Objective To investigate the difference between the different surgical methods for thoracic ossification of ligamentum flavum(OLF)combined with cervical spondylotic myelopathy(CSM).Methods From January 1991 to January 2003,56 cases with thoracic OLF combined with CSM were reviewed retrospectively.Forty of 56 cases had been followed up for more than two years.There were 22 males and 18 females with an average of 58 years(range,27-70 years).The course of the diseases were 1 to 120 months,with an average of 16.5 months.The pathological factors for thoracic myelopathy included:OLF for 25 cases,OLF combined with ossification of posterior longitudinal ligament(OPLL)for 12 cases,OLF combined with thoracic disc herniation for 3 cases.There were 23 cases combined with cervical OPLL and 17 cases combined with cervical stenosis.Eighteen cases underwent cervical laminoplasty and thoracic laminectomy,9 cases underwent only thoracic laminectomy,and 13 cases underwent both cervical and thoracic posterior decompression in multiple stages.Results Forty cases were followed up for 24 to 227 months,with an average of 67.5 months.According to Epstein standard,the excellent and good rate was 88.9% for 18 cases who underwent cervical laminaplasty and thoracic laminectomy(16/18),66.7% for 9 cases who underwent only thoracic laminectomy(6/9),and 53.8% for 13 cases who underwent both cervical and thoracic posterior decompression(7/13).Statistics analysis showed that the outcome of one-stage surgery was better than multiple stages surgeries,and outcome of those whose operation intervals less than 1 year was better than those of more than 1 year.Conclusion Thoracic and cervical decompression should be performed at one stage for those with upper thoracic OLF combined with CSM.Thoracic decompression should be performed firstly for those with severe lower extremities syndrome and few upper extremities syndrome.Thoracic and cervical decompression in one or multiple stages should be performed for those with severe upper and lower extremities syndrome,and operation interval should be less than one year.

Objective To evaluate the feasibility,safety and efficacy of surgical treatment of the thoracic and thoracolumbar disc herniations through the posterior far lateral approach,Methods From April 2005 to June 2010,24 consecutive patients with thoracic or thoracolumbar disc herniations were treated surgically,using the posterior far lateral approach.There were 15 males and 9 females with the mean age of 53.6 years old(range,25-69 years).The levels of herniated discs were located in T4-s,T5-6,T6-7 for 1 case,in T9-10 for 1 case,in T10-11 for 2 cases,in T10-11,T11-12,T12L1 for 1 case,in T11-12 for 3 eases,in T11-12,T12L1 for 3 cases,in T12L1 for 4 cases,in T12L1,L1-2 for 3 cases,and in L1-2 for 6 eases.There were one level disc herniation in 16 cases,two levels disc herniation in 6 cases and three levels disc herniation in 2 cases.16 out of 24 cases had "bony protrusions",including bony separation of the endplate,bony spur,disc calcification or OPLL.The average preoperative Cobb angle of localized kyphosis was 10.5°.According to the Frankel grading system,5 cases were classified as C,16 as D,and 3 as E,preoperatively.Results Average operation time was 3.5 h(2.0-4.5 h),and mean blood loss was 800 ml(300-4000 ml).Postoperative localized kyphosis was an average of 4.6°,with average correction rate of 56.2%.24 cases were followed up for 1 to 62 months,with an average of 18 months.According to Japanese Orthopaedic Association(JOA)criteria system,there were 12 cases(50.0%)with excellent outcome,9 cases(37.5%)with good outcome,and 3 cases(12.5%)with fair outcome.The postoperative Frankel grading were C for 1 case,D for 2 cases,and E for 21 cases.There were no complications intraoperatively and postoperatively.The symptoms were improved in all patients.Conclusion By using "safe triangular zone" and dekyphosis stabilization,the posterior far lateral approach was a relatively safe,reliable,effective and better view surgical procedure for the treatment of the thoracic and thoracolumbar disc herniations.

Objective To investigate the safety and efficiency of thoracic laminectomy with dekyphosis for thoracic myelopathy due to multi-segmental ossification of the posterior ligaments.Methods The clinical data of five cases of thoracic myelopathy due to multi-segmental ossification of longitudinal ligaments who were surgically treated in our hospital between August 2012 and March 2013 were retrospectively analyzed,among which two were male and the other three were female,with an average age of 52 (range,45-56) years old.The pre-operative duration ranged from 2 months to 6 years.All five cases were suffering from progressive bilateral partial paraplegia with an average preoperative JOA score 3.8 (range,3-6),an average segment-number of ossification of the posterior ligaments 7.6 (range,5-10),and also an average segment-number of 5.0 (range,2-10) ossification of the ligamentum flavum.All the five cases showed different kyphosis at the stenotic area of thoracic spine,with an average kyphotic angle (Cobb) of 35.8° (range,22°-56°).Their pre-operative Japanese Orthopaedic Association score (JOA) was 3.8 averagely (range,3-6).Clinical features,operation time,blood loss,perioperative complications and postoperative outcome were recorded.Results The segment number of laminectomy of these five cases was 8.2 averagely.The segment number of dekyphosis was 2 for 2 cases and 1 for the other 3 cases,with a average dekyphotic degree of 7.8° (range,2°-15°).The average operation time was 6.3 hours (range,5.5-7.0 hours) and the average blood loss was 3900 ml.The perioperative complications included cerebrospinal fluid leakage in 4 cases who were treated conservatively,and epidural hematoma in 1 case who underwent reoperation for removing the hematoma.All cases were followed up for 21 to 27 months,and their average final JOA score was 10,with an average recovery rate of 85.6％,and a rate of excellent or good was 100％ by the modified Epstein standard.Conclusion The result of thoracic laminectomy combined with dekyphosis for thoracic myelopathy due to multi-segmental ossification of longitudinal ligaments is quite satisfying,however this procedure is demanding with a long operation time,a huge blood loss and a high complication rate.

Objective: To evaluate the efficacy and safety of Smith-Petersen osteotomy (SPO) assisted by releasing disk space from posterior approach for thoracolumbar kyphosis. Methods: A review was conducted on 8 patients (3 males and 5 females) with thoracolumbar kyphosis were treated with SPO assisted by releasing disk space from posterior approach at Department of Orthopaedics, Peking University Third Hospital from June 2016 to September 2017. The age was 56.5 years (range:18-71 years). There were 3 cases of Scheuermanns kyphosis, 2 cases of degenerative kyphosis, 1 case of proximal junctional kyphosis (PJK) after lumbar surgery, and 2 cases of kyphosis after thoracolumbar laminectomy. The paired t test was used for statistical analysis in thoracolumbar kyphosis angle, osteotomy segment kyphosis angle, sagittal vertical value (SVA), visual analogue score (VAS), Oswestry dysfunction index (ODI) before and after surgery. Statistical difference was confirmed with P<0.05. Results: Osteotomy level included 2 cases in T_11-12, 3 cases in T₁₂-L₁, 3 cases in L_1-2. The average operation time was 339 min (range: 247-416 min), bleeding volume was 1 275 ml (range: 500-2 500 ml). The mean follow-up time was 16.5 months (range: 12-24 months). The average thoracolumbar kyphosis angle was 59.9° (range: 40°-73°) pre-operation, 9.5°(range:-5.1°-20°) post-operation and 13.5°(range:-1.3°-28°) at the latest follow-up. It made an average correction with 46.4°and corrective rate with 78.0%. The osteotomy segment kyphosis angle was 37.9° (range: 26°-46°) pre-operation, -1.3° (range:-11°-13°) post-operation making an 39.2° open-up angle, and 2.0° (range:-13.5°-13°) at the latest follow-up. Lumbar lordosis was 47.5° (range: 2°-76°) pre-operation, 41.2°(range:15°-62°) post-operation and 36.9°(range:15°-58°) at the latest follow-up. SVA was 54 mm(range:-34 mm-149 mm) pre-operation and 39 mm(range:-3 mm-119 mm) at the latest follow-up. VAS score of low back pain was 6.3(range:0-9) pre-operation and 3.0(range:0-6) at the latest follow-up. ODI score was 21.9(range: 0-42) pre-operation and 11.0(range: 0-26) at latest follow-up. Comparing to pre-operation value, there were statistical difference in the thoracolumbar kyphosis angle(t= 8.547, P=0.000), osteotomy segment kyphosis angle(t=9.739, P=0.000), VAS(t=3.077, P=0.018), ODI(t=5.800, P=0.001) at the latest follow-up. There was no neuropathic complication in all patients. Cerebrospinal fluid leakage occurred in 2 cases with spinal surgery history, and recovered after symptomatic treatment. Conclusions SPO assisted by releasing disk space from posterior approach could safely achieve effective correction of rigid thoracolumbar kyphosis deformity within 40°.

Objectives:To evaluate the biomechanical state of the I4-L5 segment after unilateral laminotomy for bilateral decompression(ULBD)surgery using finite element analysis,providing a theoretical basis for the treatment of lumbar degenerative diseases with ULBD.Methods:Thin-slice CT scan data from the lumbar spine of a healthy volunteer were extracted,and high-fidelity three-dimensional finite element methods were applied to establish normal I4-L5 model,post-ULBD surgery model,and post-lumbar fenestration(LF)surgery model.The L5 vertebral body's lower endplate was fully fixed in all the models,and a 500N axial load was applied at the L4 upper endplate,along with a 10N·m bending moment load in six directions of flexion,ex-tension,left lateral bending,right lateral bending,left rotation,and right rotation.Comparative analysis of the biomechanical characteristics such as intervertebral disc compression height,intervertebral range of motion(ROM),stress distribution within the intervertebral disc,and facet joint pressure was conducted under different loads for the three models.Results:The ROMs under six directions of movements were within the range of the measured results of previous cadaveric studies,verifying that the normal model was valid.Under the 500N axial load,the intervertebral disc compression heights for the normal model,post-ULBD and post-LF surgery models were 0.74mm,0.85mm,and 0.85mm,respectively.With an additional 10N·m bending moment load,the intervertebral ROM in flexion,extension,left lateral bending,right lateral bending,left rotation,and right rotation for the normal model were 6.1°,4.2°,5.1°,4.6°,2.9°,and 2.6°,respectively;for the post-ULBD model,they were 6.5°,4.8°,6.0°,5.2°,3.2°,and 2.9°,respectively;and for the post-LF model,they were 6.4°,4.6°,5.6°,5.1°,3.0°,and 2.8°,respectively.There was no significant difference in the stress dis-tribution within the intervertebral disc for the three models,with the maximum von Mises stress occurring at the outer annulus fibrosus on the compressed side of the disc.The maximum von Mises stress in the inter-vertebral disc for the normal model under flexion,extension,left lateral bending,right lateral bending,left ro-tation,and right rotation was 0.52MPa,0.66MPa,0.81 MPa,0.87MPa,0.46MPa,and 0.40MPa,respectively;for the post-ULBD model,it was 0.64MPa,0.76MPa,1.06MPa,1.13MPa,0.60MPa,and 0.64MPa,respectively;and for the post-LF model,it was 0.65MPa,0.80MPa,1.00MPa,1.06MPa,0.66MPa,and 0.65MPa,respec-tively.Significant facet joint contact pressure was observed under left and right rotation,with the normal mod-el showing contact pressure of 60N and 69N,the post-ULBD model showing 30N and 87N,and the post-LF model showing 79N and 120N.Conclusions:After ULBD surgery,there is an increase in lumbar interverte-bral disc compression height,intervertebral ROM,stress within the intervertebral disc,and facet joint pressure.Compared with LF surgery,ULBD has a smaller impact on the biomechanical stability of the lumbar segment.

STUDY DESIGN: A retrospective clinical review. PURPOSE: To investigate the difference in clinical manifestations and severity between polymicrobial and monomicrobial infections after spinal surgery. OVERVIEW OF LITERATURE: Surgical site infections (SSIs) after spinal surgery are a major diagnostic and therapeutic challenge for spinal surgeons. Polymicrobial infections after spinal surgery seem to result in poorer outcomes than monomicrobial infections because of complementary resistance to antibiotics. However, comparison of the clinical manifestations and severity between polymicrobial and monomicrobial infections are limited. METHODS: Sixty-seven patients with SSIs after spinal surgery were studied: 20 patients with polymicrobial infections and 47 with monomicrobial infections. Pathogenic bacteria identified were counted and classified. Age, sex, and body mass index were compared between the two groups to identify homogeneity. The groups were compared for clinical manifestations by surgical site, postoperative time to infection, infection site, incisional drainage, incisional swelling, incisional pain, neurological signs, temperature, white blood cell count, and the percentage of neutrophils. Finally, the groups were compared for severity by hospital stay, number of rehospitalizations, number of debridements, duration of antibiotics administration, number of antibiotics administered, and implant removal. RESULTS: Polymicrobial infections comprised 29.9% of SSIs after spinal surgery, and most polymicrobial infections (70.0%) were caused by two species of bacteria only. There was no difference between the groups in terms of clinical manifestations and severity. In total, 96 bacterial strains were isolated from the spinal wounds: 60 strains were gram-positive and 36 were gram-negative pathogenic bacteria. Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Enterobacter cloacae were cultured in order of the frequency of appearance. CONCLUSIONS: Most polymicrobial infections were caused by two bacterial species after spinal surgery. There was no difference in clinical manifestations or severity between polymicrobial and monomicrobial infections.
Anti-Bacterial Agents ; Bacteria ; Body Mass Index ; Coinfection ; Debridement ; Drainage ; Enterobacter cloacae ; Escherichia coli ; Humans ; Length of Stay ; Leukocyte Count ; Neutrophils ; Postoperative Complications ; Retrospective Studies* ; Spine ; Staphylococcus aureus ; Staphylococcus epidermidis ; Surgeons ; Surgical Wound Infection ; Wounds and Injuries

Objective To investigate the safety and effectiveness of posterior approach laminectomy combined with localized resection of ossified posterior longitudinal ligament and dekyphosis for multilevel ossification of the posterior longitudinal ligament (OPLL) in the thoracic spine.Methods Thirty-one cases of thoracic multilevel OPLL was treated with this new technique between August of 2012 and August of 2016.Twenty-nine among the 31 cases were successfully followed up more than two years.Among these 29 cases,9 were male and the other 20 were female,with an average age of 48.5±7.1 years.The average segment number of OPLLwas 6.5±2.2 (range,3-11).The average segment number of laminectomy was 7.9±2.5 (range,4-13).There were 26 cases combined with ossification of the ligamentum flavum (OLF).Posterior approach laminectomy combined with localized resection of OPLL and dekyphosis for multilevel OPLL in the thoracic spine was applied to all cases.Firstly,en-bloc laminectomy was performed to all the segments of OPLL.Then the nearest segment of ossification to the kyphotic apex and the most stenotie level was selected and limitedly resected.Finally,wedge-shaped osteotomy was conducted to decrease the kyphosis.The outcomes including recovery rate of myelopathy and the radiological changes were recorded during the post-operative follow-up.Single group pre and post analysis was conducted by using paired t-test.Results Twenty-seven cases underwent one-level circumferential decompression,and the other two case underwent two-level localized resection of the ossified posterior longitudinal ligament.The average operation time was 245.2±75.1 min (range,131-423 min).The average blood loss was 1 307.9±1 457.7 ml(range,300-6 000 ml).The average follow-up time was 40.2± 14.9 months (range,25-69 months).The kyphotic angle of the stenotic segments decreased 11.4°±3.5° averagely after the surgery,from pre-operative 28.7°±9.6° to post-operative 17.3°±8.6°.The decreased kyphotic angle was 7.4°±3.1 ° at the final follow-up with an average kyphotic angel of 22.3°± 10.3°.The average length of the resected ossified posterior longitudinal ligament was 11.3±3.9 mm,and the average shortening length of the spinal column was 5.0±3.0 mm (range,0.4-13.8 mm).The pre-operative Japanese Orthopedic Association (JOA) score was 4.3±2.2 averagely (range,1-9),and the final JOA score increased to 9.3±2.3 (rang,3-11).The average recover rate was 85.7％ (range,-100％ to 100％),and the rate of excellent or good was 89.7％.Among the 29 cases,6 cases occurred post-operative transient deterioration and regained a satisfactory recovery eventually;one case occurred post-operative paraplegia and never recovered;19 cases occurred post-operative cerebrospinal fluid leakage and healed under conservative treatment.Conclusion For the thoracic multilevel OPLL,one-stage posterior approach laminectomy combined with localized resection of the ossified posterior longitudinal ligament and dekyphosis can significantly improve the outcomes of the myelopathy with low rate of post-operative paraplegia.Therefore,this new surgery technique is a safe and effective treatment for multilevel OPLL in thoracic spine.

Objective To investigate the osteogenic differentiation potency of ligament cells in thoracic ossification of the ligamentum flavum (TOLF) and analyze further by using transcriptome high-throughput sequencing.Methods Clinically,the patients with non-TOLF and TOLF (n=10 in each group) who underwent surgery in our hospital from October 2015 to April 2016 were included in this study.The primary ligament cells that derived from the two groups were separately cultured and induced osteogenesis with 15％ strength of cyclic mechanical stress for 12h and 24h using a device called Flexcell FX-4000.The ALP activity was determined to evaluate the osteogenesis using quantitative analysis and ALP staining assay.Real-time PCR and westernblotting were used to detect the mRNA and protein expression of osteogenic-related genes including ALP,BMP-2 and Osteocalcin.Then,three patients in each group were included in the study of transcriptome high-throughput sequencing and bioinformatics analysis using Illumina HiSeqTM 2500 sequencing platform to compare further.Results The morphology of the cells that derived from two groups was basically similar,all presented an elongate spindle-shape.To evaluate the ostogenesis,ALP activity assays including quantitative and staining assays were performed.Under microscope,the ALP staining in the TOLF group was higher than non-TOLF group and increased with the longer duration of stress induction.The result of semi-quantitative analysis showed the stained area and positive cells in TOLF group were more than non-TOLF group significantly at 0 h,and were increased with the induction.The results of quantitative analysis showed ALP activity in the TOLF group was significantly higher than non-TOLF group and were increased with the induction significantly all the time.But no significant change in ALP staining or quantitative analysis was found in non-TOLF.The results of real-time PCR indicated that the expression of ostegenic markers above in the TOLF group was more than non-TOLF group significantly except the expression of OCN at 0 h.The expression of the three ostegenic markers in TOLF group was increased with the stress induction for 12 h and 24 h significantly except the expression of BMP-2 and OCN at 12 h.The results of western-blotting indicated that the expression of the three ostegenic markers above in the TOLF group was more than non-TOLF group significantly except the expression of ALP at 0 h.The expression of the three ostegenic markers in TOLF group was increased with the stress induction for 12 h and 24 h,but only the expression of ALP at 24 h was significant.And no significant change in the expression of mRNA and protein was found in non-TOLF group.In the transcriptome analysis,671 genes of TOLF group were up-regulated and 314 genes were found to be down-regulated compared to the control group.In addition,22 significant GO terms associated with upregulated genes were found to be closely related to ossification.Conclusion TOLF ligament cells have high osteogenic differentiation potency,which could express obvious osteogenesis-related gene spectrum,and differentially expressed genes including L1RL1 、PTHLH、DKK1 、BMP6、SPP1 and FGF1 may be related with the osteogenic potency of ligament cells in thoracic ossification.

Objective:To analyze the prevalence and distribution characteristics of diffuse idiopathic skeletal hyperostosis (DISH) in hospitalized patients with thoracic ossification of the ligamentum flavum (TOLF).Methods:The clinical records of 132 consecutive TOLF patients from January 2018 to June 2019 were retrospectively studied. DISH was identified by the preoperative X-ray and CT and its prevalence was calculated. The prevalence of patients with different genders, different age groups and different ossification types was compared. The segmental distribution of DISH and the distribution in the upper (T 1-T 4), middle (T 5-T 8), and lower thoracic spine (T 9-T 12) were analyzed. Ossification degree of DISH was evaluated based on the Meta scoring system. The demographic characteristics (age, gender, BMI, etc.) were compared between DISH and non-DISH group. Results:Forty-nine patients was diagnosed as DISH with the prevalence of 37.1% in all included cases. The prevalence was about twice as high in male (46.3%) than in female (23.1%) ( χ2=8.806, P=0.003). The prevalence in the age groups of <40, 40-49, 50-59, 60-69 and ≥70 years was 20.0%, 28.0%, 34.4%, 44.0%, and 66.7%, respectively. The prevalence in long-segment TOLF patients (45.1%) was significantly higher than that in short-segment TOLF patients (24.0%) ( χ2=5.937, P=0.015). DISH most frequently affected T 8,9 levels (91.8%). The total number and mean number of ossified segments were 365 and 7.4, respectively. Ossification lesions in the upper, middle, lower thoracic spine accounted for 26.03%, 40.54%, and 33.15%, respectively. Grade I, grade II, and grade III ossification accounted for 21.4%, 28.5% and 50.1%, respectively. The mean age of the DISH group was older than the non-DISH group ( t=2.024, P=0.045). The proportion of male patients in the DISH group was significantly higher than that in the non-DISH group ( χ2=8.806, P=0.003). The average height and weight in the DISH group were significantly greater than those in the non-DISH group ( t=2.564, P=0.012; t=2.191, P=0.030), whereas no significant differences in BMI and constituent ratio of concurrent diabetes, cardiac disease, hypertension between two groups were observed. Conclusion:The prevalence of DISH in patients with TOLF is 37.1%. Male, elderly and long-segment TOLF patients are associated with higher prevalence. DISH frequently occurs in the middle and lower thoracic spine, and T 8,9 is the common affected segment. Ossification lesions may develop with age. Demographic characteristics of DISH group differ, to some extent, from those of non-DISH group.

Objective:To investigate the clinical efficacy of percutaneous kyphoplasty (PKP) assisted by intuitive visual navigation orthopaedic surgery robot in the treatment of osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective analysis was conducted in Peking University Third Hospital from June 2021 to November 2022, 78 patients with OVCF were treated by the intuitive visual navigation orthopaedic surgery robot or freehand surgery with a "C" arm X-ray machine. According to the method of puncture, they were divided into robot group and freehand group. In the robot group, there were 36 cases, including 7 males and 29 females, aged 74.50±5.87 years, 32 cases of single vertebral fractures, 4 cases of double vertebral fractures, 1 case of T 8, 2 cases of T 10, 2 cases of T 11, 11 cases of T 12, 10 cases of L 1, 8 cases of L 2, 2 cases of L 3, 3 cases of L 4, and 1 case of L 5. Bone mineral density T value was -2.94±0.50; In the freehand group, there were 42 cases, including 9 males and 33 females, aged 72.86±8.84 years, 36 cases of single fracture and 6 cases of double fracture, 1 case of T 6, 2 cases of T 7, 3 cases of T 11, 9 cases of T 12, 8 cases of L 1, 9 cases of L 2, 5 cases of L 3, 6 cases of L 4, and 5 cases of L 5. Bone mineral density T value was -3.00±0.50. The effectiveness evaluation indexes of the two groups were compared, which included surgery duration, X-ray fluoroscopy times, hospitalization time, lumbar pain visual analogue scale (VAS), Oswestry disability index (ODI) and height of fractured anterior vertebrae (HFAV). Results:Both groups of patients successfully received surgical treatment. The mean operating time of the robot group was 33.44±2.50 min, which was significantly longer than that of the free hand group, which was 29.69±2.40 min ( t=6.491, P<0.001). Meanwhile, the intraoperative blood loss of the robot group was 3.54±0.89 ml, which was significantly less than that of the freehand group, which was 6.72±1.89 ml ( t=9.110, P<0.001). In terms of radiographic fluoroscopy times, the average of the robot group was 26.81±7.76 times, which was significantly less than the freehand group's 42.61±6.62 times ( t=9.294, P<0.001). The postoperative vertebral front edge height in the free hand group was 18.64±0.32 mm and in the robot group was 18.79±0.36 mm. The difference was not statistically significant ( t=2.673, P=0.067). All patients were followed up for 8.3±2.9 months (range, 6-13 months). The VAS scores of low back pain in the two groups at 1 day and 6 months after operation were significantly improved compared with those before operation ( P<0.05), and there was no significant difference between the two groups in VAS score after operation ( P>0.05). Six months after surgery, the ODI of the free hand group and the robot group were 11.67%±2.13% and 12.11%±2.33%, respectively. The ODI scores of the two groups were significantly lower at 6 months postoperative follow-up than that before surgery, and the postoperative follow-up at all had significant differences compared with that before surgery ( P<0.05), and there was no difference between the two groups in postoperative ODI scores ( P>0.05). No obvious bone cement leakage was found in all patients during operation. Conclusion:Compared with the traditional C-arm X-ray for PKP treatment of OVCF by free hand, intuitive visual navigation orthopedic robot can safely and effectively assist in the completion of the operation process, and has the advantages of less intraoperative blood loss, fewer fluoroscopy times.