Assessing the context within academic health institutions toward improving equity-based, community and patient-engaged research.

Introduction: The continued momentum toward equity-based, patient/community-engaged research (P/CenR) is pushing health sciences to embrace principles of community-based participatory research. Much of this progress has hinged on individual patient/community-academic partnered research projects and partnerships with minimal institutional support from their academic health institutions.

Methods: We partnered with three academic health institutions and used mixed methods (i.

Leveraging human-centered design and causal pathway diagramming toward enhanced specification and development of innovative implementation strategies: a case example of an outreach tool to address racial inequities in breast cancer screening.

Background: Implementation strategies are strategies to improve uptake of evidence-based practices or interventions and are essential to implementation science. Developing or tailoring implementation strategies may benefit from integrating approaches from other disciplines; yet current guidance on how to effectively incorporate methods from other disciplines to develop and refine innovative implementation strategies is limited. We describe an approach that combines community-engaged methods, human-centered design (HCD) methods, and causal pathway diagramming (CPD)-an implementation science tool to map an implementation strategy as it is intended to work-to develop innovative implementation strategies.

Study Protocol for the Social Interventions for Support During Treatment for Endometrial Cancer and Recurrence (SISTER) study: a community engaged national randomized trial.

Social isolation in cancer patients is correlated with prognosis and is a potential mediator of treatment completion. Black women with endometrial cancer (EC) are at increased risk for social isolation when compared with White patients. We developed the Social Interventions for Support during Treatment for Endometrial Cancer and Recurrence (SISTER) study to compare and evaluate interventions to address social isolation among Black women with high-risk EC in USA.

Immune activation of the p75 neurotrophin receptor: implications in neuroinflammation.

Despite structural similarity with other tumor necrosis factor receptor superfamily (TNFRSF) members, the p75 neurotrophin receptor (p75, TNFR16) mediates pleiotropic biological functions not shared with other TNFRs. The high level of p75 expression in the nervous system instead of immune cells, its utilization of co-receptors, and its interaction with soluble dimeric, rather than soluble or cell-tethered trimeric ligands are all characteristics which distinguish it from most other TNFRs. Here, we compare these attributes to other members of the TNFR superfamily.

The Integration of Value Assessment and Social Network Methods for Breast Health Navigation Among African Americans.

Objectives: A major strategy to reduce the impact of breast cancer (BC) among African Americans (AA) is patient navigation, defined here as individualized assistance for reducing barriers to healthcare use. The primary focus of this study was to estimate the added value of incorporating breast health promotion by navigated participants and the subsequent BC screenings that network members may obtain.

Methods: In this study, we compared the cost-effectiveness of navigation across 2 scenarios.

Human immunomodulatory ligand B7-1 mediates synaptic remodeling via the p75 neurotrophin receptor.

Cell surface receptors, ligands, and adhesion molecules underlie development, circuit formation, and synaptic function of the central nervous system and represent important therapeutic targets for many neuropathologies. The functional contributions of interactions between cell surface proteins of neurons and nonneuronal cells have not been fully addressed. Using an unbiased protein-protein interaction screen, we showed that the human immunomodulatory ligand B7-1 (hB7-1) interacts with the p75 neurotrophin receptor (p75NTR) and that the B7-1:p75NTR interaction is a recent evolutionary adaptation present in humans and other primates, but absent in mice, rats, and other lower mammals.

Increasing Racial and Ethnic Diversity in Cancer Clinical Trials: An American Society of Clinical Oncology and Association of Community Cancer Centers Joint Research Statement.

A concerted commitment across research stakeholders is necessary to increase equity, diversity, and inclusion (EDI) and address barriers to cancer clinical trial recruitment and participation. Racial and ethnic diversity among trial participants is key to understanding intrinsic and extrinsic factors that may affect patient response to cancer treatments. This ASCO and Association of Community Cancer Centers (ACCC) Research Statement presents specific recommendations and strategies for the research community to improve EDI in cancer clinical trials.

"We Are a Powerful Movement": Evaluation of an Endometrial Cancer Education Program for Black Women.

Background: U.S. Black women with endometrial cancer (EC) have a 90% higher mortality rate than White women, driven in part by advanced stage at diagnosis.

Zinc induced structural changes in the intrinsically disordered BDNF Met prodomain confer synaptic elimination.

Human brain derived neurotrophic factor (BDNF) encodes a protein product consisting of a C-terminal mature domain (mature BDNF) and an N-terminal prodomain, which is an intrinsically disordered protein. A common single nucleotide polymorphism in humans results in a methionine substitution for valine at position 66 of the prodomain, and is associated with memory deficits, depression and anxiety disorders. The BDNF Met66 prodomain, but not the Val66 prodomain, promotes rapid structural remodeling of hippocampal neurons' growth cones and dendritic spines by interacting directly with the SorCS2 receptor.

Assessment of Prediagnostic Experiences of Black Women With Endometrial Cancer in the United States.

Importance: Black women with endometrial cancer have a 90% higher mortality rate than white women with endometrial cancer. The advanced disease stage at which black women receive a diagnosis of endometrial cancer is a major factor in this disparity and is not explained by differences in health care access.

Objective: To describe the prediagnostic experiences of symptoms and symptom disclosure among black women with endometrial cancer.

Oncology provider and African-American breast cancer survivor perceptions of the emotional experience of transitioning to survivorship.

Purpose: To examine the emotional experience of African American breast cancer survivors (BCS), and the information exchange between providers and patients, during transitioning to post-treatment survivorship.

Research Approach: We conducted a qualitative study using interviews and focus groups.

Participants: We sought perspectives of oncology providers (n = 27) and African-American breast cancer survivors (BCS) (n = 45) who provided and received care in three counties in Washington State.

SorCS2 is required for social memory and trafficking of the NMDA receptor.

Social memory processing requires functional CA2 neurons, however the specific mechanisms that regulate their activity are poorly understood. Here, we document that SorCS2, a member of the family of the Vps10 family of sorting receptors, is highly expressed in pyramidal neurons of CA2, as well as ventral CA1, a circuit implicated in social memory. SorCS2 specifically localizes to the postsynaptic density and endosomes within dendritic spines of CA2 neurons.

Seeking Black Women's Voices in Endometrial Cancer Research via Deliberate Community Engagement.

Background: Black women with endometrial cancer (EC) are diagnosed at advanced stages and have markedly high mortality rates compared with women of other races. EC disparities research lacks both qualitative work and engagement of Black women. We sought to describe developing a community-research partnership to examine EC among Black women.

BDNF Actions in the Cardiovascular System: Roles in Development, Adulthood and Response to Injury.

The actions of BDNF (Brain-derived Neurotrophic Factor) in regulating neuronal development and modulating synaptic activity have been extensively studied and well established. Equally important roles for this growth factor have been uncovered in the cardiovascular system, through the examination of gene targeted animals to define critical actions in development, and to the unexpected roles of BDNF in modulating the response of the heart and vasculature to injury. Here we review the compartmentally distinct realm of cardiac myocytes, vascular smooth muscle cells, endothelial cells, and hematopoietic cells, focusing upon the actions of BDNF to modulate contractility, migration, neoangiogenesis, apoptosis and survival.

New Roles for an Ancient Factor.

In 1996, Hyejin Kang and Erin Schuman, in search of new functions for the secreted growth factor brain-derived neurotrophic factor (BDNF), identified the protein synthesis requirement of BDNF in regulating synaptic plasticity. This landmark paper identified one of the first tractable pathways in the quest to dissect the complex process of synaptic remodeling and revealed the critical role for this neurotrophin in regulating long-term memory.

The BDNF Val66Met Prodomain Disassembles Dendritic Spines Altering Fear Extinction Circuitry and Behavior.

A human variant in the BDNF gene (Val66Met; rs6265) is associated with impaired fear extinction. Using super-resolution imaging, we demonstrate that the BDNF Met prodomain disassembles dendritic spines and eliminates synapses in hippocampal neurons. In vivo, ventral CA1 (vCA1) hippocampal neurons undergo similar morphological changes dependent on their transient co-expression of a SorCS2/p75 receptor complex during peri-adolescence.

Community Empowerment Partners (CEPs): A Breast Health Education Program for African-American Women.

Peer educators have been shown to provide effective interventions in breast cancer screening. Few studies have compared the effects of peer education on breast cancer knowledge among peer educators and the community members who are subsequently reached through the peer education. Further, little is known as to whether those who received the education then go on to educate others in the community.

A Novel Neuroprotective Mechanism for Lithium That Prevents Association of the p75-Sortilin Receptor Complex and Attenuates proNGF-Induced Neuronal Death and .

Neurotrophins play critical roles in the survival, maintenance and death of neurons. In particular, proneurotrophins have been shown to mediate cell death following brain injury induced by status epilepticus (SE) in rats. Previous studies have shown that pilocarpine-induced seizures lead to increased levels of proNGF, which binds to the p75-sortilin receptor complex to elicit apoptosis.

Effect of Early-Life Fluoxetine on Anxiety-Like Behaviors in BDNF Val66Met Mice.

Objective: Adolescence is a developmental stage in which the incidence of psychiatric disorders, such as anxiety disorders, peaks. Selective serotonin reuptake inhibitors (SSRIs) are the main class of agents used to treat anxiety disorders. However, the impact of SSRIs on the developing brain during adolescence remains unknown.

Narp Mediates Antidepressant-Like Effects of Electroconvulsive Seizures.

Growing recognition of persistent cognitive defects associated with electroconvulsive therapy (ECT), a highly effective and commonly used antidepressant treatment, has spurred interest in identifying its mechanism of action to guide development of safer treatment options. However, as repeated seizure activity elicits a bewildering array of electrophysiological and biochemical effects, this goal has remained elusive. We have examined whether deletion of Narp, an immediate early gene induced by electroconvulsive seizures (ECS), blocks its antidepressant efficacy.

SorCS2-mediated NR2A trafficking regulates motor deficits in Huntington's disease.

Motor dysfunction is a prominent and disabling feature of Huntington's disease (HD), but the molecular mechanisms that dictate its onset and progression are unknown. The N-methyl-D-aspartate receptor 2A (NR2A) subunit regulates motor skill development and synaptic plasticity in medium spiny neurons (MSNs) of the striatum, cells that are most severely impacted by HD. Here, we document reduced NR2A receptor subunits on the dendritic membranes and at the synapses of MSNs in zQ175 mice that model HD.