Nanoassemblies designed for efficient nuclear targeting.

One of the key aspects of coping efficiently with complex pathological conditions is delivering the desired therapeutic compounds with precision in both space and time. Therefore, the focus on nuclear-targeted delivery systems has emerged as a promising strategy with high potential, particularly in gene therapy and cancer treatment. Here, we explore the design of supramolecular nanoassemblies as vehicles to deliver specific compounds to the nucleus, with the special focus on polymer and peptide-based carriers that expose nuclear localization signals. Such nanoassemblies aim at maximizing the concentration of genetic and therapeutic agents within the nucleus, thereby optimizing treatment outcomes while minimizing off-target effects. A complex scenario of conditions, including cellular uptake, endosomal escape, and nuclear translocation, requires fine tuning of the nanocarriers' properties. First, we introduce the principles of nuclear import and the role of nuclear pore complexes that reveal strategies for targeting nanosystems to the nucleus. Then, we provide an overview of cargoes that rely on nuclear localization for optimal activity as their integrity and accumulation are crucial parameters to consider when designing a suitable delivery system. Considering that they are in their early stages of research, we present various cargo-loaded peptide- and polymer nanoassemblies that promote nuclear targeting, emphasizing their potential to enhance therapeutic response. Finally, we briefly discuss further advancements for more precise and effective nuclear delivery.

[Proximal femoral varus osteotomy in Legg-Calve-Perthes disease]. / Proximale Varisationsosteotomie des Femurs beim Morbus Perthes.

OBJECTIVE: The proximal femoral varus osteotomy (FVO) aims to re-centre the femoral head in the acetabular socket after prognostically unfavourable subluxation, e.g. in Legg-Calve-Perthes disease (LCPD). INDICATIONS: No unified indication criteria have been defined yet for containment therapy in LCPD. However, specific radiographic features related to deformity development, age at diagnosis or onset and classifications describing pathomorphological changes in the femoral head related to bone necrosis can support decisionmaking. CONTRAINDICATIONS: Absolute contraindications-a hinge abducted joint; failure of femoral head reduction in the 20° abduction anteroposterior view; total epiphyseal necrosis. Relative contraindication-children < 6 years, in lateral pillar classification group A or Catteral group I and II. SURGICAL TECHNIQUE: Lateral approach to the proximal femur. Insertion of the first K­wire to mark the anteversion of the femoral neck. Additional K­wires are placed parallel to the first via the positioner aiming block. Lokalise the optimal postion for the osteotomy. Insertion of additional K­wires in the distal fragment an facilitate manipulation and serve as reference for derotation. After osteotomy proximal fixation of the plate with locking screws replacing the K-wires. Insertion of a cortical screw into the middle hole to achieve optimal interfragmentary compression. Remaining locking screws are inserted and cortical screw replaced by a locking screw. POSTOPERATIVE MANAGEMENT: Mobilization with heel-touch weight-bearing on crutches for 6 weeks. Increased weightbearing after radiographic follow-up as soon as sufficient bone union is present. Implant removal after 9-12 months. Return to sports after 3 months. RESULTS: The FVO has been used in the surgical treatment of severe LCPD for nearly 60 years and is established worldwide. Growing knowledge and consecutive optimization of the surgery indication together with the new implants contribute to improving clinical and radiological outcomes and reducing intraoperative and postoperative complications.

Re-fractures of the paediatric radius and/or ulna: A systematic review.

BACKGROUND: Fractures of the radius and/or ulna are one of the most common injuries in children. Evidence identifying risk factors for refracture, however, has not been summarised in a systematic review. Guidance for counselling patients and parents to minimise the risk of refracture is limited. The aims of this study are to 1) to determine if casting time 6 weeks or less is a risk factor for refracture after paediatric radius and/or ulna fractures, 2) to identify other risk factors for refracture after paediatric radius and/or ulna fractures and 3) to develop more accurate guidelines for counselling parents after a radius and/or ulna fracture in their child. METHODS: A thorough search was performed in accordance with the Joanna Briggs Institute (JBI) guidelines for systematic review. JBI Critical Appraisal checklists were used for risk of bias assessment. RESULTS: Diaphyseal both-bone fractures treated non-surgically should be casted for longer than 6 weeks. Surgically treated patients can be casted for less than 6 weeks. Diaphyseal and greenstick fractures have a higher risk of refracture. Residual angulation and incomplete healing in greenstick fractures may lead to a higher risk of refracture. Gender does not affect refracture risk. Falls, use of wheeled vehicles, playground activities and trampolining confer high-risk of refracture. Refracture risk is greatest up to 9 months from initial fracture. CONCLUSION: Further case-controlled studies with sub-group analysis are required to further investigate risk factors for refracture after radius and/or ulna fractures in children.