Abstract case This case report presents a novel stabilization approach for managing fragility fractures in the dysmorphic sacrum of a 71-year-old male patient. The technique addresses anatomical complexities associated with sacral dysmorphism by employing a photodynamic intramedullary implant. Conclusion The arc-technique utilizing a flexible photodynamic nail enables effective stabilization of the posterior pelvic ring, even in cases involving sacral dysmorphism.
Background:Pelvic ring injuries in elderly patients, particularly in the context of low-energy trauma, typically involve posterior ring structures due to underlying osteopenia or osteoporosis. However, symphyseal disruptions are extremely rare in this population. Pelvic ring injuries in elderly patients are increasingly common due to demographic changes, often resulting from low-energy falls. We present a unique case of a 77-year-old morbidly obese female with a Type B1.1 pelvic ring injury (APC-2, according to Young & Burgess classification), characterized by an open book lesion with no posterior fracture. Given the patient's body habitus and reduced bone quality, a minimally invasive internal fixator spine system was implanted and augmented with polymethylmethacrylate (PMMA) cement to enhance fixation strength and allow early mobilization. Case presentation:A 77-year-old female (BMI: 36 kg/m2) presented with a rare isolated Type B1.1 pelvic ring injury (Fig. 1A) following a domestic fall. After emergency stabilization using an external fixator, in a secondary definitive surgery a subcutaneous internal fixator was implanted bilaterally in a minimally invasive fashion. To improve fixation in the osteoporotic supra-acetabular bone, the screws were cement-augmented using PMMA. The patient showed good postoperative recovery, early mobilization, and stable radiographic outcomes at 6 weeks follow-up. Conclusion:This case illustrates the feasibility and benefit of cement-augmented internal fixator of the pubic symphysis with a rare case of an "open-book" injury in elderly, obese female patient. Cement augmentation may offer additional pull-out strength in patients with reduced bone quality, facilitating early mobilization and avoiding complications related to implant loosening.
War injuries are characterized by a high incidence of bone and soft tissue infections caused by multidrug-resistant (MDR) pathogens. We analyzed the influence of infections with MDR pathogens on the course and outcome of 17 Ukranian patients within the first three years of surgical therapy. To assess the clinical course of Ukrainian war-wounded patients treated in our tertiary care hospital between June 2022 and May 2025, the characteristics of hospital stay, number of operations, bacterial spectrum of wound infections and antibiotic therapies were analyzed retrospectively. Patients had sustained mostly severe extremity injuries several months (105.3 ± 25.1 days) prior to admission. The average length of hospital stay was 165.6 ± 29.6 days. An average of 13 ± 3 operations were performed per patient during this time. Secondary limb amputation was required in 3/17 patients (18
An emerging concept for plate fixation of fractured bones in humans changed from absolute stability through relative stability to a new concept of a predefined range of elastic movement with mechanical amplitude limitation (“Biphasic Plate,” 41 medical, Bettlach, Switzerland). As this represents a novel implant design, only a few studies have investigated it so far, particularly with respect to human cadaveric specimens and in vivo patient-specific cases. Therefore, this study aims to investigate the biphasic behavior using in vitro, in silico, and in vivo methodologies concerning stress distributions under realistic boundary conditions. To test this, an implantable in vivo strain measurement system (“Fracture Monitor,” AO Foundation, Davos Switzerland) and a camera system are employed for experimental data acquisition, while patient monitoring captures actual boundary conditions during daily activities. Finite element simulations are performed on patient-specific 3D models generated from computed tomography imaging, allowing for detailed stress analysis. These simulations are validated through experiments on human cadaveric specimens in a custom-designed test rig by investigating the specific behavior of the biphasic plate with its two different modes (rigid and flexible). Under axial loading, the stresses are distributed centrally; while in patient-specific cases, the stress pattern changes markedly, with maximum stresses concentrating along the lateral side of the plate. By the chosen biomechanical testing setup, the in silico simulations could be validated, demonstrating the ability to accurately replicate the postulated motion sequence of the biphasic plate. This iteration emphasizes both validation and reproducibility as the key outcomes.
Purpose:Traumatic open book injuries of the pubic symphysis require stable fixation while minimizing surgical morbidity. Traditional symphyseal plating is associated with complications such as implant failure and infections. This study aims to evaluate the biomechanical performance of a novel minimally invasive technique using an internal fixator (IF) compared to conventional plating (symphyseal locking dynamic compression plate [SLDCP]) in human cadaveric pelvises. Methods:Ten human cadaveric pelvises were assigned to two groups (n = 5 each). After anatomical reduction, either SLDCP or IF stabilization was applied. Intrasymphyseal compression forces, contact area and interfragmentary motion were assessed using pressure-sensitive sensor films and an optical tracking system under incrementally applied axial loads up to 600 N. Bone density and symphyseal dimensions were measured and were comparable across both groups. Results:At key loading stages (400 and 600 N), the IF group demonstrated significantly higher intrasymphyseal compression forces (IF 61.78 ± 31.98 N vs. SLDCP 15.98 ± 8.2 N at 400 N and IF 42.82 ± 25.2 N vs. SLDCP 9.42 ± 5.81 N at 600 N) and larger contact areas (IF 453 ± 137.6 mm2 vs. SLDCP 216 ± 135 mm2 at 400 N and IF 337.6 ± 168.45 mm2 vs. SLDCP 154 ± 59.73 mm2 at 600 N), with more homogeneous segmental force and area distributions. Higher compression forces, particularly in the caudal symphyseal region (IF 23.68 ± 18.69 N vs. SLDCP 13.78 ± 10.1 N), were achieved. Three-dimensional analysis showed reduced fragment displacement in the IF group under load. Conclusion:The proposed technique using an internal fixator provided superior biomechanical stability compared to standard plating, offering a promising minimally invasive alternative for managing open book injuries. The technique facilitates uniform force transmission and improved contact conditions, which may enhance healing and reduce complications. Level of Evidence:N/A.
Introduction:Little is known about the long-term subjective patient experience after acetabular fracture and its relationship with changes in gait patterns. Worse outcomes were hypothesized compared with healthy control participants. Methods:Patient-Reported Outcome Measure Information System (PROMIS) questionnaires and treadmill-based gait analyses were conducted. Twenty parameters derived from the ground-reaction force curve were analysed. One-way ANOVA, Mann‒Whitney U tests, and regression statistics were used to assess differences between patients and controls (26 participants) and correlations between PROMIS scores and gait parameters. Results:Twenty-six patients (19 men and 7 women, 52.09 ± 12.77 years) with previous acetabular fracture an average of 9.90 ± 2.97 years prior to the study were included, all with excellent or good quality of reduction. While significantly worse results were found in the fracture than in the control group for all tested PROMIS scores (Physical Health, p < 0.001; Mental Health, p < 0.001; Pain Interference, p = 0.011; Physical Function, p < 0.001), no changes were observed in the gait parameters. There was no correlation between the PROMIS scores and any of the gait parameters. Forty-six percent of patients reported occasional pain and twelve percent noted weather sensitivity. Discussion:Factors other than changes in gait pattern seem to cause worse PROMIS scores in patients after acetabular fracture.
Background: Chronic anterior pelvic instability may require symphyseal arthrodesis when conservative treatment and isolated plating fail. Therefore, dual plating has been clinically used to improve stability, however the technique requires extended surgical exposure. As a novel augmentation FiberTape® cerclage may provide comparable mechanical stability while reducing invasiveness and providing radiolucency for improved analysis of bone healing. Methods: Twenty-four synthetic pelvic models (n = 8 per group) were stabilized using symphyseal plating, dual plating, or plate–cerclage constructs. Cyclic axial loading (50–400 N) was applied in a unilateral stance and bilateral-leg stance biomechanical model.Results: The plate–cerclage resulted in significantly higher compression force (131.5 ± 31.7 N) compared to plate-only fixation (88.2 ± 20.9 N; p = 0.019), corresponding to a 49% increase. Dual plating reduced contact area (p ≤ 0.049). No significant differences were observed in one-leg stance.Conclusion: Fiber-Tape cerclage augmentation significantly enhances distraction resistance and preserves contact area compared to dual plating. Furthermore, this technique will allow improved radiological visualization of the area of interest in the pubic symphysis after arthrodesis to analyze bone healing and osteointegration.
The setup of experimental designs in basic bone research begins with selecting appropriate osteogenic supplements to induce differentiation. Many studies describe the use of the supplements ascorbic acid, dexamethasone, and β-glycerophosphate in varying combinations and concentrations. To clarify their individual and combined effects on MC3T3-E1 cells, we conducted a detailed study focusing on cell morphology, mineralization, and gene expression of key osteogenic markers at four time points. Cell morphology was analyzed using light and scanning electron microscopy. Mineralization was assessed via Alizarin Red staining for calcium and von Kossa staining for phosphate. Additionally, energy-dispersive X-ray analysis was used to detect calcium and phosphorus in the cell layer. Sirius Red staining was applied to characterize the fiber formation observed under electron microscopy. To evaluate the influence of the supplements on gene expression, real-time quantitative PCR was performed for the osteogenic markers alkaline phosphatase, bone sialoprotein, bone morphogenetic protein 2, collagen 1a2, osteocalcin, osterix, and runt-related transcription factor 2. Osteogenic differentiation of MC3T3-E1 cells could be induced by application of ascorbic acid and β-glycerophosphate leading to upregulation of osteogenic markers, changes in cellular morphology, and mineralizing activity. Nevertheless, this effect could be further increased by additional use of dexamethasone. While most osteogenic marker genes were already upregulated on day 7, we did not see the first signs of mineralization until day 14. We recommend using ascorbic acid, β-glycerophosphate, and dexamethasone in order to get an osteogenic phenotype of MC3T3-E1 on day 14 at the earliest.
Patients with unstable hemodynamics and unstable pelvic ring injuries are still demanding patients regarding initial treatment and survival. Several concepts were reported during the last 30 years. Mechanical stabilization of the pelvis together with hemorrhage control offer the best treatment option in these patients. While pelvic ring stabilization using pelvic binders, external fixators and the pelvic C-clamp are the basis for mechanical stability of the pelvic ring, the optimal modality for pelvic bleeding control is still under discussion. Beside angioembolization (AE) and Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA), pelvic packing PP (predominantly extraperitoneal) with direct access to the pelvic bleeding sources, are potential options. The present overview represents the present status, results and the value of pelvic packing in treating these patients. Interpretation of these results must consider the difference between the initial European concept of pelvic ring stabilization followed by PP in contrast to the North American concept with a reduced rate of pelvic ring stabilizations.
Metamizole is a commonly used analgesic drug in clinical fracture management, which does not affect the healing process under physiological conditions. However, many fracture patients suffer from co-morbidities resulting in ischemic conditions with impaired bone healing. The effect of metamizole on fracture healing under ischemic conditions has not been analyzed so far. Accordingly, in this study 44 CD-1 mice underwent ligation of the deep femoral artery to induce mild ischemia in the right hind limb. The femur was then fractured and stabilized with an intramedullary lag screw and the animals were daily treated per os with 50 mg/kg metamizole (n = 23) or vehicle (control; n = 21). Serum concentrations of the active metamizole metabolites, 4-methyl-amino-antipyrine (4-MAA) and 4-amino-antipyrine (4-AA), were determined 30, 60 and 90 min after administration. Bone healing was analyzed by biomechanical, radiological, histomorphometrical and Western blot analysis at 2 and 5 weeks postoperatively. The plasma level of 4-MAA was high at all time points, whereas 4-AA peaked at 90 min after administration. Biomechanical, radiological and histomorphometrical analyses revealed no differences between metamizole-treated and control mice, while both groups showed a delayed fracture healing. Of interest, Western blot analyses of callus tissue showed an increased expression of the pro-angiogenic factor Cyr61 and the osteoanabolic runt-related transcription factor 2 (RUNX2) as well as the osteocatabolic receptor activator of NF-κB ligand (RANKL) in metamizole-treated animals when compared to controls. Taken together, these findings indicate that the application of metamizole does not affect fracture healing under ischemic conditions. Therefore, treatment with this analgesic drug may be also recommended in fracture patients suffering from co-morbidities resulting in tissue ischemia.
The postoperative assessment of fracture healing remains a clinical challenge despite established treatment standards. The lack of reliable information on the mechanical stability of the fracture complicates individualized follow-up care. This increases the risk of delayed mobilization, implant overload or late detection of healing complications.Sensor-based implants, such as the AO Fracture Monitor enable objective, continuous measurement of implant load, offering a novel approach to evaluating the healing process. Preclinical studies demonstrate a significant correlation between mechanical load and radiological healing parameters, confirming the potential of instrumented implants for diagnostic and preventive applications. Initial clinical data are currently being collected as part of a multicenter study. Additional application areas, such as spinal fusion and hip fracture treatment are the focus of ongoing research and commercial development efforts.Continuous data acquisition enables uninterrupted remote monitoring, independent of scheduled follow-up examinations. This opens new possibilities for dynamic adjustment of treatment protocols, early detection of complications and targeted rehabilitation management; however, integrating such systems into routine clinical practice poses substantial regulatory and procedural challenges. Current studies therefore provide an essential foundation for the gradual establishment of personalized follow-up strategies in routine clinical care.
Pelvic injuries mainly arise from high-energy traumas. The preclinical application of pelvic binders is advocated for suspected pelvic fractures with hemorrhage. In vitro cadaveric studies do not provide proof of principle despite their widespread use. This study evaluates clinical experience and physician perceptions regarding the use of pelvic binders in pelvic trauma. A total of 271 physicians regularly treating polytraumatized patients were surveyed using a 22-item multiple-choice questionnaire. Participants were recruited at trauma surgery conferences in 2019 and 2020 and via the mailing list of the German Society of Trauma Surgery. Data included respondents' professional background and experience in the treatment of pelvic trauma. Most participants were experienced trauma surgeons, with 76.6% holding a consultant-level position and 68.6% having over 10 years of trauma experience. Pelvic binders were the most commonly used external stabilization device (90.4%), although only 48.9% believed they led to hemodynamic improvement in the majority of patients. Furthermore, 95% estimated that ≤ 50% of patients with pelvic fractures actually bled due to the fracture, and 88.5% reported that fewer than half of patients arriving with a binder had confirmed fractures. Despite this, 95.1% of respondents still felt pelvic binders were more effective than harmful. While pelvic binders remain widely accepted by clinicians, the survey findings indicate a disconnect between their routine use and the low observed rate of fracture-associated bleeding or confirmed pelvic injuries. These results suggest the need for more selective, evidence-based application of pelvic binders in the prehospital setting.
BACKGROUND:The individual assessment of the postoperative healing situation contributes significantly to detecting healing disorders, ensuring the mechanical stability of implants, and planning revision surgeries. METHODS:Our established workflow consists of the following steps: (1) Monitoring of the patients during their treatment course with a motion capturing system as kinematic and sensor insoles for the kinetic gait analysis, (2) transfer of the motion data into the musculoskeletal simulation system AnyBody™ to achieve the corresponding individual muscle and joint forces. (3) Clinical imaging of the patients via postoperative computed tomography scans, ideally combined with a six-rod bone density calibration phantom. (4) Segmentation of the CT images and generation of the corresponding adaptive finite element meshes of the bone-implant systems, including the material parameters based on Hounsfield units and calibration phantom via the software ScanIP™. (5) Based on the patient-specific model, all information from the musculoskeletal simulation and gait analysis is transferred to our biomechanical simulation process as patient-specific constraints. FINDINGS:This workflow allows us to simulate individual patient models based on their respective actual motion data over their treatment course. Thus, pathological processes that may lead to non-healing fractures can be detected early after surgery and prevented by adapting the postoperative treatment protocol. Furthermore, it is possible to understand the forces that affect the fracture and its healing process permanently in more detail. INTERPRETATION:The findings demonstrate that the individual motion parameters and fracture morphology influence the local healing parameters and create individual weight-bearing recommendations.
Two main influencing factors of human soft tissue healing are concomitant diseases and cellular senescence, both accumulating with increasing age. Due to the raising population of the elderly in western countries, it is essential to enhance the level of knowledge concerning the function of senescence in a granulation tissue during repair. The present study was intended to verify classic markers of senescence, like senescence-associated ß-galactosidase and the development of a senescence-associated secretory phenotype among fibroblasts during emerging senescence. The application of an in vitro model using serial passaging as inducer of replicative senescence revealed specific differences of a non-senescent and a pre-senescent fibroblast phenotype in mono-cultures, representing the basis for a detailed examination of the phenotypes in their interaction with microvascular endothelial cells in co-cultures. The results deliver new insights into the age dependent process of tissue repair. Characteristics of pre-senescent fibroblasts in terms of modified proliferation, cell morphology, cell cycle regulation, myofibroblastoid differentiation and cytokine release indicate a strong responsibility of this phenotype for the composition and function of a granulation tissue at different locations, including vascular sites. In its entirety, the results support the assumption, that a missing clearance of the senescence phenotype in late stages of tissue repair is one of the main reasons for healing failure.
Instrumented insoles have created opportunities for patient monitoring via long-term recordings of ground reaction forces (GRFs). As the GRF curve is altered in patients after lower-extremity fracture, parameters defined on established curve landmarks often cannot be used to monitor the early rehabilitation process. We aimed to screen several new GRF curve-based parameters for suitability and hypothesized an interrelation with days after surgery. In an observational longitudinal study, data were collected from 13 patients with tibial fractures during straight walking at hospital visits using instrumented insoles. Parametrized curves were fitted and regression analyses conducted to determine the best fit, reflected in the highest R2-value and lowest fitting error. A Wald Test with t-distribution was employed for statistical analysis. Strides were classified as regular or non-regular, and changes in this proportion were analyzed. Among the 12 parameters analyzed, those with the highest R2-values were the mean force between inflection points (R2 = 0.715, p < 0.001, t42 = 9.89), the absolute time between inflection points (R2 = 0.707, p < 0.001, t42 = 9.83), and the highest overall force (R2 = 0.722, p < 0.001, t42 = 10.05). There was a significant increase in regular strides on both injured (R2 = 0.427, p < 0.001, t42 = 5.83) and healthy (R2 = 0.506, p < 0.001, t42 = 6.89) sides. The proposed parameters and assessment of the regular stride ratio enable new options for analyses and monitoring during rehabilitation after tibial shaft fractures. They are robust to pathologic GRF curves, can be determined independently from spatiotemporal coherence, and thus might provide advantages over established methods.
Background: Sacroiliac screw fixation in elderly patients with pelvic fractures remains a challenging procedure for stabilization due to impaired bone quality. To improve it, we investigated the biomechanical properties of combined oblique sacroiliac and transiliosacral screw stabilization versus the additional cement augmentation of this construct in a cadaver model of osteoporotic bone, specifically with respect to the maximal force stability and fracture-site motion in the displacement and rotation of fragments. Methods: Standardized complete sacral fractures with intact posterior ligaments were created in osteoporotic cadaver pelvises and stabilized with a triangle of two oblique sacroiliac screws from each side with an additional transiliosacral screw in S1 (n = 5) and using the same pelvises with additional cement augmentation (n = 5). A short cyclic loading protocol was applied, increasing the axial force up to 125 N. Sacral fracture-site motion in displacement and rotation of the fragments was measured by optical motion tracking. Results: A maximum force of 65N +/− 12.2 N was achieved using the triangular screw stabilization of the sacrum. Cement augmentation did not provide any significant gain in maximum force (70 N +/− 29.2 N). Only low fragment displacement was observed (2.6 +/− 1.5 mm) and fragment rotation (1.3 +/− 1.2°) without increased stability (3.0 +/− 1.5 mm; p = 0.799; 1.7 +/− 0.4°; p = 0.919) following the cement augmentation. Conclusions: Triangular stabilization using two obliques and an additional transiliosacral screw provides sufficient primary stability of the sacrum. Still, the stability achieved seems very low, considering the forces acting in this area. However, additional cement augmentation did not increase the stability of the sacrum. Given its lack of beneficial abilities, it should be used carefully, due to related complications such as cement leakage or nerve irritation. Improving the surgical methods used to stabilize the posterior pelvic ring will be a topic for future research.
Background: Fragility fractures of the pelvic ring (FFPs) represent a fast-growing entity in geriatric traumatology with increasing incidence worldwide. This study aimed to analyze the epidemiology, treatment concepts, and surgical strategies for FFPs based on data collected by the German Pelvic Multicenter Study Group documented in the German Pelvic Fracture Registry. It is the largest cohort study of its kind. Methods: This retrospective cohort study included patients aged 65 years or older after FFPs, as classified according to the Rommens and Hofmann classification. Data were collected from July 2018 onward and analyzed for demographics; fracture classifications; treatment modalities (operative vs. non-operative); and details of surgery, including timing and choice of implants. Patients after high-energy trauma were excluded. Statistical analyses included descriptive metrics and subgroup comparisons. Results: Among 1242 patients (84% female; median age 83.4 years), FFP Type II was the most common fracture type (50.8%), followed by Type IV (21.1%). Non-operative management was employed in 68.8% of cases, while 30.9% underwent surgery. Surgical intervention was more frequent in higher-grade FFPs (e.g., 72.1% in Type IV). The most common surgical technique for the posterior pelvic ring was percutaneous screw fixation (61.3%), with navigation used in 47.4% of cases. Conclusions: This study highlights the variability in treatment strategies for FFPs, with conservative management predominating in lower-grade fractures and surgical approaches increasingly utilized for more complex cases. The findings underscore the need for standardized, evidence-based guidelines and further research to optimize treatment and long-term outcomes for geriatric patients with FFPs.
INTRODUCTION:An objective way to monitor bone healing in real time could provide major benefits for the rehabilitation of fracture patients. The fracture monitor T1 is a novel biofeedback sensor system designed to provide continuous data of the relative implant load, that is, a measure inversely correlated to bone healing progression as well as patient's physical activities. The primary objective of this first-in-human study is to evaluate the safety, that is, the incidence of adverse device effects (ADEs), of the investigational device fracture monitor T1 in femoral fracture patients within the first 6-months postsurgery. Secondary objectives are to collect information on clinical performance, other safety parameters and device handling and usability. METHODS AND ANALYSIS:37 adult patients with femoral fractures to be treated with a plate, which is compatible with having the fracture monitor T1 mounted on it, will be prospectively enrolled in this multicentre, interventional first-in-human study. The fracture monitor T1 will be implanted together with the osteosynthesis plate for femoral fracture fixation as well as femoral instabilities, such as post-traumatic non-unions. Standard of care will be followed for femoral fracture treatment and patients will be followed up for 6-months. Demographic data, comorbidities, prior medication, prior treatment details, injury details, treatment details and outcome measures will be documented in a cloud-based database. The primary outcome measure is ADEs. Secondary outcome measures include clinical and functional outcomes, safety outcomes, device removal, patient-reported outcomes (pain, Numeric Rating Scale, EQ-5D-5L), device handling and usability, number of visits and radiographic assessments, radiographic outcomes, relative implant load and technical performance parameters. A statistical analysis plan will be prepared before final analysis. ETHICS AND DISSEMINATION:Ethics approval is obtained at each site before patient enrolment, which follows an informed consent process approved by the responsible ethics committee. Data from this first-in-human study will be compiled into a clinical evaluation report for the application of CE (Conformité Européenne, certification mark indicating conformity with European Union health, safety and environmental protection standards) marking of the device. The results of this first-in-human study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER:NCT05410587.
Background/Objectives: Patients suffering from fractures are often treated with clopidogrel during the phase of bone healing due to multiple comorbidities. Studies indicate that clopidogrel suppresses osteoblast proliferation and the formation of trabecular bone. However, it is unknown whether clopidogrel also affects fracture healing under ischemic conditions, as they may occur in multimorbid patients. Methods: To test this in the present study, a murine ischemia model was performed in CD-1 mice by ligating the right deep femoral artery to induce mild ischemia of the right lower limb. A closed fracture of the femur was then stabilized by inserting an intramedullary lag screw. The animals received either 3 mg/kg body weight clopidogrel daily per os or vehicle (control). Bone healing was assessed by biomechanical, radiological, histomorphometrical and Western blot analyses 2 and 5 weeks postoperatively. Results: The fractured femurs in the clopidogrel group exhibited no increase in biomechanical stiffness throughout the observation period in contrast to controls. While the radiological analysis showed no differences between both groups, histomorphometric analyses demonstrated a significantly reduced bridging score, less bone and more connective tissue within the callus of clopidogrel-treated animals. Western blot analyses revealed a significantly reduced expression of the osteogenic marker bone morphogenetic protein (BMP)-4 and an increased expression of the blood vessel marker CD31. Conclusions: These results show that clopidogrel may impair fracture healing under challenging ischemic conditions, which is associated with a shift in angiogenic and osteogenic expression markers in the callus tissue. Therefore, clopidogrel treatment may not be recommended in fracture patients with tissue ischemia.