Gene therapy for epilepsy targeting neuropeptide Y and its Y2 receptor to dentate gyrus granule cells.

Gene therapy is emerging as an alternative option for individuals with drug-resistant focal epilepsy. Here, we explore the potential of a novel gene therapy based on Neuropeptide Y (NPY), a well-known endogenous anticonvulsant. We develop a lentiviral vector co-expressing NPY with its inhibitory receptor Y2 in which, for the first time, both transgenes are placed under the control of the minimal CamKIIa(0.4) promoter, biasing expression toward excitatory neurons and allowing autoregulation of neuronal excitability by Y2 receptor-mediated inhibition. Vector-induced NPY and Y2 expression and safety are first assessed in cultures of hippocampal neurons. In vivo experiments demonstrate efficient and nearly selective overexpression of both genes in granule cell mossy fiber terminals following vector administration in the dentate gyrus. Telemetry video-EEG monitoring reveals a reduction in the frequency and duration of seizures in the synapsin triple KO model. This study shows that targeting a small subset of neurons (hippocampal granule cells) with a combined overexpression of NPY and Y2 receptor is sufficient to reduce the occurrence of spontaneous seizures.

Point-of-Care Fluorescence Biosensing System for Rapid Multi-Allergen Screening.

With the steady increase in allergy prevalence worldwide, there is a strong need for novel diagnostic tools for precise, fast, and less invasive testing methods. Herein, a miniatured fluorescence-based biosensing system is developed for the rapid and quantitative detection of allergen-specific immunoglobulin-E. An antibody-based fluorescence assay in a microfluidic-patterned slide, combined with a custom-made portable fluorescence reader for image acquisition and user-friendly software for the data analysis, enables obtaining results for multiple allergens in just ~1 h with only 80 µL of blood serum. The multiplexed detection of common birch, timothy grass, cat epithelia, house dust mite, and dog epithelia shows quantitative IgE-mediated allergic responses to specific allergens in control serum samples with known total IgE concentration. The responses are verified with different control tests and measurements with a commercial fluorescence reader. These results open the door to point-of-care allergy screening for early diagnosis and broader access and for large-scale research in allergies.

Bilateral pelvic osteotomy for malunion of a vertical shear fracture with 3D-printed patient-specific cutting guides: a case report.

PURPOSE: Pelvic osteotomies present a surgical option to restore pelvic alignment, improve function and pain in sequelae of pelvic ring fractures. Understanding the three-dimensional deformity is a crucial step within preoperative planning; furthermore, accurate intraoperative execution of the planning can be challenging. In recent years, patient-specific guides and 3D modeling have emerged as promising technologies in orthopedic and trauma surgery to enhance surgical precision and facilitate intraoperative decision-making. METHODS:  We present the case of a 41-year-old male patient with a pelvic malunion, resulting from a vertical shear fracture occurring 8 years prior. The patient presented with a 4-cm cranial displacement of the right hemipelvis, accompanied by pubic symphysis disruption and fusion of S1 to L5 vertebra. Severely altered posture in the coronal and sagittal plane was associated with sitting imbalance, impaired gait, and chronic pain. RESULTS: We analyzed the deformity and planned the surgical correction on a 3D interactive virtual model. Moreover, we developed 2 patient-specific cutting guides and one patient-specific reduction guide, allowing accurate bilateral pelvic osteotomies, subsequent realignment, and restoration of the pelvic anatomy. CONCLUSION: For the first time, 3D modeling and 3D-printed patient-specific guides were effectively employed in pelvic malunion surgery, enhancing the precision of preoperative planning, and providing valuable assistance during intraoperative procedures.

Current insights into non-thermal preservation technologies alternative to conventional high-temperature short-time pasteurization of drinking milk.

Milk is an important nutritional food source characterized by a perishable nature and conventionally thermally treated to guarantee its safety. In recent years, an increasing focus on competing non-thermal food processing technologies has been driven mainly by consumers' expectations for minimally processed products. Due to the heat sensitivity of milk, much research interest has been addressed to mild non-thermal pasteurization processing to keep safety, 'fresh-like' taste and to maintain the organoleptic qualities of raw milk. This review provides an overview of the current literature on non-thermal treatments as standalone alternative technologies to high-temperature short-time (HTST) pasteurization of drinking milk. Results of lab-scale experimentations suggest the feasibility of most emerging non-thermal processing technologies, including high hydrostatic pressure, pulsed electric field, cold plasma, cavitation and light-based technologies, as alternative to thermal treatment of drinking milk with premium in shelf life duration. Nevertheless, a series of regulatory, technological and economical hurdles hinder the industrial scaling-up for most of these substitutes. To date, only high hydrostatic pressure treatments are applied as alone alternative to HTSH pasteurization for processing of "cold pasteurized" drinking milk. Milk submitted to HTST treatment combined to ultraviolet light is currently accepted in EU countries as novel food.

Sulcus Angle, Trochlear Depth, and Dejour's Classification Can Be Reliably Applied To Evaluate Trochlear Dysplasia: A Systematic Review of Radiological Measurements.

PURPOSE: To summarize data on the reliability of available imaging criteria for the assessment of trochlear dysplasia and to assess the methodological quality of the included studies. METHODS: This systematic review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. Search was performed using major electronic databases from their inception to September 2021. All studies enrolling patients of any age who underwent a radiological exam to rule out features related to trochlear dysplasia were included. After the identification of available imaging criteria, reliability studies were analyzed. Descriptive statistics were used to summarize findings. Methodological quality was assessed using the Quality Appraisal of Reliability studies checklist. RESULTS: A total of 2391 articles were identified, and 33 articles comprising 3036 patients with a mean age of 28.6 years were included. Thirty different measurements were extracted. Magnetic resonance imaging (MRI) was the most used imaging modalities (21 studies), followed by computed tomography (10 studies), conventional radiology (8 studies) and ultrasonography (US) (1 study). Sulcus angle, trochlear depth, and Dejour's classification were the most explored measurements. Overall, sulcus angle can be reliably assessed on radiography, CT and MRI, whereas trochlear depth can be reliably measured only with CT and MRI. Reliability of Dejour's classification ranged from poor or fair to very good for all imaging modalities. Methodological quality of included studies varied from 2 to 9 positive items out of 11 possible. Twenty-four studies (72.7%) were considered at high risk of bias. CONCLUSION: Trochlear dysplasia can be reliably evaluated at least with 3 measurements: sulcus angle, trochlear depth and Dejour's classification. Methodological quality assessment showed high risk of bias in most included studies. LEVEL OF EVIDENCE: Level III, systematic review of Level II-III studies.

Use of the iliac-outlet and iliac-inlet combined views in percutaneous posterior column retrograde screw fixation.

Posterior column fractures are common acetabular injuries. Although displaced fractures require open reduction and fixation, undisplaced patterns may benefit from percutaneous screw fixation. The combination of iliac oblique with inlet and outlet views offers an intuitive and panoramic rendering of the bony corridor into the posterior column; lateral cross table view completes the sequence of fluoroscopic projections. Herein we describe the use of outlet/inlet iliac views and a detailed procedure for percutaneous retrograde posterior column screw fixation.

Endosteal plating for the treatment of malunions and nonunions of distal femur fractures.

PURPOSE: To describe the surgical technique and the outcome of a case series of nonunion and malunion of distal femur fractures treated with an endosteal medial plate combined with a lateral locking plate and with autogenous bone grafting. METHODS: We retrospectively analyzed a series of patients with malunion or nonunion of the distal femur treated with a medial endosteal plate in combination with a lateral locking plate, in a period between January 2011 and December 2019, Database from chart review was obtained including all the clinical relevant available baseline data (demographics, type of fracture, mechanism of injury, time from injury to surgery, number of previous surgical procedures, type of bone graft, and type of lateral plate). Time to bone healing, limb alignment at follow-up and complications were documented. RESULTS: Ten patients were included into the study: 7 male and 3 female with mean age of 48.3 years (range 21-67). The mechanism of trauma was in 8 cases a road traffic accident and in 2 cases a fall from height. According to AO/OTA classification 5 fractures were 33 A3, 3 were 33 C1, 1 was 33 C2 and 1 was 33 C3. The average follow up was 13.5 months. In all cases but one bony union was achieved. Bone healing was observed in average 3.3 months after surgery. No intraoperative or postoperative complications were reported. CONCLUSION: A medial endosteal plate is a useful augmentation for lateral plate fixation in nonunion or malunion following distal femur fractures, particularly in cases of medial bone loss, severe comminution, or poor bone quality. LEVEL OF EVIDENCE: Level IV (retrospective case series).

Management of distal femoral fractures with metaphyseal and articular comminution (AO/OTA 33C) using nail and plate fixation: a technical note and case series of 14 patients.

PURPOSE: To describe the surgical technique and the outcome of a case series of comminuted intra-articular distal femur fractures (AO/OTA 33C) treated with a nail-plate combination (NPC) implant. METHODS: We retrospectively analyzed a case series of 14 patients with comminuted intra-articular distal femur fractures (DFF) treated with an intramedullary retrograde nail in combination with a lateral low-contact condylar locking plate, in a period between June 2020 and January 2023 at a Level 1 trauma center. Baseline demographic and clinical data were recorded. Time to bone healing, function using Schatzker Lambert Score, and complications were documented. RESULTS: Fourteen patients, 8 males and 6 females, with a total of 15 NPC implants, were included in this study. Eight out of 14 patients had open fractures, all with a Gustilo Anderson type IIIA exposure. The mean age was 48.5 ± 18.05 years. The median follow-up was 392 days, with only one patient lost to follow-up. 11 out of 15 implants achieved complete radiographic consolidation during follow-up, at a mean of 5.40 ± 1.07 months. At the 12-month follow-up, all patients could fully bear weight painlessly or with mild pain. Schatzker Lambert Score was excellent for 4 patients, good for 2 patients, fair for 5 patients, and failure for 2 patients. The main postoperative complications were rigidity (3 cases), limb shortening (2 cases), and septic non-union (1 case). CONCLUSION: This study suggests that the nail-plate combination (NPC) may provide a more effective surgical technique for addressing the challenges associated with comminuted intra-articular distal femur fractures (AO/OTA 33C).

Consensus for management of sacral fractures: from the diagnosis to the treatment, with a focus on the role of decompression in sacral fractures.

BACKGROUND: There is no evidence in the current literature about the best treatment option in sacral fracture with or without neurological impairment. MATERIALS AND METHODS: The Italian Pelvic Trauma Association (A.I.P.) decided to organize a consensus to define the best treatment for traumatic and insufficiency fractures according to neurological impairment. RESULTS: Consensus has been reached for the following statements: When complete neurological examination cannot be performed, pelvic X-rays, CT scan, hip and pelvis MRI, lumbosacral MRI, and lower extremities evoked potentials are useful. Lower extremities EMG should not be used in an acute setting; a patient with cauda equina syndrome associated with a sacral fracture represents an absolute indication for sacral reduction and the correct timing for reduction is "as early as possible". An isolated and incomplete radicular neurological deficit of the lower limbs does not represent an indication for laminectomy after reduction in the case of a displaced sacral fracture in a high-energy trauma, while a worsening and progressive radicular neurological deficit represents an indication. In the case of a displaced sacral fracture and neurological deficit with imaging showing no evidence of nerve root compression, a laminectomy after reduction is not indicated. In a patient who was not initially investigated from a neurological point of view, if a clinical investigation conducted after 72 h identifies a neurological deficit in the presence of a displaced sacral fracture with nerve compression on MRI, a laminectomy after reduction may be indicated. In the case of an indication to perform a sacral decompression, a first attempt with closed reduction through external manoeuvres is not mandatory. Transcondylar traction does not represent a valid method for performing a closed decompression. Following a sacral decompression, a sacral fixation (e.g. sacroiliac screw, triangular osteosynthesis, lumbopelvic fixation) should be performed. An isolated and complete radicular neurological deficit of the lower limbs represents an indication for laminectomy after reduction in the case of a displaced sacral fracture in a low-energy trauma associated with imaging suggestive of root compression. An isolated and incomplete radicular neurological deficit of the lower limbs does not represent an absolute indication. A worsening and progressive radicular neurological deficit of the lower limbs represents an indication for laminectomy after reduction in the case of a displaced sacral fracture in a low-energy trauma associated with imaging suggestive of root compression. In the case of a displaced sacral fracture and neurological deficit in a low-energy trauma, sacral decompression followed by surgical fixation is indicated. CONCLUSIONS: This consensus collects expert opinion about this topic and may guide the surgeon in choosing the best treatment for these patients. LEVEL OF EVIDENCE: IV. TRIAL REGISTRATION: not applicable (consensus paper).

Transmission routes, preventive measures and control strategies of SARS-CoV-2 in the food factory.

SARS-CoV-2 virus represents a health threat in food factories. This infectious virus is transmitted by direct contact and indirectly via airborne route, whereas contamination through inanimate objects/surfaces/equipment is uncertain. To limit the potential spread of the pathogen in the food industry, close working between individuals should be avoided and both personal and respiratory hygiene activities should be enforced. Despite the high infectivity, SARS-CoV-2, being an enveloped virus with a fragile lipid envelop, is sensitive to biocidal products and sanitizers commonly used in the food factory. In the context of the building design, interventions that promote healthy air quality should be adopted, especially in food areas with high-occupancy rates for prolonged times, to help minimize the potential exposure to airborne SARS-CoV-2. Air ventilation and filtration provided by heating, ventilation and air conditioning systems, are effective and easy-to-organize tools to reduce the risk of transmission through the air. In addition to conventional sanitation protocols, aerosolization of hydrogen peroxide, UV-C irradiation or in-situ ozone generation are complementary techniques for an effective virucidal treatment of the air.

Hybrid coracoclavicular and acromioclavicular reconstruction in chronic acromioclavicular joint dislocations yields good functional and radiographic results.

PURPOSE: Optimal treatment of chronic unstable acromioclavicular (AC) joint dislocations (stage 3-5 according the Rockwood classification) is still debated. Anatomic coracoclavicular (CC) reconstruction is a reliable option in terms of two-dimensional radiographic reduction, clinical outcomes, and return to sports, but there remain concerns regarding anterior-posterior stability of the AC joint with CC ligament reconstruction alone. The aim of the present study was to describe the mid-term results of a new hybrid technique with CC and AC ligament reconstruction for chronic AC joint dislocations. METHODS: Twenty-two patients surgically treated for chronic AC joint dislocations (grade 3 to 5) were retrospectively reviewed. All patients were assessed before surgery and at final follow-up with the Constant-Murley score (CMS) and the American Shoulder and Elbow Surgeons (ASES) score. The CC vertical distance (CCD) and the CCD ratio (affected side compared to unaffected side) were measured on Zanca radiographs preoperatively, at 6 months postop and at final follow-up. The same surgical technique consisting in a primary fixation with a suspensory system, coracoclavicular ligaments reconstruction with a double loop of autologous gracilis and acromioclavicular ligaments reconstruction with autologous coracoacromial ligament was performed in all cases. RESULTS: Twenty-two shoulders in 22 patients (19 males and 3 females) were evaluated with a mean age of 34.4 ± 9 years at the time of surgery. The mean interval between the injury and surgery was 53.4 ± 36.7 days. The mean duration of postoperative follow-up was 49.9 ± 11.8 months. According to the Rockwood classification, there were 5 (22.6%) type-III and 17 (77.2%) type-V dislocations. Mean preoperative ASES and CMS were 54.4 ± 7.6 and 64.6 ± 7.2, respectively. They improved to 91.8 ± 2.3 (p = 0.0001) and 95.2 ± 3.1 (p = 0.0001), respectively at final FU. The mean preoperative CCD was 22.4 ± 3.2 mm while the mean CCD ratio was 2.1 ± 0.1. At final FU, the mean CCD was 11.9 ± 1.4 mm (p = 0.002) and the mean CCD ratio was 1.1 ± 0.1 (p = 0.009). No recurrence of instability was observed. One patient developed a local infection and four patients referred some shoulder discomfort. Heterotopic ossifications were observed in three patients. CONCLUSIONS: The optimal treatment of chronic high-grade AC joint dislocations requires superior-inferior and anterior-posterior stability to ensure good clinical outcomes and return to overhead activities or sports. The present hybrid technique of AC and CC ligaments reconstruction showed good clinical and radiographic results and is a reliable an alternative to other reported techniques. LEVEL OF EVIDENCE: Level IV.

No differences between conservative and surgical management of acromioclavicular joint osteoarthritis: a scoping review.

PURPOSE: To conduct a scoping review to clarify the management of acromioclavicular joint osteoarthritis, as well as to identify any existing gaps in the current knowledge. METHODS: Studies were identified by electronic databases (Ovid, Pubmed) from their inception up to April 2nd, 2020. All studies reporting functional outcomes after conservative or surgical treatment of acromioclavicular joint osteoarthritis, either primary or secondary to trauma or distal clavicle osteolysis, were included. Following data were extracted: authors, year of publication, study design (prospective or retrospective), LOE, number of shoulders treated conservatively or surgically, patients' age, OA classification, type of conservative treatment, surgical approach, surgical technique, functional outcomes, complications, revisions, and length of follow-up. Descriptive statistics was used. Quality appraisal was assessed through the Cochrane risk of bias tool for LOE I/II studies, while the MINORS checklist was used for LOE III/IV studies. RESULTS: Nineteen studies were included for a total of 861 shoulders. Mean age of participants was 48.5 ± 7.4 years. Mean follow-up was 43.8 ± 29.9 months. Four studies reported functional results after conservative treatment, whereas 15 studies were focused on surgical management. No studies directly compared conservative and surgical treatment. Seven studies reported a surgical approach after failure of previous conservative treatment. All studies reported functional improvement and pain relief. Complication rate was low. Overall methodological quality of included studies was very low. CONCLUSION: Conservative and surgical treatments are both effective in acromioclavicular joint osteoarthritis management. However, available data did not allow to establish the superiority of one technique over another. LEVEL OF EVIDENCE: Level IV.

High-resolution remote thermometry and thermography using luminescent low-dimensional tin-halide perovskites.

Although metal-halide perovskites have recently revolutionized research in optoelectronics through a unique combination of performance and synthetic simplicity, their low-dimensional counterparts can further expand the field with hitherto unknown and practically useful optical functionalities. In this context, we present the strong temperature dependence of the photoluminescence lifetime of low-dimensional, perovskite-like tin-halides and apply this property to thermal imaging. The photoluminescence lifetimes are governed by the heat-assisted de-trapping of self-trapped excitons, and their values can be varied over several orders of magnitude by adjusting the temperature (up to 20 ns °C-1). Typically, this sensitive range spans up to 100 °C, and it is both compound-specific and shown to be compositionally and structurally tunable from -100 to 110 °C going from [C(NH2)3]2SnBr4 to Cs4SnBr6 and (C4N2H14I)4SnI6. Finally, through the implementation of cost-effective hardware for fluorescence lifetime imaging, based on time-of-flight technology, these thermoluminophores have been used to record thermographic videos with high spatial and thermal resolution.

Operational strategies of a trauma hub in early coronavirus disease 2019 pandemic.

PURPOSE: The "Spedali Civili", one of the largest hospitals in the Italian region most affected by SARS-CoV-2 infection, is managing a large number of traumatic injuries. The objective of this article is to share our operational protocols to deliver an appropriate hospital trauma care in the context of the COVID-19 pandemic. METHODS: We changed our work shifts, in consideration of the high number of patients; colleagues from smaller hospitals in the area joined us to increase the number of surgeons available. Thanks to the collaboration between orthopaedists, anaesthesiologists, and nurses, we created a flow chart and separate routes (in the emergency room, in the wards, and in the operating rooms) to optimize patient management. Our protocols allow us to always provide healthcare professionals with the correct personal protective equipment for the task they are performing. RESULTS: Our strategies proved to be practical and feasible. Having a well thought plan helped us to provide for the most robust response possible. We have not yet been able to study the effectiveness of our protocols, and our recommendations may not be applicable to all healthcare facilities. Nonetheless, sharing our early experience can help other institutions conducting and adapting such plans more quickly. CONCLUSIONS: Having a clear strategy during the COVID-19 pandemic kept our systems resilient and effective and allowed us to provide high-quality trauma care. We offer this approach for other institutions to adopt and adapt to their local setting.

CNF-Functionalization as Versatile Tool for Tuning Activity in Cellulose-Derived Product Hydrogenation.

Carbon nanofibers (CNFs) have been functionalized by introducing O, N, and P containing groups in order to investigate the effect of support functionalization in Ru catalysed hydroxymethyl furfural (HMF) and levulinic acid (LA) hydrogenation. In the case of HMF, despite the fact that no effect on selectivity was observed (all the catalysts produced selectively gamma-valerolactone (GVL)), the functionalization strongly affected the activity of the reaction. O-containing and N-containing supports presented a higher activity compared to the bare support. On the contrary, in HMF hydrogenation, functionalization of the support did not have a beneficial effect on the activity of a Ru-catalysed reaction with respect to bare support and only CNFs-O behaved similarly to bare CNFs. In fact, when CNFs-N or CNFs-P were used as the supports, a lower activity was observed, as well as a change in selectivity in which the production of ethers (from the reaction with the solvent) greatly increased.

Integration of Inverse Supercritical Fluid Extraction and Miniaturized Asymmetrical Flow Field-Flow Fractionation for the Rapid Analysis of Nanoparticles in Sunscreens.

We report the use of inverse supercritical fluid extraction (SFE) and miniaturized asymmetrical flow field-flow fractionation (mAF4) for the preparation and subsequent analysis of titanium dioxide nanoparticles in model and commercial sunscreens. The approach allows for the fast and reliable fractionation and sizing of TiO2 nanoparticles and their quantitation in commercial products. This new method represents a powerful and efficient tool for the verification of nanoparticle content in a wide range of matrixes, as demanded by recently introduced regulatory requirements. Furthermore, the use of carbon dioxide as an environmentally friendly solvent is in line with the increasing need for ecologically compatible analytical techniques.

AAV-PHP.B-Mediated Global-Scale Expression in the Mouse Nervous System Enables GBA1 Gene Therapy for Wide Protection from Synucleinopathy.

The lack of technology for direct global-scale targeting of the adult mouse nervous system has hindered research on brain processing and dysfunctions. Currently, gene transfer is normally achieved by intraparenchymal viral injections, but these injections target a restricted brain area. Herein, we demonstrated that intravenous delivery of adeno-associated virus (AAV)-PHP.B viral particles permeated and diffused throughout the neural parenchyma, targeting both the central and the peripheral nervous system in a global pattern. We then established multiple procedures of viral transduction to control gene expression or inactivate gene function exclusively in the adult nervous system and assessed the underlying behavioral effects. Building on these results, we established an effective gene therapy strategy to counteract the widespread accumulation of α-synuclein deposits throughout the forebrain in a mouse model of synucleinopathy. Transduction of A53T-SCNA transgenic mice with AAV-PHP.B-GBA1 restored physiological levels of the enzyme, reduced α-synuclein pathology, and produced significant behavioral recovery. Finally, we provided evidence that AAV-PHP.B brain penetration does not lead to evident dysfunctions in blood-brain barrier integrity or permeability. Altogether, the AAV-PHP.B viral platform enables non-invasive, widespread, and long-lasting global neural expression of therapeutic genes, such as GBA1, providing an invaluable approach to treat neurodegenerative diseases with diffuse brain pathology such as synucleinopathies.

Ruthenium on Carbonaceous Materials for the Selective Hydrogenation of HMF.

We report the use of Ru catalysts supported in the activated carbon (AC) and carbon nanofibers (CNFs) for the selective production of liquid fuel dimethylfuran (DMF) and fuel additives alkoxymethyl furfurals (AMF). Parameters such as the reaction temperature and hydrogen pressure were firstly investigated in order to optimise the synthesis of the desired products. Simply by using a different support, the selectivity of the reaction drastically changed. DMF was produced with AC as support, while a high amount of AMF was produced when CNFs were employed. Moreover, the reusability of the catalysts was tested and deactivation phenomena were identified and properly addressed. Further studies need to be performed in order to optimise the stability of the catalysts.

Amelogenesis Imperfecta: A Non-Invasive Approach to Improve Esthetics in Young Patients. Report of Two Cases.

Objective-Evaluate esthetic and functional efficacy of infiltrant resin (Icon, DMG, Hamburg, Germany) in Amelogenesis Imperfecta's treatment. STUDY DESIGN: Two adolescent patients, G.S. (13 years old) and C.M. (15 years old), affected by the hypomaturation type of Amelogenesis Imperfecta, were treated with Icon resin and were followed for twelve months. RESULTS: Treated teeth show an excellent aesthetical result immediately after the resin application, effect that lasts in the long-term (six and twelve months follow-up examinations); the dental wear's progression seems to be clinically arrested. CONCLUSIONS: Resin infiltration has proven to be a minimal invasive treatment for dental discoloration, less aggressive than conventional procedures. This approach might be recommended for a stable esthetical improvement in moderate AI's lesions especially in children and adolescents.

Viral Vector-Based Gene Therapy for Epilepsy: What Does the Future Hold?

In recent years, many pre-clinical studies have tested gene therapy approaches as possible treatments for epilepsy, following the idea that they may provide an alternative to conventional pharmacological and surgical options. Multiple gene therapy approaches have been developed, including those based on anti-sense oligonucleotides, RNA interference, and viral vectors. In this opinion article, we focus on translational issues related to viral vector-mediated gene therapy for epilepsy. Research has advanced dramatically in addressing issues like viral vector optimization, target identification, strategies of gene expression, editing or regulation, and safety. Some of these pre-clinically validated potential gene therapies are now being tested in clinical trials, in patients with genetic or focal forms of drug-resistant epilepsy. Here, we discuss the ongoing translational research and the advancements that are needed and expected in the near future. We then describe the clinical trials in the pipeline and the further challenges that will need to be addressed at the clinical and economic levels. Our optimistic view is that all these issues and challenges can be overcome, and that gene therapy approaches for epilepsy will soon become a clinical reality.