Accelerated Implementation of a Virtual Neurology Clerkship Amid a Global Crisis.

The standard neurology clinical experience in medical school focuses primarily on bedside patient encounters; however, the limitations of the clinical environment due to the current COVID-19 pandemic have accelerated the need for virtual curriculum development. To provide guidance to Neurology clerkship directors during this unprecedented time, the American Academy of Neurology (AAN) Undergraduate Education Subcommittee (UES) formed a workgroup to develop an outline for a virtual curriculum, provide recommendations, and describe models of integrating virtual curricula into the neurology clerkship. In this overview, we discuss different methods of virtual instruction, hybrid models of clerkship training and the challenges to its implementation, professionalism issues, and modification of feedback and assessment techniques specific to the virtual learning environment. We also offer suggestions for implementation of a hybrid virtual curriculum into the neurology clerkship. The virtual curriculum is intended to supplement the core neurology in-person clinical experience and should not be used for shortening or replacing the required neurology clinical clerkship.

SARS-CoV-2 Neuronal Invasion and Complications: Potential Mechanisms and Therapeutic Approaches.

Clinical reports suggest that the coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome (SARS)-coronavirus-2 (CoV-2) has not only taken millions of lives, but has also created a major crisis of neurologic complications that persist even after recovery from the disease. Autopsies of patients confirm the presence of the coronaviruses in the CNS, especially in the brain. The invasion and transmission of SARS-CoV-2 in the CNS is not clearly defined, but, because the endocytic pathway has become an important target for the development of therapeutic strategies for COVID-19, it is necessary to understand endocytic processes in the CNS. In addition, mitochondria and mechanistic target of rapamycin (mTOR) signaling pathways play a critical role in the antiviral immune response, and may also be critical for endocytic activity. Furthermore, dysfunctions of mitochondria and mTOR signaling pathways have been associated with some high-risk conditions such as diabetes and immunodeficiency for developing severe complications observed in COVID-19 patients. However, the role of these pathways in SARS-CoV-2 infection and spread are largely unknown. In this review, we discuss the potential mechanisms of SARS-CoV-2 entry into the CNS and how mitochondria and mTOR pathways might regulate endocytic vesicle-mitochondria interactions and dynamics during SARS-CoV-2 infection. The mechanisms that plausibly account for severe neurologic complications with COVID-19 and potential treatments with Food and Drug Administration-approved drugs targeting mitochondria and the mTOR pathways are also addressed.

Management of glioblastoma: a perspective from Mexico.

Access to healthcare in Mexico is available to its population via publicly and privately funded institutions. The public sector, administered by both the local and federal government under the jurisdiction of the Department of Health, provides healthcare to the majority of the country's population. Privately funded institutions vary in size and scope of practice, ranging from small clinics focused on family practice, to large tertiary hospitals with capacity for treating patients with complex conditions and performing clinical research. The evaluation and treatment of patients with cancer in Mexico is also available through both sectors. In the country's capital, Mexico City, patients with glioblastoma are primarily treated at the National Institute of Neurology and Neurosurgery and the National Institute of Oncology. Epidemiological data is incomplete due to the lack of a national cancer registry. In the case of neoplasms of the central nervous system, the available information suggests that gliomas represent 33% of all intracranial tumors. The treatment of patients in Mexico diagnosed with glioblastoma has not been standardized owing to the lack of resources in some communities and the expense of antineoplastic agents. Current options range from a biopsy only to maximal safe resection followed by adjuvant treatment with radiation and chemotherapy. Currently, basic science and clinical research is being conducted in academic institutions associated with universities and in private hospitals. Studies include the evaluation of tumor biology, neuroimaging biomarkers and new treatment options such as the use of chloroquine.

Nucleolin-based targeting strategies for cancer therapy: from targeted drug delivery to cytotoxic ligands.

Cancer is currently the second leading cause of death worldwide and current therapeutic approaches remain ineffective in several cases. Therefore, there is a need to develop more efficacious therapeutic agents, especially for subtypes of cancer lacking targeted therapies. Limited drug penetration into tumors impairs the efficacy of therapies targeting cancer cells. One of the strategies to overcome this problem is targeting the more accessible tumor vasculature via molecules such as nucleolin, which is expressed at the surface of cancer and angiogenic endothelial cells, thus enabling a dual cellular targeting strategy. In this review, we present and discuss nucleolin-based targeting strategies that have been developed for cancer therapy, with a special focus on recent antibody-based approaches.

Therapist-guided and parent-guided internet-delivered behaviour therapy for paediatric Tourette's disorder: a pilot randomised controlled trial with long-term follow-up.

OBJECTIVE: Behaviour therapy (BT) for Tourette's disorder (TD) and persistent (chronic) motor or vocal tic disorder (PTD) is rarely available. We evaluated the feasibility of adapting two existing BT protocols for TD/PTD (habit reversal training (HRT) and exposure and response prevention (ERP)) into a therapist-guided and parent-guided online self-help format. DESIGN: A pilot, single-blind, parallel group randomised controlled trial. SETTING: A specialist outpatient clinic in Sweden. PARTICIPANTS: Twenty-three young people with TD/PTD, aged 8-16. INTERVENTIONS: Two 10-week therapist-guided and parent-guided internet-delivered programmes (called BIP TIC HRT and BIP TIC ERP). OUTCOME: The primary outcome measure was the Yale Global Tic Severity Scale. Blinded evaluators rated symptoms at baseline, post-treatment and 3-month follow-up (primary endpoint). All participants were naturalistically followed up to 12 months after treatment. RESULTS: Patients and parents rated the interventions as highly acceptable, credible and satisfactory. While both interventions resulted in reduced tic-related impairment, parent-rated tic severity and improved quality of life, only BIP TIC ERP resulted in a significant improvement on the primary outcome measure. Within-group effect sizes and responder rates were, respectively: d=1.12 and 75% for BIP TIC ERP, and d=0.50 and 55% for BIP TIC HRT. The therapeutic gains were maintained up to 12 months after the end of the treatment. Adverse events were rare in both groups. The average therapist support time was around 25 min per participant per week. CONCLUSIONS: Internet-delivered BT has the potential to greatly increase access to evidence-based treatment for young people with TD/PTD. Further evaluation of the efficacy and cost-effectiveness of this treatment modality is warranted. TRIAL REGISTRATION NUMBER: NCT02864589; Pre-results.

Anticancer activity and antibody-dependent cell-mediated cytotoxicity of novel anti-nucleolin antibodies.

Nucleolin arises as a relevant target for cancer therapy, as it is overexpressed at the surface of cancer and angiogenic endothelial cells thus enabling a dual cellular targeting strategy. Immunotherapeutic strategies, albeit of proven therapeutic relevance, have been scarcely explored against this target. Therefore, this work aimed at engineering an anti-nucleolin VHH-based antibody capable of triggering anticancer immune responses. Herein, anti-nucleolin VHHs have been generated upon grafting F3 peptide-derived nucleolin-binding sequences onto a VHH CDR1 or CDR3. One of these nucleolin-binding CDR3-grafted VHH was subsequently fused to a human IgG1 Fc region, enabling a significant antibody-dependent cell-mediated cytotoxicity (ADCC). The generated anti-nucleolin VHH revealed increased binding and antiproliferative effects against cancer cells, relative to the parental VHH, while the VHH-Fc counterpart presented increased cytotoxicity relative to the corresponding VHH. This VHH-Fc also triggered an ADCC effect, in the nanomolar range, against a nucleolin-overexpressing cancer cell line. This effect was evidenced by a 2 or 1.7-fold increase of cell death, in the presence of PBMCs, relative to the parental VHH-Fc or the VHH counterpart, respectively. Overall, these formats represent the first anti-nucleolin VHHs and the first anti-nucleolin antibody with ADCC activity that have been successfully developed.