Cholestasis, or disruption in bile flow, is a common yet poorly understood feature of many liver diseases and injuries. Despite this, many engineered human tissue models of liver disease fail to recapitulate physiological bile flow. Here, we present a 3D multicellular spheroid-based model of the human hepatobiliary junction, the interface between hepatocytes and cholangiocytes often disrupted in liver disease that is required for directing bile excreted by hepatocytes into the biliary ductal system.
View Article and Find Full Text PDFWhile donation after circulatory death (DCD) has contributed significantly to growth in liver transplantation volume, 70%-80% of DCD liver allografts remain nonutilized. We suspected that neurologic exam documentation fuels concerns that potential donors would not expire within an acceptable time frame, thus discouraging the pursuit of organs. We hypothesized that the neurologic exam is an unreliable predictor of donor warm ischemia time (DWIT), but nevertheless influences clinicians' behavior with respect to organ acceptance.
View Article and Find Full Text PDFBackground: Stroke is a leading cause of long-term adult disability. Behavioral testing with animal stroke models, which offers a way to evaluate the effectiveness of new interventions, currently relies on methods that are time- and labor-intensive. Automated behavioral assessments of locomotion and gait have been proposed as an alternative, but it is currently unknown whether they are sensitive enough to assess behavioral deficits following stroke of the forepaw somatosensory cortex.
View Article and Find Full Text PDFNeural activity in the delta range (1.0-4.5 Hz) during non-rapid eye movement (NREM) sleep is crucial for brain plasticity and overall brain health.
View Article and Find Full Text PDFNanomaterials (Basel)
November 2024
Li-CO batteries (LCBs) have emerged as promising solutions for energy storage, with the added benefit of contributing to carbon neutrality by capturing and utilizing CO during operation. In this study, a high-performance LCB was developed using a Ge-doped LiAlGeTi (PO) (LAGTP) solid electrolyte, which was synthesized via a solution-based method by doping Ge into NASICON-type LATP. The ionic conductivity of the LAGTP pellets was measured as 1.
View Article and Find Full Text PDFBackground: For many surgeons, retirement is an emotionally evocative subject, tied to a sense of loss. With minimal guidelines to facilitate a smooth transition, physicians tend to be inadequately prepared. There are few qualitative studies exploring surgeons' perspectives and none focused on transplant surgeons, a population with arguably unique challenges.
View Article and Find Full Text PDFKey Points: Female overrepresentation in living kidney donation stems from higher self-referral rates, not differences in approval or follow-through. Male volunteers are not more likely to be declined as donors due to medical contraindications, contrary to common assumptions. Engaging more male volunteers in living donation could expand access to kidney transplantation and reduce waitlist times.
View Article and Find Full Text PDFBackground: The utilization of kidneys donated after circulatory death (DCD) is an important strategy to address the ongoing shortage of organs suitable for transplantation in the United States. However, the nonuse rate of DCD kidneys remains high compared with kidneys donated after brain death (DBD) because of concerns regarding the injury incurred during donor warm ischemia time (DWIT). Therefore, we investigated the impact of DWIT on the risk of death-censored graft failure after DCD kidney transplantation (KT).
View Article and Find Full Text PDFThe imbalance between organ supply and demand continues to limit the broader benefits of organ transplantation. Machine perfusion (MP) may increase the supply of donor livers by expanding the use of extended-criteria donors. Using the United Network for Organ Sharing/Organ Procurement and Transplantation Network and the Standard Transplant Analysis and Research dataset, we reviewed the effect of MP implementation on the behavior of transplant centers.
View Article and Find Full Text PDFCurr Gastroenterol Rep
December 2023
Purpose Of Review: Over the past decade, donation after circulatory death (DCD) liver transplantation has expanded in the United States due to improved surgical experience and perioperative management. Despite these advances, there remains a reluctance towards broader utilization of DCD liver allografts due to lack of standardized donation process, concern for inferior graft survival, and risk of ischemic cholangiopathy associated with temporary lack of oxygenated perfusion during withdrawal of life-supporting treatment during procurement.
Recent Findings: New perfusion technologies offer potential therapeutic options to mitigate biliary complications and expand utilization of marginal DCD grafts.
The donor operation and the hemodynamics during declaration resulting in donor warm ischemia time have been linked to the outcomes in donation after circulatory death (DCD) liver transplantation (LT). Scrutiny of the donor hemodynamics at the time of withdrawal of life support concluded that a functional donor warm ischemia time may be associated with LT graft failure. Unfortunately, the definition for functional donor warm ischemia time has not reached a consensus-but has almost always incorporated time spent in a hypoxic state.
View Article and Find Full Text PDFLiver Transpl
July 2023
NAFLD will soon be the most common indication for liver transplantation (LT). In NAFLD, HCC may occur at earlier stages of fibrosis and present with more advanced tumor stage, raising concern for aggressive disease. Thus, adult LT recipients with HCC from 20 US centers transplanted between 2002 and 2013 were analyzed to determine whether NAFLD impacts recurrence-free post-LT survival.
View Article and Find Full Text PDFProd Oper Manag
March 2022
The coronavirus disease 2019 (COVID-19) pandemic has disrupted normal operating procedures at transplant centers. With the possibility that COVID-19 infection carries an overall 4% mortality rate and potentially a 24% mortality rate among the immunocompromised transplant recipients, many transplant centers considered the possibility of slowing down and even potentially pausing all transplants. Many proposals regarding the need for pausing organ transplants exist; however, much remains unknown.
View Article and Find Full Text PDFMortality on the liver waitlist remains unacceptably high. Donation after circulatory determination of death (DCD) donors are considered marginal but are a potentially underutilized resource. Thoraco-abdominal normothermic perfusion (TA-NRP) in DCD donors might result in higher quality livers and offset waitlist mortality.
View Article and Find Full Text PDFThe incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long-term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients.
View Article and Find Full Text PDFThe rate-determining step in free radical lipid peroxidation is the propagation of the peroxyl radical, where generally two types of reactions occur: (a) hydrogen-atom transfer (HAT) from a donor to the peroxyl radical; (b) peroxyl radical addition (PRA) to a "C═C" double bond. Peroxyl radical clocks have been used to determine the rate constants of HAT reactions (), but no radical clock is available to measure the rate constants of PRA reactions (). In this work, we modified the analytical approach on the linoleate-based peroxyl radical clock to enable the simultaneous measurement of both and .
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