Robust inference of population size histories from genomic sequencing data.

Unraveling the complex demographic histories of natural populations is a central problem in population genetics. Understanding past demographic events is of general anthropological interest, but is also an important step in establishing accurate null models when identifying adaptive or disease-associated genetic variation. An important class of tools for inferring past population size changes from genomic sequence data are Coalescent Hidden Markov Models (CHMMs).

Dual Lactate Clearance in the Viability Assessment of Livers Donated After Circulatory Death With Ex Situ Normothermic Machine Perfusion.

Unlabelled: Perfusate lactate clearance (LC) is considered one of the useful indicators of liver viability assessment during normothermic machine perfusion (NMP); however, the applicable scope and potential mechanisms of LC remain poorly defined in the setting of liver donation after circulatory death.

Methods: The ex situ NMP of end-ischemic human livers was performed using the OrganOx Metra device. We further studied the extracellular signal-regulated kinases (phospho-extracellular signal-regulated kinase1/2 [pERK1/2]) pathway and several clinical parameters of these livers with successful LC (sLC, n = 5) compared with non-sLC (nLC, n = 5) in the perfusate (<2.

NRF2 assessment in discarded liver allografts: A role in allograft function and salvage.

Antioxidant defence mechanisms, such as the nuclear factor-erythroid 2-related-factor-2 (NRF2) axis, are integral to oxidative stress responses and ischemic injury. Hepatic antioxidant capacity is contingent on parenchymal quality, and there is a need to develop new insights into key molecular mechanisms in marginal liver allografts that might provide therapeutic targets. This study examines the clinical relevance of NRF2 in donor livers and its response to normothermic machine perfusion (NMP).

A Novel Multidrug Combination Mitigates Rat Liver Steatosis Through Activating AMPK Pathway During Normothermic Machine Perfusion.

Background: Hepatic steatosis is now the leading cause of liver discards in deceased donors. Previous studies [Yarmush formula (Y) defatting] have successfully reduced the fat content by treating rat steatotic livers on extracorporeal normothermic machine perfusion (NMP) with a multidrug combination including the GW compounds that were linked to an increased risk of carcinogenesis.

Methods: We developed a novel multidrug combination by replacing the GW compounds with 2 polyphenols, epigallocatechin-3-gallate (E) and resveratrol (R).

A Rare Case of Resolution of High-Degree Atrioventricular Block Associated With COVID-19.

Cardiac arrhythmias have been reported in the setting of coronavirus disease 2019 (COVID-19) infection. To date various tachyarrhythmias have been noted. This case report describes an atypical clinical hospitalization course of high-degree atrioventricular (AV) block in the setting of COVID-19 infection which required no intervention.

Improving Liver Graft Function Using CD47 Blockade in the Setting of Normothermic Machine Perfusion.

Background: Toward the goal of using more livers for transplantation, transplant centers are looking to increase the use of organs from "marginal" donors. Livers from these donors, however, have been shown to be more susceptible to preservation and reperfusion injury.

Methods: Using a porcine model of donation after circulatory death, we studied the use of antibody-mediated CD47 blockade to further improve liver graft function undergoing normothermic machine perfusion.

The Myth of Colchicine in Treating Myopericarditis: Case Report and Literature Review.

Myopericarditis is inflammation of the pericardium with concurrent myocardial involvement. The clinical presentation of myopericarditis is often with varying degrees of cardiac symptomatology. Its etiology is often idiopathic, but it may also be related to infectious and inflammatory prodrome.

Novel Coronavirus-Induced Right Ventricular Failure and Point of Care Echocardiography: A Case Report.

Various cardiovascular complications have been reported in patients with coronavirus disease 2019. Common complications include acute myocardial injury, myocarditis, arrhythmia, pericarditis, heart failure, and shock. We present a case of cor pulmonale diagnosed with serial point of care ultrasound.

Antithrombin Perfluorocarbon Nanoparticles Improve Renal Allograft Function in a Murine Deceased Criteria Donor Model.

Background: Over 100 000 patients await renal transplantation and 4000 die per year. Compounding this mismatch between supply and demand is delayed graft function which contributes to short-term and long-term graft failures. Previously, we reported that thrombin-targeted perfluorocarbon nanoparticles (PFC-NP) protect kidneys from ischemic renal injury after transient arterial occlusion.

Enhanced immunosuppression improves early allograft function in a porcine kidney transplant model of donation after circulatory death.

It remains controversial whether renal allografts from donation after circulatory death (DCD) have a higher risk of acute rejection (AR). In the porcine large animal kidney transplant model, we investigated the AR and function of DCD renal allografts compared to the non-DCD renal allografts and the effects of increased immunosuppression. We found that the AR was significantly increased along with elevated MHC-I expression in the DCD transplants receiving low-dose immunosuppression; however, AR and renal function were significantly improved when given high-dose immunosuppressive therapy postoperatively.

Anti-CD47 monoclonal antibody therapy reduces ischemia-reperfusion injury of renal allografts in a porcine model of donation after cardiac death.

We investigated whether blockade of the CD47 signaling pathway could reduce ischemia-reperfusion injury (IRI) of renal allografts donated after cardiac death (DCD) in a porcine animal model of transplantation. Renal allografts were subjected to 30 minutes of warm ischemia, 3.5 hours of cold ischemia, and then perfused with a humanized anti-CD47 monoclonal antibody (CD47mAb) in the treatment group or HTK solution in the control group (n = 4/group).

Endoscopic shaving of hair in a gastric bypass patient with a large bezoar.

Trichotillomania can be associated with the formation of trichobezoars (hair ball) usually located in the stomach. Trichobezoars may lead to complications including bowel obstruction, and perforation. Patients with a history of diabetes, certain psychiatric disorders, prior gastric surgery and poor mastication ability are at an increased risk of developing bezoars.

CD47 blockade reduces ischemia/reperfusion injury in donation after cardiac death rat kidney transplantation.

Modulation of nitric oxide activity through blockade of CD47 signaling has been shown to reduce ischemia-reperfusion injury (IRI) in various models of tissue ischemia. Here, we evaluate the potential effect of an antibody-mediated CD47 blockade in a syngeneic and an allogeneic DCD rat kidney transplant model. The donor organ was subjected to 1 hour of warm ischemia time after circulatory cessation, then flushed with a CD47 monoclonal antibody (CD47mAb) in the treatment group, or an isotype-matched immunoglobulin in the control group.

Papillary fibroelastoma of the aortic valve presenting with chronic angina and acute stroke: a case report.

Background: Papillary fibroelastomas are rare, benign cardiac tumors that are often found on cardiac valvular surfaces. Most are incidental discoveries during surgery or autopsy. The clinical presentation of fibroelastoma varies widely, ranging from clinically asymptomatic to severe thromboembolic events.

Attenuation of Ischemia-Reperfusion Injury and Improvement of Survival in Recipients of Steatotic Rat Livers Using CD47 Monoclonal Antibody.

Background: Despite the efficacy of orthotopic liver transplantation in the treatment of end-stage liver diseases, its therapeutic utility is severely limited by the availability of donor organs. The ability to rehabilitate marginal organs, such as steatotic allografts, has the potential to address some of the supply limitations of available organs for transplantation. Steatotic livers are more susceptible to ischemia-reperfusion injury (IRI), which is exacerbated by the thrombospondin-1/CD47 pathway through inhibition of nitric oxide signaling.

Novel strategy to decrease reperfusion injuries and improve function of cold-preserved livers using normothermic ex vivo liver perfusion machine.

Normothermic extracorporeal liver perfusion (NELP) can decrease ischemia/reperfusion injury to the greatest degree when cold ischemia time is minimized. Warm perfusion of cold-stored livers results in hepatocellular damage, sinusoidal endothelial cell (SEC) dysfunction, and Kupffer cell activation. However, the logistics of organ procurement mandates a period of cold preservation before NELP.

Normothermic extracorporeal liver perfusion for donation after cardiac death (DCD) livers.

Background: The susceptibility of extended criteria livers to ischemia reperfusion injury is a major obstacle in organ cold preservation. Normothermic extracorporeal liver perfusion (NELP) has been investigated to reduce ischemic damage, restore physiologic function, and assess viability of the liver prior to transplant. The goal of this study is to compare physiological parameters of livers maintained continuously on NELP to those preserved in cold solution.

Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma.

Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival times. The efficacy of current systemic therapies for HCC is limited. In this study, we used xenograft tumor models to investigate the use of antibodies that block CD47 and inhibit HCC tumor growth.

BH3-only proteins contribute to steatotic liver ischemia-reperfusion injury.

Background: Ischemia-reperfusion injury (IRI) to the liver continues to be a source of significant morbidity, especially in patients with hepatic steatosis. This is a growing problem given the increase in nonalcoholic fatty liver disease. B-cell lymphoma-2 homology3-only members of the B-cell lymphoma-2 protein family are known mediators of cellular apoptosis, although their role in hepatic IRI is still emerging.

CD47 blockade reduces ischemia/reperfusion injury and improves survival in a rat liver transplantation model.

Orthotopic liver transplantation (OLT) remains the standard treatment option for nonresponsive liver failure. Because ischemia/reperfusion injury (IRI) is an important impediment to the success of OLT, new therapeutic strategies are needed to reduce IRI. We investigated whether blocking the CD47/thrombospondin-1 inhibitory action on nitric oxide signaling with a monoclonal antibody specific to CD47 (CD47mAb400) would reduce IRI in liver grafts.

CD47 blockade reduces ischemia-reperfusion injury and improves outcomes in a rat kidney transplant model.

Background: Ischemia-reperfusion injury (IRI) significantly contributes to delayed graft function and inflammation, leading to graft loss. Ischemia-reperfusion injury is exacerbated by the thrombospondin-1-CD47 system through inhibition of nitric oxide signaling. We postulate that CD47 blockade and prevention of nitric oxide inhibition reduce IRI in organ transplantation.

Protective role of bortezomib in steatotic liver ischemia/reperfusion injury through abrogation of MMP activation and YKL-40 expression.

Steatotic liver grafts tolerate ischemia-reperfusion (I/R) injury poorly, contributing to poor survival following transplantation. However the molecular mechanisms leading to I/R injury still remain to be defined. We have previously reported that the protective effect of bortezomib towards inhibiting cold induced I/R injury in obese rat liver transplant model is through NF-κB down modulation.

The role of molecular chaperonins in warm ischemia and reperfusion injury in the steatotic liver: a proteomic study.

Background: The molecular basis of the increased susceptibility of steatotic livers to warm ischemia/reperfusion (I/R) injury during transplantation remains undefined. Animal model for warm I/R injury was induced in obese Zucker rats. Lean Zucker rats provided controls.

Novel in vitro model for studying hepatic ischemia-reperfusion injury using liver cubes.

Background: Although inflow occlusion techniques have given surgeons the ability to carry out increasingly complex liver resections, ischemia-reperfusion (IR) injury continues to be a source of morbidity. Efforts to ameliorate IR injury have been hindered in absence of adequate preclinical models. The goal of the present study was to develop a simple, efficient, and cost-effective means of studying hepatic IR injury.