The evolution of mammalian Rem2: unraveling the impact of purifying selection and coevolution on protein function, and implications for human disorders.

Rad And Gem-Like GTP-Binding Protein 2 (Rem2), a member of the RGK family of Ras-like GTPases, is implicated in Huntington's disease and Long QT Syndrome and is highly expressed in the brain and endocrine cells. We examine the evolutionary history of Rem2 identified in various mammalian species, focusing on the role of purifying selection and coevolution in shaping its sequence and protein structural constraints. Our analysis of Rem2 sequences across 175 mammalian species found evidence for strong purifying selection in 70% of non-invariant codon sites which is characteristic of essential proteins that play critical roles in biological processes and is consistent with Rem2's role in the regulation of neuronal development and function.

Association of Cerebrovascular Injury and Secondary Vascular Insult With Poor Outcomes After Gunshot Wound to the Head in a Large Civilian Population.

Background And Objectives: Cerebrovascular injury (CVI) after civilian gunshot wound to the head (GSWH) likely contributes to poor outcomes, but little supporting evidence exists. The purpose of this study was to determine whether intracranial CVI from GSWH and secondary vascular insult (stroke or rehemorrhage) were associated with poor outcomes in a large civilian population.

Methods: This was a single-institution, retrospective cohort study on patients admitted between January 2014 and July 2022 at a large, metropolitan, level-1 trauma center.

Complication rate of overlapping versus nonoverlapping functional and stereotactic surgery: a retrospective cohort study.

Objective: Overlapping surgery, in which one attending surgeon manages two overlapping operating rooms (ORs) and is present for all the critical portions of each procedure, is an important policy that improves healthcare access for patients and case volumes for surgeons and surgical trainees. Despite several studies demonstrating the safety and efficacy of overlapping neurosurgical operations, the practice of overlapping surgery remains controversial. To date, there are no studies that have investigated long-term complication rates of overlapping functional and stereotactic neurosurgical procedures.

Trans-Sulcal Parafascicular Port-Based Resection of a Subcortical Occipital High-Grade Glioma: 2-Dimensional Operative Video.

Minimally invasive trans-sulcal parafascicular port-based approaches can provide safe access to a wide variety of deep brain lesions.1,2 This surgical video illustrates the use of a minimally invasive port-based approach for resection of a subcortical right medial occipital lobe lesion in a 63-year-old woman who presented with seizures and bilateral left homonymous hemianopia. MRI showed a 2.

Double Fascicular Nerve Transfer to Musculocutaneous Branches for Restoration of Elbow Flexion in Brachial Plexus Injury.

Background Restriction of elbow flexion significantly limits upper extremity function following brachial plexus injuries. In recent years, the double fascicular nerve transfer procedure utilizing ulnar and median nerve transfer to musculocutaneous branches has shown promising functional outcomes. Objective To evaluate restoration of elbow flexion following a double fascicular transfer in patients with brachial plexus injuries and identify predictors of poor outcomes.

Combined Radial to Axillary and Spinal Accessory Nerve (SAN) to Suprascapular Nerve (SSN) Transfers May Confer Superior Shoulder Abduction Compared with Single SA to SSN Transfer.

Background: The restoration of shoulder function after brachial plexus injury is a high priority. Shoulder abduction and stabilization can be achieved by nerve transfer procedures including spinal accessory nerve (SAN) to suprascapular nerve (SSN) and radial to axillary nerve transfer. The objective of this study is to compare functional outcomes after SAN to SSN transfer versus the combined radial to axillary and SA to SSN transfer.

Association of Overlapping Surgery With Patient Outcomes in a Large Series of Neurosurgical Cases.

Importance: Overlapping surgery (OS) is common. However, there is a dearth of evidence to support or refute the safety of this practice.

Objective: To determine whether OS is associated with worsened morbidity and mortality in a large series of neurosurgical cases.

Peripheral blood detection of systemic graft-specific xeno-antibodies following transplantation of human neural progenitor cells into the porcine spinal cord.

Extensive pre-clinical and clinical studies have searched for therapeutic efficacy of cell-based therapeutics in diseases of the Central Nervous System (CNS) with no other viable options. Allogeneic cells represent the primary source of these therapies and immunosuppressive regimens have been empirically employed based on experience with solid organ transplantation, attempting to avoid immune mediated graft rejection. In this study, we aimed to 1) characterize the host immune response to stem cells transplanted into the CNS and 2) develop a non-invasive method for detecting immune response to transplanted cell grafts.

Ferumoxytol Labeling of Human Neural Progenitor Cells for Diagnostic Cellular Tracking in the Porcine Spinal Cord with Magnetic Resonance Imaging.

We report on the diagnostic capability of magnetic resonance imaging (MRI)-based tracking of ferumoxytol-labeled human neural progenitor cells (hNPCs) transplanted into the porcine spinal cord. hNPCs prelabeled with two doses of ferumoxytol nanoparticles (hNPC-F and hNPC-F ) were injected into the ventral horn of the spinal cord in healthy minipigs. Ferumoxytol-labeled grafts were tracked in vivo up to 105 days after transplantation with MRI.

Magnetic Resonance Imaging-Guided Transplantation of Neural Stem Cells into the Porcine Spinal Cord.

Background: Cell-based therapies are a promising treatment option for traumatic, tumorigenic and degenerative diseases of the spinal cord. Transplantation into the spinal cord is achieved with intravascular, intrathecal, or direct intraparenchymal injection. The current standard for direct injection is limited by surgical invasiveness, difficulty in reinjection, and the inability to directly target anatomical or pathological landmarks.

Preclinical Validation of Multilevel Intraparenchymal Stem Cell Therapy in the Porcine Spinal Cord.

Background: Although multiple clinical trials are currently testing different stem cell therapies as treatment alternatives for many neurodegenerative diseases and spinal cord injury, the optimal injection parameters have not yet been defined.

Objective: To test the spinal cord's tolerance to increasing volumes and numbers of stem cell injections in the pig.

Methods: Twenty-seven female Göttingen minipigs received human neural progenitor cell injections using a stereotactic platform device.

Cellular therapeutics delivery to the spinal cord: technical considerations for clinical application.

Current literature demonstrates the efficacy of cell-based therapeutics in small animal models of varied spinal cord diseases. However, logistic challenges remain towards development of an optimized delivery approach to the human spinal cord. Clinical trials utilize a variety of methods to achieve this aim.

Surgical technique for spinal cord delivery of therapies: demonstration of procedure in gottingen minipigs.

This is a compact visual description of a combination of surgical technique and device for the delivery of (gene and cell) therapies into the spinal cord. While the technique is demonstrated in the animal, the procedure is FDA-approved and currently being used for stem cell transplantation into the spinal cords of patients with ALS. While the FDA has recognized proof-of-principle data on therapeutic efficacy in highly characterized rodent models, the use of large animals is considered critical for validating the combination of a surgical procedure, a device, and the safety of a final therapy for human use.

Stem cell therapy for the spinal cord.

Injury and disease of the spinal cord are generally met with a poor prognosis. This poor prognosis is due not only to the characteristics of the diseases but also to our poor ability to deliver therapeutics to the spinal cord. The spinal cord is extremely sensitive to direct manipulation, and delivery of therapeutics has proven a challenge for both scientists and physicians.