Perioperative pain management after scapular tip free flap harvesting for head and neck reconstruction using mini-catheters to inject the local anesthetic.

PURPOSE: Although functional and esthetic results after the use of a scapular tip free flap (STFF) in head and neck reconstruction, and the related donor-site morbidity, have been extensively described, data regarding acute postoperative donor-site pain management are lacking. Purpose of this study is to explore the use of mini-catheters to administer local anesthetics for donor-site pain management after reconstruction using STFF. METHODS: Patients who underwent head and neck reconstruction using a STFF were prospectively enrolled and, through a perineural catheter placed in the donor site during the surgical procedure, a bolus of chirochaine was injected before the patient regained consciousness and at 8, 16, and 24 h postoperatively. Before and 40 min after each dose administration, donor-site pain on a numerical rating scale (NRS; 0-10) was evaluated. RESULTS: Study population consisted of 20 patients (40-88 years). At 8 h, the pain scores before and after the injection were 0-10 (mean 3.35) and 0-5 (mean 1.25), respectively. At 16 h, the pain scores before and after the injection were 0-8 (mean 2.55) and 0-4 (mean 0.55), respectively. At 24 h, the pain scores before and after the injection were 0-8 (mean 1.30) and 0-4 (mean 0.30), respectively. CONCLUSION: Statistical analysis confirmed a significant difference between the pain scores before and after administration at 8, 16, and 24 h (p < 0.001, p < 0.001, and p = 0.003, respectively). Mini-catheters for local anesthetic administration represent an effective strategy for pain control after STFF harvesting for head and neck reconstruction.

3D planning of ear prosthesis and navigated flapless surgery for craniofacial implants: A pilot study.

New 3D digital technologies can be applied to implant-supported ear prostheses to restore anatomical structures damaged by cancer, dysplasia, or trauma. However, several factors influence the accuracy of implant positioning using a cranial template. This pilot study describes an innovative navigated flapless surgery for craniofacial implants, prosthetically guided by 3D planning of the ear prosthesis. Laser surface scanning of the face allowed for mapping of the healthy ear onto the defect site, and projection of the volume and position of the final prosthesis. The projected ear volume was superimposed on the skull bone image obtained by cone-beam computed tomography (CBCT), performed with the navigation system marker plate positioned in the patient's mouth. The craniofacial implants were fitted optimally to the ear prosthesis. After system calibration, real-time navigated implant placement based on the virtual planning was performed with minimally invasive flapless surgery under local anesthesia. After 3 months of healing, digital impressions of the implants were made, and the digital manufacturing workflow was completed to manufacture the ear prosthesis anchored to the craniofacial implants. The proposed digital method facilitated implant positioning during flapless surgery, improving the ear prosthesis manufacturing process and reducing operation time, patient morbidity, and related costs. This protocol avoids the need for a reference tool fixed in the cranial bone, as is usually required for maxillofacial surgery, and confirmed that surgical navigation is useful for guiding the insertion of craniofacial implants during flapless surgery.

Pre-operative MRI staging of endometrial cancer in a multicentre cancer network: can we match single centre study results?

OBJECTIVES: To evaluate the staging accuracy of magnetic resonance imaging (MRI) for endometrial cancer in daily practice over a 3-year period at a tertiary referral centre receiving scans from a large number of hospitals with varying protocols. To compare these daily practice results to published data from single-centre studies. METHODS: After ethical approval, MRI staging records for 270 studies from nine network and three centre hospitals were retrospectively collected and compared with final operative histopathology. The International Federation of Gynaecology and Obstetrics (FIGO) stage, depth of invasion assessment and cervical stromal invasion were analysed and reasons for discrepancies reviewed. RESULTS: MRI-based complete FIGO stage was fully concordant with histopathology in 65.6%. MRI accuracy for depth of myometrial invasion and cervical stromal invasion was 73.3% and 89.3% respectively. Our results did not match the high accuracy previously reported in studies based on single centres. CONCLUSIONS: Published MRI staging accuracy from small single-centre studies were not replicated in a tertiary referral centre receiving scans with heterogeneous protocols over a 3-year period. These results highlight the challenges faced in daily practice and may reflect achievable and realistic MRI staging accuracies in large rapid throughput referral networks. Adherence to standardised high-quality protocols may help to improve future results. KEY POINTS: • Three-year MRI-staging accuracy for endometrial cancer in a multicentre cancer network • Daily practice MRI-staging accuracy did not meet results of single-centre studies • Large scale cancer network MRI-staging accuracies should be further evaluated • Treatment recommendations should be based on achievable MRI-staging accuracies.

Masseteric cooptation and crossfacial nerve grafting: Is it still applicable 22 months after the onset of facial palsy?

BACKGROUND: Eighteen months is usually considered the cutoff time within which recovery of the mimic muscle remains possible using facial nerve cooptation. Few reports on the use of cooptation after this interval have appeared. Purpose of this study is to investigate the feasibility of this procedure also after 22 months. METHODS: Six patients treated via crossfacial nerve grafting between healthy and paralyzed middle and middle-upper facial nerve branches and masseteric cooptation of the main trunk of the paralyzed facial nerve between 20 and 24 months after the onset of palsy were analyzed. Population consisted of two males and four females ages 8-42 years (mean 24 years). Facial palsy developed after acoustic neuroma resection in three patients, after the removal of a cerebellopontine angle astrocytoma in one, and as a consequence of Bell's palsy or cerebral hemorrhage in the other two (one each). House-Brackman and Sunnybrook clinical evaluation systems and FDI questionnaire were used to assess results. RESULTS: House-Brackman scores changed from VI before the operation for all patients to II for two patients and III for four patients. Sunnybrook scores were 0-10 before the operation, but 62-84 at the last visit. Mean FDI scores moved from 24 to 38.5 meaning a statistical high significant improvement (P < .01). CONCLUSIONS: Masseteric/crossfacial nerve grafting is feasible for patients with palsies 20-24 months in duration, affording satisfactory functional and esthetic results and a dramatic improvement in quality of life.

Inefficient skeletal muscle oxidative function flanks impaired motor neuron recruitment in Amyotrophic Lateral Sclerosis during exercise.

This study aimed to evaluate muscle oxidative function during exercise in amyotrophic lateral sclerosis patients (pALS) with non-invasive methods in order to assess if determinants of reduced exercise tolerance might match ALS clinical heterogeneity. 17 pALS, who were followed for 4 months, were compared with 13 healthy controls (CTRL). Exercise tolerance was assessed by an incremental exercise test on cycle ergometer measuring peak O2 uptake ([Formula: see text]O2peak), vastus lateralis oxidative function by near infrared spectroscopy (NIRS) and breathing pattern ([Formula: see text]E peak). pALS displayed: (1) 44% lower [Formula: see text]O2peak vs. CTRL (p < 0.0001), paralleled by a 43% decreased peak skeletal muscle oxidative function (p < 0.01), with a linear regression between these two variables (r2 = 0.64, p < 0.0001); (2) 46% reduced [Formula: see text]Epeak vs. CTRL (p < 0.0001), achieved by using an inefficient breathing pattern (increasing respiratory frequency) from the onset until the end of exercise. Inefficient skeletal muscle O2 function, when flanking the impaired motor units recruitment, is a major determinant of pALS clinical heterogeneity and working capacity exercise tolerance. CPET and NIRS are useful tools for detecting early stages of oxidative deficiency in skeletal muscles, disclosing individual impairments in the O2 transport and utilization chain.

Masseteric nerve for gracilis muscle re-innervation in unilateral facial palsy: Impact on quality of life.

BACKGROUND: Unilateral established or congenital facial palsies are usually treated with neuromuscular transplantation to reanimate the impaired side of the face. One of the most debated points is the motor nerve to choose for the reinnervation of the transplant. Contra-lateral healthy facial nerve is usually preferred, but in selected cases motor nerve to masseter is considered a valuable option. However only a few clinical studies focused on quality of life in this subset of patients are available in literature. METHODS: Twenty patients treated for established or congenital unilateral facial palsy reanimated with gracilis muscle transplant reinnervated with masseteric nerve were retrospectively analyzed. The FDI questionnaire on quality of life was administered before and after surgery and statistical analysis of results was conducted to score changes. RESULTS: Overall results of the questionnaire resulted in a statistically significant improvement after surgery, with a p value of 0.05. CONCLUSION: Facial animation with gracilis muscle transplant re-innervated with masseteric nerve is a safe and reliable procedure in selected unilateral facial palsy patients. Results reported here confirm that surgery mainly improves the functional aspects of a patient's daily life quality, while the impact on social interactions and self-perception is less significant. The comparison of these results with those obtained in patients treated with gracilis muscle transplant re-innervated via contralateral facial nerve suggests that spontaneity is probably highly relevant to improve social aspects of QOL in this subset of patients.

Phencyclidine-induced disruption of oscillatory activity in prefrontal cortex: Effects of antipsychotic drugs and receptor ligands.

The non-competitive NMDA receptor (NMDA-R) antagonist phencyclidine (PCP) markedly disrupts thalamocortical activity, increasing excitatory neuron discharge and reducing low frequency oscillations (LFO, <4Hz) that temporarily group neuronal discharge. These actions are mainly driven by PCP interaction with NMDA-R in GABAergic neurons of the thalamic reticular nucleus and likely underlie PCP psychotomimetic activity. Here we report that classical (haloperidol, chlorpromazine, perphenazine) and atypical (clozapine, olanzapine, quetiapine, risperidone, ziprasidone, aripripazole) antipsychotic drugs--but not the antidepressant citalopram--countered PCP-evoked fall of LFO in the medial prefrontal cortex (mPFC) of anesthetized rats. PCP reduces LFO by breaking the physiological balance between excitatory and inhibitory transmission. Next, we examined the role of different neurotransmitter receptors to reverse PCP actions. D2-R and D1-R blockade may account for classical antipsychotic action since raclopride and SCH-23390 partially reversed PCP effects. Atypical antipsychotic reversal may additionally involve 5-HT1A-R activation (but not 5-HT2A-R blockade) since 8-OH-DPAT and BAYx3702 (but not M100907) fully countered PCP effects. Blockade of histamine H1-R (pyrilamine) and α1-adrenoceptors (prazosin) was without effect. However, the enhancement of GABAA-R-mediated neurotransmission (using muscimol, diazepam or valproate) and the reduction of excitatory neurotransmission (using the mGluR2/3 agonist LY379268 and the preferential kainite/AMPA antagonist CNQX--but not the preferential AMPA/kainate antagonist NBQX) partially or totally countered PCP effects. Overall, these results shed new light on the neurobiological mechanisms used by antipsychotic drugs to reverse NMDA-R antagonist actions and suggest that agents restoring the physiological excitatory/inhibitory balance altered by PCP may be new targets in antipsychotic drug development.

Leishmaniasis endobronquial / No disponible

La afectación del pulmón por leishmaniasis en inmunocompetentes es rara. Presentamos el caso de un paciente de 76 años con antecedentes de EPOC y exposición a polvo inorgánico. Había precisado ingreso por agudización de su EPOC en 3 ocasiones y refería cuadros febriles intermitentes. Se decidió solicitar broncoscopia para toma de muestras microbiológicas, se objetivó una mucosa abollonada que se biopsió descartando malignidad. Realizó tratamiento antibiótico según antibiograma. Ante la persistencia de cuadros febriles de repetición, se realizó broncoscopia en dos ocasiones más, los hallazgos endobronquiales fueron similares. En la última broncoscopia se detectó en la biopsia bronquial la presencia de leishmania, iniciándose tratamiento con anfotericina B con buena respuesta clínica. Existen pocos casos en la literatura que describan afectación endobronquial. Se caracteriza por una importante reacción inflamatoria, lo que justifica la dificultad para detectar el parásito. La recidiva a pesar del tratamiento correcto es frecuente, como en el caso que nos ocupa

Visceral leishmaniasis with endobronchial involvement in an immunocompetent patient is rare. We report a case of a 76 years-old man who presented with intermittent fever and three copd exacerbations. On bronchoscopy there was an inflammatory changes throughout the bronchial tree and lower trachea. The patient was treated with antibiotic without improvement. It was necessary to repeat bronchoscopy two times because of recurrent fever. In the last one, endobronchial biopsies revealed leishmania. Antileishmanian treatmeant with anphotericine B was given with an initial good response. Endobronchial leishmaniasis is an atypical form of leishmaniasis infection. Histopathology showed severe inflammation, making it difficult to diagnose. Recurrences are common despite correct treatment

Impacto del hábito tabáquico al diagnóstico en la supervivencia de pacientes con cáncer de pulmón / Impact of smoking habit on diagnosis of survival of lung cancer patients

Objetivo. Evaluar la influencia del hábito tabáquico en el momento del diagnóstico de cáncer de pulmón sobre la supervivencia a los 5 años. Pacientes y métodos. Se incluyeron pacientes diagnosticados de cáncer de pulmón durante el año 2009 y se analizaron las siguientes variables: edad, sexo, hábito tabáquico (no fumadores, fumadores activos y exfumadores, índice paquetes-año, diagnóstico de EPOC y grado del mismo, motivo de consulta, histología, estadio quirúrgico o no, y supervivencia en meses global y según el hábito tabáquico. Resultados. Se analizaron 37 pacientes, 33 eran hombres. La edad media fue de 67 años (47-85). El 40,5% eran fumadores, 8,1% nunca fumadores, 13,5% exfumadores de menos de 5 años de cesación, 18,9%, entre 5 y 15 años y un 18,9% de más de 15 años. La mediana del índice paquetes-año de fumadores y exfumadores fue 42. El motivo de consulta fue presentar síntomas en 21 pacientes (56,8%) y hallazgo radiológico el resto. La histología fue epidermoide un 37,8%, adenocarcinoma 29,7%, microcítico 16,2%, célula grande 8,1% y otros no microcíticos 8,1%. El tumor fue quirúrgico en 13 casos (35,1%). 17 pacientes tenían EPOC. A los 5 años del diagnóstico, 23 pacientes murieron por causa atribuible al cáncer, 5 murieron por otras causas y 9 continúan vivos. La supervivencia a 5 años fue del 24%. La mediana de supervivencia de los 23 pacientes fallecidos por cáncer fue de 12,83 meses. El análisis de supervivencia respecto al hábito tabáquico no reflejó diferencias estadísticamente significativas entre fumadores activos: mediana de 24,4 meses, y los no fumadores (exfumadores y nunca fumadores): mediana 11,5 meses. Agrupando a los fumadores activos con los fumadores de < 5 años de abandono, tampoco muestra diferencias respecto a los no fumadores y exfumadores > 15 años: medianas 13,9 meses y 11,5 meses, respectivamente, en ambos grupos. Conclusión. No encontramos diferencias significativas en la supervivencia de pacientes con cáncer de pulmón según el hábito tabáquico en el momento del diagnóstico (AU)

Objective. Evaluate the influence of the smoking habit at the time of the diagnosis of lung cancer on 5-year survival rate. Patients and methods. Patients diagnosed of lung cancer during the year 2009 were included and the following variables analyzed: age, gender, smoking habit (non-smokers, active smokers and ex-smokes, package-year index, diagnosis of COPD and its grade, reason for visit, histology, surgical stage or not, and survival in overall months and according to smoking habit. Results. A total of 37 patients were analyzed, 33 of whom were men. Mean age was 67 years (47-85). Smokers accounted for 40.5%, 8.1 had never smoked, 13.5% were ex-smokers with at least 5 years since cessation, 18.9% between 5 and 15 years and 18.9% more than 15 years. Median package-year index of smokers and ex-smokers was 42. Reason for visit was having symptoms in 21 patients (56.8%) and X-ray findings in the rest. Histology was squamous cell in 37.85, adenocarcinoma 29.7%, small cell 16.2%, large cell 8.1% and others non-small cell 8.1%. The tumor was surgical in 13 cases (35.1%) and 17 patients had COPD. At 5 years of the diagnosis, 23 patients had died due to cause attributable to cancer, 5 due to other causes and 9 continued to be alive. Five-year survival was 24%. Median survival of the 23 deceased patients due to cancer was 12.83 months. Survival analysis regarding smoking cessation did not reflect statistically significant differences among active smokers: median of 24.4 months and non-smokers (ex-smokers and non-smokers): median 11.5 months. Grouping active smokers with ex-smokers having < 5 years of cessation, there were also no differences regarding the non-smokers and ex-smokers > 15 years: median 13.9 months and 11.5 months, respectively, in both groups. Conclusion. We found no significant differences in survival of patients with lung cancer according to the smoking habit at the time of diagnosis (AU)

Upper eyelid platinum chain placement for treating paralytic lagophthalmos.

For the definitive treatment of lagophthalmos and satisfactory rehabilitation of the affected eye, different surgical strategies have been proposed, including static or dynamic procedures. Although some of these can have good results, lid loading is now the most common technique for treating paralytic long-term lagophthalmos. Among the different types of loading, the use of a platinum chain is preferred to the use of a standard gold weight because platinum has a higher density than gold and is also more biocompatible. In this paper authors retrospectively analyzed 43 patients with regards to functional and cosmetic results. Questionnaires were also employed to assess changes and improvements in the patients' quality of life. Analysis of the excellent results achieved confirmed that platinum chain lid loading should be considered as a first-line treatment for paralytic lagophthalmos rehabilitation. It is a simple, reliable, and effective technique that significantly improves the health-related quality of life of patients.

Acute focal brain damage alters mitochondrial dynamics and autophagy in axotomized neurons.

Mitochondria are key organelles for the maintenance of life and death of the cell, and their morphology is controlled by continual and balanced fission and fusion dynamics. A balance between these events is mandatory for normal mitochondrial and neuronal function, and emerging evidence indicates that mitochondria undergo extensive fission at an early stage during programmed cell death in several neurodegenerative diseases. A pathway for selective degradation of damaged mitochondria by autophagy, known as mitophagy, has been described, and is of particular importance to sustain neuronal viability. In the present work, we analyzed the effect of autophagy stimulation on mitochondrial function and dynamics in a model of remote degeneration after focal cerebellar lesion. We provided evidence that lesion of a cerebellar hemisphere causes mitochondria depolarization in axotomized precerebellar neurons associated with PTEN-induced putative kinase 1 accumulation and Parkin translocation to mitochondria, block of mitochondrial fusion by Mfn1 degradation, increase of calcineurin activity and dynamin-related protein 1 translocation to mitochondria, and consequent mitochondrial fission. Here we suggest that the observed neuroprotective effect of rapamycin is the result of a dual role: (1) stimulation of autophagy leading to damaged mitochondria removal and (2) enhancement of mitochondria fission to allow their elimination by mitophagy. The involvement of mitochondrial dynamics and mitophagy in brain injury, especially in the context of remote degeneration after acute focal brain damage, has not yet been investigated, and these findings may offer new target for therapeutic intervention to improve functional outcomes following acute brain damage.

The submental island flap: pedicle elongation and indications in head and neck reconstruction.

BACKGROUND: The submental island flap is an axial pattern skin flap first described by Martin et al. in 1993. When used to reconstruct skin defects it matches the recipient site in terms of colour, texture and thickness. One of the main limitations to its application is the arc of the pedicle allowing coverage of only the lower two thirds of the face. METHODS: A retrospective review was performed of all patients who had had a submental island flap reconstruction at the Operative Unit of Maxillo-Facial Surgery of the University Hospital of Parma, Italy, between 2001 and 2011. The Authors focused on the surgical technique adopted, the clinical indications and the results obtained. They analysed the different ways to elongate the pedicle and discuss their thoughts on the choice of reconstruction. A flowchart was created to help in the decisional process. RESULTS: Between 2001 and 2011 the submental island flap was used to reconstruct head and neck defects in 22 patients. Thirteen patients had defects of the oral cavity; the remaining 9 patients had skin defects involving the pre-auricular region, the temporal area and the peri-nasal cheek skin. No major complications occurred and in one case a partial necrosis of the distal portion of the flap was observed. Five patients underwent surgical revision involving intraoral flap debulking 6-10 months after the primary procedure. DISCUSSION AND CONCLUSIONS: The techniques to elongate the pedicle used and described were: additional dissection of the pedicle, Y-V procedure, reverse flow flap, section of facial vein and microvascular anastomosis. Their choice is mainly conditioned by the site of the defect.

The masseteric nerve: a versatile power source in facial animation techniques.

The masseteric nerve has many advantages including low morbidity, its proximity to the facial nerve, the strong motor impulse, its reliability, and the fast reinnervation that is achievable in most patients. Reinnervation of a neuromuscular transplant is the main indication for its use, but it has been used for the treatment of recent facial palsies with satisfactory results. We have retrospectively evaluated 60 patients who had facial animation procedures using the masseteric nerve during the last 10 years. The patients included those with recent, and established or congenital, unilateral and bilateral palsies. The masseteric nerve was used for coaptation of the facial nerve either alone or in association with crossfacial nerve grafting, or for the reinnervation of gracilis neuromuscular transplants. Reinnervation was successful in all cases, the mean (range) time being 4 (2-5) months for facial nerve coaptation and 4 (3-7) months for neuromuscular transplants. Cosmesis was evaluated (moderate, n=10, good, n=30, and excellent, n=20) as was functional outcome (no case of impairment of masticatory function, all patients able to smile, and achievement of a smile independent from biting). The masseteric nerve has many uses, including in both recent, and established or congenital, cases. In some conditions it is the first line of treatment. The combination of combined techniques gives excellent results in unilateral palsies and should therefore be considered a valid option.

Selective deep lobe parotidectomy for pleomorphic adenomas.

The authors' experience of the selective deep lobe parotidectomy for the treatment of pleomorphic adenomas of the deep parotid lobe is presented. A retrospective analysis of 11 patients treated between 1997 and 2010 was performed; seven were males and four were females, ranging in age from 35 to 51 years. Parameters evaluated included facial nerve weakness, the occurrence of Frey's syndrome, cosmetic outcome, and recurrence. Follow-up ranged from 18 months to 11 years. No major complications, permanent facial nerve weakness, or Frey's syndrome occurred. Four patients developed temporary facial nerve impairments that lasted between 2 and 6 weeks, and two developed a sialocele that healed in 9 days in one case and 12 days in the other. The overall cosmetic assessment was excellent in eight patients, good in two, and satisfactory in the remaining one. No recurrences occurred. The selective deep lobe parotidectomy can be considered an effective technique for the management of deep parotid lobe pleomorphic adenomas. The major advantages of this procedure include a reduction in complications such as facial nerve impairments and Frey's syndrome, and an improved cosmetic outcome.

Rehabilitation with endosseous implants in fibula free-flap mandibular reconstruction: a case series of up to 10 years.

PURPOSE: To evaluate the clinical outcome and the aesthetic and functional results of implant rehabilitation of fibula free-flap reconstructed mandibles. MATERIALS AND METHODS: The charts of patients who underwent mandibular reconstruction with fibula free flap and implant prosthodontic rehabilitation between 1998 and 2008 at the Operative Unit of Maxillofacial Surgery of Parma, Italy, were reviewed. In the study the estimated survival rates of implants placed in reconstructed mandibles we identified the prognostic factors and evaluated the functional outcomes. RESULTS: Fourteen patients with a mean age of 50 years (range 15-63 years), were included in the study. A total of 62 implants were positioned. Complications occurred in 7 cases, an improvement in function and aesthetics was reported by the majority of patients. CONCLUSIONS: A high survival rate for implants placed in fibula free-flap reconstructed mandibles was observed. Although different factors were believed to be associated with a poorer prognosis (radiotherapy, composite defects, etc.) no statistically significance was found, showing no absolute contraindications to implant placement.

Free flaps in elderly patients: outcomes and complications in head and neck reconstruction after oncological resection.

INTRODUCTION: Free flaps represent the first reconstructive option for many head and neck defects. The increasing life expectancy of the population results in increasing numbers of ageing patients facing complex reconstructive surgery. In this study we evaluated our experience with free-flap transfers in older patients, analysing the post-operative reconstructive and systemic complications. MATERIALS AND METHODS: Between 2000 and 2009, 360 patients underwent free flap reconstruction of defects resulting from the treatment of head and neck tumours at the Operative Unit of Maxillofacial Surgery, University - Hospital of Parma, Italy. Fifty-five patients (15.3%) were more than 75 years old at the time of treatment. RESULTS: At the end of the follow-up successful free-flap transfer was achieved in 360 of the 373 flaps harvested (96.5%). The overall reconstructive complication rate was 31.4%, (31.8% in the younger group and 29.1% in the remaining patients). Medical complications were observed in 29.2% of cases (less than 75 years: 28.8%; more than 75 years: 30.9%). The ASA status was associated with a statistically significantly higher incidence of complications within patients less than 75 years old (p < 0.0001). DISCUSSION AND CONCLUSIONS: The results of this study, in agreement with previous studies, provide evidence that free-tissue transfer may be performed in ageing patients with a high degree of technical success. The chronologic age cannot be considered an appropriate criterion in the reconstructive decision. On the contrary, a careful selection of the patients based on comorbidities and general conditions (ASA status) is of primary importance in reducing post-operative complications and to improving the results of surgery.

Orthognathic surgery for the complete rehabilitation of Moebius patients: principles, timing and our experience.

Moebius syndrome is a rare disorder found in approximately 1/100,000 neonates and the treatment of facial palsy is now well established worldwide and consists of free-muscle transplants reinnervated with motor nerves. Dentofacial deformities are often detected in Moebius patients, and different degrees of micrognathia are often present, particularly in patients with complete expressions of Moebius syndrome. However only two published reports have described the surgical treatment of such anomalies in these patients; in both cases, the suggested approach consisted of orthognathic surgery followed by soft-tissue management. In this paper we discuss the indications and correct timing of orthognathic surgery and suggest to perform facial animation at an early age and then to wait for the completion of maxillofacial skeletal growth before performing orthognathic surgery. Finally, facial animation should precede orthognathic surgery in adult patients to prevent lower lip deformities and to ensure more predictable and satisfactory results.

Emx2 is a dose-dependent negative regulator of Sox2 telencephalic enhancers.

The transcription factor Sox2 is essential for neural stem cells (NSC) maintenance in the hippocampus and in vitro. The transcription factor Emx2 is also critical for hippocampal development and NSC self-renewal. Searching for 'modifier' genes affecting the Sox2 deficiency phenotype in mouse, we observed that loss of one Emx2 allele substantially increased the telencephalic ß-geo (LacZ) expression of a transgene driven by the 5' or 3' Sox2 enhancer. Reciprocally, Emx2 overexpression in NSC cultures inhibited the activity of the same transgene. In vivo, loss of one Emx2 allele increased Sox2 levels in the medial telencephalic wall, including the hippocampal primordium. In hypomorphic Sox2 mutants, retaining a single 'weak' Sox2 allele, Emx2 deficiency substantially rescued hippocampal radial glia stem cells and neurogenesis, indicating that Emx2 functionally interacts with Sox2 at the stem cell level. Electrophoresis mobility shift assays and transfection indicated that Emx2 represses the activities of both Sox2 enhancers. Emx2 bound to overlapping Emx2/POU-binding sites, preventing binding of the POU transcriptional activator Brn2. Additionally, Emx2 directly interacted with Brn2 without binding to DNA. These data imply that Emx2 may perform part of its functions by negatively modulating Sox2 in specific brain areas, thus controlling important aspects of NSC function in development.