Citations

Introduction: Lewy body dementia (LBD) is common, yet under-recognized and under-researched. To plan studies with the highest impact, engagement of the community personally affected by these conditions is essential. Methods: A web-based survey of people living with LBD and current and former caregivers of people with LBD queried research priorities through forced ranking and exploration of burden of LBD symptoms. Specific caregiving needs in LBD and perceptions of research participation were also investigated. Results: Between April 7, 2021 and July 1, 2021, 984 responses were recorded. Top research priorities included disease-modifying therapies and improved disease detection and staging. People with LBD were interested in pathophysiology and more bothered by motor symptoms; caregivers were interested in risk factors and symptomatic therapies and more bothered by neuropsychiatric symptoms. Few available LBD treatments and resources were rated as helpful, and many valuable services were never received. Previous participation in LBD research was infrequent, but interest was high. Discussion: People with LBD and caregivers highlighted the need for research across all aspects of LBD, from pathophysiology and disease modification to prognosis, education, symptomatic treatments, and caregiver support. Funders should increase support for all aspects of LBD research to target the many needs identified by individuals and families living with LBD.

BACKGROUND: Adult traumatic brachial plexus injuries (TBPIs) are life-altering events that can have detrimental effects on a patient's quality of life. OBJECTIVE: To examine how social determinants of health (SDOH) disparities influence the risk of developing new psychosocial conditions after TBPIs in previously psychiatric-naïve patients. METHODS: Between January 2010 and June 2019, a retrospective analysis was performed using PearlDiver's Mariner, an all-payer claims database, to create 3 cohorts: TBPI disparity cohort: patients with TBPI and presence of at least 1 SDOH disparity before injury, TBPI without disparity cohort: patients with TBPI and the absence of any SDOH disparity, and control cohort: patients without TBPIs. RESULTS: The matched population analyzed in this study consisted of 1176 patients who were equally represented in the TBPI disparity cohort (n = 392, 33.33%), TBPI without disparity cohort (n = 392, 33.33%), and control cohort (n = 392, 33.33%). A total of 301 patients developed any psychosocial condition with 4 years of their injury. Patients in the TBPI disparity cohort had significantly higher rates of developing any psychosocial condition (31.12%, P < .0005), depression (22.70%, P = .0032), anxiety (18.62%, P = .0203), drug abuse (7.91%, P = .0060), and alcohol abuse (4.85%, P = .03499) when compared with the other cohorts. Furthermore, the disparity cohort carried a significantly increased risk of developing any psychosocial condition (hazard ratio 1.42, 95% CI 1.09-1.86). The rates of suicide attempt, post-traumatic stress disorder, and divorce did not significantly differ between groups. CONCLUSION: TBPI patients with SDOH disparities are at increased risk of developing new-onset psychosocial conditions, such as depression, anxiety, drug abuse, and alcohol abuse. Level of Evidence: Prognostic Level III.

Extracellular vesicles (EVs) are membrane-bound particles released by all cells. Previous research has found that these microscopic vesicles contribute to intercellular signaling and communication. EVs carry a variety of cargo, including nucleic acids, proteins, metabolites, and lipids. The composition of EVs varies based on cell of origin. Therefore, EVs can serve as an important biomarker in the diagnosis and treatment of various cancers. EVs derived from glioblastoma (GBM) cells carry biomarkers, which could serve as the basis for a potential diagnostic strategy known as liquid biopsy. Multiple EV isolation techniques exist, including ultrafiltration, size exclusion chromatography, flow field-flow fractionation, sequential filtration, differential ultracentrifugation, and density-gradient ultracentrifugation. Recent and ongoing work aims to identify cellular markers to distinguish GBM-derived EVs from those released by noncancerous cells. Strategies include proteomic analysis of GBM EVs, identification of GBM-specific metabolites, and use of Food and Drug Administration-approved 5-aminolevulinic acid—an oral agent that causes fluorescence of GBM cells—to recognize GBM EVs in a patient's blood. In addition, accurately and precisely monitoring changes in EV cargo concentrations could help differentiate between pseudoprogression and GBM recurrence, thus preventing unnecessary surgical interventions.

Sonic hedgehog signaling regulates processes of embryonic development across multiple tissues, yet factors regulating context-specific Shh signaling remain poorly understood. Exome sequencing of families with polymicrogyria (disordered cortical folding) revealed multiple individuals with biallelic deleterious variants in TMEM161B , which encodes a multi-pass transmembrane protein of unknown function. Tmem161b null mice demonstrated holoprosencephaly, craniofacial midline defects, eye defects, and spinal cord patterning changes consistent with impaired Shh signaling, but were without limb defects, suggesting a CNS-specific role of Tmem161b. Tmem161b depletion impaired the response to Smoothened activation in vitro and disrupted cortical histogenesis in vivo in both mouse and ferret models, including leading to abnormal gyration in the ferret model. Tmem161b localizes non-exclusively to the primary cilium, and scanning electron microscopy revealed shortened, dysmorphic, and ballooned ventricular zone cilia in the Tmem161b null mouse, suggesting that the Shh-related phenotypes may reflect ciliary dysfunction. Our data identify TMEM161B as a regulator of cerebral cortical gyration, as involved in primary ciliary structure, as a regulator of Shh signaling, and further implicate Shh signaling in human gyral development.