Three-Dimensional Measurement of the Uterus on Magnetic Resonance Images: Development and Performance Analysis of an Automated Deep-Learning Tool.

Uterus measurements are useful for assessing both the treatment and follow-ups of gynaecological patients. The aim of our study was to develop a deep learning (DL) tool for fully automated measurement of the three-dimensional size of the uterus on magnetic resonance imaging (MRI). In this single-centre retrospective study, 900 cases were included to train, validate, and test a VGG-16/VGG-11 convolutional neural network (CNN). The ground truth was manual measurement. The performance of the model was evaluated using the objective key point similarity (OKS), the mean difference in millimetres, and coefficient of determination R2. The OKS of our model was 0.92 (validation) and 0.96 (test). The average deviation and R2 coefficient between the AI measurements and the manual ones were, respectively, 3.9 mm and 0.93 for two-point length, 3.7 mm and 0.94 for three-point length, 2.6 mm and 0.93 for width, 4.2 mm and 0.75 for thickness. The inter-radiologist variability was 1.4 mm. A three-dimensional automated measurement was obtained in 1.6 s. In conclusion, our model was able to locate the uterus on MRIs and place measurement points on it to obtain its three-dimensional measurement with a very good correlation compared to manual measurements.

Impact of artificial intelligence in breast cancer screening with mammography.

OBJECTIVES: To demonstrate that radiologists, with the help of artificial intelligence (AI), are able to better classify screening mammograms into the correct breast imaging reporting and data system (BI-RADS) category, and as a secondary objective, to explore the impact of AI on cancer detection and mammogram interpretation time. METHODS: A multi-reader, multi-case study with cross-over design, was performed, including 314 mammograms. Twelve radiologists interpreted the examinations in two sessions delayed by a 4 weeks wash-out period with and without AI support. For each breast of each mammogram, they had to mark the most suspicious lesion (if any) and assign it with a forced BI-RADS category and a level of suspicion or "continuous BI-RADS 100". Cohen's kappa correlation coefficient evaluating the inter-observer agreement for BI-RADS category per breast, and the area under the receiver operating characteristic curve (AUC), were used as metrics and analyzed. RESULTS: On average, the quadratic kappa coefficient increased significantly when using AI for all readers [κ = 0.549, 95% CI (0.528-0.571) without AI and κ = 0.626, 95% CI (0.607-0.6455) with AI]. AUC was significantly improved when using AI (0.74 vs 0.77, p = 0.004). Reading time was not significantly affected for all readers (106 s without AI and vs 102 s with AI; p = 0.754). CONCLUSIONS: When using AI, radiologists were able to better assign mammograms with the correct BI-RADS category without slowing down the interpretation time.

Local Tumor Staging of Breast Cancer: Digital Mammography versus Digital Mammography Plus Tomosynthesis.

Background Combined digital mammography (DM) and digital breast tomosynthesis (DBT) (hereafter, DM plus DBT) has increased cancer detection rates when compared with those achieved with DM-only screening. However, there is limited literature on DBT as an adjunct to mammography in the staging of known breast cancers. Purpose To compare the diagnostic accuracy of DM alone with that of DM plus DBT in the identification of additional ipsilateral and contralateral lesions in women with newly diagnosed breast cancer. Materials and Methods This prospective study ( https://clinicaltrials.gov , NCT01881880) included 166 women with breast cancer (mean age, 59.5 years ± 11; age range, 40-87 years) and used the aforementioned techniques, with breast MRI and pathologic verification of all suspected lesions as the reference standards. Four radiologists independently reviewed the DM and DM plus DBT images using the American College of Radiology Breast Imaging Reporting and Data Systems criteria for diagnosis of index lesions and presence of additional disease. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) obtained for DM and DM plus DBT were compared by using the McNemar test. Results Twenty-four women (14%) exhibited multifocal lesions; 20 (12%), multicentric lesions; 39 (23%), additional ipsilateral lesions; and 18 (11%), bilateral lesions. The sensitivities were higher for DM plus DBT than for DM in the diagnosis of multicentric (51% [41 of 80] vs 37% [30 of 80], P = .002) and additional ipsilateral (52% [81 of 156] vs 44% [69 of 156], P = .007) lesions. The AUC was larger for DM plus DBT than for DM (0.74 vs 0.67, P = .02) in the diagnosis of bilateral breast cancer. No significant differences in specificity were noted. The added diagnostic value of DBT was limited to the group of women with nondense breasts: For diagnosis of ipsilateral lesions, AUC of DM plus DBT versus DM was 0.74 versus 0.70 (P = .04). For diagnosis of contralateral lesions, AUC of DM plus DBT verus DM was 0.76 versus 0.68 (P = .02). Conclusion The combination of digital mammography with digital breast tomosynthesis improves diagnostic accuracy for additional ipsilateral and contralateral breast cancer in women with nondense breasts. © RSNA, 2019 See also the editorial by Moy in this issue.

Patient care for postamputation pain and the complexity of therapies: living experiences.

AIM: Limb amputation traumatically alters body image. Sensations rapidly prevail that the limb is still present and 85% of patients portray phantom limb pain. Throughout the testimonies of amputated patients with intense phantom limb pain, we show the difficulty in treating this chronic pain with current pharmacological and nonpharmacological therapies. PATIENTS & METHODS: We qualitatively analyzed the therapeutic choices of five amputees, the effectiveness of the treatments chosen and the impact on patients' quality-of-life. RESULTS & CONCLUSION: In general, patients who are refractory to pharmacological treatments are in favor of trying alternative therapies. It is therefore crucial to design a combined and personalized therapeutic plan under the coordination of a multidisciplinary team for the wellbeing of the patient.

Transcarotid transcatheter aortic valve implantation: multicentre experience in France.

OBJECTIVES: Transcatheter aortic valve implantation is a well-recognized treatment option for high-risk patients with aortic stenosis. The femoral approach is possible in 80% of cases and remains the access of choice. When this approach is not feasible, other alternative routes have been proposed such as transapical, transaortic and subclavian. Transcarotid aortic valve implantation has been proposed as another direct vascular access. Its use is relatively new and still under evaluation. METHODS: We successfully performed transcarotid aortic valve implantation in 145 consecutive patients through the left or right carotid artery in 3 different French sites over a 2-year period. Data were prospectively entered in the French transcatheter aortic valve implantation database. RESULTS: The mean age was 79.8 ± 8.7 years, with a mean logistic EuroSCORE of 20.7 ± 12.6%. The procedure was successful in all patients, and no conversion was necessary. Thirty-day survival was 93.7%, 8 (5.5%) patients presented either minor or major strokes and 1 patient had a localized asymptomatic carotid dissection. All patients were immediately extubated, and none presented respiratory complications. CONCLUSIONS: Transcarotid aortic valve implantation is a safe alternative to transfemoral transcatheter aortic valve implantation, with direct access to the aortic valve, which can be performed with limited incision.

Moderate Hypothermia Improves Cardiac and Vascular Function in a Pig Model of Ischemic Cardiogenic Shock Treated With Veno-Arterial ECMO.

Cardiogenic shock (CS) patients treated with extracorporeal membrane oxygenation (ECMO) have severe cardiac failure, associated with ischemia-reperfusion. The use of moderate hypothermia during ischemia-reperfusion syndrome is supported by experimental data. We therefore studied the effects of moderate hypothermia on cardiac and vascular function in pig ischemic CS treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). CS was induced in 12 anesthetized pigs by coronary ligation. After 1 h of CS, VA-ECMO was initiated and pigs were randomized to normothermia (38°C) or moderate hypothermia (34°C) during 8 h. Intrinsic cardiac function was measured using a left ventricular conductance catheter. At the end of the experiment, tissues were harvested for Western blotting. ECMO associated with norepinephrine infusion and volume resuscitation increased mean arterial pressure, mixed venous oxygen saturation as well as carotid, renal, and coronary blood flow without any differences between normothermia and hypothermia. Hypothermia was associated with less fluid and less norepinephrine infusion, lower lactate level, and higher urinary output. Vascular reactivity was superior in hypothermia comparatively to normothermia as expressed using norepinephrine dose-response curves. Pressure development during isovolumic contraction, left ventricular ejection fraction, and prerecruitable stroke work index were higher in the hypothermia group. There were no differences between normothermia and hypothermia with regard to carotid and mesenteric protein expression for iNOs, eNOS, and phospho AKt/AKt measured at the end of the experimentation. The incidence of surgical bleeding and coagulation disorders was the same in both groups. In conclusion, moderate and rapid hypothermia improves hemodynamics and cardiac and vascular function in a pig model of ischemic CS treated with ECMO.

Transcarotid transcatheter aortic valve implantation.

Transcatheter aortic valve implantation is a well-recognized treatment option for high-risk patients with aortic stenosis. The femoral approach is possible in 80% of cases. Initially, only the transcarotid and subclavian approaches were performed as alternative routes. Both approaches have advantages and disadvantages. The carotid approach is a new approach that offers direct vascular access to the aortic valve. The technique of access is very simple and well known to all cardiovascular surgeons, and the morbidity is minimal. It avoids a thoracotomy with all its complications. We present here our technique and results of our initial experience.

The in situ gas-phase formation of a C-glycoside ion obtained during electrospray ionization tandem mass spectrometry. A unique intramolecular mechanism involving an ion-molecule reaction.

RATIONALE: This study examines the electrospray ionization mass spectrometry (ESI-MS), in-source collision-induced dissociation (CID) fragmentation and low-energy collision-induced dissociation tandem mass spectrometry (CID-MS/MS) of a synthetic pair of ß- and α-anomers of the amphiphilic cholesteryl polyethoxy neoglycolipids containing the 2-azido-2-deoxy-D-galactosyl-D-GalN3 moiety. We describe the novel and unique in situ gas-phase formation of a C-glycoside ion formed during all these gas-phase processes and propose a reasonable mechanism for its formation. METHODS: The synthetic amphiphilic glycolipids were composed of the 2-deoxy-2-azido-D-galactosyl moiety (GalN3, the hydrophilic part) covalently attached to a polyethoxy spacer which is covalently linked to the cholesteryl moiety (hydrophobic part). The 2-azido-2-deoxy-α- and ß-D-galactosyl-containing glycolipids were studied by in-time and in-space ESI-MS and CID-MS/MS in positive ion mode, with quadrupole ion trap (QIT), quadrupole-quadrupole-time-of-flight (QqTOF), and Fourier transform ion cyclotron resonance (FTICR) instruments. RESULTS: Conventional single-stage ESI-MS analysis showed the formation of the protonated molecule. During the single-stage ESI-MS analysis and the CID-MS/MS of the [M+H](+) and [M+NH4](+) adducts obtained from both glycolipid anomers, the presence of a series of specific product ions with different intensities was observed, consistent with the [C-glycoside+H-N2](+), [cholestadiene+H](+), 2-deoxy-2-D-azido-galactosyl [GalN3](+), [GalNH](+) and [sugar-Spacer+H](+) ions. CONCLUSIONS: The gas-phase formation of the [C-glycoside+H-N2](+) ion isolated from the glycolipid anomers was observed during both the ESI-MS of the glycolipids and the CID-MS/MS analyses of the [M+H](+) ions and it was found to occur by an intramolecular rearrangement involving an ion-molecule complex. CID-QqTOF-MS/MS and CID-FTICR-MS(2) analysis allowed the differentiation of the two glycolipid anomers and showed noticeable variation in the intensities of the product ions.

Ultrasound-guided high-intensity focused ultrasound treatment of breast fibroadenoma-a multicenter experience.

BACKGROUND: The aim of our multicenter study was to assess the clinical outcome and safety of ultrasound (US)-guided high-intensity focused ultrasound (HIFU) in patients with breast fibroadenoma (FA). METHODS: From May 2011 to February 2013, 42 women with 51 FA in one or both breasts were selected for treatment with US-guided HIFU. Eight of 51 FA were treated twice. Patients' age ranged from 16 to 52 years (mean 32 years). All patients with FA underwent core needle biopsy with histological confirmation. HIFU treatment was performed as an outpatient procedure under conscious sedation. Exclusion criteria were pregnant or lactating women, microcalcifications within the lesion at mammogram, history of breast cancer, previous laser or radiation therapy, and breast implant in the same breast. All patients signed written informed consent. After the treatment, follow-up US with volume evaluation was performed at 2, 6, and 12 months. RESULTS: The FA mean baseline volume was 3.89 ml (0.34-19.66 ml). At 2-month follow-up, the mean volume reduction was 33.2% ± 19.1% and achieved significance at 6-month (59.2% ± 18.2%, p < 0.001) and 12-month (72.5% ± 16.7%, p < 0.001) follow-up. Related side effects as superficial skin burn with blister-like aspect in three patients and hyperpigmentation over the treated area in one patient were transient and resolved spontaneously. In one patient, asymptomatic subcutaneous induration persisted at the end of the study. CONCLUSIONS: US-guided HIFU treatment is an effective noninvasive method for the treatment of breast FA and well tolerated by the patients. Preliminary results are encouraging and show that HIFU could be an alternative to surgery for breast FA.

Biological and biochemical properties of two Xenopus laevis N-acetylgalactosaminyltransferases with contrasting roles in embryogenesis.

The biosynthesis of mucin-type O-linked glycans in animals is initiated by members of the large family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts), which play important roles in embryogenesis, organogenesis, adult tissue homeostasis and carcinogenesis. Until now, the mammalian forms of these enzymes have been the best characterized. However, two N-acetylgalactosaminyltransferases (xGalNAc-T6 and xGalNAc-T16) from the African clawed frog (Xenopus laevis), which are most homologous to those encoded by the human GALNT6 and GALNT16 (GALNTL1) genes, were shown to have contrasting roles in TGF-ß/BMP signaling in embryogenesis. In this study we have examined these two enzymes further and show differences in their in vivo function during X. laevis embyrogenesis as evidenced by in situ hybridization and overexpression experiments. In terms of enzymatic activity, both enzymes were found to be active towards the EA2 peptide, but display differential activity towards a peptide based on the sequence of ActR-IIB, a receptor relevant to TGF-ß/BMP signaling. In summary, these data demonstrate that these two enzymes from different branches of the N-acetylgalactosaminyltransferase do not only display differential substrate specificities, but also specific and distinct expression pattern and biological activities in vivo.

3D-fection: cell transfection within 3D scaffolds and hydrogels.

BACKGROUND: 3D matrices are widely used as cell growth supports in basic research, regenerative medicine or cell-based drug assays. In order to genetically manipulate cells cultured within 3D matrices, two novel non-viral transfection reagents allowing preparation of matrices for in situ cell transfection were evaluated. RESULTS: Two lipidic formulations, 3D-Fect™ and 3D-FectIN™, were assessed for their ability to transfect cells cultured within 3D solid scaffolds and 3D hydrogels, respectively. These reagents showed good compatibility with the most widespread types of matrices and enabled transfection of a wide range of mammalian cells of various origins. Classical cell lines, primary cells and stem cells were thus genetically modified while colonizing their growth support. Importantly, this in situ strategy alleviated the need to manipulate cells before seeding them. CONCLUSION: Results presented here demonstrated that 3D-Fect and 3D-FectIN reagents for 3D transfection are totally compatible with cells and do not impair matrix properties. 3D-Fect and 3D-FectIN, therefore, provide valuable tools for achieving localized and sustained transgene expression and should find versatile applications in fundamental research, regenerative medicine and cell-based drug assays.

Use of the model for end-stage liver disease score for guiding clinical decision-making in the selection of patients for emergency cardiac transplantation.

OBJECTIVES: The outcomes of emergency cardiac transplantation remain controversial, but recipient selection is essential for success. With a shortage of organs, it is essential to determine an objective method, such as a risk score, for choosing patients who are at too great a risk to undergo cardiac transplantation. In this study, we analysed the model for end-stage liver disease in terms of predicting operative mortality after emergency cardiac transplantation. METHODS: We analysed the Nancy University database of heart transplantation and selected all patients who underwent emergency heart transplantation between January 2005 and January 2012. The calibration and discriminatory power were evaluated to determine the model for end-stage liver disease (MELD) score. Preoperative and peri-operative variables regarding the prediction of operative mortality were analysed by univariate and multivariate logistic regression models. RESULTS: Forty-three patients underwent emergency cardiac transplantation. The operative mortality was 20.9% (n = 9). The Hosmer-Lemeshow test demonstrated a calibrated model for predicting operative mortality (P = 0.15), and the MELD score presented an excellent discrimination between survivors and non-survivors (AUC: 0.89 ± 0.05; 95% CI: 0.79-0.99). In the univariate analysis, an MELD score of ≥ 16 and bilirubin concentration were predictive markers of operative mortality. Multivariate logistic regression tested the contribution of the univariate risk predictors (P < 0.15) and confirmed that an MELD score of ≥ 16 was predictive of operative mortality. CONCLUSIONS: The MELD score appears to be adequate for predicting operative mortality among patients who undergo heart transplantation. The MELD score could therefore be used to guide clinical decision-making for emergency transplantation.

Chemoenzymatic synthesis of O-mannosylpeptides in solution and on solid phase.

O-mannosyl glycans are known to play an important role in regulating the function of α-dystroglycan (α-DG), as defective glycosylation is associated with various phenotypes of congenital muscular dystrophy. Despite the well-established biological significance of these glycans, questions regarding their precise molecular function remain unanswered. Further biological investigation will require synthetic methods for the generation of pure samples of homogeneous glycopeptides with diverse sequences. Here we describe the first total syntheses of glycopeptides containing the tetrasaccharide NeuNAcα2-3Galß1-4GlcNAcß1-2Manα, which is reported to be the most abundant O-mannosyl glycan on α-DG. Our approach is based on biomimetic stepwise assembly from the reducing end and also gives access to the naturally occurring mono-, di-, and trisaccharide substructures. In addition to the total synthesis, we have developed a "one-pot" enzymatic cascade leading to the rapid synthesis of the target tetrasaccharide. Finally, solid-phase synthesis of the desired glycopeptides directly on a gold microarray platform is described.

Cardiac surgery in cirrhotic patients: results and evaluation of risk factors.

OBJECTIVES: Liver cirrhosis increases mortality and morbidity following cardiac surgery. This study evaluated the results of cardiac surgery in cirrhotic patients and the relevance of EuroSCORE, Child-Turcotte-Pugh (CTP) class and model for end-stage liver disease (MELD) score in terms of prediction of surgical mortality and survival. METHODS: The study involved 34 patients with hepatic cirrhosis who underwent cardiac surgery between January 1996 and January 2010. RESULTS: The in-hospital mortality was 26%. Postoperative mortality of patients with CTP class A, B or C was 18, 40 and 100%, respectively. In univariate analysis, a history of cerebrovascular disease and hypoalbuminaemia was predictive of operative mortality. Multivariate exact logistic regression revealed that hypoalbuminaemia was an independent factor. Long-term survival was 63 ± 0.08% at 1 year and 40.2 ± 0.12% at 5 years. The 1-year survival for CTP A, B and C was 76.7 ± 0.09, 60 ± 15.4 and 0%, respectively, and the 5-year survival was 60 ± 15.4, 25 ± 0.19 and 0%, respectively. The EuroSCORE was not a discriminant [area under the curve (AUC): 0.57 ± 0.15]. The performance of CTP class and MELD score was better, but neither provided optimal discrimination: AUC was 0.691 ± 0.110 for MELD and 0.658 ± 0.10 for CTP class. CONCLUSIONS: Cardiac surgery can be performed safely in CTP class A patients. In CTP C patients, surgery is hazardous, and an alternative treatment must be considered. In CTP B, the MELD score could be helpful in deciding whether surgical intervention is a reasonable option.

Surgery for acute type A aortic dissection in octogenarians.

BACKGROUND AND AIM: Emergency surgery for type A aortic dissection (AAD) is associated with high mortality rates. The published outcomes of such surgery in aging patients are controversial and the optimal management for elderly patients has not been established. Our study aimed to evaluate the outcomes of surgery for AAD in patients over the age of 80 years. MATERIALS AND METHODS: Between January 1996 and January 2010, 236 patients underwent surgery for AAD, of which 15 patients were older than 80 years. We evaluated the operative mortality in the whole cohort compared to the outcomes in the elderly subgroup. We assessed the preoperative risks factors and quality of life after surgery by performance status and the patients' ability to return home. RESULTS: Operative mortality was higher in patients aged >80 years (40% vs. 18%, p = 0.04). The survival rate for patients >80 years at one, three, and five years was 53.3% ± 0.12%, 42.6% ± 0.14%, and 42.6% ± 0.12%, respectively. Of the survivors, six patients were able to return home (40%) and the postoperative performance status was "3" in one patient, "2" in six patients, and "1" in two patients. A preoperative level of 2 or greater was found to be a significant risk factor (p = 0.04). CONCLUSION: Survival in octogenarians undergoing surgery for AAD is possible, and some patients were able to return home with a reasonable level of autonomy. Larger series will be needed to define the optimal management for octogenarians presenting with AAD.

Magnetic nanoparticles enhance adenovirus transduction in vitro and in vivo.

PURPOSE: Adenoviruses are among the most powerful gene delivery systems. Even if they present low potential for oncogenesis, there is still a need for minimizing widespread delivery to avoid deleterious reactions. In this study, we investigated Magnetofection efficiency to concentrate and guide vectors for an improved targeted delivery. METHOD: Magnetic nanoparticles formulations were complexed to a replication defective Adenovirus and were used to transduce cells both in vitro and in vivo. A new integrated magnetic procedure for cell sorting and genetic modification (i-MICST) was also investigated. RESULTS: Magnetic nanoparticles enhanced viral transduction efficiency and protein expression in a dose-dependent manner. They accelerated the transduction kinetics and allowed non-permissive cells infection. Magnetofection greatly improved adenovirus-mediated DNA delivery in vivo and provided a magnetic targeting. The i-MICST results established the efficiency of magnetic nanoparticles assisted viral transduction within cell sorting columns. CONCLUSION: The results showed that the combination of Magnetofection and Adenoviruses represents a promising strategy for gene therapy. Recently, a new integrated method to combine clinically approved magnetic cell isolation devices and genetic modification was developed. In this study, we validated that magnetic cell separation and adenoviral transduction can be accomplished in one reliable integrated and safe system.

MALDI-ToF MS analysis of glycosyltransferase activities on gold surface arrays.

Glycan-processing enzymes such as glycosyltransferases and glycosidases are responsible for the makeup of the glycome. The definition of their substrate specificities is, therefore, a central task in glycomics. In addition, these enzymes are themselves useful synthetic tools for the generation of complex carbohydrate structures as an alternative to tedious chemical synthesis. There has been great interest in using microarrays for studying these glycoenzymes because it allows the specificity of the enzyme to be probed against a panel of immobilized potential substrates, and also expands the repertoire of sugar arrays available for further carbohydrate-protein interaction studies. In particular, self-assembled monolayers (SAMs) of alkanethiols on gold surfaces have proven to be a valuable platform for such studies due to their robustness and their biocompatible, well-defined structure. Furthermore, a direct observation of the change in mass of immobilized substrates due to enzymatic processing is possible through label-free MALDI-ToF MS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry) technique. In this chapter, we describe the preparation of SAMs-coated gold surface arrays presenting carbohydrate or (glyco)peptide substrates, either pre-formed or directly synthesized on-chip, and MALDI-ToF MS analysis of glycosyltransferase activities on these immobilized substrates.

High transfection efficiency of neural stem cells with magnetofection.

Primary neural stem cells (NSCs) can be cultivated and differentiated in vitro but are difficult to transfect using conventional methods. We describe a simple and rapid magnetofection-based method suitable for the lab bench as well as for high-throughput projects. Our method yields high transfection efficiency and can be used for deciphering the genetic control of neural cell differentiation.

Biochemical correlation of activity of the α-dystroglycan-modifying glycosyltransferase POMGnT1 with mutations in muscle-eye-brain disease.

Congenital muscular dystrophies have a broad spectrum of genotypes and phenotypes and there is a need for a better biochemical understanding of this group of diseases in order to aid diagnosis and treatment. Several mutations resulting in these diseases cause reduced O-mannosyl glycosylation of glycoproteins, including α-dystroglycan. The enzyme POMGnT1 (protein-O-mannose N-acetylglucosaminyltransferase 1; EC 2.4.1.-) catalyses the transfer of N-acetylglucosamine to O-linked mannose of α-dystroglycan. In the present paper we describe the biochemical characterization of 14 clinical mutants of the glycosyltransferase POMGnT1, which have been linked to muscle-eye-brain disease or similar conditions. Truncated mutant variants of the human enzyme (recombinant POMGnT1) were expressed in Escherichia coli and screened for catalytic activity. We find that three mutants show some activity towards mannosylated peptide substrates mimicking α-dystroglycan; the residues affected by these mutants are predicted by homology modelling to be on the periphery of the POMGnT1 surface. Only in part does the location of a previously described mutated residue on the periphery of the protein structure correlate with a less severe disease mutant.

[In vitro and in vivo Magnetofection : a move towards gene therapy]. / Magnétofection in vitro et in vivo : une voie vers la thérapie génique.

Gene therapy offers exciting opportunities for the treatment of innate or acquired genetic diseases. However, there is still a need for a safe and efficient strategy to deliver nucleic acids into cells while overcoming the current limitations faced with standard viral vectors. Intensive researches have been carried out over the past decade, focusing both on viral and non-viral (i.e. physical or chemical) strategies. Of these numerous attempts, magnetofection, defined as the combination of nucleic acid vectors with magnetic nanoparticles, holds the promise to achieve high transfection efficiency with reduced toxicity by magnetically focusing the genetic material to be delivered on its cellular target. In vitro as well as in vivo results already demonstrated that this strategy may become a valuable tool towards practical gene therapy.