Cathepsin D is essential for the degradomic shift of macrophages required to resolve liver fibrosis.

Background And Objectives: Fibrosis contributes to 45% of deaths in industrialized nations and is characterized by an abnormal accumulation of extracellular matrix (ECM). There are no specific anti-fibrotic treatments for liver fibrosis, and previous unsuccessful attempts at drug development have focused on preventing ECM deposition. Because liver fibrosis is largely acknowledged to be reversible, regulating fibrosis resolution could offer novel therapeutical options.

Alcoholic Foamy Degeneration, an Entity Resembling Alcohol-Associated Hepatitis: Diagnosis, Prognosis, and Molecular Profiling.

Background & Aims: Alcoholic foamy degeneration (AFD) is a condition with similar clinical presentation to alcohol-associated hepatitis (AH), but with a specific histologic pattern. Information regarding the prevalence and prognosis of AFD is scarce and there are no tools for a noninvasive diagnosis.

Methods: A cohort of patients admitted to the Hospital Clinic of Barcelona for clinical suspicion of AH who underwent liver biopsy was included.

Ductular reaction-associated neutrophils promote biliary epithelium proliferation in chronic liver disease.

Background & Aims: Ductular reaction expansion is associated with poor prognosis in patients with advanced liver disease. However, the mechanisms promoting biliary cell proliferation are largely unknown. Here, we identify neutrophils as drivers of biliary cell proliferation and the defective wound-healing response.

Hepatocyte dedifferentiation profiling in alcohol-related liver disease identifies CXCR4 as a driver of cell reprogramming.

Background & Aims: Loss of hepatocyte identity is associated with impaired liver function in alcohol-related hepatitis (AH). In this context, hepatocyte dedifferentiation gives rise to cells with a hepatobiliary (HB) phenotype expressing biliary and hepatocyte markers and showing immature features. However, the mechanisms and impact of hepatocyte dedifferentiation in liver disease are poorly understood.

Hepatocyte Dedifferentiation Profiling In Alcohol-Related Liver Disease Identifies CXCR4 As A Driver Of Cell Reprogramming.

Background And Aims: Loss of hepatocyte identity is associated with impaired liver function in alcohol-related hepatitis (AH). In this context, hepatocyte dedifferentiation gives rise to cells with a hepatobiliary (HB) phenotype expressing biliary and hepatocytes markers and showing immature features. However, the mechanisms and the impact of hepatocyte dedifferentiation in liver disease are poorly understood.

The outcome of boosting mitochondrial activity in alcohol-associated liver disease is organ-dependent.

Background And Aims: Alcohol-associated liver disease (ALD) accounts for 70% of liver-related deaths in Europe, with no effective approved therapies. Although mitochondrial dysfunction is one of the earliest manifestations of alcohol-induced injury, restoring mitochondrial activity remains a problematic strategy due to oxidative stress. Here, we identify methylation-controlled J protein (MCJ) as a mediator for ALD progression and hypothesize that targeting MCJ may help in recovering mitochondrial fitness without collateral oxidative damage.

Case Report: Spontaneous Postpartum Quadruple Cervicocephalic Arterial Dissection With a Heterozygous Variant of Unknown Significance.

Pregnancy-associated cervicocephalic arterial dissection is rare, and its pathophysiology remains poorly understood. Despite the hypothesized contribution to pathogenesis, connective tissue diseases and genetic factors are rarely identified in clinical cases. We describe a case of postpartum arterial dissection involving all four cervicocephalic arteries resulting in acute cerebral infarction.

Gene Variation at Immunomodulatory and Cell Adhesion Molecules Loci Impacts Primary Sjögren's Syndrome.

Primary Sjögren's syndrome (pSS) is an autoimmune disease triggered by a combination of environmental and host genetic factors, which results in the focal lymphocytic infiltration of exocrine glands causing eye and mouth dryness. Glandular infiltrates include T and B cell subsets positive for CD5 and/or CD6, two surface scavenger receptors involved in the fine-tuning of intracellular signals mediated by the antigen-specific receptor complex of T (TCR) and B (BCR) cells. Moreover, the epithelial cells of inflamed glands overexpress CD166/ALCAM, a CD6 ligand involved in homo and heterotypic cell adhesion interactions.

Ductular reaction promotes intrahepatic angiogenesis through Slit2-Roundabout 1 signaling.

Background And Aims: Ductular reaction (DR) expands in chronic liver diseases and correlates with disease severity. Besides its potential role in liver regeneration, DR plays a role in the wound-healing response of the liver, promoting periductular fibrosis and inflammatory cell recruitment. However, there is no information regarding its role in intrahepatic angiogenesis.

Directed differentiation of human induced pluripotent stem cells to hepatic stellate cells.

Hepatic stellate cells (HSCs) are nonparenchymal liver cells responsible for extracellular matrix homeostasis and are the main cells involved in the development of liver fibrosis following injury. The lack of reliable sources of HSCs has hence limited the development of complex in vitro systems to model liver diseases and toxicity. Here we describe a protocol to differentiate human induced pluripotent stem cells (iPSCs) into hepatic stellate cells (iPSC-HSCs).

Programmed Death Ligand 1 Is Overexpressed in Liver Macrophages in Chronic Liver Diseases, and Its Blockade Improves the Antibacterial Activity Against Infections.

Background And Aims: Bacterial infections are common and severe in cirrhosis, but their pathogenesis is poorly understood. Dysfunction of liver macrophages may play a role, but information about their function in cirrhosis is limited. Our aims were to investigate the specific profile and function of liver macrophages in cirrhosis and their contribution to infections.

A mini-review of procedural sedation and analgesia in the emergency department.

Procedural sedation and analgesia (PSA) is performed for a variety of indications in emergency departments (EDs). Although the practice of PSA in the ED is somewhat unique from other clinical areas, there is currently no guideline for this practice in Japan. Policy statements and guidelines for PSA have been published in Europe and North America.

Ductular Reaction Cells Display an Inflammatory Profile and Recruit Neutrophils in Alcoholic Hepatitis.

Chronic liver diseases are characterized by the expansion of ductular reaction (DR) cells and the expression of liver progenitor cell (LPC) markers. In alcoholic hepatitis (AH), the degree of DR expansion correlates with disease progression and short-term survival. However, little is known about the biological properties of DR cells, their impact on the pathogenesis of human liver disease, and their contribution to tissue repair.

Measuring case-mix and outcome for older people in acute hospital care across Europe: the development and potential of the ACMEplus instrument.

Aim: To identify case-mix variables measured shortly after admission to be included in a patient classification system (ACMEplus) that best explains hospital outcome for older people in different health care systems.

Design: Observational prospective cohort study collecting patient factors (sociodemographics, functional, mental, clinical, administrative and perceived health) at different time assessments.

Methods: Multicentre study involving eight hospitals in six European countries (United Kingdom, Spain, Italy, Finland, Greece and Poland).

Modelling microbial growth in structured foods: towards a unified approach.

Historically, the ability of foods to support the growth of spoilage organisms and food-borne pathogens has been assessed by inoculating a food with an organism of interest, and following its growth over a period of time. Information gained from such challenge tests, together with knowledge of the organoleptic stability of the product, can then be used to determine an appropriate shelf-life for the food. Whilst this approach may be seen as the "gold-standard" of microbiological assessment of food, it is both time-consuming and costly.

A quantitative approach for studying the effect of heat treatment conditions on resistance and recovery of Bacillus cereus spores.

When a bacterial population undergoes an unfavourable transient increase in temperature, a death phase followed by a lag and growth phase are observed for the surviving and cultivable population. The lag phase is of great interest in regard to food safety, but for bacterial spores, very few studies have been carried out on the evolution of lag time versus heat treatment duration. The experiments monitored on spores of two strains of Bacillus cereus showed a biphasic evolution of the lag time for germination of stressed spores with increase in heat treatment duration, at 90 degrees C, 95 degrees C and 100 degrees C and for different recovery conditions in laboratory medium.

Involvement of a rhamnolipid-producing strain of Pseudomonas aeruginosa in the degradation of polycyclic aromatic hydrocarbons by a bacterial community.

A rhamnolipid-producing strain of Pseudomonas aeruginosa GL1 was isolated from a bacterial community growing on a mixture of polycyclic aromatic hydrocarbons (PAH) as sole carbon source. Strain GL1 did not grow on PAH but grew on known degradation metabolites of phenanthrene (O-phthalic acid) and of naphthalene (salicylic acid). In co-culture with a phenanthrene-degrading strain, Ps.

Potential influence of previous medical pathology on use of thrombolysis in the elderly with suspected acute myocardial infarction.

A perceived reluctance by many doctors to consider the use of thrombolytic therapy in elderly patients with acute myocardial infarction prompted us to investigate the potential influence of pre-existing medical pathology on use of fibrinolysis. Of 251 patients consecutively admitted to hospital with suspected acute myocardial infarction, absolute contra-indications to thrombolysis were found in 9 (4%) patients and relative contra-indications in a further 82 (31%) patients. This study suggests that the presence of contra-indications plays a small role in influencing the potential use of thrombolysis in the elderly.