Cellular Crosstalk Promotes Hepatic Progenitor Cell Proliferation and Stellate Cell Activation in 3D Co-culture.

Background & Aims: Following liver damage, ductular reaction often coincides with liver fibrosis. Proliferation of hepatic progenitor cells is observed in ductular reaction, whereas activated hepatic stellate cells (HSCs) are the main drivers of liver fibrosis. These observations may suggest a functional interaction between these 2 cell types.

Biomarkers of sepsis-induced coagulopathy: diagnostic insights and potential therapeutic implications.

Diagnosing coagulopathy in septic patients remains challenging in intensive care. Disseminated intravascular coagulation (DIC) indeed presents with complex pathophysiology, complicating timely diagnosis. Epidemiological data indicate a significant prevalence of DIC in septic patients, with mortality rates up to 60%.

Impact of hyper- and hypothermia on cellular and whole-body physiology.

The incidence of heat-related illnesses and heatstroke continues to rise amidst global warming. Hyperthermia triggers inflammation, coagulation, and progressive multiorgan dysfunction, and, at levels above 40 °C, can even lead to cell death. Blood cells, particularly granulocytes and platelets, are highly sensitive to heat, which promotes proinflammatory and procoagulant changes.

Mitochondrial dysfunction is a major cause of thromboinflammation and inflammatory cell death in critical illnesses.

Background: Mitochondria generate the adenosine triphosphate (ATP) necessary for eukaryotic cells, serving as their primary energy suppliers, and contribute to host defense by producing reactive oxygen species. In many critical illnesses, including sepsis, major trauma, and heatstroke, the vicious cycle between activated coagulation and inflammation results in tissue hypoxia-induced mitochondrial dysfunction, and impaired mitochondrial function contributes to thromboinflammation and cell death.

Methods: A computer-based online search was performed using the PubMed and Web of Science databases for published articles concerning sepsis, trauma, critical illnesses, cell death, mitochondria, inflammation, coagulopathy, and organ dysfunction.

5-FU Weakens Defensive Functions of the Junctional Epithelium.

Aim: To investigate additional factors contributing to the pathophysiology of chemotherapy-induced oral mucositis and periodontitis beyond the systemic immune suppression caused by the chemotherapeutic agent 5-Fluorouracil (5-FU).

Methods: 5-Fluorouracil was topically delivered to the non-keratinized, rapidly proliferating junctional epithelium (JE) surrounding the dentition, and acts as an immunologic and functional barrier to bacterial ingression. Various techniques, including EdU incorporation, quantitative immunohistochemistry (qIHC), histology, enzymatic activity assays, and micro-computed tomographic (μCT) imaging, were employed to analyze the JE at multiple time points following topical 5-FU treatment.

Reactivity of a heterobinuclear heme-peroxo-Cu complex with -substituted catechols shows a p -dependent change in mechanism.

In biological systems, heme-copper oxidase (HCO) enzymes play a crucial role in the oxygen reduction reaction (ORR), where the pivotal O-O bond cleavage of the (heme)Fe-peroxo-Cu intermediate is facilitated by active-site (peroxo core) hydrogen bonding followed by proton-coupled electron transfer (PCET) from a nearby (phenolic) tyrosine residue. A useful approach to comprehend the fundamental relationships among H-bonding/proton/H-atom donors and their abilities to induce O-O bond homolysis involves the investigation of synthetic, bioinspired model systems where the exogenous substrate properties (such as p and bond dissociation energy (BDE)) can be systematically altered. This report details the reactivity of a heme-peroxo-copper HCO model complex (LS-4DCHIm) toward a series of substituted catechol substrates that span a range of p and O-H bond BDE values, exhibiting different reaction mechanisms.

Evaluation of Postoperative Outcomes Following Early and Late Palate Repair: A Preclinical Study.

Objective: To quantitatively assess the impact of early versus late surgical intervention on midfacial growth using a mouse model.

Methods: A full-thickness mucoperiosteal flap surgery was performed on newborn (P17) mice and on neonatal (P30) mice. High-resolution micro-computed tomographic imaging coupled with histomorphometric analyses was used to assess craniomaxillofacial growth.

Autophagy and autophagic cell death in sepsis: friend or foe?

In sepsis, inflammation, and nutrient deficiencies endanger cellular homeostasis and survival. Autophagy is primarily a mechanism of cellular survival under fasting conditions. However, autophagy-dependent cell death, known as autophagic cell death, is proinflammatory and can exacerbate sepsis.

Infodemics and Vaccine Confidence: Protocol for Social Listening and Insight Generation to Inform Action.

Background: In the fall of 2020, the COVID-19 infodemic began to affect public confidence in and demand for COVID-19 vaccines in the United States. While polls indicated what consumers felt regarding COVID-19 vaccines, they did not provide an understanding of why they felt that way or the social and informational influences that factored into vaccine confidence and uptake. It was essential for us to better understand how information ecosystems were affecting the confidence in and demand for COVID-19 vaccines in the United States.

The Detection of Neutrophil Activation by Automated Blood Cell Counter in Sepsis.

Neutrophils serve as the frontline defenders in the host's response to infections. However, the available methods for assessing the activated status of neutrophils are still limited. The immature cells that appear during sepsis are large with complex cytoplasmic components and rich nucleic acids, making them diagnosable by cell population data analysis using the automated cell counter.

Oxygen therapy in acute hypoxemic respiratory failure: guidelines from the SRLF-SFMU consensus conference.

Introduction: Although largely used, the place of oxygen therapy and its devices in patients with acute hypoxemic respiratory failure (ARF) deserves to be clarified. The French Intensive Care Society (Société de Réanimation de Langue Française, SRLF) and the French Emergency Medicine Society (Société Française de Médecine d'Urgence, SFMU) organized a consensus conference on oxygen therapy in ARF (excluding acute cardiogenic pulmonary oedema and hypercapnic exacerbation of chronic obstructive diseases) in December 2023.

Methods: A committee without any conflict of interest (CoI) with the subject defined 7 generic questions and drew up a list of sub questions according to the population, intervention, comparison and outcomes (PICO) model.

Barriers to female leadership in intensive care medicine: insights from an ESICM NEXT & Diversity Monitoring Group Survey.

Background: The underrepresentation of women in leadership remains a pervasive issue, prompting a critical examination of support mechanisms within professional settings. Previous studies have identified challenges women face, ranging from limited visibility to barriers to career advancement. This survey aims to investigate perceptions regarding the effectiveness of women's leadership programs, mentoring initiatives, and a specialized communication course.

Early activation of hepatic stellate cells induces rapid initiation of retinyl ester breakdown while maintaining lecithin:retinol acyltransferase (LRAT) activity.

Lecithin:retinol acyltransferase (LRAT) is the main enzyme producing retinyl esters (REs) in quiescent hepatic stellate cells (HSCs). When cultured on stiff plastic culture plates, quiescent HSCs activate and lose their RE stores in a process similar to that in the liver following tissue damage, leading to fibrosis. Here we validated HSC cultures in soft gels to study RE metabolism in stable quiescent HSCs and investigated RE synthesis and breakdown in activating HSCs.

Acquired von Willebrand syndrome during extracorporeal membrane oxygenation support: a comprehensive review of current evidence: communication from the ISTH SSC on perioperative and critical care thrombosis and hemostasis.

During extracorporeal membrane oxygenation (ECMO) support, the high shear stress in the ECMO circuit results in increased proteolysis of von Willebrand factor (VWF), loss of VWF high-molecular-weight multimers, and impaired ability to bind to platelets and collagen. These structural changes in VWF are consistent with acquired von Willebrand syndrome (AVWS) type 2A and may contribute to the bleeding diathesis frequently observed in ECMO patients. We performed a systematic review of all clinical studies evaluating the prevalence and associated outcomes of AVWS in ECMO patients.