Hepatocyte Period 1 dictates oxidative substrate selection independent of the core circadian clock.

Organisms integrate circadian and metabolic signals to optimize substrate selection to survive starvation, yet precisely how this occurs is unclear. Here, we show that hepatocyte Period 1 (Per1) is selectively induced during fasting, and mice lacking hepatocyte Per1 fail to initiate autophagic flux, ketogenesis, and lipid accumulation. Transcriptomic analyses show failed induction of the fasting hepatokine Fgf21 in Per1-deficient mice, and single-nucleus multiome sequencing defines a putative responding hepatocyte subpopulation that fails to induce the chromatin accessibility near the Fgf21 locus.

Efficacy of Occupation-Based Intervention in Promoting Well-Being Among Occupational Therapy Graduate Students.

Background: Occupational therapy graduate students report poor well-being during their educational experience.

Objective: This convergent mixed-methods study (quantitative approach presented) examined the effectiveness of an occupation-based intervention in promoting well-being.

Methodology: Forty-one entry-level doctorate students (intervention = 18, control = 23) completed four standardized measures at three timepoints.

Hepatocyte MMP14 mediates liver and inter-organ inflammatory responses to diet-induced liver injury.

The matrix metalloproteinase MMP14 is a ubiquitously expressed, membrane-bound, secreted endopeptidase that proteolyzes substrates to regulate development, signaling, and metabolism. However, the spatial and contextual events inciting MMP14 activation and its metabolic sequelae are not fully understood. Here, we introduce an inducible, hepatocyte-specific MMP14-deficient model (MMP14 mice) to elucidate cell-intrinsic and systemic MMP14 function.

Hierarchical tricarboxylic acid cycle regulation by hepatocyte arginase 2 links the urea cycle to oxidative metabolism.

Urea cycle impairment and its relationship to obesity and inflammation remained elusive, partly due to the dramatic clinical presentation of classical urea cycle defects. We generated mice with hepatocyte-specific arginase 2 deletion (Arg2) and revealed a mild compensated urea cycle defect. Stable isotope tracing and respirometry revealed hepatocyte urea and TCA cycle flux defects, impaired mitochondrial oxidative metabolism, and glutamine anaplerosis despite normal energy and glucose homeostasis during early adulthood.

Polyamine-Mediated Sensitization of to Macrolides through a Dual Mode of Action.

Chemicals bacteria encounter at the infection site could shape their stress and antibiotic responses; such effects are typically undetected under standard lab conditions. Polyamines are small molecules typically overproduced by the host during infection and have been shown to alter bacterial stress responses. We sought to determine the effect of polyamines on the antibiotic response of , a Gram-negative priority pathogen.

The PML1-WDR5 axis regulates H3K4me3 marks and promotes stemness of estrogen receptor-positive breast cancer.

The alternative splicing of PML precursor mRNA gives rise to various PML isoforms, yet their expression profile in breast cancer cells remains uncharted. We discovered that PML1 is the most abundant isoform in all breast cancer subtypes, and its expression is associated with unfavorable prognosis in estrogen receptor-positive (ER+) breast cancers. PML depletion reduces cell proliferation, invasion, and stemness, while heterologous PML1 expression augments these processes and fuels tumor growth and resistance to fulvestrant, an FDA-approved drug for ER+ breast cancer, in a mouse model.

A Structure-function Analysis of Hepatocyte Arginase 2 Reveals Mitochondrial Ureahydrolysis as a Determinant of Glucose Oxidation.

Background & Aims: Restoring hepatic and peripheral insulin sensitivity is critical to prevent or reverse metabolic syndrome and type 2 diabetes. Glucose homeostasis comprises in part the complex regulation of hepatic glucose production and insulin-mediated glucose uptake and oxidation in peripheral tissues. We previously identified hepatocyte arginase 2 (Arg2) as an inducible ureahydrolase that improves glucose homeostasis and enhances glucose oxidation in multiple obese, insulin-resistant models.

One-Year Results of a Low-Profile Endograft in Acute, Complicated Type B Aortic Dissection.

Background: The safety and effectiveness of the RelayPro endograft (Terumo Aortic) was assessed for the treatment of acute, complicated type B aortic dissection (TBAD).

Methods: A prospective pivotal trial analyzed a primary end point of all-cause mortality at 30 days. Secondary end points included technical success, major adverse events (disabling stroke, renal failure, and paraplegia/paralysis), endoleaks, patency, rupture, device integrity, false lumen perfusion, reinterventions, aortic expansion, and migration evaluated to 5 years.

The PML1-WDR5 axis regulates H3K4me3 marks and promotes stemness of estrogen receptor-positive breast cancer.

The alternative splicing of precursor mRNA gives rise to various isoforms, yet their expression profile in breast cancer cells remains uncharted. We discovered that PML1 is the most abundant isoform in all breast cancer subtypes, and its expression is associated with unfavorable prognosis in estrogen receptor-positive (ER+) breast cancers. depletion reduces cell proliferation, invasion, and stemness, while heterologous PML1 expression augments these processes and fuels tumor growth and resistance to fulvestrant, an FDA-approved drug for ER + breast cancer, in a mouse model.

Tightrope Technique for facilitating complex endovascular aortic repair in patients with severely angulated neck.

An 84-year-old presented with a large, symptomatic juxtarenal abdominal aortic aneurysm. Owing to severe angulation of the infrarenal neck, advancement of the distal bifurcated component caused dramatic lateral movement of the proximal physician-modified endovascular graft (PMEG) fenestrated device. This procedure risked aneurysm sac perforation and possible PMEG device displacement.

NGLY1 Deficiency, a Congenital Disorder of Deglycosylation: From Disease Gene Function to Pathophysiology.

-Glycanase 1 (NGLY1) is a cytosolic enzyme involved in removing -linked glycans of misfolded -glycoproteins and is considered to be a component of endoplasmic reticulum-associated degradation (ERAD). The 2012 identification of recessive mutations in a rare multisystem disorder has led to intense research efforts on the roles of NGLY1 in animal development and physiology, as well as the pathophysiology of NGLY1 deficiency. Here, we present a review of the NGLY1-deficient patient phenotypes, along with insights into the function of this gene from studies in rodent and invertebrate animal models, as well as cell culture and biochemical experiments.

Extracellular Matrix Patches for Endarterectomy Repair.

Patch repair is the preferred method for arteriotomy closure following femoral or carotid endarterectomy. Choosing among available patch options remains a clinical challenge, as current evidence suggests roughly comparable outcomes between autologous grafts and synthetic and biologic materials. Biologic patches have potential advantages over other materials, including reduced risk for infection, mitigation of an excessive foreign body response, and the potential to remodel into healthy, vascularized tissue.

Regulation of BMP4/Dpp retrotranslocation and signaling by deglycosylation.

During endoplasmic reticulum-associated degradation (ERAD), the cytoplasmic enzyme -glycanase 1 (NGLY1) is proposed to remove -glycans from misfolded -glycoproteins after their retrotranslocation from the ER to the cytosol. We previously reported that NGLY1 regulates BMP signaling in a tissue-specific manner (Galeone et al., 2017).

The Roles of Notch Signaling in Liver Development and Disease.

The Notch signaling pathway plays major roles in organ development across animal species. In the mammalian liver, Notch has been found critical in development, regeneration and disease. In this review, we highlight the major advances in our understanding of the role of Notch activity in proper liver development and function.

Sox9 Is a Modifier of the Liver Disease Severity in a Mouse Model of Alagille Syndrome.

Background And Aims: Alagille syndrome (ALGS) is a multisystem developmental disorder characterized by bile duct (BD) paucity, caused primarily by haploinsufficiency of the Notch ligand jagged1. The course of the liver disease is highly variable in ALGS. However, the genetic basis for ALGS phenotypic variability is unknown.

Determining Bile Duct Density in the Mouse Liver.

Mouse is broadly used as a model organism to study biliary diseases. To evaluate the development and function of the biliary system, various techniques are used, including serum chemistry, histological analysis, and immunostaining for specific markers. Although these techniques can provide important information about the biliary system, they often do not present a full picture of bile duct (BD) developmental defects across the whole liver.

Establishing a Long-Term Model for Analysis and Improvement of Underfilled Blood Culture Volumes.

Objectives: Underfilling of blood culture bottles decreases the sensitivity of the culture. We attempt to increase average blood culture fill volumes (ABCFVs) through an educational program.

Methods: Partnerships were established with four hospital units (surgical intensive care unit [SICU], medical intensive care unit [MICU], medical intermediate care unit [MIMCU], and hematology and oncology unit [HEME/ONC]).

The Effect of Household Oxidizing Cleaners on Chemiluminescence of Blood Using Bluestar.

This study tests the effect of three common oxidizing cleaners on the ability of the Bluestar Forensic® presumptive test for blood to identify the presence of blood on ceramic tile after cleaning. The cleaners tested were Lysol®, OxiClean®, and Arm & Hammer®. This study also tested which cleaner was the most effective at removing blood, measured by the intensity of chemiluminescence, which was quantified using RGB values in ImageJ.

Translating the ICAP Theory of Cognitive Engagement Into Practice.

ICAP is a theory of active learning that differentiates students' engagement based on their behaviors. ICAP postulates that Interactive engagement, demonstrated by co-generative collaborative behaviors, is superior for learning to Constructive engagement, indicated by generative behaviors. Both kinds of engagement exceed the benefits of Active or Passive engagement, marked by manipulative and attentive behaviors, respectively.

Isolated Harlequin Syndrome Following Brachial Plexus Nerve Block via Interscalene Approach: A Case Report.

Interscalene brachial plexus blockade is regularly used for postoperative pain management following shoulder surgery. A known but generally benign side effect of this technique is Horner syndrome. Another syndrome known as harlequin syndrome exists but does not appear to be as common.

Cp*Co(III)-Catalyzed Coupling of Benzamides with α,β-Unsaturated Carbonyl Compounds: Preparation of Aliphatic Ketones and Azepinones.

A Cp*Co -catalyzed C-H functionalization of benzamide substrates with α,β-unsaturated ketones has been optimized, providing a facile route towards aliphatic ketone products. When employing α,β-unsaturated aldehydes as coupling partners, under the optimized protocol, a cascade reaction forming azepinones has also been developed. Finally, DFT studies have demonstrated how stabilization of a metallo-enol intermediate when employing α,β-unsaturated ketones is the driving force leading to the observed aliphatic ketone product rather than olefinic products reported using α,β-unsaturated esters as coupling partners.

Intralobar Pulmonary Sequestration With Aneurysmal Feeding Vessel: Use of Hybrid Surgical Management.

We describe the endovascular exclusion and surgical resection of an intralobar pulmonary sequestration supplied by an aneurysmal feeding vessel from the aorta. Pulmonary sequestration is a rare congenital anomaly, and the presence of an aneurysmal feeding vessel is even rarer. The possibility of life-threatening hemorrhage resulting from failure to control these aberrant vessels has led many to pursue preoperative embolization.