A potential age-independent MASLD-related liver fibrosis index based on metabolic profiling.

The burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is of immediate concern, as its prevalence is increasing worldwide. MASLD often progresses to liver fibrosis, posing significant health risks. Age-independent, noninvasive tools to evaluate fibrosis are needed to improve diagnostic accuracy across all age groups.

Distinct Platelet Phenotype and Reactivity in Individuals with Permanent Atrial Fibrillation Treated with Direct Oral Anticoagulants: A Pilot Study.

Atrial fibrillation (AF) is linked to an elevated risk of thromboembolic events. Despite the use of guideline-recommended direct anticoagulants (DOACs), a significant proportion of AF patients show a residual risk of thromboembolic events, driven by mechanisms that are not fully understood.We conducted a pilot study to characterize the platelet function in DOACs-treated AF patients, to explore whether an association between platelets and the residual thromboembolic risk exists.

Chemogenetic induction of CA1 hyperexcitability triggers indistinguishable autistic traits in asymptomatic mice differing in Ambra1 expression and sex.

Among the genomic alterations identified as risk factors in mice models of autism spectrum disorders (ASD), heterozygous deletion of Ambra1 (Activating Molecule in Beclin1-Regulated Autophagy) triggers an ASD phenotype associated with hippocampal hyperexcitability exclusively in the female sex although Ambra1 protein is comparably expressed in the hippocampus of symptomatic females and asymptomatic males. Given the intricate relationship between Ambra1 deficiency and sex in the etiology of ASD, we took advantage of asymptomatic mice including Ambra1 males and wild-type (Wt) mice of both sexes to investigate whether their non-pathogenic variations in Ambra1 levels could underlie a differential susceptibility to exhibit ASD-like traits in response to experimental elevation of hippocampal excitability. Here we report that selective activation of inhibitory DREADD in CA1 parvalbumin-positive interneurons (PV-IN) reduces GABAergic currents onto pyramidal neurons (PN), causes social and attentional deficits, and augments the proportion of immature/thin spines in CA1 PN dendrites to the same extent in Ambra1 males and Wt mice of both sexes.

Breakthrough infections after COVID-19 vaccinations do not elicit platelet hyperactivation and are associated with high platelet-lymphocyte and low platelet-neutrophil aggregates.

Background: Severe COVID-19 is associated with an excessive immunothrombotic response and thromboinflammatory complications. Vaccinations effectively reduce the risk of severe clinical outcomes in patients with COVID-19, but their impact on platelet activation and immunothrombosis during breakthrough infections is not known.

Objectives: To investigate how preemptive vaccinations modify the platelet-immune crosstalk during COVID-19 infections.

Distinct platelet crosstalk with adaptive and innate immune cells after adenoviral and mRNA vaccination against SARS-CoV-2.

Background: Genetic-based COVID-19 vaccines have proved to be highly effective in reducing the risk of hospitalization and death. Because they were first distributed in a large-scale population, the adenoviral-based vaccines were linked to a very rare thrombosis with thrombocytopenia syndrome, and the interplay between platelets and vaccinations increasingly gained attention.

Objectives: The objective of this article was to study the crosstalk between platelets and the vaccine-induced immune response.

Chemogenetic rectification of the inhibitory tone onto hippocampal neurons reverts autistic-like traits and normalizes local expression of estrogen receptors in the Ambra1+/- mouse model of female autism.

Female, but not male, mice with haploinsufficiency for the proautophagic Ambra1 gene show an autistic-like phenotype associated with hippocampal circuits dysfunctions which include loss of parvalbuminergic interneurons (PV-IN), decrease in the inhibition/excitation ratio, and abundance of immature dendritic spines on CA1 pyramidal neurons. Given the paucity of data relating to female autism, we exploit the Ambra1 female model to investigate whether rectifying the inhibitory input onto hippocampal principal neurons (PN) rescues their ASD-like phenotype at both the systems and circuits level. Moreover, being the autistic phenotype exclusively observed in the female mice, we control the effect of the mutation and treatment on hippocampal expression of estrogen receptors (ER).

Sex differences at the platelet-vascular interface.

Platelets are multifunctional cells that ensure the integrity of the vascular wall and modulate the immune response at the blood/vascular interface. Their pathological activation results in both thrombosis and inflammation and implicates them in the pathogenesis of vascular disease. Vascular diseases are sexually dimorphic in terms of incidence, clinical presentation, outcome, and efficacy of anti-platelet therapy.