👤 Marco Paolini

Inflammation is increasingly implicated in the pathophysiology of mood and psychotic disorders. Integrating blood biomarkers and brain imaging may help uncover mechanistic pathways and guide targeted interventions. To identify shared and distinct multivariate patterns of peripheral inflammation and gray matter volume (GMV) in early-stage depressive and psychotic disorders using a transdiagnostic machine learning approach. The naturalistic multicenter PRONIA study was conducted between February 2014 and May 2019 with a follow-up period of up to 36 months; baseline data were analyzed between August 2021 and April 2024. Eight sites, including inpatient and outpatient facilities, in 5 European countries (Germany, Italy, Switzerland, Finland, and the United Kingdom) were included. The study included individuals with recent-onset depression (ROD, n = 163) or psychosis (ROP, n = 177) or clinical high-risk states for psychosis (CHR-P, n = 172), all with minimal medication exposure, and healthy control (HC) individuals (n = 166). Structural magnetic resonance imaging (MRI), peripheral assays of cytokines (eg, interleukin [IL] 6, IL-1β, tumor necrosis factor [TNF] α, C-reactive protein [CRP], brain-derived neurotrophic factor [BDNF], S100 calcium-binding protein B [S100B]); clinical assessments; neurocognitive testing. After data collection, sparse partial least squares was used to identify latent brain-blood signatures. Support vector machine classification evaluated psychosocial and neurocognitive predictors of signature expression using repeated nested cross-validation. A total of 678 participants (346 [51.0%] female; median [IQR] age, 24.0 [20.9-28.9] years) were included. Four signatures were identified. A psychosis signature (ρ = 0.27; P = .002) differentiated ROP from CHR-P with elevated IL-6, TNF-α, and reduced CRP, alongside GMV shifts in corticothalamic circuits. A depression signature (ρ = 0.19; P = .02) differentiated ROD from HC individuals with elevated IL-1β, IL-2, IL-4, S100B, and BDNF and GMV reductions in limbic regions. Additional signatures reflected age (ρ = 0.67) and sex or MRI quality (ρ = 0.53). Psychosocial features, including a differential childhood trauma pattern, predicted both the psychosis (balanced accuracy [BAC] = 67.2%) and depression (BAC = 78.0%) signatures. Cognitive performance predicted only the psychosis signature (BAC = 65.1%). In this study, early-stage depression and psychosis exhibited distinct neurobiological signatures involving immune and neuroanatomical markers, challenging fully dimensional disease models. These signatures are shaped by childhood trauma and cognition and may support biologically informed early interventions. Show less

Laparoscopic surgery of obese patients still represents a real challenge in clinical practice. High-pressure pneumoperitoneum and steep Trendelenburg position are the main anesthesiologic indications to laparotomic conversion. The aim of this prospective study was to assess effectiveness and safety of low-pressure laparoscopic (LPL) procedures using a subcutaneous abdominal wall-retraction (LaparoTenser ®). We enrolled obese patients (BMI ≥ 30 kg/m A total of 33 patients were included in this study. The median age was 69 (range: 40-83), with a median BMI of 39 kg/m LPL technique using the LaparoTenser ® device is feasible and safe in morbidly obese patients. The wall-lifting device enables adequate viscera exposure creating a large intra-abdominal operative space avoiding the disadvantages of intraperitoneal high-pressure and CO Show less

Hypertriglyceridemia is a common feature of metabolic syndrome (MetS), as well as of non-alcoholic fatty liver disease (NAFLD), which is considered the hepatic manifestation of MetS. Fat accumulation in hepatocytes may alter mitochondrial homeostasis predisposing to advanced liver disease. Here, we report a case of a 40-year-old woman with early aggressive NAFLD due to severe hypertriglyceridemia that ensued from a combination of genetic variants and additional metabolic risk factors. Genetic screening was performed by using whole-exome sequencing (WES), and mitochondrial structures were evaluated by TEM. At presentation, the patient is reported to have hepatomegaly, hypertriglyceridemia, and raised transaminases. Genetic analysis revealed that the patient beard heritable alterations in genes implicated in lipid handling, among which The anomalies reported may expand the phenotypic spectrum of mitochondrial abnormalities observed in patients with NAFLD, which may contribute to the switching toward a progressive disease. Show less

The regulation of translation initiation factor 2 (eIF2) is important for erythroid survival and differentiation. Lack of iron, a critical component of heme and hemoglobin, activates Heme Regulated Inhibitor (HRI). This results in phosphorylation of eIF2 and reduced eIF2 availability, which inhibits protein synthesis. Translation of specific transcripts such as Atf4, however, is enhanced. Upstream open reading frames (uORFs) are key to this regulation. The aim of this study is to investigate how tunicamycin treatment, that induces eIF2 phosphorylation, affects mRNA translation in erythroblasts. Ribosome profiling combined with RNA sequencing was used to determine translation initiation sites and ribosome density on individual transcripts. Treatment of erythroblasts with Tunicamycin (Tm) increased phosphorylation of eIF2 2-fold. At a false discovery rate of 1%, ribosome density was increased for 147 transcripts, among which transcriptional regulators such as Atf4, Tis7/Ifrd1, Pnrc2, Gtf2h, Mbd3, JunB and Kmt2e. Translation of 337 transcripts decreased more than average, among which Dym and Csde1. Ribosome profiling following Harringtonine treatment uncovered novel translation initiation sites and uORFs. Surprisingly, translated uORFs did not predict the sensitivity of transcripts to altered ribosome recruitment in presence or absence of Tm. The regulation of transcription and translation factors in reponse to eIF2 phosphorylation may explain the large overall response to iron deficiency in erythroblasts. Show less