The rising cost of liver transplantation in the United States.

Liver transplantation (LT) is the only curative treatment for end-stage liver disease and significantly improves patient outcomes. However, LT is resource-intensive and costly, with expenditures rising dramatically in recent years. Factors contributing to this increase in cost include expanded transplant criteria, utilization of marginal organs, and broader organ distribution, resulting in significant logistical expenses.

Development and Validation of a Noninvasive Model for the Detection of High-Risk Varices in Patients With Unresectable Hepatocellular Carcinoma.

Background & Aims: Noninvasive variceal risk stratification systems have not been validated in patients with hepatocellular carcinoma (HCC), which presents logistical barriers for patients in the setting of systemic HCC therapy. We aimed to develop and validate a noninvasive algorithm for the prediction of varices in patients with unresectable HCC.

Methods: We performed a retrospective cohort study in 21 centers in the United States including adult patients with unresectable HCC and Child-Pugh A5-B7 cirrhosis diagnosed between 2007 and 2019.

Bifidobacteria metabolize lactulose to optimize gut metabolites and prevent systemic infection in patients with liver disease.

Progression of chronic liver disease is precipitated by hepatocyte loss, inflammation and fibrosis. This process results in the loss of critical hepatic functions, increasing morbidity and the risk of infection. Medical interventions that treat complications of hepatic failure, including antibiotic administration for systemic infections and lactulose treatment for hepatic encephalopathy, can impact gut microbiome composition and metabolite production.

Endocrine aspects of metabolic dysfunction-associated steatotic liver disease (MASLD): Beyond insulin resistance.

While the association of metabolic dysfunction-associated steatotic liver disease (MASLD) with obesity and insulin resistance is widely appreciated, there are a host of complex interactions between the liver and other endocrine axes. While it can be difficult to definitively distinguish direct causal relationships and those attributable to increased adipocyte mass, there is substantial evidence of the direct and indirect effects of endocrine dysregulation on the severity of MASLD, with strong evidence that low levels of growth hormone, sex hormones, and thyroid hormone promote the development and progression of disease. The impact of steroid hormones, e.

Dietary Restriction Impacts Peripheral Circadian Clock Output Important for Longevity in .

Circadian clocks may mediate lifespan extension by caloric or dietary restriction (DR). We find that the core clock transcription factor is crucial for a robust longevity and fecundity response to DR in . To identify clock-controlled mediators, we performed RNA-sequencing from abdominal fat bodies across the 24 h day after just 5 days under control or DR diets.

Discarding Dichotomization: Retrieving Data in the Service of Patient Care.

Content available: Author Interview and Audio Recording.

The effect of COVID-19 on liver transplantation: impact, practice patterns, therapeutics, and next steps.

Purpose Of Review: To assess the impact of coronavirus disease 2019 (COVID-19) and the pandemic on liver transplant candidates, recipients, and donors, and review guidelines and recommendations for integrating COVID-19 therapies into current practice.

Recent Findings: COVID-19 has high morbidity and mortality for transplant candidates; interestingly, posttransplant comorbidities play a larger role than immunosuppression status. COVID-19 therapies and vaccinations are well tolerated in pre and postliver transplant patients with few exceptions, although further research is needed regarding effectiveness in this patient population.

Circadian Clocks Function in Concert with Heat Shock Organizing Protein to Modulate Mutant Huntingtin Aggregation and Toxicity.

Neurodegenerative diseases commonly involve the disruption of circadian rhythms. Studies indicate that mutant Huntingtin (mHtt), the cause of Huntington's disease (HD), disrupts circadian rhythms often before motor symptoms are evident. Yet little is known about the molecular mechanisms by which mHtt impairs circadian rhythmicity and whether circadian clocks can modulate HD pathogenesis.

Bootstrapping and Empirical Bayes Methods Improve Rhythm Detection in Sparsely Sampled Data.

There is much interest in using genome-wide expression time series to identify circadian genes. However, the cost and effort of such measurements often limit data collection. Consequently, it is difficult to assess the experimental uncertainty in the measurements and, in turn, to detect periodic patterns with statistical confidence.

miR-4728-3p Functions as a Tumor Suppressor in Ulcerative Colitis-associated Colorectal Neoplasia Through Regulation of Focal Adhesion Signaling.

Background: As mechanisms of neoplasia in patients with ulcerative colitis (UC) remain poorly understood, we sought to identify pathways of carcinogenesis in this high-risk population.

Methods: MicroRNA (miRNA) and mRNA expression was examined in nondysplastic rectosigmoid mucosa from UC patients with (n = 19) or without remote colon neoplasia (n = 23). We developed a method to identify miRNA-regulated pathways based on differentially expressed miRNAs and their putative mRNAs targets in the same samples.

An Experimental Survey on the Effect of Using the CTS-6 Tool on the Diagnosis of Carpal Tunnel Syndrome by Hand Surgeons.

Background: This controlled randomized experiment tested the research hypothesis that providing the CTS-6 quantitative diagnostic information to hand surgeons affects the diagnosis of carpal tunnel syndrome.

Methods: Surgeon members of American Association for Hand Surgery participated in an online survey. Demographic and practice pattern information was collected.

Disturbance Regimes Predictably Alter Diversity in an Ecologically Complex Bacterial System.

Unlabelled: Diversity is often associated with the functional stability of ecological communities from microbes to macroorganisms. Understanding how diversity responds to environmental perturbations and the consequences of this relationship for ecosystem function are thus central challenges in microbial ecology. Unimodal diversity-disturbance relationships, in which maximum diversity occurs at intermediate levels of disturbance, have been predicted for ecosystems where life history tradeoffs separate organisms along a disturbance gradient.

Pancreatic β cell enhancers regulate rhythmic transcription of genes controlling insulin secretion.

The mammalian transcription factors CLOCK and BMAL1 are essential components of the molecular clock that coordinate behavior and metabolism with the solar cycle. Genetic or environmental perturbation of circadian cycles contributes to metabolic disorders including type 2 diabetes. To study the impact of the cell-autonomous clock on pancreatic β cell function, we examined pancreatic islets from mice with either intact or disrupted BMAL1 expression both throughout life and limited to adulthood.

A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability.

Circadian clocks regulate membrane excitability in master pacemaker neurons to control daily rhythms of sleep and wake. Here, we find that two distinctly timed electrical drives collaborate to impose rhythmicity on Drosophila clock neurons. In the morning, a voltage-independent sodium conductance via the NA/NALCN ion channel depolarizes these neurons.

Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism.

Circadian clocks and metabolism are inextricably intertwined, where central and hepatic circadian clocks coordinate metabolic events in response to light-dark and sleep-wake cycles. We reveal an additional key element involved in maintaining host circadian rhythms, the gut microbiome. Despite persistence of light-dark signals, germ-free mice fed low or high-fat diets exhibit markedly impaired central and hepatic circadian clock gene expression and do not gain weight compared to conventionally raised counterparts.

Improved statistical methods enable greater sensitivity in rhythm detection for genome-wide data.

Robust methods for identifying patterns of expression in genome-wide data are important for generating hypotheses regarding gene function. To this end, several analytic methods have been developed for detecting periodic patterns. We improve one such method, JTK_CYCLE, by explicitly calculating the null distribution such that it accounts for multiple hypothesis testing and by including non-sinusoidal reference waveforms.

Steady-state hydrogen peroxide induces glycolysis in Staphylococcus aureus and Pseudomonas aeruginosa.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from human pathogens Staphylococcus aureus and Pseudomonas aeruginosa can be readily inhibited by reactive oxygen species (ROS)-mediated direct oxidation of their catalytic active cysteines. Because of the rapid degradation of H2O2 by bacterial catalase, only steady-state but not one-dose treatment with H2O2 rapidly induces glycolysis and the pentose phosphate pathway (PPP). We conducted transcriptome sequencing (RNA-seq) analyses to globally profile the bacterial transcriptomes in response to a steady level of H2O2, which revealed profound transcriptional changes, including the induced expression of glycolytic genes in both bacteria.

Impaired consciousness in epilepsy investigated by a prospective responsiveness in epilepsy scale (RES).

Purpose: Impaired consciousness in epileptic seizures has a major negative impact on patient quality of life. Prior work on epileptic unconsciousness has mainly used retrospective and nonstandardized methods. Our goal was to validate and to obtain initial data using a standardized prospective testing battery.

Fibonacci, littler, and the hand: a brief review.

In a landmark paper published in 1973, the eminent hand surgeon J. William Littler, MD, proposed two mathematical relationships between the anatomic and functional geometry of the hand. His proposal that the motion of the tips of the fingers follow an equiangular spiral has been experimentally supported.

Cofilin-linked changes in actin filament flexibility promote severing.

The actin regulatory protein, cofilin, increases the bending and twisting elasticity of actin filaments and severs them. It has been proposed that filaments partially decorated with cofilin accumulate stress from thermally driven shape fluctuations at bare (stiff) and decorated (compliant) boundaries, thereby promoting severing. This mechanics-based severing model predicts that changes in actin filament compliance due to cofilin binding affect severing activity.

César Roux and his original 1893 paper.

The Roux-en-Y type of gastrointestinal anastomosis, originated by the Swiss surgeon César Roux, is a valuable technique used in drainage of the stomach, esophagus, and the pancreatico-biliary tree. It is now frequently used in reconstructing the GI tract after resections for a number of diseases, and known by the general public due to its importance in bariatric surgery. This article presents, along with a brief biographical sketch, an English translation and discussion of Roux's original 1893 French report on gastrointestinal surgery that was published in Revue de Chirurgie.

Identification and characterization of NDT 9513727 [N,N-bis(1,3-benzodioxol-5-ylmethyl)-1-butyl-2,4-diphenyl-1H-imidazole-5-methanamine], a novel, orally bioavailable C5a receptor inverse agonist.

The complement system represents an innate immune mechanism of host defense that has three effector arms, the C3a receptor, the C5a receptor (C5aR), and the membrane attack complex. Because of its inflammatory and immune-enhancing properties, the biological activity of C5a and its classical receptor have been widely studied. Because specific antagonism of the C5aR could have therapeutic benefit without affecting the protective immune response, the C5aR continues to be a promising target for pharmaceutical research.