下颈椎骨折脱位并脊髓损伤的前路手术治疗

目的：探讨颈椎前路手术在治疗下颈椎骨折脱位并脊髓损伤中的复位率及临床疗效。方法：2006年1月～2011年1月,我院前路手术下颈椎骨折脱位伴脊髓损伤196例,168例患者资料完整,并得以随访,男123例,女45例,年龄18。71岁,平均38．7岁。所有患者术前先行小重量颅骨牵引（1．5～4．5kg）,随后在全麻下行颈椎前路手术进一步复位,先行损伤节段椎间盘切除,以Caspar撑开器撑开复位;不能复位者,行脱位椎体次全切除,再次复位;仍不能复位者,则一期行后路松解,再行前路手术。结果：168例中经颈前路手术复位者88．1％（148／168）,其余19．9％（20／168）则通过前路一后路一前路手术获得复位。89．9％（151／168）获得了完全复位,10．1％（17／168）获得了90％以上的复位。平均随访30．7,术后6个月均获得骨性融合,颈椎椎间高度和生理曲度维持良好,无钢板螺钉并发症。术后153例脊髓损伤者神经功能获得改善。结论：下颈椎骨折脱位并脊髓损伤,多可通过前路手术治疗,该入路可使颈椎获得即刻的稳定,防止继发性脊髓损伤,改善脊髓的功能状况。     

下颈椎骨折脱位并脊髓损伤的前路手术治疗

目的探讨前路手术在治疗下颈椎骨折脱位并脊髓损伤中的价值。方法168例下颈椎骨折脱位并脊髓损伤患者均在全麻下行颈前路减压、复位、钛网或自体髂骨植骨及颈椎带锁钢板固定。结果完全复位151例,复位90%以上17例。平均随访80.7个月,颈椎椎间高度和生理曲度维持良好,无钢板螺钉并发症。140例脊髓损伤者神经功能获改善。结论下颈椎骨折脱位并脊髓损伤选择前路手术治疗可获得满意的疗效。     

严重颈椎脱位手术治疗策略探讨

目的探讨严重颈椎骨折脱位前路手术的复位率及手术策略。方法回顾性分析2001年3月至2006年3月,手术治疗颈椎骨折移位程度在1／2以上的92例患者的临床资料。所有患者术前均行小重量颅骨牵引（1～3ks）。手术时,先行损伤节段椎间盘摘除,以Caspar撑开器撑开复位;不能复位者,行脱位椎体次全切除,再次复位;仍不能复位者,则同时行后路手术。记录患者前路手术复位成功率,气管切开率,评价植骨融合率、Frankel评分、VAS疼痛评分（10分法）。结果单纯椎间隙减压复位者38例,椎体次全切除减压复位者44例,前路-后路-前路手术解剖复位者7例,仍未完全复位者3例。行气管切开29例。末次随访时Frankel评分平均提高0．5级,VAS疼痛评分平均2分。结论严重颈椎脱位前路手术复位率可达89．2％,需联合后路手术再前路手术者占10．8％。C4以上脱位伴完全性瘫痪者以及C5以下脱位但脊髓水肿平面高于C4水平的完全性瘫痪者,应积极行气管切开,待病情稳定后再行手术治疗;而对于脊髓水肿平面低于C4水平或水肿平面高于C4水平但为不完全性瘫痪的患者,可考虑尽早手术。     

下颈椎骨折脱位合并脊髓损伤的外科手术入路选择

目的探讨下颈椎骨折脱位合并脊髓损伤的外科手术入路选择。方法回顾性分析54例下颈椎骨折脱位合并脊髓损伤患者行手术治疗的临床资料。其中颈椎压缩型骨折脱位29例,颈椎爆裂性骨折脱位7例,单侧小关节脱位3例,双侧小关节脱位15例。美国脊髓损伤学会(ASIA)评分：A级21例,B级5例,C级22例,D级6例。43例采用前路手术,11例采用后路手术。结果术中均无大血管、气管、食道、脊髓意外损伤。术后随访12～36个月,平均18个月。无一例发生钢板、螺钉松动、断裂等并发症。植骨于术后12周均获得骨性融合,无假关节、骨不连发生。96．3％患者术后获得完全复位,术后颈椎椎间高度、生理曲度无丢失。完全性脊髓损伤患者术后神经功能均无恢复,但上肢疼痛、麻木有不同程度的缓解。不完全性脊髓损伤患者术后神经功能均有一定恢复,平均ASIA评分提高1～2级。结论采用前路或后路手术治疗下颈椎骨折脱位均能达到良好的解剖复位,根据颈椎损伤的类型采取适合的手术入路是手术成功的关键。     

中重度颈椎骨折脱位伴无脊髓功能损伤患者的手术治疗

目的探讨中重度颈椎骨折脱位伴无脊髓功能损伤患者的手术治疗方法及疗效观察。方法选择近3年来我科收治的5例无脊髓损伤的单节段下颈椎骨折脱位患者,所有患者先行局麻后路切开复位内固定后再通过前路减压融合内固定手术。术后随访观察。结果 5例患者手术经过顺利,X线片示5例患者均恢复颈椎正常序列及曲度。随访4~24个月未出现脊髓损伤加重症状及再脱位。结论一期局麻下后路复位内固定联合前路减压融合对于无脊髓损伤型颈椎骨折脱位的治疗安全有效。手术复位及内固定植骨融合术是治疗无脊髓损伤型下颈椎脱位的有效方法。     

下颈椎骨折脱位并脊髓损伤的治疗术式探讨

[目的]探讨不同入路手术方式治疗下颈椎骨折脱位合并脊髓损伤的临床疗效。[方法]2011年7月~2015年6月收治下颈椎骨折脱位合并脊髓损伤患者39例,术前Frankel分级A级5例,B级12例,C级14例,D级8例。根据骨折类型、脱位程度、脊髓受压评估情况、是否存在关节突骨折及交锁或者前后复合体损伤等因素选择手术方案。其中24例椎体骨折、椎间盘损伤、术前经颅骨牵引可复位者采用前路减压椎间植骨内固定术;7例颈椎脱位伴小关节骨折或脱位但不伴明显前中柱损伤者采用后路复位侧块螺钉内固定术;8例颈椎椎体骨折、椎间盘损伤、椎小关节脱位交锁、术前经大重量颅骨牵引不能复位者采用前后路联合复位减压固定融合术。比较三种手术方式的手术时间、术中出血量和平均固定节段数;术后定期复查,观察损伤节段的稳定性和融合率,测量Cobb角、椎体水平移位和Frankel评分表,评估脊髓功能恢复与脊柱损伤重建稳定性等情况。[结果]患者获得有效随访,随访时间6~30个月,平均18个月,术后4~6个月均获得良好的骨性融合,均未出现严重并发症。联合入路组手术时间、出血量和平均固定节段数均较单纯前路或后路组长,而后路手术的手术时间、出血量和平均固定节段数明显多于前路手术组(P<0.05);除2例术前Frankel分级A级无恢复外,其余患者均有不同程度恢复,脊髓功能平均提高1.2级。所有患者的术前JOA评分和颈椎复位参数较术后均有改善,差异有统计学意义(P<0.05)。[结论]采用前路手术、后路手术或前后路联合手术治疗下颈椎骨折脱位并脊髓损伤均能获得不错的治疗效果,但应根据颈椎损伤部位及类型采取适合的手术入路,根据病情制订个性化治疗方案。     

急诊前路手术治疗下颈椎骨折脱位23例

目的探讨急诊前路手术治疗下颈椎骨折脱位的价值。方法总结了2001年3月至2006年5月收治的23例下颈椎骨折脱位临床资料,均在全麻下急诊行颈前路减压、复位、植骨及钢板固定。结果全部患者获得随访,时间6~27个月,平均13.5个月。植骨于术后12周均获得牢固骨性融合,颈椎椎间高度、生理曲度及颈椎稳定性维持良好,均获得完全复位。10例不完全性脊髓损伤者脊髓功能均获不同程度改善,13例脊髓完全性损伤者临床症状(如疼痛、麻木等)得到缓解。结论下颈椎骨折脱位可行急诊前路手术,并能获得满意的复位和重建即刻稳定性。     

颈椎前路手术在下颈椎骨折脱位治疗中的应用

目的探讨颈椎前路手术在下颈椎骨折脱位伴脊髓损伤治疗中的作用。方法12例下颈椎骨折脱位伴脊髓损伤患者全部在全麻下行颈椎前路复位、减压、自体髂骨移植及颈椎前路钢板内固定手术。结果12例患者全部得到随访。随访时间：6个月～4年,平均2年8个月。Frankel分级疗效评定较术前平均提高1．6级。摄片随访显示：颈椎脱位全部复位,颈椎序列正常,植骨全部呈骨性愈合,重建椎体高度及颈椎生理曲度无丢失。结论颈椎前路手术治疗下颈椎骨折脱位伴脊髓损伤具有复位简单,减压彻底,固定坚强,利于脊髓功能恢复及早期功能锻炼。     

前路减压植骨内固定治疗颈椎骨折脱位

目的　探讨前路手术在治疗颈椎骨折、脱位中的价值。方法　 16例颈椎骨折、脱位伴脊髓损伤的患者 ,均在全麻下行颈前路减压、复位、钛网植骨及 ORION钢板内固定。按神经功能 Frankel分级标准 ,于术前、术后对所有病例进行分级评定。结果　 16例获访患者中 ,平均随访时间 13.6个月 ,骨折、脱位复位均满意 ,植骨于术后 3～ 6个月融合 ,无钢板螺钉松动、断裂等并发症 ,术后 Frankel分级改善一级左右。结论　严重颈椎骨折脱位伴脊髓损伤选择经前路手术治疗可获得满意的复位、神经功能的改善和即刻稳定性的重建。     

持续闭合复位结合颈椎前路手术治疗颈椎脱位合并颈髓损伤

目的 探讨采用持续闭合复位结合颈椎前路手术治疗颈椎脱位引起的颈髓损伤的可行性和临床效果.方法 应用持续闭合复位结合颈椎前路手术治疗颈椎脱位引起的颈髓损伤136例.结果 本组获随访6～27个月,所有骨折脱位均闭合复位成功,没有发生颈髓损伤加重的现象.术后出现下肢深静脉血栓形成(DVT)14例,低钠血症9例,泌尿系统感染16例,呼吸道感染1例,异位骨化3例.结论 持续闭合复位对下颈椎骨折脱位的矫正安全有效,结合颈椎前路手术固定,在恢复脊柱的稳定性、椎间隙高度和颈椎生理曲度上有效,利于护理和脊髓功能的康复.     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.