Use of the Electronic Health Record to Improve Nursing Chart Preparation.

In a medical specialty clinic located in a rural community, a nursing team identified an opportunity to decrease the time nursing staff spent preparing charts for patients' upcoming clinical appointments. In collaboration with an informaticist, the nursing project team implemented a quality improvement project with a target goal of decreasing the average time spent preparing charts per patient by 20%, without increasing the number of discrepancies in the chart preparation process. The team used the define, measure, analyze, improve, and control framework to identify two interventions that could decrease time for chart preparation. A standardized chart preparation process was developed, and a condensed nursing view was created within the electronic health record. After the quality improvement project, the average time nurses spent on chart preparation per patient decreased by 18% after the standardized process and 16% after the condensed view was implemented.

Haploinsufficiency of Syngap1 in striatal indirect pathway neurons alters motor and goal-directed behaviors in mice.

SYNGAP1 is a high-confidence autism spectrum disorder (ASD) risk gene and mutations in SYNGAP1 lead to a neurodevelopmental disorder (NDD) that presents with epilepsy, ASD, motor developmental delay, and intellectual disability. SYNGAP1 codes for Ras/Rap GTP-ase activating protein SynGAP (SynGAP). In mice, SynGAP is located in the postsynaptic density of glutamatergic synapses and regulates glutamate receptor trafficking in an activity-dependent manner. In addition to forebrain glutamatergic neurons, Syngap1 is highly expressed in the striatum, although the functions of SynGAP in the striatum have not been extensively studied. Here we show that Syngap1 is expressed in both direct and indirect pathway striatal projection neurons (dSPNs and iSPNs) in mice of both sexes. In a mouse model of Syngap1 haploinsufficiency, dendritic spine density, morphology, and intrinsic excitability are altered primarily in iSPNs, but not dSPNs. At the behavioral level, SynGAP reduction alters striatal-dependent motor learning and goal-directed behavior. Several behavioral phenotypes are reproduced by iSPN-specific Syngap1 reduction and, in turn, prevented by iSPN-specific Syngap1 rescue. These results establish the importance of SynGAP to striatal neuron function and pinpoint the indirect pathway as a key circuit in the neurobiology of SYNGAP1-related NDD.Significance statement SYNGAP1 mutations cause a neurodevelopmental disorder presenting with intellectual disability, motor problems, epilepsy, autism spectrum disorder, and a constellation of other behavioral and psychiatric conditions. SynGAP protein is highly expressed in the striatum but its functions in this brain region have not yet been explored. This study shows that loss of one copy of the Syngap1 gene from striatal indirect, but not direct, pathway neurons alters synaptic properties, cellular excitability, motor behaviors, and goal-directed responding in mice. This work provides a new perspective on the functions of SynGAP and suggests that altered activity in striatal circuits may be an important driver of the motor and learning alterations in people with SYNGAP1 disorder.

Neuroinflammation and blood-brain barrier breakdown in acute, clinical intracerebral hemorrhage.

Neuroinflammation is a promising therapeutic target in intracerebral hemorrhage (ICH), characterized in the brain by microglial activation and blood-brain barrier (BBB) breakdown. In this study, 36 acute, spontaneous, supratentorial ICH patients underwent dynamic contrast-enhanced MRI to measure BBB permeability (Ktrans) 1-3 days post-onset and 16 returned for [11C](R)-PK11195 PET to quantify microglial activation (BPND), 2-7 days post-onset. We first tested if these markers were increased and co-localized in the perihematomal brain and found that perihematomal Ktrans and BPND were increased vs. the contralateral brain, but regions of high Ktrans and BPND only overlapped by a mean of 4.9%. We then tested for associations of perihematomal Ktrans and BPND with clinical characteristics (age, ICH volume & location, blood pressure), other markers of inflammation (edema, IL-6, and CRP), and long-term functional outcome (90-day mRS). Lower perihematomal BPND was associated with increasing age. Lobar hemorrhage was associated with greater Ktrans than deep, but Ktrans and BPND were not associated with ICH volume, or other inflammatory markers. While perihematomal Ktrans and BPNDwere not associated with outcome, contralateral Ktrans was significantly associated with greater 90-day mRS. Exploratory analyses demonstrated that blood pressure variability over 72 h was also associated with contralateral Ktrans.

Mantled howler monkeys (Alouatta palliata) alter activity and spatial cohesion across a continuous forest and forest fragment in Costa Rica.

Habitat loss due to deforestation is a primary threat to global biodiversity. Clearing tropical rainforests for agriculture or development leads to forest fragmentation. Forest fragments contain fewer large trees and provide lower food availability for primates compared to continuous forests. Mantled howler monkeys (Alouatta palliata) inhabit fragmented rainforests and may need to alter their activity budgets and spatial cohesion to mitigate competition and conserve energy in fragments where food quality is lower. We compared howler monkey activity and spatial cohesion across a small forest fragment (La Suerte Biological Research Station, LSBRS) and a large, continuous forest (La Selva Research Station) in Costa Rica. We predicted that monkeys at LSBRS would rest more, feed more, travel less, and be less spatially cohesive compared to La Selva to contend with fewer resources in the small fragment. Using instantaneous scan sampling at 2-min intervals during 30-min focal samples, we recorded activity and the number of individuals within 5 m of the focal animal. We collected 1505 h of data from 2017-2024. Monkey activity and spatial cohesion differed significantly across sites. As predicted, monkeys at LSBRS spent more time feeding than at La Selva, but contrary to our predictions, they rested less and traveled more. The mean number of individuals within 5 m was significantly lower at LSBRS compared to La Selva. The ability to modify their activity and spatial cohesion in response to fragmentation provides insight into how primates can contend with fewer resources and higher competition in changing ecosystems worldwide.

Climate Anxiety: Current Evidence and Future Directions.

PURPOSE OF REVIEW: Challenging cognitive, somatic, and behavioral responses to climate change are often conceptualized as climate anxiety (CA). Due to the increased recognition of the impacts of climate change on mental health, a growing body of scientific literature is developing. The purpose of this manuscript is to review the current evidence base for CA and propose future research needs for this emerging construct. RECENT FINDINGS: Early evidence supports underlying psychological mechanisms in the development and maintenance of CA, which are similar to other anxiety-related conditions. However, the study of CA poses unique challenges to researchers. The psychological impacts that occur in the context of climate change may be adaptive depending on the imminent threat of natural disasters, forced migration, or other climate-related challenges. Due to the potentially adaptive nature of CA and limited current evidence, a coordinated research program of climate-related distress is necessary. A review of the extant literature identified current gaps in understanding the epidemiology and individual differences that promote CA. Current evidence supports the prominent role of neuroticism, intolerance of uncertainty, and rumination. The development of evidence-based models of climate-related distress may provide a more valid and comprehensive depiction of the impacts of climate change on mental health. Transdiagnostic treatment methods are likely the most appropriate intervention for climate-related distress. As models, measures, and treatments of climate-related distress are developed, it is crucial to incorporate studies of populations most at risk for climate change-related mental health effects.

Adult Caretaker Engagement and School Connectedness and Association with Substance Use, Indicators of Emotional Well-Being and Suicide Risk, and Experiences with Violence Among American Indian or Alaska Native High School Students - Youth Risk Behavior Survey, United States, 2023.

The strength of American Indian and Alaska Native (AI/AN) communities comes from generations of Indigenous traditions, language, culture, and knowledge. These strengths have been challenged by a complex set of systemic, structural, and social factors related to historical and intergenerational trauma that affects the health of AI/AN communities. Furthermore, AI/AN population health data often are inaccurate because of analytic coding practices that do not account for multiracial and ethnic AI/AN identification and inadequate because of statistical suppression. The 2023 national Youth Risk Behavior Survey included a supplemental sample of AI/AN high school students. Coding of race and ethnicity was inclusive of all AI/AN students, even if they also identified as another race or as Hispanic or Latino, providing comprehensive data on health behaviors and experiences among AI/AN high school students nationwide. Adult caretaker engagement and school connectedness and their association with 13 health behaviors and experiences were examined, including five types of current substance use, four indicators of emotional well-being and suicide risk, and four types of violence. Pairwise t-tests and adjusted prevalence ratios from logistic regression models identified significant associations between exposure and outcome variables. Among AI/AN students, having an adult who always tried to meet their basic needs, high parental monitoring, and high school connectedness were associated with lower prevalence of certain measures of substance use, poor emotional well-being and suicide risk, and violence. Compared with non-AI/AN students, the prevalence of current electronic vapor product use, current marijuana use, attempted suicide, and experience of sexual violence was higher among AI/AN students.This report presents the most comprehensive, up-to-date data on substance use, indicators of emotional well-being and suicide risk, and experiences with violence among AI/AN high school students nationwide. The findings suggest the importance of engaged household adults and school connectedness in promoting emotional well-being and preventing substance use, suicide-related behavior, and experiences of violence among AI/AN students. Understanding the historical context and incorporating Indigenous knowledge when developing interventions focused on AI/AN youths are critical to ensure such interventions are successful in improving AI/AN health and well-being.

Investigating Exposure and Hazards of Micro- and Nanoplastics During Pregnancy and Early Life (AURORA Project): Protocol for an Interdisciplinary Study.

BACKGROUND: Micro- and nanoplastics (MNPs) are emerging pollutants of concern with ubiquitous presence in global ecosystems. MNPs pose potential implications for human health; however, the health impacts of MNP exposures are not yet understood. Recent evidence suggests that MNPs can cross the placental barrier, underlying the urgent need to understand their impact on reproductive health and development. OBJECTIVE: The Actionable eUropean ROadmap for early-life health Risk Assessment of micro- and nanoplastics (AURORA) project will investigate MNP exposures and their biological and health effects during pregnancy and early life, which are critical periods due to heightened vulnerability to environmental stressors. The AURORA project will enhance exposure assessment capabilities for measuring MNPs, MNP-associated chemicals, and plastic additives in human tissues, including placenta and blood. METHODS: In this interdisciplinary project, we will advance methods for in-depth characterization and scalable chemical analytical strategies, enabling high-resolution and large-scale toxicological, exposure assessment, and epidemiological studies. The AURORA project performs observational studies to investigate determinants and health impacts of MNPs by including 800 mother-child pairs from 2 existing birth cohorts and 110 women of reproductive age from a newly established cohort. This will be complemented by toxicological studies using a tiered-testing approach and epidemiological investigations to evaluate associations between maternal and prenatal MNP exposures and health perturbations, such as placental function, immune-inflammatory responses, oxidative stress, accelerated aging, endocrine disruption, and child growth and development. The ultimate goal of the AURORA project is to create an MNP risk assessment framework and identify the remaining knowledge gaps and priorities needed to comprehensively assess the impact of MNPs on early-life health. RESULTS: In the first 3 years of this 5-year project (2021-2026), progress was made toward all objectives. This includes completion of recruitment and data collection for new and existing cohorts, development of analytical methodological protocols, and initiation of the toxicological tiered assessments. As of September 2024, data analysis is ongoing and results are expected to be published starting in 2025. CONCLUSIONS: As plastic pollution increases globally, it is imperative to understand the impact of MNPs on human health, particularly during vulnerable developmental stages such as early life. The contributions of the AURORA project will inform future risk assessment. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/63176.

A matter of the metric? Sugar content overestimation is less pronounced in sugar cubes versus grams.

To make healthy food choices, consumers need to be aware of the sugar content of foods. Units act as an environmental cue that might influence sugar content estimation accuracy. The present study (1) tested whether estimations of sugar content are more accurate in sugar cubes vs grams, (2) compared accuracy of sugar content to estimations of the foods' weight and energy content, and (3) investigated gender, education, and body mass index as potential correlates. A sample of 886 adults was randomly assigned to estimating the sugar content of 10 common foods in grams or cubes. Estimations of sugar content diverged considerably from actual values in both groups (0.22 ≤ Cohen's dsgrams ≤ 1.20; 0.20 ≤ Cohen's dscubes ≤ 1.10), but were more pronounced for sugar content estimations in grams in 7 out of 10 foods (ts ≥ 4.04, Ps < .001, Cohen's ds ≥ 0.14). Sugar content misestimation was somewhat more pronounced than misestimation of weight (0.05 ≤ Cohen's ds ≤ 1.43) and energy content (0.04 ≤ Cohen's ds ≤ 1.19). Relationships between sugar content misestimation and gender (0.00 ≤ Cohen's ds ≤ 0.33), education (-0.07 ≤ r ≤ 0.11), and body mass index (-0.08 ≤ r ≤ 0.06) were mostly negligible. Although sugar content estimations were somewhat more accurate in sugar cubes vs grams, estimation accuracy is generally low. In addition to promoting consumers' knowledge through labeling and education, additional avenues for interventions might need to be explored for sizeable effects on food choices.

Unsustainable: Why I Left Primary Care.

A physician reflects on what drove her out of primary care, and how it might be fixed.

Digital Cognitive Behavioral Therapy vs Education for Pain in Adults with Sickle Cell Disease.

Despite the significant burden of chronic pain in sickle cell disease (SCD), non-pharmacological approaches to manage pain in SCD are lacking. Behavioral interventions incorporating digital cognitive-behavioral therapy CBT) for pain should be compared to available education efforts. To compare a CBT intervention tailored for adults with SCD to a digital pain/SCD education intervention (Education) on improving pain and associated symptoms. Multisite randomized comparative effectiveness trial. Seven comprehensive SCD centers and virtual recruitment through community organizations in the United States. Adults (age 18+) with SCD-related chronic pain and/or daily opioid use randomized to CBT or Education. Over 12 weeks, the CBT arm received an app-based intervention for pain management; the Education arm received digital pain/SCD education. Both groups received interactive chatbot lessons plus personalized health coach support. Changes in pain interference scale (primary); and other patient-reported outcomes (secondary), including pain intensity, depression, anxiety, quality of life, and self-efficacy over 6 months. 453 participants completed screening, 359 (79%) were randomized to CBT (n=181) or Education (n=178), 332 (92%) were Black African American, 238 (66.3%) female. At 6 months, 250 (70%) participants (n=125 per arm) completed follow-up assessments, 93 (26%) missed their follow-up window, 16 (4%) withdrew. Engagement with the chatbot content was variable (76% connected, 48% completed ≥1 lesson). However, 80% of participants completed ≥1 session with a health coach via phone, video, or text. The 6 month change in pain interference for CBT (-2.13; 95% CI, -3.42 to -0.84) and Education (-2.66; 95%CI, -3.97 to -1.36) was not significantly different (mean difference: 0.54; 95%CI, -1.30 to 2.37; *P=*0.57). Daily pain intensity ratings did not change for either group. There were no between-arm differences in depression, anxiety, and quality of life. CBT and Education did not differ in their effect on pain and mental health in SCD when combined with health coaching. Variable engagement with digital components and high engagement with health coaching may explain the lack of between-group differences, but these findings also provide insights into delivering digital interventions in racial minority and hard-to-reach populations. Trial Registration: ClinicalTrials.gov NCT04419168.

Corrigendum: Neuroprotection by upregulation of the major histocompatibility complex class I (MHC I) in SOD1G93A mice.

[This corrects the article DOI: 10.3389/fncel.2023.1211486.].

Network Analysis to Visualize Qualitative Results: Example From a Qualitative Content Analysis of The National Child Abuse Hotline.

Data visualization, such as figures created through network analysis, may be one way to present more complete information from qualitative analysis. Segments of qualitatively coded data can be treated as objects in network analysis, thus creating visual representations of the code frequency (i.e., nodes) and the co-occurrence (i.e., edges). By sharing an example of network analysis applied to qualitative data, and then comparing our process with other applications, our goal is to help other researchers reflect on how this approach may support their interpretation and visualization of qualitative data. A total of 265 de-identified transcripts between help-seekers and National Child Abuse Hotline crisis counselors were included in the network analysis. Post-conversation surveys, including help-seekers' perceptions of the conversations, were also included in the analysis. Qualitative content analysis was conducted, which was quantified as the presence or absence of each code within a transcript. Then, we divided the dataset based on help-seekers' perceptions. Individuals who responded that they "Yes/Maybe" felt more hopeful after the conversation were in the "hopeful" dataset, while those who answered "No" were in the "unhopeful" dataset. This information was imported to UCINET to create co-occurrence matrices. Gephi was used to visualize the network. Overall, code co-occurrence networks in hopeful conversations were denser. Furthermore, the average degree was higher in these hopeful conversations, suggesting more codes were consistently present. Codes in hopeful conversations included information, counselor support, and problem-solving. Conversely, non-hopeful conversations focused on information. Overall, network analysis revealed patterns that were not evident through traditional qualitative analysis.

Midkine is upregulated in the hippocampus following both spatial and olfactory reward association learning and enhances memory.

Hippocampal neuronal plasticity is a fundamental process underpinning learning and memory formation and requiring elaborate molecular mechanisms that result in the dynamic remodelling of synaptic connectivity. The neurotrophic properties of midkine (Mdk) have been implicated in the development and repair of the nervous system, while Mdk knockout resulted in deficits in the formation of certain types of memory. The role of Mdk in the process of memory-associated neuronal plasticity, however, remains poorly understood. We investigated the learning-induced regulation of Mdk in spatial navigation and association learning using the water maze and the odour reward association learning paradigms, characterising a temporal profile of Mdk protein expression post-learning. Both learning events revealed similar patterns of upregulation of expression of the protein in the rat hippocampal dentate gyrus, which were rapid and transient. Moreover, administration of recombinant Mdk during the endogenous Mdk upregulation following learning enhanced memory in the water maze task revealing a pro-cognitive action of Mdk. We further show that, within the adult hippocampus, Mdk mRNA is predominantly expressed in granular and pyramidal neurons and that hippocampal neuronal Mdk expression is regulated by the canonical plasticity-associated neurotransmitter glutamate. Finally, we confirm that the positive action of Mdk on neurite outgrowth previously noted in cortical and cerebellar neurons extends to hippocampal neurons. Together, our findings suggest a role for Mdk in glutamate-mediated hippocampal neuronal plasticity important for long-term memory consolidation.

Merkel Cell Polyomavirus Antibody in Tumor and Plasma Specimens in Patients with Merkel Cell Carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is associated with Merkel cell polyomavirus (MCPyV) infection. MCPyV antibodies (MCPyV-Ab) in plasma correlate with survival, while MCPyV-Ab within the tumor has never been investigated. This study evaluated plasma MCPyV-Ab and tumor MCPyV-Ab titers to evaluate their role in outcomes and prognostication. METHODS: A single-institution, prospective database was retrospectively reviewed for patients diagnosed with MCC from 2014 to 2021. MCPyV-Ab plasma and tumor titers, as well as patient and treatment factors, were collected. Two-year overall survival (OS) and disease-free survival (DFS) were examined based on MCPyV-Ab presence in tumor. RESULTS: Forty patients were identified, with a median follow-up of 27.6 months. Patients were stratified into four groups based on the presence of MCPyV-Ab in plasma (P+, P-) and tumor (T+, T-). Most patients (60.0%) were P-/T-. Of the remaining patients, 22.5% were P+/T+, 12.5% were P-/T+, and 5.0% were P+/T-. Two-year DFS of the P-/T- group was 16.6 months, which was not different from the other groups (p = 0.79). Two-year OS of P-/T- was 18.3 months, and 2-year OS of P-/T+ was 28.1 months, which was similar between groups (p = 0.80). CONCLUSIONS: Most patients P+ for MCPyV had antibody-positive tumors (T+), and P- patients were also T-; however, there was a subset of patients where plasma and tumor antibody findings were incongruent. Patients with MCPyV-Ab in either plasma or tumor had a trend toward improved 2-year DFS and OS, but was limited by a small cohort. This study offers an exploratory investigation into the relationship between plasma and tumor antibodies to MCPyV on which to base future work.

Robotic availability, not payor status, determines access to robotic emergency general surgery hernia repair in California and Florida.

BACKGROUND: Previous studies have demonstrated that access to robotic surgery is influenced by socioeconomic factors, including insurance status. The 2010 Affordable Care Act established an avenue for states to expand Medicaid coverage, which has increased access to surgical care for many conditions. We hypothesized that socioeconomic disparities in access to robotic repair of non-elective emergency general surgery (EGS) hernias are less prevalent in California, a Medicaid expansion state, compared to Florida, which has not adopted Medicaid expansion. METHODS: The 2021 California and Florida State Inpatient Databases were used to identify all EGS admissions with an ICD-10 procedure code for ventral or inguinal hernia repair. Elective procedures and those with concurrent unrelated abdominal procedures were excluded. Patient demographics, comorbidity burden, payor status, and income quartile were abstracted. Aggregation of hospital data identified high-volume trauma, robotic, and EGS centers. RESULTS: There were 15,683 EGS hernia procedures of which 11% underwent robotic repair: 14% in Florida and 8% in California. On multivariable logistic regression, older age, male sex, lower income, and Medicare insurance were associated with reduced odds of robotic hernia repair in California, but not in Florida, despite an uninsured rate of 10%. The greatest predictor of robotic surgery in both states was treatment at a robotic surgery center. Overall, accounting for patient- and hospital-level factors, hernia surgeries in Florida were more likely to involve robotics (OR 1.61, CI 1.42-1.81, p < 0.001) compared to California. CONCLUSION: There were fewer disparities in access to EGS robotic hernia repairs in Florida than in California. This suggests that robotic surgery access for EGS hernia repairs is primarily determined by institutional adoption of robotic surgery, not income or payor status. Compared to California, Florida appears to have greater market penetration of robotic surgery, which has increased access to robotic EGS for all patients.

The endoplasmic reticulum as an active liquid network.

The peripheral endoplasmic reticulum (ER) forms a dense, interconnected, and constantly evolving network of membrane-bound tubules in eukaryotic cells. While individual structural elements and the morphogens that stabilize them have been described, a quantitative understanding of the dynamic large-scale network topology remains elusive. We develop a physical model of the ER as an active liquid network, governed by a balance of tension-driven shrinking and new tubule growth. This minimalist model gives rise to steady-state network structures with density and rearrangement timescales predicted from the junction mobility and tubule spawning rate. Several parameter-independent geometric features of the liquid network model are shown to be representative of ER architecture in live mammalian cells. The liquid network model connects the timescales of distinct dynamic features such as ring closure and new tubule growth in the ER. Furthermore, it demonstrates how the steady-state network morphology on a cellular scale arises from the balance of microscopic dynamic rearrangements.

Clinical outcomes of children with COVID-19 and appendicitis: a propensity score matched analysis.

OBJECTIVE: Early in the COVID-19 pandemic, many children with appendicitis and COVID-19 were initially treated non-operatively and later underwent interval appendectomy. Currently, children with both appendicitis and COVID-19 frequently undergo upfront appendectomy. The impact of this return to upfront surgical management on patient outcomes is unknown. This study compared outcomes of pediatric patients with and without COVID-19 infection undergoing appendectomy. STUDY DESIGN: A retrospective cohort study of children < 21y who underwent appendectomy from 3/19/2020 to 7/31/2022 at 50 Pediatric Health Information System children's hospitals was conducted. Children with documented COVID-19 were identified. Exclusions included preoperative ventilator or supplemental oxygen dependence, and missing data. To evaluate COVID-19 positive versus COVID-19 negative patients, we used a propensity score matched on sociodemographics, comorbidities, laparoscopy, perforation, and hospital. Chi-square and Mann-Whitney U tests identified differences between groups in length of stay, postoperative drain placement, 30-day re-admission, and mechanical ventilation requirements. RESULTS: Overall, 51,861 children of median age 11y (IQR: 8-14) underwent appendectomy, of whom 1,440 (2.3%) had COVID-19. Most were male (60.3%), White (72.1%) and non-Hispanic (61.4%). Public insurance was the most common (47.5%). We created a matched cohort of 1,360 COVID-19 positive and 1,360 COVID-19 negative children. Children with COVID-19 had shorter hospitalizations (1d, IQR: 1-4 vs. 2d, IQR: 1-5, p = 0.03), less postoperative peritoneal drain placement (2.4% vs. 4.1%, p = 0.01), and fewer 30-day readmissions (9.0% vs. 11.4%, p = 0.04). However, no difference in incidence or duration of mechanical ventilation (p > 0.05) was detected. CONCLUSIONS: Our findings suggest that upfront appendectomy for children with appendicitis and COVID-19 has similar outcomes compared to children without COVID-19. LEVEL OF EVIDENCE: Level III.

Dilution of broiler breeder diets with oat hulls prolongs feeding but does not affect central control of appetite.

The parents of broiler (meat) chickens (ie, broiler breeders) are food-restricted until sexual maturity, ensuring good health and reproduction, but resulting in hunger. We investigated whether diets with added insoluble fiber promote satiety and reduce behavioral, motivational, and physiological signs of hunger. Ninety-six broiler breeders were fed 1 of 4 feed treatments (n = 24 per diet) from 6 to 12 wk of age: 1) a commercial diet fed to the recommended ration (R) or 2) ad libitum (AL), the same diet as R but mixed with oat hulls at 3) 20% (OH20%) or 4) 40% (OH40%). The R, OH20% and OH40% diets were approximately iso-energetic and resulted in mean 12 wk of age weights within 2.5% of each other (1.21 kg), while AL birds weighed 221% as much (2.67kg). At 12 wk of age, agouti-related protein (AGRP) expression, was, on average, more than 12 times lower in AL birds (P < 0.001) but did not differ between the fiber diet treatments and R. Pro-opiomelanocortin (POMC) expression, was, on average, over 1.5 times higher in AL birds, but was not statistically significantly affected by feed treatments (P = 0.33). In their home pens, AL birds stood/sat more, foraged less and fed more in total (P < 0.001) and OH40% birds spent longer feeding than R (P = 0.001). Motivation to forage tested by willingness to walk through water to access an area of wood shavings (without food) was not significantly affected by diet (P = 0.33). However, restricted birds were willing to cross in only 7.3% to 12.5% of tests. Mostly birds stayed on the start platform, where AL birds sat more than other treatments and OH40% birds reduced walking relative to R birds (P = 0.016). Across the behavioral and physiological measurements there was a dichotomy of effects in response to approximately iso-energetic diets differing in fiber. There were some potentially beneficial behavioral effects related to reduced foraging and walking. However, there was no evidence that these diets significantly improved physiological measures of satiety of broiler breeders.

Rare variant contribution to the heritability of coronary artery disease.

Whole genome sequences (WGS) enable discovery of rare variants which may contribute to missing heritability of coronary artery disease (CAD). To measure their contribution, we apply the GREML-LDMS-I approach to WGS of 4949 cases and 17,494 controls of European ancestry from the NHLBI TOPMed program. We estimate CAD heritability at 34.3% assuming a prevalence of 8.2%. Ultra-rare (minor allele frequency ≤ 0.1%) variants with low linkage disequilibrium (LD) score contribute ~50% of the heritability. We also investigate CAD heritability enrichment using a diverse set of functional annotations: i) constraint; ii) predicted protein-altering impact; iii) cis-regulatory elements from a cell-specific chromatin atlas of the human coronary; and iv) annotation principal components representing a wide range of functional processes. We observe marked enrichment of CAD heritability for most functional annotations. These results reveal the predominant role of ultra-rare variants in low LD on the heritability of CAD. Moreover, they highlight several functional processes including cell type-specific regulatory mechanisms as key drivers of CAD genetic risk.