Temperature modulates dominance of a superinfecting Arctic virus in its unicellular algal host.

Complex virus-virus interactions can arise when multiple viruses coinfect the same host, impacting infection outcomes with broader ecological and evolutionary significance for viruses and host. Yet, our knowledge regarding virus competition is still limited, especially for single-celled eukaryotic host-virus systems. Here, we report on mutual interference of two dsDNA viruses, MpoV-45 T and MpoV-46 T, competing for their Arctic algal host Micromonas polaris. Both viruses affected each other's gene expression and displayed reduced genome replication during coinfection. MpoV-45 T was the dominant virus, likely due to interference in the DNA replication of is competitor. Even when its coinfection was delayed, the dominant virus still prevailed while genome production of the other virus was strongly suppressed. This contrasts with typical superinfection exclusion, where the primary infection prevents secondary infection by other viruses. Higher temperature made the suppressed virus a stronger competitor, signifying that global warming is likely to alter virus-virus interactions in Arctic waters.

Adaptively triggered comparisons enhance perceptual category learning: evidence from face learning.

Categorical learning is important and often challenging in both specialized domains, such as medical image interpretation, and commonplace ones, such as face recognition. Research has shown that comparing items from different categories can enhance the learning of perceptual classifications, particularly when those categories appear highly similar. Here, we developed and tested novel adaptively triggered comparisons (ATCs), in which errors produced during interactive learning dynamically prompted the presentation of active comparison trials. In a facial identity paradigm, undergraduate participants learned to recognize and name varying views of 22 unknown people. In Experiment 1, single-item classification trials were compared to a condition in which ATC trials were generated whenever a participant repeatedly confused two faces. Comparison trials required discrimination between simultaneously presented exemplars from the confused categories. In Experiment 2, an ATC condition was compared to a non-adaptive comparison condition. Participants learned to accuracy and speed criteria, and completed immediate and delayed posttests. ATCs substantially enhanced learning efficiency in both experiments. These studies, using a novel adaptive procedure guided by each learner's performance, show that adaptively triggered comparisons improve category learning.

Correction: Odegaard et al. Distinct Synaptic Vesicle Proteomic Signatures Associated with Pre- and Post-Natal Oxycodone-Exposure. Cells 2022, 11, 1740.

In the original publication [...].

Circulating Neutrophil Extracellular Trap (NET)-forming neutrophils in rheumatoid arthritis exacerbation are majority dual endothelin-1/signal peptide receptor (DEspR)+ subtype.

Neutrophil extracellular traps (NETs) are associated with rheumatoid arthritis pathogenesis and severity. Since homeostatic NET-forming neutrophils [NET+Ns] have beneficial roles in defense against pathogens, their distinction from pro-injury [NET+N] subtypes is important, especially if they are to be therapeutically-targeted. Having identified circulating, pro-injury DEspR+CD11b+ [NET+Ns] in patients with neutrophilic secondary tissue injury, we determined whether DEspR+ [NET+Ns] are present in RA-flares. Whole blood samples of patients with RA-flares on maintenance therapy (n=6), were analyzed by flow cytometry (FCM) and immunofluorescence cytology followed by semi-automated quantitative confocal microscopy (qIFC). We assessed clinical parameters, levels of neutrophils and [NET+Ns], and plasma S100A8/A9. qIFC detected circulating DEspR+CD11b+ neutrophils and [NET+Ns] in RA-flare patients but not healthy controls. DEspR+ [NET+Ns] were positive for citrullinated histone H3 (citH3+), extruded DNA, decondensed but recognizable polymorphic nuclei, and [NET+N] doublet-interactions in mostly non-ruptured NET-forming neutrophils. Circulating DNA+/DEspR+/CD11b+/citH3+ microvesicles (netMVs) were observed. FCM detected increased %DEspR+CD11b+ neutrophils and DEspR+ cell-cell doublets whose levels trended with DAS28 scores, as did plasma S100A8/A9 levels. This study identifies circulating DEspR+/CD11b+ neutrophils and [NET+Ns] in RA-flare patients on maintenance therapy. Detection of circulating DEspR+citH3+ [NET+Ns] and netMVs indicate a systemic neutrophilic source of citH3-antigen concordant with multi-joint RA pathogenesis. Increased S100A8/A9 alarmin levels are associated with cell injury and released upon NET-formation. As a ligand for TLR4, S100A8/A9 forms a positive feedback loop for TLR4-induced DEspR+ neutrophils. These data identify DEspR+ neutrophils and [NET+Ns] in RA pathogenesis as a potential biomarker and/or therapeutic target.

Associations between Statin Use and Glaucoma in the All of Us Research Program.

PURPOSE: To investigate associations between statin use and glaucoma in the 2017-2022 All of Us (AoU) Research Program. DESIGN: Cross-sectional, population-based. PARTICIPANTS: 79,742 adult participants aged ≥ 40 years with hyperlipidemia and with electronic health record (EHR) data in the AoU database. METHODS: Hyperlipidemia, glaucoma status, and statin use were defined by diagnoses and medication information in EHR data collected by AoU. Logistic regression analysis was performed to evaluate the association between statin use and glaucoma likelihood. Logistic regression modeling was used to examine associations between glaucoma and all covariates included in adjusted analysis. Serum low-density lipoprotein cholesterol (LDL-C) was used to assess hyperlipidemia severity. Analyses stratified by LDL-C level and age were performed. MAIN OUTCOME MEASURES: Any glaucoma as defined by International Classification of Diseases (ICD) codes found in EHR data. RESULTS: Of 79,742 individuals with hyperlipidemia in AoU, there were 6,365 (8.0%) statin users. Statin use was associated with increased glaucoma prevalence when compared with statin non-use (adjusted odds ratio [aOR]: 1.13, 95% confidence interval [CI]: 1.01-1.26). Higher serum levels of LDL-C were associated with increased odds of glaucoma (aOR: 1.003, 95% CI: 1.003, 1.004). Statin users had significantly higher LDL-C levels compared to nonusers (144.9 mg/dL versus 136.3 mg/dL, p-value < 0.001). Analysis stratified by LDL-C identified positive associations between statin use and prevalence of glaucoma among those with optimal (aOR = 1.39, 95% CI = 1.05-1.82) and high (aOR = 1.37, 95% CI = 1.09-1.70) LDL-C levels. Age-stratified analysis showed a positive association between statin use and prevalence of glaucoma in individuals aged 60-69 years (aOR = 1.28, 95% CI = 1.05-1.56). CONCLUSIONS: Statin use was associated with increased glaucoma likelihood in the overall adult AoU population with hyperlipidemia, in individuals with optimal or high LDL-C levels, and in individuals 60-69 years old. Findings suggest that statin use may be an independent risk factor for glaucoma, which may furthermore be affected by one's lipid profile and age.

Synthesis, structural studies and Hirshfeld surface analysis of 2-[(4-phenyl-1H-1,2,3-triazol-1-yl)methyl]pyridin-1-ium hexa-kis-(nitrato-κ2 O,O')thorate(IV).

Reaction of thorium(IV) nitrate with 2-[(4-phenyl-1H-1,2,3-triazol-1-yl)meth-yl]pyridine (L) yielded (LH)2[Th(NO3)6] or (C14H13N4)2[Th(NO3)6] (1), instead of the expected mixed-ligand complex [Th(NO3)4 L 2], which was detected in the mass spectrum of 1. In the structure, the [Th(NO3)6]2- anions display an icosa-hedral coordination geometry and are connected by LH+ cations through C-H⋯O hydrogen bonds. The LH+ cations inter-act via N-H⋯N hydrogen bonds. Hirshfeld surface analysis indicates that the most important inter-actions are O⋯H/H⋯O hydrogen-bonding inter-actions, which represent a 55.2% contribution.

Effect of parenteral lipids on essential fatty acid deficiency in pediatric intestinal failure: A retrospective cohort study.

BACKGROUND: Pediatric patients with intestinal failure require long-term parenteral nutrition owing to impaired enteral nutrition absorption. A potential complication is essential fatty acid deficiency (EFAD), resulting from decreased linoleic and α-linolenic acid concentrations and defined by an increased triene:tetraene ratio (TTR; Mead acid:arachidonic acid). Historically, soybean oil lipid emulsion (SOLE) was the only commercially available parenteral lipid in the United States. Recently, a composite lipid emulsion (CLE) and fish oil lipid emulsion (FOLE) received US Food and Drug Administration approval. This study investigated whether lipid emulsion regimen impacts EFAD incidence in pediatric patients with intestinal failure. METHODS: This study was a 10-year retrospective cohort study of pediatric patients with intestinal failure who received parenteral SOLE, CLE, or FOLE. The primary outcome was EFAD incidence, defined as a TTR ≥ 0.2. Secondary outcomes included TTR ≥ 0.05, cholestasis incidence, lipid dose effect on EFAD incidence, and fatty acid parameter differences. RESULTS: A total of 144 fatty acid profiles from 47 patients were reviewed. EFAD did not occur in any lipid emulsion group. There were no differences in the incidence of TTR ≥ 0.05 or cholestasis. The effect of dose could not be evaluated because of no EFAD incidence. Lastly, although each group had varied fatty acid parameters, none saw decreased essential fatty acid levels. CONCLUSION: This study found that, with close monitoring, the lipid emulsion regimen did not impact EFAD incidence. This suggests that FOLE and CLE do not increase EFAD risk compared with SOLE in pediatric patients with intestinal failure.

Compromised heat loss leads to a delayed ice slurry induced reduction in heat storage.

Compromised heat loss due to limited convection and evaporation can increase thermal strain. We aimed to determine the effectiveness of ice slurry ingestion to reduce thermal strain following hyperthermia in a state of compromised heat loss. Twelve healthy males (age: 25 ± 4y) underwent hot water immersion to elevate rectal temperature (Trec) by 1.82 ± 0.08°C on four occasions. In the subsequent 60-min of seated recovery, participants ingested either 6.8 g·kg-1 of ice slurry (-0.6°C) or control drink (37°C) in ambient conditions (21 ± 1°C, 39 ± 10% relative humidity), wearing either t-shirt and shorts (2 trials: ICE and CON) or a whole-body sweat suit (2 trials: ICE-SS and CON-SS). Trec and mean skin temperature (Tsk) were recorded and a two-compartment thermometry model of heat storage was calculated. Heat storage was lower in ICE compared with CON at 20-40min (p ≤ 0.044, d ≥ 0.88) and for ICE-SS compared with CON-SS at 40-60 min (p ≤ 0.012, d ≥ 0.93). Trec was lower in ICE compared with CON from 30-60min (p ≤ 0.034, d ≥ 0.65), with a trend for a reduced Trec in ICE-SS compared with CON-SS at 40min (p = 0.079, d = 0.60). A greater Tsk was found in ICE-SS and CON-SS compared with ICE and CON (p < 0.001, d ≥ 3.37). A trend for a lower Tsk for ICE compared with CON was found at 20-40min (p ≤ 0.099, d ≥ 0.53), no differences were found for ICE-SS vs CON-SS (p ≥ 0.554, d ≤ 0.43). Ice slurry ingestion can effectively reduce heat storage when heat loss through convection and evaporation is compromised, relevant to those wearing personal protective equipment or those with compromised sweat loss. Compromised heat loss delays the reduction in heat storage, possibly related to ice slurry ingestion not lowering Tsk.

General Skills Amidst the Details: Alternative Learning Objectives and a Framework of Competencies for Human Anatomy.

The field of anatomy is often seen by non-anatomists as concerned primarily with the tasks of locating, naming, and describing structures; these tasks, in turn, are often assumed to require only lower-order cognitive skills (LOCS), i.e., the Knowledge or Comprehension levels of Bloom's taxonomy. Many non-anatomists may thus believe that studying anatomy does not develop transferable higher-order cognitive skills. Published lists of anatomy learning objectives (LOs) might reinforce this view by focusing attention on numerous details of specific structures and regions. To explore this issue further, we have analyzed the structure of published peer-reviewed LOs by characterizing their organization (single-tiered or multi-tiered), inclusion of function, use of action verbs, and dependence on or independence of context. Our results suggest that previously published LO lists, despite their value, may not fully showcase opportunities for students to develop higher-order skills. In the hope of stimulating further discussion and scholarship, we present here a two-tiered framework of human anatomy competencies, i.e., generalizable skills beyond straightforward recognition and memorization. This framework, which is intended to be both student-facing and faculty-facing, illustrates how anatomy courses may be reframed as opportunities to think critically and develop sophisticated, professionally relevant skills.

Fostering Organizational Excellence through Inclusive Leadership: Practical Guide for Radiology Leaders.

Inclusive leadership styles value team members, invite diverse perspectives, and recognize and support the contributions of employees. The authors provide guidance to radiology leaders interested in developing inclusive leadership skills and competencies to improve workforce recruitment and retention and unlock the potential of a rapidly diversifying health care workforce. As health care organizations look to attract the best and brightest talent, they will be increasingly recruiting millennial and Generation Z employees, who belong to the most diverse generations in American history. Additionally, radiology departments currently face critical workforce shortages in radiologists, radiology technicians, staff, and advanced practice providers. In the context of these shortages, the costs of employee turnover have emphasized the need for radiology leaders to develop leadership behaviors that promote recruitment and retention. Radiology department leaders who perceive and treat valued employees as replaceable commodities will be forced to deal with the extremely high costs associated with recruitment and training, decreased morale, and increased burnout. The authors review inclusive versus exclusive leadership styles, describe key attributes and skills of inclusive leaders, provide radiology leaders with concrete methods to make their organizations more inclusive, and outline key steps in change management. By adopting and implementing inclusive leadership strategies, radiology groups can position themselves to succeed in rapidly diversifying health care environments. ©RSNA, 2024 See the invited commentary by Siewert in this issue.

Multivariable Mendelian randomization with incomplete measurements on the exposure variables in the Hispanic Community Health Study/Study of Latinos.

Multivariable Mendelian randomization allows simultaneous estimation of direct causal effects of multiple exposure variables on an outcome. When the exposure variables of interest are quantitative omic features, obtaining complete data can be economically and technically challenging: the measurement cost is high, and the measurement devices may have inherent detection limits. In this paper, we propose a valid and efficient method to handle unmeasured and undetectable values of the exposure variables in a one-sample multivariable Mendelian randomization analysis with individual-level data. We estimate the direct causal effects with maximum likelihood estimation and develop an expectation-maximization algorithm to compute the estimators. We show the advantages of the proposed method through simulation studies and provide an application to the Hispanic Community Health Study/Study of Latinos, which has a large amount of unmeasured exposure data.

Insulin Resistance in Women Correlates with Chromatin Histone Lysine Acetylation, Inflammatory Signaling, and Accelerated Aging.

BACKGROUND: Epigenetic changes link medical, social, and environmental factors with cardiovascular and kidney disease and, more recently, with cancer. The mechanistic link between metabolic health and epigenetic changes is only starting to be investigated. In our in vitro and in vivo studies, we performed a broad analysis of the link between hyperinsulinemia and chromatin acetylation; our top "hit" was chromatin opening at H3K9ac. METHODS: Building on our published preclinical studies, here, we performed a detailed analysis of the link between insulin resistance, chromatin acetylation, and inflammation using an initial test set of 28 women and validation sets of 245, 22, and 53 women. RESULTS: ChIP-seq identified chromatin acetylation and opening at the genes coding for TNFα and IL6 in insulin-resistant women. Pathway analysis identified inflammatory response genes, NFκB/TNFα-signaling, reactome cytokine signaling, innate immunity, and senescence. Consistent with this finding, flow cytometry identified increased senescent circulating peripheral T-cells. DNA methylation analysis identified evidence of accelerated aging in insulin-resistant vs. metabolically healthy women. CONCLUSIONS: This study shows that insulin-resistant women have increased chromatin acetylation/opening, inflammation, and, perhaps, accelerated aging. Given the role that inflammation plays in cancer initiation and progression, these studies provide a potential mechanistic link between insulin resistance and cancer.

Evaluation of Cocurricular Learning and the Influence of Student Choice.

OBJECTIVE: The primary objective of this study was to evaluate the students' choice of activities and perception of a cocurricular program (CCP). Attitude and skill development and areas for program improvement were also assessed. METHODS: Data were evaluated from 2 sources: a student survey administered to all Doctor of Pharmacy students to determine student perceptions of the CCP and barriers to success and student activity reporting data from postexperience submissions to evaluate the CCP. Data were stratified by student demographics to identify trends. A comparison of data was conducted from both sources on the students' perception of learning value. RESULTS: Data for 405 students were available for analysis. The highest preference overall from students for hosts of activities were professional student organizations; the highest preference of location was online, asynchronous. The most meaningful benefits were learning information about a new subject (n = 258, 63.7%), ability to extend learning from the classroom to real life (n = 247, 61%), and networking opportunities (n = 218, 53.8%). The top barriers for completion of the program included scheduling challenges (n = 296, 73.1%), lack of time (n = 249, 61.5%), and lack of interest (n = 187, 46.2%). Subpopulations identified different benefits and barriers to completion. CONCLUSION: Students have overall positive perceptions of the CCP and its value for skill development. Findings were applied to adjust the CCP at the institution, including a reduction in total hours required. The continuous evaluation of CCPs is important to optimize student learning and address curricular overload.

Predictors of COVID-19 vaccine uptake among youth with bipolar disorder spectrum disorders and their caregivers.

BACKGROUND: Little is known about rates of COVID-19 vaccine uptake among youth with bipolar spectrum disorders (BSD). As such, the aim of this study is to assess rates and predictors of COVID-19 vaccine uptake among youth with BSD and their caregivers in the United States. METHODS: Youth and their main caregiver were recruited from a large pragmatic study cohort. Youth who were aged 8-22 at the time of this data collection, had a bipolar-spectrum disorder diagnosis, had overweight or obesity, and were treated with a second-generation antipsychotic were invited to participate in an online survey and interview assessing the impact of the COVID-19 pandemic. RESULTS: A total of 453 surveys and 341 interviews were completed 07/2021-05/2022 by youth and their caregivers. Sixty-seven percent of caregivers and 63 % of youth reported receiving the COVID-19 vaccine. Vaccine uptake rates among youth and caregivers were highly correlated. Predictors of vaccine uptake among youth were older age and living in the Northeast Region of the United States. Predictors of caregiver vaccine uptake were male sex, higher annual household income and not having to quarantine due to COVID-19. LIMITATIONS: The sample was small and not a full representation of a population with bipolar-spectrum disorders therefore, the results may not be generalizable. The study design and statistical method do not allow for causal inferences to be made. CONCLUSIONS: These findings may aid in targeting interventions to maximize COVID-19 and other vaccine uptake in youth with bipolar disorders and their families.

Identification of novel bromodomain inhibitors of Trypanosoma cruzi bromodomain factor 2 (TcBDF2) using a fluorescence polarization-based high-throughput assay.

Bromodomains are structural folds present in all eukaryotic cells that bind to other proteins recognizing acetylated lysines. Most proteins with bromodomains are part of nuclear complexes that interact with acetylated histone residues and regulate DNA replication, transcription, and repair through chromatin structure remodeling. Bromodomain inhibitors are small molecules that bind to the hydrophobic pocket of bromodomains, interfering with the interaction with acetylated histones. Using a fluorescent probe, we have developed an assay to select inhibitors of the bromodomain factor 2 of Trypanosoma cruzi (TcBDF2) using fluorescence polarization. Initially, a library of 28,251 compounds was screened in an endpoint assay. The top 350-ranked compounds were further analyzed in a dose-response assay. From this analysis, seven compounds were obtained that had not been previously characterized as bromodomain inhibitors. Although these compounds did not exhibit significant trypanocidal activity, all showed bona fide interaction with TcBDF2 with dissociation constants between 1 and 3 µM validating these assays to search for bromodomain inhibitors.

Integrating trauma- and violence-informed care for adolescent mothers in Rwanda: a qualitative study with community health workers.

INTRODUCTION: In Rwanda, maternal community health workers play a critical role to improving maternal, newborn and child health, but little is known about their specific experiences with adolescent mothers, who face unique challenges, including trauma, ongoing violence, stigma, ostracism, mental health issues, barriers within the healthcare system, and lack of access to the social determinants of health. This study explored the experiences of maternal community health workers when caring for adolescent mothers in Rwanda to inform the delivery of trauma- and violence-informed care in community maternal services. METHODS: Interpretive Description methodology was used to understand the experiences of 12 community health workers purposively recruited for interviews due to their management roles. To gain additional insights about the context, seven key informants were also interviewed. FINDINGS: Maternal community health workers provided personalized support to adolescent mothers through the provision of continuity of care, acting as a liaison, engaging relationally and tailoring home visits. They reported feeling passionate about their work, supporting each other, and receiving support from their leaders as facilitators in caring for adolescent mothers. Challenges in their work included handling disclosures of violence, dealing with adolescent mothers' financial constraints, difficulties accessing these young mothers, and transportation issues. Adolescent mothers' circumstances are generally difficult, leading to self-reports of vicarious trauma among this sample of workers. CONCLUSION: Maternal community health workers play a key role in addressing the complex needs of adolescent mothers in Rwanda. However, they face individual and structural challenges highlighting the complexities of their work. To sustain and enhance their roles, it is imperative for government and other stakeholders to invest in resources, mentorship, and support. Additionally, training in equity-oriented approaches, particularly trauma- and violence-informed care, is essential to ensure safe and effective care for adolescent mothers and to mitigate vicarious trauma among maternal community health workers.

Geographic Trends in Ophthalmology Resident Physician Compensation and Cost-of-Living Expenses.

Importance: Given that resident physician financial strain has been associated with poor outcomes, objective metrics to forecast financial well-being may be useful to (1) applicants when evaluating ophthalmology residency programs and (2) programs when determining resident benefits. Objectives: To determine and compare the relative value of ophthalmology resident stipends plus benefits when adjusted for cost-of-living expenses and to analyze program characteristics associated with greater resident net incomes. Design, Setting, and Participants: In this cross-sectional study, the American Medical Association's Fellowship and Residency Electronic Interactive Database was used to identify US Accreditation Council for Graduate Medical Education-accredited ophthalmology residency programs. Resident physician stipends and stipends plus benefits as well as residency program characteristics from the 2023-2024 academic year were noted for all eligible programs. The Massachusetts Institute of Technology's Living Wage Calculator's required annual income (RAI) was selected as a surrogate to approximate cost-of-living expenses. Exposure: Residency program characteristics, including affiliation, size, ranking, presence of housing benefit, and training year. Main Outcomes and Measures: The primary outcome was the annual stipend plus benefits income surplus (SPBIS) for each residency program, defined as the resident's stipend plus benefits (SPB) minus the RAI for the county in which the residency program is located. Secondary outcomes included income surplus variation by program characteristics. Results: Of 116 ophthalmology residency programs analyzed, 37 (31.9%) were located in the Northeast, 36 (31.0%) in the South, 29 (25.0%) in the Midwest, and 14 (12.1%) in the West. The mean (SD) postgraduate year 1 resident annual SPB was $65 397 ($8205), and the median (IQR) was $63 986 ($59 992-$69 698). After adjusting for the cost of living, the mean (SD) SPBIS was $27 459 ($5734) and the median (IQR) was $27 380 ($23 625-$31 796). Annual cost-of-living expenses varied by as much as $8628 (95% CI, $6310-$10 947) and SPBIS varied by as much as $6283 (95% CI, $3367-$9198) between regions. Resident SPB increased by a mean (SD) of 3.97% (0.98%) for each subsequent training year (range, 0.93%-7.26%). Annual SPBIS increased by a mean (SD) of 9.48% (3.60%) for each subsequent training year. Conclusions and Relevance: After adjusting for living costs, intraregional and interregional differences in SPBIS among ophthalmology residents can vary by thousands of dollars, impacting residents' financial security. Further discussion regarding compensation may lead to innovative strategies that aim to improve resident well-being and performance.