The Impact of Leadership Training on Burnout and Fulfillment Among Direct Reports.

Goal: Burnout, decreased professional fulfillment, and resultant attrition across the medical professions are increasingly recognized as threats to sustainable and cost-effective healthcare delivery. While the skill level of leaders as perceived by their direct reports has been correlated with rates of burnout and fulfillment, no studies, to our knowledge, have directly evaluated whether intervention via leadership training impacts burnout and fulfillment among direct reports. The goal of this study was to evaluate the effectiveness of a leadership training intervention on direct reports' perceptions of the leadership skills of supervising residents and subsequently on the well-being of the direct reports.

Idiopathic Intracranial Hypertension Is Associated with Recurrent CSF Leak and Reoperation for Spontaneous Temporal Encephalocele.

 Spontaneous temporal encephaloceles (STEs) are increasingly recognized as sequelae of idiopathic intracranial hypertension (IIH), which in turn may further complicate their management. We endeavored to review the University of Pennsylvania institutional experience on operative management of STEs, with a focus on factors which may influence surgical outcomes, particularly IIH.  Retrospective chart review over 9 years from 2013 to 2022.

A multi-institutional machine learning algorithm for prognosticating facial nerve injury following microsurgical resection of vestibular schwannoma.

Vestibular schwannomas (VS) are the most common tumor of the skull base with available treatment options that carry a risk of iatrogenic injury to the facial nerve, which can significantly impact patients' quality of life. As facial nerve outcomes remain challenging to prognosticate, we endeavored to utilize machine learning to decipher predictive factors relevant to facial nerve outcomes following microsurgical resection of VS. A database of patient-, tumor- and surgery-specific features was constructed via retrospective chart review of 242 consecutive patients who underwent microsurgical resection of VS over a 7-year study period.

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Essential Tremor Under General Anesthesia: Technical Note.

Background: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an incisionless therapy for the treatment of medication-resistant essential tremor. Although its safety and efficacy has been demonstrated, MRgFUS is typically performed with the patient awake, with intraprocedural neurological assessments to guide lesioning.

Objective: To report the first case of MRgFUS thalamotomy under general anesthesia in a patient whose medical comorbidities prohibit him from being in a supine position without a secured airway.

Neurologically Devastating Intraparenchymal Hemorrhage in COVID-19 Patients on Extracorporeal Membrane Oxygenation: A Case Series.

Background And Importance: Extracorporeal membrane oxygenation (ECMO) represents a life-saving therapy in cases of refractory hypoxia and has been utilized in patients suffering from the most severe forms of coronavirus disease 2019 (COVID-19). A strikingly high mortality rate of 94% was described in early reports of patients with COVID-19 transitioned to ECMO. Later case reports and series demonstrating successful recovery from COVID-19 after ECMO have revived interest in this therapeutic modality, including the recent approval of ECMO for COVID-19 patients by the Food and Drug Administration (FDA).

Thalamic Deep Brain Stimulation for Essential Tremor: Relation of the Dentatorubrothalamic Tract with Stimulation Parameters.

Background: In deep brain stimulation (DBS) for essential tremor, the primary target ventrointermedius (VIM) nucleus cannot be clearly visualized with structural imaging. As such, there has been much interest in the dentatorubrothalamic tract (DRTT) for target localization, but evidence for the DRTT as a putative stimulation target in tremor suppression is lacking. We evaluated proximity of the DRTT in relation to DBS stimulation parameters.

Doublecortin-like Kinase 1 Regulates α-Synuclein Levels and Toxicity.

α-Synuclein (α-Syn) accumulation is a pathological hallmark of Parkinson's disease. Duplications and triplications of , the gene coding for α-Syn, cause genetic forms of the disease, which suggests that increased α-Syn dosage can drive PD. To identify the proteins that regulate α-Syn, we previously performed a screen of potentially druggable genes that led to the identification of 60 modifiers.

Atypical Schwannoma: A 10-year experience.

Objective: The goal of this study was to describe the clinical presentation associated with atypical schwannoma of the cerebellopontine angle, characterize the pathologic findings and describe the long-term outcome.

Materials And Methods: The study design was retrospective case review of patients with the histopathologic diagnosis of atypical and benign schwannoma of the cerebellopontine angle diagnosed at the study institution over a 10-year period.

Setting: Tertiary referral center.

Alpha-synuclein induces the unfolded protein response in Parkinson's disease SNCA triplication iPSC-derived neurons.

The recent generation of induced pluripotent stem cells (iPSCs) from a patient with Parkinson's disease (PD) resulting from triplication of the α-synuclein (SNCA) gene locus allows unprecedented opportunities to explore its contribution to the molecular pathogenesis of PD. We used the double-nicking CRISPR/Cas9 system to conduct site-specific mutagenesis of SNCA in these cells, generating an isogenic iPSC line with normalized SNCA gene dosage. Comparative gene expression analysis of neuronal derivatives from these iPSCs revealed an ER stress phenotype, marked by induction of the IRE1α/XBP1 axis of the unfolded protein response (UPR) and culminating in terminal UPR activation.

Precision Modulation of Neurodegenerative Disease-Related Gene Expression in Human iPSC-Derived Neurons.

The ability to reprogram adult somatic cells into induced pluripotent stem cells (iPSCs) and the subsequent development of protocols for their differentiation into disease-relevant cell types have enabled in-depth molecular analyses of multiple disease states as hitherto impossible. Neurons differentiated from patient-specific iPSCs provide a means to recapitulate molecular phenotypes of neurodegenerative diseases in vitro. However, it remains challenging to conduct precise manipulations of gene expression in iPSC-derived neurons towards modeling complex human neurological diseases.

Extracellular vesicles in neurodegenerative disease - pathogenesis to biomarkers.

To develop effective disease-modifying therapies for neurodegenerative diseases, reliable markers of diagnosis, disease activity and progression are a research priority. The fact that neurodegenerative pathology is primarily associated with distinct subsets of cells in discrete areas of the CNS makes the identification of relevant biomarker molecules a challenge. The trafficking of macromolecules from the CNS to the cerebrospinal fluid and blood, mediated by extracellular vesicles (EVs), presents a promising source of CNS-specific biomarkers.

RISC in PD: the impact of microRNAs in Parkinson's disease cellular and molecular pathogenesis.

Parkinson's disease (PD) is a debilitating neurodegenerative disease characterized primarily by the selective death of dopaminergic (DA) neurons in the substantia nigra pars compacta of the midbrain. Although several genetic forms of PD have been identified, the precise molecular mechanisms underlying DA neuron loss in PD remain elusive. In recent years, microRNAs (miRNAs) have been recognized as potent post-transcriptional regulators of gene expression with fundamental roles in numerous biological processes.

High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagy.

An increasing body of evidence points to mitochondrial dysfunction as a contributor to the molecular pathogenesis of neurodegenerative diseases such as Parkinson's disease. Recent studies of the Parkinson's disease associated genes PINK1 (ref. 2) and parkin (PARK2, ref.

Functional screening assays with neurons generated from pluripotent stem cell-derived neural stem cells.

Rapid and effective drug discovery for neurodegenerative disease is currently impeded by an inability to source primary neural cells for high-throughput and phenotypic screens. This limitation can be addressed through the use of pluripotent stem cells (PSCs), which can be derived from patient-specific samples and differentiated to neural cells for use in identifying novel compounds for the treatment of neurodegenerative diseases. We have developed an efficient protocol to culture pure populations of neurons, as confirmed by gene expression analysis, in the 96-well format necessary for screens.

MHC class II epitope nesting modulates dendritic cell function and improves generation of antigen-specific CD4 helper T cells.

CD4 Th cells are critical to the development of coordinated immune responses to infections and tumors. Th cells are activated through interactions of the TCR with MHC class II complexed with peptide. T cell activation is dependent on the density of MHC peptide complexes as well as the duration of interaction of the TCR with APCs.