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Objective: To evaluate latency and duration of a brachial plexus block technique in eastern box turtles performed with 2% lidocaine at three dose rates., Study Design: Prospective, randomized, blinded crossover study., Animals: Adult eastern box turtles, two for drug dose evaluation and a group of six (three male, three female) weighing 432 ± 40 g (mean ± standard deviation) for the main study., Methods: Animals were randomly assigned to four brachial plexus blocks with lidocaine at 5, 10 and 20 mg kg -1 or 0.9% saline (treatments LID5, LID10, LID20 and CON, respectively), separated by 1 week. Treatment side was randomized and blocks were performed unilaterally. Baseline observations of mentation, heart rate (HR), respiratory rate (f R ), skin temperature and limb response to manipulation or toe pinch were evaluated. Assessments were made every 10 minutes until 1 hour of normal sensory and motor function to the treated thoracic limb, or for a total of 2 hours if no block was evident., Results: Motor and sensory blockade was achieved in treatments LID10 and LID20 in one turtle, with a latency of 10 minutes and duration of 50 minutes for both doses. Raising of the ipsilateral lower palpebra occurred with both blocks. Turtles administered lidocaine experienced higher HR compared with CON, and HR decreased over time for all individuals. Mentation and f R were not changed with any lidocaine dose., Conclusions: The technique was unreliable in producing brachial plexus motor and sensory blockade at the lidocaine doses evaluated in this study. HR was higher in lidocaine-administered turtles but remained within normal limits for the species. No change in mentation or f R was observed among treatments., Clinical Relevance: General anesthesia with systemic analgesia is recommended for surgical procedures involving the chelonian thoracic limb. Further studies are needed to optimize a brachial plexus block in this species., (Copyright © 2022 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Inflammation often accompanies preterm birth and contributes to poor neurodevelopment in preterm infants. The purpose of this study was to describe postnatal cytokine trajectories among non-infected very preterm infants during the first weeks of life. Blood samples for cytokine analysis were collected weekly from infants born between 28 and 31 weeks post-menstrual age. We used linear mixed models to calculate slopes for each cytokine and allowed the slopes to differ by infant biological sex and post-menstrual age at birth. Levels of interleukin-6, interleukin-8, and interleukin-1 receptor antagonist decreased, on average, during the neonatal period. Monocyte chemoattractant protein-1 levels increased over time, and tumor necrosis factor-alpha levels were stable. Interleukin-6 and interleukin-8 slopes differed by post-menstrual age at birth but were unaffected by infant sex. Knowledge of average cytokine trajectories may be useful in identifying infants with unresolving inflammation that increases their risk for poor neurodevelopment.

Background and Objectives: Sleep and physical activity have gained traction as modifiable risk factors for Alzheimer's disease. Sleep duration is linked to amyloid-β clearance while physical activity is associated with brain volume maintenance. We investigate how sleep duration and physical activity are associated with cognition by testing if the associations between sleep duration or physical activity to cognition are explained by amyloid-β burden and brain volume, respectively. Additionally, we explore the mediating role of tau deposition in sleep duration-cognition and physical activity-cognition relationships., Methods: This cross-sectional study obtained data from participants in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study, a randomized clinical trial. In trial screening, cognitively unimpaired participants (age 65-85 years) underwent amyloid PET and brain MRI; APOE genotype and lifestyle questionnaire data were obtained. Cognitive performance was assessed using the Preclinical Alzheimer Cognitive Composite (PACC). Self-reported nightly sleep duration and weekly physical activity were the primary predictors. Regional Aβ and tau pathologies and volumes were the proposed variables influencing relationships between sleep duration or physical activity and cognition., Results: Aβ data were obtained from 4322 participants (1208 with MRI, 59% female, 29% amyloid positive). Sleep duration was associated with a Aβ composite score (β = -0.005, CI: (-0.01, -0.001)) and Aβ burden in the anterior cingulate (ACC) (β = -0.012, CI: (-0.017, -0.006)) and medial orbitofrontal cortices (MOC) (β = -0.009, CI: (-0.014, -0.005)). Composite (β = -1.54, 95% CI:(-1.93, -1.15)), ACC (β = -1.22, CI:(-1.54, -0.90)) and MOC (β = -1.44, CI:(-1.86, -1.02)) Aβ deposition was associated with PACC. Sleep duration-PACC association was explained by Aβ burden in path analyses. Physical activity was associated with hippocampal (β = 10.57, CI: (1.06, 20.08)), parahippocampal (β = 9.3, CI: (1.69, 16.91)), entorhinal (β = 14.68, CI: (1.75, 27.61), and fusiform gyral (β = 38.38, CI: (5.57, 71.18)) volumes, which were positively associated with PACC (p < 0.02 for hippocampus, entorhinal cortex and fusiform gyrus). Physical activity-cognition relationship was explained by regional volumes. PET tau imaging was available for 443 participants. No direct sleep duration-tau burden, physical activity by tau burden, or mediation by regional tau was observed in sleep duration-cognition or physical activity-cognition relationships., Discussion: Sleep duration and physical activity are associated with cognition through independent paths of brain Aβ and brain volume, respectively. These findings implicate neural and pathological mechanisms for the relationships between sleep duration and physical activity on cognition. Dementia risk reduction approaches that emphasize the adequate sleep duration and a physically active lifestyle may benefit those with risk for Alzheimer's disease., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: To characterize and quantify touch experienced by preterm infants in the NICU during essential nursing care, identify instances of skin-to-skin touch between infants and caregivers, and identify clinical/demographic variables associated with touch experiences. Design: Cross-sectional study. Sample: Preterm infants ( N = 20) born 27-32 weeks post-menstrual age. Main Outcome Variable: Categories of touch during observations. Results: Touch experienced by infants during day and night shifts was primarily direct touch that was further categorized as general handling. During day shifts, 30 percent of direct touch was provided for comfort, but only 9.7 percent of touch was provided exclusively for comfort (i.e., without more intrusive touch). During night shifts, 10.6 percent of direct touch was provided for comfort, and 3 percent was categorized as exclusive comforting touch. Caregivers wore gloves for >89 percent of infant touch. Only the level of respiratory support was associated with touch categories during both shifts., (© Copyright 2023 Springer Publishing Company, LLC.)

Accurate measurement of Alzheimer's disease (AD) pathology in older adults without significant clinical impairment is critical to assessing intervention strategies aimed at slowing AD-related cognitive decline. The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (POINTER) is a 2-year randomized controlled trial to evaluate the effect of multicomponent risk reduction strategies in older adults (60-79 years) who are cognitively unimpaired but at increased risk for cognitive decline/dementia due to factors such as cardiovascular disease and family history. The POINTER Imaging ancillary study is collecting tau-PET ([ 18 F]MK6240), beta-amyloid (Aβ)-PET ([ 18 F]florbetaben [FBB]) and MRI data to evaluate neuroimaging biomarkers of AD and cerebrovascular pathophysiology in this at-risk sample. Here 481 participants (70.0±5.0; 66% F) with baseline MK6240, FBB and structural MRI scans were included. PET scans were coregistered to the structural MRI which was used to create FreeSurfer-defined reference regions and target regions of interest (ROIs). We also created off-target signal (OTS) ROIs to examine the magnitude and distribution of MK6240 OTS across the brain as well as relationships between OTS and age, sex, and race. OTS was unimodally distributed, highly correlated across OTS ROIs and related to younger age and sex but not race. Aiming to identify an optimal processing approach for MK6240 that would reduce the influence of OTS, we compared our previously validated MRI-guided standard PET processing and 6 alternative approaches. The alternate approaches included combinations of reference region erosion and meningeal OTS masking before spatial smoothing as well as partial volume correction. To compare processing approaches we examined relationships between target ROIs (entorhinal cortex (ERC), hippocampus or a temporal meta-ROI (MetaROI)) SUVR and age, sex, race, Aβ and a general cognitive status measure, the Modified Telephone Interview for Cognitive Status (TICSm). Overall, the processing approaches performed similarly, and none showed a meaningful improvement over standard processing. Across processing approaches we observed previously reported relationships with MK6240 target ROIs including positive associations with age, an Aβ+> Aβ- effect and negative associations with cognition. In sum, we demonstrated that different methods for minimizing effects of OTS, which is highly correlated across the brain within subject, produced no substantive change in our performance metrics. This is likely because OTS contaminates both reference and target regions and this contamination largely cancels out in SUVR data. Caution should be used when efforts to reduce OTS focus on target or reference regions in isolation as this may exacerbate OTS contamination in SUVR data., Competing Interests: Declaration of Competing Interests SLB consults for Genentech. DRG serves on advisory boards for Lilly and Danone, consults for Genentech / Roche and holds industry sponsored grants from Abbvie, Biogen, Cassava, Eisai and Lilly. HMS is a full-time employee of the Alzheimer's Association, which provided funding for the parent study of U.S. POINTER. WJJ consults for Lilly, Eisai Bioclinica, and Prothena. SML is on the advisory board for KeifeRX and NIH IPAT study and has received speaker fees from Eisai. TMH, TJW, AM, PAD, RK, SNL, DJH, LL, JM, HO, NA, LDB and CD have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Higher neuroticism is a risk factor for Alzheimer's disease (AD), and is implicated in disordered stress responses. The locus coeruleus (LC)-catecholamine system is activated during perceived threat and is a centerpiece of developing models of the pathophysiology of AD, as it is the first brain region to develop abnormal tau. We examined relationships among the "Big 5" personality traits, LC catecholamine synthesis capacity measured with [ 18 F]Fluoro-m-tyrosine PET, and tau burden measured with [ 18 F]Flortaucipir PET in cognitively normal older adults (n = 47). β-amyloid (Aβ) status was determined using [ 11 C]Pittsburgh compound B PET (n = 14 Aβ positive). Lower LC catecholamine synthesis capacity was associated with higher neuroticism, more depressive symptoms as measured by the Geriatric Depression Scale, and higher amygdala tau-PET binding. Exploratory analyses with other personality traits revealed that low trait conscientiousness was also related to both lower LC catecholamine synthesis capacity, and more depressive symptoms. A significant indirect path linked both high neuroticism and low conscientiousness to greater amygdala tau burden via their mutual association with low LC catecholamine synthesis capacity. Together, these findings reveal LC catecholamine synthesis capacity to be a promising marker of affective health and pathology burden in aging, and identifies candidate neurobiological mechanisms for the effect of personality on increased vulnerability to dementia., Competing Interests: Declaration of Competing Interest Dr. Jagust has served as a consultant to Biogen and Bioclinica, and holds an equity interest in Optoceutics. All other authors have no financial disclosures., (Copyright © 2022. Published by Elsevier Inc.)

Problem: Preterm infants experience numerous stressors in the neonatal intensive care unit. Non-pharmacological interventions, including maternal comforting touch, reduce stress responses of preterm infants; however, the effects of clinician-administered comforting touch are unclear. The purpose of this integrative review was to synthesize findings from clinical trials to determine the effect of clinician-administered comforting touch on preterm infants' acute stress responses., Eligibility Criteria: Eligible clinical trials were published in English between 2001 and October 2021 and reported effects of clinician-administered comforting touch on acute stress responses in preterm infants., Sample: Thirty clinical trials were included., Results: Researchers tested the effect of comforting static touch, massage, massage with kinesthetic stimulation, sensorial saturation, and Yakson. There was significant heterogeneity in study design, comparison condition, and context of intervention delivery. Results varied; some studies demonstrated efficacy of comforting touch in reducing acute stress responses and others showed no effect. Generally, comforting touch provided during stressful procedures was associated with lower stress responses compared to standard care and was an effective adjunct to other stress management strategies. However, comforting touch alone was insufficient for managing pain, especially during skin-breaking procedures., Conclusions: While comforting touch may be a useful part of stress management plans for preterm infants, additional research is needed to determine when comforting touch is appropriate and effective., Implications: Comforting touch is beneficial to preterm infants and should be provided for stress management. For highly intrusive or painful procedures, comforting touch can be provided as part of a comprehensive stress management plan., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Patients with anorexia nervosa (AN) have autonomic nervous system (ANS) dysfunction as measured by heart rate variability (HRV). Omega-3 fatty acids may improve heart rate regulation. Our aim was to describe ANS response to a mid-day meal in adolescent females with AN in a 12-week treatment program, randomized to receive either omega-3 supplements or placebo., Methods: This pilot study was a longitudinal, double-blind, randomized controlled trial. Each group was subdivided into an acutely ill cohort and a chronically ill cohort. Linear and non-linear measures of slope, mean, and pre/post-meal changes in HRV were measured at baseline, 6 weeks, and 12 weeks., Results: Twenty-four women (n = 12 placebo; n = 12 omega-3) were enrolled. By program end, the acute omega-3 group alone showed no change in any pre-meal slope. Acute and chronic omega-3 groups, but not placebo groups, demonstrated physiologically expected post-meal heart rate increases at 12 weeks. For all measures at 6 and 12 weeks, the chronic placebo and omega-3 groups had smaller physiologic responses to the meal compared with the acute groups., Conclusions: Participation in a 12-week partial hospitalization program may improve autonomic function in response to mealtime, with possible additional benefit from omega-3 PUFA, particularly in those with acute illness., Impact: Autonomic function with meals improves with a 12-week partial hospitalization program in adolescent females with anorexia nervosa. Omega-3 polyunsaturated fatty acids may improve autonomic function, especially in adolescent females with acute forms of anorexia nervosa. Longer duration of illness in adolescent females with anorexia nervosa is associated with blunted autonomic response to meals., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Delirium is a serious complication of pediatric critical illness. Sleep disruption is frequently observed in children with delirium, and circadian rhythm dysregulation is one proposed cause of delirium. Children admitted to the pediatric intensive care unit (PICU) experience multiple environmental exposures with the potential to disrupt sleep. Although researchers have measured PICU light and sound exposure, sleep, and delirium, these variables have not yet been fully explored in a single study. Furthermore, caregiving patterns have not often been included as a component of the PICU environment. Measuring the light and sound exposure, caregiving patterns, and sleep of critically ill children requires continuous PICU bedside data collection. This presents multiple methodological challenges. In this paper, we describe the protocol for an observational pilot study of the PICU environment, sleep, and delirium experienced by a sample of 10 critically ill children 1-4 years of age. We also evaluate and discuss the feasibility (i.e., acceptability, implementation, practicality) of the study protocol. Light and sound exposure were measured with bedside sensors. Caregiving was quantified through video recording. Sleep was measured via actigraphy and confirmed by video recording. Delirium screening with the Cornell Assessment of Pediatric Delirium was conducted twice daily, either in person or via video review. This study provides a refined measurement framework to inform future, large-scale studies and the development of nurse-driven sleep promotion interventions., (© 2022 Wiley Periodicals LLC.)

Two co-housed 17-yr-old male lions ( Panthera leo ) and one 15-yr-old female lion in an adjacent enclosure developed acute lethargy, depression, anorexia, and ataxia at a zoological park in central North Carolina, United States. One of the male lions and the female lion were found dead 5 and 4 d after the onset of clinical signs, respectively. The other male lion recovered without any clinical treatment. A third male lion housed with the female lion never developed clinical signs. Postmortem examination, microscopic evaluation, and bacterial culture of the liver from both deceased lions confirmed systemic Yersinia pseudotuberculosis infection. Susceptibility testing revealed resistance to amoxicillin-clavulanic acid and cefazolin. To investigate the extent of the outbreak, qualitative real-time polymerase chain reaction (PCR) for Y. pseudotuberculosis was performed on feces and substrate from 15 enclosures housing nondomestic felids and canids, resulting in a positive sample from one enclosure housing four asymptomatic lions. This enclosure was adjacent to housing of the deceased female lion. Enrofloxacin was administered to all animals in the vicinity at doses of 5 mg/kg in nondomestic felids and 10 mg/kg in nondomestic canids, orally q24h for 14 d. Repeated fecal PCR performed 1 wk after completing the antibiotic treatment protocol found no positive samples. The source of the infection was not identified despite PCR testing of environmental samples from all enclosures in the vicinity, the remains of a prey item fed out prior to the outbreak, and a single dead rodent found on grounds. No further clinical cases have occurred within the following year.

Reproductive tumors can impact conception, pregnancy, and birth in mammals. These impacts are well documented in humans, while data in other mammals are limited. An urgent need exists to understand the reproductive impact of these lesions in endangered species, because some endangered species have a documented high prevalence of reproductive tumors. This article documents that the prevalence of both benign and malignant neoplasia differs between African and Asian elephants, with Asian elephants more frequently diagnosed and negatively affected by both. The prevalence of these tumors across mammalian species is compared, and impact plus treatment options in human medicine are reviewed to inform decision making in elephants. Evidence suggests that reproductive tumors can negatively impact elephant conservation. Future studies that document reproductive outcomes, including the success of various treatment approaches in elephants with tumors will benefit conservation efforts.

Approximately 30% of elderly adults are cognitively unimpaired at time of death despite the presence of Alzheimer's disease neuropathology at autopsy. Studying individuals who are resilient to the cognitive consequences of Alzheimer's disease neuropathology may uncover novel therapeutic targets to treat Alzheimer's disease. It is well established that there are sex differences in response to Alzheimer's disease pathology, and growing evidence suggests that genetic factors may contribute to these differences. Taken together, we sought to elucidate sex-specific genetic drivers of resilience. We extended our recent large scale genomic analysis of resilience in which we harmonized cognitive data across four cohorts of cognitive ageing, in vivo amyloid PET across two cohorts, and autopsy measures of amyloid neuritic plaque burden across two cohorts. These data were leveraged to build robust, continuous resilience phenotypes. With these phenotypes, we performed sex-stratified [n (males) = 2093, n (females) = 2931] and sex-interaction [n (both sexes) = 5024] genome-wide association studies (GWAS), gene and pathway-based tests, and genetic correlation analyses to clarify the variants, genes and molecular pathways that relate to resilience in a sex-specific manner. Estimated among cognitively normal individuals of both sexes, resilience was 20-25% heritable, and when estimated in either sex among cognitively normal individuals, resilience was 15-44% heritable. In our GWAS, we identified a female-specific locus on chromosome 10 [rs827389, β (females) = 0.08, P (females) = 5.76 × 10-09, β (males) = -0.01, P(males) = 0.70, β (interaction) = 0.09, P (interaction) = 1.01 × 10-04] in which the minor allele was associated with higher resilience scores among females. This locus is located within chromatin loops that interact with promoters of genes involved in RNA processing, including GATA3. Finally, our genetic correlation analyses revealed shared genetic architecture between resilience phenotypes and other complex traits, including a female-specific association with frontotemporal dementia and male-specific associations with heart rate variability traits. We also observed opposing associations between sexes for multiple sclerosis, such that more resilient females had a lower genetic susceptibility to multiple sclerosis, and more resilient males had a higher genetic susceptibility to multiple sclerosis. Overall, we identified sex differences in the genetic architecture of resilience, identified a female-specific resilience locus and highlighted numerous sex-specific molecular pathways that may underly resilience to Alzheimer's disease pathology. This study illustrates the need to conduct sex-aware genomic analyses to identify novel targets that are unidentified in sex-agnostic models. Our findings support the theory that the most successful treatment for an individual with Alzheimer's disease may be personalized based on their biological sex and genetic context., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Amyloid plaque aggregation is a pathologic hallmark of Alzheimer's disease (AD) that occurs early in the disease. However, little is known about its progression throughout the brain. Using Pittsburgh Compound B (PIB)-PET imaging, we investigated the progression of regional amyloid accumulation in cognitively normal older adults. We found that all examined regions reached their peak accumulation rates 24-28 years after an estimated initiation corresponding to the mean baseline PIB-PET signal in amyloid-negative older adults. We also investigated the effect of increased genetic risk conferred by the apolipoprotein-E ɛ4 allele on rates of amyloid accumulation, as well as the relationship between regional amyloid accumulation and regional tau pathology, another hallmark of AD, measured with Flortaucipir-PET. Carriers of the ɛ4 allele had faster amyloid accumulation in all brain regions. Furthermore, in all regions excluding the temporal lobe, faster amyloid accumulation was associated with greater tau burden. These results indicate that amyloid accumulates near-simultaneously throughout the brain and is associated with higher AD pathology, and that genetic risk of AD is associated with faster amyloid accumulation., (Copyright © 2022. Published by Elsevier Inc.)

Background and Objectives: Hepatocellular carcinoma occurs frequently in prosimians, but the cause of these liver cancers in this group is unknown. Characterizing the genetic changes associated with hepatocellular carcinoma in prosimians may point to possible causes, treatments and methods of prevention, aiding conservation efforts that are particularly crucial to the survival of endangered lemurs. Although genomic studies of cancer in non-human primates have been hampered by a lack of tools, recent studies have demonstrated the efficacy of using human exome capture reagents across primates., Methodology: In this proof-of-principle study, we applied human exome capture reagents to tumor-normal pairs from five lemurs with hepatocellular carcinoma to characterize the mutational landscape of this disease in lemurs., Results: Several genes implicated in human hepatocellular carcinoma, including ARID1A , TP53 and CTNNB1 , were mutated in multiple lemurs, and analysis of cancer driver genes mutated in these samples identified enrichment of genes involved with TP53 degradation and regulation. In addition to these similarities with human hepatocellular carcinoma, we also noted unique features, including six genes that contain mutations in all five lemurs. Interestingly, these genes are infrequently mutated in human hepatocellular carcinoma, suggesting potential differences in the etiology and/or progression of this cancer in lemurs and humans., Conclusions and Implications: Collectively, this pilot study suggests that human exome capture reagents are a promising tool for genomic studies of cancer in lemurs and other non-human primates., Lay Summary: Hepatocellular carcinoma occurs frequently in prosimians, but the cause of these liver cancers is unknown. In this proof-of-principle study, we applied human DNA sequencing tools to tumor-normal pairs from five lemurs with hepatocellular carcinoma and compared the lemur mutation profiles to those of human hepatocellular carcinomas., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.)

The locus coeruleus (LC) is the brain's major source of the neuromodulator norepinephrine, and is also profoundly vulnerable to the development of Alzheimer's disease (AD)-related tau pathology. Norepinephrine plays a role in neuroprotective functions that may reduce AD progression, and also underlies optimal memory performance. Successful maintenance of LC neurochemical function represents a candidate mechanism of protection against the propagation of AD-related pathology and may facilitate the preservation of memory performance despite pathology. Using [ 18 F]Fluoro-m-tyrosine ([ 18 F]FMT) PET imaging to measure catecholamine synthesis capacity in LC regions of interest, we examined relationships among LC neurochemical function, AD-related pathology, and memory performance in cognitively normal older adults (n = 49). Participants underwent [ 11 C]Pittsburgh compound B and [ 18 F]Flortaucipir PET to quantify β-amyloid (n = 49) and tau burden (n = 42) respectively. In individuals with substantial β-amyloid, higher LC [ 18 F]FMT net tracer influx (Ki vis ) was associated with lower temporal tau. Longitudinal tau-PET analyses in a subset of our sample (n = 30) support these findings to reveal reduced temporal tau accumulation in the context of higher LC [ 18 F]FMT Ki vis . Higher LC catecholamine synthesis capacity was positively correlated with self-reported cognitive engagement and physical activity across the lifespan, established predictors of successful aging measured with the Lifetime Experiences Questionnaire. LC catecholamine synthesis capacity moderated tau's negative effect on memory, such that higher LC catecholamine synthesis capacity was associated with better-than-expected memory performance given an individual's tau burden. These PET findings provide insight into the neurochemical mechanisms of AD vulnerability and cognitive resilience in the living human brain., (© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

The Turtle Rescue Team (TRT) at North Carolina State University College of Veterinary Medicine currently sees over 500 chelonian cases a year. Each turtle receives a thorough physical examination as the main evaluation of its health because further diagnostics are cost prohibitive in a donation-based facility. Thus, there is a need to further understand how a few economical diagnostics can evaluate the prognosis of chelonians. The objectives were to evaluate lactate, PCV, total solids, glucose, temperature, and HR as prognostic indicators in multiple chelonian species and to determine how the change in lactate concentrations over a 24 h period affects prognosis. Eastern box turtles ( Terrapene carolina carolina ), yellow-bellied sliders ( Trachemys scripta scripta ), river cooters ( Pseudemys concinna ), painted turtles ( Chrysemys picta ), and common snapping turtles ( Chelydra serpentina ) were evaluated because of prevalence of presentation to the TRT, differences in habitat, and differences in physiology. Hyperlactatemia, an increased lactate over 24 h when the initial lactate concentration was greater than 5 mM/L, and anemia were determined to be significant prognostic indicators of mortality for all turtles, and hypoglycemia was a significant prognostic indicator of mortality for male turtles ( P < 0.05).

Clinical evaluation of neurodevelopmental impairments before 6 months of age is needed in congenital heart disease (CHD) to promote early referral to developmental interventions. The objective was to identify the risk of cerebral palsy (CP) and to compare neurodevelopment outcomes in infants with and without CHD. In a longitudinal study, 30 infants with CHD and 15 infants without CHD were assessed at 1 month, 3 months, and 6 months of age. Included measures were General Movement Assessment (GMA), Test of Infant Motor Performance (TIMP) and the Bayley Scale of Infant Development, third edition (Bayley-III), selected to identify the risk of CP, document neurodevelopmental impairments and infants' eligibility for early intervention services. Abnormal GMA categories were found in the CHD group where 48% had poor repertoire and 15% were at high risk of CP. At 3 months of age, CHD group had significantly lower TIMP scores compared to infants without CHD [t(41) = 6.57, p = 0.01]. All infants in the study had higher Bayley-III scores at 6 months than at 3 months of age. Infants with CHD had lower gross motor, fine motor and cognitive Bayley-III scores compared to their peers without CHD. Over time infants without CHD outperformed the CHD group in the gross motor skills [F (1,41)  = 11.76, p = .001]. Higher prevalence of abnormal GMs, lower TIMP and Bayley-III were found in infants with single ventricle physiology compared to two-ventricle physiology. The risk of CP exists in infants with CHD, and these infants have worse outcomes compared to their peers without CHD. These differences are intensified in the single ventricle population.Clinical Trial Registration National Institute of Health, Unique identifier: NCT03104751; Date of registration-April 7, 2017., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mechanisms underlying the initial accumulation of tau pathology across the human brain are largely unknown. We examined whether baseline factors including age, amyloid-β (Aβ), and neural activity predicted longitudinal tau accumulation in temporal lobe regions that reflect distinct stages of tau pathogenesis. Seventy cognitively normal human older adults (77 ± 6 years, 59% female) received two or more 18 F-flortaucipir (FTP) and 11 C-Pittsburgh Compound B (PiB) PET scans (mean follow-up, 2.5 ± 1.1 years) to quantify tau and (Aβ). Linear mixed-effects models were used to calculate the slopes of FTP change in entorhinal cortex (EC), parahippocampal cortex (PHC), and inferior temporal gyrus (IT), and slopes of global PiB change. Thirty-seven participants underwent functional MRI to measure baseline activation. Older age predicted EC tau accumulation, and baseline EC tau levels predicted subsequent tau accumulation in EC and PHC. In IT, however, baseline EC tau interacted with Aβ to predict IT tau accumulation. Higher baseline local activation predicted tau accumulation within EC and PHC, and higher baseline hippocampal activation predicted EC tau accumulation. Our findings indicate that factors predicting tau accumulation vary as tau progresses through the temporal lobe. Older age is associated with initial tau accumulation in EC, while baseline EC tau and neural activity drive tau accumulation within medial temporal lobe. Aβ subsequently facilitates tau spread from medial to lateral temporal lobe. Our findings elucidate potential drivers of tau accumulation and spread in aging, which are critical for understanding Alzheimer's disease pathogenesis. SIGNIFICANCE STATEMENT To further understand the mechanisms leading to tau pathogenesis and spread, we tested whether baseline factors such as age, amyloid-β pathology, and activation predicted longitudinal tau accumulation in cognitively normal older adults. We found that distinct mechanisms contribute to tau accumulation as tau progresses across the temporal lobe, with initial tau accumulation in entorhinal cortex driven by age and subsequent spread driven by neural activity and amyloid-β. We demonstrate that higher baseline activation predicts increased longitudinal tau accumulation, providing novel evidence that activation-dependent tau production may occur in the human brain. Our findings support major hypotheses generated from preclinical research, and have important translational implications, suggesting that the reduction of hyperactivation may help prevent the development of tau pathology., (Copyright © 2022 the authors.)

Acupuncture has been used extensively in domestic animal medicine to treat a variety of medical conditions and diseases as an adjunct or primary therapy. Exotic animals are becoming increasingly common as pets. Owners are expecting therapies for these non-domestic animals to be similar to those available to their other domestic pets. Additionally, zoological and aquatic facilities provide medical care for the entire lives of the animals that are housed in their facilities. Many conditions similar to those observed in domestic animals can develop in zoological species and can benefit from treatment with acupuncture. Through operant conditioning or routine medical examinations, the use of acupuncture as an adjunct therapy is becoming more common. The following paper presents a summary of the types of non-domestic animals treated, for which conditions, and how these methods are commonly used.

This multi-institutional collaborative study of neoplasia in snakes reviewed medical records of snakes at each facility to determine species prevalence, survival, and methods of treatment. Complete species numbers of snakes were also collected at each facility. In total, 65 species, 133 snakes, and 149 unique neoplasias were included in this study. Affected species, age, sex, and their tumor prevalence, tumor type and location, metastasis, treatment, and survival data are reported. The highest species-specific tumor prevalence was in Common or Northern Watersnakes ( Nerodia sipedon ) (30.8%, n = 4 of 13), Eastern Diamond-Backed Rattlesnakes ( Crotalus adamanteus ) (26.3%, n = 5 of 19), and Timber rattlesnakes ( Crotalus horridus ) (22.7%, n = 5 of 22). Malignant tumors predominated (86.6%, n = 129 of 149) with soft tissue sarcomas being the most common (30.2%, n = 45 of 149). Snakes with malignant neoplasia, metastases, or indeterminate presence of metastases were statistically more likely to die from their neoplasms than snakes having either benign neoplasia or no diagnosed metastases ( p < 0.05). Gender, taxonomic family, and species of those evaluated did not significantly affect the outcome of snakes with neoplasia. Only 27.1% ( n = 36 of 133) of snakes received a reported form of treatment and, for those treated, surgical excision was the most common treatment modality. There was not a significant difference in outcome based on treatment; however, surgery and chemotherapy were associated with death from a cause other than their tumor.

Objective: To evaluate income and family planning decisions of American College of Zoological Medicine (ACZM) diplomates., Sample: 98 ACZM diplomates., Procedures: An online survey was sent to 201 ACZM diplomates. Participation was voluntary., Results: 98 (49%) diplomates responded to the survey. The most commonly reported income categories were $90,000 to $94,999, $100,000 to $104,999, and $110,000 to $114,999. Overall, the mean of the salary-category midpoint responses was $105,357 but was $122,917 for those in academia and $94,508 for those working in zoos and aquaria. When incomes of males and females were matched (24 pairs matched for gender and age), no difference in income was observed. There were no significant differences in income between males and females with and without children. Diplomates who did not complete a residency had significantly higher incomes than diplomates who did. Sixteen of 21 (76%) females and 9 of 19 (47%) males reported delaying having children because of their career. Additionally, a higher percentage of females with children (13/20 [65%]) than males with children (3/19 [16%]) felt that having children had had a negative effect on their career. Thirty-five of 41 (85%) females without children and 4 of 9 (44%) males without children thought having children would have negatively affected their careers., Clinical Relevance: Although substantial differences in income between female and male ACZM diplomates were not identified, differences in family planning and perceptions of the impact of having children on their careers did exist.

Positive tactile experiences in the newborn period are critical to normal sensory development. Universal gloving in the neonatal intensive care unit has become a controversial issue in neonatal nursing practice. Intended to prevent infection among neonatal patients, universal gloving also hinders the provision of human touch. The purpose of this survey study was to (1) describe gloving policies in neonatal intensive care units, and (2) describe the gloving and touch practices of neonatal nurses and identify associations between these practices and demographic characteristics. The investigators developed a 19-question, anonymous survey. The survey link was distributed through the National Association of Neonatal Nurses' social media and newsletter. Of the 137 responses, only 22.1% of nurses reported unit policy requiring universal gloving. While nurses reported some ambiguity about gloving policies, surveyed nurses commonly used gloves when performing general care activities. Institutional gloving policies varied in this geographically diverse sample, but routine, bare-handed touch was an uncommon practice among neonatal nurses. Research evidence is needed to guide nursing practice and inform policy decisions regarding glove use in the neonatal intensive care unit., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Difficulty retrieving proper names is common in older adults, coinciding with the accumulation of aggregated proteins in mid-life. We investigated the ability of healthy older adults to retrieve the names of famous faces in relation to positron emission tomography measurements of amyloid-β plaques and tau neurofibrillary tangles. More tau in the left fusiform and parahippocampal gyrus was related to reduced proper name retrieval performance and this effect was potentiated by amyloid-β. These findings provide an explanation for a common complaint of older adults and link proper name retrieval to neural systems involved in face perception, memory, and naming. ANN NEUROL 2021;90:988-993., (© 2021 American Neurological Association.)

Tau PET has allowed for critical insights into in vivo patterns of tau accumulation and change in individuals early in the Alzheimer's disease (AD) continuum. A key methodological step in tau PET analyses is the selection of a reference region, but there is not yet consensus on the optimal region especially for longitudinal tau PET analyses. This study examines how reference region selection influences results related to disease stage at baseline and over time. Longitudinal flortaucipir ([18F]-AV1451) PET scans were examined using several common reference regions (e.g., eroded subcortical white matter, inferior cerebellar gray matter) in 62 clinically unimpaired amyloid negative (CU A-) individuals, 73 CU amyloid positive (CU A+) individuals, and 64 amyloid positive individuals with mild cognitive impairment (MCI A+) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cross-sectionally, both reference regions resulted in robust group differences between CU A-, CU A+, and MCI A+ groups, along with significant associations with CSF phosphorylated tau (pTau-181). However, these results were more focally specific and akin to Braak Staging when using eroded white matter, whereas effects with inferior cerebellum were globally distributed across most cortical regions. Longitudinally, utilization of eroded white matter revealed significant accumulation greater than zero across more regions whereas change over time was diminished using inferior cerebellum. Interestingly, the inferior temporal target region seemed most robust to reference region selection with expected cross-sectional and longitudinal signal across both reference regions. With few exceptions, baseline tau did not significantly predict longitudinal change in tau in the same region regardless of reference region. In summary, reference region selection deserves further evaluation as this methodological step may lead to disparate findings. Inferior cerebellar gray matter may be more sensitive to cross-sectional flortaucipir differences, whereas eroded subcortical white matter may be more sensitive for longitudinal analyses examining regional patterns of change., Competing Interests: Declaration of Competing Interest Dr. Landau serves on the Advisory Board for KeifeRx; Dr. Mormino has served as a consultant to Roche, Genentech, Eli Lilly, and Alector; remaining authors do not have possible conflicts of interest related to this work., (Copyright © 2021. Published by Elsevier Inc.)

The mechanisms underlying accumulation of Alzheimer's disease (AD)-related tau pathology outside of the medial temporal lobe (MTL) in older adults are unknown but crucial to understanding cognitive decline. A growing body of evidence from human and animal studies strongly implicates neural connectivity in the propagation of tau in humans, but the pathways of neocortical tau spread and its consequences for cognitive function are not well understood. Using resting state functional magnetic resonance imaging (fMRI) and tau PET imaging from a sample of 97 male and female cognitively normal older adults, we examined MTL structures involved in medial parietal tau accumulation and associations with memory function. Functional connectivity between hippocampus (HC) and retrosplenial cortex (RsC), a key region of the medial parietal lobe, was associated with tau in medial parietal lobe. By contrast, connectivity between entorhinal cortex (EC) and RsC did not correlate with medial parietal lobe tau. Further, greater hippocampal-retrosplenial (HC-RsC) connectivity was associated with a stronger correlation between MTL and medial parietal lobe tau. Finally, an interaction between connectivity strength and medial parietal tau was associated with episodic memory performance, particularly in the visuospatial domain. This pattern of tau accumulation thus appears to reflect pathways of neural connectivity, and propagation of tau from EC to medial parietal lobe via the HC may represent a critical process in the evolution of cognitive dysfunction in aging and AD. SIGNIFICANCE STATEMENT The accumulation of tau pathology in the neocortex is a fundamental process underlying Alzheimer's disease (AD). Here, we use functional connectivity in cognitively normal older adults to track the accumulation of tau in the medial parietal lobe, a key region for memory processing that is affected early in the progression of AD. We show that the strength of connectivity between the hippocampus (HC) and retrosplenial cortex (RsC) is related to medial parietal tau burden, and that these tau and connectivity measures interact to associate with episodic memory performance. These findings establish the HC as the origin of medial parietal tau and implicate tau pathology in this region as a crucial marker of the beginnings of AD., (Copyright © 2021 the authors.)

Background and Purpose: The prenatal preparing women do for infant caregiving is understudied. In this pilot, multimethods study, we examined motivation for preparing for infant caregiving of women in their third trimester of pregnancy expecting either a healthy infant or an infant with complex congenital heart disease (CCHD)., Methods: Eleven women expecting a healthy infant and four expecting an infant with CCHD completed a questionnaire and were interviewed. Preparing was reported in context of expectations, intentions, and goals and in personal, family, and infant conditions. Motivation for preparing was expressed through an interview about caregiving issues women were working on. Intensity of motivation was estimated by self-report of the time infant caregiving issues were in thought or action. Effect sizes were calculated for between group differences in motivation intensity. Interview data were examined with directed content analysis., Results: Intensity of motivation was higher for women expecting an infant with CCHD for issues of Knowing What and How to prepare. Women expecting an infant with CCHD reported uncertainty about how they would feed their babies given their health condition. Interviews yielded new motivations encompassing issues of family and working with the parent partner., Implications: Assessment of issues women are working on prenatally, indicating motivations for preparing for infant caregiving, and of the intensity of motivations advances culturally-attuned and family-centered preparation. Knowledge of these issues and motivation intensity could orient clinical care to supporting women in developing well-informed expectations, intentions, and goals culturally suited to postnatal learning and infant needs., (© Copyright 2022 Springer Publishing Company, LLC.)

Alzheimer's disease is associated with poor sleep, but the impact of tau and β-amyloid (Aβ) pathology on sleep remains largely unknown. Here, we test the hypothesis that tau and Aβ predict unique impairments in objective and self-perceived human sleep under real-life, free-living conditions. Eighty-nine male and female cognitively healthy older adults received 18 F-FTP-tau and 11 C-PIB-Aβ PET imaging, 7 nights of sleep actigraphy and questionnaire measures, and neurocognitive assessment. Tau burden, but not Aβ, was associated with markedly worse objective sleep. In contrast, Aβ and tau were associated with worse self-reported sleep quality. Of clinical relevance, Aβ burden predicted a unique perceptual mismatch between objective and subject sleep evaluation, with individuals underestimating their sleep. The magnitude of this mismatch was further predicted by worse executive function. Thus, early-stage tau and Aβ deposition are linked with distinct phenotypes of real-world sleep impairment, one that includes a cognitive misperception of their own sleep health. SIGNIFICANCE STATEMENT Alzheimer's disease is associated with sleep disruption, often before significant memory decline. Thus, real-life patterns of sleep behavior have the potential to serve as a window into early disease progression. In 89 cognitive healthy older adults, we found that tau burden was associated with worse wristwatch actigraphy-measured sleep quality, and that both tau and β-amyloid were independently predictive of self-reported sleep quality. Furthermore, individuals with greater β-amyloid deposition were more likely to underestimate their sleep quality, and sleep quality underestimation was associated with worse executive function. These data support the role of sleep impairment as a key marker of early Alzheimer's disease, and offer the possibility that actigraphy may be an affordable and scalable tool in quantifying Alzheimer's disease-related behavioral changes., (Copyright © 2021 the authors.)

Objective: To describe the anatomy of the brachial plexus in eastern box turtles (Terrapene carolina carolina), develop a blind perineural injection technique for brachial plexus blockade and evaluate the distribution of three volumes of new methylene blue dye for injection in cadavers., Study Design: Prospective, randomized, blinded cadaveric study., Animals: A total of 24 frozen-thawed box turtle cadavers; two turtles identified with shoulder injuries were subsequently excluded from the study. The remaining 22 turtles weighed 397 (190-581) g, median (range)., Methods: The brachial plexus and regional anatomy were identified by dissection of seven cadavers to determine anatomic landmarks for a perineural injection technique. This technique was tested by randomizing 15 cadavers into one of three groups to be injected bilaterally with one of three volumes (0.1, 0.2 or 0.3 mL) of methylene blue dye 1% aqueous solution. Investigators blinded to the assigned group dissected cadavers 15 minutes after injection and used staining of the four cervical spinal nerves (C5-C8; 25% for each nerve) to record a staining score of the brachial plexus (0-100%)., Results: Based on descriptions of the anatomy of the brachial plexus, an injection technique was designed. Injections of 0.1 mL methylene blue dye resulted in nine/10 injections with 100% nerve stained, and one/10 injection with 50% (two) nerves stained. All injections of 0.2 or 0.3 mL of methylene blue dye resulted in 100% nerves stained., Conclusions and Clinical Relevance: Perineural injection of the brachial plexus with 0.1, 0.2 or 0.3 mL methylene blue dye was successful in 29/30 injections in box turtle cadavers weighing 190-581 g. Further studies are needed to determine the minimum volume of injectate that can be successfully used for this technique, and to evaluate its application and efficacy in live turtles., (Copyright © 2021 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

In presymptomatic Alzheimer's disease (AD), beta-amyloid plaques (Aβ) and tau tangles accumulate in distinct spatiotemporal patterns within the brain, tracking closely with episodic memory decline. Here, we tested whether age-related changes in the segregation of the brain's intrinsic functional episodic memory networks-anterior-temporal (AT) and posterior-medial (PM) networks-are associated with the accumulation of Aβ, tau, and memory decline using fMRI and PET. We found that AT and PM networks were less segregated in older than that in younger adults and this reduced specialization was associated with more tau and Aβ in the same regions. The effect of network dedifferentiation on memory depended on the amount of Aβ and tau, with low segregation and pathology associated with better performance at baseline and low segregation and high pathology related to worse performance over time. This pattern suggests a compensation phase followed by a degenerative phase in the early, preclinical phase of AD., (Published by Oxford University Press 2021.)

Disease susceptibility and resistance are important factors for the conservation of endangered species, including elephants. We analyzed pathology data from 26 zoos and report that Asian elephants have increased neoplasia and malignancy prevalence compared with African bush elephants. This is consistent with observed higher susceptibility to tuberculosis and elephant endotheliotropic herpesvirus (EEHV) in Asian elephants. To investigate genetic mechanisms underlying disease resistance, including differential responses between species, among other elephant traits, we sequenced multiple elephant genomes. We report a draft assembly for an Asian elephant, and defined 862 and 1,017 conserved potential regulatory elements in Asian and African bush elephants, respectively. In the genomes of both elephant species, conserved elements were significantly enriched with genes differentially expressed between the species. In Asian elephants, these putative regulatory regions were involved in immunity pathways including tumor-necrosis factor, which plays an important role in EEHV response. Genomic sequences of African bush, forest, and Asian elephant genomes revealed extensive sequence conservation at TP53 retrogene loci across three species, which may be related to TP53 functionality in elephant cancer resistance. Positive selection scans revealed outlier genes related to additional elephant traits. Our study suggests that gene regulation plays an important role in the differential inflammatory response of Asian and African elephants, leading to increased infectious disease and cancer susceptibility in Asian elephants. These genomic discoveries can inform future functional and translational studies aimed at identifying effective treatment approaches for ill elephants, which may improve conservation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Objective: To use CT-derived measurements to calculate a shape constant (K constant) and create a formula to calculate body surface area (BSA) on the basis of body weight in bearded dragons ( Pogona vitticeps )., Animals: 12 adult client-owned bearded dragons that underwent CT between December 4, 2019, and April 2, 2020., Procedures: Each bearded dragon in this prospective cohort study underwent physical examination, body weight measurement, and CT. A 3-D surface model was then reconstructed from CT data with available software and used for BSA calculations. Animals were considered collectively and grouped by sex and age. Nonlinear regression analysis of BSA versus body weight was performed, and a species-specific formula was derived for calculating BSA in bearded dragons., Results: Mean age, body weight, and CT-derived BSA were 2.1 years, 356 g, and 580 cm 2 . The calculated K constant was 11.6 ( R 2 = 0.994; SE = 0.275) for the 12 bearded dragons, and the CT-derived BSA formula was as follows: BSA in cm 2 = 11.6 × (body weight in g) 2/3 . The K constant differed substantially for bearded dragons grouped by age (12.1 for younger [between 1 and ≤ 2 years of age; n = 8] vs 10.9 for older [> 2 years of age; 4] animals) but did not differ on the basis of sex., Conclusions and Clinical Relevance: Results indicated that because the K constant for bearded dragons in the present study was larger than the preexisting K constant of 10 used for reptiles or the various K constants established for some companion mammals, doses of chemotherapeutic drugs needed to treat affected bearded dragons may be higher than previously thought.

Introduction: Published reports of associations between β-amyloid (Aβ) and cortical integrity conflict. Tau biomarkers may help elucidate the complex relationship between pathology and neurodegeneration in aging., Methods: We measured cortical thickness using magnetic resonance imaging, Aβ using Pittsburgh compound B positron emission tomography (PiB-PET), and tau using flortaucipir (FTP)-PET in 125 cognitively normal older adults. We examined relationships among PET measures, cortical thickness, and cognition., Results: Cortical thickness was reduced in PiB+/FTP+ participants compared to the PiB+/FTP- and PiB-/FTP- groups. Continuous PiB associations with cortical thickness were weak but positive in FTP- participants and negative in FTP+. FTP strongly negatively predicted thickness regardless of PiB status. FTP was associated with memory and cortical thickness, and mediated the association of PiB with memory., Discussion: Past findings linking Aβ and cortical thickness are likely weak due to opposing effects of Aβ on cortical thickness relative to tau burden. Tau, in contrast to Aβ, is strongly related to cortical thickness and memory., (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Tau deposition begins in the medial temporal lobe (MTL) in aging and Alzheimer's disease (AD), and MTL neural dysfunction is commonly observed in these groups. However, the association between tau and MTL neural activity has not been fully characterized. We investigated the effects of tau on repetition suppression, the reduction of activity for repeated stimulus presentations compared to novel stimuli. We used task-based functional MRI (fMRI) to assess MTL subregional activity in 21 young adults (YA) and 45 cognitively normal human older adults (OA; total sample: 37 females, 29 males). AD pathology was measured with position emission tomography (PET), using 18 F-Flortaucipir for tau and 11 C-Pittsburgh compound B (PiB) for amyloid-β (Aβ). The MTL was segmented into six subregions using high-resolution structural images. We compared the effects of low tau pathology, restricted to entorhinal cortex and hippocampus (Tau- OA), to high tau pathology, also occurring in temporal and limbic regions (Tau+ OA). Low levels of tau (Tau- OA vs YA) were associated with reduced repetition suppression activity specifically in anterolateral entorhinal cortex (alEC) and hippocampus, the first regions to accumulate tau. High tau pathology (Tau+ vs Tau- OA) was associated with widespread reductions in repetition suppression across MTL. Further analyses indicated that reduced repetition suppression was driven by hyperactivity to repeated stimuli, rather than decreased activity to novel stimuli. Increased activation was associated with entorhinal tau, but not Aβ. These findings reveal a link between tau deposition and neural dysfunction in MTL, in which tau-related hyperactivity prevents deactivation to repeated stimuli, leading to reduced repetition suppression. SIGNIFICANCE STATEMENT Abnormal neural activity occurs in the medial temporal lobe (MTL) in aging and Alzheimer's disease (AD). Because tau pathology first deposits in the MTL in aging, this altered activity may be due to local tau pathology, and distinct MTL subregions may be differentially vulnerable. We demonstrate that in older adults (OAs) with low tau pathology, there are focal alterations in activity in MTL subregions that first develop tau pathology, while OAs with high tau pathology have aberrant activity throughout MTL. Tau was associated with hyperactivity to repeated stimulus presentations, leading to reduced repetition suppression, the discrimination between novel and repeated stimuli. Our data suggest that tau deposition is related to abnormal activity in MTL before the onset of cognitive decline., (Copyright © 2021 the authors.)

Beyond the complex logistical task of prioritizing, distributing and safely storing millions of doses of COVID-19 vaccines, state and local governments must simultaneously devise and carry out transparent plans that center equity and overcome the barriers to vaccination facing minority communities. Using insights gleaned from four focus groups conducted with health care and social service professionals serving minority communities in New York State as well as from existing research on vaccination, our results emphasize that vaccine hesitancy and access barriers-particularly within minority communities-pose significant hurdles to achieving widespread uptake of COVID-19 vaccines. Overcoming barriers requires community-engaged campaigns that acknowledge and address the historical injustices and on-going inequities that drive distrust within communities of color, emphasize understandable and culturally appropriate messages that directly address people's concerns about vaccine safety and access, and tap existing community infrastructure to make full use of trusted voices to deliver timely and accurate information about vaccines. Given emerging data and changing conditions, campaigns must also be self-reflective and adaptive, assessing progress and outcomes and reevaluating strategies as needed. However, above all, primary goals should remain focused on transparency, equity and building trust., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Strully, Harrison, Pardo and Carleo-Evangelist.)

Case Description: 2 male and 3 female adult bearded dragons ( Pogona vitticeps ) were evaluated at the North Carolina State University College of Veterinary Medicine's Exotic Animal Medicine Service between September 2018 and October 2019 because of severe lymphocytosis., Clinical Findings: All 5 bearded dragons had nonspecific clinical signs, including lethargy, poor appetite, ocular discharge, and weight loss. Clinicopathologic testing revealed extremely high lymphocyte counts with morphological findings consistent with lymphocytic leukemia., Treatment and Outcome: All 5 patients were treated with lomustine, prednisolone, and antimicrobials. In addition, 1 or 2 doses of L-asparaginase were administered when the drug was available. Partial remission was achieved in all 5 patients. One patient, after disease progression was documented, was treated with cyclophosphamide and achieved a second partial remission. One of the 5 patients was still alive and continuing to receive chemotherapy at the time of final follow-up 244 days after the initial diagnosis. Survival times (ie, times from initial diagnosis to euthanasia) for the other 4 patients were 57, 157, 330, and 416 days., Clinical Relevance: The present report represented the first description of lomustine as a primary chemotherapeutic agent for the treatment of lymphocytic leukemia in bearded dragons and provided information on response to treatment, adverse effects, and survival times.

Studies suggest that tau deposition starts in the anterolateral entorhinal cortex (EC) with normal aging, and that the presence of β-amyloid (Aβ) facilitates its spread to neocortex, which may reflect the beginning of Alzheimer's disease (AD). Functional connectivity between the anterolateral EC and the anterior-temporal (AT) memory network appears to drive higher tau deposition in AT than in the posterior-medial (PM) memory network. Here, we investigated whether this differential vulnerability to tau deposition may predict different cognitive consequences of EC, AT, and PM tau. Using 18 F-flortaucipir (FTP) and 11 C-Pittsburgh compound-B (PiB) positron emission tomography (PET) imaging, we measured tau and Aβ in 124 cognitively normal human older adults (74 females, 50 males) followed for an average of 2.8 years for prospective cognition. We found that higher FTP in all three regions was individually related to faster memory decline, and that the effects of AT and PM FTP, but not EC, were driven by Aβ+ individuals. Moreover, when we included all three FTP measures competitively in the same model, only AT FTP significantly predicted memory decline. Our data support a model whereby tau, facilitated by Aβ, transits from EC to cortical regions that are most closely associated with the anterolateral EC, which specifically affects memory in the initial stage of AD. Memory also appears to be affected by EC tau in the absence of Aβ, which may be less clinically consequential. These findings may provide clarification of differences between normal aging and AD, and elucidate the transition between the two stages. SIGNIFICANCE STATEMENT Tau and β-amyloid (Aβ) are hallmarks of Alzheimer's disease (AD) but are also found in cognitively normal people. It is unclear whether, and how, this early deposition of tau and Aβ may affect cognition in normal aging and the asymptomatic stage of AD. We show that tau deposition in the entorhinal cortex (EC), which is common in advanced age, predicts memory decline in older adults independent of Aβ, likely reflecting normal, age-related memory loss. In contrast, tau in anterior-temporal (AT) regions is most predictive of memory decline in Aβ+ individuals. These data support the idea that tau preferentially spreads to specific cortical regions, likely through functional connections, which plays a primary role in memory decline in the early stage of AD., (Copyright © 2021 the authors.)

Little is known about the association between personality and Alzheimer's disease (AD) biomarkers, and existing results are inconsistent. We aimed to determine whether personality was associated with β-amyloid (Aβ) accumulation in cognitively normal aging. One hundred twenty-nine participants were included in this cross-sectional study. Personality was measured with the Big Five Inventory (BFI) and brain Aβ deposition was assessed with [11C] Pittsburgh compound B (PiB)-positron emission tomography (PET) imaging. Conscientiousness scores had a negative association with global PiB distribution volume ratio (DVR) in all participants after adjusting for age, sex, education, and vascular risk factors (β[SE] = -0.19[0.09], 95% confidence interval [CI: -0.35, -0.02], p = .031), while agreeableness, extraversion, neuroticism, and openness had no association with global PiB DVR. Assuming the relative stability of personality traits, these findings suggest that conscientiousness may protect against Aβ accumulation in cognitively normal aging through mechanisms that are as yet unknown. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background: Congenital heart disease (CHD) survivors are at risk for cardiovascular comorbidities exacerbated by obesity., Objectives: Determine relationships between overweight/obesity and medical factors across the lifespan of CHD., Methods: Lesion severity, weight, blood pressure, cardiac and other comorbidities, and cardiac medications were abstracted from the medical records of 3790 CHD patients, aged ≥6 years, who attended CHD care in the Midwestern U.S., Results: The proportion of patients with overweight/obesity increased across the lifespan, with 73% of adults affected by overweight/obesity. Obesity was more prevalent among patients with moderate lesions (29%). Overweight/obesity was associated with elevated blood pressure across age and lesion severity. Young adults with obesity and simple or moderate lesions had more comorbidities (simple: IRR = 3.1, moderate: IRR = 2.3) and cardiac medications (simple: IRR = 2.2, moderate: IRR = 1.7)., Conclusions: Obesity and its cardiovascular correlates are present across the lifespan for CHD survivors, highlighting the need for early prevention and intervention., Competing Interests: Declaration of Competing Interest The authors have no conflicts to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Developmental delay is a significant concern for infants born with complex congenital heart disease (CCHD). Environmental exposures (e.g., excessive light and sound exposure, sleep disruption) in neonatal intensive care are associated with poor developmental outcomes. However, the environmental experience of newborn infants in cardiac care is unknown., Objectives: The aim of the study was to examine the feasibility of continuous environmental data collection (i.e., light and sound exposure, sleep pattern) in pediatric cardiac care units and describe the environmental experience of three hospitalized infants with CCHD., Methods: A case series of three infants undergoing cardiac surgery for CCHD within the first month of life was performed. Measures of light, sound, and sleep were collected in 24-hour periods on three to four separate hospital days. For each day, light and sound meters were attached to the hospital bed, and an actigraphy band was placed on the infant's lower leg to measure sleep/wake states. Feasibility of continuous environmental data collection was assessed through acceptability of data collection for families and clinical staff, usability of data collection equipment for research staff, and study protocol adherence. Descriptive statistics were used to calculate the count and duration of episodes of excessive light and sound exposure, hourly levels of light and sound exposure, total sleep time, duration of individual sleep episodes, and number of arousals from sleep., Results: Although continuous environmental data collection was generally acceptable to families and clinical staff, multiple usability issues were identified by research staff, and study protocol adherence was variable. Missing data were a major limitation. User error during equipment setup was a main contributor to missing data. Infants experienced frequent episodes of sound exposure above recommended maximum levels, whereas light exposure generally remained below recommended maximum levels. Infant sleep patterns were highly fragmented, with frequent arousals and short duration of individual sleep episodes., Discussion: Lessons learned during preliminary data collection with the infants in this case series will inform methods and prevent missing data in future, large-scale studies of this vulnerable, hard-to-recruit population. Data reflect a cardiac care environment characterized by excessive sound exposure and highly disrupted sleep. These environmental stressors may affect developmental outcomes in infants with CCHD.

Background: Extended hospitalization in neonatal intensive care units subjects preterm infants to multiple stress exposures that affect long-term cognitive functioning, motor development, and stress reactivity. Measurement of stress exposure is challenging with multiple measures of stress exposure in use, including counts of skin-breaking or invasive procedures or counts of noxious sensory exposures., Objectives: The purpose of this analysis was to compare measures of stress exposure commonly used by researchers and to determine the predictive validity of these measures for early neurobehavior. We accomplished this objective through the following specific aims: (a) describe the stress exposures of preterm infants in the first 2 weeks of life, (b) determine the correlations among measures of stress exposure, and (c) compare the predictive validity of measures of stress exposure for early neurobehavior., Methods: Very preterm infants born between 28 and 31 weeks postmenstrual age were enrolled from four neonatal intensive care units in a large Midwest city. We measured stress exposure over the first 14 days of life for each infant as a count of skin-breaking procedures, a count of invasive procedures, and cumulative scores derived from the Neonatal Infant Stressor Scale. Neurobehavior was assessed at 35 weeks postmenstrual age using the motor development and vigor and alertness/orientation subscales from the Neurobehavioral Assessment of the Preterm Infant. We used Spearman's rho to determine correlations among the measures of stress exposure and multiple linear regression to determine the predictive validity of each stress exposure measure for neurobehavioral outcomes., Results: Seventy-one preterm infants were included in the analysis. We found marked variance across individuals in all measures of stress exposure. There were moderate-high correlations among the measures of stress exposure. No measure of stress exposure was associated with early neurobehavior., Discussion: The stress experiences of hospitalized preterm infants vary. This variance is reflected in all measures of stress exposure. Because measures of stress exposure are highly correlated, the most objective measure requiring the least interpretation should be used. However, the currently available measures of stress exposure used in this analysis may not reflect the infant's physiological stress responses and fail to associate with early neurobehavior.

We studied domestic ferrets ( Mustela putorius furo ) to evaluate the physiologic effects of routine surgery. Standard plasma biochemistry panels and 1 H-NMR spectroscopy of heparinized whole blood were performed on samples taken 24 h prior to and immediately after surgery from female and male ferrets undergoing routine gonadectomy. Increases in plasma glucose, phosphorus, potassium, and creatine kinase concentrations associated with the duration of surgery were identified on plasma biochemistry panels. Whole-blood NMR spectra allowed us to identify 42 metabolites and one drug residue. Variations between pre- and postoperative metabolite concentrations were most pronounced for female ferrets, which underwent more prolonged surgery than males. Affected metabolites included organic acids and osmolytes (betaine, methylmalonate, D-lactate), fatty acids and lipids (2-hydroxy-3-methylbutyric acid), and amino acid groups (acetylglycine, alloisoleucine, leucine, and isoleucine). These findings indicate that 1 H-NMR spectroscopy of whole blood provides insight into metabolic perturbations in domestic ferrets undergoing surgery that are not detected in routine clinical chemistry panels.

Background: Infants with complex congenital heart defects (CCHDs) experience alterations in growth that develop following surgical intervention and persist throughout early infancy, but the roles of nutritional intake and method of feeding require further exploration as their roles are not fully explained., Objectives: The purpose of this study was to characterize trends in growth and nutritional intake during the first 6 months of life in infants with CCHD., Methods: We conducted a secondary analysis of growth and nutritional data from a pilot study designed to test the feasibility of nurse-guided participatory intervention with parents of infants with CCHD. Measures included demographic data, anthropometric data at birth, hospital discharge, and 6 months of age, nutritional intake at 2 and 6 months of age from parent-completed 24-hour nutrition diaries, and assessment of oral-motor skills between 1 and 2 months of age. Descriptive statistics and correlation and group differences were examined., Results: Data for 28 infants were analyzed. Infants demonstrated a decrease in weight-for-age z score (WAZ) and length-for-age z score (LAZ) from birth to hospital discharge and an increase in WAZ and LAZ by 6 months of age. Many of the infants developed failure to thrive. Across the study period, one third of the infants were receiving enteral nutrition. Infants who were orally fed had better growth WAZ and LAZ at 6 months of age when compared to infants who were enterally fed., Discussion: Infants with CCHD exhibit growth faltering throughout early infancy. Reliance on enteral nutrition did not improve growth outcomes in these infants. Findings suggest nutritional intake may not be enough to meet the nutrient requirements to stimulate catch-up growth.

Background: Pain management is an essential component of care for pediatric patients following surgery. Massage reduces self-reported postoperative pain in adults with heart disease but has received little attention in postoperative pediatric patients with complex congenital heart disease (CCHD)., Objectives: The aim of the study was to evaluate the effectiveness of massage compared to a rest period on postoperative pain scores and physiological responses in infants with CCHD., Methods: We used a two-group randomized clinical trial design with a sample of 60 infants with CCHD between 1 day and 12 months of age following their first cardiothoracic surgery. Both groups received standard postoperative care. Group 1 received a daily 30-minute restriction of nonessential caregiving (quiet time), and Group 2 received a daily 30-minute massage. Interventions continued for seven consecutive days. Pain was measured six times daily using the Face, Legs, Activity, Cry, Consolability Pain Assessment Tool (FLACC). Average daily doses of analgesics were recorded. Heart rates (HRs), respiratory rates (RRs), and oxygen saturations (SpO2) were recorded continuously. Daily averages, pre- and postintervention FLACC scores, and physiological responses were analyzed using descriptive statistics, generalized linear mixed models repeated measures, latent growth models, and/or regression discontinuity analysis. Fentanyl-equivalent narcotic values were used as a time-varying covariate., Results: Adjusted pain scores were lower for the massage group on all days except Day 7. Overall, there were no group effects on level of pain or differential rate of change in pain. However, the massage group had lower daily pain scores with small to medium effect size differences, largest at Days 4, 5, and 6, and lower average daily HR and RR. There was little difference between groups in SpO2. Infants demonstrated immediate effects of massage, with HR and RR decreasing and oxygen saturations increasing., Discussion: This study provides beginning evidence that postoperative massage may reduce pain and improve physiological parameters in infants with congenital heart disease. This nonpharmacological adjunct to pain management may provide a particular benefit for this population by reducing demand on the cardiorespiratory system.

Accurately quantifying the composition of continental crust on Hadean and Archean Earth is critical to our understanding of the physiography, tectonics, and climate of our planet at the dawn of life. One longstanding paradigm involves the growth of a relatively mafic planetary crust over the first 1 to 2 billion years of Earth history, implying a lack of modern plate tectonics and a paucity of subaerial crust, and consequently lacking an efficient mechanism to regulate climate. Others have proposed a more uniformitarian view in which Archean and Hadean continents were only slightly more mafic than at present. Apart from complications in assessing early crustal composition introduced by crustal preservation and sampling biases, effects such as the secular cooling of Earth's mantle and the biologically driven oxidation of Earth's atmosphere have not been fully investigated. We find that the former complicates efforts to infer crustal silica from compatible or incompatible element abundances, while the latter undermines estimates of crustal silica content inferred from terrigenous sediments. Accounting for these complications, we find that the data are most parsimoniously explained by a model with nearly constant crustal silica since at least the early Archean., Competing Interests: The authors declare no competing interest.

Biochemical testing is an important clinical tool in evaluating the physiology of reptiles and amphibians. Suitable point of care analyzers can allow for rapid delivery of results, but small patient size can inhibit sufficient sample collection. This study evaluated the utility of sample dilution with sterile distilled water as a means of biochemical evaluation when sample volume is limited. Blood was collected from 12 eastern box turtles ( Terrapene carolina carolina ) and 12 marine toads (Rhinella marinus ) and analyzed via i-STAT CHEM8+ cartridges. Two undiluted samples and two samples diluted 1 : 1 with sterile water were evaluated immediately following collection for each animal in the study. Analytes reported in the diluted samples were limited to glucose, ionized calcium, and total carbon dioxide. The expected dilution ratio value of diluted to undiluted samples was 0.5, of which glucose in both turtles and toads was nearest. Dilution ratio values for ionized calcium, however, were higher than expected in both turtles and toads. Sample dilution is not recommended for most analytes included on the CHEM8+ cartridge due to values occurring outside the limits of detection for the analyzer. Glucose and ionized calcium values obtained on diluted samples should be interpreted with caution but may provide clinical utility in reptile and amphibian patients where sample volume is limited., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 John A. Griffioen et al.)

Cancer has deep evolutionary roots and is an important source of selective pressure in organismal evolution. Yet, we find a great deal of variation in cancer vulnerabilities across the tree of life. Comparative oncology offers insights into why some species vary in their susceptibility to cancer and the mechanisms responsible for the diversity of cancer defenses. Here we provide an overview for why cancer persists across the tree of life. We then summarize current data on cancer in mammals, reptiles, and birds in comparison with commonly reported human cancers. We report on both novel and shared mechanisms of cancer protection in animals. Cross-discipline collaborations, including zoological and aquarium institutions, wildlife and evolutionary biologists, veterinarians, medical doctors, cancer biologists, and oncologists, will be essential for progress in the field of comparative oncology. Improving medical treatment of humans and animals with cancer is the ultimate promise of comparative oncology., Competing Interests: Declaration of Interests Dr. Abegglen is shareholder and consultant to PEEL Therapeutics, Inc., a company developing evolution-inspired medicines based on cancer resistance in elephants., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The abnormal deposition of tau begins before the onset of clinical symptoms and seems to target specific brain networks. The aim of this study is to identify the spatial patterns of tau deposition in cognitively normal older adults and assess whether they are related to amyloid-β (Aβ), APOE, sex, and longitudinal cognitive decline., Methods: We included 114 older adults with cross-sectional flortaucipir (FTP) and Pittsburgh Compound-B PET in addition to longitudinal cognitive testing. A voxel-wise independent component analysis was applied to FTP images to identify the spatial patterns of tau deposition. We then assessed whether tau within these patterns differed by Aβ status, APOE genotype, and sex. Linear mixed effects models were built to test whether tau in each component predicted cognitive decline. Finally, we ordered the spatial components based on the frequency of high tau deposition to model tau spread., Results: We found 10 biologically plausible tau patterns in the whole sample. There was greater tau in medial temporal, occipital, and orbitofrontal components in Aβ-positive compared with Aβ-negative individuals; in the parahippocampal component in ε3ε3 compared with ε2ε3 carriers; and in temporo-parietal and anterior frontal components in women compared with men. Higher tau in temporal and frontal components predicted longitudinal cognitive decline in memory and executive functions, respectively. Tau deposition was most frequently observed in medial temporal and ventral cortical areas, followed by lateral and primary areas., Conclusions: These findings suggest that the spatial patterns of tau in asymptomatic individuals are clinically meaningful and are associated with Aβ, APOE ε2ε3, sex and cognitive decline. These patterns could be used to predict the regional spread of tau and perform in vivo tau staging in older adults.