Activity-dependent bulk endocytosis proteome reveals a key presynaptic role for the monomeric GTPase Rab11.

Activity-dependent bulk endocytosis (ADBE) is the dominant mode of synaptic vesicle endocytosis during high-frequency stimulation, suggesting it should play key roles in neurotransmission during periods of intense neuronal activity. However, efforts in elucidating the physiological role of ADBE have been hampered by the lack of identified molecules which are unique to this endocytosis mode. To address this, we performed proteomic analysis on purified bulk endosomes, which are a key organelle in ADBE. Bulk endosomes were enriched via two independent approaches, a classical subcellular fractionation method and isolation via magnetic nanoparticles. There was a 77% overlap in proteins identified via the two protocols, and these molecules formed the ADBE core proteome. Bioinformatic analysis revealed a strong enrichment in cell adhesion and cytoskeletal and signaling molecules, in addition to expected synaptic and trafficking proteins. Network analysis identified Rab GTPases as a central hub within the ADBE proteome. Subsequent investigation of a subset of these Rabs revealed that Rab11 both facilitated ADBE and accelerated clathrin-mediated endocytosis. These findings suggest that the ADBE proteome will provide a rich resource for the future study of presynaptic function, and identify Rab11 as a regulator of presynaptic function.

Perfusion magnetic resonance imaging in pediatric brain tumors.

PURPOSE: The use of DSC-MR imaging in pediatric neuroradiology is gradually growing. However, the number of studies listed in the literature remains limited. We propose to assess the perfusion and permeability parameters in pediatric brain tumor grading. METHODS: Thirty children with a brain tumor having benefited from a DSC-MR perfusion sequence have been retrospectively explored. Relative CBF and CBV were computed on the ROI with the largest lesion coverage. Assessment of the lesion's permeability was also performed through the semi-quantitative PSR parameter and the K2 model-based parameter on the whole-lesion ROI and a reduced ROI drawn on the permeability maps. A statistical comparison of high- and low-grade groups (HG, LG) as well as a ROC analysis was performed on the histogram-based parameters. RESULTS: Our results showed a statistically significant difference between LG and HG groups for mean rCBV (p < 10-3), rCBF (p < 10-3), and for PSR (p = 0.03) but not for the K2 factor (p = 0.5). However, the ratio K2/PSR was shown to be a strong discriminating factor between the two groups of lesions (p < 10-3). For rCBV and rCBF indicators, high values of ROC AUC were obtained (> 0.9) and mean value thresholds were observed at 1.07 and 1.03, respectively. For K2/PSR in the reduced area, AUC was also superior to 0.9. CONCLUSIONS: The implementation of a dynamic T2* perfusion sequence provided reliable results using an objective whole-lesion ROI. Perfusion parameters as well as a new permeability indicator could efficiently discriminate high-grade from low-grade lesions in the pediatric population.

Microsurgical anatomy of branches of musculocutaneous nerve: clinical relevance for spastic elbow surgery.

PURPOSE: The neurotomy of musculocutaneous nerve is a treatment for patients who suffer from spastic elbow flexion when medical and reeducative treatments have failed. It consists in sectioning motor branches of musculocutaneous nerve which are destined to the biceps brachii and brachialis muscles, both being the main elbow flexor muscles. The aim of this study was to analyse the distance, where each motor branch arises from the musculocutaneous nerve to both biceps brachii and brachialis muscles, to establish precisely the localisation and length of the necessary incision to reach its branches for surgery. MATERIALS AND METHODS: Eighteen musculocutaneous nerves from ten cadavers were dissected. None of them reported with a previous pathology. The cadavers were laid on the back with 30-35° of abduction, a complete extension, and supination of the upper limb. RESULTS: The localization of motor branches was to be found in the middle third of the upper arm, with an average from the base of the humeral major tubercle of 11.46, 12.40, and 12.87 cm for the biceps brachii and 16.36, 19.10, and 16.88 cm for the brachialis muscle. CONCLUSION: The incision needed to reach the motor branches of the musculocutaneous nerve should be localised between 10 and 20 cm from the major humeral tubercle and may be shorter than usual.

[Microsurgical anatomy of perforating branches of anterior communicating artery]. / Anatomie microchirurgicale des branches perforantes de l'artère communicante antérieure.

INTRODUCTION: The anterior communicating artery (ACoA) gives perforating branches to the optic chiasma, the hypothalamus and the corpus callosum. Perforating branches are variable (number, direction). Nevertheless, their knowledge is crucial during surgery of this area to spare injuries leading to ischemic post-operative complications. OBJECTIVE: The objective was to update the anatomical knowledge about perforating branches of the ACoA. METHODS: The study was led on a series of seven brains taken from human cadavers. An injection of latex neoprene was performed for every case. The region of interest was observed under operating microscope. Were examined: the length of the ACoA, its diameter, its orientation, its configuration and perforating branches (number and areas). RESULTS: Three cases on five presented with an anatomical variation at the level of the ACoA. The average length of AcoA was 2.1 millimeters (min: 2, max: 2.2). The average diameter of the ACoA was 1.67 mm (min: 1.1, max: 2.1). The average number of perforating branches was 4.2 (min: 2, max: 6). The presence of a median artery of the corpus callosum seemed to correlated with a low number of perforating branches. Branches supplying the optic chiasma seemed to be more numerous.

[Persistent Müllerian ducts syndrome: one case of late hypofertility]. / Syndrome de persistance des canaux de Müller de type féminin : un cas de diagnostic tardif dans le cadre d'une infertilité

We report the case of a 35-year-old patient with a syndrome of persistent Müllerian ducts (PMDS) of the female type (group A). The diagnosis was made in adulthood during an infertility workup. Clinical examination revealed an empty scrotum, a normal penis and bilateral inguinal cystic masses. The spermogram found azoospermia. Imaging using MRI and tomotensidometry found the presence of an uterus, two fallopian tubes and two inguinal positions of polycystic testes. A surgical management was performed for surgical testicular biopsy. Histological examination then found a cystic formation of multi-celled mesothelial origin, with atrophic testis Sertoli cell involution and without sperm. PMDS is a rare form of pseudo-internal hermaphroditism characterized by the presence in a man of the uterus, fallopian tubes and upper vagina with external male genitalia and virilized characters. About 200 cases are reported in the literature. The diagnosis is often made in children intraoperatively during a cure of testicular ectopia. The karyotype is 46 XY type. The pathogenesis is related to a deficiency of anti-Müllerian hormone (AMH) or tissue resistance to its action by receptor abnormalities. The regression of the Müllerian duct derivatives can give three types of PMDS : masculine type, feminine type and a transverse type. Surgical treatment is difficult but necessary because of the risk of infertility and ectopic testicular degeneration.

[The occipital sinus: a radioanatomic study]. / Étude radioanatomique du sinus occipital.

INTRODUCTION: The aim of this study was to assess the presence of an occipital sinus in both children and adults, and to detail its main associated anatomical characteristics. METHODS: One hundred of patients' MRI (3D T1 EG) between 0 and 86 years old were studied, in sagittal and axial sections, with the software DxMM. Occipital sinus length, perimeter, and cerebellar falx length measurements were performed with the software's tools. RESULTS: Forty-three percent of patients had an occipital sinus (average perimeter was 3.02 mm, average length was 19.85 mm), and 23.26% of these patients had a cerebellar falx, 30.23% of these patients had one vein or more draining into the occipital sinus. Sixty-two percent of children had an occipital sinus (average perimeter was 2.87 mm, average length was 21.63 mm), and 29.03% of them had a cerebellar falx. Twenty-four percent of adults had an occipital sinus (average perimeter was 3.4mm, average length was 15.28 mm), and 8.33% of them had a cerebellar falx. CONCLUSION: This work highlights a link between the age and the occipital sinus existence. The perimeter of this sinus seems to be superior for adults, but its length seems to be superior for children. A cerebellar falx with the occipital sinus was found more frequently for children.

An unusual superolateral origin of ophthalmic artery: an anatomic case report.

BACKGROUND AND IMPORTANCE: If ophthalmic artery's (OphA) origin anomalies are frequent, the superolateral origin of the OphA was rarely described. CLINICAL PRESENTATION: During an aneurysmal surgery, a superolateral origin of the left OphA was found. This variation was associated with a sylvian aneurysm. The anatomical, embryological features, the neurosurgical implications of this origin such as treatment of carotid-ophthalmic aneurysm or intra arterial retinoblastoma chemotherapy are discussed. CONCLUSION: To the best of our knowledge, this is a very rare operative case of both superolateral origin and initial course of OphA.

Unusual course of the aberrant right hepatic artery running through the pancreatic parenchyma during modified Frey's procedure.

We report a variation of an aberrant right hepatic artery arising from the superior mesenteric artery and crossing into pancreatic head without other hepatic artery substitution. The variant was discovered during radiological examinations in a patient with symptomatic chronic pancreatitis requiring Frey's procedure with reinsertion of the common bile duct into the pancreatic head. An aberrant right hepatic artery arising from the superior mesenteric artery is present in 10 to 20% of case and its course is usually retro-pancreatic. The course of this artery into the pancreatic head is uncommon and can be present up to 10% in case of ARHA. Knowledge of an aberrant right hepatic artery crossing into the pancreatic head is important before pancreatic surgery in order to avoid surgical complications, especially for liver necrosis.

[Relationships between piriformis muscle and sciatic nerve: radioanatomical study with 104 buttocks]. / Les rapports entre le muscle piriforme et le nerf ischiatique : étude radioanatomique de 104 régions glutéales.

OBJECTIVE: The relationships between the piriformis muscle and the sciatic nerve are close and may be changing. In some cases, these relationships are the cause of a piriformis syndrome, an under-diagnosed etiology of non discal sciatica. The aim of the study was to explore, by the MRI, the sciatic nerve and the piriformis muscle. MATERIELS AND METHODS: One hundred and four buttocks were explored by MRI for 52 randomly selected patients. RESULTS: In 59.6% of cases, no variation of the piriformis muscle and sciatic nerve were found. In 26% of cases, the sciatic nerve was divided into the pelvis. In 9.6% of cases, it was divided into the pelvis, the piriformis muscle was bifid and the common peroneal nerve ran between both heads. The piriformis muscle was bifid in 10.6% of cases, hypertrophic in 13.5% of cases and atrophic in 2.9% of cases.

[The conflict between obturator nerve and ovary: a cadaveric and radioanatomic study]. / Le conflit ovaro-obturateur : une étude cadavérique et radio-anatomique.

The aim of this study was to describe the anatomical relationships between the ovary and the obturator nerve in its intrapelvic portion. Seven embalmed cadavers were dissected; 20 MRIs were then analyzed. The main distance between the lateral pole of the ovary and the obturator nerve was 29 mm. The authors describe various etiologies responsible for obturator neuralgia. An underdiagnosed cause is gonadal hypertrophy.

The TcdE holin drives toxin secretion and virulence in Clostridioides difficile.

Clostridioides difficile is the leading cause of healthcare associated infections. The Pathogenicity Locus (PaLoc) toxins TcdA and TcdB promote host disease. These toxins lack canonical N-terminal signal sequences for translocation across the bacterial membrane, suggesting alternate mechanisms of release, which have included targeted secretion and passive release from cell lysis. While the holin TcdE has been implicated in TcdA and TcdB release, its role in vivo remains unknown. Here, we show profound reductions in toxin secretion in ΔtcdE mutants in the highly virulent strains UK1 (epidemic ribotype 027, Clade 3) and VPI10463 (ribotype 087, Clade 1). Notably, tcdE deletion in either strain rescued highly susceptible gnotobiotic mice from lethal infection by reducing acute extracellular toxin to undetectable levels, limiting mucosal damage, and enabling long-term survival, in spite of continued toxin gene expression in ΔtcdE mutants. Our findings confirm TcdE's critical functions in vivo for toxin secretion and C. difficile virulence.

The impact of social, cognitive and attitudinal dimensions on college students' support for organ donation.

This study investigates how college students can be social support catalysts for organ donation and how social, cognitive and attitudinal dimensions impact organ donor registration. A total of 317 people participated in the exploratory portion of the project and a total of 1800 responses were obtained from an online survey to members of a national student organization. The findings show that perceptions of the benefits of organ donation and altruistic motives had the greatest impact on the support for organ donation while respondents' knowledge about how to register to be an organ donor was the dominant dimension for donor registration status. Social-based communications had the next greatest impact for both support and donor registration. Based on the findings, an 18-month social media campaign was launched with the student organization that had 20 421 website visitors, 4473 Facebook members, 1189 YouTube video submissions with 164 000 views, motivated 19 623 people to go to a state's organ donor registration page, and had 9000 documented organ donor registrations. Within the student organization, organ donor registration increased by 28%. On the basis of these project results, Donate Life America and other sponsors have provided funding for two additional years.

Perfusion MRI as a neurosurgical tool for improved targeting in stereotactic tumor biopsies.

OBJECTIVE: Stereotactic biopsies are subject to sampling errors (essentially due to target selection). The presence of contrast enhancement is not a reliable marker of malignancy. The goal of the present study was to determine whether perfusion-weighted imaging can improve target selection in stereotactic biopsies. METHODS: We studied 21 consecutive stereotactic biopsies between June 2009 and March 2010. Perfusion-weighted magnetic resonance imaging (MRI) was integrated into our neuronavigator. Perfusion-weighted imaging was used as an adjunct to conventional MRI data for target determination. Conventional MRI alone was used to determine the trajectory. RESULTS: We found a linear correlation between regional cerebral blood volume (rCBV) and vessel density (number of vessels per mm(2); R = 0.64; p < 0.001). Perfusion-weighted imaging facilitated target determination in 11 cases (52.4%), all of which were histopathologically diagnosed as glial tumors. For glial tumors, which presented with contrast enhancement, perfusion-weighted imaging identified a more precisely delimited target in 9 cases, a different target in 1 case, and exactly the same target in 1 other case. In all cases, perfusion-selected sampling provided information on cellular features and tumor grading. rCBV was significantly associated with grading (p < 0.01), endothelial proliferation (p < 0.01), and vessel density (p < 0.01). For lesions with rCBV values ≤1, perfusion-weighted MRI did not help to determine the target but was useful for surgical management. CONCLUSIONS: For stereotactic biopsies, targeting based on perfusion-weighted imaging is a feasible method for reducing the sampling error and improving target selection in the histopathological diagnosis of tumors with high rCBVs.

A hierarchical communication model of the antecedents of health care professionals' support for donations after cardiac death.

Using structural equation modeling, the direct and indirect impact of five variables on the support of donation after cardiac death from the perspective of health care professionals were investigated: knowledge, trust in the transplant team, whether patients are in a state of irreversibility, whether health care professionals participate in a patient's death, and perceptions about the brain death versus cardiac death donation process. In total, 10/15 relationships posited in the model had significant pathways. The results provide insight into sequential communication strategies for generating support for donations after cardiac death.

Renal transplantation in patients with AA amyloidosis nephropathy: results from a French multicenter study.

Although end-stage renal disease related to AA amyloidosis nephropathy is well characterized, there are limited data concerning patient and graft outcome after renal transplantation. We performed a multicentric retrospective survey to assess the graft and patient survival in 59 renal recipients with AA amyloidosis. The recurrence rate of AA amyloidosis nephropathy was estimated at 14%. The overall, 5- and 10-year patient survival was significantly lower for the AA amyloidosis patients than for a control group of 177 renal transplant recipients (p = 0.0001, 0.028 and 0.013, respectively). In contrast, we did not observe any statistical differences in the 5- and 10- year graft survival censored for death between two groups. AA amyloidosis-transplanted patients exhibited a high proportion of infectious complications after transplantation (73.2%). Causes of death included both acute cardiovascular events and fatal septic complications. Multivariate analysis demonstrated that the recurrence of AA amyloidosis on the graft (adjusted OR = 14.4, p = 0.01) and older recipient age (adjusted OR for a 1-year increase = 1.06, p = 0.03) were significantly associated with risk of death. Finally, patients with AA amyloidosis nephropathy are eligible for renal transplantation but require careful management of both cardiovascular and infectious complications to reduce the high risk of mortality.

Dual, minimally invasive fixation in acute, double, thoracic spine fracture.

BACKGROUND: We report on a dual percutaneous fixation in 2 patients with a double thoracic spine fracture. The advantages and limitations of this new approach for treating traumatic spinal fractures are reviewed. CLINICAL PRESENTATION: A 67-year-old male was admitted following a fall from a height of 3 m. A neurological examination revealed sub-T11 motor and sensory paraparesis. There were a T6 vertical body and bi-articular fracture and a T11 vertebral burst fracture with > 75% posterior wall damage. A 40-year-old male was admitted after a suicide attempt. A neurological examination revealed sub-T11 paraplegia. There were a T7 vertebral body fracture with intact posterior wall and a T11 burst fracture with > 75% posterior wall damage. SURGICAL TECHNIQUE: The same technique was used in both cases. 2 minimally invasive percutaneous fixations of the 2 fractures were performed. In a third step, we performed a T10-T12 open laminectomy. This technique helped to limit blood loss and avoid an over-long fixation. Pedicle screw targeting was optimal. 16 months later, the neurological status was normal in patient 1 and there was neurological improvement in patient 2. No secondary segmental kyphotic deformities appeared.Percutaneous fixation enables the treatment of an acute thoracic spine fracture. With appropriate presurgical planning, this technique can be applied to all thoracic vertebrae. Spinal cord injuries justify the use of laminectomy together with percutaneous fixation, in order to limit erector muscle injury and blood loss.

[Paraclinoid region: descriptive anatomy and radiological correlations with MR imaging]. / La région paraclinoïdienne: anatomie descriptive et corrélations radiologiques en imagerie par résonance magnétique.

OBJECTIVE: The paraclinoid region has a complex anatomy. The purpose of this study was to depict in details its anatomical landmarks and their radiological translations with magnetic resonance imaging (MRI). MATERIAL AND METHOD: Ten anatomical specimens (20 paraclinoid regions) were prepared, then dissected and further analyzed with MRI in order to describe their important radio-anatomical structures (dural folds, osseous surfaces, arteries and nerves) along with their course and measurements, and the reference points of the carotid distal dural ring. The paraclinoid MR protocol consisted in a T2 high-resolution sequence with thin and contiguous slices acquired in a coronal (diaphragmatic) and sagittal oblique (carotid) plane. Reproducibility in living subjects was evaluated on 15 patients (30 paraclinoid regions). Statistical comparison was made between laboratory and MR measurements obtained on cadavers. RESULTS: A detailed description of paraclinoid anatomy and structures was provided. Its landmarks were satisfactorily identified with the dedicated MR protocol. Reproducibility in living subjects was obtained. No statistical difference was found between laboratory and MR measurements. CONCLUSION: This study provides a precise description of paraclinoid anatomical structures and their radiological correlations. This paraclinoid MR protocol allows locating paraclinoid lesions in comparison with the cavernous sinus roof, which is of paramount importance for the management of paraclinoid carotid artery aneurysms.

Security and reliability of CUSTOMBONE cranioplasties: A prospective multicentric study.

BACKGROUND: Repairing bone defects generated by craniectomy is a major therapeutic challenge in terms of bone consolidation as well as functional and cognitive recovery. Furthermore, these surgical procedures are often grafted with complications such as infections, breaches, displacements and rejections leading to failure and thus explantation of the prosthesis. OBJECTIVE: To evaluate cumulative explantation and infection rates following the implantation of a tailored cranioplasty CUSTOMBONE prosthesis made of porous hydroxyapatite. One hundred and ten consecutive patients requiring cranial reconstruction for a bone defect were prospectively included in a multicenter study constituted of 21 centres between December 2012 and July 2014. Follow-up lasted 2 years. RESULTS: Mean age of patients included in the study was 42±15 years old (y.o), composed mainly by men (57.27%). Explantations of the CUSTOMBONE prosthesis were performed in 13/110 (11.8%) patients, significantly due to infections: 9/13 (69.2%) (p<0.0001), with 2 (15.4%) implant fracture, 1 (7.7%) skin defect and 1 (7.7%) following the mobilization of the implant. Cumulative explantation rates were successively 4.6% (SD 2.0), 7.4% (SD 2.5), 9.4% (SD 2.8) and 11.8% (SD 2.9%) at 2, 6, 12 and 24 months. Infections were identified in 16/110 (14.5%): 8/16 (50%) superficial and 8/16 (50%) deep. None of the following elements, whether demographic characteristics, indications, size, location of the implant, redo surgery, co-morbidities or medical history, were statistically identified as risk factors for prosthesis explantation or infection. CONCLUSION: Our study provides relevant clinical evidence on the performance and safety of CUSTOMBONE prosthesis in cranial procedures. Complications that are difficulty incompressible mainly occur during the first 6 months, but can appear at a later stage (>1 year). Thus assiduous, regular and long-term surveillances are necessary.

[Brain abscess and Osler-Weber-Rendu syndrome: Do not forget to look for pulmonary arteriovenous malformations]. / Abcès cérébral et maladie de Rendu-Osler-Weber : pensez à rechercher des malformations artério-veineuses pulmonaires.

INTRODUCTION: Osler-Rendu-Weber syndrome or hereditary hemorrhagic telangiectasia affects between 1/5000 and 1/8000 people. It is characterized by presence of recurrent epistaxis, mucocutaneous telangiectasia and visceral arteriovenous malformations. It is a genetic disease with autosomal dominant transmission inducing an endothelial cells hyper-proliferation. CASE REPORT: A 68-year-old women with Osler-Rendu-Weber syndrome was referred for management of general impairment with confusional syndrome and hyperthermia. Various examinations have allowed us to conclude at diagnosis of brain abscess with ventriculitis probably favored by right-left shunt secondary to pulmonary arteriovenous malformations. Evolution was favorable after antibiotic treatment and endovascular embolization. CONCLUSION: In case of brain abscess without obvious promoting factor, don't forget to looking for a right-left shunt providing septic or aseptic emboli. Furthermore, diagnosis of Rendu-Osler-Weber syndrome should be considered presence of telangiectasias and/or epistaxis.

Surgical anatomy and surgical approaches to the lateral ventricles.

This study focuses on the surgical approaches to intraventricular tumors which have developed within the cavity of the lateral ventricle. The first section is dedicated to embryology and describes the wrapping of the telencephalic vesicles around the thalamus and the morphogenesis of basal nuclei and commissures. In the second section, the anatomy of the lateral ventricles is described, along with their arterial and venous vasculature, their relationship with the eloquent cortical areas and cortical sulci, and their relationship with white matter fascicles, especially the optic radiations. In the third part, the main surgical approaches to the frontal horn, to the ventricular atrium and to the temporal horn are detailed.