Accelerated Cardiac Diffusion Tensor Imaging Using Joint Low-Rank and Sparsity Constraints

Objective: The purpose of this manuscript is to accelerate cardiac diffusion tensor imaging (CDTI) by integrating low-rankness and compressed sensing. Methods: Diffusion-weighted images exhibit both transform sparsity and low-rankness. These properties can jointly be exploited to accelerate CDTI, especially when a phase map is applied to correct for the phase inconsistency across diffusion directions, thereby enhancing low-rankness. The proposed method is evaluated both ex vivo and in vivo, and is compared to methods using either a low-rank or sparsity constraint alone. Results: Compared to using a low-rank or sparsity constraint alone, the proposed method preserves more accurate helix angle features, the transmural continuum across the myocardium wall, and mean diffusivity at higher acceleration, while yielding significantly lower bias and higher intraclass correlation coefficient. Conclusion: Low-rankness and compressed sensing together facilitate acceleration for both ex vivo and in vivo CDTI, improving reconstruction accuracy compared to employing either constraint alone. Significance: Compared to previous methods for accelerating CDTI, the proposed method has the potential to reach higher acceleration while preserving myofiber architecture features which may allow more spatial coverage, higher spatial resolution and shorter temporal footprint in the future.Comment: 11 pages, 16 figures, published on IEEE Transactions on Biomedical Engineerin

Epidemiology and Impact of Abdominal Oblique Injuries in Major and Minor League Baseball.

BACKGROUND: Oblique injuries are known to be a common cause of time out of play for professional baseball players, and prior work has suggested that injury rates may be on the rise in Major League Baseball (MLB). PURPOSE: To better understand the current incidence of oblique injuries, determine their impact based on time out of play, and to identify common injury patterns that may guide future injury prevention programs. STUDY DESIGN: Descriptive epidemiological study. METHODS: Using the MLB Health and Injury Tracking System, all oblique injuries that resulted in time out of play in MLB and Minor League Baseball (MiLB) during the 2011 to 2015 seasons were identified. Player demographics such as age, position/role, and handedness were included. Injury-specific factors analyzed included the following: date of injury, timing during season, days missed, mechanism, side, treatment, and reinjury status. RESULTS: A total of 996 oblique injuries occurred in 259 (26%) MLB and 737 (74%) MiLB players. Although the injury rate was steady in MiLB, the MLB injury rate declined (P = .037). A total of 22,064 days were missed at a mean rate of 4413 days per season and 22.2 days per injury. The majority of these occurred during batting (n = 455, 46%) or pitching (n = 348, 35%), with pitchers losing 5 days more per injury than batters (P \u3c .001). The leading side was injured in 77% of cases and took 5 days longer to recover from than trailing side injuries (P = .009). Seventy-nine (7.9%) players received either a corticosteroid or platelet-rich plasma injection, and the mean recovery time was 11 days longer compared with those who did not receive an injection (P \u3c .001). CONCLUSION: Although the rate of abdominal oblique injuries is on the decline in MLB, this is not the case for MiLB, and these injuries continue to represent a significant source of time out of play in professional baseball. The vast majority of injuries occur on the lead side, and these injuries result in the greatest amount time out of play. The benefit of injections for the treatment of oblique injuries remains unknown

The β-blocker Nebivolol Is a GRK/β-arrestin Biased Agonist

Nebivolol, a third generation β-adrenoceptor (β-AR) antagonist (β-blocker), causes vasodilation by inducing nitric oxide (NO) production. The mechanism via which nebivolol induces NO production remains unknown, resulting in the genesis of much of the controversy regarding the pharmacological action of nebivolol. Carvedilol is another β-blocker that induces NO production. A prominent pharmacological mechanism of carvedilol is biased agonism that is independent of Gαs and involves G protein-coupled receptor kinase (GRK)/β-arrestin signaling with downstream activation of the epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK). Due to the pharmacological similarities between nebivolol and carvedilol, we hypothesized that nebivolol is also a GRK/β-arrestin biased agonist. We tested this hypothesis utilizing mouse embryonic fibroblasts (MEFs) that solely express β2-ARs, and HL-1 cardiac myocytes that express β1- and β2-ARs and no detectable β3-ARs. We confirmed previous reports that nebivolol does not significantly alter cAMP levels and thus is not a classical agonist. Moreover, in both cell types, nebivolol induced rapid internalization of β-ARs indicating that nebivolol is also not a classical β-blocker. Furthermore, nebivolol treatment resulted in a time-dependent phosphorylation of ERK that was indistinguishable from carvedilol and similar in duration, but not amplitude, to isoproterenol. Nebivolol-mediated phosphorylation of ERK was sensitive to propranolol (non-selective β-AR-blocker), AG1478 (EGFR inhibitor), indicating that the signaling emanates from β-ARs and involves the EGFR. Furthermore, in MEFs, nebivolol-mediated phosphorylation of ERK was sensitive to pharmacological inhibition of GRK2 as well as siRNA knockdown of β-arrestin 1/2. Additionally, nebivolol induced redistribution of β-arrestin 2 from a diffuse staining pattern into more intense punctate spots. We conclude that nebivolol is a β2-AR, and likely β1-AR, GRK/β-arrestin biased agonist, which suggests that some of the unique clinically beneficial effects of nebivolol may be due to biased agonism at β1- and/or β2-ARs. © 2013 Erickson et al

A biomimetic pancreatic cancer on-chip reveals endothelial ablation via ALK7 signaling

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, lethal malignancy that invades adjacent vasculatures and spreads to distant sites before clinical detection. Although invasion into the peripancreatic vasculature is one of the hallmarks of PDAC, paradoxically, PDAC tumors also exhibit hypovascularity. How PDAC tumors become hypovascular is poorly understood. We describe an organotypic PDAC-on-a-chip culture model that emulates vascular invasion and tumor-blood vessel interactions to better understand PDAC-vascular interactions. The model features a 3D matrix containing juxtaposed PDAC and perfusable endothelial lumens. PDAC cells invaded through intervening matrix, into vessel lumen, and ablated the endothelial cells, leaving behind tumor-filled luminal structures. Endothelial ablation was also observed in in vivo PDAC models. We also identified the activin-ALK7 pathway as a mediator of endothelial ablation by PDAC. This tumor-on-a-chip model provides an important in vitro platform for investigating the process of PDAC-driven endothelial ablation and may provide a mechanism for tumor hypovascularity.R01 EB000262 - NIBIB NIH HHS; TL1 TR001410 - NCATS NIH HHS; UC4 DK104196 - NIDDK NIH HHS; UH3 EB017103 - NIBIB NIH HHSPublished versio

Nerve-targeted probes for fluorescence-guided intraoperative imaging.

A fundamental goal of many surgeries is nerve preservation, as inadvertent injury can lead to patient morbidity including numbness, pain, localized paralysis and incontinence. Nerve identification during surgery relies on multiple parameters including anatomy, texture, color and relationship to surrounding structures using white light illumination. We propose that fluorescent labeling of nerves can enhance the contrast between nerves and adjacent tissue during surgery which may lead to improved outcomes. Methods: Nerve binding peptide sequences including HNP401 were identified by phage display using selective binding to dissected nerve tissue. Peptide dye conjugates including FAM-HNP401 and structural variants were synthesized and screened for nerve binding after topical application on fresh rodent and human tissue and in-vivo after systemic IV administration into both mice and rats. Nerve to muscle contrast was quantified by measuring fluorescent intensity after topical or systemic administration of peptide dye conjugate. Results: Peptide dye conjugate FAM-HNP401 showed selective binding to human sural nerve with 10.9x fluorescence signal intensity (1374.44 ± 425.96) compared to a previously identified peptide FAM-NP41 (126.17 ± 61.03). FAM-HNP401 showed nerve-to-muscle contrast of 3.03 ± 0.57. FAM-HNP401 binds and highlight multiple human peripheral nerves including lower leg sural, upper arm medial antebrachial as well as autonomic nerves isolated from human prostate. Conclusion: Phage display has identified a novel peptide that selectively binds to ex-vivo human nerves and in-vivo using rodent models. FAM-HNP401 or an optimized variant could be translated for use in a clinical setting for intraoperative identification of human nerves to improve visualization and potentially decrease the incidence of intra-surgical nerve injury

Post-weaning blood transcriptomic differences between Yorkshire pigs divergently selected for residual feed intake

Meta data for RNA-seq and RT-qPCR assays. (XLSX 20 kb

Establishment of a Percutaneous Coronary Intervention Registry in Vietnam: Rationale and Methodology

Copyright: © 2020 The Author(s). Background: In lower- and middle-income countries across Asia there has been a rapid expansion and uptake of percutaneous coronary intervention (PCI). However, there has been limited routine collection of related data, particularly around quality, safety and cost. The aim of this study was to assess the viability of implementing routine collection of PCI data in a registry at a leading hospital in Hanoi, Vietnam. Method: A Vietnamese data collection form and collection strategy were developed in collaboration with the Vietnam National Heart Institute. Information on patient characteristics, treatments, and outcomes was collected through direct interviews using a standardised form and medical record abstraction, while PCI data was read and coded into paper forms by interventional cardiologists. Viability of the registry was determined by four main factors: 1) being able to collect a representative sample; 2) quality of data obtained; 3) costs and time taken for data collection by hospital staff; and 4) level of support from key stakeholders in the institute. Results: Between September 2017 and May 2018, 1,022 patients undergoing PCI were recruited from a total of 1,041 procedures conducted during that time frame. The estimated mean time to collect information from patients before discharge was 60 minutes. Of the collected data fields, 98% were successfully completed. Most hospital staff surveyed indicated support for the continuation of the activity following the implementation of the pilot study. Conclusions: The proposed methodology for establishing a PCI registry in a large hospital in Vietnam produced high quality data and was considered worthwhile by hospital staff. The model has the potential opportunity for replication in other cardiac catheterisation sites, leading to a national PCI registry in Vietnam

Ketone bodies for the failing heart:fuels that can fix the engine?

Accumulating evidence suggests that the failing heart reverts energy metabolism toward increased utilization of ketone bodies. Despite many discrepancies in the literature, evidence from both bench and clinical research demonstrates beneficial effects of ketone bodies in heart failure. Ketone bodies are readily oxidized by cardiomyocytes and can provide ancillary fuel for the energy-starved failing heart. In addition, ketone bodies may help to restore cardiac function by mitigating inflammation, oxidative stress, and cardiac remodeling. In this review, we hypothesize that a therapeutic approach intended to restore cardiac metabolism through ketone bodies could both refuel and ‘repair’ the failing heart