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Transgender and gender diverse people report encountering binary language and assumptions in maternity and parenting spaces. Maternity health and educational spaces can operate on the assumption that parents identify as either men or women and that the birthing and feeding parent is a woman. Midwives are well placed to support feelings of safety and inclusion, however there is a recognised gap in knowledge and understanding around what gender inclusive language means and how to use it in conjunction with women-centred language. The NSW LGBTQIA+ Strategy states that using gender-inclusive language supports trust and safety for LGBTQIA+ people, and supports the co-design of resources with LGBTQI+ people and organisations. The poster demonstrates inclusive language and terminology used to describe bodies, gender and sexuality. The poster as a resource contributes to ongoing dialogue between midwives and can also be used in academic spaces by faculty and students. It complements other initiatives and strategies such as professional education modules offered by the ACM and includes details of relevant peer organisations and resources for those with further questions. This poster is informed by a range of resources including a review of current literature, the NSW LGBTIQ+ Health Strategy, and collaboration with Rainbow Families. The poster will be professionally designed and printed. A simple, easy to download reference guide developed by midwives for midwives, in consultation with community organisations who contribute their expertise. Something to put on your education noticeboard! This accessible poster meets the needs of midwives wanting to use gender inclusive language, supporting respectful conversations between midwifery colleagues and students, and contributing to best practice and better health outcomes for LGBTQIA+ individuals. [ABSTRACT FROM AUTHOR]

Circadian rhythms are critical for human health and are highly conserved across species. Disruptions in these rhythms contribute to many diseases, including psychiatric disorders. Previous results suggest that circadian genes modulate behavior through specific cell types in the nucleus accumbens (NAc), particularly dopamine D1-expressing medium spiny neurons (MSNs). However, diurnal rhythms in transcript expression have not been investigated in NAc MSNs. In this study we identified and characterized rhythmic transcripts in D1- and D2-expressing neurons and compared rhythmicity results to homogenate as well as astrocyte samples taken from the NAc of male and female mice. We find that all cell types have transcripts with diurnal rhythms and that top rhythmic transcripts are largely core clock genes, which peak at approximately the same time of day in each cell type and sex. While clock-controlled rhythmic transcripts are enriched for protein regulation pathways across cell type, cell signaling and signal transduction related processes are most commonly enriched in MSNs. In contrast to core clock genes, these clock-controlled rhythmic transcripts tend to reach their peak in expression about 2-h later in females than males, suggesting diurnal rhythms in reward may be delayed in females. We also find sex differences in pathway enrichment for rhythmic transcripts peaking at different times of day. Protein folding and immune responses are enriched in transcripts that peak in the dark phase, while metabolic processes are primarily enriched in transcripts that peak in the light phase. Importantly, we also find that several classic markers used to categorize MSNs are rhythmic in the NAc. This is critical since the use of rhythmic markers could lead to over- or under-enrichment of targeted cell types depending on the time at which they are sampled. This study greatly expands our knowledge of how individual cell types contribute to rhythms in the NAc., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Alterations in multiple subregions of the human prefrontal cortex (PFC) have been heavily implicated in psychiatric diseases. Moreover, emerging evidence suggests that circadian rhythms in gene expression are present across the brain, including in the PFC, and that these rhythms are altered in disease. However, investigation into the potential circadian mechanisms underlying these diseases in animal models must contend with the fact that the human PFC is highly evolved and specialized relative to that of rodents. Here, we use RNA sequencing to lay the groundwork for translational studies of molecular rhythms through a sex-specific, cross species comparison of transcriptomic rhythms between the mouse medial PFC (mPFC) and two subregions of the human PFC, the anterior cingulate cortex (ACC) and the dorsolateral PFC (DLPFC). We find that while circadian rhythm signaling is conserved across species and subregions, there is a phase shift in the expression of core clock genes between the mouse mPFC and human PFC subregions that differs by sex. Furthermore, we find that the identity of rhythmic transcripts is largely unique between the mouse mPFC and human PFC subregions, with the most overlap (20%, 236 transcripts) between the mouse mPFC and the human ACC in females. Nevertheless, we find that basic biological processes are enriched for rhythmic transcripts across species, with key differences between regions and sexes. Together, this work highlights both the evolutionary conservation of transcriptomic rhythms and the advancement of the human PFC, underscoring the importance of considering cross-species differences when using animal models., Competing Interests: Competing interesting The authors have nothing to disclose.

Previous studies have shown that there are rhythms in gene expression in the mouse prefrontal cortex (PFC); however, the contribution of different cell types and potential variation by sex has not yet been determined. Of particular interest are excitatory pyramidal cells and inhibitory parvalbumin (PV) interneurons, as interactions between these cell types are essential for regulating the excitation/inhibition balance and controlling many of the cognitive functions regulated by the PFC. In this study, we identify cell-type specific rhythms in the translatome of PV and pyramidal cells in the mouse PFC and assess diurnal rhythms in PV cell electrophysiological properties. We find that while core molecular clock genes are conserved and synchronized between cell types, pyramidal cells have nearly twice as many rhythmic transcripts as PV cells (35% vs. 18%). Rhythmic transcripts in pyramidal cells also show a high degree of overlap between sexes, both in terms of which transcripts are rhythmic and in the biological processes associated with them. Conversely, in PV cells, rhythmic transcripts from males and females are largely distinct. Moreover, we find sex-specific effects of phase on action potential properties in PV cells that are eliminated by environmental circadian disruption. Together, this study demonstrates that rhythms in gene expression and electrophysiological properties in the mouse PFC vary by both cell type and sex. Moreover, the biological processes associated with these rhythmic transcripts may provide insight into the unique functions of rhythms in these cells, as well as their selective vulnerabilities to circadian disruption., Competing Interests: The authors declare no competing financial interests.

Context: Contributing to the evidence base, by disseminating findings through written products such as journal articles, is a core competency for public health practitioners. Disseminating practice-based evidence that supports improving cardiovascular health is necessary for filling literature gaps, generating health policies and laws, and translating evidence-based strategies into practice. However, a gap exists in the dissemination of practice-based evidence in public health. Public health practitioners face various dissemination barriers (eg, lack of time and resources, staff turnover) which, more recently, were compounded by the COVID-19 pandemic., Program: The Centers for Disease Control and Prevention's Division for Heart Disease and Stroke Prevention (DHDSP) partnered with the National Network of Public Health Institutes to implement a multimodal approach to build writing capacity among recipients funded by three DHDSP cooperative agreements. This project aimed to enhance public health practitioners' capacity to translate and disseminate their evaluation findings., Implementation: Internal evaluation technical assistance expertise and external subject matter experts helped to implement this project and to develop tailored multimodal capacity-building activities. These activities included online peer-to-peer discussion posts, virtual writing workshops, resource documents, one-to-one writing coaching sessions, an online toolkit, and a supplemental issue in a peer-reviewed journal., Evaluation: Findings from an informal process evaluation demonstrate positive results. Most participants were engaged and satisfied with the project's activities. Across eight workshops, participants reported increased knowledge (≥94%) and enhanced confidence in writing (≥98%). The majority of participants (83%) reported that disseminating evaluation findings improved program implementation. Notably, 30 abstracts were submitted for a journal supplement and 23 articles were submitted for consideration., Discussion: This multimodal approach serves as a promising model that enhances public health practitioners' capacity to disseminate evaluation findings during times of evolving health needs., Competing Interests: The authors declare no potential conflicts of interests with respect to the authorship and/or publication of this article. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

The human striatum can be subdivided into the caudate, putamen, and nucleus accumbens (NAc). In mice, this roughly corresponds to the dorsal medial striatum (DMS), dorsal lateral striatum (DLS), and ventral striatum (NAc). Each of these structures have some overlapping and distinct functions related to motor control, cognitive processing, motivation, and reward. Previously, we used a "time-of-death" approach to identify diurnal rhythms in RNA transcripts in these three human striatal subregions. Here, we identify molecular rhythms across similar striatal subregions collected from C57BL/6J mice across 6 times of day and compare results to the human striatum. Pathway analysis indicates a large degree of overlap between species in rhythmic transcripts involved in processes like cellular stress, energy metabolism, and translation. Notably, a striking finding in humans is that small nucleolar RNAs (snoRNAs) and long non-coding RNAs (lncRNAs) are among the most highly rhythmic transcripts in the NAc and this is not conserved in mice, suggesting the rhythmicity of RNA processing in this region could be uniquely human. Furthermore, the peak timing of overlapping rhythmic genes is altered between species, but not consistently in one direction. Taken together, these studies reveal conserved as well as distinct transcriptome rhythms across the human and mouse striatum and are an important step in understanding the normal function of diurnal rhythms in humans and model organisms in these regions and how disruption could lead to pathology., (© 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Background: The Patient Cloud ePRO app was adopted by the National Cancer Institute National Clinical Trials Network (NCTN) to facilitate capturing electronic patient-reported (ePRO) outcome data, but use has been low. The study objectives were to test whether a patient-targeted ePRO educational resource (ePRO-E) would increase ePRO intent (number of users) and improve data quality (high quality: ≥80% of the required surveys submitted) within an ongoing NCTN study., Methods: The ePRO-E intervention, a patient-targeted educational resource (written material and 6-minute animated YouTube video), was designed to address ePRO barriers. ePRO intent and data quality were compared between 2 groups (N = 69): a historical control group and a prospectively recruited intervention group exposed to ePRO-E. Covariates included technology attitudes, age, sex, education, socioeconomic status, and comorbidity., Results: Intervention group ePRO intent (78.8%) was statistically significantly higher than historical control group intent (47.1%) (P = .03). Patients choosing ePRO versus paper surveys had more positive and higher technology attitudes scores (P = .03). The odds of choosing ePRO were 4.7 times higher (95% Confidence Interval [CI] = 1.2 to 17.8) (P = .02) among intervention group patients and 5.2 times higher (95% CI = 1.3 to 21.6) (P = .02) among patients with high technology attitudes scores, after controlling for covariates. However, the 80% submission rate (percentage submitting ≥80% of required surveys) in the ePRO group (30.6%) was statistically significantly lower than in the paper group (57.9%) (P = .05)., Conclusions: ePRO-E exposure increased ePRO intent. High technology attitudes scores were associated with ePRO selection. Since the ePRO survey submission rate was low, additional strategies are needed to promote high-quality data submission., (© The Author(s) 2024. Published by Oxford University Press.)

Clinically normal females exhibit higher 18 F-flortaucipir (FTP)-PET signal than males across the cortex. However, these sex differences may be explained by neuroimaging idiosyncrasies such as off-target extracerebral tracer retention or partial volume effects (PVEs). 343 clinically normal participants (female = 58%; mean[SD]=73.8[8.5] years) and 55 patients with mild cognitive impairment (female = 38%; mean[SD] = 76.9[7.3] years) underwent cross-sectional FTP-PET. We parcellated extracerebral FreeSurfer areas based on proximity to cortical ROIs. Sex differences in cortical tau were then estimated after accounting for local extracerebral retention. We simulated PVE by convolving group-level standardized uptake value ratio means in each ROI with 6 mm Gaussian kernels and compared the sexes across ROIs post-smoothing. Widespread sex differences in extracerebral retention were observed. Although attenuating sex differences in cortical tau-PET signal, covarying for extracerebral retention did not impact the largest sex differences in tau-PET signal. Differences in PVE were observed in both female and male directions with no clear sex-specific bias. Our findings suggest that sex differences in FTP are not solely attributed to off-target extracerebral retention or PVE, consistent with the notion that sex differences in medial temporal and neocortical tau are biologically driven. Future work should investigate sex differences in regional cerebral blood flow kinetics and longitudinal tau-PET., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Associations of plasma total tau levels with future risk of AD have been described., Objective: To examine the extent to which plasma tau reflects underlying AD brain pathology in cognitively healthy individuals., Methods: We examined cross-sectional associations of plasma total tau with 11C-Pittsburgh Compound-B (PiB)-PET and 18F-Flortaucipir (FTP)-PET in middle-aged participants at the community-based Framingham Heart Study., Results: Our final sample included 425 participants (mean age 57.6± 9.9, 50% F). Plasma total tau levels were positively associated with amyloid-β deposition in the precuneus region (β±SE, 0.11±0.05; p = 0.025). A positive association between plasma total tau and tau PET in the rhinal cortex was suggested in participants with higher amyloid-PET burden and in APOEɛ4 carriers., Conclusions: Our study highlights that plasma total tau is a marker of amyloid deposition as early as in middle-age.

This review focuses on recent advances made towards understanding the neurobiology of bipolar disorder (BD), a chronic neuropsychiatric illness characterized by altered mood and energy states. The past few years have seen the completion of the largest genetic studies by far, which have emphasized the polygenic nature of BD as well as it's connection to other psychiatric illnesses. Furthermore, the use of inducible pluripotent stem cells has rapidly expanded. These studies support previous work that implicates dysregulation of neurodevelopment, mitochondria, and calcium homeostasis, while also allowing for investigation into the underlying mechanisms of individual responsivity to lithium. Sleep and circadian rhythms have also been heavily implicated in BD, from disruptions in activity patterns to molecular abnormalities., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Introduction: With the increasing use of the internet for health information, it is essential to prioritize resources that match the reading level of patients and parents. Limited health literacy is a notable issue in the United States, creating a financial burden and negatively affecting patient outcomes. This study aimed to assess the availability and readability of pediatric hospital web pages concerning two prevalent spine conditions in children, spondylolisthesis and spondylolysis, specifically examining whether the available resources meet the recommended sixth grade reading level., Methods: A total of 179 pediatric hospital web pages were assessed for their availability and readability of spondylolisthesis and spondylolysis patient information. The web pages' readability was assessed using five readability formulae. Descriptive statistics and Student t-tests were performed on the collected scores with significance set at P < 0.05., Results: Among the analyzed hospitals, 40.2% had no information on spondylolisthesis or spondylolysis, 20.1% mentioned treating these conditions, 7.8% had < 100 dedicated words, and only 31.8% had dedicated web pages with more than 100 words on these conditions. The average reading grade level for the evaluated web pages was 12.0, indicating a high school education level is required for comprehension. None of the web pages were written below the recommended sixth grade reading level., Discussion: The readability of the limited resources was markedly higher than the recommended reading level. In addition, this study emphasizes the need for enhanced accessibility and readability of online patient information from pediatric hospitals to improve parental comprehension and informed decision-making. Physicians should consider identifying online resources that they consider of high quality and acceptable readability to support better patient understanding and outcomes., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Background: Preclinical studies highlight the importance of endogenous cannabinoids (endocannabinoids; eCBs) in neurodegeneration. Yet, prior observational studies focused on limited outcome measures and assessed only few eCB compounds while largely ignoring the complexity of the eCB system. We examined the associations of multiple circulating eCBs and eCB-like molecules with early markers of neurodegeneration and neuro-injury and tested for effect modification by sex., Methods: This exploratory cross-sectional study included a random sample of 237 dementia-free older participants from the Framingham Heart Study Offspring cohort who attended examination cycle 9 (2011-2014), were 65 years or older, and cognitively healthy. Forty-four eCB compounds were quantified in serum, via liquid chromatography high-resolution mass spectrometry. Linear regression models were used to examine the associations of eCB levels with brain MRI measures (i.e., total cerebral brain volume, gray matter volume, hippocampal volume, and white matter hyperintensities volume) and blood biomarkers of Alzheimer's disease and neuro-injury (i.e., total tau, neurofilament light, glial fibrillary acidic protein and Ubiquitin C-terminal hydrolase L1). All models were adjusted for potential confounders and effect modification by sex was examined., Results: Participants mean age was 73.3 ± 6.2 years, and 40% were men. After adjustment for potential confounders and correction for multiple comparisons, no statistically significant associations were observed between eCB levels and the study outcomes. However, we identified multiple sex-specific associations between eCB levels and the various study outcomes. For example, high linoleoyl ethanolamide (LEA) levels were related to decreased hippocampal volume among men and to increased hippocampal volume among women (β ± SE =  - 0.12 ± 0.06, p = 0.034 and β ± SE = 0.08 ± 0.04, p = 0.026, respectively)., Conclusions: Circulating eCBs may play a role in neuro-injury and may explain sex differences in susceptibility to accelerated brain aging. Particularly, our results highlight the possible involvement of eCBs from the N-acyl amino acids and fatty acid ethanolamide classes and suggest specific novel fatty acid compounds that may be implicated in brain aging. Furthermore, investigation of the eCBs contribution to neurodegenerative disease such as Alzheimer's disease in humans is warranted, especially with prospective study designs and among diverse populations, including premenopausal women., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Population-based autopsy studies provide valuable insights into the causes of dementia but are limited by sample size and restriction to specific populations. Harmonisation across studies increases statistical power and allows meaningful comparisons between studies. We aimed to harmonise neuropathology measures across studies and assess the prevalence, correlation, and co-occurrence of neuropathologies in the ageing population., Methods: We combined data from six community-based autopsy cohorts in the US and the UK in a coordinated cross-sectional analysis. Among all decedents aged 80 years or older, we assessed 12 neuropathologies known to be associated with dementia: arteriolosclerosis, atherosclerosis, macroinfarcts, microinfarcts, lacunes, cerebral amyloid angiopathy, Braak neurofibrillary tangle stage, Consortium to Establish a Registry for Alzheimer's disease (CERAD) diffuse plaque score, CERAD neuritic plaque score, hippocampal sclerosis, limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and Lewy body pathology. We divided measures into three groups describing level of confidence (low, moderate, and high) in harmonisation. We described the prevalence, correlations, and co-occurrence of neuropathologies., Findings: The cohorts included 4354 decedents aged 80 years or older with autopsy data. All cohorts included more women than men, with the exception of one study that only included men, and all cohorts included decedents at older ages (range of mean age at death across cohorts 88·0-91·6 years). Measures of Alzheimer's disease neuropathological change, Braak stage and CERAD scores, were in the high confidence category, whereas measures of vascular neuropathologies were in the low (arterioloscerosis, atherosclerosis, cerebral amyloid angiopathy, and lacunes) or moderate (macroinfarcts and microinfarcts) categories. Neuropathology prevalence and co-occurrence was high (2443 [91%] of 2695 participants had more than one of six key neuropathologies and 1106 [41%] of 2695 had three or more). Co-occurrence was strongly but not deterministically associated with dementia status. Vascular and Alzheimer's disease features clustered separately in correlation analyses, and LATE-NC had moderate associations with Alzheimer's disease measures (eg, Braak stage ρ=0·31 [95% CI 0·20-0·42])., Interpretation: Higher variability and more inconsistency in the measurement of vascular neuropathologies compared with the measurement of Alzheimer's disease neuropathological change suggests the development of new frameworks for the measurement of vascular neuropathologies might be helpful. Results highlight the complexity and multi-morbidity of the brain pathologies that underlie dementia in older adults and suggest that prevention efforts and treatments should be multifaceted., Funding: Gates Ventures., Competing Interests: Declaration of interests SS reports consulting fees from Biogen and Eisai. JS reports consulting fees from AVID, Alnylam Pharmaceuticals, and Cerveau Technologies. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Twelve-hour (12 h) ultradian rhythms are a well-known phenomenon in coastal marine organisms. While 12 h cycles are observed in human behavior and physiology, no study has measured 12 h rhythms in the human brain. Here, we identify 12 h rhythms in transcripts that either peak at sleep/wake transitions (approximately 9 AM/PM) or static times (approximately 3 PM/AM) in the dorsolateral prefrontal cortex, a region involved in cognition. Subjects with schizophrenia (SZ) lose 12 h rhythms in genes associated with the unfolded protein response and neuronal structural maintenance. Moreover, genes involved in mitochondrial function and protein translation, which normally peak at sleep/wake transitions, peak instead at static times in SZ, suggesting suboptimal timing of these essential processes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Scott et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Psychosis is a defining feature of schizophrenia and highly prevalent in bipolar disorder. Notably, individuals with these illnesses also have major disruptions in sleep and circadian rhythms, and disturbances of sleep and circadian rhythms can precipitate or exacerbate psychotic symptoms. Psychosis is associated with the striatum, though to our knowledge, no study to date has directly measured molecular rhythms and determined how they are altered in the striatum of subjects with psychosis., Methods: We performed RNA sequencing and both differential expression and rhythmicity analyses to investigate diurnal alterations in gene expression in human postmortem striatal subregions (nucleus accumbens, caudate, and putamen) in subjects with psychosis (n = 36) relative to unaffected comparison subjects (n = 36)., Results: Across regions, we found differential expression of immune-related transcripts and a substantial loss of rhythmicity in core circadian clock genes in subjects with psychosis. In the nucleus accumbens, mitochondrial-related transcripts had decreased expression in subjects with psychosis, but only in those who died at night. Additionally, we found a loss of rhythmicity in small nucleolar RNAs and a gain of rhythmicity in glutamatergic signaling in the nucleus accumbens of subjects with psychosis. Between-region comparisons indicated that rhythmicity in the caudate and putamen was far more similar in subjects with psychosis than in matched comparison subjects., Conclusions: Together, these findings reveal differential and rhythmic gene expression differences across the striatum that may contribute to striatal dysfunction and psychosis in psychotic disorders., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Summary: Circadian oscillations of gene expression regulate daily physiological processes, and their disruption is linked to many diseases. Circadian rhythms can be disrupted in a variety of ways, including differential phase, amplitude and rhythm fitness. Although many differential circadian biomarker detection methods have been proposed, a workflow for systematic detection of multifaceted differential circadian characteristics with accurate false positive control is not currently available. We propose a comprehensive and interactive pipeline to capture the multifaceted characteristics of differentially rhythmic biomarkers. Analysis outputs are accompanied by informative visualization and interactive exploration. The workflow is demonstrated in multiple case studies and is extensible to general omics applications., Availability and Implementation: R package, Shiny app and source code are available in GitHub (https://github.com/DiffCircaPipeline) and Zenodo (https://doi.org/10.5281/zenodo.7507989)., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2023. Published by Oxford University Press.)

Autosomal-dominant, Dutch-type cerebral amyloid angiopathy (D-CAA) offers a unique opportunity to develop biomarkers for pre-symptomatic cerebral amyloid angiopathy (CAA). We hypothesized that neuroimaging measures of white matter injury would be present and progressive in D-CAA prior to hemorrhagic lesions or symptomatic hemorrhage. In a longitudinal cohort of D-CAA carriers and non-carriers, we observed divergence of white matter injury measures between D-CAA carriers and non-carriers prior to the appearance of cerebral microbleeds and >14 years before the average age of first symptomatic hemorrhage. These results indicate that white matter disruption measures may be valuable cross-sectional and longitudinal biomarkers of D-CAA progression. ANN NEUROL 2022;92:358-363., (© 2022 American Neurological Association.)

Introduction: Physical activity (PA) promotes resilience with respect to cognitive decline, although the underlying mechanisms are not well understood. We examined the associations between objectively measured PA and resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) across seven anatomically distributed neural networks., Methods: rs-fcMRI, amyloid beta (Aβ) positron emission tomography (PET), PA (steps/day × 1 week), and longitudinal cognitive (Preclinical Alzheimer's Cognitive Composite) data from 167 cognitively unimpaired adults (ages 63 to 90) were used. We used linear and linear mixed-effects regression models to examine the associations between baseline PA and baseline network connectivity and between PA, network connectivity, and longitudinal cognitive performance., Results: Higher PA was associated selectively with greater connectivity in three networks previously associated with cognitive decline (default, salience, left control). This association with network connectivity accounted for a modest portion of PA's effects on Aβ-related cognitive decline., Discussion: Although other mechanisms are likely present, PA may promote resilience with respect to Aß-related cognitive decline, partly by increasing connectivity in a subset of cognitive networks., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

We propose a Dual-stream Pyramid Registration Network (referred as Dual-PRNet) for unsupervised 3D brain image registration. Unlike recent CNN-based registration approaches, such as VoxelMorph, which computes a registration field from a pair of 3D volumes using a single-stream network, we design a two-stream architecture able to estimate multi-level registration fields sequentially from a pair of feature pyramids. Our main contributions are: (i) we design a two-stream 3D encoder-decoder network that computes two convolutional feature pyramids separately from two input volumes; (ii) we propose sequential pyramid registration where a sequence of pyramid registration (PR) modules is designed to predict multi-level registration fields directly from the decoding feature pyramids. The registration fields are refined gradually in a coarse-to-fine manner via sequential warping, which equips the model with a strong capability for handling large deformations; (iii) the PR modules can be further enhanced by computing local 3D correlations between the feature pyramids, resulting in the improved Dual-PRNet ++ able to aggregate rich detailed anatomical structure of the brain; (iv) our Dual-PRNet ++ can be integrated into a 3D segmentation framework for joint registration and segmentation, by precisely warping voxel-level annotations. Our methods are evaluated on two standard benchmarks for brain MRI registration, where Dual-PRNet ++ outperforms the state-of-the-art approaches by a large margin, i.e., improving recent VoxelMorph from 0.511 to 0.748 (Dice score) on the Mindboggle101 dataset. In addition, we further demonstrate that our methods can greatly facilitate the segmentation task in a joint learning framework, by leveraging limited annotations., Competing Interests: Declaration of Competing Interest The authors have no affiliation with any organization with a direct or indirect financial interest in the subject matter discussed in the manuscript., (Copyright © 2022. Published by Elsevier B.V.)

Animal and human imaging research reported that the presence of cortical Alzheimer's Disease's (AD) neuropathology, beta-amyloid and neurofibrillary tau, is associated with altered neuronal activity and circuitry failure, together facilitating clinical progression. The locus coeruleus (LC), one of the initial subcortical regions harboring pretangle hyperphosphorylated tau, has widespread connections to the cortex modulating cognition. Here we investigate whether LC's in-vivo neuronal activity and functional connectivity (FC) are associated with cognitive decline in conjunction with beta-amyloid. We combined functional MRI of a novel versus repeated face-name paradigm, beta-amyloid-PET and longitudinal cognitive data of 128 cognitively unimpaired older individuals. We show that LC activity and LC-FC with amygdala and hippocampus was higher during novelty. We also demonstrated that lower novelty-related LC activity and LC-FC with hippocampus and parahippocampus were associated with steeper beta-amyloid-related cognitive decline. Our results demonstrate the potential of LC's functional properties as a gauge to identify individuals at-risk for AD-related cognitive decline., (© 2022. The Author(s).)