StARD9 is a novel lysosomal kinesin required for membrane tubulation, cholesterol transport and Purkinje cell survival.

The pathological accumulation of cholesterol is a signature feature of Niemann-Pick type C (NPC) disease, in which excessive lipid levels induce Purkinje cell death in the cerebellum. NPC1 encodes a lysosomal cholesterol-binding protein, and mutations in NPC1 drive cholesterol accumulation in late endosomes and lysosomes (LE/Ls). However, the fundamental role of NPC proteins in LE/L cholesterol transport remains unclear. Here, we demonstrate that NPC1 mutations impair the projection of cholesterol-containing membrane tubules from the surface of LE/Ls. A proteomic survey of purified LE/Ls identified StARD9 as a novel lysosomal kinesin responsible for LE/L tubulation. StARD9 contains an N-terminal kinesin domain, a C-terminal StART domain, and a dileucine signal shared with other lysosome-associated membrane proteins. Depletion of StARD9 disrupts LE/L tubulation, paralyzes bidirectional LE/L motility and induces accumulation of cholesterol in LE/Ls. Finally, a novel StARD9 knock-out mouse recapitulates the progressive loss of Purkinje cells in the cerebellum. Together, these studies identify StARD9 as a microtubule motor protein responsible for LE/L tubulation and provide support for a novel model of LE/L cholesterol transport that becomes impaired in NPC disease.

Mental health symptoms and association with COVID-19 vaccination receipt and intention to vaccinate among adults, United States.

Early studies suggest that adults with mental health conditions are at greater risk for COVID-19 infection, severe complications, and higher mortality, yet face barriers in accessing timely health services. Data from the Census Bureau's Household Pulse Survey, a large, nationally representative survey fielded from March 17-29, 2021 (n = 77,104) were analyzed to examine COVID-19 vaccination and intention among adults with mental health symptoms. Separate multivariable regression models were conducted to examine associations between symptoms of anxiety, depression, and anxiety or depression on vaccine receipt (≥ 1 dose) and intention to be vaccinated. Reasons for not being vaccinated were also assessed. Approximately 35% of adults had symptoms of anxiety or depression. This population was less likely to receive COVID-19 vaccination (adjusted prevalence ratio (aPR) = 0.94, 95%CI: 0.91-0.98) but more likely to intend to get a vaccine (aPR = 1.13, 95%CI: 1.08-1.19) than those without these conditions. Females with mental health symptoms were less likely to receive a COVID-19 vaccination but more likely to intend to get vaccinated, while there were fewer significant associations between mental health symptoms and vaccination coverage and intentions to vaccinate among males. Reasons for not getting vaccinated, including concerns about possible vaccine side effects, efficacy, cost, dislike of vaccines, as well as lack of trust in the government and vaccines, were all greater among those with any symptoms of anxiety or depressive disorders than those without symptoms. Efforts are needed to increase vaccination uptake and confidence among this vulnerable population by increasing vaccine confidence and addressing concerns about the vaccine.

HIV-Related Stigma Research as a Priority at the National Institutes of Health.

The National Institutes of Health (NIH) recognizes that, despite HIV scientific advances, stigma and discrimination continue to be critical barriers to the uptake of evidence-based HIV interventions. Achieving the Ending the HIV Epidemic: A Plan for America (EHE) goals will require eliminating HIV-related stigma. NIH has a significant history of supporting HIV stigma research across its Institutes, Centers, and Offices (ICOs) as a research priority. This article provides an overview of NIH HIV stigma research efforts. Each ICO articulates how their mission shapes their interest in HIV stigma research and provides a summary of ICO-relevant scientific findings. Research gaps and/or future opportunities are identified throughout, with key research themes and approaches noted. Taken together, the collective actions on the part of the NIH, in tandem with a whole of government and whole of society approach, will contribute to achieving EHE's milestones.

RESUMEN: Los Institutos de Salud Nacional (NIH, siglas en inglés) reconocen que, a pesar de los avances en la prevención y el tratamiento, el estigma y la discriminación continúan siendo barreras críticas a la adopción de la prevención y el cuido basados en la evidencia. Las metas de Logrando el Fin de la Epidemia de VIH: Plan para América (EHE, siglas en inglés) requerirán la eliminación del estigma relacionado al VIH. Los NIH tienen una historia significativa apoyando la investigación del estigma relacionado al VIH a través de sus Institutos, Centros, y Oficinas (ICOs, siglas en inglés). Esta investigación es una prioridad fundamental y entrelazada para los ICOs. En este artículo, los autores de los NIH proveen una reseña sobre la investigación del estigma relacionado al VIH a través de los ICOs selectos. Cada ICO articula como su misión y prioridad dan forma a su interés en la investigación del estigma al VIH y provee una breve reseña de los hallazgos científicos pertinentes al ICO. Lagunas en la investigación relacionada a la misión, prioridades, y/o áreas de investigación futuras se identifican a través del artículo. También se apuntan en el resumen los temas de investigación claves y sus estrategias. En conjunto, las acciones colectivas de parte de los NIH, junto a la estrategia necesaria de parte del gobierno en su totalidad y de la sociedad en su totalidad, contribuirán al logro de las metas del EHE.

NIH-Funded CBPR: Self-Reported Community Partner and Investigator Perspectives.

The community-based participatory research (CBPR) approach across health contexts has matured greatly over the last 20 years. Though contributions to the literature on the development and effectiveness of CBPR interventions have grown, the number of publications on the function and evaluation of actual community-research partnerships has not kept pace. To help address that gap, we searched National Institutes of Health archival data and identified a set of 489 CBPR projects including collaboration-building, exploratory/pilot, research, and program project grants. We found community partner contact information commonly was absent from grant records and contacted principal investigators (PIs) for community-partner contact information. Subsequently, we built upon established measures to ask principal investigators and community partners for their perceptions of participation in NIH-funded CBPR projects. Many principal investigators and community partners reported existing collaborations-between academicians and community organizations as well as among community organizations. Partners tended to agree on the appropriateness of funding levels to accomplish projects and on the community partners' ability to recruit and retain participants, collect data, and implement interventions. Partners differed in perceptions of participation in research design, data analyses, manuscript and presentation production, and dissemination of findings. Suggestions include collection of lead community partner information without undue burden and increased standard education and involvement of community organizations in research vocabulary and practices.

Parent report of conversations with their adolescents with intellectual disability.

BACKGROUND: The purpose of this study was to examine parent report of conversations about difference and disability in families of adolescents with intellectual disability. MATERIALS AND METHODS: Participants included 50 parents (44 mothers, four fathers, and two other caregivers) and their adolescents with intellectual disability (M age = 15.9). Parents provided written responses to open-ended questions regarding conversations with their adolescent. Adolescents completed measures of self-concept and self-determination. RESULTS: The majority (66%) of parents reported talking to their adolescent about difference and/or disability. Consistent with previous research, some of these conversations were in response to social exclusion (e.g. child was bullied). Parents who knew the aetiology of their child's disability were significantly more likely to talk with their child about his or her disabling condition. CONCLUSIONS: Parents' narratives illustrate their struggle to explain disability to their adolescent. Professionals are challenged to consider how to promote proactive conversations between parents and adolescents.

Access to inflatable penile prosthesis surgery as indicated by distances traveled among US men with Medicare.

Background: The significance of geographic barriers to receiving inflatable penile prosthesis (IPP) treatment is uncertain according to the existing medical literature. Aim: To describe the travel patterns of men with erectile dysfunction (ED) in the United States who underwent IPP surgery. Methods: This retrospective cohort study utilized data from the 100% Medicare Standard Analytical Files. Men aged ≥65 years with an ED diagnosis who underwent IPP surgery between January 2016 and December 2021 were identified from the database. Federal Information Processing Series codes from the National Bureau of Economic Research's County Distance Database were used to determine geographic distances from patients' homes to the facilities at which surgery was performed. Outcomes: Evaluations included the proportions of men who traveled outside their county of residence or state for IPP treatment and the average distances in miles traveled. Results: Among 15 954 men with ED undergoing IPP treatment, 56.4% received care out of their county for IPP, at a mean distance of 125.6 miles (range, 3.8-4935.0). Although patients aged ≥80 years were less likely to travel outside their county as compared with men aged 65 to 69 years (48.1% vs 57.1%, P < .001), if they traveled, they were likely to travel farther (mean, 171.8 vs 117.7 miles; P < .001). South Dakota had the highest proportion of men traveling outside their county for IPP treatment (91.3%; mean, 514.2 miles), while Vermont had the highest proportion traveling outside their home state (73.7%). Clinical Implications: By unveiling disparities in access, this study will potentially lead to tailored interventions that enhance patient care and health outcomes. Strengths and Limitations: Strengths include the uniqueness in (1) evaluating the proportions of patients who travel out of their county of residence or home state for IPP treatment and (2) quantifying the average distances that patients traveled. An additional strength is the large sample size due to the retrospective design and database used. The analysis did not capture all Medicare enrollees; however, it did encompass all traditional Medicare enrollees, representing approximately half of all men in the US aged ≥65 years. Limitations include not being generalizable to entire population of the US, as the study examined only Medicare enrollees. In addition, the study period includes the pandemic, which could have affected travel patterns. Furthermore, the coding and accuracy of the data are limitations of using administrative claims data for research. Conclusion: Study findings showed that many men with Medicare and ED traveled from their home geographic location for IPP treatment.

The Complex, Unique, and Powerful Imaging Instrument for Dynamics (CUPI2D) at the Spallation Neutron Source (invited).

The Oak Ridge National Laboratory is planning to build the Second Target Station (STS) at the Spallation Neutron Source (SNS). STS will host a suite of novel instruments that complement the First Target Station's beamline capabilities by offering an increased flux for cold neutrons and a broader wavelength bandwidth. A novel neutron imaging beamline, named the Complex, Unique, and Powerful Imaging Instrument for Dynamics (CUPI2D), is among the first eight instruments that will be commissioned at STS as part of the construction project. CUPI2D is designed for a broad range of neutron imaging scientific applications, such as energy storage and conversion (batteries and fuel cells), materials science and engineering (additive manufacturing, superalloys, and archaeometry), nuclear materials (novel cladding materials, nuclear fuel, and moderators), cementitious materials, biology/medical/dental applications (regenerative medicine and cancer), and life sciences (plant-soil interactions and nutrient dynamics). The innovation of this instrument lies in the utilization of a high flux of wavelength-separated cold neutrons to perform real time in situ neutron grating interferometry and Bragg edge imaging-with a wavelength resolution of δλ/λ ≈ 0.3%-simultaneously when required, across a broad range of length and time scales. This manuscript briefly describes the science enabled at CUPI2D based on its unique capabilities. The preliminary beamline performance, a design concept, and future development requirements are also presented.

The supply of multiple ecosystem services requires biodiversity across spatial scales.

The impact of local biodiversity loss on ecosystem functioning is well established, but the role of larger-scale biodiversity dynamics in the delivery of ecosystem services remains poorly understood. Here we address this gap using a comprehensive dataset describing the supply of 16 cultural, regulating and provisioning ecosystem services in 150 European agricultural grassland plots, and detailed multi-scale data on land use and plant diversity. After controlling for land-use and abiotic factors, we show that both plot-level and surrounding plant diversity play an important role in the supply of cultural and aboveground regulating ecosystem services. In contrast, provisioning and belowground regulating ecosystem services are more strongly driven by field-level management and abiotic factors. Structural equation models revealed that surrounding plant diversity promotes ecosystem services both directly, probably by fostering the spill-over of ecosystem service providers from surrounding areas, and indirectly, by maintaining plot-level diversity. By influencing the ecosystem services that local stakeholders prioritized, biodiversity at different scales was also shown to positively influence a wide range of stakeholder groups. These results provide a comprehensive picture of which ecosystem services rely most strongly on biodiversity, and the respective scales of biodiversity that drive these services. This key information is required for the upscaling of biodiversity-ecosystem service relationships, and the informed management of biodiversity within agricultural landscapes.

Ending Sexual Harassment in Science: Designing and Administering a Survey That Can Lead to an Improved Organizational Climate.

Workplace harassment, particularly sexual harassment, has substantial negative implications for individuals and organizations and for scientific advancement. The National Institutes of Health (NIH) is uniquely positioned to lead the effort to prevent sexual harassment in the scientific community and mitigate its detrimental effects. Recognizing the need for benchmark data, NIH developed and validated the 2019 NIH Workplace Climate and Harassment Survey. The goal was to use best practices in survey design methods to create an instrument for rigorous assessment of harassment incidence and organizational climate predictors of sexual harassment in scientific research environments. This article summarizes the processes used to design and administer the NIH survey and provides brief descriptions of 3 products of the process developed to guide scientific institutions wishing to embark on a data-driven approach to assess and prevent harassment: a document detailing survey development and methods, a survey implementation guide, and the key findings obtained from the survey, including recommendations for interventions targeting the organizational climate at NIH and limitations of the survey. The survey identified that 1 in 5 respondents had experienced sexual harassment in the 12 months preceding their participation in the survey and that women, sexual and gender minorities, younger respondents, trainees/students, and individuals with a disability were more likely to have experienced sexual harassment. Those who had experienced sexual harassment during that period were also more likely to have experienced incivility, bullying, and intimidating behaviors in the workplace. NIH intends to use the survey findings as a quality assurance and quality improvement guide to inform future activities to prevent and address harassment across NIH.

The Power of Documentary Theatre to Promote Cross-National Understanding: Personal Impact of Performing With Their Voices Raised by Japanese and American Youth Actors.

PURPOSE: The purpose of this article is to share descriptions of the personal impact for cross-national youth actors (Japanese, American) who performed With Their Voices Raised (Voices), a documentary theater script that shares the stories of Pearl Harbor and Hiroshima survivors who lived through the bombings of December 7, 1941, and August 6, 1945, respectively. DESIGN/METHODS: This was a descriptive exploratory focus group study conducted immediately after student-actors from Funairi High School in Hiroshima (n = 15) and Farrington High School in Oahu, Hawaii (n = 8), performed Voices. Data were content analyzed by a cross-national research team to address the question "What was the personal impact of performing Voices for Japanese and American youth actors?" FINDINGS: There were three themes that crossed national boundaries: sense of power of the message from real-life people, new cross-national awareness, and moving beyond familiar history to engage and learn. The fourth theme distinguished the youth groups: for Japanese youth, performing Voices inspired an awareness of their local focus; for American youth, it enlivened youth-to-youth engagement as a learning approach. CONCLUSIONS: Documentary theater script is a creative, holistic approach with the potential to bridge divisiveness and promote cross-national understanding.

A Study of Reliance Agreement Templates Used by U.S. Research Institutions.

We performed a content analysis of reliance agreement templates from 73 of the top U.S. research institutions ranked by research funding. 67.1% of institutions in our sample use the Office of Human Research Protections (OHRP) template and 8.2% use the SMART IRB template. Although a significant percentage of institutions (45.2%) use their own custom template, many of these also use the OHRP template or the SMART IRB template. 21.9% of institutional templates have only the OHRP minimum 10 contractual provisions (or elements), 27.4% have 11 elements, 26% have 12-19 elements, and 24.7% have 20 or more elements. 5.5% of institutional templates require the relied-upon institution to indemnify the relying institution, 6.8% require the relying institution to indemnify the relied-upon institution, 8.2% require the relied-upon institution to have liability insurance, 15.1% require the relying institution to have liability insurance, 2.7% require the relied-upon institution to have accreditation, and none require the relying institution to have accreditation. The number of elements in the template was positively associated with total research funding and private institutional control. Our data indicate that institutions which are seeking reliance agreements for cooperative research involving human subjects are not likely to encounter many difficulties because most are using commonly employed templates and are not imposing potentially disputable requirements on parties to the agreement.

The Childhood Obesity Declines Project: Implications for Research and Evaluation Approaches.

BACKGROUND: Childhood obesity remains prevalent and is increasing in some disadvantaged populations. Numerous research, policy and community initiatives are undertaken to impact this pandemic. Understudied are natural experiments. The need to learn from these efforts is paramount. Resulting evidence may not be readily available to inform future research, community initiatives, and policy development/implementation. METHODS: We discuss the implications of using an adaptation of the Systematic Screening and Assessment (SSA) method to evaluate the Childhood Obesity Declines (COBD) project. The project examined successful initiatives, programs and policies in four diverse communities which were concurrent with significant declines in child obesity. In the context of other research designs and evaluation schemas, rationale for use of SSA is presented. Evidence generated by this method is highlighted and guidance suggested for evaluation of future studies of community-based childhood obesity prevention initiatives. Support for the role of stakeholder collaboratives, in particular the National Collaborative on Childhood Obesity Research, as a synergistic vehicle to accelerate research on childhood obesity is discussed. RESULTS/DISCUSSION: SSA mapped active processes and provided contextual understanding of multi-level/component simultaneous efforts to reduce rates of childhood obesity in community settings. Initiatives, programs and policies were not necessarily coordinated. And although direct attribution of intervention/initiative/policy components could not be made, the what, by who, how, to whom was temporally associated with statistically significant reductions in childhood obesity. CONCLUSIONS: SSA provides evidence for context and processes which are not often evaluated in other data analytic methods. SSA provides an additional tool to layer with other evaluation approaches.

Oxidized lipid accumulates in the presence of alpha-tocopherol in atherosclerosis.

Oxidative modification of low-density lipoproteins in the arterial wall is a key feature of atherogenesis and widely believed to cause and/or accelerate lesion development. Linked to this is the expectation that vascular antioxidants are depleted during oxidation in vivo. However, whether alpha-tocopherol (vitamin E), an important lipid-soluble antioxidant, is depleted early in atherogenesis and can prevent lipid peroxidation in vivo is unresolved. To address this we examined the content of specific configurational isomers (cis/trans) of lipid hydro(pero)xides in lesions, which represent the major non-enzymic oxidation products, as formation and accumulation of cis/trans isomers is influenced by alpha-tocopherol in studies in vitro. Concordant with our previous findings that large amounts of oxidized lipid co-exist with relatively normal alpha-tocopherol levels in human lesions, we now show that cis/trans isomers predominate over other products in human carotid and aortic lesions and in lesion lipoproteins. Further, dietary vitamin E supplementation of rabbits after arterial injury significantly increases both the aortic levels of alpha-tocopherol and the overall content of cis/trans isomers. These data are fully consistent with alpha-tocopherol acting as a hydrogen donor during lipid oxidation in vivo and suggest that alpha-tocopherol does not prevent lipoprotein lipid oxidation in the diseased vessel wall.