Microcirculatory changes in the liver of patients with refractory ascites and their relationship with diabetes and alcohol.

Objectives: The determinants of refractory ascites have not been fully characterized. The aims of this study were to assess liver histopathological alterations associated with refractory ascites and their relationship with comorbidities.

Methods: Consecutive patients with cirrhosis who underwent liver transplantation were retrospectively included.

Amyloid-β Interactions with Lipid Rafts in Biomimetic Systems: A Review of Laboratory Methods.

Biomimetic lipid bilayer systems are a useful tool for modeling specific properties of cellular membranes in order to answer key questions about their structure and functions. This approach has prompted scientists from all over the world to create more and more sophisticated model systems in order to decipher the complex lateral and transverse organization of cellular plasma membranes. Among a variety of existing biomembrane domains, lipid rafts are defined as small, dynamic, and ordered assemblies of lipids and proteins, enriched in cholesterol and sphingolipids.

Potential of regulatory T-cell-based therapies in the management of severe COVID-19.

https://bit.ly/3eKqWPo

Germline genetic factors in the pathogenesis of myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPN) are clonal hematological malignancies that lead to overproduction of mature myeloid cells. They are due to acquired mutations in genes encoding for AK2, MPL and CALR that result in the activation of the cytokine receptor/JAK2 signaling pathway. In addition, it exists germline variants that can favor the initiation of the disease or may affect its phenotype.

Transposable elements, circular RNAs and mitochondrial transcription in age-related genomic regulation.

Our understanding of the molecular regulation of aging and age-related diseases is still in its infancy, requiring in-depth characterization of the molecular landscape shaping these complex phenotypes. Emerging classes of molecules with promise as aging modulators include transposable elements, circRNAs and the mitochondrial transcriptome. Analytical complexity means that these molecules are often overlooked, even though they exhibit strong associations with aging and, in some cases, may directly contribute to its progress.

Verotoxin-1-Induced ER Stress Triggers Apoptotic or Survival Pathways in Burkitt Lymphoma Cells.

Shiga toxins (Stxs) expressed by the enterohaemorrhagic and enteric pathogens are protein synthesis inhibitors. Stxs have been shown to induce apoptosis via the activation of extrinsic and intrinsic pathways in many cell types (epithelial, endothelial, and B cells) but the link between the protein synthesis inhibition and caspase activation is still unclear. Endoplasmic reticulum (ER) stress induced by the inhibition of protein synthesis may be this missing link.

Effect of High-Speed Blade Coating on Electrical Characteristics in Polymer Based Transistors.

We explore the effect of high-speed blade coating on electrical characteristics of conjugated polymer-based thin-film transistors (TFTs). As the blade-coating speed increased, the thickness of the polymer thin-film was naturally increased while the surface roughness was found to be unchanged. Polymer TFTs show two remarkable tendencies on the magnitude of field-effect mobility with increasing blade-coating speed.

Targeted lipidomics reveals extensive changes in circulating lipid mediators in patients with acutely decompensated cirrhosis.

Background & Aims: Acute-on-chronic liver failure (ACLF) is a newly described syndrome, which develops in patients with acute decompensation of cirrhosis, and is characterized by intense systemic inflammation, multiple organ failures and high short-term mortality. The profile of circulating lipid mediators, which are endogenous signaling molecules that play a major role in inflammation and immunity, is poorly characterized in ACLF.

Methods: In the current study, we assessed the profile of lipid mediators by liquid chromatography coupled to tandem mass spectrometry in plasma from patients with acute decompensation of cirrhosis, with (n = 119) and without (n = 127) ACLF, and from healthy controls (n = 18).

Appointment reminders to increase uptake of HIV retesting by at-risk individuals: a randomized controlled study in Thailand.

Introduction: Frequent HIV testing of at-risk individuals is crucial to detect and treat infections early and prevent transmissions. We assessed the effect of reminders on HIV retesting uptake.

Methods: The study was conducted within a programme involving four facilities providing free-of-charge HIV, syphilis and hepatitis B and C testing and counselling in northern Thailand.

Innate immune cells in cirrhosis.

Cirrhosis is a multisystemic disease wherein inflammatory responses originating from advanced liver disease and its sequelae affect distant compartments. Patients with cirrhosis are susceptible to bacterial infections, which may precipitate acute decompensation and acute-on-chronic liver failure, both of which are associated with high short-term mortality. Innate immune cells are an essential first line of defence against pathogens.

Improved Characterization of Raft-Mimicking Phase-Separation Phenomena in Lipid Bilayers Using Laurdan Fluorescence with Log-Normal Multipeak Analysis.

The study of biomimetic model membrane systems undergoing liquid-ordered (Lo)-liquid-disordered (Ld) phase separation using spectroscopic methods has played an important role in understanding the properties of lipid rafts in plasma membranes. In particular, the membrane-associated fluorescence probe Laurdan has proved to be a very efficient reporter of Lo-Ld phase separation in lipid bilayers using the general polarization (GP) parameter. A limitation of the GP approach is that it monitors only global average packing so that the contribution of each phase remains undetermined.

The Central Role of Small Vertical Substrates for the Origin of Grasping in Early Primates.

The manual and pedal grasping abilities of primates, characterized by an opposable hallux, flat nails, and elongated digits, constitute a unique combination of features that likely promoted their characteristic use of arboreal habitats. These hand and foot specificities are central for understanding the origins and early evolution of primates and have long been associated with foraging in a fine-branch milieu. However, other arboreal mammals occupy similar niches, and it remains unclear how substrate type may have exerted a selective pressure on the acquisition of nails and a divergent pollex/hallux in primates or in what sequential order these traits evolved.

The Gene Balance Hypothesis: Epigenetics and Dosage Effects in Plants.

Dosage effects in plants are caused by changes in the copy number of chromosomes, segments of chromosomes, or multiples of individual genes. Genes often exhibit a dosage effect in which the amount of product is closely correlated with the number of copies present. However, when larger segments of chromosomes are varied, there are trans-acting effects across the genome that are unleashed that modulate gene expression in cascading effects.

Six-month outcomes of teduglutide treatment in adult patients with short bowel syndrome with chronic intestinal failure: A real-world French observational cohort study.

Background & Aims: Teduglutide, a GLP-2-analog, has proven effective in two placebo-controlled studies in reducing parenteral support (PS) in patients with short bowel syndrome-associated intestinal failure (SBS-IF) after 24 weeks. The aim of this study was to describe in a real-life situation the effects of teduglutide treatment and their predictive factors.

Methods: We included 54 consecutive SBS-IF patients treated with teduglutide in France for at least 6 months from 10 expert centers.

Innate immune receptor NOD2 mediates LGR5 intestinal stem cell protection against ROS cytotoxicity via mitophagy stimulation.

The nucleotide-binding oligomerization domain-containing protein 2 (NOD2) agonist muramyl dipeptide (MDP), a peptidoglycan motif common to all bacteria, supports leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) intestinal stem cell (ISC) survival through NOD2 activation upon an otherwise lethal oxidative stress-mediated signal. However, the underlying protective mechanisms remain unknown. Here, using irradiation as stressor and primarily murine-derived intestinal organoids as a model system, we show that MDP induced a significant reduction of total and mitochondrial reactive oxygen species (ROS) within ISCs, which was associated with mitophagy induction.

Iron chelation by curcumin suppresses both curcumin-induced autophagy and cell death together with iron overload neoplastic transformation.

Iron overload, notably caused by hereditary hemochromatosis, is an excess storage of iron in various organs that causes tissue damage and may promote tumorigenesis. To manage that disorder, free iron depletion can be induced by iron chelators like deferoxamine that are of increasing interest also in the cancer field since iron stock could be a potent target for managing tumorigenesis. Curcumin, a well-known active substance extracted from the turmeric rhizome, destabilizes endoplasmic reticulum, and secondarily lysosomes, thereby increasing mitophagy/autophagy and subsequent apoptosis.

Identification of Electrostatic Epitopes in Flavivirus by Computer Simulations: The PROCEEDpKa Method.

Viruses are enthusiastically studied due to the great impact that these organisms can have on human health. Computational approaches can contribute offering tools that can shed light on important molecular mechanisms that help to design new diagnostic procedures. Several cellular processes between the immune-host system and the pathogenic organism are dependent on specific intermolecular interactions.

One-year outcome of patients admitted after cardiac arrest compared to other causes of ICU admission. An ancillary analysis of the observational prospective and multicentric FROG-ICU study.

Objective: While cardiac arrest (CA) patients discharged alive from intensive care unit (ICU) are considered to have good one-year survival but potential neurological impairment, comparisons with other ICU sub-populations non-admitted for CA purpose are still lacking. This study aimed to compare long-term outcome and health-related quality of life (HRQOL) between CA patients and patients admitted to ICU for all other causes.

Methods: In 1635 patients discharged alive from 21 European ICUs in an ancillary analysis of a prospective multicentric cohort, we compared CA causes of ICU admission to all other causes of ICU admissions (named non-CAs).

Impact of Counseling Methods on HIV Retesting Uptake in At-Risk Individuals: A Randomized Controlled Study.

Systematic face-to-face pre-HIV test counseling is costly and may discourage clients to present for regular testing. In a randomized, controlled, non-inferiority trial conducted in four facilities providing free-of-charge anonymous HIV testing in Thailand, participants received either: standard counseling according to national guidelines (reference); computer-assisted counseling: interactive counseling on a tablet computer followed by an invitation to ask questions to the counselor; or on-demand counseling: invitation to ask questions to the counselor. Primary endpoint was a HIV retest within 7 months after enrolment visit.