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SummaryAccumulation of α-synuclein (α-syn) into insoluble aggregates occurs in several related disorders collectively referred to as synucleinopathies. To date, studies have used neural stem cells (NSCs) to examine questions about α-syn propagation, but have overlooked the therapeutic potential of NSC transplantation to modulate cognition in disorders such as dementia with Lewy bodies or Parkinson’s disease dementia. Here, we show that striatal transplantation of NSCs into aged α-syn transgenic mice significantly improves performance in multiple cognitive and motor domains. This recovery is associated with NSC expression of brain-derived neurotrophic factor (BDNF), which restores depleted levels and modulates dopaminergic and glutamatergic systems. Most importantly, transplantation of BDNF-depleted NSCs fails to improve behavior, whereas AAV-mediated BDNF delivery mimics the benefits of NSC transplantation, supporting a critical role for this neurotrophin in functional improvement. Thus, NSC transplantation could offer a promising approach to treat the understudied yet devastating cognitive components of many synucleinopathies.

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Background: Prostate biopsy (Bx) sampling-based diagnosis of prostate cancer (PCa) has well-described inaccuracy when compared against whole gland analysis upon prostatectomy. Although upgrading of PCa Grade Group (GG) is often described, the occurrence and prognostic implications of downgrading PCa GG at the time of radical prostatectomy (RP) is less understood. Our objective was to evaluate whether downgrading PCa GG at the time of RP was associated with future tumor behavior. Methods:The SEER database was searched from 2010 to 2017 and patients were included if they were assigned pathological grades on both Bx and RP specimen.Patients were stratified into Bx GG > RP GG and Bx GG ≤ RP GG groups, and tumor behavior after treatment was examined. Cox regression was used for the survival analysis.Results: Here, 99,835 patients were included in this study. A total of 18,516 (18.5%) patients encountered downgrading from Bx GG to RP GG. A downgrading of 1 grade occurred in 13,969 (75.4%) of these patients and of 2 or more grades occurred in 4547 (24.6%) patients. A history of higher Bx GG compared with RP GG increased the risk of cancer-specific mortality (CSM) for each given RP GG controlling for age, race, preop prostate-specific antigen level, percentage of positive biopsy cores, and pathologic TNM stages. Specifically, a history of high Bx GG conferred a 45% increased risk of CSM for any given RP GG (hazard ratio = 1.45 95% confidence interval = 1.16-1.82, p < 0.001). Conclusion:A history of higher Bx GG, and hence downgrading at the time of RP, demonstrates some value as a risk-stratification tool for future cancer outcomes after prostatectomy.

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Species distribution models (SDMs) have been widely used to project terrestrial species’ responses to climate change and are increasingly being used for similar objectives in the marine realm. These projections are critically needed to develop strategies for resource management and the conservation of marine ecosystems. SDMs are a powerful and necessary tool; however, they are subject to many sources of uncertainty. To ensure that SDM projections are informative for management and conservation decisions, sources of uncertainty must be considered and properly addressed. Here we provide ten overarching guidelines that will aid researchers to identify, minimize, and account for uncertainty through the entire model development process, from the formation of a study question to the presentation of results. These guidelines were developed at an international workshop attended by over 50 researchers and practitioners. Although our guidelines are broadly applicable across biological realms, we provide particular focus to the challenges and uncertainties associated with projecting the impacts of climate change on marine species and ecosystems.

This study focused on the association between type of community health interventions and lay health educator variables. Lay health educators are volunteers from local faith communities who complete a healthcare training program, taught by physicians in-training. Lay health educators are instructed to implement health-related initiatives in their respective communities after graduation. Of the 72 graduates since 2011, we surveyed 55 lay health educators to gain insight into their involvement with their congregation and the type of health projects they have implemented. We dichotomized the health projects into "raising awareness" and "teaching new health skills." Using adjusted logistic regression models, variables associated with implementing health projects aimed at teaching health skills included length of time as a member of their congregation, current employment, and age. These results may help future programs prepare lay health community educators for the type of health interventions they intend to implement in their respective communities.

Purpose The purpose of this study was to compare autoregulation of retinal arteriolar and venular blood flow in patients with glaucoma, glaucoma suspect participants, and control participants using erythrocyte mediated velocimetry. Methods This prospective cohort pilot study included 7 eyes of 5 participants with glaucoma, 15 eyes of 8 glaucoma suspect participants, and 11 eyes of 6 control participants. Mean erythrocyte velocity in retinal arterioles and venules was measured using erythrocyte mediated velocimetry at room air and after oxygen supplementation. Change in erythrocyte velocity was compared among all groups using generalized estimating equations. Results In total, 64 vessels (18 with glaucoma, 31 that were glaucoma suspect, and 15 controls) of 33 eyes of 19 participants were analyzed. There was no significant difference in baseline velocities in arterioles or venules among the three groups. With induction of hyperoxia, mean arterial erythrocyte velocity decreased in glaucoma (−7.2 ± 13.7%), which differed from controls and glaucoma suspects where erythrocyte velocity increased with hyperoxia by 4.6 ± 13.3% ( P = 0.002) and 7.2 ± 21.7% ( P = 0.03), respectively. A higher baseline arteriolar velocity (β = −3.9% per mm/s, P = 0.002), glaucoma diagnosis (β = −21.1%, P = 0.03), and White race (β = −20.0%, P = 0.01) were associated with decreased velocity in response to arterial hyperoxia. Conclusions Hyperoxia increased erythrocyte velocity in control and glaucoma suspect participants, but decreased erythrocyte velocity in glaucoma participants, possibly due to impaired autoregulation. Baseline velocity, glaucoma diagnosis, and White race were associated with a decrease in velocity with induction of hyperoxia. Translational Relevance The European Medicines Agency (EMA) permits precision measurements of blood flow which may aid in the development of biomarkers of glaucoma-related dysregulation of blood flow.