Critical investigation of the pre-surgical anatomic factors that influence the aesthetic result in post-extractive implantology and immediate prosthetic.

The aesthetic goals of implant dentistry should be similar to those of conventional prostheses. In implant-prosthetic rehabilitations of the anterior sectors, the quantity and quality of hard and soft tissue play a fundamental role in achieving the desired aesthetics and in integrating the restoration in a complete and harmonious way into the existing anterior dentition. Post-extraction implantology is a treatment option for implant therapy after the extraction of a single tooth in the anterior jaw. This article presents some key factors to analyze and follow in order to achieve a predictable and acceptable aesthetic result. The creation of a predictable peri-implant aesthetics requires adequate preservation of the bone and soft tissues around the teeth that will be extracted and a correct positioning of the 3D implant. Furthermore, aesthetic success requires the creation of a correct transmucosal path, during the provisional prosthetic phases, which must be replicated and maintained with the definitive crowns.

Guided sinus lift: virtual planning of surgical templates for lateral access.

The sinus lift with lateral approach is a regenerative technique nowadays considered predictable to increase the height of bone in the atrophic posterior maxilla. Knowledge of sinus anatomy and evaluation of risk factors are the basis of regenerative and rehabilitative surgical success. The positioning and size of the lateral antrostomy represent critical factors in the execution of regenerative surgery, due to the difficulty in transferring radiological information to the lateral wall of the maxillary sinus even for skilled surgeons. The knowhow of guided implant surgery in recent years is also finding use in planning and precisely delineating the lateral access to the maxillary sinus using CBCT imaging and dimensional reconstruction software, through the realization of surgical guides with 3D printing, as shown in the presented case.

Endodontic retreatment and bioceramics: A case report.

The success rate in endodontic retreatment can be significantly boosted by using materials that guarantee both intimate adhesion to the canal walls and long-term stability. Bioceramic cements used in root filling show interesting properties including extraordinary sealing capacities, antimicrobial activity that stimulates periapical healing and the continuous production of hydroxyopathitis for a long time. This case report deals with the application of bioceramic cement in endodontic retreatment. The Bioroot RCS (Septodont), thanks to its ability to firmly adhere both to the gutta-percha and to the walls of the canal and to definitively seal the apical third, can allow to obtain extraordinary healing in a relatively short time by exploiting its antimicrobial abilities. However, further studies are needed to assess the effectiveness of this technique over the long term.

"There's always something else": Patient perspectives on improving the implementation of obesity guidelines in general practice.

OBJECTIVES: The prevalence of obesity in Australia is rising. National guidelines for the management of overweight and obesity exist but our previous work demonstrates poor implementation of key elements in general practice. The aim of this study was to describe patient perspectives on the implementation of obesity guidelines in general practice. METHODS: Qualitative study of 40 people living with obesity (PwO) who were recruited through general practices in Melbourne, Australia. PwO had a recorded BMI in the overweight range or above (>25), had attended a consultation in the last 6 months and had a diagnosis of at least one of the following: diabetes, kidney disease, hyperlipidemia, hypertension, or cardiovascular disease. Semi-structured telephone interviews were conducted with patients. Interviews were audio-recorded, transcribed verbatim and analysed thematically. RESULTS: While a strong general practitioner (GP)-patient relationship enabled conversation to occur about weight management there was uncertainty as to whether patients or GPs should broach the topic of weight. Patients described complacency regarding their weight and often being unprepared to take up GP advice. Other health issues were felt to take precedence, and patients described inconsistent provision of information and resources to assist them in tackling their weight problems. CONCLUSIONS: It is imperative to take into account patient perspectives on obesity management in general practice in order to improve health outcomes. This study provides valuable insights into how PwO can be better managed. Interventions should also include strategies to help patients maintain motivation in making lifestyle changes to support healthy weight loss.

Patient chosen gap payments in primary care: Predictions of patient acceptability, uptake and willingness to pay from a discrete choice experiment.

Compulsory co-payments limit access and may compromise quality in primary care. Patient Chosen Gap Payments (PCGPs) allow patients to specify a (voluntary) out-of-pocket contribution, creating an incentive for patient-centred care without the need for complex outcomes-based funding formulae. It is not yet known if widespread use of PCGP services is consistent with consumer preferences. We conducted a discrete choice experiment (DCE) in a sample of the adult Australian general population (n = 1457) during April 2019 to simulate patient choice between alternative primary care services and describe preferences for PCGP services. Participants also completed a supplementary valuation task in which participants reported their intended PCGP contribution for PCGP services. Finally, we conducted policy-simulations to predict market shares when PCGP clinics operate alongside the two existing models of primary care funding in Australia. Results suggest that patients prefer shorter wait time, longer consults, lower compulsory copayments, services with higher patient satisfaction ratings, choice of doctor and $0 suggested voluntary contribution for PCGP services. Policy-simulations suggest that high-quality PCGP services could obtain market share of up to 39% and voluntary contributions of up to $25.36 per service (95%CI: $10.24, $40.47), potentially adding $1.48 billion AUD in revenues and funding for primary care at no cost to government. Low-quality PCGP services are unlikely to capture significant market share and PCGP contributions were lowest for low-quality PCGP services ($12.12, 95%CI: $2.09, $26.34). Further field testing is recommended where (i) patients make consequential choices (e.g. real payments for simulated services), and (ii) dynamic effects on quality of care and utilisation can be observed; particularly in vulnerable populations. We conclude that PCGP services aligned with patient preferences could capture significant market share and substantially increase revenue to general practice.

MRI findings of working and non-working TMJ during unilateral molar clenching on hard bolus.

The aim of this study is to evaluate with MRI the TMJs behavior during one-side clenching on a hard bolus. The sample consisted of 13 patients. an MRI of TMJ using a 1.5 Tesla superconducting magnet and a dedicated surface coil was performed in all patients. Parasagittal scans of the TMJ (perpendicular to the long axis of the condyles) were made with the mouth closed, open and with a plastic thickness 10 mm high, 15 mm wide and 20 mm long always interposed between the molars of the left side; TSE T2W and DPW sequences were used. The working condyle is always positioned behind the non-working contralateral condyle and the morphology of the retrodiscal tissue upper lamina was curvilinear in all TMJs examined. This work confirmed that, during clenching on a unilateral hard bolus, the working condyle translates less than the balancing one and that the condyle-disc ratios are substantially the same in both sides. The study of the retrodiscal tissue imaging in the different functional phases, suggest that it does not exert any pulling force towards the disc.

Appearance of normal MRI anatomy of the lingual nerve using steady-state free precession sequences at 3-T.

The aim of this study is to assess the value of SSFP MRI sequence in depicting the normal anatomy of the lingual nerve (LN), particularly in the molar region, in order to help the periodontists, dentists and oral surgeons in their daily practice. The study group included 24 patients who were to undergo MR study for a reason unrelated to our purpose. All imaging was performed by using a 3.0T system with a head and neck multiarray coil. The evaluation criteria included image quality factors such as the identification of the LN, its demarcation and its contrast to surrounding tissues on a five-point scale. The LN is clearly visible throughout its course from its origin from the mandibular nerve (MN) to the mylohyoid muscle. In edentulous patients, the LN could be damaged during surgical procedures especially it during the dissection and retraction of a lingual flap and, above all, during the suture due to a direct trauma caused by the needle or indirectly during tying the knot.

Lateral meniscal cysts: long-term clinical and radiological results of a partial meniscectomy and percutaneous decompressive needling.

INTRODUCTION: The aim of this study was to describe clinical and radiological long-term results of an arthroscopic partial meniscectomy associated with an outside-in decompressive needling of the cyst for lateral parameniscal cyst. METHODS: Eighteen patients with symptomatic parameniscal cysts treated between April 2002 and September 2009 were retrospectively included in the study. All patients underwent arthroscopic partial meniscectomy (preserving peripheral rim) and needling of the cyst using a 20-gauge needle. Pre- and post-operative IKDC, Tegner, and Lysholm scores were used to evaluate clinical results. Radiological results were obtained from pre- and post-operative radiographies and post-operative MRI scans. Both supine and weight bearing MRI examinations were performed. Kellgren-Lawrence and WORMS scales were used to evaluate osteoarthritis development of the knee. RESULTS: The mean follow-up period was 11.6 ± 2.6 years (range 7-15). Horizontal lesions were found in 56% of patients. All patients fully recovered. Mean Lysholm scores passed from mean pre-operative value 52 ± 16.9 to post-operative 85 ± 11.9 (P < 0.01) and mean IKDC scale score changed from 49.5 ± 14.7 to 67 ± 23.5 (P < 0.01). Mean Tegner scores did not change significantly. Post-operative radiographies showed a Kellgren-Lawrence scale grade 0 in six patients (33%), a grade I in eight (44%), a grade II in three (17%), and a grade III in one patient (6%). No patients were found with a Kellgren-Lawrence scale grade IV. No significant differences with pre-operative radiographies were found (chi-square = 1.867; df = 3; P = 0.60) in osteoarthritis development of the knee. Reported WORMS scores had an average of 12.4 ± 5.1. No recurrence of any cysts was observed. DISCUSSION: Different treatments for lateral meniscal cysts have been proposed, but proper management of the cyst is still controversial. The results of this study suggest that the outside-in needling of the cyst associated with partial meniscectomy is a highly effective, simple, and repeatable technique. Excellent clinical outcomes were reported at a mean follow-up of 11.6 ± 2.6 years (range 7-15). Imaging evaluation showed no significant evolution to osteoarthritis of the knee. CONCLUSIONS: Partial arthroscopic meniscectomy associated with percutaneous decompressive needling of the cyst wall under arthroscopic visualization showed positive clinical and radiological long-term results. Neither traditional radiographies nor innovative standing MRIs showed findings of osteoarthritis.

"90% of the time, it's not just weight": General practitioner and practice staff perspectives regarding the barriers and enablers to obesity guideline implementation.

OBJECTIVE: To identify the views of GPs and general practice staff regarding barriers and enablers to implementation of obesity guideline recommendations in general practice. METHODS: Twenty general practitioners (GPs) and 18 practice staff from inner-eastern Melbourne, Australia, participated in semi-structured telephone interviews. The interview schedule was informed by the Theoretical Domains Framework (TDF). Interviews were audio-recorded, transcribed verbatim and underwent thematic analysis. RESULTS: Participants lacked familiarity with and knowledge of the NHMRC obesity guidelines. Barriers and enablers were predominantly related to five theoretical domains: (1) environmental context and resources, (2) knowledge, (3) emotion, (4) beliefs about consequences, and (5) motivation and goals. Time pressures in consultations, costs for the patient, reluctance to add to patient burden particularly in those with comorbidities such as mental health issues, lack of awareness about services to refer patients to and GPs' fear of embarrassing patients and losing them were significant barriers. Enablers included having a strong doctor-patient relationship and a sense of responsibility to the patient to address weight. CONCLUSIONS: Obesity guidelines and policy makers need to better engage with issues of multimorbidity, socioeconomic disadvantage and workforce issues if recommendations are to be widely adopted in general practice. Tasksharing, teamwork and technology are potential solutions to some of the barriers. Patient perspectives and approaches to being able to overcome stigma and legitimise obesity management in primary care consultations could also assist.

Cancer, ageing, multimorbidity and primary care.

Cancer care is complex, and made more so by multimorbidity and ageing. Multimorbidity affects all stages of cancer care from prevention and early detection through to end of life care. The effectiveness of cancer treatments in multimorbid patients may not be understood, as many conditions common in older people may be exclusion criteria in oncology clinical trials. The interaction between pre-existing physical capacity, multiple medical conditions and ageing can delay diagnosis, impact on treatments, complicate survivor care, and impact on decisions about starting and ceasing treatments. General Practitioners (GPs) manages multimorbidity routinely, yet the GP role in comprehensive cancer care is limited. Integration of GP management of multimorbidity in conjunction with oncology services should improve patient outcomes. Integration of care for these patients can educate patients on the minimisation of multimorbidity, develop personalised screening plans and contribute to the wholistic management of people in the surveillance period. GPs should have a major role in end of life care. Integration of general practice and oncology should benefit patient care.

Nonsurgical treatment of Mason type II radial head fractures in athletes. A retrospective study.

OBJECTIVE: The best treatment for moderately displaced radial head fractures (Mason type II) still remains controversial. In cases of isolated fractures, there is no evidence that a fragment displacement of ≥ 2 mm gives poor results in conservatively treated fractures. PATIENTS AND METHODS: We retrospectively reviewed 52 patients (31M, 21F) affected by an isolated Mason type II fracture, treated with a long arm cast for two weeks between 2008 and 2013. All patients had practiced sports before being injured. They were all either bicyclists, or baseball, boxers, basketball, rugby, tennis or football players. The mean follow-up was 36 months. Elbow and forearm range of motion were measured. The Mayo Elbow Performance Score, the Broberg and Morrey rating system and the Disabilities of the Arm, Shoulder and Hand Score (DASH score) were analyzed. Follow-up radiographs were examined for evidence of consolidation, late displacement, early arthritis and non-unions. RESULTS: Flexion was slightly impaired in the injured limb when compared to the uninjured limb (137°± 6° versus 139°±5°) as were extension (-3°±6° versus 1°±4°, p < 0.05), supination (86°±6° versus 88°±3°), pronation (87°±4° versus 88°±6°) and valgus deviation (10°±4° versus 8°±3°, p < 0.05). 40 patients had no elbow complaints; 9 patients experienced occasional pain, 2 a mild instability of the elbow, and 4 a mild loss of grip strength. The DASH score was excellent in 48 patients (92.31%). In only 6 cases (11.53%) degenerative changes were greater in formerly injured elbows than in uninjured elbows. All patients returned to their previous sports activities. CONCLUSIONS: Isolated Mason type II fractures can have a good or excellent mid-term functional outcome even when treated conservatively.

Nanohydroxyapatite promotes the healing process in open-wedge high tibial osteotomy: A CT study.

BACKGROUND: The aim of this prospective and randomized study was to evaluate the effectiveness of adding nanohydroxyapatite (NHA) to heterologous bone graft in open wedge high tibial osteotomy (OWHTO) by measuring the bone density of the tibial osteotomy gap. METHODS: Twenty-seven patients (26 knees) were operated by OWHTO and randomly divided into two groups: pure graft group, in which the osteotomy gap was filled with only heterologous bone graft; nanohydroxyapatite group, in which the osteotomy gap was filled with heterologous bone graft and NHA. All patients underwent computed tomography (CT) examination within one week after operation (Time 0), and after two months (Time 1) and 12months (Time 2). CT volume acquired Hounsfield Units (HU) were calculated and the mean value of bone density on three planes was measured. RESULTS: At Time 0, the mineral density of the nanohydroxyapatite group appeared significantly higher compared with the pure graft group, due to the presence of NHA. At Time 1, the mineral density of the nanohydroxyapatite group had decreased relative to Time 0, while in the pure graft group it remained unchanged. At Time 2, the mineral density in the nanohydroxyapatite group had further decreased, reaching values close to the mineral density of normal bone. In contrast, in the pure graft group the mineral density had increased, probably due to the lack of reabsorption of the graft and the development of sclerosis in the osteotomy borders. CONCLUSIONS: The results of the present study show better osseointegration of the heterologous graft when nanohydroxyapatite is added.

Static and dynamic MR imaging in the evaluation of temporomandibular disorders.

OBJECTIVE: The aim of this study is to prove if dynamic HASTE (half-Fourier acquisition single-shot turbo spin-echo) sequences can be used in the diagnosis of internal derangement disorders of temporomandibular joint (TMJ) as an alternative to static proton density (PD) weighted/turbo spin echo (TSE) T2-weighted sequences which are considered up to now as the gold standard in the evaluation of TMJ disorders (TMDs). PATIENTS AND METHODS: 194 patients for a total of 388 TMJs were examined with a 1.5 Tesla field strength superconducting magnet. Sagittal static PD-weighted/TSE T2-weighted and dynamic HASTE sequences have been used. Three experts in the field of oral radiology (specialist A, B and C) independently and blinded to clinical symptoms and any treatment, assessed the articular disc position in each TMJ (rated as normal or disc displacement with reduction or disc displacement without reduction). The agreement between static and dynamic images and between the three different specialists in the assessment of the articular disc position was evaluated using kappa statistic. RESULTS: The agreement between static and dynamic images is: for specialist A, K = 0.862; for specialist B, K = 0.870 and for specialist C, K = 0.862. CONCLUSIONS: Since there is no complete agreement between these two MR techniques, dynamic sequences can not be used as a reliable alternative to static sequences in the evaluation of internal derangement disorders of TMJ.

ACL reconstruction with hamstrings: how different technique and fixation devices influence bone tunnel enlargement.

BACKGROUND: Bone tunnel enlargement after anterior cruciate ligament (ACL) reconstruction is well documented in the literature. The cause of this tunnel enlargement is unclear, but is thought to be multifactorial, with mechanical and biological factors playing a role. AIM: The aim of this prospective study was to evaluate how the different techniques may affect the bone tunnel enlargement and clinical outcome. PATIENTS AND METHODS: Forty-five consecutive patients undergoing ACL reconstruction with autologous doubled semitendinosus and gracilis tendons entered this study. They were randomly assigned to enter group A (In-Out technique, with cortical fixation and Interference screw) and group B (Out-In technique, metal cortical fixation on the femour and tibia). At a mean follow-up of 10 months, all the patients underwent CT scan exam to evaluate the post-operative diameters of both femoral and they underwent tibial tunnels clinical examination after 24 months. RESULTS: The mean femoral tunnel diameter increased significantly from 9.05±0.3 mm to 10.01±2.3 mm in group A and from 9.04±0.8 mm to 9.3±1.12 mm in group B. The mean increase in femoral tunnel diameters observed in group A was significantly higher than that observed in group B (p < 0.05) The mean tibial tunnel diameter increased significantly from 9.03±0.04 mm to 10.68±2.5 mm in group A and from 9.04±0.03 mm to 10.±0.78 mm in group B. The mean increase in tibial tunnel diameters observed in group A was significantly higher than that observed in group B (p < 0.05). No clinical differences were found between two groups and no correlations between clinical and radiological results were found in any patients of both groups. CONCLUSIONS: Results of the study suggest that different mechanical fixation devices could influence tunnel widening. The lower stiffness of the fixation devices is probably responsible of the tunnel widening through the fixation devices's micromotions in the femoral and tibial tunnels.

PCAF ubiquitin ligase activity inhibits Hedgehog/Gli1 signaling in p53-dependent response to genotoxic stress.

The Hedgehog (Hh) signaling regulates tissue development, and its aberrant activation is a leading cause of malignancies, including medulloblastoma (Mb). Hh-dependent tumorigenesis often occurs in synergy with other mechanisms, such as loss of p53, the master regulator of the DNA damage response. To date, little is known about mechanisms connecting DNA-damaging events to morphogen-dependent processes. Here, we show that genotoxic stress triggers a cascade of signals, culminating with inhibition of the activity of Gli1, the final transcriptional effector of Hh signaling. This inhibition is dependent on the p53-mediated elevation of the acetyltransferase p300/CBP-associated factor (PCAF). Notably, we identify PCAF as a novel E3 ubiquitin ligase of Gli1. Indeed PCAF, but not a mutant with a deletion of its ubiquitination domain, represses Hh signaling in response to DNA damage by promoting Gli1 ubiquitination and its proteasome-dependent degradation. Restoring Gli1 levels rescues the growth arrest and apoptosis effect triggered by genotoxic drugs. Consistently, DNA-damaging agents fail to inhibit Gli1 activity in the absence of either p53 or PCAF. Finally, Mb samples from p53-null mice display low levels of PCAF and upregulation of Gli1 in vivo, suggesting PCAF as potential therapeutic target in Hh-dependent tumors. Together, our data define a mechanism of inactivation of a morphogenic signaling in response to genotoxic stress and unveil a p53/PCAF/Gli1 circuitry centered on PCAF that limits Gli1-enhanced mitogenic and prosurvival response.

Nanohydroxyapatite-based bone graft substitute in tunnel enlargement after ACL surgery: RMN study.

BACKGROUND AND AIM: A successful anterior cruciate ligament reconstruction (ACL) requires solid healing of the tendon graft in the bone tunnel. New biological strategies have already been proposed with the aim of improving ACL graft healing and therefore allowing a faster rehabilitative program. The aim of this prospective study was to clinically and radiologically evaluate the efficacy of nanohydroxyapatite bone-base grafts in facilitating bone-tendon incorporation after ACL reconstruction with hamstrings (HS). As far as we know, this is the first study that has tried to asses the efficacy of such a type of bone substitute on human beings. MATERIALS AND METHODS: 40 male patients with chronic ACL rupture who underwent surgical reconstruction with 4-strand semitendinosus and gracilis tendon autograft via a single-bundle technique. Patients were randomly assigned to enter group A (20 patients, nanohydroxyapatite group) or group B (20 patients, control group). Preoperative and postoperative clinical evaluation was always performed, in a blinded way, assessing the Lachman and Pivot-shift tests and range of motion (ROM) of the affected knee. The Lysholm knee score, Tegner activity level, subjective and objective International Knee Documentation Committee (IKDC) forms, and 30 lb KT-1000 arthrometer evaluations. Patients underwent a magnetic resonance imaging (MRI) exam at 30, 90 and 180 days after surgery by the same musculoskeletal radiologist in a blinded way. RESULTS: As for the clinical evaluation, Lysholm, Tegner, IKDC scales, and KT-1000 arthrometer results did not show any significant difference between the two groups. Radiological data show a tendency toward better results in regard to the graft strength signal, the graftbone interface, and bone edema remodeling process, these parameters show significant differences between the two groups only at the short or mid-term follow-ups, while they are never significant at the mid-to long-term follow-up. CONCLUSIONS: In conclusion the use of nanohydroxyapatite bone substitute does not provide significant clinical improvements in terms of better knee stability or patient satisfaction.

The role of MRI and CT in diagnosis and treatment planning of cherubism: a 13-year follow-up case report.

AIM: Cherubism is characterised by mesenchymal alterations during the development of the jaws secondary to perivascular fibrosis. According to the ALARA (As Low As Reasonably Achievable) principle, it is important to avoid conditions where the amount of radiation used is more than that needed for the procedure, because there is no benefit from unnecessary radiation. However, the use of MRI has been poorly studied in cherubism. MATERIALS AND METHODS: The patient underwent head and neck MRI and 3D CT for imaging assessment. RESULTS: MRI is necessary to evaluate the extension of dysplastic tissue and the cystic part of the lesions. Bone window CT only allows evaluation of strong densitometric alterations of cherubism lesions. Moreover, on radiographic film it is not always possible to distinguish fibrous tissue from mucous pseudocystic tissue. By contrast, these differences are readily evident on MRI. CONCLUSION: MRI, in addition to other traditional radiographs and CT, could be useful in helping the clinician in the diagnosis and treatment of cherubism.

Accuracy of manual instrumentation of tibial cutting guide in total knee arthroplasty.

PURPOSE: The aim of this study was to evaluate the accuracy of conventional instrumentation for tibial resection in total knee arthroplasty (TKA) as assessed by a computer-based navigation system during each phase of the surgical procedure. The hypothesis is that conventional instrumentation fails to achieve optimal accuracy in final implant positioning, thus leading to surgical errors. METHODS: Forty primary TKAs were performed. The resection guide was placed using an extramedullary guide. Accurate guide positioning was assessed by the navigation system prior to the osteotomy. The alignment measurement was repeated after resection and after component implantation in order to quantify the deviation caused by the manual positioning of the prosthetic components. A deviation ≥2° was considered unsatisfactory. RESULTS: In the frontal plane, unsatisfactory results observed were as follows: 15 % with reference to manual positioning of the resection guide and 10 % with reference to definition of the resection plane with a tendency towards varus malalignment. In the sagittal plane, unsatisfactory results were as follows: 45 % with reference to manual positioning of the resection guide and 40 % with reference to definition of the resection plane with a trend of decreased tibial slope angle. The deviation between bone resection and subsequent implant placement was ≥2° in none of the cases. CONCLUSIONS: The study confirms the hypothesis that conventional instrumentation fails to achieve optimal accuracy in the positioning of the tibial component. During each phase of the surgical procedure, a tendency towards varus malalignment and a decreased tibial slope angle were observed. LEVELS OF EVIDENCE: II.

Computer-assisted surgery: a teacher of TKAs.

INTRODUCTION: The hypothesis of this study is that computer-aided navigation experience could improve the ability to better place components in the coronal plane and to improve visual/spatial awareness based on the ability of navigation to provide instant feedback. The purpose of this study is to demonstrate the educational role of the navigation system to obtain a better alignment of the prosthetic components with standard instrumentation after a computer-aided navigation experience. MATERIALS AND METHODS: One hundred fifty patients were operated by the same surgeon, with more than 5 years experience with TKA. They were equally divided in three groups: group A (operated with non-navigated technique by surgeon without computer-assisted experience); group B (operated with computer-assisted surgery by the same surgeon); group C (operated with non-navigated technique by the same surgeon after the computer-navigated experience). We evaluated by full-length weight-bearing radiographs the overall alignment of the lower limb in the coronal plane. The optimum placement of the components was considered when the angle was within the limits of ±3° varus/valgus on the coronal x-rays. Comparison between groups was done using one-way ANOVA followed by post hoc Bonferroni test and Pearson chi-square statistics for proportions of optimum placement (P<0.05). RESULTS: In the group A 34 patients (68%) had the optimum placement on the coronal x-rays; in the group B they were 46 (92%) and in the group 41 (82%). The difference is statistically significant in comparing group A and Group B (<0.001), group A and group C (P=0.04), but not for group B and C (P=0.2). CONCLUSION: We believe that the navigation system has an educational role to improve the ability of surgeon of positioning prosthetic components precisely in the coronal plane.

Numb activates the E3 ligase Itch to control Gli1 function through a novel degradation signal.

Hedgehog pathway regulates tissue patterning and cell proliferation. Gli1 transcription factor is the major effector of Hedgehog signaling and its deregulation is often associated to medulloblastoma formation. Proteolytic processes represent a critical mechanism by which this pathway is turned off. Here, we characterize the regulation of an ubiquitin-mediated mechanism of Gli1 degradation, promoted by the coordinated action of the E3 ligase Itch and the adaptor protein Numb. We show that Numb activates the catalytic activity of Itch, releasing it from an inhibitory intramolecular interaction between its homologous to E6-AP C-terminus and WW domains. The consequent activation of Itch, together with the recruitment of Gli1 through direct binding with Numb, allows Gli1 to enter into the complex, resulting in Gli1 ubiquitination and degradation. This process is mediated by a novel Itch-dependent degron, composed of a combination of two PPXYs and a phospho-serine/proline motifs, localized in Gli1 C-terminal region, indicating the role of two different WW docking sites in Gli1 ubiquitination. Remarkably, Gli1 protein mutated in these modules is no longer regulated by Itch and Numb, and determines enhanced Gli1-dependent medulloblastoma growth, migration and invasion abilities, as well as in vitro transforming activity. Our data reveal a novel mechanism of regulation of Gli1 stability and function, which influences Hedgehog/Gli1 oncogenic potential.