Protein is expressed in all major organs after intravenous infusion of mRNA-lipid nanoparticles in swine.

delivery of mRNA is promising for the study of gene expression and the treatment of diseases. Lipid nanoparticles (LNPs) enable efficient delivery of mRNA constructs, but protein expression has been assumed to be limited to the liver. With specialized LNPs, delivery to extrahepatic tissue occurs in small animal models; however, it is unclear if global delivery of mRNA to all major organs is possible in humans because delivery may be affected by differences in innate immune response and relative organ size.

siRNA-mediated reduction of a circulating protein in swine using lipid nanoparticles.

Genetic manipulation of animal models is a fundamental research tool in biology and medicine but is challenging in large animals. In rodents, models can be readily developed by knocking out genes in embryonic stem cells or by knocking down genes through delivery of nucleic acids. Swine are a preferred animal model for studying the cardiovascular and immune systems, but there are limited strategies for genetic manipulation.

Ruggedized Self-Propelling Hemostatic Gauze Delivers Low Dose of Thrombin and Systemic Tranexamic Acid and Achieves High Survival in Swine With Junctional Hemorrhage.

Introduction: Hemorrhage is responsible for 91% of preventable prehospital deaths in combat. Bleeding from anatomic junctions such as the groin, neck, and axillae make up 19% of these deaths, and reports estimate that effective control of junctional hemorrhage could have prevented 5% of fatalities in Afghanistan. Hemostatic dressings are effective but are time-consuming to apply and are limited when proper packing and manual pressure are not feasible, such as during care under fire.

Danon disease in a Sardinian family: different aspects of the same mutation-a case report.

Background: Danon disease (DD) is a rare X-linked disorder due to mutations in the lysosome-associated membrane protein 2 gene. It is characterized by a clinical triad of hypertrophic cardiomyopathy, skeletal myopathy, and a variable degree of intellectual disability.

Case Summary: In this case series, we describe a mother and her son affected by DD, highlighting consistent clinical severity despite the expected variability related to gender.

First-line cetuximab + platinum-based therapy for recurrent/metastatic head and neck squamous cell carcinoma: A real-world observational study-ENCORE.

Background: ENCORE, an observational, prospective, open-label study, investigated real-world treatment practices and outcomes with cetuximab plus platinum-based therapy (PBT) in first-line (1L) recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

Aims: This multinational study aimed to investigate the long-term use of cetuximab plus PBT for 1L R/M SCCHN in a clinical setting. In particular, this study aimed to explore clinical considerations such as the decision to prescribe cetuximab plus PBT in R/M SCCHN, the mode and duration of treatment, and patient outcomes.

Self-propelling thrombin powder enables hemostasis with no observable recurrent bleeding or thrombosis over 3 days in a porcine model of upper GI bleeding.

Background And Aims: Hemostatic powders used to manage upper GI bleeding continue to exhibit high recurrent bleeding rates. Previously, self-propelling thrombin powder (SPTP) sprayed endoscopically managed severe Forrest class 1A bleeding. Here, we evaluate SPTP in a 3-day recovery model of diffuse ulcerated bleeding.

Liquid-infused microstructured bioadhesives halt non-compressible hemorrhage.

Non-compressible hemorrhage is an unmet clinical challenge that accounts for high mortality in trauma. Rapid pressurized blood flows under hemorrhage impair the function and integrity of hemostatic agents and the adhesion of bioadhesive sealants. Here, we report the design and performance of bioinspired microstructured bioadhesives, formed with a macroporous tough xerogel infused with functional liquids.

A peculiar family with recurrent self-limited epileptic syndrome and associated developmental disorders in six girls.

We describe a complex family with two couples (two sisters who married two brothers) with consistent social and neuropsychiatric problems, originally from Sardinia. Each couple had three daughters, which shared electroclinical epileptic syndrome and developmental disorders. All patients suffered from mild to moderate intellectual disability, speech difficulties and behavioural disorders.

Percutaneous delivery of self-propelling thrombin-containing powder increases survival from noncompressible truncal hemorrhage in a swine model of coagulopathy and hypothermia.

Background: Noncompressible truncal hemorrhage (NCTH) remains a leading cause of preventable death on the battlefield. Definitively managing severe NCTH requires surgery within the first hour after injury, which is difficult when evacuating casualties from remote and austere environments. During delays to surgery, hemostatic interventions that are performed prehospital can prevent coagulopathy and hemorrhagic shock and increase the likelihood that casualties survive to receive definitive care.

Toward Optimal Learning of the Gesture in Laparoscopic Surgery: Methodology and Performance.

Classical surgical education has to face both a forensic reality and a technical issue: to train a learner in more complex techniques in an increasingly short time. Moreover, surgical training is still based on an empirical hierarchical relationship in which learners must reproduce a sequence of actions in a situation of strong emotional pressure. However, the effectiveness of learning and its quality are linked to the emotional states in which learners find themselves.

Videoconferencing for Large Animal Trauma Experiments During COVID-19: A Cross-Continent Experience.

Introduction: COVID-19 shutdowns in many research facilities across North America impacted preclinical trauma-related research and development. Shutdown limited the speed and resources available for large animal experiments necessary for advancing medical devices and technologies. However, the pandemic led to the rapid adoption and expansion of videoconferencing in social circles, workplaces, and primary care health settings.

Percutaneous delivery of self-propelling hemostatic powder for managing non-compressible abdominal hemorrhage: a proof-of-concept study in swine.

Introduction: Non-compressible intra-abdominal hemorrhage (NCIAH) is a major cause of preventable death on the battlefield and in civilian trauma. Currently, it can only be definitively managed with surgery, as there are limited strategies for controlling ongoing NCIAH in the prehospital environment. We hypothesized that a self-propelling thrombin-containing powder (SPTP) could increase survival in a swine model of NCIAH when delivered percutaneously into the closed abdomen using an engineered spray system.

Emerging gene therapies for enhancing the hemostatic potential of platelets.

Platelet transfusions are an integral component of balanced hemostatic resuscitation protocols used to manage severe hemorrhage following trauma. Enhancing the hemostatic potential of platelets could lead to further increases in the efficacy of transfusions, particularly for non-compressible torso hemorrhage or severe hemorrhage with coagulopathy, by decreasing blood loss and improving overall patient outcomes. Advances in gene therapies, including RNA therapies, are leading to new strategies to enhance platelets for better control of hemorrhage.

Severe upper gastrointestinal bleeding is halted by endoscopically delivered self-propelling thrombin powder: A porcine pilot study.

Hemostatic powders have emerged recently to treat upper gastrointestinal bleeding (UGIB). Previously, we developed a novel self-propelling thrombin powder (SPTP) that effectively manages external pulsatile arterial bleed without compression, by effervescing and carrying thrombin into the wound. Here, we tested if SPTP, sprayed endoscopically, can manage severe UGIB in a live porcine model.

Prognostic nomogram in patients with metastatic adenoid cystic carcinoma of the salivary glands.

Background: Distant metastases in adenoid cystic carcinoma (ACC) are common. There is no consensus on the management of metastatic disease because no therapeutic approach has demonstrated improvement in overall survival (OS) and because of prolonged life expectancy. The aim of this study is to build and validate a prognostic nomogram for metastatic ACC patients.

The Genetic Landscape of Dystrophin Mutations in Italy: A Nationwide Study.

Dystrophinopathies are inherited diseases caused by mutations in the dystrophin () gene for which testing is mandatory for genetic diagnosis, reproductive choices and eligibility for personalized trials. We genotyped the gene in our Italian cohort of 1902 patients (BMD n = 740, 39%; DMD n =1162, 61%) within a nationwide study involving 11 diagnostic centers in a 10-year window (2008-2017). In DMD patients, we found deletions in 57%, duplications in 11% and small mutations in 32%.

Topical tranexamic acid inhibits fibrinolysis more effectively when formulated with self-propelling particles.

Background: Endogenous fibrinolytic activation contributes to coagulopathy and mortality after trauma. Administering tranexamic acid (TXA), an antifibrinolytic agent, is one strategy to reduce bleeding; however, it must be given soon after injury to be effective and minimize adverse effects. Administering TXA topically to a wound site would decrease the time to treatment and could enable both local and systemic delivery if a suitable formulation existed to deliver the drug deep into wounds adequately.

Why has transparency evolved in aposematic butterflies? Insights from the largest radiation of aposematic butterflies, the Ithomiini.

Defended species are often conspicuous and this is thought to be an honest signal of defences, i.e. more toxic prey are more conspicuous.

Outcome of recurrent and metastatic head and neck squamous cell cancer patients after first line platinum and cetuximab therapy.

Objectives: Second-line chemotherapy in recurrent and/or metastatic head and neck cancer (r/mHNSCC) patients showed dismal results with limited tumor response and reduced life expectancy. Outside of clinical trials, data on efficacy of second line treatment after first line anti-EGFR-AB combination therapy are not available.

Material And Methods: Data regarding r/mHNSCC consecutive pts treated with cetuximab and platinum from 2009 to 2014 at our center were retrospectively collected.

Presence of Contracaecum spp. in teleosts cultured and fished in Sardinia.

This study reports the results of the finding of Contracaecum spp. during a survey on endoparasites isolated from cultured and wild fish and also from some cephalopods caught in Sardinian waters. Contracaecum spp.

Triplet-primed PCR is more sensitive than southern blotting-long PCR for the diagnosis of myotonic dystrophy type1.

Genetic testing of myotonic dystrophy type 1 (DM1) is very important because it enables the diagnosis and indicates the severity of the disease. Mutation analysis is based on the detection of the number of CTG triplets in the 3' untranslated region of the myotonic dystrophy protein kinase (DMPK) gene. Sometimes it could be complicated by the presence of different patterns of repeat interruptions in the 5' and 3' ends of the expanded alleles recently described in about 3% to 5% of patients.

A new deletion in 5'-end of dystrophin gene removing M and P promoters and dystrophin muscle enhancers.

We describe a 3-year-old boy who, at age of 8 months, during investigations for upper respiratory tract infection was found to have an incidental grossly elevated CK of 20,000 UI/l. Investigations showed only mild calf hypertrophy and absent Gower's sign, normal cognitive function. Electromyography (EMG) showed myopathic features.