Spatial cognitive ability is associated with longevity in food-caching chickadees.

Cognitive abilities are hypothesized to affect survival and life span in nonhuman animals. However, most tests of this hypothesis have relied on interspecific comparisons of indirect measures of cognitive ability, such as brain size. We present direct evidence that individual variation in cognitive abilities is associated with differences in life span in a wild food caching bird. We measured the spatial cognitive abilities and tracked the life span of 227 mountain chickadees (Poecile gambeli) in their natural environment and found that individuals with better spatial learning and memory abilities involved in food caching lived longer. These results confirm that enhanced cognitive abilities can be associated with longer life in wild animals and that selection on cognitive abilities can lead to increased life span.

A Novel De Novo Gain-of-Function CACNA1D Variant in Neurodevelopmental Disease With Congenital Tremor, Seizures, and Hypotonia.

Background and Objectives: De novo gain-of-function variants in the CACNA1D gene, encoding the L-type voltage-gated Ca2+ channel CaV1.3, cause a multifaceted syndrome. Patients show variable degrees of autism spectrum disorder, developmental delay, epilepsy, and other neurologic and endocrine abnormalities (primary aldosteronism and/or hyperinsulinemic hypoglycemia). We study here a novel variant [c.3506G>A, NM_000720.4, p.(G1169D)] in 2 children with the same CACNA1D mutation but different disease severity. Methods: The clinical data of the study patients were collected. After molecular analysis and cloning by site-directed mutagenesis, patch-clamp recordings of transfected tsA201 cells were conducted in whole-cell configuration. The functional effects of wild-type and mutated channels were analyzed. Results: One child is a severely affected boy with a novel de novo CACNA1D variant with additional clinical symptoms including prenatal-onset tremor, congenital respiratory insufficiency requiring continuous positive airway pressure ventilation, and sensorineural deafness. Despite episodes of hypoglycemia, insulin levels were normal. Aldosterone:renin ratios as a screening parameter for primary aldosteronism were variable. In the second patient, putative mosaicism of the p.(G1169D) variant was associated with a less severe phenotype. Patch-clamp electrophysiology of the p.(G1169D) variant in a heterologous expression system revealed pronounced activity-enhancing gating changes, including a shift of channel activation and inactivation to more hyperpolarized potentials, as well as impaired channel inactivation and deactivation. Despite retained sensitivity to the Ca2+ channel blocker isradipine in vitro, no beneficial effects of isradipine or nifedipine treatment were observed in the index case. Discussion: Through this report, we expand the knowledge about the disease presentation in patients with CACNA1D variants and show the novel variant's modulatory effects on CaV1.3 gating.

Promotion of DNA end resection by BRCA1-BARD1 in homologous recombination.

The licensing step of DNA double-strand break repair by homologous recombination entails resection of DNA ends to generate a single-stranded DNA template for assembly of the repair machinery consisting of the RAD51 recombinase and ancillary factors1. DNA end resection is mechanistically intricate and reliant on the tumour suppressor complex BRCA1-BARD1 (ref. 2). Specifically, three distinct nuclease entities-the 5'-3' exonuclease EXO1 and heterodimeric complexes of the DNA endonuclease DNA2, with either the BLM or WRN helicase-act in synergy to execute the end resection process3. A major question concerns whether BRCA1-BARD1 directly regulates end resection. Here, using highly purified protein factors, we provide evidence that BRCA1-BARD1 physically interacts with EXO1, BLM and WRN. Importantly, with reconstituted biochemical systems and a single-molecule analytical tool, we show that BRCA1-BARD1 upregulates the activity of all three resection pathways. We also demonstrate that BRCA1 and BARD1 harbour stand-alone modules that contribute to the overall functionality of BRCA1-BARD1. Moreover, analysis of a BARD1 mutant impaired in DNA binding shows the importance of this BARD1 attribute in end resection, both in vitro and in cells. Thus, BRCA1-BARD1 enhances the efficiency of all three long-range DNA end resection pathways during homologous recombination in human cells.

Client-based evaluation of the effects of localized vibration therapy on pain and mobility scores in dogs with radiographic bilateral hip dysplasia.

Introduction: This study evaluated the effects of localized vibration (LV) in 37 dogs with bilateral hip dysplasia (HD). HD is a common cause of lameness in dogs, and is a contributory factor to osteoarthritis, which can reduce the dog's overall quality of life. Materials and methods: This was a multi-center, prospective survey-based study of 37 dogs with bilateral HD and no prior history of surgical management. Dogs were given LV therapy daily for 14 consecutive days using the same commercially available handheld vibration device. Canine Brief Pain Index (CBPI) data was collected prior to the initiation of therapy, then for 14 days following daily LV therapy. The dogs' medications, supplements, additional rehabilitation modalities, and activity level were unchanged during the study period. Baseline CBPI pain severity and pain interference scores were compared to scores after 7 or 14 days of LV. Results: There were significant decreases in average pain severity and average pain interference CBPI scores in response to 7 and 14 days of therapy compared to baseline. When response to therapy was defined as a decrease in both pain severity score and pain interference score, 62% (23/37) of dogs responded to therapy at 7 days of treatment and 73% (27/37) responded at 14 days of treatment. Of the individuals that responded to treatment at 7 days, 91% (21/23) continued to respond at 14 days. Conclusion: Daily LV resulted in a significant reduction in CBPI scores in 73% of dogs with bilateral HD in this study. Randomized and blinded studies should be performed to further assess daily LV as a treatment modality for canine HD.

Single-cell analysis of breast cancer metastasis reveals epithelial-mesenchymal plasticity signatures associated with poor outcomes.

Metastasis is the leading cause of cancer-related deaths. It is unclear how intratumor heterogeneity (ITH) contributes to metastasis and how metastatic cells adapt to distant tissue environments. The study of these adaptations is challenged by the limited access to patient material and a lack of experimental models that appropriately recapitulate ITH. To investigate metastatic cell adaptations and the contribution of ITH to metastasis, we analyzed single-cell transcriptomes of matched primary tumors and metastases from patient-derived xenograft models of breast cancer. We found profound transcriptional differences between the primary tumor and metastatic cells. Primary tumors upregulated several metabolic genes, whereas motility pathway genes were upregulated in micrometastases, and stress response signaling was upregulated during progression. Additionally, we identified primary tumor gene signatures that were associated with increased metastatic potential and correlated with patient outcomes. Immune-regulatory control pathways were enriched in poorly metastatic primary tumors, whereas genes involved in epithelial-mesenchymal transition were upregulated in highly metastatic tumors. We found that ITH was dominated by epithelial-mesenchymal plasticity (EMP), which presented as a dynamic continuum with intermediate EMP cell states characterized by specific genes such as CRYAB and S100A2. Elevated expression of an intermediate EMP signature correlated with worse patient outcomes. Our findings identified inhibition of the intermediate EMP cell state as a potential therapeutic target to block metastasis.

COVID-19 diagnosis, vaccination during pregnancy, and adverse pregnancy outcomes of 865,654 women in England and Wales: a population-based cohort study.

Background: The extent to which COVID-19 diagnosis and vaccination during pregnancy are associated with risks of common and rare adverse pregnancy outcomes remains uncertain. We compared the incidence of adverse pregnancy outcomes in women with and without COVID-19 diagnosis and vaccination during pregnancy. Methods: We studied population-scale linked electronic health records for women with singleton pregnancies in England and Wales from 1 August 2019 to 31 December 2021. This time period was divided at 8th December 2020 into pre-vaccination and vaccination roll-out eras. We calculated adjusted hazard ratios (HRs) for common and rare pregnancy outcomes according to the time since COVID-19 diagnosis and vaccination and by pregnancy trimester and COVID-19 variant. Findings: Amongst 865,654 pregnant women, we recorded 60,134 (7%) COVID-19 diagnoses and 182,120 (21%) adverse pregnancy outcomes. COVID-19 diagnosis was associated with a higher risk of gestational diabetes (adjusted HR 1.22, 95% CI 1.18-1.26), gestational hypertension (1.16, 1.10-1.22), pre-eclampsia (1.20, 1.12-1.28), preterm birth (1.63, 1.57-1.69, and 1.68, 1.61-1.75 for spontaneous preterm), very preterm birth (2.04, 1.86-2.23), small for gestational age (1.12, 1.07-1.18), thrombotic venous events (1.85, 1.56-2.20) and stillbirth (only within 14-days since COVID-19 diagnosis, 3.39, 2.23-5.15). HRs were more pronounced in the pre-vaccination era, within 14-days since COVID-19 diagnosis, when COVID-19 diagnosis occurred in the 3rd trimester, and in the original variant era. There was no evidence to suggest COVID-19 vaccination during pregnancy was associated with a higher risk of adverse pregnancy outcomes. Instead, dose 1 of COVID-19 vaccine was associated with lower risks of preterm birth (0.90, 0.86-0.95), very preterm birth (0.84, 0.76-0.94), small for gestational age (0.93, 0.88-0.99), and stillbirth (0.67, 0.49-0.92). Interpretation: Pregnant women with a COVID-19 diagnosis have higher risks of adverse pregnancy outcomes. These findings support recommendations towards high-priority vaccination against COVID-19 in pregnant women. Funding: BHF, ESRC, Forte, HDR-UK, MRC, NIHR and VR.

Traumatic stress in parents of children with congenital heart disease: a scoping review.

Congenital heart disease is the most common birth defect in the United States, with many of the affected infants requiring surgical and/or interventional procedures within their first year of life. The parental impacts of a child's diagnosis, subsequent hospitalization, and transition to home after discharge are numerous and burdensome, and many experience symptoms of traumatic stress along this trajectory. The purpose of this scoping review was to summarize current available literature related to the traumatic stress experienced by parents of children with heart disease to better understand the prevalence, related factors, and consequences. The Joanna Briggs Institute Scoping Review Framework was implemented to identify 31 relevant peer-reviewed articles published between 2000 and early 2024, including 25 quantitative studies, 3 qualitative studies, and 3 systematic reviews or meta-analyses. This scoping review provides an overview of parent traumatic stress for clinicians caring for children with heart disease at every stage of their clinical course.

Susceptibilities and viral shedding of peridomestic wildlife infected with clade 2.3.4.4b highly pathogenic avian influenza virus (H5N1).

We tested the ability of six peridomestic wildlife species to replicate a highly pathogenic (HP) clade 2.3.4.4b AIV (H5N1) isolated in the U.S. during 2022. All tested species replicated and shed virus, at least to some degree. Of the six species evaluated (house sparrows (Passer domesticus), European starlings (Sturnus vulgaris), feral pigeons (Columba livia), striped skunks (Mephitis mephitis), Virginia opossums (Didelphis virginiana), and cottontails (Sylvilagus sp.)), striped skunks and Virginia opossums shed the highest viral titers of 106.3 PFU/mL and 105.0 PFU/mL, respectively. Overall, the results of this study indicate that certain peridomestic species could pose a biosecurity threat to poultry operations in some situations. In addition, this study and field reports indicate that the HP AIVs circulating in the U.S. during 2022-2024 may have an extremely broad range of species that can be impacted by and/or replicate and shed these viruses.

Effect of Nitrite-Embedded Packaging Film on Growth of Listeria monocytogenes in Nitrite-free and Conventionally-Cured Bologna Sausage.

Listeria monocytogenes is a pathogen frequently associated with ready-to-eat (RTE) meat and poultry products. Nitrite is a key antimicrobial additive that can offer some degree of protection against L. monocytogenes when included in meat product formulations. The objectives of this study were to determine the potential of nitrite-embedded film to affect growth of L. monocytogenes following post-thermal processing of conventionally-cured and nitrite-free bologna. Two bologna treatment formulations, a conventionally-cured control formulation (CON) and a nitrite-free formulation (UCC), were manufactured, packaged in conventional (CF) or nitrite-embedded (NEF) film, inoculated with 3.5 log CFU/cm2 of a cocktail of L. monocytogenes strains, and stored at 10 ± 1°C. CON-NEF and UCC-NEF treatments had significantly slower (P < 0.05) growth of L. monocytogenes than CON-CF and UCC-CF, with populations in UCC-CF (which contained no nitrite) increasing by 3.4 logs after 10 d of storage in UCC-CF and 3.6 logs after 50 d in CON-CF (which had formulated nitrite only), while in the NEF-packaged samples, with or without formulated nitrite, they did not exceed the inoculum level until after day 40. Initial (day 0) residual nitrite was significantly greater (P < 0.05) in the control formulation. Packaging in NEF, however, resulted in an increase of 27-28 ppm by day 3, regardless of formulation, after which it decreased rapidly. Results suggest NEF can be used as a post-lethality antimicrobial intervention in food safety intervention strategies, in both cured and uncured processed meat products.

The intersection of systems thinking and structural empowerment in the work of public health dietitians.

BACKGROUND: Public health dietitians navigate complex professional landscapes amid dwindling resources, organisational disruptions and limited advancement opportunities. Cultivating systems thinking and structural empowerment competencies may enable this workforce to address multifaceted public health challenges more effectively. This study explored the extent to which public health dietitians apply systems thinking and perceive access to structural empowerment and the relationship between these constructs. METHODS: A quantitative online survey incorporating the systems thinking scale (STS) and conditions for work effectiveness questionnaire-II (CWEQ-II) was conducted among US public health dietitians who worked in governmental public health. Data were collected from September 2022 to October 2022. Descriptive and inferential statistical analyses were conducted. RESULTS: Among 216 respondents, 98% demonstrated moderate-to-high systems thinking competency (mean STS score = 60.3 ± 8.74, range 28-78). Over 88% reported moderate-to-high perceived structural empowerment (mean CWEQ-II score = 18.3 ± 0.96, range 8-29). Higher systems thinking scores were associated with greater decision-making authority (p = 0.01) but not budget oversight. Higher structural empowerment scores correlated with increased job responsibilities and decision-making authority (p < 0.001). A significant positive correlation existed between systems thinking and structural empowerment (r = 0.24, p < 0.001). Public health dietitians exhibited substantial systems thinking capabilities and perceived access to organisational power structures. CONCLUSIONS: This study offers baseline understanding of systems thinking and structural empowerment among public health dietitians. The positive interplay between these constructs underscores their potential to drive systems-level change and influence population health outcomes. Integrating systems thinking and structural empowerment into dietetic education and professional development may enhance the workforce's preparedness for navigating complexities.

The American Cancer Society National Lung Cancer Roundtable strategic plan: Implementation of high-quality lung cancer screening.

More than a decade has passed since researchers in the Early Lung Cancer Action Project and the National Lung Screening Trial demonstrated the ability to save lives of high-risk individuals from lung cancer through regular screening by low dose computed tomography scan. The emergence of the most recent findings in the Dutch-Belgian lung-cancer screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek [NELSON]) further strengthens and expands on this evidence. These studies demonstrate the benefit of integrating lung cancer screening into clinical practice, yet lung cancer continues to lead cancer mortality rates in the United States. Fewer than 20% of screen eligible individuals are enrolled in lung cancer screening, leaving millions of qualified individuals without the standard of care and benefit they deserve. This article, part of the American Cancer Society National Lung Cancer Roundtable (ACS NLCRT) strategic plan, examines the impediments to successful adoption, dissemination, and implementation of lung cancer screening. Proposed solutions identified by the ACS NLCRT Implementation Strategies Task Group and work currently underway to address these challenges to improve uptake of lung cancer screening are discussed. PLAIN LANGUAGE SUMMARY: The evidence supporting the benefit of lung cancer screening in adults who previously or currently smoke has led to widespread endorsement and coverage by health plans. Lung cancer screening programs should be designed to promote high uptake rates of screening among eligible adults, and to deliver high-quality screening and follow-up care.

New therapies on the horizon: Targeted protein degradation in neuroscience.

This minireview explores the burgeoning field of targeted protein degradation (TPD) and its promising applications in neuroscience and clinical development. TPD offers innovative strategies for modulating protein levels, presenting a paradigm shift in small-molecule drug discovery and therapeutic interventions. Importantly, small-molecule protein degraders specifically target and remove pathogenic proteins from central nervous system cells without the drug delivery challenges of genomic and antibody-based modalities. Here, we review recent advancements in TPD technologies, highlight proteolysis targeting chimera (PROTAC) protein degrader molecules with proximity-induced degradation event-driven and iterative pharmacology, provide applications in neuroscience research, and discuss the high potential for translation of TPD into clinical settings.

Cost-effectiveness of vaccinating adults aged 60 years and older against respiratory syncytial virus.

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults. In May 2023, two subunit RSV vaccines (Arexvy [GSK] and Abrysvo [Pfizer]) received approval from the U.S. Food and Drug Administration (FDA). In June 2023, ACIP recommended that adults aged ≥60 years may receive a single dose of RSV vaccine, using shared clinical decision-making. In support of development of this policy, our objective was to assess the cost-effectiveness of RSV vaccination in the general population in this age group. We used a decision-analytical model of RSV over a two-year timeframe using data from published literature, FDA documents, epidemiological databases, and manufacturer data. We tracked RSV-associated outpatient, emergency department, inpatient healthcare utilization, RSV-attributable deaths, quality-adjusted life-years lost (QALYs), and societal costs. The societal cost per QALY saved from RSV vaccination depended on age group and product: adults aged ≥60 years, $196,842 for GSK's vaccine and $176,557 for Pfizer's vaccine; adults ≥65 years, $162,138 for GSK and $146,543 for Pfizer; adults 60- <65 years, $385,829 for GSK and $331,486 for Pfizer. Vaccine efficacy, incidence of RSV hospitalization, and vaccine cost had the greatest influence on cost per QALY. Cost per QALY saved decreased as the age of those vaccinated increased. Inputs such as long-term efficacy are uncertain. RSV vaccination in adults aged ≥60 years may be cost-effective, particularly in those of more advanced age. Lower vaccine acquisition costs and persistent efficacy beyond two RSV seasons would render RSV vaccination more cost-effective for a broader target population. PRIMARY FUNDING SOURCE: US Centers for Disease Control and Prevention.

Patient perspectives and preferences for rehabilitation among people living with frailty and chronic kidney disease: a qualitative evaluation.

BACKGROUND: Understanding the patient perspective of frailty is critical to offering holistic patient-centred care. Rehabilitation strategies for patients with advanced chronic kidney disease (CKD) and frailty are limited in their ability to overcome patient-perceived barriers to participation, resulting in high rates of drop-out and non-adherence. The aim of this study was to explore patient perspectives and preferences regarding experiences with rehabilitation to inform a CKD/Frailty rehabilitation model. METHODS: This qualitative study involved two focus groups, six individual semi-structured interviews and three caregiver semi-structured interviews with lived experience of advanced kidney disease and frailty. Interviews were recorded, transcribed, and coded for meaningful concepts and analysed using inductive thematic analysis using constant comparative method of data analysis employing Social Cognitive Theory. RESULTS: Six major themes emerged including accommodating frailty is an act of resilience, exercise is endorsed for rehabilitation but existing programs have failed to meet end-users' needs. Rehabilitation goals were framed around return to normative behaviours and rehabilitation should have a social dimension, offering understanding for "people like us". Participants reported on barriers and disruptors to frailty rehabilitation in the CKD context. Participants valued peer-to-peer education, the camaraderie of socialisation and the benefit of feedback for maintaining motivation. Patients undertaking dialysis described the commodity of time and the burden of unresolved symptoms as barriers to participation. Participants reported difficulty envisioning strategies for frailty rehabilitation, maintaining a focus on the immediate and avoidance of future uncertainty. CONCLUSIONS: Frailty rehabilitation efforts in CKD should leverage shared experiences, address comorbidity and symptom burden and focus on goals with normative value.

Microfiltration Membrane Pore Functionalization with Primary and Quaternary Amines for PFAS Remediation: Capture, Regeneration, and Reuse.

The widespread production and use of multi-fluorinated carbon-based substances for a variety of purposes has contributed to the contamination of the global water supply in recent decades. Conventional wastewater treatment can reduce contaminants to acceptable levels, but the concentrated retentate stream is still a burden to the environment. A selective anion-exchange membrane capable of capture and controlled release could further concentrate necessary contaminants, making their eventual degradation or long-term storage easier. To this end, commercial microfiltration membranes were modified using pore functionalization to incorporate an anion-exchange moiety within the membrane matrix. This functionalization was performed with primary and quaternary amine-containing polymer networks ranging from weak to strong basic residues. Membrane loading ranged from 0.22 to 0.85 mmol/g membrane and 0.97 to 3.4 mmol/g membrane for quaternary and primary functionalization, respectively. Modified membranes exhibited a range of water permeances within approximately 45-131 LMH/bar. The removal of PFASs from aqueous streams was analyzed for both "long-chain" and "short-chain" analytes, perfluorooctanoic acid and perfluorobutyric acid, respectively. Synthesized membranes demonstrated as high as 90% rejection of perfluorooctanoic acid and 50-80% rejection of perfluorobutyric acid after 30% permeate recovery. Regenerated membranes maintained the capture performance for three cycles of continuous operation. The efficiency of capture and reuse can be improved through the consideration of charge density, water flux, and influent contaminant concentration. This process is not limited by the substrate and, thus, is able to be implemented on other platforms. This research advances a versatile membrane platform for environmentally relevant applications that seek to help increase the global availability of safe drinking water.

Genomics and synthetic community experiments uncover the key metabolic roles of acetic acid bacteria in sourdough starter microbiomes.

While research on the sourdough microbiome has primarily focused on lactic acid bacteria (LAB) and yeast, recent studies have found that acetic acid bacteria (AAB) are also common members. However, the ecology, genomic diversity, and functional contributions of AAB in sourdough remain unknown. To address this gap, we sequenced 29 AAB genomes, including three that represent putatively novel species, from a collection of over 500 sourdough starters surveyed globally from community scientists. We found variations in metabolic traits related to carbohydrate utilization, nitrogen metabolism, and alcohol production, as well as in genes related to mobile elements and defense mechanisms. Sourdough AAB genomes did not cluster when compared to AAB isolated from other environments, although a subset of gene functions was enriched in sourdough isolates. The lack of a sourdough-specific genomic cluster may reflect the nomadic lifestyle of AAB. To assess the consequences of AAB on the emergent function of sourdough starter microbiomes, we constructed synthetic starter microbiomes, varying only the AAB strain included. All AAB strains increased the acidification of synthetic sourdough starters relative to yeast and LAB by 18.5% on average. Different strains of AAB had distinct effects on the profile of synthetic starter volatiles. Taken together, our results begin to define the ways in which AAB shape emergent properties of sourdough and suggest that differences in gene content resulting from intraspecies diversification can have community-wide consequences on emergent function. IMPORTANCE: This study is a comprehensive genomic and ecological survey of acetic acid bacteria (AAB) isolated from sourdough starters. By combining comparative genomics with manipulative experiments using synthetic microbiomes, we demonstrate that even strains with >97% average nucleotide identity can shift important microbiome functions, underscoring the importance of species and strain diversity in microbial systems. We also demonstrate the utility of sourdough starters as a model system to understand the consequences of genomic diversity at the strain and species level on multispecies communities. These results are also relevant to industrial and home-bakers as we uncover the importance of AAB in shaping properties of sourdough starters that have direct impacts on sensory notes and the quality of sourdough bread.

The "Other" race category on birth certificates and its impact on analyses of preterm birth inequity.

OBJECTIVE: Not all individuals self-identify with race categories on birth certificates, selecting "Other" and writing in identities. Our hypothesis was that curating write-in responses in the "Other" race category would contribute to understanding preterm birth inequities. METHODS: We analyzed Pennsylvania birth certificates (2006-2014). Two independent coders reviewed each write-in response among those who selected "Other" race. We compared preterm birth rates across subpopulations within "Other" race category using a Monte Carlo simulated Chi-square test. RESULTS: Among 1,196,125 singleton births, 72,891 (6.1%) exclusively selected "Other" race; Hispanic more often than non-Hispanic individuals (54.5% vs 0.7%), p < 0.0001). Only 545 (0.8%) of Hispanic individuals wrote in responses aligned with preestablished race categories compared to 2,601 (33.2%) of non-Hispanic individuals. Preterm birth rates varied significantly across identities within the "Other" group (P < 0.001). CONCLUSION: Utilizing combinations of self-identified race, ethnicity, and continental origin may facilitate public health efforts focused on birth outcome equity.

Parity and post-reproductive mortality among U.S. Black and White women: Evidence from the health and retirement study.

Population health research finds women's mortality risk associated with childlessness, low parity (one child), and high parity (6+ children) in a U-shaped pattern, although U.S. studies are inconsistent overall and by race/ethnicity. Parity, however, is contingent on women's biophysiological likelihood of (in)fecundity as well as voluntary control practices that limit fertility. No studies have empirically examined infecundity differentials among women and their potential contribution to the parity-post-reproductive mortality relationship or the race/ethnic-related mortality gap. We examine 7,322 non-Hispanic Black and White women, born 1920-1941, in the Health and Retirement Study, using zero-inflation methods to estimate infecundity risk and parity by race/ethnicity. We estimate proportional hazards models [t0 1992/1998, t1 2018] to examine associations of infecundity risk, parity, early-life-course health and social statuses, and post-reproductive statuses with all-cause mortality. We find Black women's infecundity probability to be twice that of White women and their expected parity 40% higher. Infecundity risk increases mortality risk for all women, but parity-post-reproductive mortality associations differ by race/ethnicity. White women with one and 5+ children (U-shaped curve) have increased mortality risk, adjusting for infecundity risk and early-life factors; further adjustment for post-reproductive health and social status attenuates all parity-related mortality risk. Black women's parity-post-reproductive mortality associations are not statistically significant. Black women's post-reproductive mortality risk is anchored in earlier-life conditions that elevate infecundity risk. Results suggest a need to focus upstream to better elucidate race/ethnic-related social determinants of reproductive health, infecundity, parity, and mortality.

Total Thrombotic Occlusion of an Extracardiac Fontan Conduit in a Hemodynamically Stable Patient.

Cardiac and extracardiac complications of single-ventricle physiology are well described and carry significant morbidity and mortality risks. We present the case of a 32-year-old patient with a Fontan circulation who presented to the emergency department with epigastric pain, and with chest computed tomography angiography concerning for total thrombosis of the extracardiac conduit.