Targeting N-Myc in neuroblastoma with selective Aurora kinase A degraders.

The N-Myc transcription factor, encoded by MYCN, is a mechanistically validated, yet challenging, target for neuroblastoma (NB) therapy development. In normal neuronal progenitors, N-Myc undergoes rapid degradation, while, in MYCN-amplified NB cells, Aurora kinase A (Aurora-A) binds to and stabilizes N-Myc, resulting in elevated protein levels. Here, we demonstrate that targeted protein degradation of Aurora-A decreases N-Myc levels.

Mapping the Landscape of Those Left Behind When a Person With Dementia Dies: Roles of Race and Ethnicity.

Introduction: People with dementia can have many family and friends who might be affected by their deaths. Pursuing the long-term aim of understanding how dementia deaths affect close family and friends, this project lays groundwork through estimates of who those close family and friends are, with special attention to race and ethnicity.

Method: Regression models estimated associations between dementia, race/ethnicity, and close family and friend network size, controlling for age, sex, education, marital status, and household wealth for 1386 deceased people with dementia from the Health and Retirement Study (2004 to 2018).

Measuring Consumer-Reported Quality of Life Among Recipients of Publicly Funded Home- and Community-Based Services: Implications for Health Equity.

Objectives: Despite an increased policy focused on home- and community-based services (HCBS), little is known about their quality of life (QoL)-a key measure of person-centered care. This paper addresses this gap by measuring consumers' self-reported QoL and identifying factors associated with disparities in QoL.

Methods: We analyzed the 2015-2016 National Core Indicators-Aging and Disability survey for 3426 respondents in Minnesota, using factor analyses to identify latent QoL domains.

Protocol for a telephonic mixed methods study to understand needs and find solutions for bereaved dementia caregivers.

Introduction: Most caregivers of people living with dementia will experience bereavement within 10 years, but study of and support for their needs rarely persists following the death of their care recipients. A single model that leverages theoretical insights as well as observation from lived experience might help identify who will have greater difficulty following dementia-related bereavement and suggest core mechanisms to target to relieve clinical and subclinical consequences. The millions of existing bereaved dementia caregivers likely have considerable insight into ways to improve experience.

Exploring the conformational landscapes of protein kinases: perspectives from FRET and DEER.

Conformational changes of catalytically-important structural elements are a key feature of the regulation mechanisms of protein kinases and are important for dictating inhibitor binding modes and affinities. The lack of widely applicable methods for tracking kinase conformational changes in solution has hindered our understanding of kinase regulation and our ability to design conformationally selective inhibitors. Here we provide an overview of two recently developed methods that detect conformational changes of the regulatory activation loop and αC-helix of kinases and that yield complementary information about allosteric mechanisms.

Efficacy of the residential care transition module: A telehealth intervention for dementia family caregivers of relatives living in residential long-term care settings.

The purpose of this study was to evaluate the efficacy of the Residential Care Transition Module, a six-session, psychosocial, and psychoeducational telehealth intervention for family caregivers of cognitively impaired relatives living in a residential long-term care setting. Eligible participants (including care recipients, regardless of time since admission) were randomized to treatment or usual care control conditions. Survey data were collected at baseline, 4 months, 8 months, and 12 months ( = 240).

Shared Activities as a Protective Factor Against Behavioral and Psychological Symptoms of Dementia and Caregiver Stress.

Background And Objectives: Most persons with dementia experience behavioral and psychological symptoms (BPSD). While there is evidence that structured activity programs can be beneficial for persons with dementia and their caregivers, it is not well understood how joint engagement in shared activities affects BPSD and caregiver stress. The purpose of this study was to examine the moderating effect of doing a shared activity on the BPSD and caregiver stress.

Evidence Map of Non-Pharmacological Dementia Care Partner Interventions Implemented in the US: Gaps and Impact Opportunities.

There are 200+ tested interventions for care partners (family, friends, and fictive kin) of people living with dementia (PLWD). But these interventions do not systematically cover relevant settings. Nor do these interventions affect all relevant outcomes that matter to people and healthcare systems.

Patterns of recombination in snakes reveal a tug-of-war between PRDM9 and promoter-like features.

In some mammals, notably humans, recombination occurs almost exclusively where the protein PRDM9 binds, whereas in vertebrates lacking an intact , such as birds and canids, recombination rates are elevated near promoter-like features. To determine whether PRDM9 directs recombination in nonmammalian vertebrates, we focused on an exemplar species with a single, intact ortholog, the corn snake (). Analyzing historical recombination rates along the genome and crossovers in pedigrees, we found evidence that PRDM9 specifies the location of recombination events, but we also detected a separable effect of promoter-like features.

A Qualitative Analysis of Mechanisms of Benefit in the Residential Care Transition Module: A Telehealth Intervention for Caregivers of Relatives With Dementia Living in Residential Long-Term Care.

This study sought to determine the perceived benefits of the Residential Care Transition Module (RCTM), a novel multi-component, psychoeducational/psychosocial, telehealth intervention for caregivers of cognitively impaired relatives living in residential long-term care (RLTC). Few support programs exist for these caregivers. Determining the intervention's mechanisms of benefit will provide actionable clinical and research information regarding which key features aspects RLTC and public health agencies should offer their families.

"I Have Accepted My Father's Death; I was not Sad but Relieved." Adaptive Grief Responses for Bereaved Dementia Family Caregivers: A Scoping Review.

This scoping review explores findings from the psychological and medical literature on the adaptive grieving experiences of bereaved dementia family caregivers and integrates what healthcare professionals can do to support bereaved dementia family caregivers transition into a post-death role. Bereaved dementia family caregivers are particularly susceptible to prolonged grief disorder post-death due to the protracted caregiving demands and progressive course of the illness. The mention of caregiver grief while the person with dementia is living is quite common in the literature; however, limited research focuses on the bereaved dementia family caregiver and the methods they use to grieve adaptively.

Down the Penrose stairs, or how selection for fewer recombination hotspots maintains their existence.

In many species, meiotic recombination events tend to occur in narrow intervals of the genome, known as hotspots. In humans and mice, double strand break (DSB) hotspot locations are determined by the DNA-binding specificity of the zinc finger array of the PRDM9 protein, which is rapidly evolving at residues in contact with DNA. Previous models explained this rapid evolution in terms of the need to restore PRDM9 binding sites lost to gene conversion over time, under the assumption that more PRDM9 binding always leads to more DSBs.

Connecting Dementia Caregivers to Recommended Services: Care to Plan.

The current mixed methods, embedded study evaluated the use of an online tool (Care to Plan [CtP]) that generates tailored service and support recommendations for dementia caregivers as well as information that can connect dementia caregiver users to recommended resources. Forty-three dementia caregivers identified in a health care system were randomly assigned to receive either CtP or usual care. The embedded, mixed methods design resulted in no quantitative, direct evidence for CtP's efficacy.

Using Hybrid Effectiveness Studies to Facilitate Implementation in Community-Based Settings: Three Case Studies in Dementia Care Research.

The pipeline from discovery to testing and then implementing evidence-based innovations in real-world contexts may take 2 decades or more to achieve. Implementation science innovations, such as hybrid studies that combine effectiveness and implementation research questions, may help to bridge the chasm between intervention testing and implementation in dementia care. This paper describes hybrid effectiveness studies and presents 3 examples of dementia care interventions conducted in various community-based settings.

Healthcare Utilization and Advance Care Planning among Older Adults Across Cognitive Levels.

This study examined the impact of advance care planning (ACP) on healthcare utilization among older adults with normal cognition and impaired cognition/dementia. Using datasets from the Health and Retirement Study, we conducted a cross-sectional study on 17,698 participants aged 51 years and older. Our analyses included survey descriptive and logistic regression procedures.

Patterns of recombination in snakes reveal a tug of war between PRDM9 and promoter-like features.

In vertebrates, there are two known mechanisms by which meiotic recombination is directed to the genome: in humans, mice, and other mammals, recombination occurs almost exclusively where the protein PRDM9 binds, while in species lacking an intact , such as birds and canids, recombination rates are elevated near promoter-like features. To test if PRDM9 also directs recombination in non-mammalian vertebrates, we focused on an exemplar species, the corn snake (). Unlike birds, this species possesses a single, intact ortholog.

Racial Differences in Nursing Home Quality of Life Among Residents Living With Alzheimer's Disease and Related Dementias.

ObjectivesAmong nursing home (NH) residents with Alzheimer's disease (AD) and AD-related dementias (AD/ADRD), racial/ethnic disparities in quality of care exist. However, little is known about quality of life (QoL). This study examines racial/ethnic differences in self-reported QoL among NH residents with AD/ADRD.

"We Moved Her Too Soon": Navigating Guilt Among Adult Child and Spousal Caregivers of Persons Living with Dementia Following a Move into Residential Long-Term Care.

Guilt is a complex and multifaceted emotion navigated by many family caregivers. Guilt is sometimes experienced following a transition into a residential long-term care facility, even when the move is necessary given high care needs related to Alzheimer's disease and related dementias. This mixed methods study identifies and compares areas of guilt most frequently experienced by spouse and adult child caregivers (N=83) of a family member with dementia following transition into residential long-term care.

The Basic Psychological Need Satisfaction and Frustration Scales probably do not validly measure need frustration.

In basic psychological needs theory (BPNT), the separable constructs of need satisfaction and need frustration are theorized as pivotally related to psychopathology and broader aspects of well-being. The Basic Psychological Need Satisfaction and Frustration Scales (BPNSFS; Chen et al., 2015) have rapidly emerged as the dominant self-report measure in the BPNT domain, with translated versions available in a wide range of languages and a plethora of versions adapted for specific populations and life contexts.

CVR-MRICloud: An online processing tool for CO2-inhalation and resting-state cerebrovascular reactivity (CVR) MRI data.

Cerebrovascular Reactivity (CVR) provides an assessment of the brain's vascular reserve and has been postulated to be a sensitive marker in cerebrovascular diseases. MRI-based CVR measurement typically employs alterations in arterial carbon dioxide (CO2) level while continuously acquiring Blood-Oxygenation-Level-Dependent (BOLD) images. CO2-inhalation and resting-state methods are two commonly used approaches for CVR MRI.

Simultaneously Developing Interventions for Low-/Middle-Income and High-Income Settings: Considerations and Opportunities.

Most older adults reside in low- and middle-income countries (LMICs) but most research dollars spent on interventions to improve the lives of older adults are awarded to researchers in high-income countries (HICs). One approach to improve the implementation of evidence-based innovations for older adults in LMICs is designing interventions that are relevant to LMICs and HICs simultaneously. We propose that researchers in HICs could partner with stakeholders in an LMIC throughout the intervention design process to better position their intervention for the implementation in that LMIC.

Delivering Personalized Recommendations to Support Caregivers of People Living With Dementia: Mixed Methods Study.

Background: Estimates suggest that 6.2 million Americans aged ≥65 years are living with Alzheimer dementia in 2021, and by 2060, this number could more than double to 13.8 million.

Rehabilitation of a misbehaving microbiome: phages for the remodeling of bacterial composition and function.

The human gut microbiota is considered an adjunct metabolic organ owing to its health impact. Recent studies have shown correlations between gut phage composition and host health. Whereas phage therapy has popularized virulent phages as antimicrobials, both virulent and temperate phages have a natural ecological relationship with their cognate bacteria.

losses in vertebrates are coupled to those of paralogs and .

In most mammals and likely throughout vertebrates, the gene specifies the locations of meiotic double strand breaks; in mice and humans at least, it also aids in their repair. For both roles, many of the molecular partners remain unknown. Here, we take a phylogenetic approach to identify genes that may be interacting with PRDM9 by leveraging the fact that arose before the origin of vertebrates but was lost many times, either partially or entirely-and with it, its role in recombination.