Relationship between Neighborhood-Level Social Risk Factor Measures and Presenting Glaucoma Severity Utilizing Multilevel Modeling.

Purpose: The neighborhood and built environment social determinant of health domain has several social risk factors (SRFs) that are modifiable through policy efforts. We investigated the impact of neighborhood-level SRFs on presenting glaucoma severity at a tertiary eye care center. Design: A cross-sectional study from August 2012 to May 2022 in the University of Michigan electronic health record (EHR). Participants: Patients with a diagnosis of any open-angle glaucoma with ≥1 eye care visit at the University of Michigan Kellogg Eye Center and ≥1 reliable visual field (VF). Methods: Participants who met inclusion criteria were identified by International Classification of Diseases ninth and tenth revision codes (365.x/H40.x). Data extracted from the EHR included patient demographics, address, presenting mean deviation (MD), and VF reliability. Addresses were mapped to SRF measures at the census tract, block group, and county levels. Multilevel linear regression models were used to estimate the fixed effects of each SRF on MD, after adjusting for patient-level demographic factors and a random effect for neighborhood. Interactions between each SRF measure with patient-level race and Medicaid status were tested for an additive effect on MD. Main Outcome Measures: The main outcome measure was the effect of SRF on presenting MD. Results: In total, 4428 patients were included in the analysis who were, on average, 70.3 years old (standard deviation = 11.9), 52.6% self-identified as female, 75.8% self-identified as White race, and 8.9% had Medicaid. The median value of presenting MD was -4.94 decibels (dB) (interquartile range = -11.45 to -2.07 dB). Neighborhood differences accounted for 4.4% of the variability in presenting MD. Neighborhood-level measures, including worse area deprivation (estimate, ß = -0.31 per 1-unit increase; P < 0.001), increased segregation (ß = -0.92 per 0.1-unit increase in Theil's H index; P < 0.001), and increased neighborhood Medicaid (ß = -0.68; P < 0.001) were associated with worse presenting MD. Significant interaction effects with race and Medicaid status were found in several neighborhood-level SRF measures. Conclusions: Although patients' neighborhood SRF measures accounted for a minority of the variability in presenting MD, most neighborhood-level SRFs are modifiable and were associated with clinically meaningful differences in presenting MD. Policies that aim to reduce neighborhood inequities by addressing allocation of resources could have lasting impacts on vision outcomes. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Applying the theoretical domains framework to identify determinants to mental healthcare use among older African Americans with type 2 diabetes: a qualitative study.

OBJECTIVES: There is a paucity of research focused on enhancing access to mental healthcare for older African Americans with type 2 diabetes (T2D), who may be at risk for or living with comorbid depression. This study aims to identify barriers and facilitators to mental healthcare utilisation among this population, guided by the theoretical domains framework (TDF). DESIGN: This qualitative study involved 30 interviews with older African American adults diagnosed with T2D. The interview questions were aligned with TDF domains to capture participant perspectives on barriers and facilitators to mental healthcare use. SETTING: Interviews were conducted via telephone by a licensed clinician trained in social work. Each session lasted 60-90 min and was transcribed and analysed. PARTICIPANTS: The study included 30 African American adults (15 males and 15 females), aged 60 and above, living in an urban area in the Midwest. PRIMARY AND SECONDARY OUTCOMES: The primary outcome was the identification of themes from participant responses, analysed using thematic content techniques and categorised into TDF constructs. Demographic data served as the secondary outcome. RESULTS: Nine key themes were identified, categorised under major TDF domains and constructs. Significant barriers included (1) systemic racism ('knowledge'), (2) normalisation of depressive symptoms ('beliefs about consequences'), (3) perceived stigma ('beliefs about consequences') and 4) costs of medications and healthcare ('environmental context and resources'). Facilitators to seeking mental healthcare included (1) empowerment ('beliefs about capabilities'), (2) perceived benefits of mental health exams ('beliefs about consequences'), (3) positive provider experiences ('reinforcement'), (4) recognition of depressive symptoms as a motivator ('goals') and (5) support networks ('social influences'). CONCLUSION AND IMPLICATIONS: Key findings highlight that fostering positive patient-provider relationships and enhancing self-recognition of depressive symptoms can significantly encourage mental healthcare utilisation among older African Americans with T2D. These findings suggest that future interventions should focus on strengthening these relationships and improving self-awareness to better mental health outcomes.

Empowering WHISE women: usability testing of a mobile application to enhance blood pressure control.

Background: High blood pressure (hypertension) disproportionately affects African American/Black (Black) women. Previous research suggests that self-managing hypertension may be challenging, yet mobile applications (apps) can help to empower patients and increase medication adherence. We developed questions to test the usability of evaluating the WHISE (Wellness, Hypertension, Information Sharing, Self-Management, Education) mobile app for Black women with hypertension. Methods: Fifteen participants completed usability testing; five were potential app users (Black women with hypertension); each invited two of their peers to participate. Each testing session (n=5) included a brief overview of the app, time for participants to complete surveys and have an active discussion about the app (concurrent and retrospective think-aloud, concurrent and retrospective probing, per usability.gov), and observation of participants' body language during the session. Testing sessions were designed to familiarize participants with the app's features and examine their navigating ability. Results: The app received overwhelmingly positive feedback, with 80% of participants finding it to be a valuable tool in hypertension management. Participants praised the app's user-friendliness and educational value, with one stating, 'It is a good educational piece for helping people manage hypertension, at least to understand its basics.' Another participant highlighted the potential for community support, saying, 'Having a community, having some people to be accountable, to check in with and see how things are going, could encourage and motivate people to be more diligent about managing their hypertension.' Some participants also provided constructive feedback, suggesting font size adjustments (73%) and color scheme changes (60%) for certain screens. Conclusions: Based on the feedback we received, we were able to mitigate the participants' concerns about font size and color and create tutorial videos to guide future users in using the app. We completed these changes prior to deploying the app in our randomized clinical controlled trial.

Health Social Networks of Black Women With Hypertension.

BACKGROUND: The prevalence of hypertension is 55% among African American/Black women, who have a higher risk for poor health outcomes compared to women from other racial and ethnic groups, in part because of uncontrolled blood pressure. Previous research results suggest that peers may positively influence self-management of chronic conditions like hypertension. However, few studies have described the personal characteristics of peers in the health social networks of Black women. OBJECTIVE: This substudy aimed to examine health social networks and describe the peers' characteristics, as reported by a convenience sample of Black women with hypertension. METHODS: In this analysis of data from a larger study, 94 Black women with hypertension attending a church conference participated in a cross-sectional, descriptive study. Their mean age was 59 years, and their mean systolic blood pressure was 143 mm Hg. All participants completed a survey to gather data about (a) the characteristics of individuals they discussed health matters with (their peers or health social network) and (b) their perceptions about hypertension status and knowledge of hypertension among the peers in their health social network. RESULTS: Collectively, participants from the larger study named a total of 658 peers who were part of their health social networks; the mean health social network size was six peers. The peers were mostly women, Black, family members, and, on average, 54 years old. The participants discussed hypertension with 71% of the peers, reported that 36% had hypertension, and felt that 67% were somewhat or very knowledgeable about the condition. A small, positive correlation existed between the participants' health social network size (number of peers named) and their systolic blood pressure levels. DISCUSSION: The health social network peers were similar to those in the larger study, with most of the same gender, race, and age. The findings of this analysis may be used to help practitioners and scientists guide patients in building health social networks for support in self-managing hypertension and conducting future studies to examine the best strategies for developing and using health social networks to improve health outcomes and reduce health disparities.

Integrated transcriptome landscape of ALS identifies genome instability linked to TDP-43 pathology.

Amyotrophic Lateral Sclerosis (ALS) causes motor neuron degeneration, with 97% of cases exhibiting TDP-43 proteinopathy. Elucidating pathomechanisms has been hampered by disease heterogeneity and difficulties accessing motor neurons. Human induced pluripotent stem cell-derived motor neurons (iPSMNs) offer a solution; however, studies have typically been limited to underpowered cohorts. Here, we present a comprehensive compendium of 429 iPSMNs from 15 datasets, and 271 post-mortem spinal cord samples. Using reproducible bioinformatic workflows, we identify robust upregulation of p53 signalling in ALS in both iPSMNs and post-mortem spinal cord. p53 activation is greatest with C9orf72 repeat expansions but is weakest with SOD1 and FUS mutations. TDP-43 depletion potentiates p53 activation in both post-mortem neuronal nuclei and cell culture, thereby functionally linking p53 activation with TDP-43 depletion. ALS iPSMNs and post-mortem tissue display enrichment of splicing alterations, somatic mutations, and gene fusions, possibly contributing to the DNA damage response.

The Support, Educate, Empower personalized glaucoma coaching trial design.

BACKGROUND: Glaucoma is a chronic disease that affects 3 million Americans. Glaucoma is most often asymptomatic until very late in its course when treatment is more difficult and extensive peripheral vision loss has already occurred. Taking daily medications can mitigate this vision loss, but at least half of people with glaucoma do not take their prescribed medications regularly. The purpose of this study is to improve glaucoma medication adherence among those with medically treated glaucoma and poor self-reported adherence using the Support, Educate, Empower personalized coaching program. METHODS/DESIGN: This study is a two-site randomized controlled trial enrolling 230 participants with poor self-reported glaucoma medication adherence. The trial has two arms, an intervention arm and a control arm. Participants in the intervention arm receive personalized glaucoma education and motivational interviewing-based coaching over 6 months from a trained non-physician interventionist for three in-person sessions with between visit phone calls for check-ins where current adherence level is reported to participants. Participants also can elect to have visual, audio, text or automated phone call medication dose reminders. Participants in the control arm continue usual care with their physician and receive non-personalized glaucoma educational materials via mail in parallel to the three in-person coaching sessions to control for glaucoma knowledge content. All participants receive a medication adherence monitor. The primary outcome is the proportion of prescribed doses taken on schedule during the 6-month period. The secondary outcome is glaucoma related distress. The exploratory outcome is intraocular pressure. DISCUSSION: The personalized education and motivational-interviewing-based intervention that we are testing is comprehensive in that it addresses the wide range of barriers to adherence that people with glaucoma encounter. Leveraging a custom-built web-based application to generate the personalized content and the motivational-interviewing-based prompts to guide the coaching sessions will make this program both replicable and scalable and can be integrated into clinical care utilizing trained non-physician providers. Although this type of self-management support is not currently reimbursed for glaucoma as it is for diabetes, this trial could help shape future policy change should the intervention be found effective.

Michigan men's diabetes project II: Protocol for peer-led diabetes self-management education and long-term support in Black men.

Previous literature has indicated that Black men are twice as likely to develop type 2 diabetes compared to their non-Hispanic White counterparts and are also more likely to have associated complications. Furthermore, Black men have lower access to quality health care, and masculinity norms have been shown to hinder them from seeking the limited care that is available. In this study, we aim to investigate the effect of peer-led diabetes self-management education and long-term ongoing support on glycemic management. The first phase of our study will consist of modification of existing diabetes education content to be more appropriate for the population of interest, Then, in the second phase, we will conduct a randomized controlled trial to test the intervention. Participants randomized to the intervention arm will receive diabetes self-management education, structured diabetes self-management support, and a more flexible ongoing support period. Participants randomized to the control arm will receive diabetes self-management education. Diabetes self-management education will be taught by certified diabetes care and education specialists, while the diabetes self-management support and ongoing support period will be facilitated by fellow Black men with diabetes who will be trained in group facilitation, patient-provider communication strategies, and empowerment techniques. The third phase of this study will consist of post-intervention interviews and dissemination of findings to the academic community. The primary goal of our study is to determine whether long-term peer-led support groups in conjunction with diabetes self-management education are a promising solution to improve self-management behaviors and decrease A1C levels. We will also evaluate the retention of participants throughout the study, which has historically been an issue in clinical studies focused on the Black male population. Finally, the results from this trial will determine whether we can proceed to a fully-powered R01 trial or if other modifications of the intervention are necessary. Trial registration: Registered at ClinicalTrials.gov with an ID of NCT05370781 on May 12, 2022.

Virtual Reality Job Interview Training for Adults Receiving Prison-Based Employment Services: A Randomized Controlled Feasibility and Initial Effectiveness Trial.

Returning citizens struggle to obtain employment after release from prison, and navigating job interviews is a critical barrier they encounter. Implementing evidence-based interview training is a major gap in prison-based vocational services. We conducted a randomized controlled trial (RCT) to evaluate the feasibility and initial effectiveness of Virtual Reality Job Interview Training within two prisons. Forty-four male returning citizens were randomized to receive service-as-usual (SAU) with VR-JIT (SAU+VR-JIT, n = 28) or SAU (n = 16). Participants reported VR-JIT was highly acceptable and usable. SAU+VR-JIT, as compared to SAU, had significant improvements (with large effect sizes) in interview skills, interview training motivation, and interview anxiety (all p < .05; ηp2 > .15), and greater employment by 6-month follow-up (OR = 7.4, p = .045). VR-JIT can potentially help fill a major gap in prison-based services. Future research is needed to validate VR-JIT effectiveness and evaluate VR-JIT implementation strategies within prisons.

Consulting Program by and for Older Detroiters.

This article profiles a program in Detroit, MI, funded by the National Institute on Aging, called the Michigan Center for African American Aging Research and its key offshoot the Healthier Black Elders Center (HBEC). Board members of its Community Advisory Board weigh in on key programming and offer perspectives and recommendations on health and social issues. The HBEC Consulting Program is a blend of formal volunteering and paid work through consulting fees. The article also outlines next steps for HBEC.

Using Path Analysis and Linear Regression to Test for Gender and Participation: Effects in a Culturally Tailored Diabetes Intervention for Latino Adults.

While the incidence and prevalence of type 2 diabetes is higher among Latino/as, Latino men are disproportionately affected and have poorer outcomes. We aimed to determine whether gender impacted any outcomes in a culturally tailored type 2 diabetes (T2D) intervention and to evaluate the effects of gender and intervention participation intensity on outcomes at 6-month follow-up. Nested path and regression models were compared with the likelihood ratio test and information criteria in a sample of Latino/a adults with T2D (n = 222) participating in a T2D community health worker (CHW)-led intervention. Path analysis showed that the effect of the intervention did not vary by gender. The intervention was associated with significant improvements in knowledge of T2D management 0.24 (0.10); p = 0.014, diabetes distress, -0.26 (0.12); p = 0.023, and self-efficacy, 0.61 (0.21); p = 0.005. At 6-month follow-up, improved self-management was associated with greater self-efficacy and Hemoglobin A1c (HbA1c) was lower by -0.18 (0.08); p = 0.021 for each unit of self-management behavior. Linear regressions showed that class attendance and home visits contributed to positive intervention results, while gender was non-significant. Pathways of change in a CHW-led culturally tailored T2D intervention can have a significant effect on participant behaviors and health status outcomes, regardless of gender.

Demonstration of Managed Aquifer Recharge in a Coastal Plain Aquifer: Lessons Learned.

The sustainable water initiative for tomorrow (SWIFT) is a 378,000 m3 /day (100 MGD) managed aquifer recharge (MAR) program designed by the Hampton Roads Sanitation District (HRSD) to rehabilitate the Potomac Aquifer System (PAS) in the Coastal Plain of Eastern Virginia. Groundwater is a primary water source in Eastern Virginia with over 93% of reported use derived from the PAS. Starting in May 2018, HRSD has operated a 3780 m3 /day (1.0 MGD) MAR demonstration facility at the SWIFT Research Center (SWIFT-RC) in Suffolk, Virginia. The primary aim of the SWIFT-RC is to demonstrate, at a meaningful scale, the feasibility of MAR using deep well recharge into confined PAS hydrostratigraphic unit. The SWIFT-RC employs advanced water treatment technology to bring secondary effluent from an HRSD wastewater treatment plant to drinking water standards. Lessons learned include the evaluation and selection of a multiple barrier carbon-based treatment system to ensure water quality and maintain geochemical compatibility between MAR water and native groundwater, and the evaluation and selection of aluminum chlorohydrate for stabilizing aquifer clays immediately around the well to accept the fresher recharge water. The distribution of flow in the SWIFT-RC multiscreen recharge well and associated well injectivity were variable with time resulting from changing conditions in the well. Dynamic recharge well performance was quantified through the combined analysis of intrinsic and artificial tracer transport, in situ flowmeter testing, and water level analysis. Monitoring well nests and a depth-discrete sampling system supported a robust sampling plan to analyze chemical transport and attenuation in SWIFT-RC groundwater.

Effector mechanisms in the baroreceptor control of blood pressure.

While the effects of changing heart rate and systemic vascular resistance have been generally understood and appreciated, the effects of changes in left ventricular contractility on end-systolic volume may have been less understood and appreciated and the effects of changes in venous capacitance on end-diastolic volume may have been unknown to many readers. Herein, we have provided a brief review for the medical student and beginning graduate student highlighting these sometimes-complex relationships.

Technical Report: Reducing Lens Fogging Associated with Patient Mask Wearing with Heated Diagnostic Fundoscopy Lenses.

SIGNIFICANCE: Severe acute respiratory syndrome coronavirus 2 has indirectly created challenges to the ophthalmic retinal examinations because of lens fogging related to patients wearing masks. To date, there are no objective data on the degree of diagnostic ophthalmic lens fogging associated with mask wearing or on the effectiveness of proposed solutions to ophthalmologic lens fogging. PURPOSE: The purposes of this study were to investigate the degree of ophthalmologic lens fogging in patients wearing masks and to assess the efficacy lens warming in reducing lens fogging and facilitating ophthalmologic retinal examinations. METHODS: This study quantified the degree of lens fogging in mask-wearing subjects using ImageJ to measure lens surface area fogged in slit-lamp photographs of 90 D lenses before and after the use of a lens warmer. We investigated the clinical relevance of diagnostic lens fogging via a survey study of eye care providers. Subjects rated on a Likert scale their experience with diagnostic lens fogging during retinal examination in mask-wearing patients with and without the use of a lens warming device. RESULTS: For mask-wearing subjects, the percentage of fogged lens area in a 90 D lens averaged 32.5% using an unheated lens and 1.1% using a heated lens. Survey responders noted significantly less fogging of the 78 and 90 D lenses on retinal examination when using the lens warmer (P < .001) and found that using the lens warmer facilitated their retinal examination (P < .001). CONCLUSIONS: This study shows that there is significant fogging of ophthalmic slit-lamp lenses associated with patients wearing masks and that using a lens warmer significantly reduces fogging and facilitates retinal examinations. Eye care providers would benefit from the use of a lens warmer to reduce diagnostic lens fogging during retinal examination.

Challenges to dietary hypertension self-management as described by a sample of African American older adults.

BACKGROUND: Hypertension rates are disproportionately higher among Black or African Americans (Black/African American) compared to other racial and ethnic groups in the United States. However, research on self-management strategies to control hypertension through healthy eating such as the Dietary Approaches to Stop Hypertension (DASH), and ketogenic diets has underexplored the use of dietary strategies among older Black/African American adults. In reporting contemporary challenges with implementing dietary strategies targeting blood pressure control among Black/African American older adults living with hypertension, this study addresses a clear need. AIMS: Prior research has only partially addressed the challenges older Black/African Americans face in implementing and maintaining dietary strategies to control hypertension, therefore the current study aimed to address this gap by reporting contemporary challenges, as reported by a sample of Black/African American older adults living with hypertension. METHODS: Nineteen Black/African American older adults living with hypertension participated in a focus group. An interview guide with open-ended questions on dietary approaches to self-management hypertension was used to guide data collection. Responses were audio-recorded, transcribed verbatim, and interpreted using qualitative thematic analysis. RESULTS: Study participants were 71.6 years (SD = 8.3), 87.1% were women, and all were self-identified as Black/African American. Overall, participants shared that they were interested in improving their hypertension self-management skills. They expressed uncertainty about dietary strategies related in part to a lack of knowledge about incorporating or excluding certain foods and adhering to complex dietary recommendations. Participants also related financial concerns about accessing the recommended foods to control hypertension and expressed confusion about how to manage hypertension alongside other comorbidities. LINKING EVIDENCE TO ACTION: This study highlights several barriers that Black/African American older adults face (lack of dietary knowledge, lack of financial resources, and unique barriers to managing multiple comorbid health conditions), which often pose simultaneous and intersecting barriers to managing hypertension using existing evidence-based dietary strategies.

Demographic, Clinical, and Psychosocial Predictors of Change in Medication Adherence in the Support, Educate, Empower Program.

PURPOSE: To investigate whether demographic, clinical, or psychosocial factors act as moderators of change in medication adherence in the Support, Educate, Empower (SEE) program. DESIGN: Prospective, single-arm pilot study with a pre-post design. PARTICIPANTS: Patients with glaucoma aged ≥ 40 years and taking ≥ 1 glaucoma medication were recruited from the University of Michigan Kellogg Eye Center. Those who had electronically measured adherence ≤ 80% in the 3-month eligibility monitoring period were enrolled in the SEE program. METHODS: Medication adherence was monitored electronically during the 7-month intervention and calculated as the percentage of doses taken correctly. Change in adherence at different points in the SEE program and cumulative change in adherence were modeled with linear regression, and baseline demographic, clinical, and psychosocial factors were investigated for significant associations. MAIN OUTCOME MEASURES: Demographic, clinical, and psychosocial variables associated with change in medication adherence in the SEE program. RESULTS: Thirty-nine participants completed the SEE program. These participants were on average 63.9 years old (standard deviation [SD], 10.7 years), 56% (n = 22) were male, 44% (n = 17) were White, and 49% (n = 19) were Black. Medication adherence improved from an average of 59.9% (SD, 18.5%) at baseline to 83.6% (SD, 17.5%) after the final SEE session, for an increase of 23.7% (SD, 17.5%). Although participants with lower income (< $25 000 and $25 000-50 000 vs. >$50 000) had lower baseline adherence (48.4% and 64.1% vs. 70.4%), these individuals had greater increases in adherence during the first month of medication reminders (19.6% and 21.6% vs. 10.2%; P = 0.05 and P = 0.007, respectively). Participants taking fewer glaucoma medications also had significantly greater increases in adherence with medication reminders (P < 0.001). Those with higher levels of glaucoma-related distress (GD) had lower baseline adherence and greater increases in adherence with glaucoma coaching (P = 0.06). CONCLUSIONS: Patient-level factors associated with relatively greater improvements in medication adherence through the SEE Program included lower income, fewer glaucoma medications, and increased GD. These findings demonstrate that the SEE program can improve glaucoma self-management even among participants with social and psychological barriers to medication adherence.

"It Takes Some Empathy, Sympathy, and Listening": Telephone Outreach to Older Detroiters in a Pandemic as a Modality to Gain an Understanding of Challenges and Resiliency.

This manuscript describes a telephone outreach project for members of a research registry program for older adults in Detroit, Michigan. From April until December 2020, the Healthier Black Elders Center designed and implemented a telephone outreach program, calling 1204 older adults utilizing 15 staff and volunteers. The calls served to check in on registry members and collect data on mental health, coping mechanisms, access to services, masks, testing, and tele-health. This paper details the methods of developing and implementing an innovative engagement program that collected time-sensitive data from older Black adults that has directly been applied to create virtual health education programs, share resource information, and create a program to reduce social isolation.

Factors Associated With Racial/Ethnic Group-Based Medical Mistrust and Perspectives on COVID-19 Vaccine Trial Participation and Vaccine Uptake in the US.

Importance: The impact of COVID-19 in the US has been far-reaching and devastating, especially in Black populations. Vaccination is a critical part of controlling community spread, but vaccine acceptance has varied, with some research reporting that Black individuals in the US are less willing to be vaccinated than other racial/ethnic groups. Medical mistrust informed by experiences of racism may be associated with this lower willingness. Objective: To examine the association between race/ethnicity and rejection of COVID-19 vaccine trial participation and vaccine uptake and to investigate whether racial/ethnic group-based medical mistrust is a potential mediator of this association. Design, Setting, and Participants: This cross-sectional survey study was conducted from June to December 2020 using a convenience sample of 1835 adults aged 18 years or older residing in Michigan. Participants were recruited through community-based organizations and hospital-academic networks. Main Outcomes and Measures: Separate items assessed whether respondents, if asked, would agree to participate in a research study to test a COVID-19 vaccine or to receive a COVID-19 vaccine. Participants also completed the suspicion subscale of the Group-Based Medical Mistrust Scale. Results: Of the 1835 participants, 1455 (79%) were women, 361 (20%) men, and 19 (1%) other gender. The mean (SD) age was 49.4 (17.9) years, and 394 participants (21%) identified as Black individuals. Overall, 1376 participants (75%) reported low willingness to participate in vaccine trials, and 945 (52%) reported low willingness to be vaccinated. Black participants reported the highest medical mistrust scores (mean [SD], 2.35 [0.96]) compared with other racial/ethnic groups (mean [SD] for the total sample, 1.83 [0.91]). Analysis of path models revealed significantly greater vaccine trial and vaccine uptake rejection among Black participants (vaccine trial: B [SE], 0.51 [0.08]; vaccine uptake: B [SE], 0.51 [0.08]; both P < .001) compared with the overall mean rejection. The association was partially mediated by medical mistrust among Black participants (vaccine trial: B [SE], 0.04 [0.01]; P = .003; vaccine uptake: B [SE], 0.07 [0.02]; P < .001) and White participants (vaccine trial: B [SE], -0.06 [0.02]; P = .001; vaccine uptake: B [SE], -0.10 [0.02]; P < .001). Conclusions and Relevance: In this survey study of US adults, racial/ethnic group-based medical mistrust partially mediated the association between individuals identifying as Black and low rates of acceptance of COVID-19 vaccine trial participation and actual vaccination. The findings suggest that partnerships between health care and other sectors to build trust and promote vaccination may benefit from socially and culturally responsive strategies that acknowledge and address racial/ethnic health care disparities and historical and contemporary experiences of racism.

MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration.

The human genome expresses thousands of natural antisense transcripts (NAT) that can regulate epigenetic state, transcription, RNA stability or translation of their overlapping genes1,2. Here we describe MAPT-AS1, a brain-enriched NAT that is conserved in primates and contains an embedded mammalian-wide interspersed repeat (MIR), which represses tau translation by competing for ribosomal RNA pairing with the MAPT mRNA internal ribosome entry site3. MAPT encodes tau, a neuronal intrinsically disordered protein (IDP) that stabilizes axonal microtubules. Hyperphosphorylated, aggregation-prone tau forms the hallmark inclusions of tauopathies4. Mutations in MAPT cause familial frontotemporal dementia, and common variations forming the MAPT H1 haplotype are a significant risk factor in many tauopathies5 and Parkinson's disease. Notably, expression of MAPT-AS1 or minimal essential sequences from MAPT-AS1 (including MIR) reduces-whereas silencing MAPT-AS1 expression increases-neuronal tau levels, and correlate with tau pathology in human brain. Moreover, we identified many additional NATs with embedded MIRs (MIR-NATs), which are overrepresented at coding genes linked to neurodegeneration and/or encoding IDPs, and confirmed MIR-NAT-mediated translational control of one such gene, PLCG1. These results demonstrate a key role for MAPT-AS1 in tauopathies and reveal a potentially broad contribution of MIR-NATs to the tightly controlled translation of IDPs6, with particular relevance for proteostasis in neurodegeneration.

A Non-Toxic Concentration of Telomerase Inhibitor BIBR1532 Fails to Reduce TERT Expression in a Feeder-Free Induced Pluripotent Stem Cell Model of Human Motor Neurogenesis.

Several studies have shown that human induced pluripotent stem cell (iPSC)-derivatives are essentially fetal in terms of their maturational status. Inducing ageing in iPSC-motor neuron (MN) models of amyotrophic lateral sclerosis (ALS) has the potential to capture pathology with higher fidelity and consequently improve translational success. We show here that the telomerase inhibitor BIBR1532, hypothesised to recapitulate the telomere attrition hallmark of ageing in iPSC-MNs, was in fact cytotoxic to feeder-free iPSCs when used at doses previously shown to be effective in iPSCs grown on a layer of mouse embryonic fibroblasts. Toxicity in feeder-free cultures was not rescued by co-treatment with Rho Kinase (ROCK) inhibitor (Y-27632). Moreover, the highest concentration of BIBR1532 compatible with continued iPSC culture proved insufficient to induce detectable telomerase inhibition. Our data suggest that direct toxicity by BIBR1532 is the most likely cause of iPSC death observed, and that culture methods may influence enhanced toxicity. Therefore, recapitulation of ageing hallmarks in iPSC-MNs, which might reveal novel and relevant human disease targets in ALS, is not achievable in feeder-free culture through the use of this small molecule telomerase inhibitor.

Demonstration-scale evaluation of ozone-biofiltration-granular activated carbon advanced water treatment for managed aquifer recharge.

The Sustainable Water Initiative for Tomorrow (SWIFT) program is the effort of the Hampton Roads Sanitation District to implement indirect potable reuse to recharge the depleted Potomac Aquifer. This initiative is being demonstrated at the 1-MGD SWIFT Research Center with a treatment train including coagulation/flocculation/sedimentation (floc/sed), ozonation, biofiltration (BAF), granular activated carbon (GAC) adsorption, and UV disinfection, followed by managed aquifer recharge. Bulk total organic carbon (TOC) removal occurred via multiple treatment barriers including, floc/sed (26% removal), ozone/BAF (30% removal), and adsorption by GAC. BAF acclimation was observed during the first months of plant operation which coincided with the establishment of biological nitrification and dissolved metal removal. Bromate formation during ozonation was efficiently controlled below 10 µg/L using preformed monochloramine and preoxidation with free chlorine. N-nitrosodimethylamine (NDMA) was formed at an average concentration of 53 ng/L post-ozonation and was removed >70% by the BAFs after several months of operation. Contaminants of emerging concern were removed by multiple treatment barriers including oxidation, biological degradation, and adsorption. The breakthrough of these contaminants and bulk TOC will likely determine the replacement interval of GAC. The ozone/BAC/GAC treatment process was shown to meet all defined treatment goals for managed aquifer recharge. PRACTITIONER POINTS: Floc/sed, biofiltration, and GAC adsorption provide important barriers in carbon-based treatment trains for bulk TOC and trace organic contaminant removal. Biofilter acclimation was observed during the first three months of operation in each operating period as evidenced by the establishment of nitrification. Bromate was effectively controlled during ozonation of a high bromide water with monochloramine doses of 3-5 mg/L. NDMA was formed at an average concentration of 53 ng/L by ozonation and complete removal was achieved by BAFs after several months of biological acclimation. An average 25% removal of 1,4-dioxane was achieved via oxidation by hydroxyl radicals during ozonation.