically, 92% of patients reached satisfactory outcomes: Stulberg grade I, 0 cases; Stulberg grade II, 4 cases (34%); Stulberg III, 7 cases (58%), Stulberg IV, 1 case (8%); and Stulberg V, 0 cases. There was no osteoarthritis by Tonnis classification. CONCLUSIONS: The surgical outcomes for combined shelf acetabuloplasty with femoral varus osteotomy in severe LCPD patients over 8 years old are comparable with other advanced surgical methods. In the cases of severe disease that match our inclusion criteria, our containment method could be another treatment option.

Prognostic Factors of Septic Arthritis of Hip in Infants and Neonates: Minimum 5-Year Follow-up

BACKGROUND: The authors conducted the present study to identify clinical and radiological prognostic factors in infants and neonates with septic arthritis of the hip. METHODS: The authors retrospectively reviewed the records of 31 patients with septic arthritis of the hip. All of the patients were younger than 18 months old. Follow-up periods ranged from 5 to 17 years. The following potential variables for predicting the prognosis were included in the assessment: gender, age, underlying diseases, duration of symptoms, changes of hip joint in X-ray, concomitant osteomyelitis, elevation of erythrocyte sedimentation rate and C-reactive protein, sepsis, pus drainage, synovial fluid culture, and infecting organisms. Clinical and radiological prognoses were analyzed at the final follow-up. RESULTS: Univariate analysis demonstrated that radiological prognoses were poorer in patients who had underlying diseases, a longer duration of symptoms, and pus drainage. However, on multivariate analysis, only the variable-duration of symptoms-was found to be statistically related with a poor radiological prognosis. CONCLUSIONS: Although poor prognosis for patients with several underlying diseases and radiological changes has already been established, a favorable outcome might be expected with prompt surgical drainage and appropriate antibiotics.

Surgical Treatment of Congenital Hallux Varus

BACKGROUND: The purpose of this study was to report outcomes of congenital hallux varus deformity after surgical treatment. METHODS: We evaluated ten feet of eight patients with a congenital hallux varus deformity, including four feet combined with a longitudinal epiphyseal bracket (LEB). There were seven male patients and one female patient with a mean age of 33 months (range, 7 to 103 months) at the time of surgery. Two patients were bilaterally involved. The mean duration of follow-up was 5.9 years (range, 2.3 to 13.8 years). Clinical outcomes were assessed according to the criteria of Phelps and Grogan. Surgical procedures included the Farmer procedure, the McElvenny procedure or an osteotomy at the first metatarsal or proximal phalanx. RESULTS: The clinical results were excellent in two feet, good in six and poor in two feet. The LEB was associated with hallux varus in four feet and were treated by osteotomy alone or in conjunction with soft tissue procedure. CONCLUSIONS: Congenital hallux varus was successfully corrected by surgery with overall favorable outcome. Preoperatively, a LEB should be considered as a possible cause of the deformity in order to prevent recurrent or residual varus after surgery.

Recent Trends in Treatment of Supracondylar Fracture of Distal Humerus in Children

No abstract available.

Treatment of Neglected Monteggia Fracture-Dislocation in Children / 대한정형외과학회잡지

PURPOSE: Our purpose is to evaluate the results of the operative treatment in neglected Monteggia fracture-dislocation in children. MATERIALS AND METHODS: We retrospectively analyzed 10 elbows in 10 patients who underwent surgery. All patients were classified as Bado type I, except one with type III. The mean duration of follow up was 2 years and 5 months. The mean age at the time of operation was 10 years and the mean time from injury to operation was 7 months. All 10 patients underwent open reduction of the radial head and reconstruction of annular ligament. Ulnar osteotomy was performed in 9 cases. Clinical assessment was done by Bruce et al.'s rating system. RESULTS: All 10 patients gained a mean of 35degrees of extension-flexion arc, however lost a mean of 29degrees of pronation-supination arc. And there were three complications, including dislocation of radial head in two patients and breakage of transarticular K-wire in one patient. According to Bruce et al.'s rating system, there were 4 excellent, 1 good, 3 fair, and 2 poor results. CONCLUSION: We found that the effect of the operative treatment of neglected Monteggia fracturedislocation in children was limited in majority of the patients. Particularly, the loss of pronation-supination arc was noticed postoperatively in most patients.

Congenital Clubfoot Treated with the Ponseti Method / 대한정형외과학회잡지

PURPOSE: This study examined the Ponseti method for the nonsurgical treatment of a congenital clubfoot. MATERIALS AND METHODS: A total of 35 patients (52 clubfeet) were evaluated. All patients were treated by serial manipulation and casting as described by Ponseti. The patients were divided in two groups (Group 1: the result was successful and did not require extensive corrective surgery, Group 2: the result was unsuccessful and required extensive corrective surgery). The outcome in the two groups was compared in terms of the severity of initial deformity, initial roentgenographic findings, Achilles tenotomy, numbers of Ponseti casts before the Achilles tenotomy, total numbers of casting, age at the initial treatment, bilaterality, gender and compliance of the brace. RESULTS: Twenty eight patients (42 feet, 80.7%) were corrected successfully without extensive corrective surgery (Group 1). Six patients (10 feet, 19.3%) required extensive corrective surgery (Group 2). The requirement of extensive corrective surgery was not related to the initial roentgenographic findings, number of Ponseti casts before the Achilles tenotomy, total numbers of castings, age at the initial treatment, bilaterality and gender. However, it was related to the severity of the initial deformity and compliance of the brace. CONCLUSION: The result of a congenital clubfoot treated with the Ponseti method was successful in more than 80% of patients. It was affected by the severity of the initial deformity and compliance of the brace. However, a long-term follow-up will be needed to evaluate the recurrence and residual deformities.

Congenital Pseudarthrosis of the Clavicle: Report of 4 Cases Treated with Surgical Methods / 대한정형외과학회잡지

Congenital pseudarthrosis of the clavicle is a rare condition, and optimal treatment strategies are controversial because this benign condition rarely produces functional disabilities except for an unsightly lump and occasional mild weakness of muscle strength around the shoulder girdle. Nevertheless, its prominence increases with age and it can cause cosmetic problems by drooping and shortening of the shoulder. Thoracic outlet syndromes have been reported in a few patients who did not receive treatment. The authors here report on congenital pseudarthrosis of a unilateral clavicle in 3 patients and bilateral clavicles in 1 patient. All patients were treated with autogenous iliac bone grafts and internal fixation, with a complete union and cosmetically satisfying results.

Lateral Closing Wedge Supracondylar Osteotomy of the Humerus in Children with Cubitus Varus Deformity / 대한정형외과학회잡지

PURPOSE: To evaluate the effectiveness, cosmetic and functional improvement of a supracondylar lateral closing wedge osteotomy of the humerus as a treatment for cubitus varus deformity in children. MATERIALS AND METHODS: Forty-eight children with cubitus varus underwent a lateral closing wedge osteotomy, and were followed up for at least 1 year. RESULTS: There were no complications such as a loss of correction, infection, or neurapraxia. The immediate postoperative lateral condylar prominence and secondary lazy S deformity was in proportion to the preoperative severity of the cubitus varus. However, it was lower at the last follow-up, and was related to the extent of preoperative cubitus varus, length of follow-up and age. CONCLUSION: A supracondylar lateral closing wedge osteotomy of humerus is an easy and effective surgical treatment for a posttraumatic cubitus varus of children. In addition, it shows good cosmetic results with good remodeling of the lateral condylar prominence of children.

Upper Extremity Fractures in Children: Prospective Epidemiological Study of Tertiary Medical Institutes / 대한정형외과학회잡지

PURPOSE: To investigate the general epidemiologic features of upper extremity fractures in children. MATERIALS AND METHODS: The records of the 589 in-patient children treated for upper extremity fractures over a 1-year period at 7 different hospitals were collected prospectively and analyzed. The severity of trauma was classified as slight, moderate or severe. This study examined the incidence of various upper extremity fractures and performed statistical analysis according to the epidemiologic parameters including age, gender and season. RESULTS: The average age of the children was 7.8 years. The average age of boys (8.5 years) was older than girls (6.4 years). The majority of fractures occurred at between 4 and 7 years of age (36%). The male to female ratio was approximately 2:1. The male predominance increased with age and increased dramatically in the age group, 12-16 years (5.8:1). The left side was injured more frequently (56%), and there was no difference between genders. The occurrence of fractures varied with the seasons with peaks in May (14.1%) and August (12.2%), and it was closely related to the temperature (r=0.778). The most common fractures were the supracondylar fractures of the humerus (32.6%), followed by distal radius fractures (18.2%), lateral condylar fractures (15.8%), radio-ulna shaft fractures (8%), clavicle fractures (4.2%), proximal humerus fractures (2.6%) and humerus shaft fractures (2.4%). Ninety seven percent of fractures were caused by a slight and moderate trauma. Fifty four percent of injured children underwent surgery, and 84% of operations were performed on the fractures around the elbow. CONCLUSION: This study examined the epidemiologic features of the upper extremity fractures in children.

Congenital Trigger Thumb; Developmental Flexion Contracture of the Thumb / 대한정형외과학회잡지

PURPOSE: To investigate the etiology, pathologic finding, main symptom, and ideal age for operative correction, trigger thumb in children, without any residual symptom and complications. MATERIALS AND METHODS: 162 children (199 thumbs), who underwent operative treatment, formed the basis of this study. We investigate the main symptom, trauma history, other medical history, age of operation, relief of symptoms and complications after surgery. Two specimens were examined histolgically. RESULTS: Only four (2.5%) thumbs demonstrated triggering at birth. All patients had flexion contracture of the interphalangeal joint of the thumb. There were nodules in 50 thumbs (25.3%) and triggering in 38 thumbs (19.2%). The average age at the time of surgery was forty months. All patients, had complete resolution of triggering after surgery and at the time of follow-up examinations, except for one patient who demonstrated a prominent wound scar. In the histological analysis, proliferation of fibroblasts and dense collagen material without inflammation and degeneration were characteristic findings. CONCLUSION: Trigger thumb in children is a developmental condition caused by A1 pulley hypertrophy. The main symptom was flexion contracture. Therefore the term, developmental flexion contracture of the thumb, "rather than congenital trigger thumb, " is more appropriate. Surgical intervention is inexpensive, simple, safe and successful in preschool-aged children with persistent symptoms.

Operative Treatment of Congenital Muscular Torticollis in Children / 대한정형외과학회잡지

PURPOSE: To analyze the clinical result of surgically treated congenital muscular torticollis in children. MATERIALS AND METHODS: Forty seven patients who had not received any prior medical treatment or who recurred after the initial operation were included in this study. The patients were divided into two groups (Group 1, 1-4 years old and Group 2, 5-16 years old). The average follow-up period was 46 months. Clinical results were assessed by using motion deficits, craniofacial asymmetry, scar, band, subjective assessment, and by head tilt. RESULTS: There were no statistical differences between two groups in craniofacial asymmetry, band, subjective assessment, head tilt and overall scores. But motion deficit, scar, and head tilt revealed more successful results in Group 2 than Group 1. CONCLUSION: Generally, the older age group had better understanding and compliance to postoperative program. Therefore, the surgical treatment of the muscular torticolis should be postponed until the patients can successfully cooperate with the postoperative brace and exercise program.

Joint Contracture and Radiologic Features in Mucopolysaccharidosis / 대한정형외과학회잡지

PURPOSE: To evaluate the clinical manifestations of contracted joints and the radiological features in mucopolysaccharidosis(MPS). MATERIALS AND METHODS: From January 1996 to March 2002, 15 children from a pool of children diagnosed with MPS through a fibroblast culture and an enzyme assay, who could tolerate a large umber of examinations, underwent orthopedic physical and radiological examinations. RESULTS: There were limitations in the abduction and internal rotation of the shoulder, extension limitation of the wrist, and internal rotation of the hip joint and flexion contractures of the elbow and DIP joints. Scoliotic deformities were all within the physiological curve. There were only three cases of a dorsolumbar kyphotic change and there were no neurological deficits due to the spinal deformities. The mean bone age was delayed compared with the mean chronological age. As the chronological age increased, the gap between the chronological age and the bone age increased. CONCLUSION: Joint contracture, which is the most severe symptom in orthopedic aspect, was more severe in the upper extremities than in the lower extremities. The spinal deformity was relatively mild and there were no neurological problems. The bone age tended to be delayed as the chronological age increased.

Treatment of Brachymetatarsia by Distraction Osteogenesis: Operative Technique and Results / 대한정형외과학회잡지

PURPOSE: To report on a new operative technique of distraction osteogenesis and it's results in brachymetatarsia. MATERIALS AND METHODS: 17 patients (39 metatarsal bones) formed the basis of this study (male: female-2: 15). To prevent varus deformity of the hindfoot after lengthening, all screws were inserted at the same level from the medial aspect of the first metatarsal bone for horizontal distraction in the anterior direction, rather than distraction in the direction of the anatomical axis. Also, care was taken to ensure that the screw for the fourth metatarsal bone did not interpose with the fifth extensor tendon. RESULTS: All cases achieved satisfactory lengthening and bony union, except 1 case. The healing index increased with patient's age. Plantar capsular release was performed in seven cases, six of which had been previously operated on bilaterally. There was no hindfoot varus deformity or entrapment of the fifth extensor tendon on final follow up. CONCLUSION: Varus deformity of the hindfoot can be prevented by horizontal distraction of the first metatarsal bone. Also, entrapment of the fifth extensor tendon can be prevented by careful handling of the fifth extensor tendon during operation on the 4th metatarsal bone. Complications of stiffness or of an increase in treatment period were mainly found in bilaterally operated or relatively old (over 20 year-old) patients.