Contrast-enhanced computed tomography for ex vivo assessment of human kidneys: A proof-of-concept study.

Background: Ex vivo perfusion of transplant-declined human organs has emerged as a promising platform to study the response of an organ to novel therapeutic strategies. However, to fully realize the capability of this platform for performing translational research in human organ pathophysiology, there is a need for robust assays to assess organ function and disease. State-of-the-art research methods rely on analyses of biopsies taken during perfusion, which both damages the organ and only provides localized information.

Cardiovascular safety of dihydroergotamine mesylate delivered by precision olfactory delivery (INP104) for the acute treatment of migraine.

Objective: To report the cardiovascular (CV) safety of dihydroergotamine mesylate (DHE) administered by precision olfactory delivery (INP104) from two clinical trials.

Background: Although the absolute risk is low, migraine is associated with an increased risk of CV events. DHE is a highly effective acute treatment for migraine, but due to its theoretical risk of promoting arterial vasoconstriction, DHE is contraindicated in patients with CV disease or an unfavorable risk factor profile.

Risk factors for migraine disease progression: a narrative review for a patient-centered approach.

Background: In individuals with migraine, attacks may increase in frequency, severity, or both. Preventing migraine progression has emerged as a treatment goal in headache subspecialty practice, but there may be less awareness in general neurology or primary care settings where most people with migraine who seek treatment consult. Herein, we review the definition of and risk factors for migraine progression and consider strategies that could reduce its risk.

Adult Moyamoya Disease and Syndrome: Current Perspectives and Future Directions: A Scientific Statement From the American Heart Association/American Stroke Association.

Adult moyamoya disease and syndrome are rare disorders with significant morbidity and mortality. A writing group of experts was selected to conduct a literature search, summarize the current knowledge on the topic, and provide a road map for future investigation. The document presents an update in the definitions of moyamoya disease and syndrome, modern methods for diagnosis, and updated information on pathophysiology, epidemiology, and both medical and surgical treatment.

An optimized visualization and quantitative protocol for in-depth evaluation of lymphatic vessel architecture in the liver.

The liver lymphatic system is essential for maintaining tissue fluid balance and immune function. The detailed structure of lymphatic vessels (LVs) in the liver remains to be fully demonstrated. The aim of this study is to reveal LV structures in normal and diseased livers by developing a tissue-clearing and coimmunolabeling protocol optimized for the tissue size and the processing time for three-dimensional (3-D) visualization and quantification of LVs in the liver.

Honoring the gift: The transformative potential of transplant-declined human organs.

For decades, transplantation has been a life-saving treatment for those fortunate enough to gain access. Nevertheless, many patients die waiting for an organ and countless more never make it onto the waitlist because of a shortage of donor organs. Concurrently, thousands of donated organs are declined for transplant each year because of concerns about poor outcomes post-transplant.

Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications.

Vascular endothelial cells (ECs) play a central role in the pathophysiology of many diseases. The use of targeted nanoparticles (NPs) to deliver therapeutics to ECs could dramatically improve efficacy by providing elevated and sustained intracellular drug levels. However, achieving sufficient levels of NP targeting in human settings remains elusive.

Blood Transcriptomes of SARS-CoV-2-Infected Kidney Transplant Recipients Associated with Immune Insufficiency Proportionate to Severity.

Background: Among patients with COVID-19, kidney transplant recipients (KTRs) have poor outcomes compared with non-KTRs. To provide insight into management of immunosuppression during acute illness, we studied immune signatures from the peripheral blood during and after COVID-19 infection from a multicenter KTR cohort.

Methods: We ascertained clinical data by chart review.

Cellular recovery after prolonged warm ischaemia of the whole body.

After cessation of blood flow or similar ischaemic exposures, deleterious molecular cascades commence in mammalian cells, eventually leading to their death. Yet with targeted interventions, these processes can be mitigated or reversed, even minutes or hours post mortem, as also reported in the isolated porcine brain using BrainEx technology. To date, translating single-organ interventions to intact, whole-body applications remains hampered by circulatory and multisystem physiological challenges.

Revisiting the Principles of Preservation in an Era of Pandemic Obesity.

The current obesity epidemic has caused a significant decline in the health of our donor population. Organs from obese deceased donors are more prone to ischemia reperfusion injury resulting from organ preservation. As a consequence, these donors are more likely to be discarded under the assumption that nothing can be done to make them viable for transplant.

Surface conjugation of antibodies improves nanoparticle uptake in bronchial epithelial cells.

Background: Advances in Molecular Therapy have made gene editing through systemic or topical administration of reagents a feasible strategy to treat genetic diseases in a rational manner. Encapsulation of therapeutic agents in nanoparticles can improve intracellular delivery of therapeutic agents, provided that the nanoparticles are efficiently taken up within the target cells. In prior work we had established proof-of-principle that nanoparticles carrying gene editing reagents can mediate site-specific gene editing in fetal and adult animals in vivo that results in functional disease improvement in rodent models of β-thalassemia and cystic fibrosis.

Wanted: An endothelial cell targeting atlas for nanotherapeutic delivery in allograft organs.

Despite the profound shortage of organs available for transplant in the U.S., over 5,000 donated organs were declined for use in 2020.

Nanotherapeutics in transplantation: How do we get to clinical implementation?

Patients undergoing organ transplantation transition from one life-altering issue (organ dysfunction) to a lifelong commitment-immunosuppression. Regimens of immunosuppressive agents (ISAs) come with significant side effects and comorbidities. Recently, the use of nanoparticles (NPs) as a solution to the problems associated with the long-term and systemic use of ISAs in transplantation has emerged.

Blood transcriptomes of SARS-CoV-2 infected kidney transplant recipients demonstrate immune insufficiency.

Background: Kidney transplant recipients (KTRs) with COVID-19 have poor outcomes compared to non-KTRs. To provide insight into management of immunosuppression during acute illness, we studied immune signatures from the peripheral blood during and after COVID-19 infection from a multicenter KTR cohort.□.

A digital pathology tool for quantification of color features in histologic specimens.

In preclinical research, histological analysis of tissue samples is often limited to qualitative or semiquantitative scoring assessments. The reliability of this analysis can be impaired by the subjectivity of these approaches, even when read by experienced pathologists. Furthermore, the laborious nature of manual image assessments often leads to the analysis being restricted to a relatively small number of images that may not accurately represent the whole sample.

Evaluation and treatment of headache associated with moyamoya disease - a narrative review.

Background: Headache in patients with moyamoya disease is an under-addressed topic in the medical literature. Delay in the diagnosis of moyamoya disease or inappropriate treatment of headache could lead to devastating cerebrovascular outcome. With the evolving understanding of moyamoya disease, migraine pathophysiology, and various migraine-specific medications that have become available, it is crucial to provide an updated overview on this topic.

How Tim proteins differentially exploit membrane features to attain robust target sensitivity.

Immune surveillance cells such as T cells and phagocytes utilize integral plasma membrane receptors to recognize surface signatures on triggered and activated cells such as those in apoptosis. One such family of plasma membrane sensors, the transmembrane immunoglobulin and mucin domain (Tim) proteins, specifically recognize phosphatidylserine (PS) but elicit distinct immunological responses. The molecular basis for the recognition of lipid signals on target cell surfaces is not well understood.

Adverse Childhood Experiences and Frequent Headache by Adolescent Self-Report.

Background: The association between exposure to adverse childhood experiences (ACEs) and increased headache in adults has been well characterized. Childhood adversity and its effect on headache in children have not been as robustly investigated. This study examines the relationship of self-reported ACEs to frequent headache in an adolescent cohort.

Neurological Predictors of Clinical Outcomes in Hospitalized Patients With COVID-19.

Multiple risk factors of mortality have been identified in patients with COVID-19. Here, we sought to determine the effect of a history of neurological disorder and development of neurological manifestations on mortality in hospitalized patients with COVID-19. From March 20 to May 20, 2020, hospitalized patients with laboratory confirmed or highly suspected COVID-19 were identified at four hospitals in Ohio.

Efficacy of Galcanezumab for Migraine Prevention in Patients With a Medical History of Anxiety and/or Depression: A Post Hoc Analysis of the Phase 3, Randomized, Double-Blind, Placebo-Controlled REGAIN, and Pooled EVOLVE-1 and EVOLVE-2 Studies.

Objective: This post hoc analysis evaluated the efficacy of galcanezumab for the prevention of migraine in patients with and without comorbid anxiety and/or depression.

Background: Patients with migraine have a higher risk of anxiety and/or depression. Given the high prevalence of psychiatric symptoms and their potential negative prognostic impact, determining the efficacy of migraine treatments in patients with these comorbidities is important.

Lysis of cold-storage-induced microvascular obstructions for ex vivo revitalization of marginal human kidneys.

Thousands of kidneys from higher-risk donors are discarded annually because of the increased likelihood of complications posttransplant. Given the severe organ shortage, there is a critical need to improve utilization of these organs. To this end, normothermic machine perfusion (NMP) has emerged as a platform for ex vivo assessment and potential repair of marginal organs.

Ex vivo isolated human vessel perfusion system for the design and assessment of nanomedicines targeted to the endothelium.

Endothelial cells play a central role in the process of inflammation. Their biologic relevance, as well as their accessibility to IV injected therapeutics, make them a strong candidate for treatment with molecularly-targeted nanomedicines. Typically, the properties of targeted nanomedicines are first optimized in vitro in cell culture and then in vivo in rodent models.