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The hippocampal complex is affected early in Alzheimer's disease (AD). Increasingly, altered functional connectivity of the hippocampus is recognized as an important feature of preclinical AD. Carriers of the APOEeɛ4 allele are at an increased risk for AD, which could lead to altered hippocampal connectivity even in healthy older adults. To test this hypothesis, we used a paired-associates memory task to examine differences in task-dependent functional connectivity of the anterior and posterior hippocampus in nondemented APOEeɛ4 carriers (n = 34, 18F) and noncarriers (n = 46, 31F). We examined anterior and posterior portions of the hippocampus separately to test the theory that APOEeɛ4-mediated differences would be more pronounced in the anterior region, which is affected earlier in the AD course. This study is the first to use a psychophysiological interaction approach to query the context-dependent connectivity of subregions of the hippocampus during a memory task in adults at increased genetic risk for AD. During encoding, APOEeɛ4 carriers had lower functional connectivity change compared to baseline between the anterior hippocampus and right precuneus, anterior insula and cingulate cortex. During retrieval, bilateral supramarginal gyrus and right precuneus showed lower functional connectivity change with anterior hippocampus in carriers. Also during retrieval, carriers showed lower connectivity change in the posterior hippocampus with auditory cortex. In each case, APOEeɛ4 carriers showed strong negative connectivity changes compared to noncarriers where positive connectivity change was measured. These differences may represent prodromal functional changes mediated in part by APOEeɛ4 and are consistent with the anterior-to-posterior theory of AD progression in the hippocampus. © 2015 Wiley Periodicals, Inc.

The early accumulation of AD pathology such as Aβ and tau in cognitively normal older people is predictive of cognitive decline, but it has been difficult to dissociate the cognitive effects of these two proteins. Early Aβ and tau target distinct brain regions that have different functional roles. Here, we assessed specific longitudinal pathology-cognition associations in seventy-six cognitively normal older adults from the Berkeley Aging Cohort Study who underwent longitudinal PiB PET, FTP PET, and cognitive assessments. Using linear mixed-effects models to estimate longitudinal changes and residual approach to characterizing cognitive domain-specific associations, we found that Aβ accumulation, especially in frontal/parietal regions, was associated with faster decline in executive function, not memory, whereas tau accumulation, especially in left entorhinal/parahippocampal regions, was associated with faster decline in memory, not executive function, supporting an "Aβ-executive function, tau-memory" double-dissociation in cognitively normal older people. These specific relationships between accumulating pathology and domain-specific cognitive decline may be due to the particular vulnerabilities of the frontal-parietal executive network to Aβ and temporal memory network to tau., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is evaluating lifestyle interventions in older adults at risk for cognitive decline and dementia. Here we characterize the baseline data set of the POINTER Imaging ancillary study., Methods: Participants underwent health and cognitive assessments and neuroimaging with multimodal positron emission tomography (PET) (beta-amyloid [Aβ] and tau) and magnetic resonance imaging (MRI). Framingham risk score (FRS) was used to quantify cardiovascular disease (CVD) risk., Results: A total of 1052 participants (31% from underrepresented ethnoracial groups) were enrolled. Compared to Aβ-, Aβ+ (29%) participants were older, had higher apolipoprotein E (APOE) ε4 carriage rate and white matter hyperintensity volume, and greater temporal tau. FRS was related to MRI measures, but not AD biomarkers. FRS and tau had independent effects on cognition., Discussion: In this heterogenous, at-risk cohort, CVD risk was related to more abnormal brain structure and poorer cognition, representing a putative non-AD (Alzheimer's disease) pathway to brain injury and cognitive decline., Highlights: ·The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) cohort is enriched for cardiovascular disease (CVD) and poor lifestyle ·POINTER Imaging collected multimodal neuroimaging data in this unique, at-risk cohort ·Amyloid burden was related to age, apolipoprotein E (APOE) ε4 carriage, and measures of disease progression ·Associations between amyloid and tau, and tau and cognition, were relatively weak ·CVD risk and tau pathology were independently related to memory., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Tau pathology spread into neocortex indicates a transition from healthy aging to Alzheimer's disease (AD). Connectivity between tau epicenters and later accumulating regions of cortex has been proposed as a mechanism of tau spread, but how this relationship changes with greater AD pathology burden or genotype is not understood. We investigated tau accumulation in two key regions, precuneus and inferior temporal cortex, using resting state functional connectivity (rsFC) and longitudinal PET imaging from a multicohort sample of cognitively unimpaired older adults. We examined how baseline tau PET, Aβ PET, and ApoE4 genotype status interact with rsFC between hippocampus and these downstream regions to predict rate of tau accumulation in neocortex. We found that the 3-way interaction between connectivity, baseline tau, and baseline Aβ or ApoE4 status was associated with neocortical tau accumulation in precuneus and inferior temporal cortex. In addition, baseline tau, Aβ, and ApoE4 status also moderated the association between connectivity and rate of memory decline. Together, these results suggest that the extent and distribution of future tau accumulation may be predicted by the interaction of baseline connectivity, AD pathology, and genetic risk., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Introduction: Factors responsible for the deposition of pathological tau in the brain are incompletely understood. This study links macroscale tau deposition in the human brain to cerebrospinal fluid (CSF) flow dynamics using resting-state functional magnetic resonance imaging (rsfMRI)., Methods: Low-frequency (< 0.1 Hz) resting-state global brain activity is coupled with CSF flow and potentially reflects CSF dynamics-related clearance. We examined the correlation between rsfMRI measures of CSF inflow and global activity (gBOLD-CSF coupling) as a predictor, interacting with amyloid beta (Aβ), of tau and cortical thickness (dependent variables) across Alzheimer's Disease Neuroimaging Initiative (ADNI) participants from cognitively unimpaired through mild cognitive impairment (MCI) and Alzheimer's disease (AD)., Results: Tau deposition in Aβ+ participants, accompanied by cortical thinning and cognitive decline, is associated with decreased gBOLD-CSF coupling. Tau mediates the relationship between coupling and thickness., Discussion: Findings suggest that resting-state global brain activity and CSF movements comodulate Alzheimer's tau deposition, presumably related to CSF clearance., Highlights: A non-invasive functional magnetic resonance imaging (fMRI) assessment of a CSF clearance-related process is carried out. Global brain activity is coupled with CSF inflow in human fMRI during resting state. Global fMRI-CSF coupling is correlated with tau in Alzheimer's disease (AD). This coupling measure is also associated with cortical thickness, mediated by tau., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objective: The objective of this study was to use body surface area (BSA) obtained via computed tomography (CT) to calculate a species-specific shape constant (K) and provide a formula for BSA based on body weight (BW) in Atlantic Stingrays Hypanus sabina. Ultimately, this information can be used to more accurately calculate chemotherapeutic doses and other metabolic-related measures., Methods: Six deceased Atlantic Stingrays of unknown age and with a range of sizes were collected during a natural mortality event and underwent CT scans. Following the scans, three-dimensional surface models were created from the imaging data to measure BSAs and derive a BSA formula based on BW. Nonlinear regression analysis of BSA versus thawed BW was performed, and a species-specific formula was derived., Result: Body surface area (mean ± standard deviation) was 2015.01 ± 1115.02 cm 2 (median = 1841.40 cm 2 ; range = 844.2-4043.12 cm 2 ). The calculated K-constant was 14.9 for the six Atlantic Stingrays, and the CT-derived BSA formula was as follows: BSA (cm 2 ) = 14.9 × (BW, g) 2/3 ., Conclusion: These results provide a method for calculating BSA in Atlantic Stingrays. The CT-derived BSA formula can be used for allometric dosing of chemotherapeutic agents and other drugs in a clinical setting; in a broader sense, the formula can be applied to studies of nutrition, metabolic rate, and physiology., (© 2024 The Author(s). Journal of Aquatic Animal Health published by Wiley Periodicals LLC on behalf of American Fisheries Society.)

Introduction: A key goal of the Alzheimer's Disease NeuroImaging Initiative (ADNI) positron emission tomography (PET) Core is to harmonize quantification of β-amyloid (Aβ) and tau PET image data across multiple scanners and tracers., Methods: We developed an analysis pipeline (Berkeley PET Imaging Pipeline, B-PIP) for ADNI Aβ and tau PET images and applied it to PET data from other multisite studies. Steps include image pre-processing, refacing, magnetic resonance imaging (MRI)/PET co-registration, visual quality control (QC), quantification of tracer uptake, and standardization of Aβ and tau standardized uptake value ratios (SUVrs) across tracers., Results: Measurements from 10,105 cross-sectional and longitudinal Aβ and tau PET scans acquired in several studies between 2010 and 2024 can be processed, harmonized, and directly merged across tracers and cohorts., Discussion: The B-PIP developed in ADNI is a scalable image harmonization approach used in several observational studies and clinical trials that facilitates rigorous Aβ and tau PET quantification and data sharing., Highlights: Quantitative results from ADNI Aβ and tau PET data are generated using a rigorous, scalable image processing pipeline This pipeline has been applied to PET data from several other large, multisite studies and trials Quantitative outcomes are harmonizable across studies and are shared with the scientific community., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Blood-brain barrier disruption (BBBd) occurs in aging, particularly in regions vulnerable to Alzheimer's disease (AD) pathology. However, its relationship to pathological protein accumulation, neurodegeneration, and cognitive impairment in normal aging is unclear. We used dynamic contrast-enhanced MRI (DCE-MRI) and positron emission tomography (PET) imaging in cognitively normal older adults to explore how BBBd correlates with brain atrophy and cognitive function, and whether these relationships are influenced by Aβ or tau. We found that greater BBBd in the hippocampus (HC) and an averaged BBBd-susceptible ROI were linked to worse episodic memory, with interactions between BBBd and atrophy influencing this relationship, independent of Aβ and tau. However, there were no significant relationships between BBBd and non-memory cognitive performance. In participants with longitudinal AD biomarker and cognitive data acquired prior to DCE-MRI, faster longitudinal entorhinal cortex (EC) tau accumulation and episodic memory decline were associated with greater HC BBBd, independent of global Aβ changes and regional atrophy. These findings enhance our understanding of the complex relationships between AD biomarkers, cognitive decline, and BBBd., Competing Interests: Conflicts of Interest Dr. Jagust has served as a consultant to Clario, Lilly and Eisai. Dr. Baker consults for Genentech. There are no other disclosures., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cancer is pervasive across multicellular species, but what explains the differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades of tetrapods (amphibians, sauropsids, and mammals), we found that neoplasia and malignancy prevalence increases with adult mass (contrary to Peto's paradox) and somatic mutation rate but decreases with gestation time. The relationship between adult mass and malignancy prevalence was only apparent when we controlled for gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%), the black-footed penguin (<0.4%), ferrets (63%), and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer. Significance: Evolution has discovered mechanisms for suppressing cancer in a wide variety of species. By analyzing veterinary necropsy records, we can identify species with exceptionally high or low cancer prevalence. Discovering the mechanisms of cancer susceptibility and resistance may help improve cancer prevention and explain cancer syndromes., (©2024 The Authors; Published by the American Association for Cancer Research.)

The last few years have seen a surge of interest from field ecologists and evolutionary biologists to study neoplasia and cancer in wildlife. This contributes to the One Health Approach, which investigates health issues at the intersection of people, wild and domestic animals, together with their changing environments. Nonetheless, the emerging field of wildlife cancer is currently constrained by methodological limitations in detecting cancer using non-invasive sampling. In addition, the suspected differential susceptibility and resistance of species to cancer often make the choice of a unique model species difficult for field biologists. Here, we provide an overview of the importance of pursuing the study of cancer in non-model organisms and we review the currently available methods to detect, measure and quantify cancer in the wild, as well as the methodological limitations to be overcome to develop novel approaches inspired by diagnostic techniques used in human medicine. The methodology we propose here will help understand and hopefully fight this major disease by generating general knowledge about cancer, variation in its rates, tumour-suppressor mechanisms across species as well as its link to life history and physiological characters. Moreover, this is expected to provide key information about cancer in wildlife, which is a top priority due to the accelerated anthropogenic change in the past decades that might favour cancer progression in wild populations., (© 2024 The Author(s). Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.)

The Alzheimer's Disease Neuroimaging Initiative (ADNI) PET Core has evolved over time, beginning with positron emission tomography (PET) imaging of a subsample of participants with [ 18 F]fluorodeoxyglucose (FDG)-PET, adding tracers for measurement of β-amyloid, followed by tau tracers. This review examines the evolution of the ADNI PET Core, the novel aspects of PET imaging in each stage of ADNI, and gives an accounting of PET images available in the ADNI database. The ADNI PET Core has been and continues to be a rich resource that provides quantitative PET data and preprocessed PET images to the scientific community, allowing interrogation of both basic and clinically relevant questions. By standardizing methods across different PET scanners and multiple PET tracers, the Core has demonstrated the feasibility of large-scale, multi-center PET studies. Data managed and disseminated by the PET Core has been critical to defining pathophysiological models of Alzheimer's disease (AD) and helped to drive methods used in modern therapeutic trials. HIGHLIGHTS: The ADNI PET Core began with FDG-PET and now includes three amyloid and three tau PET ligands. The PET Core has standardized acquisition and analysis of multitracer PET images. The ADNI PET Core helped to develop methods that have facilitated clinical trials in AD., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Photobiomodulation therapy, also termed as low-level laser therapy, is commonly used as an adjunctive therapy for various medical conditions in veterinary practice. The ACTIVet PRO low-level laser has been used for treatment of various nondomestic species, yet the effects of dermal attributes such as pigment, feathers, or scales have not been evaluated. The effects of low-level laser therapy with the ACTIVet PRO have been investigated in laboratory animals, including a study in rats that evaluated the passage of laser light through the skin in postmortem samples. The objective of this study was to measure the power of a low-level laser (ACTIVet PRO) after penetration through dermal tissue (∼1 mm thickness) in a variety of postmortem animal tissue. This study sought to determine the impact of fur, feathers, scales, and different pigments on the ability of the laser to penetrate. Frozen and thawed skin tissue samples from various species were placed inside a light restricted laser box and exposed to a preprogrammed laser level from a Multi Radiance ACTIVet PRO photobiomodulation (PBM) device, with a power meter to measure the light penetration through the tissue samples. Light penetration measurements via power output measurements (mW) were recorded at 7 time points (range, 1-150 sec). A Friedman test was performed to evaluate the difference of the mean tissue penetration by each species at each time point. Lighter colored specimens had higher power readings than darker colored or pigmented samples, and feathers appeared to inhibit the laser, showing minimal to no power readings on bird skin covered in covert and down feathers. There was statistically significant mean tissue penetration for all time points between the rabbit and green sea turtle ( p =0.0046), the red-tailed hawk and green iguana ( p =0.0046), and the red-tailed hawk and green sea turtle ( p =0.000034). Overall findings found that certain skin coverings, such as feathers, appear to inhibit passage of laser light through tissue to the photo meter. Darker pigmented areas of tissue appeared to absorb the laser light, which also did not allow light passage through the tissue to the photo meter. All of this illustrates that there are differences in tissue penetration between different animal species, at least in postmortem tissues. This could necessitate adjustment of machine settings for therapeutic effect in different species, though further studies would be warranted to determine the extent to which this would be necessary. Additional studies evaluating biologically active tissues would be needed as a next step, as photobiomodulation has an effect at the cellular level and the exact amount of medical benefit is not measurable in skin samples that are separate from a living organism., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Faith Ramsey et al.)

Background and Objectives: Cancer develops across nearly every species. However, cancer occurs at unexpected and widely different rates throughout the animal kingdom. The reason for this variation in cancer susceptibility remains an area of intense investigation. Cancer evolves in part through the accumulation of mutations, and therefore, we hypothesized that germline mutation rates would be associated with cancer prevalence and mortality across species., Methodology: We collected previously published data on germline mutation rate and cancer mortality data for 37 vertebrate species., Results: Germline mutation rate was positively correlated with cancer mortality (P-value = 0.0008; R2 = 0.13). Controlling for species' average parental age, maximum longevity, adult body mass or domestication did not improve the model fit (the change (Δ) in Akaike Information Criterion (AIC) was less than 2). However, this model fit was better than a model controlling for species trophic level (ΔAIC > 2)., Conclusions and Implications: The increased death rate from cancer in animals with increased germline mutation rates may suggest underlying hereditary cancer predisposition syndromes similar to those diagnosed in human patients. Species with higher germline mutation rates may benefit from close monitoring for tumors due to increased genetic risk for cancer development. Early diagnoses of cancer in these species may increase their chances of overall survival, especially for threatened and endangered species., Competing Interests: J.D.S. is a co-founder and shareholder employed by Peel Therapeutics, Inc., and L.M.A. is a shareholder and consultant to Peel Therapeutics, Inc., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.)

Introduction: Amyloid positron emission tomography (PET) acquisition timing impacts quantification., Methods: In florbetaben (FBB) PET scans of 245 adults with and without cognitive impairment, we investigated the impact of post-injection acquisition time on Centiloids (CLs) across five reference regions. CL equations for FBB were derived using standard methods, using FBB data collected between 90 and 110 min with paired Pittsburgh compound B data. Linear mixed models and t-tests evaluated the impact of acquisition time on CL increases., Results: CL values increased significantly over the scan using the whole cerebellum, cerebellar gray matter, and brainstem as reference regions, particularly in amyloid-positive individuals. In contrast, CLs based on white matter-containing reference regions decreased across the scan., Discussion: The quantification of CLs in FBB PET imaging is influenced by both the overall scan acquisition time and the choice of reference region. Standardized acquisition protocols or the application of acquisition time-specific CL equations should be implemented in clinical protocols., Highlights: Acquisition timing affects florbetaben positron emission tomography (PET) scan quantification, especially in amyloid-positive participants. The impact of acquisition timing on quantification varies across common reference regions. Consistent acquisitions and/or appropriate post-injection adjustments are needed to ensure comparability of PET data., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objective: Cross-sectional definitions of successful cognitive aging have been widely utilized, but longitudinal measurements can identify people who do not decline. We performed this study to contrast maintenance with declining trajectories, including clinical conversion., Methods: We included baseline cognitively unimpaired Alzheimer's Disease Neuroimaging Initiative participants with 3 or more cognitive testing sessions (n = 539, follow-up 6.1 ± 3.5 years) and calculated slopes of an episodic memory composite (MEM) to classify them into two groups: maintainers (slope ≥ 0) and decliners (slope < 0). Within decliners, we examined a subgroup of individuals who became clinically impaired during follow-up. These groups were compared on baseline characteristics and cognitive performance, as well as both cross-sectional and longitudinal Alzheimer disease (AD) biomarker measures (beta-amyloid [Aβ], tau, and hippocampal volume)., Results: Forty-one percent (n = 221) of the cohort were MEM maintainers, and 33% (n = 105) of decliners converted to clinical impairment during follow-up. Compared to those with superior baseline scores, maintainers had lower education and were more likely to be male. Maintainers and decliners did not differ on baseline MEM scores, but maintainers did have higher non-MEM cognitive scores. Maintainers had lower baseline global Aβ, lower tau pathology, and larger hippocampal volumes than decliners, even after removing converters. There were no differences in rates of change of any AD biomarkers between any cognitive trajectory groups except for a higher rate of hippocampal atrophy in clinical converters compared to maintainers., Interpretation: Using longitudinal data to define cognitive trajectory groups reduces education and sex bias and reveals the prognostic importance of early onset of accumulation of AD pathology. ANN NEUROL 2024;96:378-389., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background and Objectives: Cancer is a disease that affects nearly all multicellular life, including the broad and diverse taxa of Aves. While little is known about the factors that contribute to cancer risk across Aves, life history trade-offs may explain some of this variability in cancer prevalence. We predict birds with high investment in reproduction may have a higher likelihood of developing cancer. In this study, we tested whether life history traits are associated with cancer prevalence in 108 species of birds., Methodology: We obtained life history data from published databases and cancer data from 5,729 necropsies from 108 species of birds across 24 taxonomic orders from 25 different zoological facilities. We performed phylogenetically controlled regression analyses between adult body mass, lifespan, incubation length, clutch size, sexually dimorphic traits, and both neoplasia and malignancy prevalence. We also compared the neoplasia and malignancy prevalence of female and male birds., Results: Providing support for a life history trade-off between somatic maintenance and reproduction, we found a positive relationship between clutch size and cancer prevalence across Aves. There was no significant association with body mass, lifespan, incubation length, sexual dimorphism, and cancer., Conclusions and Implications: Life history theory presents an important framework for understanding differences in cancer defenses across various species. These results suggest a trade-off between reproduction and somatic maintenance, where Aves with small clutch sizes get less cancer., Competing Interests: We declare we do not have any conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.)

Neoplasia has been reported in lizards, but more research is needed to accurately document the prevalence and prognosis of the various known neoplasms that affect lizards. This study reviewed medical records from an online database, the Exotic Species Cancer Research Alliance (ESCRA), and reviewed published literature to determine the prevalence of neoplasia, malignancy, metastasis, treatment strategies, and outcomes by species and sex. Records from 55 individual lizards, 20 different species, and 37 different tumors were identified. In the literature, 219 lizards, 59 species, and 86 unique tumors were identified from 72 published case reports. Potential signalment factors such as age, sex, and species were evaluated to see if they affected case outcome. Additional factors including neoplasia type, presence of metastasis, and types of pursued treatments were also evaluated. Statistical analysis was performed to determine whether a factor was significantly associated with animal death due to the identified neoplasia or with animal survival or death due to other causes (non-neoplastic outcomes). Komodo dragons and savannah monitors were more likely to die from neoplasia compared to other lizard species. Cases where the status of metastasis was unknown were significantly associated with death due to neoplasia. Having an unknown status of male versus female was significantly associated with non-neoplastic outcomes of death. Leukemia and islet cell carcinoma were significantly associated with death due to neoplastic causes. Chondrosarcoma, myxosarcoma, osteosarcoma, and squamous cell carcinoma were significantly associated with non-neoplastic outcomes of death. Surgery alone and radiation therapy alone each were significantly associated with non-neoplastic outcomes of death, while lizards not receiving treatment were significantly associated with death due to neoplasia. Benign neoplasia was significantly associated with non-neoplastic outcomes of death. These results will aid in the improved diagnosis and management of neoplasia in lizard species, as well as expanding our understanding of prognostic indicators of neoplasia in lizards.

Purpose: Quantify and describe screen time (screen type, child engagement, adult co-viewing) in eight critically ill children and determine its association with sleep duration before (parent report) and during (actigraphy) a 24-h period in the PICU., Design and Methods: Exploratory secondary analysis of 24-h video and actigraphy recordings in eight children 1-4 years old in the PICU. Videos were coded for screen time using Noldus Observer XT® software. Screen time was compared to American Academy of Pediatrics recommendations (0 h/day <2 years, ≤1 h/day 2-5 years). Parents completed the Brief Infant Sleep Questionnaire-Revised-Short Form (BISQ-R-SF) to understand children's pre-hospital sleep. Actigraphy was used to measure PICU sleep duration. Associations between screen time and sleep were determined with bivariate analyses., Results: Average age was 23.1 months (SD = 9.7). Daily screen time was 10.7 h (SD = 7), ranging from 2.4 to 21.4 h. Children (15.1% of sampling intervals) and adults (16.3%) spent little time actively engaged with screen media. BISQ-R-SF scores ranged from 48.9 to 97.7. Children had an average of 7.9 (SD = 1.2) night shift (19:00-6:59) sleep hours. Screen time was associated with worse pre-hospital sleep quality and duration with large effect sizes (r s = -0.7 to -1) and fewer nighttime sleep hours with a medium effect size (r s = -0.5)., Conclusions: All children exceeded screen time recommendations. Screen time was associated with worse pre-hospital sleep quality and duration, and decreased PICU sleep duration. Large-scale studies are needed to explore PICU screen time and sleep disruption., Practice Implications: Clinicians should model developmentally appropriate screen media use in PICU., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Laura Beth Kalvas reports financial support was provided by National Institutes of Health. Laura Beth Kalvas reports financial support was provided by American Association of Critical-Care Nurses. Laura Beth Kalvas reports financial support was provided by Sigma Theta Tau International. Laura Beth Kalvas reports financial support was provided by Council for the Advancement of Nursing Science. Laura Beth Kalvas reports financial support was provided by Midwest Nursing Research Society. Laura Beth Kalvas reports financial support was provided by Ohio Nurses Foundation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sound levels in the pediatric intensive care unit (PICU) are often above recommended levels, but few researchers have identified the sound sources contributing to high levels., Objectives: To identify sources of PICU sound exposure., Methods: This was a secondary analysis of continuous bedside video and dosimeter data (n = 220.7 hours). A reliable coding scheme developed to identify sound sources in the adult ICU was modified for pediatrics. Proportions of sound sources were compared between times of high (≥45 dB) and low (<45 dB) sound, during day (7 AM to 6:59 PM) and night (7 PM to 6:59 AM) shifts, and during sound peaks (≥70 dB)., Results: Overall, family vocalizations (38% of observation time, n = 83.9 hours), clinician vocalizations (32%, n = 70.6 hours), and child nonverbal vocalizations (29.4%, n = 64.9 hours) were the main human sound sources. Media sounds (57.7%, n = 127.3 hours), general activity (40.7%, n = 89.8 hours), and medical equipment (31.3%, n = 69.1 hours) were the main environmental sound sources. Media sounds occurred in more than half of video hours. Child nonverbal (71.6%, n = 10.2 hours) and family vocalizations (63.2%, n = 9 hours) were highly prevalent during sound peaks. General activity (32.1%, n = 33.2 hours), clinician vocalizations (22.5%, n = 23.3 hours), and medical equipment sounds (20.6, n = 21.3 hours) were prevalent during night shifts., Conclusions: Clinicians should partner with families to limit nighttime PICU noise pollution. Large-scale studies using this reliable coding scheme are needed to understand the PICU sound environment., (©2024 American Association of Critical-Care Nurses.)

Objective: Evaluate SARS-CoV-2 morbidity, mortality, clinical signs, treatment interventions, and vaccination practices in tigers under professional care., Animals: Amur (Panthera tigris altaica), Sumatran (Panthera tigris sumatrae), and Malayan (Panthera tigris jacksoni) tigers managed under the Tiger Species Survival Plan (SSP)., Methods: A retrospective, voluntary online survey was sent to all North American zoos holding SSP tigers between January 2020 and June 2023., Results: Responses were received from 55 of 108 institutions (51%) housing 162 tigers in total, and SARS-CoV-2 infection was diagnosed in 39 tigers from 15 institutions (20 Amur, 8 Sumatran, and 11 Malayan [1 to 18 years old; 17 males and 22 females]). This corresponds to a minimum study group infection incidence of 24% over 42 months. Clinical signs included dry cough (82%), inappetence (64%), lethargy (62%), nasal discharge (46%), wheezing (31%), wet cough (18%), and ocular discharge (15%). Most cases were characterized as mild (n = 22) or moderate (14). A single case was characterized as severe. Two cases were asymptomatic. Seventeen positive tigers had been vaccinated once (n = 8) or twice (9) for SARS-CoV-2 prior to infection. No deaths due to SARS-CoV-2 were reported in the study group. Treatment interventions included antibiotics (49%), NSAIDs (18%), antiemetics (15%), and fluids (13%). No treatments were administered in 19 of 39 cases (49%). Amongst participating institutions, 69% reported fully vaccinating tigers for SARS-CoV-2 (≥ 2 doses)., Clinical Relevance: Most SARS-CoV-2-infected tigers presented with mild to moderate clinical signs and recovered with limited to no treatment interventions. Asymptomatic SARS-CoV-2 infections can occur in tigers and may be underreported. Tigers vaccinated for SARS-CoV-2 remain susceptible to infection.

Introduction: Amyloid beta (Aβ) and tau pathology are cross-sectionally associated with atrophy and cognitive decline in aging and Alzheimer's disease (AD)., Methods: We investigated relationships between concurrent longitudinal measures of Aβ (Pittsburgh compound B [PiB] positron emission tomography [PET]), tau (flortaucipir [FTP] PET), atrophy (structural magnetic resonance imaging), episodic memory (EM), and non-memory (NM) in 78 cognitively healthy older adults (OA)., Results: Entorhinal FTP change was correlated with EM decline regardless of Aβ, but meta-temporal FTP and global PiB change were only associated with EM and NM decline in Aβ+ OA. Voxel-wise analyses revealed significant associations between temporal lobe FTP change and EM decline in all groups. PiB and FTP change were not associated with structural change, suggesting a functional or microstructural mechanism linking these measures to cognitive decline., Discussion: Our results show that longitudinal Aβ is linked to cognitive decline only in the presence of elevated Aβ, but longitudinal temporal lobe tau is associated with memory decline regardless of Aβ status., Highlights: Entorhinal tau change was associated with memory decline in older adults (OA), regardless of amyloid beta (Aβ). Greater meta-region of interest (ROI) tau change correlated with memory decline in Aβ+ OA. Voxel-wise temporal tau change correlated with memory decline, regardless of Aβ. Meta-ROI tau and global amyloid change correlated with non-memory change in Aβ+ OA. Tau and amyloid accumulation were not associated with structural change in OA., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Tau pathology is associated with cognitive impairment in both aging and Alzheimer's disease, but the functional and structural bases of this relationship remain unclear. We hypothesized that the integrity of behaviorally meaningful functional networks would help explain the relationship between tau and cognitive performance. Using resting state fMRI, we identified unique networks related to episodic memory and executive function cognitive domains. The episodic memory network was particularly related to tau pathology measured with positron emission tomography in the entorhinal and temporal cortices. Further, episodic memory network strength mediated the relationship between tau pathology and cognitive performance above and beyond neurodegeneration. We replicated the association between these networks and tau pathology in a separate cohort of older adults, including both cognitively unimpaired and mildly impaired individuals. Together, these results suggest that behaviorally meaningful functional brain networks represent a functional mechanism linking tau pathology and cognition., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Abnormal amyloid-beta (Aβ) and tau deposition define Alzheimer's Disease (AD), but non-elevated tau is relatively frequent in patients on the AD pathway., Methods: We examined characteristics and regional patterns of 397 Aβ+ unimpaired and impaired individuals with low tau (A+T-) in relation to their higher tau counterparts (A+T+)., Results: Seventy-one percent of Aβ+ unimpaired and 42% of impaired Aβ+ individuals were categorized as A+T- based on global tau. In impaired individuals only, A+T- status was associated with older age, male sex, and greater cardiovascular risk. α-synuclein was linked to poorer cognition, particularly when tau was low. Tau burden was most frequently elevated in a common set of temporal regions regardless of T+/T- status., Discussion: Low tau is relatively common in patients on the AD pathway and is linked to comorbidities that contribute to impairment. These findings have implications for the selection of individuals for Aβ- and tau-modifying therapies., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Adverse neurodevelopment is a common comorbidity associated with congenital heart disease (CHD). The consequences of adverse neurodevelopment are seen across the life course. The cause of adverse neurodevelopment is multifactorial, and use of a life course perspective can assist with understanding and enhancing neurodevelopment in individuals with CHD., Purpose: The purposes of this article are to (1) apply the Life Course Health Development framework to neurodevelopment in the population with CHD and (2) discuss how exposure to the pediatric cardiac intensive care unit (PCICU) environment during infancy is a point of intervention for improving neurodevelopmental outcomes., Conclusion: Individuals with CHD are at an increased risk for adverse neurodevelopment across the life course. The PCICU environment is a point of intervention for improving neurodevelopmental outcomes. Stress can lead to changes in brain structure and function that are associated with negative outcomes in terms of outward behavioral and functional capacity, and the PCICU environment is a source of stressful stimuli. Infancy is a period of rapid brain growth, and the brain is more susceptible to stress during this period of the life course, putting infants receiving care in the PCICU at an increased risk of adverse neurodevelopment., Clinical Implications: Interventions to support optimal neurodevelopment should focus on the PCICU environment during infancy. Developmentally supportive care models should be explored as a means of modifying the PCICU environment. In addition, more research is needed on the relationship between the PCICU and neurodevelopment. The conceptual model introduced can serve as a starting point for this research., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Tau pathology is recognized as a primary contributor to neurodegeneration and clinical symptoms in Alzheimer's disease (AD). This study aims to localize the early tau pathology in cognitively normal older people that is predictive of subsequent neurodegeneration and memory decline, and delineate factors underlying tau-related memory decline in individuals with and without β-amyloid (Aβ)., Methods: A total of 138 cognitively normal older individuals from the Berkeley Aging Cohort Study underwent 11 C-Pittsburgh Compound-B (PiB) positron emission tomography (PET) to determine Aβ positivity and 18 F-Flortaucipir (FTP) PET to measure tau deposition, with prospective cognitive assessments and structural magnetic resonance imaging. Voxel-wise FTP analyses examined associations between baseline tau deposition and longitudinal memory decline, longitudinal hippocampal atrophy, and longitudinal cortical thinning in AD signature regions. We also examined whether hippocampal atrophy and cortical thinning mediate tau effects on future memory decline., Results: We found Aβ-dependent tau associations with memory decline in the entorhinal and temporoparietal regions, Aβ-independent tau associations with hippocampal atrophy within the medial temporal lobe (MTL), and that widespread tau was associated with mean cortical thinning in AD signature regions. Tau-related memory decline was mediated by hippocampal atrophy in Aβ- individuals and by mean cortical thinning in Aβ+ individuals., Interpretation: Our results suggest that tau may affect memory through different mechanisms in normal aging and AD. Early tau deposition independent of Aβ predicts subsequent hippocampal atrophy that may lead to memory deficits in normal older individuals, whereas elevated cortical tau deposition is associated with cortical thinning that may lead to more severe memory decline in AD. ANN NEUROL 2024;95:249-259., (© 2023 American Neurological Association.)

This study evaluated neoplasia in fish using medical records from zoos, aquariums, and exotic animal veterinarians. The parameters evaluated included geographic location, habitat type, signalment, anatomic location of neoplasia, type of neoplasia as confirmed with histologic examination, survival time, and treatments provided for each patient. These data were entered into the Exotic Species Cancer Research Alliance (ESCRA) database. Out of 455 cases from across the United States and England, most animals submitted were from zoologic parks or aquariums (62.9%), followed by private ownership (1.5%). The percent of female (19.3%) and male (17.8%) patients were similar, and the mean age at the time of diagnosis was 99.45 months, with a range of 12 to 300 months. The species with the highest neoplasia prevalence was koi (18.5%), followed by goldfish (10.8%). The eye was the most commonly reported site for a primary neoplasm (8.4%), and the most prevalent diagnosis across all organ systems was soft tissue sarcoma (26.2%). Only 13 patients in this study (2.9%) received any form of treatment, with a mean survival time of 8.85 months post-treatment. These data demonstrate that while information related to clinical therapy of cancer in fish species is lacking, surgical excision of tumors in fish, when feasible for the patient and client, may improve patient outcomes.

Growing digital access accelerates digital transformation of clinical trials where digital solutions (DSs) are increasingly and widely leveraged for improving trial efficiency, effectiveness, and accessibility. Many factors impact DS success including technology barriers, privacy concerns, or user engagement activities. It is unclear how those factors are considered or reported in the literature. Here, we perform a formative feasibility scoping review to identify gaps impacting DS quality and reproducibility in trials. Articles containing digital terms published in English from 2009 to 2022 were collected (n=4,167). 130 articles published between 2016 and 2022 were randomly selected for full-text review. Eligible articles (n=100) were sorted into four identified categories: 16% Education, 59% Intervention, 8% Patient, 17% Treatment. Initial findings about DS trends and reporting practices inform protocol development for a large-scale study urging the generation of fundamental knowledge on reporting standardization, best practice guidelines, and evaluation methodologies related to DS for clinical trials., (©2023 AMIA - All rights reserved.)

Introduction: There is no consensus on either the definition of successful cognitive aging (SA) or the underlying neural mechanisms., Methods: We examined the agreement between new and existing definitions using: (1) a novel measure, the cognitive age gap (SA-CAG, cognitive-predicted age minus chronological age), (2) composite scores for episodic memory (SA-EM), (3) non-memory cognition (SA-NM), and (4) the California Verbal Learning Test (SA-CVLT)., Results: Fair to moderate strength of agreement was found between the four definitions. Most SA groups showed greater cortical thickness compared to typical aging (TA), especially in the anterior cingulate and midcingulate cortices and medial temporal lobes. Greater hippocampal volume was found in all SA groups except SA-NM. Lower entorhinal 18 F-Flortaucipir (FTP) uptake was found in all SA groups., Discussion: These findings suggest that a feature of SA, regardless of its exact definition, is resistance to tau pathology and preserved cortical integrity, especially in the anterior cingulate and midcingulate cortices., Highlights: Different approaches have been used to define successful cognitive aging (SA). Regardless of definition, different SA groups have similar brain features. SA individuals have greater anterior cingulate thickness and hippocampal volume. Lower entorhinal tau deposition, but not amyloid beta is related to SA. A combination of cortical integrity and resistance to tau may be features of SA., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Bronchiectasis is irreversible bronchial dilation that can be congenital or acquired secondary to chronic airway obstruction. Feline bronchiectasis is rare and, to our knowledge, has not been reported previously in a non-domestic felid. An ~10-y-old female jungle cat ( Felis chaus ) was presented for evaluation of an abdominal mass and suspected pulmonary metastasis. The animal died during exploratory laparotomy and was submitted for postmortem examination. Gross examination revealed consolidation of the left caudal lung lobe and hila of the cranial lung lobes. Elsewhere in the lungs were several pale-yellow pleural foci of endogenous lipid pneumonia. On cut section, there was severe distension of bronchi with abundant white mucoid fluid. The remaining lung lobes were multifocally expanded by marginal emphysema. Histologically, ectatic bronchi, bronchioles, and fewer alveoli contained degenerate neutrophils, fibrin, and mucin (suppurative bronchopneumonia) with rare gram-negative bacteria. Aerobic culture yielded low growth of Proteus mirabilis and Escherichia coli . There was chronic bronchitis, marked by moderate bronchial gland hyperplasia, lymphoplasmacytic inflammation, and lymphoid hyperplasia. The palpated abdominal mass was a uterine endometrial polyp, which was considered an incidental, but novel, finding. Chronic bronchitis and bronchopneumonia should be considered as a cause of bronchiectasis and a differential diagnosis for respiratory disease in non-domestic felids., Competing Interests: Declaration of conflicting interestsThe authors declared no conflicts of interest regarding the research, authorship, and/or publication of this article.

Objective: To determine the K-constant for body surface area calculation from body weight in corn snakes (Pantherophis guttatus) through the use of computed tomography (CT) measurements., Animals: 12 adult corn snakes held by North Carolina State University for research purposes underwent CT between November 2022 and January 2023., Methods: Each snake had a CT scan, physical examination, and body weight measurement. CT images were uploaded into software able to perform 3-D reconstruction and measure body surface area. The species-specific K-constant was determined using nonlinear regression analysis between body surface area and (body weight in grams)2/3., Results: The mean body weight of the 12 adult corn snakes was 228 g, with a mean body surface area of 505.1 cm2. The calculated K-constant was 13.6 (P < .001). The resulting formula for body surface area in corn snakes is BSA in cm2 = 13.6 X (body weight in grams)2/3., Clinical Relevance: The body surface area formula developed for corn snakes will allow for improved dosing accuracy for medications with low therapeutic safety margins. Additional pharmacokinetic and pharmacodynamic studies are necessary to determine the safety and efficacy of individual medications.

Background: Stress exposure in the neonatal intensive care unit (NICU) is associated with poor outcomes in preterm infants. However, factors predicting subsequent NICU stress exposure have not been identified., Purpose: To characterize NICU stressors experienced by preterm infants during the first 2 weeks of life and identify demographic, perinatal, and institutional variables associated with stress exposure., Methods: A secondary analysis of data from a nonexperimental, prospective study was conducted using data from 60 very preterm infants born 28 to 31 weeks gestational age. Stress exposures during the first 2 weeks of life, operationalized as number of invasive procedures, were characterized by type and quantity for each infant using data extracted from electronic health records. Associations between number of invasive procedures and demographic, perinatal, or institutional variables were analyzed using linear regressions with robust standard errors., Results: Preterm infants experienced, on average, 98 (SD = 41.8) invasive procedures. Of these invasive procedures, nasal and/or oral suctioning episodes (58.1%), followed by skin-breaking procedures (32.6%), were most frequent. Differences in the number of invasive procedures were found for maternal race; infants born to Black mothers experienced fewer total invasive procedures than infants born to White mothers. The number of invasive procedures also varied across NICUs., Implications for Practice and Research: Preterm infant stress exposure differed by maternal race and NICU, consistent with research findings of differential treatment of diverse infants. Further research is needed to understand the reasons for these differences and to identify best practices to standardize neonatal care., (Copyright © 2023 by The National Association of Neonatal Nurses.)

Background: Sleep disruption is frequently observed in children with delirium in the pediatric intensive care unit (PICU)., Objectives: This observational pilot study explores relationships among modifiable characteristics of the PICU environment (i.e., light, sound, clinician caregiving patterns), sleep disruption, and delirium., Methods: Ten children, 1 to 4 years old, were recruited within 48 h of PICU admission and followed until discharge. A light meter, dosimeter, and video camera were placed at bedside to measure PICU environmental exposures. Sleep was measured via actigraphy. Twice daily delirium screening was conducted. Descriptive statistics were used to describe the PICU environment, sleep, and delirium experienced by children. Bivariate analyses were performed to determine relationships among variables., Results: Average participant age was 21 (SD = 9.6) months. Eight (80%) were admitted for respiratory failure. Median PICU length of stay was 36.7 (IQR[29.6, 51.5]) hours, which limited data collection duration. Delirium prevalence was 60% (n = 6). Children experienced low daytime light levels (x¯ = 112.8 lux, SD = 145.5) and frequent peaks (x¯ = 1.9/hr, SD = 0.5) of excessive sound (i.e., ≥ 45 A-weighted decibels). Clinician caregiving episodes were frequent (x¯ = 4.5/hr, SD = 2.6). Children experienced 7.3 (SD = 2.1) awakenings per hour of sleep and a median sleep episode duration of 1.4 (IQR[0.6, 2.3]) hours. On average, children with delirium experienced 1.1 more awakenings per sleep hour and 42 fewer minutes of sleep per sleep episode during the night shift. Increased clinician care frequency and duration were associated with worse sleep quality and delirium., Conclusions: Study results will inform future, large-scale research and nurse-driven sleep promotion interventions., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Laura Beth Kalvas reports financial support was provided by National Institutes of Health. Laura Beth Kalvas reports financial support was provided by American Association of Critical-Care Nurses. Laura Beth Kalvas reports financial support was provided by Sigma Theta Tau International. Laura Beth Kalvas reports financial support was provided by Council for the Advancement of Nursing Science. Laura Beth Kalvas reports financial support was provided by Midwest Nursing Research Society. Laura Beth Kalvas reports financial support was provided by Ohio Nurses Foundation. Nancy Redeker is the Editor of Heart & Lung., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Feeding difficulty is common in infants with CHD., Objective: The purpose of this study was to describe the feeding skills and behaviours of infants with CHD at 6-12 months of age and explore relationships between feeding, gastrointestinal distress, and gastroesophageal reflux., Methods: Parents of 30 infants with CHD completed online surveys when their infant was 6, 8, 10, and 12 months old. Surveys included parent-report measures of feeding skills (Child Oral and Motor Proficiency Scale), feeding behaviours (Pediatric Eating Assessment Tool), symptoms of gastrointestinal distress (Infant Gastrointestinal Symptoms Questionnaire), and gastroesophageal reflux (Infant Gastroesophageal Reflux Questionnaire-Revised)., Results: We found that 95, 32, 67, and 30% of infants were delayed in their feeding skill development at 6, 8, 10, and 12 months, respectively. Symptoms of problematic feeding behaviours were similarly high, with 90, 62, 29, and 38% of infants meeting criteria for problematic feeding at 6, 8, 10, and 12 months, respectively. Feeding skills and behaviours were related but unique contributors. Feeding behaviours were related to both gastrointestinal distress and gastroesophageal reflux, but feeding skills were rarely related to either., Conclusions: Delayed acquisition of feeding skills and problematic feeding were common in infants with CHD. Infants with more gastrointestinal and gastroesophageal reflux symptoms had more symptoms of problematic feeding behaviours., Clinical Implications: Comprehensive assessment, targeted interventions, and early involvement of feeding specialists are important to support feeding in infants with CHD through at least the first year of life.

This study examined the associations of grandparent-grandchild relational closeness and conflict with grandchildren's socioemotional and behavioral problems, including emotional symptoms, conduct problems, hyperactivity, peer problems, and abnormal prosocial behaviors. We analyzed primary cross-sectional survey data collected from custodial grandparents in the United States using logistic regression models. The results indicated that grandparent-grandchild relational closeness was significantly associated with lower odds of custodial grandchildren having emotional symptoms, conduct problems, peer problems, and abnormal prosocial behaviors, whereas grandparent-grandchild relational conflict was significantly associated with higher odds of emotional symptoms, conduct problems, hyperactivity, peer problems, and abnormal prosocial behaviors. Implications for increasing grandparent-grandchild relational closeness and decreasing relational conflicts among grandparent-headed families are discussed, which might improve grandchildren's socioemotional and behavioral well-being.

Large-scale brain networks undergo widespread changes with older age and in neurodegenerative diseases such as Alzheimer's disease (AD). Research in young adults (YA) suggest that the underlying functional architecture of brain networks remains relatively consistent between rest and task states. However, it remains unclear whether the same is true in aging and to what extent any changes may be related to accumulation of AD pathology such as β-amyloid (Aβ) and tau. Here, we examined age-related differences in functional connectivity (FC) between rest and an object-scene mnemonic discrimination task using fMRI in young and older adults (OA; both females and males). We used an a priori episodic memory network (EMN) parcellation scheme associated with object and scene processing, that included anterior-temporal regions and posterior-medial regions. We also used positron emission topography to measure Aβ and tau in older adults. The correlation between rest and task FC (i.e., FC similarity) was reduced in older compared with younger adults. Older adults with lower FC similarity in EMN had higher levels of tau in the same EMN regions and performed worse during object, but not scene, trials during the fMRI task. These findings link AD pathology, particularly tau, to a less stable functional architecture in memory networks. They also suggest that smaller changes in FC organization between rest and task states may facilitate better performance in older age. Interpretations are limited by methodological factors related to different acquisition directions and durations between rest and task scans. SIGNIFICANCE STATEMENT The brain's large-scale network organization is relatively consistent between rest and task states in young adults (YA). We found that memory networks in older adults (OA) were less correlated between rest and (memory) task states compared with young adults. Older adults with less correlated brain networks also had higher levels of Alzheimer's disease (AD) pathology in the same regions, suggesting that a less stable network architecture may reflect the early evolution of AD. Older adults with less correlated brain networks also performed worse during the memory task suggesting that more similar network organization between rest and task states may facilitate better performance in older age., (Copyright © 2023 the authors.)

Objective: To use CT measurements to define the body surface area (BSA) formula in American bullfrogs (Lithobates catesbeianus) and calculate the species-specific shape constant (K) to suggest chemotherapeutic doses., Animals: 12 American bullfrogs owned by the North Carolina State College of Veterinary Medicine Department of Laboratory Animal Resources underwent CT scans without anesthesia or sedation in November 2022., Methods: As part of this prospective study, each American bullfrog underwent a complete physical exam and CT scan. 3-D surface models were created using CT data, and the resulting measurements were used for BSA calculations. Animals were grouped by sex. Nonlinear regression analysis of BSA versus body weight was performed, and a species-specific formula was derived for calculating BSA in American bullfrogs., Results: The mean body weight of the bullfrogs was 354 grams. The mean CT-derived BSA was 414.92 cm2. The calculated K constant was 8.28 for the 12 American bullfrogs, and the CT-derived BSA formula was BSA in cm2 = 8.28 X (body weight in g)2/3. The K constant was 8.07 for females and 8.44 for males and was not significantly different between sexes (P = .5)., Clinical Relevance: Results indicated that the species-specific K constant for American bullfrogs is 8.28. This is the first calculated K constant that exists for amphibians to our knowledge.

Could diet and mean plasma glucose concentration (MPGluC) explain the variation in cancer prevalence across species? We collected diet, MPGluC, and neoplasia data for 160 vertebrate species from existing databases. We found that MPGluC negatively correlates with cancer and neoplasia prevalence, mostly of gastrointestinal organs. Trophic level positively correlates with cancer and neoplasia prevalence even after controlling for species MPGluC. Most species with high MPGluC (50/78 species = 64.1%) were birds. Most species in high trophic levels (42/53 species = 79.2%) were reptiles and mammals. Our results may be explained by the evolution of insulin resistance in birds which selected for loss or downregulation of genes related to insulin-mediated glucose import in cells. This led to higher MPGluC, intracellular caloric restriction, production of fewer reactive oxygen species and inflammatory cytokines, and longer telomeres contributing to longer longevity and lower neoplasia prevalence in extant birds relative to other vertebrates., Competing Interests: Competing interests We declare we do not have any conflicts of interest.

Cancer is pervasive across multicellular species, but what explains differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades (amphibians, sauropsids and mammals) we found that neoplasia and malignancy prevalence increases with adult weight (contrary to Peto's Paradox) and somatic mutation rate, but decreases with gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%) the black-footed penguin (<0.4%), ferrets (63%) and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer., Competing Interests: Competing interests: JDS is co-founder, shareholder, and employed by Peel Therapeutics, Inc., a company developing evolution-inspired medicines based on cancer resistance in elephants. LMA is share-holder and consultant to Peel Therapeutics, Inc. The other authors declare that they have no competing interests (ZTC, VKH, WM, SR, DM, SEK, MW, RK, KN, CB, LR, AP, BM, SS, SA, GF, OV, MG, EGD, SS, EF, HD, AZ, TAG, BT, TMH, MT, AA, AMB, CCM)

The basal forebrain cholinergic system (BFCS) has long been implicated in age-related cognitive changes and the pathophysiology of Alzheimer's disease (AD). Limitations of cholinergic interventions helped to inspire a shift away from BFCS in AD research. A resurgence in interest in the BFCS following methodological and analytical advances has resulted in a call for the BFCS to be examined in novel frameworks. We outline the basic structure and function of the BFCS, its role in supporting cognitive and affective function, and its vulnerability to aging and AD. We consider the BFCS in the context of the amyloid hypothesis and evolving concepts in AD research: resilience and resistance to pathology, selective neuronal vulnerability, trans-synaptic pathology spread and sleep health. We highlight 1) the potential role of the BFCS in cognitive resilience, 2) recent work refining understanding about the selective vulnerability of BFCS to AD, 3) BFCS connectivity that suggests it is related to tau spreading and neurodegeneration and 4) the gap between BFCS involvement in AD and sleep-wake cycles., Competing Interests: Competing Interests The authors have no competing interests to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Four clinically healthy red wolves ( Canis rufus ) developed hyperkalemia during routine anesthetic procedures. All cases were anesthetized using a combination of dexmedetomidine (10-24 mcg/kg), ketamine (2-3 mg/kg), and either midazolam (0.25-0.5 mg/kg) or butorphanol (0.2-0.48 mg/kg). Additional anesthetics were given to effect. Total anesthetic time ranged from 60 to 420 min. Three out of four cases were treated using terbutaline (0.01 mg/kg SC), which successfully resolved the hyperkalemia. No bradyarrhythmias were seen in any cases where electrocardiography (ECG) was monitored (3/4). All cases recovered from anesthesia, with one prolonged recovery. All animals are clinically healthy at the time of writing. Factors including anesthetic duration, the use of α-2 agonists, hyperthermia, and genetics are discussed as possible triggers for hyperkalemia. Serial blood gases, with electrolyte measurements, are recommended during anesthesia of red wolves, particularly when anesthetic time may be prolonged or the patient suffers from hyperthermia. Terbutaline appears to be a successful treatment should hyperkalemia arise.

Chimerism is a widespread phenomenon across the tree of life. It is defined as a multicellular organism composed of cells from other genetically distinct entities. This ability to 'tolerate' non-self cells may be linked to susceptibility to diseases like cancer. Here we test whether chimerism is associated with cancers across obligately multicellular organisms in the tree of life. We classified 12 obligately multicellular taxa from lowest to highest chimerism levels based on the existing literature on the presence of chimerism in these species. We then tested for associations of chimerism with tumour invasiveness, neoplasia (benign or malignant) prevalence and malignancy prevalence in 11 terrestrial mammalian species. We found that taxa with higher levels of chimerism have higher tumour invasiveness, though there was no association between malignancy or neoplasia and chimerism among mammals. This suggests that there may be an important biological relationship between chimerism and susceptibility to tissue invasion by cancerous cells. Studying chimerism might help us identify mechanisms underlying invasive cancers and also could provide insights into the detection and management of emerging transmissible cancers., Competing Interests: We declare we do not have conflicts of interest., (Copyright: © 2023 Kapsetaki 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.)

Cancer is a disease that affects nearly all multicellular life, including birds. However, little is known about what factors explain the variance in cancer prevalence among species. Litter size is positively correlated with cancer prevalence in managed species of mammals, and larger body size, but not incubation or nestling period, is linked to tumor prevalence in wild birds. Also, birds that produce more elaborate sexual traits are expected to have fewer resources for cancer defenses and thus higher cancer prevalence. In this study, we examined whether cancer prevalence is associated with a wide variety of life history traits (clutch size, incubation length, body mass, lifespan, and the extent of sexual dimorphism) across 108 species of managed birds in 25 different zoological facilities, sanctuaries, and veterinary clinics. We found that clutch size was positively correlated with cancer and neoplasia (both benign and malignant) prevalence, even after controlling for body mass. Cancer prevalence was not associated with incubation length, body mass, lifespan, or sexual dimorphism. The positive correlations of clutch size with cancer prevalence and neoplasia prevalence suggest that there may be life-history trade-offs between reproductive investment and somatic maintenance (in the form of cancer prevention mechanisms) in managed birds., Competing Interests: Competing interests We declare we do not have any conflicts of interest.

Developmental disorders, disabilities, and delays are a common outcome for individuals with complex congenital heart disease, yet targeting early factors influencing these conditions after birth and during the neonatal hospitalization for cardiac surgery remains a critical need. The purpose of this science advisory is to (1) describe the burden of developmental disorders, disabilities, and delays for infants with complex congenital heart disease, (2) define the potential health and neurodevelopmental benefits of developmental care for infants with complex congenital heart disease, and (3) identify critical gaps in research aimed at evaluating developmental care interventions to improve neurodevelopmental outcomes in complex congenital heart disease. This call to action targets research scientists, clinicians, policymakers, government agencies, advocacy groups, and health care organization leadership to support funding and hospital-based infrastructure for developmental care in the complex congenital heart disease population. Prioritization of research on and implementation of developmental care interventions in this population should be a major focus in the next decade.