Reconstruction of the symphysis pubis to repair a complex midline hernia in the setting of congenital bladder exstrophy.

PURPOSE: A 40-year-old man with congenital midline defect and wide pubic symphysis diastasis secondary to bladder exstrophy presented with a massive incisional hernia resulting from complications of multiple prior abdominal repairs. Using a multi-disciplinary team of general, plastic, and urologic surgeons, we performed a complex hernia repair including creation of a pubic symphysis with rib graft for inferior fixation of mesh. METHODS: The skin graft overlying the peritoneum was excised, and the posterior rectus sheath mobilized, then re-approximated. The previously augmented bladder and urethra were mobilized into the pelvis, after which a rib graft was constructed from the 7th rib and used to create a symphysis pubis using a mortise joint. This rib graft was used to fix the inferior portion of a 20 × 25 cm porcine xenograft mesh in a retro-rectus position. With the defect closed, prior skin scars were excised and the wound closed over multiple drains. RESULTS: The patient tolerated the procedure well. His post-operative course was complicated by a vesico-cutaneous fistula and associated urinary tract and wound infections. This resolved by drainage with a urethral catheter and bilateral percutaneous nephrostomies. The patient has subsequently healed well with an intact hernia repair. The increased intra-abdominal pressure from his intact abdominal wall has been associated with increased stress urinary incontinence. CONCLUSIONS: Although a difficult operation prone to serious complications, reconstruction of the symphysis pubis is an effective means for creating an inferior border to affix mesh in complex hernia repairs associated with bladder exstrophy.

The transforming growth factor-beta 3 knock-out mouse: an animal model for cleft palate.

The recent report of a transforming growth factor-beta 3 (TGF-beta 3) knock-out mouse in which 100 percent of the homozygous pups have cleft palate raised the question as to the potential usefulness of these animals as a model for cleft palate research. The specific aim in this study was to carefully document the anatomy of the cleft palate in the TGF-beta 3 knock-out mice as compared with wild type controls. Special attention was paid to the levator veli palatini muscle, the tensor veli palatini muscle, and their respective innervation. Because the TGF-beta 3 knock-out is lethal in the early perinatal period and because the heterozygotes are phenotypically normal, polymerase chain reaction was required to genotype the animals before mating. Time-mated pregnancies between proven heterozygotes were then delivered by cesarean section at gestational day 18.5 to prevent maternal cannibalism of homozygote pups. All delivered pups were killed and their tails processed by polymerase chain reaction to verify genotype. The heads were then fixed and sectioned in axial, coronal, or sagittal planes. Sections were stained with hematoxylin and eosin or processed for immunohistochemistry with nerve specific protein gene product 9.5 and calcitonin gene-related peptide antibodies. Sections were analyzed in a serial fashion. Nine wild type control animals were analyzed along with nine TGF-beta 3 knock-out homozygotes. Time matings between proven heterozygotes yielded wild type pups, heterozygote pups, and homozygote knock-out pups in the expected mendelian ratios (28 percent to 46 percent to 26 percent; n = 43). The results demonstrated 100 percent clefting in the homozygous TGF-beta 3 knock-out pups. Complete clefting of the secondary palate was seen in four of nine and incomplete clefting was seen in five of nine. The levator veli palatini and tensor veli palatini muscles were demonstrated coursing parallel to the cleft margin in all cleft mice. The orientation of these muscles differs from the normal transverse sling of the levator veli palatini muscle and the normal palatine aponeurosis of the tensor veli palatini muscle at the soft palate in control animals. Innervation of the levator veli palatini muscle by cranial nerve IX and the tensor veli palatini muscle by cranial nerve V were demonstrated in both cleft and control animals by use of immunohistochemistry with nerve-specific antibodies. Demonstration of a teratogen-free, reproducible animal model of clefting of the palate with a known, single-gene etiology is an important step in the systematic understanding of a congenital defect whose multifactorial etiology has hampered previous research efforts. This study presents a detailed anatomic description of such a model, including a description of the muscular anatomy and the innervation of the muscles of the palate. Because of early perinatal mortality, this model has limited applications for postnatal studies.

Unilateral aplasia of the middle cranial fossa floor in atypical hemifacial microsomia.

We present the first report of a patient with atypical hemifacial microsomia (HFM) and unilateral aplasia of the floor of the middle cranial fossa, glenoid fossa, and portions of her posterior fossa. The patient also developed a Chiari I malformation with cervical syrinx over a 3-year interval. This case report highlights the critical role of imaging in revealing serious, but clinically occult, structural abnormalities, as well as the evolution in the pathogenetic understanding of HFM.

Abnormal coagulation during pediatric craniofacial surgery.

INTRODUCTION: This prospective study of children undergoing major craniofacial surgery was undertaken to determine whether abnormal hemostasis occurred and to characterize any coagulopathy found. METHODS: Coagulation tests, blood loss and blood product transfusions were recorded perioperatively. Packed red blood cells (PRBC) were transfused to maintain target hematocrit. Patients with blood loss >100 ml/kg (group A, n = 5) were compared to patients with blood loss <100 ml/kg (group B, n = 22) using Mann-Whitney U test (p < 0.05). RESULTS: Twenty-seven children (age range 2.9--27.9 months) had median total blood loss of 64 ml/kg. At completion of surgery, median coagulation values differed significantly between groups for prothrombin time (A: 16.6 s; B: 13.8 s), partial thromboplastin time (A: 44 s; B: 29 s), thrombin time (A: 28 s; B: 23 s), thromboelastograph reaction time (A: 7 mm; B: 4 mm), prothrombin fragment F1.2 (A: 1.9 nmol/l; B: 3.3 nmol/l) and platelet count (A: 174 K/mm(-3); B: 239 K/mm(-3)). Fibrinolysis was not associated with blood loss. Median units transfused were in group A 3 units and group B 1 unit (p = 0.001). All patients received PRBC transfusions but only group A patients received other blood products (fresh frozen plasma, platelets). CONCLUSION: Children transfused with PRBC during craniosynostosis repair can become coagulopathic from coagulation factor depletion when hemorrhage approaches 1.5 times estimated blood volume.

Results with Furlow palatoplasty in management of velopharyngeal insufficiency.

A retrospective study was undertaken to assess speech outcomes in patients undergoing Furlow palatoplasty. Since 1994, the authors have used the position of the levator veli palatini musculature to determine type of surgical intervention recommended for the management of velopharyngeal insufficiency. Furlow palatoplasty has been used in patients with clinical evidence of sagittally oriented levator veli palatini musculature. Forty-eight patients who underwent a Furlow palatoplasty between June of 1994 and August of 1998 were included. All patients underwent preoperative and postoperative perceptual speech analyses to describe velopharyngeal insufficiency severity, nasal air emissions, and resonance, and preoperative nasendoscopy to assess velopharyngeal gap size and palatal and lateral pharyngeal wall movement. Other patient characteristics considered included gender, age at time of surgery, previously repaired cleft palate, submucous cleft palate, and syndrome diagnosis. Speech outcomes were determined on the basis of postoperative perceptual speech analyses and were categorized in one of three ways: (1) complete resolution of velopharyngeal insufficiency, (2) substantial improvement of velopharyngeal insufficiency, and (3) audible residual velopharyngeal insufficiency. Complete resolution of velopharyngeal insufficiency was defined as normal resonance and an absence of nasal air emissions. Substantial improvement of velopharyngeal insufficiency was defined as an improvement of at least two categories in velopharyngeal insufficiency severity in those patients without complete resolution. Audible residual velopharyngeal insufficiency refers to patients with postoperative velopharyngeal insufficiency severity ratings of mild, moderate, or severe. The male:female ratio in the study was 27:21. Twelve patients were syndromic; three had velocardiofacial syndrome. The median age at surgery was 6.5 years (range, 2 to 22 years). The average duration of follow-up was 14.7 months (range, 1.3 to 58.6 months). Postoperatively, the severity of velopharyngeal insufficiency was rated as none in 19 of the 48 patients (39.6 percent), minimal in eight (16.7 percent), mild in six (12.5 percent), moderate in nine (18.75 percent), and severe in six (12.5 percent). Substantial improvement was seen in seven of the 29 patients without complete resolution. There was a significant association between male gender and complete resolution of velopharyngeal insufficiency (p < 0.05). Presence of syndrome and female gender was associated with audible residual velopharyngeal insufficiency (p < 0.05). The main complication was palatal fistula (two cases). In conclusion, most patients who underwent a Furlow palatoplasty had a complete resolution or substantial improvement of velopharyngeal insufficiency postoperatively, and there were few surgical complications.

Inhibition of apoptosis: a potential mechanism for syndromic craniosynostosis.

The biologic pathogenesis of syndromic craniosynostosis remains unknown. The purpose of this investigation was to determine whether specific biologic differences exist between normal calvarial osteoblasts and osteoblasts derived from patients with syndromic craniosynostosis. This study (1) examined the apoptotic rate and cell cycle of osteoblasts derived from patients with syndromic craniosynostosis, and (2) investigated for the presence of soluble factors released from syndrome-derived osteoblasts. Osteoblast cell lines were established from calvarial specimens of patients with clinically diagnosed syndromic synostosis and from normal controls. A co-culture technique was used to investigate for the presence of elaborated soluble factors. Apoptotic rate and cell cycle analyses were performed by using flow cytometry after staining with annexin V-fluorescein isothiocyanate and propidiumiodide, respectively. The apoptotic rate was significantly reduced in syndrome-derived osteoblasts as compared with control osteoblasts. Control osteoblasts co-cultured with syndromic osteoblasts demonstrated a dramatic reduction in their apoptotic rate as compared with those co-cultured with control osteoblasts. These results indicate that osteoblasts derived from patients with syndromic craniosynostosis display a lower apoptotic rate, a normal DNA synthetic rate, and the capability to reduce the apoptotic rate in normal calvarial osteoblasts through the elaboration of soluble factors.

Atypical hemifacial microsomia associated with Chiari I malformation and syrinx: further evidence indicating that chiari I malformation is a disorder of the paraaxial mesoderm. Case report and review of the literature.

The authors present the first known reported case of hemifacial microsomia associated with a Chiari I malformation and syrinx. A 14-year-old girl presented with progressive torticollis of 3 years' duration and headaches exacerbated by exercise. Computerized tomography scanning and magnetic resonance imaging revealed extensive craniofacial and vertebral abnormalities, including aplasia of the floor of the left middle fossa and posterior fossa cranium, articulation of the left mandibular condyle with the left temporal lobe, and progressive development of a Chiari I malformation with associated syringomyelia. The patient first underwent posterior fossa decompression, duraplasty, and occipitocervical fusion. This procedure was later followed by reconstruction of the floor of the left middle fossa and temporomandibular joint. The patient's outcome was excellent. In this case report the authors review the complex embryological development of craniofacial and craniovertebral structures, and emphasize the use of a staged approach to treat pathophysiological consequences of this congenital anomaly.

Update on craniofacial surgery: the differential diagnosis of lambdoid synostosis/posterior plagiocephaly.

There has been an evolution of thought on the diagnosis and treatment of posterior plagiocephaly. Synostotic posterior plagiocephaly (lambdoid synostosis) can be diagnosed and differentiated from non-synostotic posterior plagiocephaly (positional molding) based on specific cosmetic and radiologic criteria. The advent of high-resolution three-dimensional CT analysis of cranial morphology combined with meticulous clinical studies of the two major causes of posterior plagiocephaly has added much to our understanding of this skull deformity. Children with lambdoid synostosis have a trapezoid-shaped skull with posterior displacement of their ipsilateral ear, ipsilateral mastoid bossing, contralateral occipital bossing, and a fused lambdoid suture that appears as a ridge. Children with posterior plagiocephaly without lambdoid synostosis have a characteristic parallelogram-shaped skull with anterior displacement of the ipsilateral ear and ipsilateral frontal bossing. This subject is surrounded in controversy because many of the children in the past thought to have lambdoid synostosis probably did not, based in part on the aforementioned specific criteria. This is an important point, as most patients with posterior plagiocephaly without synostosis will improve without surgery. One should thus be appropriately conservative in the selection of patients for surgery. The majority of infants evaluated at craniofacial clinics presumably have posterior plagiocephaly without synostosis and can be successfully treated with frequent head turning, helmet, or band therapy. Patients with clinically and radiologically proven synostotic posterior plagiocephaly and a severe deformity should undergo craniofacial surgery. The technique of biparieto-occipital craniotomy is safe, simple, and delivers a good cosmetic result. Our postoperative photographic evaluations have shown an immediate, aesthetically pleasing change in the contour of the occiput, which tends to improve with time.

Lessons learnt from the management of 1500 complex facial fractures.

The lessons learnt from the management of 1500 consecutive patients with complex facial fractures have been analysed. This analysis and the major changes in treatment principles have resulted in dramatic improvement in results. The application of craniofacial surgical principles, extended exposure of the craniofacial skeleton, accurate fracture reduction with rigid internal bony fixation and primary bone graft reconstruction has revolutionised the care of these patients. The reattachment of the soft tissue to the reconstructed skeleton provides the final link in this comprehensive one stage reconstruction. Analysis of results has demonstrated the majority of complications and failures to be due to inadequate exposure and reduction of fractures with bone segments rigidly plated in their unreduced position. Inadequate bone grafting and failure to re-suspend the soft tissue and canthi results in post treatment deformity even if the bony reconstruction is adequate. Adherence to the principles of reconstruction will almost always result in a one-stage correction no matter how severe the initial injury.

State of the art in craniofacial surgery: nonsyndromic craniosynostosis.

Craniosynostosis refers to the premature fusion of one of the six major sutures of the cranial vault. Functionally, craniosynostosis may be defined as the premature conversion of the dynamic region of growth and resorption between two adjacent bones of the cranium into a static region of bony union. Molecular analysis has blurred the traditional categories of nonsyndromic and syndromic synostosis to some extent, but, in general, the distinctions between the two groups still hold true. The complexity of the congenital anomalies may be limited with the former, whereas the latter usually requires reoperations and correction of the facial skeleton. This article briefly outlines the characteristic deformities produced from nonsyndromic craniosynostosis. Various approaches to surgical correction of the deformities are described. Finally, new biomaterials that are used in the correction of nonsyndromic craniosynostosis are reviewed.

Desmoplastic fibroma of the zygoma.

Desmoplastic fibroma is an exceedingly rare primary bone tumor. Previous reports have not included the presentation of this tumor associated with the zygoma. This report describes the unusual presentation and surgical management of a desmoplastic fibroma of the zygoma.

Results with sphincter pharyngoplasty and pharyngeal flap.

OBJECTIVE: To evaluate speech outcomes and complications of sphincter pharyngoplasty and pharyngeal flap performed for management of velopharyngeal insufficiency (VPI). DESIGN: Case series. SETTING: Tertiary care children's hospital. PATIENTS: All patients who underwent pharyngeal flap or sphincter pharyngoplasty from 1990 to 1995. METHODS: Perceptual speech analysis was used to assess severity of VPI, presence of nasal air emissions and quality of nasal resonance (hyper, hypo, or normal). Pre-operative measures of velopharyngeal function were based upon nasendoscopy and videofluoroscopic speech assessment. Recommendations for management were made by the attending surgeon. Complications of hyponasality and obstructive sleep symptoms (OSS) were noted. Patient characteristics were compared using univariate analysis. RESULTS: Sixteen patients underwent sphincter pharyngoplasty and 18 patients underwent superiorly based pharyngeal flap. Patients were similar in terms of lateral pharyngeal wall medial motion and palatal elevation. The groups were also similar with regard to VPI severity, though there was a trend for more severe VPI in patients undergoing sphincter pharyngoplasty than pharyngeal flap (50 vs. 33.3%, respectively). Patients with pharyngoplasty had a higher rate of resolution of VPI than those who had pharyngeal flap (50 vs. 22.2%, respectively), although this was not statistically significant. Post-operative hyponasality and obstructive sleep symptoms were present in both groups. However, only patients who underwent PF and had postoperative OSS had obstructive sleep apnea (OSA). CONCLUSIONS: There were no detectable anatomic differences between treatment groups implying that treatment selection during the study period was not guided by strict anatomic criteria. Sphincter pharyngoplasty may have a higher success rate with a lower risk of OSS.

Sphincter pharyngoplasty: speech outcome and complications.

OBJECTIVES: To assess the speech outcomes and complications in children who had undergone sphincter pharyngoplasty (SP) for management of velopharyngeal insufficiency (VPI). STUDY DESIGN: Retrospective chart review. METHODS: Charts from patients who had sphincter pharyngoplasty between January 1993 and June 1996 were reviewed. Syndrome diagnosis and presence of repaired cleft palate were reviewed. Preoperative speech assessment, videofluoroscopic and nasopharyngoscopic evaluations, age at time of surgery, and postoperative speech assessments were reviewed for all patients. Postoperative videofluoroscopy and nasopharyngoscopy were performed for those patients who had persistent VPI. Obstructive sleep symptoms were also assessed. RESULTS: Thirty patients were identified; six patients had no follow-up evaluation, leaving 24 patients included in this study. Average follow-up was 11.7 months (range, 2-35 mo). Velocardiofacial syndrome (VCFS) was the most commonly identified syndrome. Postoperatively, 15 of 24 patients (62.5%) had complete resolution of their VPI; five of 24 (20.8%) had significant improvement; one of 24 (4.2%) had minimal to no change; and three of 24 (12.5%) were hyponasal. Of the six patients with some degree of persistent VPI, three underwent revision surgery. All three patients had complete resolution of their VPI after revision surgery, resulting in an overall success rate of 18 of 24 (75%). CONCLUSIONS: Sphincter pharyngoplasty has wide application in the management of children with VPI, including those with VCFS. The procedure is readily modified to accommodate an individual patient's needs as determined by preoperative VPI evaluation. A modification of the procedure is described to minimize the risk of postoperative airway obstruction and hyponasality, both regarded as airway complications of sphincter pharyngoplasty.

The differential diagnosis of abnormal head shapes: separating craniosynostosis from positional deformities and normal variants.

The correct differential diagnosis of an abnormal head shape in an infant or a child is vital to the management of this common condition. Establishing the presence of craniosynostosis, which warrants surgical correction, versus non-synostotic causes of head deformity, which do not, is not always straightforward. This paper deals with three groups of abnormal head shape that may cause diagnostic confusion: the spectrum of metopic synostosis; the dolichocephaly of prematurity versus sagittal synostosis; and the differential diagnosis of plagiocephaly. Special emphasis has been placed on the problem of posterior plagiocephaly, in the light of recent evidence demonstrating that lambdoid synostosis has been overdiagnosed. Metopic synostosis presents as a wide spectrum of severity. Although only severe forms of the disorder are corrected surgically, all cases should be monitored for evidence of developmental problems. The dolichocephalic head shape of preterm infants is non-synostotic in origin and is managed nonsurgically. The scaphocephalic head shape resulting from sagittal synostosis requires surgical intervention for correction. Posterior plagiocephaly may be due to unilambdoid synostosis or positional molding, which have very different clinical and imaging features. True lambdoid synostosis is rare. Most cases of posterior plagiocephaly are due to positional molding, which can usually be managed nonsurgically. Regardless of the suture(s) involved, all children with confirmed craniosynostosis should be monitored for increased intracranial pressure and developmental problems.

Congenital bony syngnathia: a proposed classification.

Congenital bony syngnathia is an extremely rare condition characterized by bony fusion of the jaws. Five new cases are described and the existent literature is reviewed. A classification system is proposed and treatment recommendations based on this classification are presented.

The surgical management of giant cervicofacial lymphatic malformations.

Giant cervicofacial lymphatic malformation, a potentially life-threatening congenital malformation, historically has been removed in staged resections. However, complete surgical extirpation is desirable and can be achieved with the aid of a multidisciplinary team. The authors present the case of a 12-year-old girl who had an extensively enlarged cervicofacial lymphatic malformation. Effective treatment involved aggressive surgical excision, facilitated by mandibular osteotomies to provide access to the floor of the mouth, the tongue, and the pharyngeal wall. In addition, total removal of involved facial and neck skin was performed. The remaining soft tissue defect was reconstructed primarily with an abdominal musculocutaneous free flap. In the 5 years since the procedure, there has been no recurrence. Based on this experience, excision of involved skin and mandibular access osteotomies are important techniques to help completely remove cervicofacial lymphatic malformations with oral involvement, thus potentially reducing the number of recurrences. In addition, these cases require the best efforts of a multidisciplinary team to achieve a successful result so that complete and radical excision can be performed with the hope of avoiding the pitfalls of multiple resections.

The differential diagnosis of posterior plagiocephaly: true lambdoid synostosis versus positional molding.

The diagnosis and treatment of posterior plagiocephaly is one of the most controversial aspects of craniofacial surgery. The features of true lambdoid synostosis versus those of deformational plagiocephaly secondary to positional molding are inadequately described in the literature and poorly understood. This has resulted in many infants in several craniofacial centers across the United States undergoing major intracranial procedures for non-synostotic plagiocephaly. The purpose of this study was to describe the detailed clinical, imaging, and operative features of true lambdoid synostosis and contrast them with the features of positional plagiocephaly. During a 4-year period from 1991 to 1994, 102 patients with posterior plagiocephaly were assessed in a large multidisciplinary craniofacial program. During the same period, 130 patients with craniosynostosis received surgical treatment. All patients were examined by a pediatric dysmorphologist, craniofacial surgeon, and pediatric neurosurgeon. Diagnostic imaging was performed where indicated. Patients diagnosed with lambdoid synostosis and severe and progressive positional molding underwent surgical correction using standard craniofacial techniques. Only 4 patients manifested the clinical, imaging, and operative features of unilambdoid synostosis, giving an incidence among all cases of craniosynostosis of 3.1 percent. Only 3 among the 98 patients with positional molding required surgical intervention. All the patients with unilambdoid synostosis had a thick ridge over the fused suture, identical to that found in other forms of craniosynostosis, with compensatory contralateral parietal and frontal bossing and an ipsilateral occipitomastoid bulge. The skull base had an ipsilateral inferior tilt, with a corresponding inferior and posterior displacement of the ipsilateral ear. These characteristics were completely opposite to the findings in the 98 patients who had positional molding with open lambdoid sutures and prove conclusively that true unilambdoid synostosis exists as a specific but rare entity. Awareness of the features of unilambdoid synostosis will allow more accurate diagnosis and appropriate treatment of posterior plagiocephaly in general and in particular will avoid unnecessary surgical intervention in patients with positional molding.

Intracranial and extracranial reduction osteoplasty for craniodiaphyseal dysplasia.

Craniodiaphyseal dysplasia is a rare, sporadic form of craniotubular bone dysplasia, characterized by massive generalized hyperostosis and sclerosis, particularly of the skull and facial bones, leading to severe deformity. The clinical course is typically characterized by progressive encroachment of the craniofacial foramina and brain by the relentless deposition of bone. Compression of cranial nerves, the foramen magnum, and intracranial contents commonly leads to blindness, loss of hearing, and death. This report describes a unique case of craniodiaphyseal dysplasia manifesting with asymmetric craniofacial and axial hyperostosis. The tubular bones demonstrated the characteristic diaphyseal endostosis, undertubulation, and relative overgrowth on the involved side. Significant brain compression with signs and symptoms of increased intracranial pressure was managed successfully with decompressing craniectomy at age 12 years, enlarging the anterior and middle fossae. Calvarial thickness measured nearly 4 cm. Further calvarial, midfacial, and mandibular recontouring were performed 6 and 22 months later. Follow-up in our case indicates that close observation is mandatory to manage further progression of the disease.

Monocyte chemoattractant protein-1 mRNA expression in hemangiomas and vascular malformations.

Hemangiomas are vascular tumors that appear at or shortly after birth and undergo a rapid growth before involuting. During the proliferative phase, hemangiomas are infiltrated by macrophages, cells that are capable of initiating angiogenesis. Vascular malformations grow slowly, commensurate with the child, and do not regress or become infiltrated by macrophages. We demonstrate by in situ hybridization increased monocyte chemoattractant protein-1 (MCP-1) mRNA expression during hemangioma and vascular malformation growth. We found markedly upregulated expression of MCP-1 mRNA in all proliferative hemangioma specimens, expressed by alpha-actin perivascular smooth muscle cells and interstitial HAM 56+ macrophages. In contrast, 9 of 10 clinically involuting hemangiomas displayed no expression of MCP-1 mRNA. We found no expression of MCP-1 mRNA in vascular malformations, which correlates with the minimal monocytic infiltration of these lesions. We also showed that dexamethasone and interferon-alpha downregulate MCP-1 mRNA in cultured human vascular smooth muscle cells. Glucocorticoids can be efficacious in 30-50% of cases when given in the proliferative phase of hemangioma growth, but have no beneficial effect on vascular malformations. Interferon-alpha has been used to dramatically induce regression of steroid-refractory hemangiomas. Both of these agents' beneficial action on proliferative hemangiomas may, in part, result from reduced MCP-1 production and reduced influx of angiogenic macrophages.