187 research outputs found

    Parental recovered acute kidney injury causes prenatal renal dysfunction and fetal growth restriction with sexually dimorphic implications for adult offspring

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    Introduction: Acute kidney injury (AKI) is rapidly increasing in global incidence and a healthcare burden. Prior maternal AKI diagnosis correlates with later pregnancy complications. As pregnancy influences developmental programming, we hypothesized that recovered parental AKI results in poor pregnancy outcomes, impaired fetal growth, and adult offspring disease.Methods: Using a well-characterized model of rhabdomyolysis-induced acute kidney injury (RIAKI), a form of AKI commonly observed in young people, we confirmed functional renal recovery by assessing glomerular filtration rate (GFR) 2 weeks following RIAKI. We bred sham and recovered RIAKI sires and dams in timed, matched matings for gestational day (GD) 16.5 and offspring (birth–12 weeks, 6 months) study.Results: Despite a normal GFR pre-pregnancy, recovered RIAKI dams at GD16.5 had impaired renal function, resulting in reduced fetoplacental ratios and offspring survival. Pregnant RIAKI dams also had albuminuria and less renal megalin in the proximal tubule brush border than shams, with renal subcapsular fibrosis and higher diastolic blood pressure. Growth-restricted offspring had a reduced GFR as older adults, with evidence of metabolic inefficiency in male offspring; this correlated with reduced renal AngII levels in female offspring from recovered RIAKI pairings. However, the blood pressures of 6-month-old offspring were unaffected by parental RIAKI.Conclusions: Our mouse model demonstrated a causal relationship among RIAKI, gestational risk, and developmental programming of the adult-onset offspring GFR and metabolic dysregulation despite parental recovery

    Development and evaluation of a new fully automatic motion detection and correction technique in cardiac SPECT imaging

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    In cardiac SPECT perfusion imaging, motion correction of the data is critical to the minimization of motion introduced artifacts in the reconstructed images. Software-based (data-driven) motion correction techniques are the most convenient and economical approaches to fulfill this purpose. However, the accuracy is significantly affected by how the data complexities, such as activity overlap, non-uniform tissue attenuation, and noise are handled. We developed STASYS, a new, fully automatic technique, for motion detection and correction in cardiac SPECT. We evaluated the performance of STASYS by comparing its effectiveness of motion correcting patient studies with the current industry standard software (Cedars-Sinai MoCo) through blind readings by two readers independently. For 204 patient studies from multiple clinical sites, the first reader identified (1) 69 studies with medium to large axial motion, of which STASYS perfectly or significantly corrected 86.9% and MoCo 72.5%; and (2) 20 studies with medium to large lateral motion, of which STASYS perfectly or significantly corrected 80.0% and MoCo 60.0%. The second reader identified (1) 84 studies with medium to large axial motion, of which STASYS perfectly or significantly corrected 82.2% and MoCo 76.2%; and (2) 34 studies with medium to large lateral motion, of which STASYS perfectly or significantly corrected 58.9% and MoCo 50.0%. We developed a fully automatic software-based motion correction technique, STASYS, for cardiac SPECT. Clinical studies showed that STASYS was effective and corrected a larger percent of cardiac SPECT studies than the current industrial standard software

    Analytical Challenges and Metrological Approaches to Ensuring Dietary Supplement Quality: International Perspectives

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    The increased utilization of metrology resources and expanded application of its’ approaches in the development of internationally agreed upon measurements can lay the basis for regulatory harmonization, support reproducible research, and advance scientific understanding, especially of dietary supplements and herbal medicines. Yet, metrology is often underappreciated and underutilized in dealing with the many challenges presented by these chemically complex preparations. This article discusses the utility of applying rigorous analytical techniques and adopting metrological principles more widely in studying dietary supplement products and ingredients, particularly medicinal plants and other botanicals. An assessment of current and emerging dietary supplement characterization methods is provided, including targeted and non-targeted techniques, as well as data analysis and evaluation approaches, with a focus on chemometrics, toxicity, dosage form performance, and data management. Quality assessment, statistical methods, and optimized methods for data management are also discussed. Case studies provide examples of applying metrological principles in thorough analytical characterization of supplement composition to clarify their health effects. A new frontier for metrology in dietary supplement science is described, including opportunities to improve methods for analysis and data management, development of relevant standards and good practices, and communication of these developments to researchers and analysts, as well as to regulatory and policy decision makers in the public and private sectors. The promotion of closer interactions between analytical, clinical, and pharmaceutical scientists who are involved in research and product development with metrologists who develop standards and methodological guidelines is critical to advance research on dietary supplement characterization and health effects

    Vaccine Potential of Nipah Virus-Like Particles

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    Nipah virus (NiV) was first recognized in 1998 in a zoonotic disease outbreak associated with highly lethal febrile encephalitis in humans and a predominantly respiratory disease in pigs. Periodic deadly outbreaks, documentation of person-to-person transmission, and the potential of this virus as an agent of agroterror reinforce the need for effective means of therapy and prevention. In this report, we describe the vaccine potential of NiV virus-like particles (NiV VLPs) composed of three NiV proteins G, F and M. Co-expression of these proteins under optimized conditions resulted in quantifiable amounts of VLPs with many virus-like/vaccine desirable properties including some not previously described for VLPs of any paramyxovirus: The particles were fusogenic, inducing syncytia formation; PCR array analysis showed NiV VLP-induced activation of innate immune defense pathways; the surface structure of NiV VLPs imaged by cryoelectron microscopy was dense, ordered, and repetitive, and consistent with similarly derived structure of paramyxovirus measles virus. The VLPs were composed of all the three viral proteins as designed, and their intracellular processing also appeared similar to NiV virions. The size, morphology and surface composition of the VLPs were consistent with the parental virus, and importantly, they retained their antigenic potential. Finally, these particles, formulated without adjuvant, were able to induce neutralizing antibody response in Balb/c mice. These findings indicate vaccine potential of these particles and will be the basis for undertaking future protective efficacy studies in animal models of NiV disease
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