Financial Health Among Louisiana Medicaid Enrollees.

This cross-sectional study compares average credit scores and unpaid medical and nonmedical debts in collections among Black, Hispanic, and White adults with Medicaid coverage.

Digoxin and its Na+/K+-ATPase-targeted actions on cardiovascular diseases and cancer.

Na+/K+-ATPase (NKA) is a plasma membrane ion-transporting protein involved in the generation and maintenance of Na+ and K+ gradients across the cell membrane, which can produce a driving force for the secondary transport of metabolic substrates. NKA also regulates intracellular calcium that is responsible for modulating numerous cellular processes, while it interacts with many other proteins and functions as a signal transducer, with several signaling pathways being involved. Thus, NKA has become an important target for the treatment of human diseases. Cardiac glycosides are well-known NKA inhibitors, of which (+)-digoxin or digoxin has been long used for the treatment of congestive heart failure. Also, digoxin has exhibited potential antitumor activity, by targeting directly HIF-1α, NKA, and NF-κB. Thus, the function of NKA in human cardiovascular diseases and cancer and the therapeutic effects of digoxin on these diseases are summarized in the present review, with the correlations among digoxin, NKA, cardiovascular diseases, and cancer being discussed. Presented herein are also the antitumor potential of monosaccharide cardiac glycoside analogues of digoxin, including (-)-cryptanoside A, (-)-oleandrin, (-)-ouabain, and (+)-strebloside. It is hoped that this contribution will provide some helpful information for the design and discovery of new cardiac glycoside-type therapeutic agents for the treatment of cardiovascular diseases and cancer.

A framework for three-dimensional statistical shape modeling of the proximal femur in Legg-Calvé-Perthes disease.

PURPOSE: The pathomorphology of Legg-Calvé-Perthes disease (LCPD) is a key contributor to poor long-term outcomes such as hip pain, femoroacetabular impingement, and early-onset osteoarthritis. Plain radiographs, commonly used for research and in the clinic, cannot accurately represent the full extent of LCPD deformity. The purpose of this study was to develop and evaluate a methodological framework for three-dimensional (3D) statistical shape modeling (SSM) of the proximal femur in LCPD. METHODS: We developed a framework consisting of three core steps: segmentation, surface mesh preparation, and particle-based correspondence. The framework aims to address challenges in modeling this rare condition, characterized by highly heterogeneous deformities across a wide age range and small sample sizes. We evaluated this framework by producing a SSM from clinical magnetic resonance images of 13 proximal femurs with LCPD deformity from 11 patients between the ages of six and 12 years. RESULTS: After removing differences in scale and pose, the dominant shape modes described morphological features characteristic of LCPD, including a broad and flat femoral head, high-riding greater trochanter, and reduced neck-shaft angle. The first four shape modes were chosen for the evaluation of the model's performance, together describing 87.5% of the overall cohort variance. The SSM was generalizable to unfamiliar examples with an average point-to-point reconstruction error below 1mm. We observed strong Spearman rank correlations (up to 0.79) between some shape modes, 3D measurements of femoral head asphericity, and clinical radiographic metrics. CONCLUSION: In this study, we present a framework, based on SSM, for the objective description of LCPD deformity in three dimensions. Our methods can accurately describe overall shape variation using a small number of parameters, and are a step toward a widely accepted, objective 3D quantification of LCPD deformity.

Elucidating the assembly of gas vesicles by systematic protein-protein interaction analysis.

Gas vesicles (GVs) are gas-filled microbial organelles formed by unique 3-nm thick, amphipathic, force-bearing protein shells, which can withstand multiple atmospheric pressures and maintain a physically stable air bubble with megapascal surface tension. However, the molecular process of GV assembly remains elusive. To begin understanding this process, we have devised a high-throughput in vivo assay to determine the interactions of all 11 proteins in the pNL29 GV operon. Complete or partial deletions of the operon establish interdependent relationships among GV proteins during assembly. We also examine the tolerance of the GV assembly process to protein mutations and the cellular burdens caused by GV proteins. Clusters of GV protein interactions are revealed, proposing plausible protein complexes that are important for GV assembly. We anticipate our findings will set the stage for designing GVs that efficiently assemble in heterologous hosts during biomedical applications.

Effect of ageing on attended visual stimuli in the presence of cognitive mental load.

PURPOSE: This study was designed to compare the effects of mental load, caused by concurrent auditory tasks, on attended and non-attended visual stimuli in older and younger adults. METHODS: Participants performed a visual orientation discrimination task involving two spatially separated Gabor patches of 4 cycles/degree and 55% contrast. Participants received either a valid-cue, invalid-cue or a neutral-cue for the patch whose orientation they were required to determine. An auditory n-back task was performed simultaneously to impose mental load. Repeated-measures ANOVA was used for investigation of main effects and interactions of ageing, mental load and attention condition on orientation discrimination. RESULTS: A total of 27 younger (mean age ± SD, 22.6 ± 1.3 years) and 23 older adults (54.7 ± 4.3 years) participated in the study. There was a significant effect of age (p = 0.01) and mental load (p < 0.001) on the proportion of correct orientation discrimination responses. Attentional condition significantly affected the proportion of correct responses (p = 0.02), but there was no significant interaction between attention, mental load and age group (p = 0.85). There was no overall difference in the proportion of no responses (the proportion of trials in which the participants failed to respond) between the two age groups (p = 0.53) nor on the overall effect of attention on the proportion of no responses (p = 0.25). There was, however, a significant effect of mental load on the proportion of no responses (p = 0.002). CONCLUSION: Although mental load reduced performance equally for both age groups and for all attentional conditions, older adults had poorer overall performance. Therefore, a given mental load is more likely to drive older observers to unacceptable levels of task performance.

Race and Ethnicity and Diagnostic Testing for Common Conditions in the Acute Care Setting.

Importance: Overuse of diagnostic testing is pervasive, but the extent to which it varies by race and ethnicity in the acute care setting is poorly understood. Objective: To use a previously validated diagnostic intensity index to evaluate differences in diagnostic testing rates by race and ethnicity in the acute care setting, which may serve as a surrogate for diagnostic test overuse. Design, Setting, and Participants: This was a cross-sectional study of emergency department (ED) discharges, hospital observation stays, and hospital admissions using administrative claims among EDs and acute care hospitals in Kentucky, Maryland, North Carolina, and New Jersey, from 2016 through 2018. The diagnostic intensity index pairs nonspecific principal discharge diagnoses (nausea and vomiting, abdominal pain, chest pain, and syncope) with related diagnostic tests to estimate rates of nondiagnostic testing. Adults with an acute care encounter with a principal discharge diagnosis of interest were included. Data were analyzed from January to February 2024. Exposure: Race and ethnicity (Asian, Black, Hispanic, White, other [including American Indian, multiracial, and multiethnic], and missing). Main Outcomes and Measures: Receipt of a diagnostic test. Generalized linear models with a hospital-specific indicator variable were estimated to calculate the adjusted odds ratio of receiving a test related to the principal discharge diagnosis by race and ethnicity, controlling for primary payer and zip code income quartile. Results: Of 3 683 055 encounters (1 055 575 encounters [28.7%] for Black, 300 333 encounters [8.2%] for Hispanic, and 2 140 335 encounters [58.1%] for White patients; mean [SD] age of patients with encounters, 47.3 [18.8] years; 2 233 024 encounters among females [60.6%]), most (2 969 974 encounters [80.6%]) were ED discharges. Black compared with White patients discharged from the ED with a diagnosis of interest had an adjusted odds ratio of 0.74 (95% CI, 0.72-0.75) of having related diagnostic testing. No other racial or ethnic disparities of a similar magnitude were observed in any acute care settings. Conclusions and Relevance: In this study, White patients discharged from the ED with a nonspecific diagnosis of interest were significantly more likely than Black patients to receive related diagnostic testing. The extent to which this represents diagnostic test overuse in White patients vs undertesting and missed diagnoses in Black patients deserves further study.

Development of Potential Therapeutic Agents from Black Elderberries (the Fruits of Sambucus nigra L.).

Elderberry (Sambucus nigra L.) is a widespread deciduous shrub, of which the fruits (elderberries) are used in the food industry to produce different types of dietary supplement products. These berries have been found to show multiple bioactivities, including antidiabetic, anti-infective, antineoplastic, anti-obesity, and antioxidant activities. An elderberry extract product, Sambucol®, has also been used clinically for the treatment of viral respiratory infections. As the major components, phenolic compounds, such as simple phenolic acids, anthocyanins and other flavonoids, and tannins, show promising pharmacological effects that could account for the bioactivities observed for elderberries. Based on these components, salicylic acid and its acetate derivative, aspirin, have long been used for the treatment of different disorders. Dapagliflozin, an FDA-approved antidiabetic drug, has been developed based on the conclusions obtained from a structure-activity relationship study for a simple hydrolyzable tannin, ß-pentagalloylglucoside (ß-PGG). Thus, the present review focuses on the development of therapeutic agents from elderberries and their small-molecule secondary metabolites. It is hoped that this contribution will support future investigations on elderberries.

Development of an augmented reality system for tracheal intubation guidance of airway management.

Tracheal intubation is a crucial procedure performed in airway management to sustain life during various procedures. However, difficult airways can make intubation challenging, which is associated with increased mortality and morbidity. This is particularly important for children who undergo intubation where the situation is difficult. Improved airway management will decrease incidences of repeated attempts, decrease hypoxic injuries in patients, and decrease hospital stays, resulting in better clinical outcomes and reduced costs. Currently, 3D printed models based on CT scans and ultrasound-guided intubation are being used or tested for device fitting and procedure guidance to increase the success rate of intubation, but both have limitations. Maintaining a 3D printing facility can be logistically inconvenient, and it can be time consuming and expensive. Ultrasound-guided intubation can be hindered by operator dependence, limited two-dimensional visualization, and potential artifacts. In this study, we developed an augmented reality (AR) system that allows the overlay of intubation tools and internal airways, providing real-time guidance during the procedure. A child manikin was used to develop and test the AR system. Three-dimensional CT images were acquired from the manikin. Different tissues were segmented to generate the 3D models that were imported into Unity to build the holograms. Phantom experiments demonstrated the AR-guided system for potential applications in tracheal intubation guidance.

Phase transition of GvpU regulates gas vesicle clustering in bacteria.

Gas vesicles (GVs) are microbial protein organelles that support cellular buoyancy. GV engineering has multiple applications, including reporter gene imaging, acoustic control and payload delivery. GVs often cluster into a honeycomb pattern to minimize occupancy of the cytosol. The underlying molecular mechanism and the influence on cellular physiology remain unknown. Using genetic, biochemical and imaging approaches, here we identify GvpU from Priestia megaterium as a protein that regulates GV clustering in vitro and upon expression in Escherichia coli. GvpU binds to the C-terminal tail of the core GV shell protein and undergoes a phase transition to form clusters in subsaturated solution. These properties of GvpU tune GV clustering and directly modulate bacterial fitness. GV variants can be designed with controllable sensitivity to GvpU-mediated clustering, enabling design of genetically tunable biosensors. Our findings elucidate the molecular mechanisms and functional roles of GV clustering, enabling its programmability for biomedical applications.

The relationship between sexual dimorphism and androgen response element proliferation in primate genomes.

In males of many vertebrate species, sexual selection has led to the evolution of sexually dimorphic traits, which are often developmentally controlled by androgen signaling involving androgen response elements (AREs). Evolutionary changes in the number and genomic locations of AREs can modify patterns of receptor regulation and potentially alter gene expression. Here, we use recently sequenced primate genomes to evaluate the hypothesis that the strength of sexual selection is related to the genome-wide number of AREs in a diversifying lineage. In humans, we find a higher incidence of AREs near male-biased genes and androgen-responsive genes when compared with randomly selected genes from the genome. In a set of primates, we find that gains or losses of AREs proximal to genes are correlated with changes in male expression levels and the degree of sex-biased expression of those genes. In a larger set of primates, we find that an increase in one indicator of sexual selection, canine size sexual dimorphism, is correlated with genome-wide ARE counts. Our results suggest that the responsiveness of the genome to androgens in humans and their close relatives has been shaped by sexual selection that arises from competition among males for mating access to females.

Conceptualizing and Measuring Trust, Mistrust, and Distrust: Implications for Advancing Health Equity and Building Trustworthiness.

Trust is vital to public confidence in health and science, yet there is no consensus on the most useful way to conceptualize, define, measure, or intervene on trust and its related constructs (e.g., mistrust, distrust, and trustworthiness). In this review, we synthesize literature from this wide-ranging field that has conceptual roots in racism, marginalization, and other forms of oppression. We summarize key definitions and conceptual frameworks and offer guidance to scholars aiming to measure these constructs. We also review how trust-related constructs are associated with health outcomes, describe interventions in this field, and provide recommendations for building trust and institutional trustworthiness and advancing health equity. We ultimately call for future efforts to focus on improving the trustworthiness of public health professionals, scientists, health care providers, and systems instead of aiming to increase trust in these entities as they currently exist and behave.

Modeling Brain Representations of Words' Concreteness in Context Using GPT-2 and Human Ratings.

The meaning of most words in language depends on their context. Understanding how the human brain extracts contextualized meaning, and identifying where in the brain this takes place, remain important scientific challenges. But technological and computational advances in neuroscience and artificial intelligence now provide unprecedented opportunities to study the human brain in action as language is read and understood. Recent contextualized language models seem to be able to capture homonymic meaning variation ("bat", in a baseball vs. a vampire context), as well as more nuanced differences of meaning-for example, polysemous words such as "book", which can be interpreted in distinct but related senses ("explain a book", information, vs. "open a book", object) whose differences are fine-grained. We study these subtle differences in lexical meaning along the concrete/abstract dimension, as they are triggered by verb-noun semantic composition. We analyze functional magnetic resonance imaging (fMRI) activations elicited by Italian verb phrases containing nouns whose interpretation is affected by the verb to different degrees. By using a contextualized language model and human concreteness ratings, we shed light on where in the brain such fine-grained meaning variation takes place and how it is coded. Our results show that phrase concreteness judgments and the contextualized model can predict BOLD activation associated with semantic composition within the language network. Importantly, representations derived from a complex, nonlinear composition process consistently outperform simpler composition approaches. This is compatible with a holistic view of semantic composition in the brain, where semantic representations are modified by the process of composition itself. When looking at individual brain areas, we find that encoding performance is statistically significant, although with differing patterns of results, suggesting differential involvement, in the posterior superior temporal sulcus, inferior frontal gyrus and anterior temporal lobe, and in motor areas previously associated with processing of concreteness/abstractness.

Transposon wave remodeled the epigenomic landscape in the rapid evolution of X-Chromosome dosage compensation.

Sex chromosome dosage compensation is a model to understand the coordinated evolution of transcription; however, the advanced age of the sex chromosomes in model systems makes it difficult to study how the complex regulatory mechanisms underlying chromosome-wide dosage compensation can evolve. The sex chromosomes of Poecilia picta have undergone recent and rapid divergence, resulting in widespread gene loss on the male Y, coupled with complete X Chromosome dosage compensation, the first case reported in a fish. The recent de novo origin of dosage compensation presents a unique opportunity to understand the genetic and evolutionary basis of coordinated chromosomal gene regulation. By combining a new chromosome-level assembly of P. picta with whole-genome bisulfite sequencing and RNA-seq data, we determine that the YY1 transcription factor (YY1) DNA binding motif is associated with male-specific hypomethylated regions on the X, but not the autosomes. These YY1 motifs are the result of a recent and rapid repetitive element expansion on the P. picta X Chromosome, which is absent in closely related species that lack dosage compensation. Taken together, our results present compelling support that a disruptive wave of repetitive element insertions carrying YY1 motifs resulted in the remodeling of the X Chromosome epigenomic landscape and the rapid de novo origin of a dosage compensation system.

Sex and Biology: Broader Impacts Beyond the Binary.

What are the implications of misunderstanding sex as a binary, and why is it essential for scientists to incorporate a more expansive view of biological sex in our teaching and research? This roundtable will include many of our symposium speakers, including biologists and intersex advocates, to discuss these topics and visibilize the link between ongoing reification of dyadic sex within scientific communities and the social, political, and medical oppression faced by queer, transgender, and especially intersex communities. As with the symposium as a whole, this conversation is designed to bring together empirical research and implementation of equity, inclusion, and justice principles, which are often siloed into separate rooms and conversations at academic conferences. Given the local and national attacks on the rights of intersex individuals and access to medical care and bodily autonomy, this interdisciplinary discussion is both timely and urgent.

The Ancestral Modulation Hypothesis: Predicting Mechanistic Control of Sexually Heteromorphic Traits Using Evolutionary History.

AbstractAcross the animal kingdom there are myriad forms within a sex across, and even within, species, rendering concepts of universal sex traits moot. The mechanisms that regulate the development of these trait differences are varied, although in vertebrates, common pathways involve gonadal steroid hormones. Gonadal steroids are often associated with heteromorphic trait development, where the steroid found at higher circulating levels is the one involved in trait development for that sex. Occasionally, there are situations in which a gonadal steroid associated with heteromorphic trait development in one sex is involved in heteromorphic or monomorphic trait development in another sex. We propose a verbal hypothesis, the ancestral modulation hypothesis (AMH), that uses the evolutionary history of the trait-particularly which sex ancestrally possessed higher trait values-to predict the regulatory pathway that governs trait expression. The AMH predicts that the genomic architecture appears first to resolve sexual conflict in an initially monomorphic trait. This architecture takes advantage of existing sex-biased signals, the gonadal steroid pathway, to generate trait heteromorphism. In cases where the other sex experiences evolutionary pressure for the new phenotype, that sex will co-opt the existing architecture by altering its signal to match that of the original high-trait-value sex. We describe the integrated levels needed to produce this pattern and what the expected outcomes will be given the evolutionary history of the trait. We present this framework as a testable hypothesis for the scientific community to investigate and to create further engagement and analysis of both ultimate and proximate approaches to sexual heteromorphism.

Does vision therapy for visual information processing improve academic performance? A randomised clinical trial.

PURPOSE: To determine whether a typical vision therapy (VT) programme designed to improve visual information processing (VIP) skills is effective in improving these skills and/or academic performance. METHODS: We used a double-blind, randomised clinical trial to compare VIP VT to placebo training. Participating schools referred a sample of 579 early primary school children identified as being within the lower third of their class for literacy. From the referred sample, we identified 247 children eligible to participate (passed visions and auditory processing screening, and VIP performance <34th percentile), 94 of whom participated. Matching IQ, school grade and sex was achieved by sorting hierarchically on these values and then alternately allocating to VT or placebo groups. Both programmes ran for 10 weeks and consisted of 33 h working at home and 4 h working in office. The VT programme was indicative of that employed in Australian paediatric optometry practices, with the placebo programme containing similar activities, except targeting skills within a child's competencies and with specific VIP development activities removed. The main outcome measures were score change on three standardised educational tests (reading comprehension, spelling and mathematics) and six VIP tests, both immediately post-intervention (PI) and 6 months later. RESULTS: Sixty-nine children completed the programmes. The VT programme produced no significant improvement in the three educational tests or in five of the six VIP tests compared to the control. The VT programme improved visual sequential memory (VSM) by a moderate amount compared to the control (Cohen's d = 0.57 and 0.52, immediately PI and at 6 months, respectively: p < 0.03 and p < 0.02). CONCLUSIONS: The VIP and academic performance benefits from a VT programme were largely identical to those from a control programme, both immediately and 6-month PI. Placebo effects and general effects such as improvements in executive function and/or regression-to-the-mean could be mistaken for specific programme effectiveness.

A Correspondence-Based Network Approach for Groupwise Analysis of Patient-Specific Spatiotemporal Data.

Methods for statistically analyzing patient-specific data that vary both spatially and over time are currently either limited to summary statistics or require elaborate surface registration. We propose a new method, called correspondence-based network analysis, which leverages particle-based shape modeling to establish correspondence across a population and preserve patient-specific measurements and predictions through statistical analysis. Herein, we evaluated this method using three published datasets of the hip describing cortical bone thickness of the proximal femur, cartilage contact stress, and dynamic joint space between control and patient cohorts to evaluate activity- and group-based differences, as applicable, using traditional statistical parametric mapping (SPM) and our proposed spatially considerate correspondence-based network analysis approach. The network approach was insensitive to correspondence density, while the traditional application of SPM showed decreasing area of the region of significance with increasing correspondence density. In comparison to SPM, the network approach identified broader and more connected regions of significance for all three datasets. The correspondence-based network analysis approach identified differences between groups and activities without loss of subject and spatial specificity which could improve clinical interpretation of results.

Public trust is earned: Historical discrimination, carceral violence, and the COVID-19 pandemic.

OBJECTIVE: To assess whether knowledge of Tuskegee, the U.S. Immigration and Customs Enforcement (ICE) agency's detainment of children, and satisfaction with the George Floyd death investigation were associated with trust in actors involved in the development and distribution of coronavirus vaccines. DATA SOURCES AND STUDY SETTING: National survey with a convenience sample of Black (n = 1019) and Hispanic (n = 994) adults between July 1 and 26, 2021. STUDY DESIGN: Observational study using stratified adjusted logistic regression models to measure the association between ratings of the trustworthiness of actors involved in the development and distribution of coronavirus vaccines. PRINCIPAL FINDINGS: Among Black respondents, lower satisfaction with the George Floyd death investigation was associated with lower trustworthiness ratings of pharmaceutical companies (ME: -0.09; CI: -0.15, 0.02), the FDA (ME: -0.07; CI: -0.14, -0.00), the Trump Administration (ME: -0.09; CI: -0.16, -0.02), the Biden Administration (ME: -0.07, CI: -0.10, 0.04), and elected officials (ME: -0.10, CI: -0.18, -0.03). Among Hispanic respondents, lower satisfaction was associated with lower trustworthiness ratings of the Trump Administration (ME: -0.14, CI: -0.22, -0.06) and elected officials (ME: -0.11; CI: -0.19, -0.02). Greater knowledge of ICE's detainment of children and families among Hispanic respondents was associated with lower trustworthiness ratings of state elected officials (ME: -0.09, CI: -0.16, 0.01). Greater knowledge of the US Public Health Service Study of Syphilis in Tuskegee was associated with higher trustworthiness ratings of their usual source of care (ME: 0.09; CI: 0.28, 0.15) among Black respondents (ME: 0.09; CI: 0.01, 0.16). CONCLUSIONS: Among Black respondents, lower satisfaction with the George Floyd death investigation was associated with lowered levels of trust in pharmaceutical companies, some government officials, and administrators; it was not associated with the erosion of trust in direct sources of health care delivery, information, or regulation. Among Hispanic respondents, greater knowledge of the ICE detainments was associated with lower trustworthiness ratings of elected state officials. Paradoxically, higher knowledge of the Study of Syphilis in Tuskegee was associated with higher trustworthiness ratings in usual sources of care.

The relationship between central and mid-peripheral motion perception and the hazard perception test in younger and older adults.

INTRODUCTION: Vision standards for driving are typically based on visual acuity, despite evidence that it is a poor predictor of driving safety and performance. However, visual motion perception is potentially relevant for driving, as the vehicle and surroundings are in motion. This study explored whether tests of central and mid-peripheral motion perception better predict performance on a hazard perception test (HPT), which is related to driving performance and crash risk, than visual acuity. Additionally, we explored whether age influences these associations, as healthy ageing impairs performance on some motion sensitivity tests. METHODS: Sixty-five visually healthy drivers (35 younger, mean age: 25.5; SD 4.3 years; 30 older adults, mean age: 71.0; SD 5.4 years) underwent a computer-based HPT, plus four different motion sensitivity tests both centrally and at 15° eccentricity. Motion tests included minimum displacement to identify motion direction (Dmin ), contrast detection threshold for a drifting Gabor (motion contrast), coherence threshold for a translational global motion stimulus and direction discrimination for a biological motion stimulus in the presence of noise. RESULTS: Overall, HPT reaction times were not significantly different between age groups (p = 0.40) nor were maximum HPT reaction times (p = 0.34). HPT response time was associated with motion contrast and Dmin centrally (r = 0.30, p = 0.02 and r = 0.28, p = 0.02, respectively) and with Dmin peripherally (r = 0.34, p = 0.005); these associations were not affected by age group. There was no significant association between binocular visual acuity and HPT response times (r = 0.02, p = 0.29). CONCLUSIONS: Some measures of motion sensitivity in central and mid-peripheral vision were associated with HPT response times, whereas binocular visual acuity was not. Peripheral testing did not show an advantage over central testing for visually healthy older drivers. Our findings add to the growing body of evidence that the ability to detect small motion changes may have potential to identify unsafe road users.