Characterization of a novel conditional knockout mouse model to assess efficacy of mRNA therapy in the context of severe ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle disorder, characterized by hyperammonemia and accompanied by a high unmet patient need. mRNA therapies have been shown to be efficacious in hypomorphic Sparse-fur abnormal skin and hair (Spf-ash) mice, a model of late-onset disease. However, studying the efficacy of ornithine transcarbamylase (OTC) mRNA therapy in traditional knockout mice, a model for severe early-onset OTCD, is hampered by the rapid lethality of the model, and poor lipid nanoparticle (LNP) uptake into neonatal mouse liver.

Multidisciplinary high resolution Geophysical Imaging of Pantano Ripa Rossa Segment of the Irpinia Fault (Southern Italy).

The Irpinia Fault, also known as the Monte Marzano Fault System, located in the Southern Apennines (Italy), is one of the most seismically active structures in the Mediterranean. It is the source of the 1980, Ms 6.9, multi-segment rupture earthquake that caused significant damage and nearly 3,000 casualties.

Oncological Outcomes of Open Versus Minimally Invasive Surgery for Ductal Adenocarcinomas of Pancreatic Head: A Propensity Score Matching Analysis.

Background: Minimally invasive pancreatic resections (MIPRs) have been shown to be safe and feasible, but there is still a lack of high-level evidence on oncological outcomes for cephalic pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to compare the oncological outcomes of patients undergoing MIPR and open pancreatic resection (OPR) for pancreatic head cancer in a single high-volume center.

Methods: Data from a prospectively collected database of patients who underwent radical-intent surgery for resectable and borderline resectable PDAC of the head at our institution between January 2013 and May 2023 were retrieved and analyzed, comparing the surgical and oncological outcomes of MIPR and OPR, using a propensity score matching analysis.

Antibiotic-Loaded Hydrogel for the Treatment of Lower-Limb Fracture-Related Infections: A Single Center's Multidisciplinary Experience.

A fracture-related infection (FRI) is a severe complication of an orthopedic trauma, often leading to challenging treatments and poor outcomes. The surgical strategies are typically categorized into one-stage or two-stage procedures, with the use of systemic and local antibiotics being crucial for infection management. This study assessed the efficacy of an antibiotic-loaded hydrogel (ALH) applied over the internal fixation devices for treating FRIs, comparing the outcomes between the one-stage (OS) and two-stage (TS) reconstructions.

Systemic messenger RNA replacement therapy is effective in a novel clinically relevant model of acute intermittent porphyria developed in non-human primates.

Objective: Acute intermittent porphyria (AIP) is a rare metabolic disorder caused by haploinsufficiency of hepatic porphobilinogen deaminase (PBGD), the third enzyme of the heme biosynthesis. Individuals with AIP experience neurovisceral attacks closely associated with hepatic overproduction of potentially neurotoxic heme precursors.

Design: We replicated AIP in non-human primates (NHPs) through selective knockdown of the hepatic gene and evaluated the safety and therapeutic efficacy of human PBGD (hPBGD) mRNA rescue.