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.

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.

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.

Disparities in Telemedicine Use Among Louisiana Medicaid Beneficiaries During the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic led to an increased reliance on telemedicine. Whether this exacerbated existing disparities within vulnerable populations is not yet known. OBJECTIVES: Characterize changes in outpatient telemedicine evaluation and management (E&M) services for Louisiana Medicaid beneficiaries by race, ethnicity, and rurality during the COVID-19 pandemic. RESEARCH DESIGN: Interrupted time series regression models estimated pre-COVID-19 trends and changes in E&M service use at the April and July 2020 peaks in COVID-19 infections in Louisiana and in December 2020 after those peaks had subsided. SUBJECTS: Louisiana Medicaid beneficiaries continuously enrolled between January 2018 and December 2020 who were not also enrolled in Medicare. MEASURES: Monthly outpatient E&M claims per 1000 beneficiaries. RESULTS: Prepandemic differences in service use between non-Hispanic White and non-Hispanic Black beneficiaries narrowed by 34% through December 2020 (95% CI: 17.6%-50.6%), while differences between non-Hispanic White and Hispanic beneficiaries increased by 10.5% (95% CI: 0.1%-20.7%). Non-Hispanic White beneficiaries used telemedicine at higher rates than non-Hispanic Black (difference=24.9 claims per 1000 beneficiaries, 95% CI: 22.3-27.4) and Hispanic beneficiaries (difference=42.3 claims per 1000 beneficiaries, 95% CI: 39.1-45.5) during the first wave of COVID-19 infections in Louisiana. Telemedicine use increased slightly for rural beneficiaries compared with urban beneficiaries (difference=5.3 claims per 1000 beneficiaries, 95% CI: 4.0-6.6). CONCLUSIONS: The COVID-19 pandemic narrowed gaps in outpatient E&M service use between non-Hispanic White and non-Hispanic Black Louisiana Medicaid beneficiaries, though gaps in telemedicine use emerged. Hispanic beneficiaries experienced large reductions in service use and relatively small increases in telemedicine use.

Effect of Cognitive Mental Load on Attended and Nonattended Visual Stimuli.

SIGNIFICANCE: In the real word, visual tasks may be concurrent with other activity that imposes mental load. Although the brain's capacity to process information is limited, attention can improve visual performance by selectively allocating processing resources. Therefore, measuring visual performance under such circumstances can reflect patients' vision more accurately. PURPOSE: The aim of this study was to evaluate the effect of nonvisual task-induced mental load on visual performance at both attended and unattended locations in stimulus-driven captured attention. METHODS: Visual function was measured with an orientation discrimination task for Gabor patches with contrasts of 10, 15, 30, 50, and 80%. Three attentional conditions (valid-cue, invalid-cue, and neutral-cue) were randomly interleaved within runs. To modulate mental load, the visual task was performed either with or without a simultaneous auditory n-back task (two-back for maximum mental load and zero-back to control for the effect of having to perform a simultaneous task). RESULTS: Our result showed that the effect of mental load on correct responses was significant ( P = .02). Correct responses decreased significantly during the two-back task when compared with the baseline condition ( P = .03), but there was no significant difference between baseline and zero-back conditions ( P = .06). The effect of attention and spatial frequencies on the percentage of correct responses was significant ( P < .001). There was no significant interaction between mental load and spatial frequency, contrast level, or attention ( P > .05). CONCLUSIONS: Mental load had a similar decreasing effect on attended and unattended visual stimuli. This may be due to a generalized effect on processing resources upstream to where spatial attention is allocated.

Is critical flicker-fusion frequency a valid measure of visual fatigue? A post-hoc analysis of a double-masked randomised controlled trial.

PURPOSE: Critical flicker-fusion frequency (CFF) has been used in clinical studies as a measure of visual fatigue. We examine the correlation between CFF and subjective reports of visual fatigue in a group of symptomatic computer users, to consider whether CFF may be used as a surrogate measure of visual fatigue symptoms. METHODS: We analysed data from a previous randomised controlled trial. One hundred and twenty adults, diagnosed with computer vision syndrome, had CFF and visual fatigue symptoms quantified before and after a visually demanding 2-h computer task. Symptoms were assessed using a questionnaire with nine subcomponents that summed to a total score of 900. CFF was measured using a two-interval forced-choice method, with the flicker rate altered by a computer-controlled staircase procedure. For our primary analysis, we determined Spearman correlation coefficients between post-task symptom scores and CFF, and between change from baseline symptom scores and CFF. We also used a bootstrap procedure to consider whether symptom score subcomponents were significantly (Bonferroni-corrected) different from overall scores with regard to their correlations with CFF. RESULTS: Although visual fatigue symptom scores altered significantly post-task (mean change: 92 units; 95% confidence interval [CI]: 11 to 122), CFF did not (mean change -0.7 Hz; 95% CI: -1.7 to 0.3). There was no significant correlation between overall symptom scores and CFF, either for the post-task (r = -0.13; 95% CI: -0.31 to 0.05) or the change from baseline (r = -0.18; 95% CI: -0.35 to 0.01) analysis. Subcomponents of the symptom questionnaire did not show a significant correlation with CFF, either for the post-task or the change from baseline analysis. CONCLUSIONS: We find that CFF is not a useful surrogate for symptoms of visual fatigue, given its low correlation with scores on a visual fatigue symptom questionnaire.

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.

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.

Telemedicine Use by Age in Louisiana Medicaid During COVID-19: Claims-Based Longitudinal Analysis.

BACKGROUND: Limited availability of in-person health care services and fear of contracting COVID-19 during the pandemic promoted an increased reliance on telemedicine. However, long-standing inequities in telemedicine due to unequal levels of digital literacy and internet connectivity among different age groups raise concerns about whether the uptake of telemedicine has exacerbated or alleviated those inequities. OBJECTIVE: The aim of this study is to examine changes in telemedicine and in-person health service use during the COVID-19 pandemic across age groups for Medicaid beneficiaries in the state of Louisiana. METHODS: Interrupted time series models were used on Louisiana Medicaid claims data to estimate trends in total, in-person, and telemedicine monthly office visit claims per 1000 Medicaid beneficiaries between January 2018 and December 2020. Changes in care pattern trends and levels were estimated around the infection peaks (April 2020 and July 2020) and for an end-of-year infection leveling off period (December 2020). Four mutually exclusive age categories (0 to 17, 18 to 34, 35 to 49, and 50 to 64 years) were used to compare the differences. RESULTS: Prior to the COVID-19 pandemic, telemedicine services accounted for less than 1% of total office visit claim volume across the age groups. Each age group followed similar patterns of sharp increases in April 2020, downward trends until sharp increases again in July 2020, followed by flat trends thereafter until December 2020. These sharp increases were most pronounced for older patients, with those aged 50 to 64 years seeing increases of 184.09 telemedicine claims per 1000 Medicaid beneficiaries in April 2020 (95% CI 172.19 to 195.99) and 120.81 in July 2020 (95% CI 101.32 to 140.31) compared with those aged 18 to 34 years, seeing increases of 84.47 (95% CI 78.64 to 90.31) and 57.00 (95% CI 48.21 to 65.79), respectively. This resulted in overall changes from baseline to December 2020 levels of 123.65 (95% CI 112.79 to 134.51) for those aged 50 to 64 years compared with 59.07 (95% CI 53.89 to 64.24) for those aged 18 to 34 years. CONCLUSIONS: Older Medicaid beneficiaries in Louisiana had higher rates of telemedicine claim volume during the COVID-19 pandemic compared with younger beneficiaries.

The Economic Burden of Racial, Ethnic, and Educational Health Inequities in the US.

Importance: Health inequities exist for racial and ethnic minorities and persons with lower educational attainment due to differential exposure to economic, social, structural, and environmental health risks and limited access to health care. Objective: To estimate the economic burden of health inequities for racial and ethnic minority populations (American Indian and Alaska Native, Asian, Black, Latino, and Native Hawaiian and Other Pacific Islander) and adults 25 years and older with less than a 4-year college degree in the US. Outcomes include the sum of excess medical care expenditures, lost labor market productivity, and the value of excess premature death (younger than 78 years) by race and ethnicity and the highest level of educational attainment compared with health equity goals. Evidence Review: Analysis of 2016-2019 data from the Medical Expenditure Panel Survey (MEPS) and state-level Behavioral Risk Factor Surveillance System (BRFSS) and 2016-2018 mortality data from the National Vital Statistics System and 2018 IPUMS American Community Survey. There were 87 855 survey respondents to MEPS, 1 792 023 survey respondents to the BRFSS, and 8 416 203 death records from the National Vital Statistics System. Findings: In 2018, the estimated economic burden of racial and ethnic health inequities was $421 billion (using MEPS) or $451 billion (using BRFSS data) and the estimated burden of education-related health inequities was $940 billion (using MEPS) or $978 billion (using BRFSS). Most of the economic burden was attributable to the poor health of the Black population; however, the burden attributable to American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander populations was disproportionately greater than their share of the population. Most of the education-related economic burden was incurred by adults with a high school diploma or General Educational Development equivalency credential. However, adults with less than a high school diploma accounted for a disproportionate share of the burden. Although they make up only 9% of the population, they bore 26% of the costs. Conclusions and Relevance: The economic burden of racial and ethnic and educational health inequities is unacceptably high. Federal, state, and local policy makers should continue to invest resources to develop research, policies, and practices to eliminate health inequities in the US.

The anterior center edge angle has limited ability to predict three-dimensional coverage of the femoral head in patients with developmental dysplasia of the hip undergoing curved periacetabular osteotomy.

INTRODUCTION: Femoral head coverage in patients with hip dysplasia (DDH) is typically quantified using 2D measurements of the lateral center edge angle (LCEA) and anterior center edge angle (ACEA). However, as the morphology of DDH is complex and varies between patients, 2D measurements may not predict the true 3D femoral head coverage. Herein, 2D and 3D coverage were quantified before and after curved periacetabular osteotomy (CPO) and their relationships were assessed. MATERIALS AND METHODS: Forty-three hips that underwent CPO for DDH were analyzed. For 2D evaluation, LCEA was quantified from X-rays and CT images. The ACEA was measured from CT images (CT-ACEA) and digitally reconstructed radiographs generated from CT images (DRR-ACEA). Three-dimensional coverage was quantified from CT reconstructions of the hip and evaluated in the anterior, superior, posterior, and inferior regions of the femoral head. Two-dimensional measurements were correlated to 3D coverage to assess their relationships. RESULTS: The median preoperative 3D percent coverage was 17.7, 36.1, 56.1, and 14.6% for the anterior, superior, posterior, and inferior region, respectively. After CPO, all LCEAs and ACEAs increased significantly (all p < 0.001). For the 3D coverage, anterior and superior coverage significantly increased while the posterior and inferior coverage decreased (all p < 0.001). Moderate to strong correlations were detected between the two LCEAs and the 3D superior coverage in both the preoperative and postoperative period. For the correlation between 3D anterior coverage, no significant correlation was found between the CT-ACEA while a moderate correlation was found between the DRR-ACEA (rs = 0.41, p = 0.023). CONCLUSIONS: Our results indicate that the LCEA can be used to predict 3D coverage in the superior region of the femoral head. However, as the CT-ACEA or DRR-ACEA had no or only moderate correlation between the 3D anterior coverage, these measurements are not recommended for evaluating/estimating the 3D anterior coverage in patients with DDH.

Deep Artificial Neural Networks Reveal a Distributed Cortical Network Encoding Propositional Sentence-Level Meaning.

Understanding how and where in the brain sentence-level meaning is constructed from words presents a major scientific challenge. Recent advances have begun to explain brain activation elicited by sentences using vector models of word meaning derived from patterns of word co-occurrence in text corpora. These studies have helped map out semantic representation across a distributed brain network spanning temporal, parietal, and frontal cortex. However, it remains unclear whether activation patterns within regions reflect unified representations of sentence-level meaning, as opposed to superpositions of context-independent component words. This is because models have typically represented sentences as "bags-of-words" that neglect sentence-level structure. To address this issue, we interrogated fMRI activation elicited as 240 sentences were read by 14 participants (9 female, 5 male), using sentences encoded by a recurrent deep artificial neural-network trained on a sentence inference task (InferSent). Recurrent connections and nonlinear filters enable InferSent to transform sequences of word vectors into unified "propositional" sentence representations suitable for evaluating intersentence entailment relations. Using voxelwise encoding modeling, we demonstrate that InferSent predicts elements of fMRI activation that cannot be predicted by bag-of-words models and sentence models using grammatical rules to assemble word vectors. This effect occurs throughout a distributed network, which suggests that propositional sentence-level meaning is represented within and across multiple cortical regions rather than at any single site. In follow-up analyses, we place results in the context of other deep network approaches (ELMo and BERT) and estimate the degree of unpredicted neural signal using an "experiential" semantic model and cross-participant encoding.SIGNIFICANCE STATEMENT A modern-day scientific challenge is to understand how the human brain transforms word sequences into representations of sentence meaning. A recent approach, emerging from advances in functional neuroimaging, big data, and machine learning, is to computationally model meaning, and use models to predict brain activity. Such models have helped map a cortical semantic information-processing network. However, how unified sentence-level information, as opposed to word-level units, is represented throughout this network remains unclear. This is because models have typically represented sentences as unordered "bags-of-words." Using a deep artificial neural network that recurrently and nonlinearly combines word representations into unified propositional sentence representations, we provide evidence that sentence-level information is encoded throughout a cortical network, rather than in a single region.

More than words: Neurophysiological correlates of semantic dissimilarity depend on comprehension of the speech narrative.

Speech comprehension relies on the ability to understand words within a coherent context. Recent studies have attempted to obtain electrophysiological indices of this process by modelling how brain activity is affected by a word's semantic dissimilarity to preceding words. Although the resulting indices appear robust and are strongly modulated by attention, it remains possible that, rather than capturing the contextual understanding of words, they may actually reflect word-to-word changes in semantic content without the need for a narrative-level understanding on the part of the listener. To test this, we recorded electroencephalography from subjects who listened to speech presented in either its original, narrative form, or after scrambling the word order by varying amounts. This manipulation affected the ability of subjects to comprehend the speech narrative but not the ability to recognise individual words. Neural indices of semantic understanding and low-level acoustic processing were derived for each scrambling condition using the temporal response function. Signatures of semantic processing were observed when speech was unscrambled or minimally scrambled and subjects understood the speech. The same markers were absent for higher scrambling levels as speech comprehension dropped. In contrast, word recognition remained high and neural measures related to envelope tracking did not vary significantly across scrambling conditions. This supports the previous claim that electrophysiological indices based on the semantic dissimilarity of words to their context reflect a listener's understanding of those words relative to that context. It also highlights the relative insensitivity of neural measures of low-level speech processing to speech comprehension.

Interventions for the Management of Computer Vision Syndrome: A Systematic Review and Meta-analysis.

TOPIC: To evaluate the efficacy and safety of interventions for treating eye strain related to computer use relative to placebo or no treatment. CLINICAL RELEVANCE: Computer use is pervasive and often associated with eye strain, referred to as computer vision syndrome (CVS). Currently, no clinical guidelines exist to help practitioners provide evidence-based advice about CVS treatments, many of which are marketed directly to patients. This systematic review and meta-analysis was designed to help inform best practice for eye care providers. METHODS: Eligible randomized controlled trials (RCTs) were identified in Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and trial registries, searched from inception through November 23, 2021. Eligible studies were appraised for risk of bias and were synthesized. The certainty of the body of evidence was judged using the Grading of Recommendations, Assessment, Development, and Evaluation system. Standardized mean differences (SMDs) were used when differently scaled measures were combined. RESULTS: Forty-five RCTs, involving 4497 participants, were included. Multifocal lenses did not improve visual fatigue scores compared with single-vision lenses (3 RCTs; SMD, 0.11; 95% confidence interval [CI], -0.14 to 0.37; P = 0.38). Visual fatigue symptoms were not reduced by blue-blocking spectacles (3 RCTs), with evidence judged of low certainty. Relative to placebo, oral berry extract supplementation did not improve visual fatigue (7 RCTs; SMD, -0.27; 95% CI, -0.70 to 0.16; P = 0.22) or dry eye symptoms (4 RCTs; SMD, -0.10; 95% CI, -0.54 to 0.33; P = 0.65). Likewise, berry extract supplementation had no significant effects on critical flicker-fusion frequency (CFF) or accommodative amplitude. Oral omega-3 supplementation for 45 days to 3 months improved dry eye symptoms (2 RCTs; mean difference [MD], -3.36; 95% CI, -3.63 to -3.10 on an 18 unit scale; P < 0.00001) relative to placebo. Oral carotenoid supplementation improved CFF (2 RCTs; MD, 1.55 Hz; 95% CI, 0.42 to 2.67 Hz; P = 0.007) relative to placebo, although the clinical significance of this finding is unclear. DISCUSSION: We did not identify high-certainty evidence supporting the use of any of the therapies analyzed. Low-certainty evidence suggested that oral omega-3 supplementation reduces dry eye symptoms in symptomatic computer users.

Follow-up Post-discharge and Readmission Disparities Among Medicare Fee-for-Service Beneficiaries, 2018.

BACKGROUND: Previous studies have identified disparities in readmissions among Medicare beneficiaries hospitalized for the Hospital Readmissions Reduction Program's (HRRP's) priority conditions. Evidence suggests timely follow-up is associated with reduced risk of readmission, but it is unknown whether timely follow-up reduces disparities in readmission. OBJECTIVE: To assess whether follow-up within 7 days after discharge from a hospitalization reduces risk of readmission and mitigates identified readmission disparities. DESIGN: A retrospective cohort study using Cox proportional hazards models to estimate the associations between sociodemographic characteristics (race and ethnicity, dual-eligibility status, rurality, and area social deprivation), follow-up, and readmission. Mediation analysis was used to examine if disparities in readmission were mitigated by follow-up. PARTICIPANTS: We analyzed data from 749,402 Medicare fee-for-service beneficiaries hospitalized for acute myocardial infarction, chronic obstructive pulmonary disease, heart failure, or pneumonia, and discharged home between January 1 and December 1, 2018. MAIN MEASURE: All-cause unplanned readmission within 30 days after discharge. KEY RESULTS: Post-discharge follow-up within 7 days of discharge was associated with a substantially lower risk of readmission (HR: 0.52, 95% CI: 0.52-0.53). Across all four HRRP conditions, beneficiaries with dual eligibility and beneficiaries living in areas with high social deprivation had a higher risk of readmission. Non-Hispanic Black beneficiaries had higher risk of readmission after hospitalization for pneumonia relative to non-Hispanic Whites. Mediation analysis suggested that 7-day follow-up mediated 21.2% of the disparity in the risk of readmission between dually and non-dually eligible beneficiaries and 50.7% of the disparity in the risk of readmission between beneficiaries living in areas with the highest and lowest social deprivation. Analysis suggested that after hospitalization for pneumonia, 7-day follow-up mediated nearly all (97.5%) of the increased risk of readmission between non-Hispanic Black and non-Hispanic White beneficiaries. CONCLUSIONS: Improving rates of follow-up could be a strategy to reduce readmissions for all beneficiaries and reduce disparities in readmission based on sociodemographic characteristics.

Measuring the Trustworthiness of Health Care Organizations and Systems.

Policy Points Current efforts to measure and improve trust in health care focus on changing patients' attitudes rather than measuring and improving the trustworthiness of health care organizations and systems. We present a conceptual model to understand and explain the constructs of trust and trustworthiness in the context of health care through the application of existing theories of human behavior. Developing and publicly reporting measures that can enable patients, particularly from historically marginalized groups, to better assess the trustworthiness of providers is necessary to promote health care equity.

Oxidative damage diminishes mitochondrial DNA polymerase replication fidelity.

Mitochondrial DNA (mtDNA) resides in a high ROS environment and suffers more mutations than its nuclear counterpart. Increasing evidence suggests that mtDNA mutations are not the results of direct oxidative damage, rather are caused, at least in part, by DNA replication errors. To understand how the mtDNA replicase, Pol γ, can give rise to elevated mutations, we studied the effect of oxidation of Pol γ on replication errors. Pol γ is a high fidelity polymerase with polymerase (pol) and proofreading exonuclease (exo) activities. We show that Pol γ exo domain is far more sensitive to oxidation than pol; under oxidative conditions, exonuclease activity therefore declines more rapidly than polymerase. The oxidized Pol γ becomes editing-deficient, displaying a 20-fold elevated mutations than the unoxidized enzyme. Mass spectrometry analysis reveals that Pol γ exo domain is a hotspot for oxidation. The oxidized exo residues increase the net negative charge around the active site that should reduce the affinity to mismatched primer/template DNA. Our results suggest that the oxidative stress induced high mutation frequency on mtDNA can be indirectly caused by oxidation of the mitochondrial replicase.

The effect of mental load on psychophysical and visual evoked potential visual acuity.

PURPOSE: Under real-world conditions, tasks dependent on visual acuity may need to be performed in the presence of a mental load arising from concurrent, non-visual tasks. Therefore, measuring visual acuity concurrently with mentally demanding tasks may reflect a patient's vision more accurately. This study was designed to evaluate the impact of task-induced mental load on high contrast visual acuity, as measured using a letter chart and estimated via sweep visual evoked potentials (sweep VEP). METHODS: Visual acuity was determined using the Freiburg Vision Test, and also using sweep VEP tested stepwise, from coarse to fine, over 13 spatial frequencies, in 31 healthy participants (aged 22.4 ± 3.6 years). Recordings were repeated while participants concurrently performed an auditory 2-back task. Mental load of the n-back task was confirmed through subjective ratings. RESULTS: Visual acuity determined with the Freiburg Vision Test worsened from -0.02 ± 0.12 to 0.04 ± 0.15 logMAR under mental load (p = 0.03). Visual acuities estimated by sweep VEPs worsened from 0.38 ± 0.1 to 0.47 ± 0.1 logMAR (p < 0.001). While the slope of the VEP amplitude versus spatial frequency function steepened significantly with mental load (p = 0.01), VEP noise levels were not significantly affected (p = 0.07). CONCLUSION: Visual acuity reduces significantly with a concurrent task that produces mental load. At least part of this reduction appears to be related to alterations in responses within the visual cortex, rather than being purely attributable to higher-level distraction effects.

How Does Chondrolabral Damage and Labral Repair Influence the Mechanics of the Hip in the Setting of Cam Morphology? A Finite-Element Modeling Study.

BACKGROUND: Individuals with cam morphology are prone to chondrolabral injuries that may progress to osteoarthritis. The mechanical factors responsible for the initiation and progression of chondrolabral injuries in these individuals are not well understood. Additionally, although labral repair is commonly performed during surgical correction of cam morphology, the isolated mechanical effect of labral repair on the labrum and surrounding cartilage is unknown. QUESTION/PURPOSES: Using a volunteer-specific finite-element analysis, we asked: (1) How does cam morphology create a deleterious mechanical environment for articular cartilage (as evaluated by shear stress, tensile strain, contact pressure, and fluid pressure) that could increase the risk of cartilage damage compared with a radiographically normal hip? (2) How does chondrolabral damage, specifically delamination, delamination with rupture of the chondrolabral junction, and the presence of a chondral defect, alter the mechanical environment around the damage? (3) How does labral repair affect the mechanical environment in the context of the aforementioned chondrolabral damage scenarios? METHODS: The mechanical conditions of a representative hip with normal bony morphology (characterized by an alpha angle of 37°) and one with cam morphology (characterized by an alpha angle of 78°) were evaluated using finite-element models that included volunteer-specific anatomy and kinematics. The bone, cartilage, and labrum geometry for the hip models were collected from two volunteers matched by age (25 years with cam morphology and 23 years with normal morphology), BMI (both 24 kg/m2), and sex (both male). Volunteer-specific kinematics for gait were used to drive the finite-element models in combination with joint reaction forces. Constitutive material models were assigned to the cartilage and labrum, which simulate a physiologically realistic material response, including the time-dependent response from fluid flow through the cartilage, and spatially varied response from collagen fibril reinforcement. For the cam hip, three models were created to represent chondrolabral damage conditions: (1) "delamination," with the acetabular cartilage separated from the bone in one region; (2) "delamination with chondrolabral junction (CLJ) rupture," which includes separation of the cartilage from the labrum tissue; and (3) a full-thickness chondral defect, referred to throughout as "defect," where the acetabular cartilage has degraded so there is a void. Each of the three conditions was modeled with a labral tear and with the labrum repaired. The size and location of the damage conditions simulated in the cartilage and labrum were attained from reported clinical prevalence of the location of these injuries. For each damage condition, the contact area, contact pressure, tensile strain, shear stress, and fluid pressure were predicted during gait and compared. RESULTS: The cartilage in the hip with cam morphology experienced higher stresses and strains than the normal hip. The peak level of tensile strain (25%) and shear stress (11 MPa) experienced by the cam hip may exceed stable conditions and initiate damage or degradation. The cam hip with simulated damage experienced more evenly distributed contact pressure than the intact cam hip, as well as decreased tensile strain, shear stress, and fluid pressure. The peak levels of tensile strain (15% to 16%) and shear stress (2.5 to 2.7 MPa) for cam hips with simulated damage may be at stable magnitudes. Labral repair only marginally affected the overall stress and strain within the cartilage, but it increased local tensile strain in the cartilage near the chondrolabral junction in the hip with delamination and increased the peak tensile strain and shear stress on the labrum. CONCLUSION: This finite-element modeling pilot study suggests that cam morphology may predispose hip articular cartilage to injury because of high shear stress; however, the presence of simulated damage distributed the loading more evenly and the magnitude of stress and strain decreased throughout the cartilage. The locations of the peak values also shifted posteriorly. Additionally, in hips with cam morphology, isolated labral repair in the hip with a delamination injury increased localized strain in the cartilage near the chondrolabral junction. CLINICAL RELEVANCE: In a hip with cam morphology, labral repair alone may not protect the cartilage from damage because of mechanical overload during the low-flexion, weightbearing positions experienced during gait. The predicted findings of redistribution of stress and strain from damage in the cam hip may, in some cases, relieve disposition to damage progression. Additional studies should include volunteers with varied acetabular morphology, such as borderline dysplasia with cam morphology or pincer deformity, to analyze the effect on the conclusions presented in the current study. Further, future studies should evaluate the combined effects of osteochondroplasty and chondrolabral treatment.

Pre-COVID-19 Disparities in Telemedicine Use Among Louisiana Medicaid Beneficiaries.

Background: We examine trends in telemedicine use by race, geography, and age among Louisiana Medicaid beneficiaries in the months preceding the COVID-19 pandemic. Methods: Using Louisiana Medicaid claims data from January 2018 through February 2020, we calculated a relative ratio of telemedicine use as the share of telemedicine claims by race, age, and geography and conducted two-sample t-tests. Results: In 2018, White beneficiaries used telemedicine at a relative ratio of 1.92 compared with Black beneficiaries (p < 0.001) and 2.02 compared with Hispanic beneficiaries (p < 0.001). Rural beneficiaries used telemedicine at a relative ratio of 1.27 (p < 0.001) compared with urban beneficiaries. Children and adolescents used telemedicine at a higher rate than other age groups. Racial and geographic disparities narrowed in the first months of 2020. Conclusions: Telemedicine use in Louisiana Medicaid was low but growing before the pandemic with narrowing disparities by race and geography and emerging disparities by age.