Transgender and Gender Diverse People's Fear of Seeking and Receiving Care in Later Life: A Multiple Method Analysis.

The purpose of the current research is to understand concerns about receiving care in a sample of transgender, gender nonbinary, and gender diverse (TGD) adults across the lifespan. A total of 829 participants, predominantly from the United States and Canada, aged 18-70, completed the Trans Metlife Survey on Later-Life Preparedness and Perceptions in Transgender-Identified Individuals (TMLS) section on caregiving and are included in this study. We found middle-aged adults, people of Color, and people living with a disability reported the highest level of concern for their ability to function independently because of financial resources, physical concerns, cognitive impairment, or a lack of someone to care for them. Researchers found five overarching thematic categories: (a) No concerns, (b) Anticipated discrimination, (c) Loss of control, (d) Quality of life, and (e) General concerns. Practice implications include recommendations for practitioners to develop care plans with TGD residents and clients to learn the best strategies for affirming their gender identity (e.g., clothing preferences) and to assist TGD residents and clients with the completion of advance directives to allow them to outline their end-of-life care plan, including instructions for gender affirmative care in the event of incapacitation (e.g., dementia, stroke).

Implementation of an Adult ADHD Toolkit in Primary Care: A Prospective Cohort Survey.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) in adulthood presents unique challenges for primary care providers, and many lack confidence addressing it. To support them, a workgroup of volunteer primary care and mental health providers created an Adult ADHD Toolkit containing information about the disorder and treatment advice. The objective of this study was to establish the impact of implementing the toolkit in primary care. METHODS: Providers completed a survey immediately before and 5 months after the toolkit was implemented. Participation was voluntary and anonymous. Also, prescriptions for stimulant and nonstimulant adult ADHD medications were tracked 6 months before and 6 months after the toolkit was introduced. RESULTS: The response rate was 77.4% (n=24) at baseline and 64.5% (n=20) at follow-up. At follow-up compared to baseline, participants reported significantly higher comfort for assessment of adult ADHD (P=.039). Participants also reported higher comfort for nonmedication management (P=.10). There was no difference for comfort with medication management or prescribing practices pre versus post toolkit rollout, although participants were more comfortable with and prescribed a greater number of stimulants than nonstimulants. CONCLUSIONS: Given the complexities of addressing adult ADHD, the results of this study are encouraging. Our findings highlight ways primary care providers can be supported, as well as areas that require greater attention. Still, more research is needed with a larger sample size to further explore and validate the efficacy of the toolkit.

A dyadic perspective on assessment in Alzheimer's dementia: Supporting both care partners across the disease continuum.

Written from a dyadic strength-based perspective, this article first provides a brief overview of the Education, Information, and Support section of the 2018 Alzheimer's Disease Dementia Care Practice Recommendations.1 Subsequent sections present a comprehensive overview of available valid and reliable psychosocial measures that assess a selection of important domains for dementia care planning that can be used by families from early stage until end-of-life. Measures selected for the purposes of this article will focus on concepts that are strength-based and most relevant to care dyads as they navigate the difficult disease trajectory: readiness, knowledge, coping, dyadic relationship, care values and preferences. We will also highlight measures that have traditionally targeted the family care partner but can potentially be considered for use with the care partner with dementia, with adjustments, beyond the early stages. Part of this discussion will include various strategies for including persons with dementia in all aspects of their own care using a strength-based perspective, potentially enabling them to answer questions more reliably across disease stages. Last, gaps in existing measures will be identified to provide options to better assess areas of need most meaningful to families, and in ways that positively contribute to the successful aging of those living with dementia and their care partners.

Impact of Anticipated Bias from Healthcare Professionals on Perceived Successful Aging Among Transgender and Gender Nonconforming Older Adults.

PURPOSE: Transgender and gender nonconforming (TGNC) persons have routinely experienced high rates of violence and discrimination. Discrimination in healthcare can affect the ability of TGNC persons to age successfully as it often deters them from seeking care. The purpose of this study was to determine if anticipation of bias from healthcare professionals, as well as other variables, predicted perceived successful aging in a sample of TGNC adults. METHODS: A total of 384 (of the original 1963) participants older than 50 years completed the relevant parts of an 83-item online survey as part of the Trans MetLife Survey on Later-Life Preparedness and Perceptions in Transgender-Identified Individuals. RESULTS: Larger social support networks and higher levels of confidence that a healthcare professional will treat them with dignity and respect as a TGNC person at the end of their life were associated with increased odds of perceiving that they were aging successfully. CONCLUSION: With high rates of discrimination and prejudice toward TGNC persons in various contexts (e.g., healthcare, education, and housing), it is imperative that practitioners, researchers, policymakers, and institutions work together to eradicate healthcare disparities, promote social change, and support an environment that encourages successful aging. This calls for a coordinated, proactive outreach effort to put trust back into a system that has historically let down an entire subset of the population.

Examining the relationship between home literacy environment and neural correlates of phonological processing in beginning readers with and without a familial risk for dyslexia: an fMRI study.

Developmental dyslexia is a language-based learning disability characterized by persistent difficulty in learning to read. While an understanding of genetic contributions is emerging, the ways the environment affects brain functioning in children with developmental dyslexia are poorly understood. A relationship between the home literacy environment (HLE) and neural correlates of reading has been identified in typically developing children, yet it remains unclear whether similar effects are observable in children with a genetic predisposition for dyslexia. Understanding environmental contributions is important given that we do not understand why some genetically at-risk children do not develop dyslexia. Here, we investigate for the first time the relationship between HLE and the neural correlates of phonological processing in beginning readers with (FHD+, n = 29) and without (FHD-, n = 21) a family history of developmental dyslexia. We further controlled for socioeconomic status to isolate the neurobiological mechanism by which HLE affects reading development. Group differences revealed stronger correlation of HLE with brain activation in the left inferior/middle frontal and right fusiform gyri in FHD- compared to FHD+ children, suggesting greater impact of HLE on manipulation of phonological codes and recruitment of orthographic representations in typically developing children. In contrast, activation in the right precentral gyrus showed a significantly stronger correlation with HLE in FHD+ compared to FHD- children, suggesting emerging compensatory networks in genetically at-risk children. Overall, our results suggest that genetic predisposition for dyslexia alters contributions of HLE to early reading skills before formal reading instruction, which has important implications for educational practice and intervention models.

RNase P protein subunit Rpp29 represses histone H3.3 nucleosome deposition.

In mammals, histone H3.3 is a critical regulator of transcription state change and heritability at both euchromatin and heterochromatin. The H3.3-specific chaperone, DAXX, together with the chromatin-remodeling factor, ATRX, regulates H3.3 deposition and transcriptional silencing at repetitive DNA, including pericentromeres and telomeres. However, the events that precede H3.3 nucleosome incorporation have not been fully elucidated. We previously showed that the DAXX-ATRX-H3.3 pathway regulates a multi-copy array of an inducible transgene that can be visualized in single living cells. When this pathway is impaired, the array can be robustly activated. H3.3 is strongly recruited to the site during activation where it accumulates in a complex with transcribed sense and antisense RNA, which is distinct from the DNA/chromatin. This suggests that transcriptional events regulate H3.3 recruited to its incorporation sites. Here we report that the nucleolar RNA proteins Rpp29, fibrillarin, and RPL23a are also components of this H3.3/RNA complex. Rpp29 is a protein subunit of RNase P. Of the other subunits, POP1 and Rpp21 are similarly recruited suggesting that a variant of RNase P regulates H3.3 chromatin assembly. Rpp29 knockdown increases H3.3 chromatin incorporation, which suggests that Rpp29 represses H3.3 nucleosome deposition, a finding with implications for epigenetic regulation.

'I wish they would remember that I forget:' The effects of memory loss on the lives of individuals with mild-to-moderate dementia.

PURPOSE OF STUDY: Due to changing cognitive and functional capabilities, individuals with dementia face challenging care-related issues such as feelings of embarrassment, relationship strain, and symptoms of depression and anxiety. Limited research exists examining individuals with dementia's perceptions and concerns about these issues and how their perspectives can impact the quality and process of their illness experience. DESIGN AND METHODS: As part of a larger study, individuals with dementia (n = 114) answered five open-ended questions about their illness experience including: (1) daily routine, (2) concerns about memory loss, (3) relationships with others, (4) fears, and (5) what they wish others understood/knew. For each question, individuals with dementia's responses were analyzed for common themes within and across questions. RESULTS: Individuals with dementia commented on a wide range of issues involving their memory loss, including negative emotional impacts, future concerns and illness progression, forgetting, loss of independence, and the negative and positive influences on interpersonal relationships. Across questions, many individuals also stated that their memory loss did not significantly impact their lives. IMPLICATIONS: Discussion highlights how these findings can be used to expand our understanding of individuals with dementia's illness experience and to develop efficacious interventions for addressing negative aspects of living with memory loss while supporting positive aspects.

Measuring cultural justifications for caregiving in African American and White caregivers.

OBJECTIVES: This report will elucidate the psychometric properties of the Cultural Justifications for Caregiving Scale (CJCS) and evaluate the differences in cultural values and demographic variables among a group of African American and White caregivers. The CJCS measures the cultural reasons for and expectations about providing care to an older relative. METHODS: CJCS data were collected from 202 adults caring for an older relative with memory loss. The factor structure of the CJCS was analyzed for reliability and its correlation with other measures pertaining to the caregiving experience. RESULTS: Exploratory factor analyses suggested two underlying factors relating to Duty and Reciprocity with high levels of reliability. The two factors showed different correlational patterns with other measures associated with the caregiving experience (CG demographics and well-being). DISCUSSION: Findings provide further evidence that the CJCS is a reliable measure for use with African American and White caregivers. Moreover, cultural motivations to provide care may differ for ethnically diverse CGs based on religious backgrounds and beliefs about family expectations surrounding the care of loved ones. The application of the CJCS is also discussed.

Trajectories of social support and well-being across the first two years of widowhood.

The death of a spouse can be one of the most challenging events an older adult can face, yet many exhibit resilience. The present study examined the trajectories of structural and functional social support components, depression, and life satisfaction across the first two years of widowhood. The majority of structural and functional support trajectories exhibited stability across the first two years postloss. However, emotional support and support provided by family members did display a slight decline across time. Depression showed a linear pattern across time (e.g., decline in depressive symptomology) and life satisfaction demonstrated evidence of a one-year anniversary effect.

Single cell analysis of RNA-mediated histone H3.3 recruitment to a cytomegalovirus promoter-regulated transcription site.

Unlike the core histones, which are incorporated into nucleosomes concomitant with DNA replication, histone H3.3 is synthesized throughout the cell cycle and utilized for replication-independent (RI) chromatin assembly. The RI incorporation of H3.3 into nucleosomes is highly conserved and occurs at both euchromatin and heterochromatin. However, neither the mechanism of H3.3 recruitment nor its essential function is well understood. Several different chaperones regulate H3.3 assembly at distinct sites. The H3.3 chaperone, Daxx, and the chromatin-remodeling factor, ATRX, are required for H3.3 incorporation and heterochromatic silencing at telomeres, pericentromeres, and the cytomegalovirus (CMV) promoter. By evaluating H3.3 dynamics at a CMV promoter-regulated transcription site in a genetic background in which RI chromatin assembly is blocked, we have been able to decipher the regulatory events upstream of RI nucleosomal deposition. We find that at the activated transcription site, H3.3 accumulates with sense and antisense RNA, suggesting that it is recruited through an RNA-mediated mechanism. Sense and antisense transcription also increases after H3.3 knockdown, suggesting that the RNA signal is amplified when chromatin assembly is blocked and attenuated by nucleosomal deposition. Additionally, we find that H3.3 is still recruited after Daxx knockdown, supporting a chaperone-independent recruitment mechanism. Sequences in the H3.3 N-terminal tail and αN helix mediate both its recruitment to RNA at the activated transcription site and its interaction with double-stranded RNA in vitro. Interestingly, the H3.3 gain-of-function pediatric glioblastoma mutations, G34R and K27M, differentially affect H3.3 affinity in these assays, suggesting that disruption of an RNA-mediated regulatory event could drive malignant transformation.

Predictors of self-reported psychosocial outcomes in individuals with dementia.

PURPOSE: Little is known about the illness experience from the perspective of individuals with dementia (IWDs), as most quantitative research has focused on IWDs' psychosocial issues from proxy reports. The primary aim of this study was to better understand the impact of the illness experience on well-being from the perspective of the IWD through the framework of the Stress Process Model for Individuals with Dementia (SPM for IWDs). DESIGN AND METHODS: Guided by the SPM for IWDs, self-report data were collected from IWDs (N = 131) about their illness experience, including primary objective and subjective stressors, secondary role and intrapsychic strains, and well-being outcomes. Using multiple linear regression, primary stressors, secondary strains, and background and context characteristics were entered into 3 prediction models for each outcome: anxiety, depression, and quality of life (QoL). RESULTS: Three distinct prediction patterns emerged for each of the outcome measures. Embarrassment about memory loss was the unique predictor of anxiety, whereas physical health strain and role captivity uniquely predicted depression. Unique predictors for QoL included lower perceived instrumental activities of daily living (IADL) difficulty and higher self-efficacy. IMPLICATIONS: This study provided valuable insight into the illness experience from the perspective of the IWD and identified key areas amenable to interventions, such as managing embarrassment about memory problems as well as improving self-efficacy and inner strength. Moreover, this study provided additional support for the inclusion of IWDs in the research process and highlighted the need for further research regarding clinical application of findings, testing of hypotheses, and analyzing efficacy of interventions.

Including individuals with memory impairment in the research process: the importance of scales and response categories used in surveys.

Several ethical considerations emerge when conducting research with memory-impaired individuals, including the individuals' ability to comprehend and accurately respond to survey questions. However, little empirical research exists on how to format surveys to decrease cognitive demands, thereby allowing researchers to more accurately survey this population. The current study presents data from structured interviews with 125 community-residing, memory-impaired older adults about their illness experience. The interview contained 14 scales varying in subjectivity, directionality, and response choice content. While objectivity did not affect participants' ability to use the full range of responses, participants with greater cognitive impairment tended to use simpler, dichotomous response categories, especially when questions had bidirectional response choices. Results suggest that memory-impaired individuals can participate in survey research, that such surveys should contain unidirectional frequency/amount items when possible, and that not all memory-impaired individuals will have difficulty completing surveys.

Reduced exposure using asymmetric cone beam processing for wide area detector cardiac CT.

The purpose of this study was to estimate dose reduction after implementation of asymmetrical cone beam processing using exposure differences measured in a water phantom and a small cohort of clinical coronary CTA patients. Two separate 320 × 0.5 mm detector row scans of a water phantom used identical cardiac acquisition parameters before and after software modifications from symmetric to asymmetric cone beam acquisition and processing. Exposure was measured at the phantom surface with Optically Stimulated Luminescence (OSL) dosimeters at 12 equally spaced angular locations. Mean HU and standard deviation (SD) for both approaches were compared using ROI measurements obtained at the center plus four peripheral locations in the water phantom. To assess image quality, mean HU and standard deviation (SD) for both approaches were compared using ROI measurements obtained at five points within the water phantom. Retrospective evaluation of 64 patients (37 symmetric; 27 asymmetric acquisition) included clinical data, scanning parameters, quantitative plus qualitative image assessment, and estimated radiation dose. In the water phantom, the asymmetric cone beam processing reduces exposure by approximately 20% with no change in image quality. The clinical coronary CTA patient groups had comparable demographics. The estimated dose reduction after implementation of the asymmetric approach was roughly 24% with no significant difference between the symmetric and asymmetric approach with respect to objective measures of image quality or subjective assessment using a four point scale. When compared to a symmetric approach, the decreased exposure, subsequent lower patient radiation dose, and similar image quality from asymmetric cone beam processing supports its routine clinical use.

Noninvasive vascular images for face transplant surgical planning.

OBJECTIVE: Face transplantation replaces substantial defects with anatomically identical donor tissues; preoperative vascular assessment relies on noninvasive imaging to separate and characterize the external carotid vessels and branches. The objective is to describe and illustrate vascular considerations for face transplantation candidates. METHODS: Novel noninvasive imaging using computed tomography and magnetic resonance imaging over 3 spatial dimensions plus time was developed and tested in 4 face transplant candidates. Precontrast images assessed bones and underlying metal. Contrast media was used to delineate and separate arteries from veins. For computed tomography, acquisition over multiple time points enabled the computation of tissue perfusion metrics. Time-resolved magnetic resonance angiography was performed to separate arterial and venous phases. RESULTS: The range of circulation times for the external carotid system was 6 to 14 seconds from arterial blush to loss of venous enhancement. Precontrast imaging provided a roadmap of bones and metal. Among the 4 patients, 3 had surgical clips, metal implants, or both within 1 cm of major vessels considered for surgery. Contrast-enhanced wide area detector computed tomographic data acquired in the axial mode separated these structures and provided arterial and venous images for planning the surgical anastomoses. Magnetic resonance imaging was able to distinguish between the large vessels from the external carotid systems. CONCLUSIONS: Vascular imaging maps are challenging in face transplantation because of the rapid circulation times and artifact from the initial injury, prior reconstructive attempts, or both. Nevertheless, face transplant candidates require high spatial and temporal resolution vascular imaging to determine those vessels appropriate for surgical anastomoses.

Preoperative vascular mapping for facial allotransplantation: four-dimensional computed tomographic angiography versus magnetic resonance angiography.

BACKGROUND: Facial allotransplantation requires a detailed arterial and venous assessment for surgical planning. Target vessels are often depleted by multiple reconstructive attempts or the severe facial injury itself. The purpose of this study was to retrospectively compare the diagnostic performance of computed tomography and magnetic resonance angiography in the preoperative assessment. METHODS: Four-dimensional (three spatial planes plus time) computed tomographic and magnetic resonance images including 126 potential vessels (76 arteries and 50 veins) from five candidates were analyzed independently by two radiologists using a four-point image quality scale. Computed tomographic versus magnetic resonance image quality was compared directly, using a computed tomographic angiography consensus read as reference standard. Vessels with metal artifact on magnetic resonance imaging, computed tomography, or both underwent separate analyses to determine the impact of metal implants on image quality. RESULTS: Considering all 126 vessels, the mean computed tomographic image quality was superior to that of magnetic resonance angiography. When considering individual vessels, all except for major neck vessels were better visualized by computed tomography. Images of 26 vessels were degraded by metal artifact; magnetic resonance image quality was inferior for those vessels. Considering images of major vessels with no metal artifact, there was no significant mean image quality difference between computed tomography and magnetic resonance imaging. CONCLUSIONS: Computed tomographic angiography should be used as the first-choice modality for preoperative imaging of facial transplant patients because, when compared with magnetic resonance imaging, the visualization of small vessels is far superior and images have fewer artifacts. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

Surgical planning for composite tissue allotransplantation of the face using 320-detector row computed tomography.

We report initial surgical planning computed tomographic protocols for composite tissue allotransplantation of the face. This complex procedure replaces missing facial structures with anatomically identical tissues, restoring form and function. Achieved results are superior to those accomplished with conventional techniques. As a growing number of patients/recipients have undergone multiple reconstructions, vascular imaging plays an increasingly critical role in surgical planning and successful execution of the operation.

Single cell analysis of transcriptional activation dynamics.

BACKGROUND: Gene activation is thought to occur through a series of temporally defined regulatory steps. However, this process has not been completely evaluated in single living mammalian cells. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the timing and coordination of gene activation events, we tracked the recruitment of GCN5 (histone acetyltransferase), RNA polymerase II, Brd2 and Brd4 (acetyl-lysine binding proteins), in relation to a VP16-transcriptional activator, to a transcription site that can be visualized in single living cells. All accumulated rapidly with the VP16 activator as did the transcribed RNA. RNA was also detected at significantly more transcription sites in cells expressing the VP16-activator compared to a p53-activator. After alpha-amanitin pre-treatment, the VP16-activator, GCN5, and Brd2 are still recruited to the transcription site but the chromatin does not decondense. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that a strong activator can rapidly overcome the condensed chromatin structure of an inactive transcription site and supercede the expected requirement for regulatory events to proceed in a temporally defined order. Additionally, activator strength determines the number of cells in which transcription is induced as well as the extent of chromatin decondensation. As chromatin decondensation is significantly reduced after alpha-amanitin pre-treatment, despite the recruitment of transcriptional activation factors, this provides further evidence that transcription drives large-scale chromatin decondensation.

Imaging features of intramural hematoma of the aorta.

Intramural hematoma (IMH) is defined as localized hemorrhage within the aortic wall and is included in the acute aortic syndrome spectrum with aortic dissection and penetrating aortic ulcer. The mortality from IMH is similar to classic aortic dissection (21%). 16% of patients with IMH will evolve to classic aortic dissection over time. Despite this confusion exists regarding the precise definitions and radiologic features of IMH versus penetrating ulcers with mural thrombus and overt aortic dissection.

PDI improves secretion of redox-inactive beta-glucosidase.

Although manipulation of the endoplasmic reticulum (ER) folding environment in the yeast Saccharomyces cerevisiae has been shown to increase the secretory productivity of recombinant proteins, the cellular interactions and processes of native enzymes and chaperones such as protein disulfide isomerase (PDI) are still unclear. Previously, we reported that overexpression of the ER chaperone PDI enabled up to a 3-fold increase in secretion levels of the Pyrococcus furiosus beta-glucosidase in the yeast S. cerevisiae. This result was surprising since beta-glucosidase contains only one cysteine per monomer and no disulfide bonds. Two possible mechanisms were proposed: PDI either forms a transient disulfide bond with the lone cysteine residue of the nascent beta-glucosidase during the folding and assembly process or acts as a chaperone to aid in proper folding. To discern between the two mechanisms, the single cysteine residue was mutated to serine, and the secretion of the two protein variants was determined. The serine mutant still showed increased secretion in vivo when PDI levels were elevated. When the folding bottleneck is removed by increasing expression temperatures to 37 degrees C rather than 30 degrees C, PDI no longer has an improvement on secretion. These results suggest that, unexpectedly, PDI acts in a chaperone-like capacity or possibly cooperates with the cell's folding or degradation mechanisms regardless of whether the protein is redox-active.