We evaluated the impact of sex and mitochondrial-haplotype on the age-related changes in the fecal gut microbiome of the genetically heterogeneous rodent model, the OKC-HET rat. Alpha-diversity, measuring richness and evenness of gut microbiome composition, did not change with age or mitochondrial-haplotype. However, beta-diversity, a measure of microbial differences among samples, was significantly modulated by age in male and female rats in both mitochondrial-haplotypes.
View Article and Find Full Text PDFLung nodules are frequently detected on low-dose computed tomography scans performed for lung cancer screening and incidentally detected on imaging performed for other reasons. There is wide variability in how lung nodules are managed by general practitioners and subspecialists, with high rates of guideline-discordant care. This may be due in part to the level of evidence underlying current practice guideline recommendations (primarily based on findings from uncontrolled studies of diagnostic accuracy).
View Article and Find Full Text PDFBackground: Radiotherapy is key in the treatment of primary and secondary brain tumors. However, normal tissue is inevitably irradiated, causing toxicity and contributing to cognitive dysfunction. The relative importance of vascular damage to cognitive decline is poorly understood.
View Article and Find Full Text PDFThe European Bioanalysis Forum, in collaboration with several key industry stakeholders, has recently led discussions that address international immunogenicity guidance documents, specifically the three tier approach for immunogenicity testing strategies, after more than 20 years of experience with biotherapeutics. As part of this, the strategy and methods used to assess drug tolerance across all immunogenicity assays are challenged, emphasizing that bioanalytical scientists need to consider the context-of-use of each assay. Here, recommendations for drug tolerance assessments, driven by strong scientific rationale and subject to reevaluation as needed, are provided.
View Article and Find Full Text PDFThe decrease in emission efficiency with increasing drive current density, known as 'droop', of -plane wurtzite InGaN/GaN quantum wells presently limits the use of light-emitting diodes based on them for high brightness lighting applications. InGaN/GaN quantum wells grown in the alternative zincblende phase are free of the strong polarisation fields that exacerbate droop and so were investigated by excitation-dependent photoluminescence and photoreflectance studies. Polarisation-resolved measurements revealed that for all excitation densities studied the emission from such samples largely originates from similar microstructures or combinations of microstructures that form within the quantum well layers.
View Article and Find Full Text PDFHeparin, a widely used clinical anticoagulant, is generally well-tolerated; however, approximately 1% of patients develop heparin-induced thrombocytopenia (HIT), a serious side effect. While efforts to understand the role of chemokines in HIT development are ongoing, certain aspects remain less studied, such as the stabilization of chemokine oligomers by heparin. Here, we conducted a combined ion mobility-native mass spectrometry study to investigate the stability of chemokine oligomers and their complexes with fondaparinux, a synthetic heparin analog.
View Article and Find Full Text PDFPurpose: Normative values for intracardiac and extracardiac vascular structures help in understanding normal growth and changes over time in children; this normative data are not currently available for ECG-gated Computed Tomography Angiography (CTA). We sought to establish ECG-gated CTA derived normative values for the aortic root, aorta and aortic arch in children.
Methods And Results: Aortic root, ascending aorta, aortic arch, and descending aorta were measured in systole and diastole in 100 subjects who had ECG-gated CTA at our center between January 2015 through December 2020 and met our inclusion criteria.
Background: There is increasing awareness of the necessity and importance for physician leadership in health care. Despite this, formal leadership training is not widespread in medical education.
Approach: We describe the structure, curriculum and development of a robust two-tiered leadership development programme within a community-based family medicine residency programme.
J Phys Chem Lett
December 2023
Break junction experiments allow investigating electronic and spintronic properties at the atomic and molecular scale. These experiments generate by their very nature broad and asymmetric distributions of the observables of interest, and thus, a full statistical interpretation is warranted. We show here that understanding the complete lifetime distribution is essential for obtaining reliable estimates.
View Article and Find Full Text PDFThe endothelial glycocalyx is an integral component of the brain vascular barrier. Visualizing its structure in vivo is essential to understand its physiological and pathophysiological mechanisms. Here, we present a surgical protocol for chronic cranial window implantation in mice, alongside the use of multiphoton microscopy tools to image the cortical vasculature.
View Article and Find Full Text PDFIntroduction: CXCL17 is a mucosally secreted protein, and the most recently identified human chemokine, an assignment based on protein fold prediction and chemotactic activity for leukocytes. However, these credentials have been the subject of much recent discussion and no experimental evidence has been presented regarding the definitive structure of CXCL17. In this study, we evaluated the structural and chemoattractant credentials of CXCL17 to better characterize this molecule, and gain deeper insights into its functional role as a glycosaminoglycan (GAG) binding protein.
View Article and Find Full Text PDFChemokine-driven leukocyte recruitment is a key component of the immune response and of various diseases. Therapeutically targeting the chemokine system in inflammatory disease has been unsuccessful, which has been attributed to redundancy. We investigated why chemokines instead have specific, specialized functions, as demonstrated by multiple studies.
View Article and Find Full Text PDFBackground: Patients with cardiogenic shock or end-stage heart failure can be maintained on mechanical circulatory support (MCS) devices. Once a patient undergoes placement of a device, obtaining and maintaining therapeutic anticoagulation is vital. Guidelines recommend the use of institutional protocols to assist in dosing and titration of anticoagulants.
View Article and Find Full Text PDFFront Fungal Biol
October 2022
This study assess the population diversity and temporal variability of caused by f. sp. (FOV) races/genotypes infecting cotton cultivars with either FOV or resistance.
View Article and Find Full Text PDFBackground: Anxiety and emotional distress have not been studied in large, diverse samples of patients with pulmonary nodules.
Research Question: How common are anxiety and distress in patients with newly identified pulmonary nodules, and what factors are associated with these outcomes?
Study Design And Methods: This study surveyed participants in the Watch the Spot Trial, a large, pragmatic clinical trial of more vs less intensive strategies for radiographic surveillance of patients with small pulmonary nodules. The survey included validated instruments to measure patient-centered outcomes such as nodule-related emotional distress (Impact of Event Scale-Revised) and anxiety (Six-Item State Anxiety Inventory) 6 to 8 weeks following nodule identification.
Objective: To investigate the role of endogenous TSG-6 in human osteoarthritis (OA) and assess the disease-modifying potential of a TSG-6-based biological treatment in cell, explant and animal models of OA.
Design: Knee articular cartilages from OA patients were analyzed for TSG-6 protein and mRNA expression using immunohistochemistry and RNAscope, respectively. The inhibitory activities of TSG-6 and its isolated Link module (Link_TSG6) on cytokine-induced degradation of OA cartilage explants were compared.
, the causative agent of the disease melioidosis, has been isolated from the environment in 45 countries. The treatment of melioidosis is complex, requiring lengthy antibiotic regimens, which can result in the relapse of the disease following treatment cessation. It is important that novel therapies to treat infections with be assessed in appropriate animal models, and discussions regarding the different protocols used between laboratories are critical.
View Article and Find Full Text PDFFor decades, immunologists have studied the role of circulating immune cells in host protection, with a more recent appreciation of immune cells resident within the tissue microenvironment and the intercommunication between nonhematopoietic cells and immune cells. However, the extracellular matrix (ECM), which comprises at least a third of tissue structures, remains relatively underexplored in immunology. Similarly, matrix biologists often overlook regulation of complex structural matrices by the immune system.
View Article and Find Full Text PDFBackground: There is evidence that macrophage infiltration in the tumor microenvironment promotes vestibular schwannoma (VS) growth. Efficacy of bevacizumab in NF2-associated VS demonstrates the value of therapies targeting the microvascular tumor microenvironment, and tumor-associated macrophages (TAMs) may represent another druggable target.
Objective: To characterize the relationship between growth, TAM infiltration, and circulating monocyte chemokines in a large cohort of patients with VS.
Leukocyte recruitment from the vasculature into tissues is a crucial component of the immune system but is also key to inflammatory disease. Chemokines are central to this process but have yet to be therapeutically targeted during inflammation due to a lack of mechanistic understanding. Specifically, CXCL4 (Platelet Factor 4, PF4) has no established receptor that explains its function.
View Article and Find Full Text PDFPurpose: The US Preventive Services Task Force has recommended lung cancer screening (LCS) with low-dose CT (LDCT) in high-risk individuals since 2013. Because LDCT encompasses the lower neck, chest, and upper abdomen, many incidental findings (IFs) are detected. The authors created a quick reference guide to describe common IFs in LCS to assist LCS program navigators and ordering providers in managing the care continuum in LCS.
View Article and Find Full Text PDFPulmonary nodules are managed on the basis of their size and morphologic characteristics. Radiologists are familiar with assessing nodule size by measuring diameter using manually deployed electronic calipers. Size may also be assessed with 3D volumetric measurements (referred to as volumetry) obtained with software.
View Article and Find Full Text PDFTurfgrass management relies on frequent watering events from natural precipitation or irrigation. However, most irrigation scheduling strategies in turfgrass ignore the magnitude of canopy interception. Interception is the process by which precipitation or irrigation water is intercepted by and evaporated from plant canopies or plant residue.
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