Historical Redlining, Social Determinants of Health, and Stroke Prevalence in Communities in New York City.

Importance: Historical redlining was a discriminatory housing policy that placed financial services beyond the reach of residents in inner-city communities. The extent of the impact of this discriminatory policy on contemporary health outcomes remains to be elucidated. Objective: To evaluate the associations among historical redlining, social determinants of health (SDOH), and contemporary community-level stroke prevalence in New York City. Design, Setting, and Participants: An ecological, retrospective, cross-sectional study was conducted using New York City data from January 1, 2014, to December 31, 2018. Data from the population-based sample were aggregated on the census tract level. Quantile regression analysis and a quantile regression forests machine learning model were used to determine the significance and overall weight of redlining in relation to other SDOH on stroke prevalence. Data were analyzed from November 5, 2021, to January 31, 2022. Exposures: Social determinants of health included race and ethnicity, median household income, poverty, low educational attainment, language barrier, uninsurance rate, social cohesion, and residence in an area with a shortage of health care professionals. Other covariates included median age and prevalence of diabetes, hypertension, smoking, and hyperlipidemia. Weighted scores for historical redlining (ie, the discriminatory housing policy in effect from 1934 to 1968) were computed using the mean proportion of original redlined territories overlapped on 2010 census tract boundaries in New York City. Main Outcomes and Measures: Stroke prevalence was collected from the Centers for Disease Control and Prevention 500 Cities Project for adults 18 years and older from 2014 to 2018. Results: A total of 2117 census tracts were included in the analysis. After adjusting for SDOH and other relevant covariates, the historical redlining score was independently associated with a higher community-level stroke prevalence (odds ratio [OR], 1.02 [95% CI, 1.02-1.05]; P < .001). Social determinants of health that were positively associated with stroke prevalence included educational attainment (OR, 1.01 [95% CI, 1.01-1.01]; P < .001), poverty (OR, 1.01 [95% CI, 1.01-1.01]; P < .001), language barrier (OR, 1.00 [95% CI, 1.00-1.00]; P < .001), and health care professionals shortage (OR, 1.02 [95% CI, 1.00-1.04]; P = .03). Conclusions and Relevance: This cross-sectional study found that historical redlining was associated with modern-day stroke prevalence in New York City independently of contemporary SDOH and community prevalence of some relevant cardiovascular risk factors.

Dysregulated coordination of MAPT exon 2 and exon 10 splicing underlies different tau pathologies in PSP and AD.

Understanding regulation of MAPT splicing is important to the etiology of many nerurodegenerative diseases, including Alzheimer disease (AD) and progressive supranuclear palsy (PSP), in which different tau isoforms accumulate in pathologic inclusions. MAPT, the gene encoding the tau protein, undergoes complex alternative pre-mRNA splicing to generate six isoforms. Tauopathies can be categorized by the presence of tau aggregates containing either 3 (3R) or 4 (4R) microtubule-binding domain repeats (determined by inclusion/exclusion of exon 10), but the role of the N-terminal domain of the protein, determined by inclusion/exclusion of exons 2 and 3 has been less well studied. Using a correlational screen in human brain tissue, we observed coordination of MAPT exons 2 and 10 splicing. Expressions of exon 2 splicing regulators and subsequently exon 2 inclusion are differentially disrupted in PSP and AD brain, resulting in the accumulation of 1N4R isoforms in PSP and 0N isoforms in AD temporal cortex. Furthermore, we identified different N-terminal isoforms of tau present in neurofibrillary tangles, dystrophic neurites and tufted astrocytes, indicating a role for differential N-terminal splicing in the development of disparate tau neuropathologies. We conclude that N-terminal splicing and combinatorial regulation with exon 10 inclusion/exclusion is likely to be important to our understanding of tauopathies.

Same-day vs. delayed buprenorphine prescribing and patient retention in an office-based buprenorphine treatment program.

BACKGROUND: Buprenorphine is a safe and effective treatment for opioid use disorder (OUD), yet a small fraction of people with OUD receive it, and rates of retention in treatment are suboptimal. Dropout most commonly occurs within 30 days of treatment initiation. Therefore, research needs to investigate modifiable factors contributing to early dropout. Requiring multiple visits for evaluation prior to providing an initial buprenorphine prescription (delayed prescription) may lead to more early dropout when compared with prescribing at the first medical visit (same-day prescription). Our objective was to determine whether same-day (vs. delayed) buprenorphine prescription was associated with 30-day retention in treatment. METHODS: We conducted a retrospective cohort study of 237 patients who initiated buprenorphine treatment at an urban federally qualified community health center (FQHC) between June 1, 2015, and December 31, 2017. We measured prescription delays by determining the time between patients' first request for buprenorphine treatment (by calling, presenting to the FQHC in-person, or requesting treatment during a visit) and when providers wrote buprenorphine prescriptions. We included only patients with prescription delays less than or equal to 30 days in the analysis. We defined same-day prescription as the patient experiencing no delays in starting treatment and receiving a prescription during the first medical visit. We examined whether patients who received same-day prescriptions had different sociodemographic and clinical characteristics than patients who received delayed prescriptions. We also evaluated whether there was an association between the initial provider who made the decision about same-day vs. delayed buprenorphine prescribing and same-day prescription. We built a multivariable logistic regression model to evaluate the independent association between same-day vs. delayed prescription receipt and odds of 30-day retention in treatment. RESULTS: Of the 237 patients who initiated buprenorphine treatment from June 1, 2015, to December 31, 2017, 222 had delays less than or equal to 30 days and we included them in the analysis. Of the 222 patients, the mean age was 46 (SD 10.4), the majority were Hispanic (n = 160, 72%), male (n = 175, 79%), and publicly insured (n = 165, 74%). The majority of patients experienced delayed buprenorphine prescription receipt (n = 133, 60%). The median time to buprenorphine prescription was 5 days (IQR 0-11). Of those who experienced a delay (n = 133), the median delay time was 8 days (IQR 5-20). Compared to those with same-day prescription receipt, more patients with delayed prescription receipt were non-Hispanic white (11% vs. 2%, p = 0.01), had a history of alcohol use (43% vs. 21%, p < 0.01) or benzodiazepine use (22% vs. 9%, p = 0.01), and had the buprenorphine coordinator as their initial provider (57 vs. 13%, p < 0.01). Same-day prescription receipt was not significantly associated with 30-day treatment retention in the adjusted analysis (AOR 1.92, 95% CI 0.81-4.56). CONCLUSION: Patients who received buprenorphine prescriptions on the same day as their initial evaluation differed from those who received delayed prescriptions. After adjustment for these differences, same-day prescription was not significantly associated with higher 30-day treatment retention. Providers may be delaying treatment when there is concern about alcohol and/or benzodiazepine use; however, providers could institute enhanced monitoring based on clinical concern for sedation or overdose risk without delaying buprenorphine prescription. Prospective studies of same-day vs. delayed buprenorphine receipt would elucidate the association between delays and retention more definitively.

Reduced variability of neural progenitor cells and improved purity of neuronal cultures using magnetic activated cell sorting.

Genetic and epigenetic variability between iPSC-derived neural progenitor cells (NPCs) combined with differences in investigator technique and selection protocols contributes to variability between NPC lines, which subsequently impacts the quality of differentiated neuronal cultures. We therefore sought to develop an efficient method to reduce this variability in order to improve the purity of NPC and neuronal cultures. Here, we describe a magnetic activated cell sorting (MACS) method for enriching NPC cultures for CD271-/CD133+ cells at both early (<2-3) and late (>10) passage. MACS results in a similar sorting efficiency to fluorescence activated cell sorting (FACS), while achieving an increased yield of live cells and reduced cellular stress. Furthermore, neurons derived from MACS NPCs showed greater homogeneity between cell lines compared to those derived from unsorted NPCs. We conclude that MACS is a cheap technique for incorporation into standard NPC differentiation and maintenance protocols in order to improve culture homogeneity and consistency.