Perfusion Pressures and Weight Loss During Normothermic Machine Perfusion of Human Donor Livers.

Background: Normothermic machine perfusion (NMP) is increasingly used to preserve and assess donor livers prior to transplantation. Due to its success, it is expected that more centers will start using this technology. However, NMP may also cause adverse effects.

CARE-SD: classifier-based analysis for recognizing provider stigmatizing and doubt marker labels in electronic health records: model development and validation.

Objective: To detect and classify features of stigmatizing and biased language in intensive care electronic health records (EHRs) using natural language processing techniques.

Materials And Methods: We first created a lexicon and regular expression lists from literature-driven stem words for linguistic features of stigmatizing patient labels, doubt markers, and scare quotes within EHRs. The lexicon was further extended using Word2Vec and GPT 3.

Comparative Analysis of Digestion Methods for Bile Proteomics: The Key to Unlocking Biliary Biomarker Potential.

Background: Bile's potential to reflect the health of the biliary system has led to increased attention, with proteomic analysis offering deeper understanding of biliary diseases and potential biomarkers. With the emergence of normothermic machine perfusion (NMP), bile can be easily collected and analyzed. However, the composition of bile can make the application of proteomics challenging.

Comparison of the Genomic Activity of an EP-Receptor and β-Adrenoceptor Agonist in BEAS-2B Human Bronchial Epithelial Cells: In Search of Compartmentalized, cAMP-Dependent Gene Expression.

It has been proposed that inhaled E-prostanoid 4 (EP)-receptor agonists could represent a new class of bronchodilators for the treatment of asthma that are as effective as -adrenoceptor agonists. However, the genomic impact of such drugs is unknown despite being potentially deleterious to respiratory health. Herein, we used mRNA-seq to compare the transcriptomic responses produced by 2-[3-[(1R,2S,3R)-3-hydroxy-2-[(E,3S)-3-hydroxy-5-[2-(methoxymethyl)phenyl]pent-1-enyl]-5-oxo-cyclopentyl]sulphanylpropylsulphanyl] acetic acid (ONO-AE1-329; an EP-receptor agonist) and vilanterol (a -adrenoceptor agonist) in BEAS-2B human airway epithelial cells.

Misaligned feeding uncouples daily rhythms within brown adipose tissue and between peripheral clocks.

Extended food consumption during the rest period perturbs the phase relationship between circadian clocks in the periphery and the brain, leading to adverse health effects. Beyond the liver, how metabolic organs respond to a timed hypocaloric diet is largely unexplored. We investigated how feeding schedules impacted circadian gene expression in epididymal white and brown adipose tissue (eWAT and BAT) compared to the liver and hypothalamus.

Inducible gene expression of IκB-kinase ε is dependent on nuclear factor-κB in human pulmonary epithelial cells.

While IκB-kinase-ε (IKKε) induces immunomodulatory genes following viral stimuli, its up-regulation by inflammatory cytokines remains under-explored. Since airway epithelial cells respond to airborne insults and potentiate inflammation, IKKε expression was characterized in pulmonary epithelial cell lines (A549, BEAS-2B) and primary human bronchial epithelial cells grown as submersion or differentiated air-liquid interface cultures. IKKε expression was up-regulated by the pro-inflammatory cytokines, interleukin-1β (IL-1β) and tumour necrosis factor-α (TNFα).

Clinical Utility of Repeat Magnetic Resonance Imaging Studies Among Children With Acute Hematogenous Osteomyelitis.

Background And Objectives: There is limited guidance for whether repeat magnetic resonance imaging (MRI) studies are clinically impactful among children with acute hematogenous osteomyelitis (AHO) who fail to improve as expected. This study aimed to determine whether repeat MRIs changed management among children with AHO and identify clinical characteristics predictive of which patients benefit from repeat MRIs.

Methods: Children admitted to a quaternary care pediatric hospital with AHO were identified during a 9-year period.

Prolonged hypothermic machine perfusion enables daytime liver transplantation - an IDEAL stage 2 prospective clinical trial.

Background: Liver transplantation is traditionally performed around the clock to minimize organ ischemic time. However, the prospect of prolonging preservation times holds the potential to streamline logistics and transform liver transplantation into a semi-elective procedure, reducing the need for nighttime surgeries. Dual hypothermic oxygenated machine perfusion (DHOPE) of donor livers for 1-2 h mitigates ischemia-reperfusion injury and improves transplant outcomes.

Bile proteome reveals biliary regeneration during normothermic preservation of human donor livers.

Normothermic machine perfusion (NMP) after static cold storage is increasingly used for preservation and assessment of human donor livers prior to transplantation. Biliary viability assessment during NMP reduces the risk of post-transplant biliary complications. However, understanding of molecular changes in the biliary system during NMP remains incomplete.

Synergy between Interleukin-1, Interferon-, and Glucocorticoids to Induce TLR2 Expression Involves NF-B, STAT1, and the Glucocorticoid Receptor.

Glucocorticoids act via the glucocorticoid receptor (GR; NR3C1) to downregulate inflammatory gene expression and are effective treatments for mild to moderate asthma. However, in severe asthma and virus-induced exacerbations, glucocorticoid therapies are less efficacious, possibly due to reduced repressive ability and/or the increased expression of proinflammatory genes. In human A549 epithelial and primary human bronchial epithelial cells, toll-like receptor (TLR)-2 mRNA and protein were -additively induced by interleukin-1 (IL-1) plus dexamethasone (IL-1+Dex), interferon- (IFN-) plus dexamethasone (IFN-+Dex), and IL-1 plus IFN- plus dexamethasone (IL-1+IFN-+Dex).

Differential regulation of BIRC2 and BIRC3 expression by inflammatory cytokines and glucocorticoids in pulmonary epithelial cells.

Roles for the baculoviral inhibitor of apoptosis repeat-containing (BIRC) genes, BIRC2 and BIRC3, may include signaling to the inflammatory transcription factor, nuclear factor-κB (NF-κB) and protection from cell death. However, distinct functions for each BIRC are not well-delineated. Given roles for the epithelium in barrier function and host defence, BIRC2 and BIRC3 expression was characterized in pulmonary epithelial cell lines and primary human bronchial epithelial cells (pHBECs) grown as undifferentiated cells in submersion culture (SC) or as highly differentiated cells at air-liquid interface (ALI).

Evaluating the effects of a global pandemic on the operation of an investigational drug service.

Purpose: This study is an analysis of the changes to workload and operations of UNC Health's investigational drug service (IDS) brought about by the coronavirus disease 2019 (COVID-19) pandemic.

Methods: Workload statistics were collected and analyzed for trend changes to illustrate operational changes necessitated by the COVID-19 pandemic within the IDS pharmacy at UNC Health.

Results: Multiple workload metrics declined at the beginning of the COVID-19 pandemic, followed by an increase in the metrics for many categories as the pandemic continued.

Restoration of Bile Duct Injury of Donor Livers During Ex Situ Normothermic Machine Perfusion.

Background: End-ischemic ex situ normothermic machine perfusion (NMP) enables assessment of donor livers prior to transplantation. The objective of this study was to provide support for bile composition as a marker of biliary viability and to investigate whether bile ducts of high-risk human donor livers already undergo repair during NMP.

Methods: Forty-two livers that were initially declined for transplantation were included in our NMP clinical trial.

Appropriate Medical Staffing Improves Patient Safety, Training and Doctor Wellbeing.

Background Cross-covering of medical and surgical specialities out-of-hours is a problem in many hospitals, leaving trainee doctors responsible out-of-hours for patients they have never met, in specialities where they do not normally work. This has implications for patient safety and doctor wellbeing. In our Trust, a historical decision resulted in trainee doctors in Trauma & Orthopaedics and Ear Nose and Throat Surgery being reallocated out-of-hours to cross-cover medical inpatients.

Magnetic resonance imaging predictors (cartilage, osteophytes and meniscus) of prevalent and 3-year incident medial and lateral tibiofemoral knee joint tenderness and patellofemoral grind.

Objective: To identify magnetic resonance imaging (MRI) predictors (cartilage [C], osteophytes [O] and meniscus [M] scores) of prevalent and 3-year incident medial tibiofemoral (MTF) and lateral tibiofemoral (LTF) knee joint tenderness and patellofemoral (PF) grind.  METHODS: Population-based knee pain cohort aged 40-79 was assessed at baseline (N = 255), 3- and 7-year follow-up (N = 108 × 2 = 216). COM scores were measured at 6/8/6 subregions respectively.

Time-restricted feeding mitigates obesity through adipocyte thermogenesis.

Misalignment of feeding rhythms with the light-dark cycle leads to disrupted peripheral circadian clocks and obesity. Conversely, restricting feeding to the active period mitigates metabolic syndrome through mechanisms that remain unknown. We found that genetic enhancement of adipocyte thermogenesis through ablation of the zinc finger protein 423 (ZFP423) attenuated obesity caused by consumption of a high-fat diet during the inactive (light) period by increasing futile creatine cycling in mice.

The Hitchhiker Position in Endoscopic Pituitary Surgery.

Background: Technically and ergonomically correct positioning is essential in endoscopic transsphenoidal pituitary surgery.

Objective: To propose a safe, ergonomic approach to conduct endoscopic endonasal pituitary and skull base surgery in large patients without sacrificing important aspects of current standard practice.

Methods: The patient's right arm is outstretched and secured in a supine position, with the primary surgeon standing in the axillary area.

Sequential hypothermic and normothermic machine perfusion enables safe transplantation of high-risk donor livers.

Ex situ normothermic machine perfusion (NMP) is increasingly used for viability assessment of high-risk donor livers, whereas dual hypothermic oxygenated machine perfusion (DHOPE) reduces ischemia-reperfusion injury. We aimed to resuscitate and test the viability of initially-discarded, high-risk donor livers using sequential DHOPE and NMP with two different oxygen carriers: an artificial hemoglobin-based oxygen carrier (HBOC) or red blood cells (RBC). In a prospective observational cohort study of 54 livers that underwent DHOPE-NMP, the first 18 procedures were performed with a HBOC-based perfusion solution and the subsequent 36 procedures were performed with an RBC-based perfusion solution for the NMP phase.

Nonlinearity in bone-conducted amplitude-modulated cervical vestibular-evoked myogenic potentials: harmonic distortion products.

Otolith organs of the balance system, the saccule and utricle, encode linear acceleration. Integrity of the saccule is commonly assessed using cervical vestibular-evoked myogenic potentials (cVEMPs) arising from an inhibitory reflex along the vestibulospinal pathway. Conventional approaches to eliciting these responses use brief, transient sounds to elicit onset responses.

Integrative omics reveals subtle molecular perturbations following ischemic conditioning in a porcine kidney transplant model.

Background: Remote Ischemic Conditioning (RIC) has been proposed as a therapeutic intervention to circumvent the ischemia/reperfusion injury (IRI) that is inherent to organ transplantation. Using a porcine kidney transplant model, we aimed to decipher the subclinical molecular effects of a RIC regime, compared to non-RIC controls.

Methods: Kidney pairs (n = 8 + 8) were extracted from brain dead donor pigs and transplanted in juvenile recipient pigs following a period of cold ischemia.

Oxygenated versus non-oxygenated flush out and storage of donor livers: An experimental study.

Background: During donor organ procurement and subsequent static cold storage (SCS), hepatic adenosine triphosphate (ATP) levels are progressively depleted, which contributes to ischemia-reperfusion injury (IRI). We sought to investigate a simple approach to prevent ATP depletion and IRI using a porcine donation after circulatory death (DCD) liver reperfusion model.

Methods: After 30 min warm ischemia, porcine livers were flushed via the portal vein with cold (4°C) non-oxygenated University of Wisconsin (UW) preservation solution (n = 6, control group) or with oxygenated UW (n = 6, OxyFlush group).