Effect of Maternal Race, Residential Rurality, and Social Vulnerability on Critical Congenital Heart Defect Risk.

The development of a congenital heart defect (CHD) is multifactorial, with many cases having an unknown etiology. This study explored whether maternal race and lived environment were associated with an infant being born with a critical CHD. A cross-sectional, case-control design was conducted utilizing secondary data analysis. The CHD group (N = 199) consisted of infants diagnosed with a critical CHD within the first year of life identified from hospital databases. The non-CHD group (N = 548) was a random sample of infants selected from the state's vital statistics database. The primary outcome was a critical CHD diagnosis. Maternal race, residential rurality, and the Social Vulnerability Index (SVI) were assessed for associations with a critical CHD using bivariate and multilevel regression models. Bivariate findings reported significance among residential rurality (p < 0.001), SVI ranking overall (p = 0.017), and SVI by theme (theme 1 p = 0.004, theme 2 p < 0.001, theme 3 p = 0.007, and theme 4 p = 0.049) when comparing infants with and without a critical CHD diagnosis. Results of multilevel logistic regression analyses further identified living in a rural residential area compared to urban areas (OR = 7.32; p < 0.001) as a predictor for a critical CHD diagnosis. The findings of lived environmental level associations provides information needed for continued investigation as the burden of a critical CHD continues to impact families, suggesting further research efforts are needed to improve health disparities.

Integrating Reference Intervals into Chimpanzee Welfare Research.

Animal welfare researchers are committed to developing novel approaches to enhance the quality of life of chimpanzees living in professional care. To systematically monitor physical, mental, and emotional states, welfare scientists highlight the importance of integrating non-invasive, animal-based welfare indicators. This study aimed to create species-specific reference intervals for behavioral measures and physiological biomarkers. Specifically, we analyzed data from 40 adult chimpanzees (22 females, 18 males) residing at 16 zoological facilities to generate reference intervals for behavioral states and events, behavioral diversity, fecal glucocorticoid metabolites (GCMs), and fecal immunoglobulin-A (IgA). Comparisons of sex and age using linear regression models revealed significant differences for several behaviors. The proportion of time spent engaged in mutual/multiple social grooming significantly decreased as individuals aged. Furthermore, males spent a higher proportion of time performing aggressive contact behaviors and displaying to other chimpanzees when compared to females. Males also performed sexual examination behaviors at a higher rate than females. Behavioral diversity, fecal GCM, and fecal IgA did not vary by sex or age. In the future, values for individual chimpanzees can be compared to the ranges reported here for particular age/sex classes. Ultimately, animal care professionals can utilize reference intervals to make evidence-based decisions regarding management practices and environmental conditions.

Increasing Critical Thinking Opportunities Through Post-Conference Simulation in a Pediatric Baccalaureate Nursing Course.

ABSTRACT: Traditional clinical experiences offer opportunities for nursing students to practice critical thinking. However, there are many limitations to planning these clinical experiences. The purpose of this educational activity is to incorporate post-conference simulation with traditional clinical to allow undergraduate nursing students expanded opportunities for enhancing critical thinking. The faculty created high-acuity simulation scenarios, which included a child experiencing respiratory, hematologic, neurological, or cardiovascular complications. After participating in the activity, students completed evaluation and reported increased confidence and preparedness to identify, think critically, and intervene in high-acuity situations.

Molecular Evidence for Epithelial Origin of Mixed Ovarian Epithelial-Germ Cell Neoplasms: Report of 2 Cases and Review of Literature.

Ovarian germ cell tumors (GCT) account for 2% to 3% of malignant ovarian neoplasms in Western countries and typically occur within the first 2 decades. When presenting later in life, GCTs may be associated with epithelial malignancies. In these circumstances, it has been theorized that these tumors may originate from a somatic, rather than germ cell origin, especially in the postmenopausal setting; however, the true derivation is not fully understood. Our database was searched for primary ovarian GCTs associated with a malignant epithelial component in patients above 35 yr of age, from 2006 to 2021. Two cases were identified and in each case, slides were reviewed and targeted next-generation sequencing was utilized to identify and compare gene mutation variants in morphologically distinct components. Patient A is a 58-yr-old, with choriocarcinoma and minor component of mucinous adenocarcinoma, and patient B is a 43-yr-old, with yolk sac tumor and minor component of endometrioid adenocarcinoma. The morphologically distinct areas in each case showed disparate staining patterns; however, next-generation sequencing demonstrated identical mutation variants within both the germ cell and epithelial components. Variants in CDKN2A , PIK3CA , PIK3R1 , and TP53 were present in patient A's tumor, while patient B's tumor showed CTNNB1 , PIK3R1 , and 2 PTEN variants. These mutational patterns are similar to those seen in pure epithelial counterparts, suggesting somatic derivation of the germ cell component. These rare tumors portend a poor prognosis and understanding their origin has clinical and therapeutic implications.

Factors influencing terrestriality in primates of the Americas and Madagascar.

Among mammals, the order Primates is exceptional in having a high taxonomic richness in which the taxa are arboreal, semiterrestrial, or terrestrial. Although habitual terrestriality is pervasive among the apes and African and Asian monkeys (catarrhines), it is largely absent among monkeys of the Americas (platyrrhines), as well as galagos, lemurs, and lorises (strepsirrhines), which are mostly arboreal. Numerous ecological drivers and species-specific factors are suggested to set the conditions for an evolutionary shift from arboreality to terrestriality, and current environmental conditions may provide analogous scenarios to those transitional periods. Therefore, we investigated predominantly arboreal, diurnal primate genera from the Americas and Madagascar that lack fully terrestrial taxa, to determine whether ecological drivers (habitat canopy cover, predation risk, maximum temperature, precipitation, primate species richness, human population density, and distance to roads) or species-specific traits (body mass, group size, and degree of frugivory) associate with increased terrestriality. We collated 150,961 observation hours across 2,227 months from 47 species at 20 sites in Madagascar and 48 sites in the Americas. Multiple factors were associated with ground use in these otherwise arboreal species, including increased temperature, a decrease in canopy cover, a dietary shift away from frugivory, and larger group size. These factors mostly explain intraspecific differences in terrestriality. As humanity modifies habitats and causes climate change, our results suggest that species already inhabiting hot, sparsely canopied sites, and exhibiting more generalized diets, are more likely to shift toward greater ground use.

Relationship Between Environmental Air Quality and Congenital Heart Defects.

BACKGROUND: Congenital heart defects (CHDs) affect 40,000 U.S. infants annually. One fourth of these infants have a critical CHD, requiring intervention within the first year of life for survival. Over 80% of CHDs have an unknown etiology. Fine particulate matter ≤2.5 (PM2.5) and ozone (O3) may be air pollutants associated with CHD. OBJECTIVES: The purpose of this study was to explore relationships between first-trimester maternal exposure to air pollutants PM2.5 and O3 and a critical CHD diagnosis. METHODS: A retrospective cohort study with nested case controls was conducted using data from January 1, 2014, to December 31, 2016, and consisted of 199 infants with a diagnosed critical CHD and 550 controls. Air pollution data were obtained from the U.S. Environmental Protection Agency air monitors. Geographic information system software was used to geocode monitoring stations and infant residential locations. Data analysis included frequencies, chi-square, independent t-test analysis, and binary logistic regression for two time periods: the entire first trimester (Weeks 1-12) and the critical exposure window (Weeks 3-8 gestation). RESULTS: Critical CHD odds were not significantly increased by exposure during the first trimester. However, weekly analyses revealed CHD odds were higher in Weeks 5 and 8 as PM2.5 increased and decreased in Week 11 with increased O3 exposure. DISCUSSION: Our study shows no evidence to support the overall association between air pollutants PM2.5 and O3 and a critical CHD diagnosis. However, analyses by week suggested vulnerability in certain weeks of gestation and warrant additional surveillance and study.

Potential Influencers of COVID-19 Vaccine Acceptance Among Adults Living in the United States Who Have Accepted or Plan to Accept the Vaccine: An Online Survey.

PURPOSE: The purpose of this study was to 1) determine the demographic differences between adults who have accepted, or plan to accept, the COVID-19 vaccine and those who will not accept the COVID-19 vaccine and 2) describe the potential influencers in deciding to accept the COVID-19 vaccine among adults living in the United States who have accepted or plan to accept the vaccine. DESIGN: A cross-sectional design utilizing an online survey was deployed using social media and a crowdsourcing platform. SETTING: United States. SUBJECTS: One thousand three hundred ninety-five (1395) adults completed the survey. The majority were white, male, between the ages of 25 and 45, and with representation from 50 states and Puerto Rico. MEASURES: A two-branched survey was used to assess demographic information, vaccination intention, and 19 potential influencers of COVID-19 vaccine acceptance. ANALYSIS: Analysis included descriptive statistics and Chi-square tests to determine differences between groups. RESULTS: A higher proportion of male (P < .001), married (P < .001), and college-educated (P < .001) participants reported acceptance of the vaccine. The factors with the highest mean score of reported level of influence were duty to protect the vulnerable and contribution to move society back to a sense of normalcy. CONCLUSION: Understanding the potential influencers of vaccine acceptance may provide insight into strategies that could increase vaccination uptake.

Cardioprotection of Immature Heart by Simultaneous Activation of PKA and Epac: A Role for the Mitochondrial Permeability Transition Pore.

Metabolic and ionic changes during ischaemia predispose the heart to the damaging effects of reperfusion. Such changes and the resulting injury differ between immature and adult hearts. Therefore, cardioprotective strategies for adults must be tested in immature hearts. We have recently shown that the simultaneous activation of protein kinase A (PKA) and exchange protein activated by cAMP (Epac) confers marked cardioprotection in adult hearts. The aim of this study is to investigate the efficacy of this intervention in immature hearts and determine whether the mitochondrial permeability transition pore (MPTP) is involved. Isolated perfused Langendorff hearts from both adult and immature rats were exposed to global ischaemia and reperfusion injury (I/R) following control perfusion or perfusion after an equilibration period with activators of PKA and/or Epac. Functional outcome and reperfusion injury were measured and in parallel, mitochondria were isolated following 5 min of reperfusion to determine whether cardioprotective interventions involved changes in MPTP opening behaviour. Perfusion for 5 min preceding ischaemia of injury-matched adult and immature hearts with 5 µM 8-Br (8-Br-cAMP-AM), an activator of both PKA and Epac, led to significant reduction in post-reperfusion CK release and infarct size. Perfusion with this agent also led to a reduction in MPTP opening propensity in both adult and immature hearts. These data show that immature hearts are innately more resistant to I/R injury than adults, and that this is due to a reduced tendency of MPTP opening following reperfusion. Furthermore, simultaneous stimulation of PKA and Epac causes cardioprotection, which is additive to the innate resistance.

Onset of morning activity in bumblebee foragers under natural low light conditions.

Foraging on flowers in low light at dusk and dawn comes at an additional cost for insect pollinators with diurnal vision. Nevertheless, some species are known to be frequently active at these times. To explore how early and under which light levels colonies of bumblebees, Bombus terrestris, initiate their foraging activity, we tracked foragers of different body sizes using RFID over 5 consecutive days during warm periods of the flowering season. Bees that left the colony at lower light levels and earlier in the day were larger in size. This result extends the evidence for alloethism in bumblebees and shows that foragers differ in their task specialization depending on body size. By leaving the colony earlier to find and exploit flowers in low light, larger-sized foragers are aided by their more sensitive eyes and can effectively increase their contributions to the colony's food influx. The decision to leave the colony early seems to be further facilitated by knowledge about profitable food resources in specific locations. We observed that experience accrued over many foraging flights determined whether a bee started foraging under lower light levels and earlier in the morning. Larger-sized bees were not more experienced than smaller-sized bees, confirming earlier observations of wide size ranges among active foragers. Overall, we found that most foragers left at higher light levels when they could see well and fly faster. Nevertheless, a small proportion of foragers left the colony shortly after the onset of dawn when light levels were below 10 lux. Our observations suggest that bumblebee colonies have the potential to balance the benefits of deploying large-sized or experienced foragers during dawn against the risks and costs of foraging under low light by regulating the onset of their activity at different stages of the colony's life cycle and in changing environmental conditions.

Receptor-ligand supplementation via a self-cleaving 2A peptide-based gene therapy promotes CNS axonal transport with functional recovery.

Gene replacement approaches are leading to a revolution in the treatment of previously debilitating monogenic neurological conditions. However, the application of gene therapy to complex polygenic conditions has been limited. Down-regulation or dysfunction of receptor expression in the disease state or in the presence of excess ligand has been shown to compromise therapeutic efficacy. Here, we offer evidence that combined overexpression of both brain-derived neurotrophic factor and its receptor, tropomyosin receptor kinase B, is more effective in stimulating axonal transport than either receptor administration or ligand administration alone. We also show efficacy in experimental glaucoma and humanized tauopathy models. Simultaneous administration of a ligand and its receptor by a single gene therapy vector overcomes several problems relating to ligand deficiency and receptor down-regulation that may be relevant to multiple neurodegenerative diseases. This approach shows promise as a strategy to target intrinsic mechanisms to improve neuronal function and facilitate repair.

Systemic α-synuclein injection triggers selective neuronal pathology as seen in patients with Parkinson's disease.

Parkinson's disease (PD) is an α-synucleinopathy characterized by the progressive loss of specific neuronal populations. Here, we develop a novel approach to transvascularly deliver proteins of complex quaternary structures, including α-synuclein preformed fibrils (pff). We show that a single systemic administration of α-synuclein pff triggers pathological transformation of endogenous α-synuclein in non-transgenic rats, which leads to neurodegeneration in discrete brain regions. Specifically, pff-exposed animals displayed a progressive deterioration in gastrointestinal and olfactory functions, which corresponded with the presence of cellular pathology in the central and enteric nervous systems. The α-synuclein pathology generated was both time dependent and region specific. Interestingly, the most significant neuropathological changes were observed in those brain regions affected in the early stages of PD. Our data therefore demonstrate for the first time that a single, transvascular administration of α-synuclein pff can lead to selective regional neuropathology resembling the premotor stage of idiopathic PD. Furthermore, this novel delivery approach could also be used to deliver a range of other pathogenic, as well as therapeutic, protein cargos transvascularly to the brain.

Treatment Preferences of Patients with Chronic Obstructive Pulmonary Disease: Results from Qualitative Interviews and Focus Groups in the United Kingdom, United States, and Germany.

BACKGROUND: A wide range of therapeutic regimens, including single-inhaler triple therapies (SITTs), are now available for the maintenance treatment of chronic obstructive pulmonary disease (COPD). Thus, an improved understanding of patient preferences may be valuable to inform physician prescribing decisions. This study was performed to assess the factors considered by patients when making decisions about their COPD treatments using qualitative techniques. METHODS: In the United Kingdom, United States and Germany, individual qualitative interviews (n=10 per country) and focus groups (1 per country; [United Kingdom, n=4; United States, n=6; Germany, n=6 participants]) were conducted. Interviews and focus groups were semi­structured, lasting approximately 60 minutes, and focused on treatment preferences. Data were analyzed according to emerging themes identified from the interviews; qualitative thematic analysis of the data was performed using specialist software. RESULTS: In interviews and focus groups, efficacy, ease of use, and lower frequency of use were favored attributes for current treatment, while side effects, medication taste, and more complex administration techniques were key dislikes. In interviews, most participants would consider a switch in medication, mainly for improved efficacy, but also to reduce medication frequency or following physician advice. Overall, efficacy and ease of use were the 2 most important attributes reported in interviews in all 3 countries. CONCLUSION: Patients with COPD have preferences for certain attributes of medication, highlighting the multi-faceted nature of treatment effectiveness and the importance of the delivery device.These results were subsequently used to inform the design of a discrete choice experiment.

Correction to: Development of a conceptual model and patient-reported outcome measures for assessing symptoms and functioning in patients with heart failure.

The article Development of a conceptual model and patient-reported outcome measures for assessing symptoms and functioning in patients with heart failure.

Development of a conceptual model and patient-reported outcome measures for assessing symptoms and functioning in patients with heart failure.

PURPOSE: Heart failure (HF) is a common condition that places considerable burden on patients. We aimed to develop a patient-reported outcome (PRO) measure to assess the symptoms and impacts of HF. METHODS: Phase 1: a targeted literature review, expert interviews, and concept elicitation (CE) interviews with patients with HF (n = 26) were used to develop a conceptual model of the core symptoms and impacts of HF. To capture these concepts, three new fit-for-purpose PRO questionnaires were constructed in accordance with US Food and Drug Administration PRO guidance. Phase 2: three 'waves' of cognitive interviews were conducted with patients with HF (n = 28) to validate and refine the questionnaires. RESULTS: Three key symptoms-shortness of breath, oedema, and fatigue-were identified across the literature review, expert interviews and CE interviews. Several additional symptoms, cognitive changes and impacts of HF were reported in the CE interviews and included in the conceptual model. A 10-item symptom questionnaire (Heart Failure-Daily Symptom Diary) was constructed; cognitive testing showed that the final PRO measure was easy to understand/complete and relevant to patients with HF, confirming content validity. Two HF impact questionnaires were developed (Assessing Dyspnoea's Impact on Mobility and Sleep and Heart Failure-Functional Status Assessment), but required refinement to ensure patient understanding. CONCLUSIONS: Patient input contributed to the development of a PRO instrument for assessing physical and cognitive symptoms important to patients with HF using novel measurement strategies. Inclusion of daily metrics offers differentiation from other qualified instruments and may provide clinical insight for improving lifestyles. Additionally, two draft PRO measures may, after further validation, be useful to assess the impacts of HF.

Chimpanzees Rarely Settle on Consistent Patterns of Play in the Hawk Dove, Assurance, and Prisoner's Dilemma Games, in a Token Exchange Task.

Games derived from experimental economics can be used to directly compare decision-making behavior across primate species, including humans. For example, the use of coordination games, such as the Assurance game, has shown that a variety of primate species can coordinate; however, the mechanism by which they do so appears to differ across species. Recently, these games have been extended to explore anti-coordination and cooperation in monkeys, with evidence that they play the Nash equilibria in sequential games in these other contexts. In the current paper, we use the same methods to explore chimpanzees' behavior in the Assurance Game; an anti-coordination game, the Hawk Dove game; and a cooperation game with a temptation to defect, the Prisoner's Dilemma game. We predicted that they would consistently play the Nash equilibria, as do the monkeys, and that, as in previous work, the subjects' level of experience with cognitive experiments would impact performance. Surprisingly, few of our pairs consistently played the same outcome (i.e., no statistically significant preferences), although those who did showed evidence consistent with Nash equilibria play, the same pattern seen more consistently in the monkeys. We consider reasons for their inconsistent performance; for instance, perhaps it was due to lack of interest in a task that rewarded them almost every trial no matter what option they chose, although this does not explain why they were inconsistent when the monkeys were not. A second goal of our study was to ascertain the effects of exogenous oxytocin in their decision making in one population. In line with recent work showing complex effects of oxytocin on social behavior, we found no effect on subjects' outcomes. We consider possible explanations for this as well.

Association between maternal exposure to pollutant particulate matter 2.5 and congenital heart defects: a systematic review.

OBJECTIVE: The objective of this review was to determine if there was an association between maternal exposure to pollutant particulate matter 2.5 during the first trimester of pregnancy and congenital heart defects within the first year of life. INTRODUCTION: The environment is recognized as an important determinant of health for both the individual and population. Air pollution specifically is a major environmental risk factor impacting health with links to asthma, heart disease, obesity, and fetal developmental complications. Of the commonly monitored air pollutants, particulate matter 2.5 has associations with health, especially among vulnerable populations such as children and pregnant women. A congenital heart defect is a fetal complication that impacts 34.3 million infants globally, with more than 80% of the diagnoses having an unknown etiology. Although environmental risk factors such as air pollution are thought to be a risk factor in the diagnosis of a congenital heart defect, epidemiologic research evidence is limited. INCLUSION CRITERIA: This review considered studies that evaluated maternal exposure to the air pollutant particulate matter 2.5 during the first trimester (weeks 1-12) of fetal development. The primary outcome was a diagnosis of a congenital heart defect in an infant within the first year of life. METHODS: A three-step search strategy was utilized in this review and included 11 databases and two websites. Studies published from January 2002 to September 2018 were eligible for inclusion. Only papers published in English were included. Eligible studies underwent critical appraisal by two independent reviewers using standardized critical appraisal instruments from JBI. Quantitative data were extracted from the included studies independently by two reviewers. Odds ratios (ORs) and 95% confidence intervals (CIs) were extracted for the individual outcome measures, specifically atrial septal defect, ventricular septal defect, and tetralogy of fallot, respectively. The defects were identified and pooled, where possible, in statistical meta-analysis. Where statistical pooling was not possible, findings were reported narratively. RESULTS: Five studies were identified that met the inclusion criteria, including three cohort and two case-control designs. Each individual study identified at least one statistically significant increase or inverse association between particulate matter 2.5 and a congenital heart defect. An increased risk was identified with more than seven isolated and two groupings of congenital heart defects. An inverse risk was identified with two isolated and one grouping of congenital heart defects. Meta-analysis results were: atrial septal defect, OR = 0.65 (95% CI, 0.37 to 1.15); ventricular septal defect, OR = 1.02 (95% CI, 075 to 1.37); and tetralogy of fallot, OR = 1.16 (95% CI, 0.78 to 1.73), indicating no statistically significant findings. CONCLUSION: There was no significant evidence to support an association between air pollutant particulate matter 2.5 and a congenital heart defect in the first year of life. However, few studies met the rigorous inclusion criteria, and the studies that did had high heterogeneity, making it difficult to complete a meta-analysis with such a limited number of articles. Further research is needed to standardize the outcomes and pollutant monitoring methods, and provide comparable analysis results so that future synthesis of the literature can be conducted.

Untargeted adductomics of Cys34 modifications to human serum albumin in newborn dried blood spots.

Metabolism of chemicals from the diet, exposures to xenobiotics, the microbiome, and lifestyle factors (e.g., smoking, alcohol intake) produce electrophiles that react with nucleophilic sites in circulating proteins, notably Cys34 of human serum albumin (HSA). To discover potential risk factors resulting from in utero exposures, we are investigating HSA-Cys34 adducts in archived newborn dried blood spots (DBS) that reflect systemic exposures during the last month of gestation. The workflow includes extraction of proteins from DBS, measurement of hemoglobin (Hb) to normalize for blood volume, addition of methanol to enrich HSA by precipitation of Hb and other interfering proteins, digestion with trypsin, and detection of HSA-Cys34 adducts via nanoflow liquid chromatography-high-resolution mass spectrometry. As proof-of-principle, we applied the method to 49 archived DBS collected from newborns whose mothers either actively smoked during pregnancy or were nonsmokers. Twenty-six HSA-Cys34 adducts were detected, including Cys34 oxidation products, mixed disulfides with low molecular weight thiols (e.g., cysteine, homocysteine, glutathione, cysteinylglycine), and other modifications. Data were normalized with a novel method ("scone") to remove unwanted technical variation arising from HSA digestion, blood volume, DBS age, mass spectrometry analysis, and batch effects. Using an ensemble of linear and nonlinear models, the Cys34 adduct of cyanide was found to consistently discriminate between newborns of smoking and nonsmoking mothers with a mean fold change (smoking/nonsmoking) of 1.31. These results indicate that DBS adductomics is suitable for investigating in utero exposures to reactive chemicals and metabolites that may influence disease risks later in life.