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    Integration of modern technologies to advance dietary assessment.

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    Diet is a key determinant of human and planetary health, but accurately measuring dietary intake remains challenging. Traditional self-reporting tools are imprecise, compromising our ability to accurately link diets with health outcomes. Modern technologies, including smartphone apps, image-based methods and biomarkers of food intake (BFIs), offer promise but bring their own caveats. App- and image-based methods reduce bias and reporting burden, but remain partly self-reported, and are thus prone to errors similar to those of traditional methods. Omics-based BFIs (that is, metabolites, food-related DNA or food proteins) are objective measures derived from biological samples; however, they mostly reflect recent intake, and require careful sampling alignment to estimate habitual diets. Here we discuss the drawbacks and opportunities for all dietary tools and propose strategies to integrate technologies along with multisampling for longitudinal measurements, for a new era in dietary assessment that can clarify the impact of diets, dietary components and dietary behaviour on human and planetary health

    Development of Validity Evidence of a Standardized Competency Tool for Internal Jugular Vein Point of Care Ultrasound: Consensus Recommendations from International Experts.

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    BACKGROUND: Central venous pressure (CVP) is traditionally evaluated by visually estimating the jugular venous pressure (JVP), but this examination can vary with patient anatomy and operator skill. Point-of-care ultrasound (POCUS) of the internal jugular vein (IJV) presents a promising alternative for evaluating the JVP but a standardized competency-based assessment tool is lacking. OBJECTIVE: This study aimed to develop educational tools for assessing competency in IJV POCUS using a modified Delphi method. DESIGN: Two ultrasound competency checklists were developed by five Internal Medicine physicians experienced in IJV ultrasound. Checklist 1 focused on ultrasound JVP (u-JVP) evaluation with patients positioned at 30-45°, while Checklist 2 focused on upright-JVP with patients in an upright or 90° position based on previously published techniques. Nine expert physicians in POCUS participated in three rounds of a modified Delphi process to determine consensus on checklist items. Consensus was defined as agreement of 80% or more; items that did not reach consensus after three rounds were excluded. A subsequent modified Angoff method was used to establish passing scores and identify critical items. KEY RESULTS: After three rounds of the Delphi process, 18 of 23 items (77%) in Checklist 1 and 15 of 18 items (83%) in Checklist 2 reached consensus for inclusion. Passing scores were established at 69.6% for Checklist 1 and 70.2% for Checklist 2. Additionally, 4/18 items (22%) in Checklist 1 and 3/15 items (20%) in checklist 2 were identified as critical. CONCLUSION: Using a modified Delphi method to appraise two competency assessment tools for POCUS evaluation of the IJV, we reached consensus on an 18-item checklist for u-JVP and a 15-item checklist for upright JVP, of which 4 and 3 items were deemed critical, respectively. By defining critical items and setting passing scores, these tools may help standardize the assessment of trainee proficiency in IJV POCUS

    Fluorescence tracking Treg movement identifies anti-CCR8 and radiation as a therapeutic combination.

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    Radiation therapy (RT) is recognized for its ability to induce DNA damage within cancer cells, leading to cancer cell death and promotion of anti-tumor immune responses. However, this beneficial effect is often counterbalanced by the presence of suppressive Tregs. Although factors such as RT-induced transforming growth factor β (TGF-β) can contribute to increased Treg accumulation within the tumor, the dynamics of Treg movement, and recruitment in the post-RT tumor microenvironment are not fully understood. Our study examined Treg migration following RT, revealing that RT disrupts Treg migration to the tumor-draining lymph node (TdLN) and alters their phenotype. Combining RT with anti-CCR8 therapy, which selectively depletes Tregs within the tumor, significantly reduced tumor burden, and increased survival in preclinical models. This combination also proved effective against distant and unirradiated tumors. Additionally, efficacy of combination therapy was CD8 T cell dependent. These findings highlight the potential of combining RT with Treg-targeting therapies to enhance anti-tumor immunity

    Sex Differences in Spontaneous Coronary Artery Dissection: A Report of the iSCAD Registry.

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    Background: Spontaneous coronary artery dissection is a cause of myocardial infarction, which predominantly affects middle-aged women. There are limited data on men with spontaneous coronary artery dissection. Methods: Information on demographics, presenting characteristics, in-hospital outcomes including major adverse cardiovascular events (composite of myocardial infarction, cerebrovascular accident, or heart failure), length of stay, and discharge medications in men and women were obtained from the multicenter iSCAD (International Spontaneous Coronary Artery Dissection) registry. Results: Of 1252 patients enrolled from 2019 to 2023, 80 (6.4%) were men. Mean age did not significantly differ between sexes (men, 50.2±10.3 versus women 49.7±10.4; P=0.792). Women reported more emotional stress preceding spontaneous coronary artery dissection (10.2% versus 2.5% men; P=0.025). Men reported more physical stress (22.5% versus 7.7% women; P\u3c 0.001), both isometric exertion (12.5% versus 2.4% women; P\u3c 0.001) and aerobic exertion (12.5% versus 5.6% women, P\u3c 0.013). Chest discomfort was the major symptom, although women reported more non-chest discomfort, shortness of breath, and nausea/vomiting. Men had fewer autoimmune conditions, systemic inflammatory disorders, and fibromuscular dysplasia but more recreational drug use. In-hospital major adverse cardiovascular events did not significantly differ (4.1% men versus 8.5% women; P=0.178). The median length of stay was 3.0 (interquartile range, 3.0-4.0) days for males versus 4.0 (interquartile range, 3.0-5.0) days for women (P=0.003). At discharge, more men were prescribed statins (72.5% men versus 55.3% women; P=0.003) and dual antiplatelet therapy (66.3% men versus 53.7% women) (P=0.049). Conclusions: In a large spontaneous coronary artery dissection registry, there were significant sex differences in presentation, baseline medical conditions, and triggers. In-hospital outcomes were similar, but length of stay was longer for women. Men were more often discharged on statins and dual antiplatelet therapy

    Platy-1 SINEs from Thirteen Diverse Genomes Reveal Callithrichidae Unique Amplification, Recent

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    Background/objectives: In 2023, we reported that the tamarins (genus Saguinus) Saguinus imperator and Saguinus midas have had an extensive independent expansion of Platy-1 SINEs compared to previously characterized platyrrhine genomes among traditional cebids. This study investigates the amplification dynamics of Platy-1 insertions across thirteen diverse genomes representing each Platyrrhini family, including two from Pitheciidae and three from Atelidae. Methods: By comparing the distribution of Platy-1 subfamily content, total interspersed repeat content and the proximity of Platy-1 insertions to, or within, other repeats across evolutionary taxa, this study begins to identify genomic landscape features that are unique to family Callithrichidae that correlate with LINE (L1). Results: Platy-1 radiation in non-callithrichid taxa derives primarily from older subfamilies 1-4, 1-4a (as reported here for genus Alouatta) and 1-5, whereas callithrichids proliferate higher numbers of Platy-1 copies via independent bursts from much younger sources. Linage-specific Platy-1 activity was notable in two of the new genomes studied, Bolivian titi and mantled howler monkey, both with a relatively low copy number. Variable presence/absence patterns across evolutionary taxa support the traditional platyrrhine branching order Pitheciidae-Atelidae-Cebidae. Only one Platy-1-4a insertion polymorphism placed Aotidae between Atelidae and Cebidae, as opposed to between Cebidae and Callithrichidae. Conclusions: This study shows that callithrichids, and Saguinus tamarins in particular, are unique among platyrrhines with regard to their extensive rate of Platy-1 mobilization, a dynamic that appears to be correlated with LINE (L1) genomic content. Alouatta has two young lineage-specific Platy-1 subfamilies. With strong evidence of incomplete lineage sorting (ILS) and rapid radiation, the accurate placement of Aotus remains elusive

    Single-cell transcriptomics showed that maternal polychlorinated biphenyl exposure dysregulated cell type-specific metabolic responses in the livers of female mouse offsprings.

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    Polychlorinated biphenyls (PCBs) are persistent environmental toxicants that bioaccumulate in the food chain and readily cross the placenta, raising concerns for developmental toxicity. Although PCB exposure has been associated with metabolic and neurodevelopmental disorders, its cell type-specific effects on liver development remain poorly understood. This study aimed to investigate how maternal exposure to an environmentally relevant Fox River PCB mixture affects liver development in female offspring at single-cell resolution. We hypothesized that developmental PCB exposure disrupts hepatic metabolic and immune function in a cell-type-specific manner. Using single-cell RNA sequencing on liver tissue from postnatal day 28 female mice exposed to PCBs throughout gestation and lactation, we identified major hepatic and immune cell populations and assessed cell-specific transcriptional responses. PCB exposure significantly altered the proportions of endothelial cells and Kupffer cells and reduced neutrophil abundance in the liver. Transcriptomic analysis revealed that PCBs dysregulated key functional pathways in hepatocytes and nonparenchymal cells, including endoplasmic reticulum stress responses, drug metabolism, and glucose/insulin signaling. Notably, hepatocytes exhibited upregulation of phase I drug-metabolizing enzymes and uptake transporters, but downregulation of phase II enzymes and efflux transporters. Kupffer cells and endothelial cells exhibited altered immune and metabolic gene expression, and intercellular communication analysis predicted that PCB exposure disrupted fibronectin, collagen, and chemokine signaling. Reverse transcription-quantitative polymerase chain reaction validation confirmed increased expression of hepatic endoplasmic reticulum stress markers. Together, these findings demonstrate that developmental PCB exposure induces persistent, cell-type-specific transcriptomic reprogramming in the liver, impairing metabolic and immune functions. This study highlights the utility of single-cell transcriptomics for revealing toxicant effects with cellular precision during critical windows of development. SIGNIFICANCE STATEMENT: Our findings showed that developmental exposure to a persistent organic pollutant led to transcriptomic changes that differed across cell types that form the liver. Our study highlights the use of single cell technology to investigate toxic effects for mechanistic insights with greater precision

    Co-Var, a Measure to Determine Intra-protein, Inter-protein, Protein-DNA, or Protein-RNA Coevolution.

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    Interacting biomolecules tend to coevolve, and compensatory or coordinated residue changes may occur to preserve functional interactions. Predicting coevolutionary pairings could be important for determining structurally and functionally important residues in complexes or interfaces. Correlated variation (Co-Var) aims to determine both intramolecular and intermolecular coevolving residues in proteins, protein-protein, protein-DNA, or protein-RNA complexes. It utilizes two statistical parameters namely mutual information and Bhattacharyya coefficient. In this article, we have described how to utilize the Co-Var method to identify coevolutionary parings within and/or across biomolecules

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