Design and preclinical assessment of mRNA-1345 prefusion F glycoprotein-encoding mRNA vaccine for respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract disease in young children and older adults. We designed a codon-optimized mRNA vaccine, mRNA-1345, encoding the RSV F-glycoprotein stabilized in the prefusion (preF) conformation and with a deletion at the cytoplasmic tail. mRNA-1345 cell surface protein expression was higher and detected for longer versus previous mRNA-based RSV vaccine candidates evaluated clinically.

Parenteral Anticoagulation at First Medical Contact Improves Infarct Related Artery Patency in STEMI.

(1) : Acute ST-segment elevation myocardial infarction (STEMI) remains one of the main morbidity and mortality contributors worldwide. Its main treatment, primary percutaneous coronary intervention (pPCI), can only be performed with a high anticoagulation regimen, usually with heparin. There is still not enough evidence regarding the timing of heparin administration.

Peptide-functionalized chitosan-based microcapsules for dual active targeted treatment of lung infections.

Lung infections, such as: pneumonia, chronic obstructive cystic fibrosis, tuberculosis are generally caused by viruses, bacteria and fungi. As these infections are very difficult to treat, new therapeutic approaches are investigated in order to maximize the efficiency of the treatment and to reduce the major complications that can occur. The main objective of this study was focused on the preparation of drug-loaded peptides-functionalized microcapsules, obtained by a double emulsion, based on carboxylated chitosan (CMCS), poly(vinyl alcohol) (PVA) and an activator [4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride] (DMT-MM), for the dual active targeting and treatment of pulmonary infections.

Amnio acid substitution at position 298 of human glucose-6 phosphatase-α significantly impacts its stability in mammalian cells.

Glucose-6-phosphatase-α (G6Pase-α) catalyzes the hydrolysis of glucose-6-phosphate to glucose and functions as a key regulator in maintaining blood glucose homeostasis. Deficiency in G6Pase-α causes glycogen storage disease 1a (GSD1a), an inherited disorder characterized by life-threatening hypoglycemia and other long-term complications. We have developed a potential mRNA-based therapy for GSD1a and demonstrated that a human G6Pase-α (hG6Pase-α) variant harboring a single serine (S) to cysteine (C) substitution at the amino acid site 298 (S298C) had > twofold increase in protein expression, resulting in improved in vivo efficacy.

The Profile and All-Cause In-Hospital Mortality Dynamics of St-Segment Elevation Myocardial Infarction Patients during the Two Years of the COVID-19 Pandemic.

During the coronavirus pandemic 2019 (COVID-19), some studies showed differences in the profile of subjects presenting with acute coronary syndromes as well as in overall mortality due to the delay of presentation and other complications. The purpose of this study was to compare the profile and outcomes, with emphasis on all-cause in-hospital mortality, of ST-elevation myocardial infarction (STEMI) subjects presenting to the emergency department during the pandemic period compared with a control group from the previous year, 2019. The study enrolled 2011 STEMI cases, which were divided into two groups-pre-pandemic (2019-2020) and pandemic period (2020-2022).

Pulmonary Embolism Risk Assessment Using Blood Copeptin Concentration and Pulmonary Arteries Thrombotic Burden Evaluated by Computer Tomography.

(1) Background: Pulmonary embolism (PE) represents the third most important cardiovascular cause of death after myocardial infarction and stroke. The proper management of this condition is dependent on adequate risk stratification, due to the life-threatening complications of more aggressive therapies such as thrombolysis. Copeptin is a surrogate marker of vasopressin which is found increased in several cardiovascular conditions.

Nanoporous Membranes for the Filtration of Proteins from Biological Fluids: Biocompatibility Tests on Cell Cultures and Suggested Applications for the Treatment of Alzheimer's Disease.

Background: Alzheimer's disease has a significant epidemiological and socioeconomic impact, and, unfortunately, the extensive research focused on potential curative therapies has not yet proven to be successful. However, in recent years, important steps have been made in the development and functionalization of nanoporous alumina membranes, which might be of great interest for medical use, including the treatment of neurodegenerative diseases. In this context, the aim of this article is to present the synthesis and biocompatibility testing of a special filtrating nano-membrane, which is planned to be used in an experimental device for Alzheimer's disease treatment.

Artificial intelligence and cloud based platform for fully automated PCI guidance from coronary angiography-study protocol.

Ischemic heart disease represent a heavy burden for the medical systems irrespective of the methods used for diagnosis and treatment of such patients in the daily medical routine. The present paper depicts the protocol of a study whose main aim is to develop, implement and test an artificial intelligence algorithm and cloud based platform for fully automated PCI guidance using coronary angiography images. We propose the utilisation of multiple artificial intelligence based models to produce three-dimensional coronary anatomy reconstruction and assess function- post-PCI FFR computation- for developing an extensive report describing and motivating the optimal PCI strategy selection.

Increasing clinical impact and microbiological difficulties in diagnosing coagulase-negative staphylococci in infective endocarditis - a review starting from a series of cases.

Coagulase-negative staphylococci (CoNS) are an emergent aetiology of infective endocarditis (IE) on native valves in previously healthy individuals, its presence is associated with prosthetic valves or with other cardiac implants. The identification of CoNS in cultures was customarily seen as contamination, but more recent epidemiological studies have revealed an increasing number of causative and virulent new CoNS species. Starting from two clinical cases of community-acquired CoNS IE on native valves, the review debates the difficulties in identifying CoNS as the causal pathogens, comprising differentiation of contamination from infection in IE, alongside the challenges raised by antibiotic resistance.

uNGAL Predictive Value for Serum Creatinine Decrease in Critically Ill Children.

Acute kidney injury (AKI) occurs frequently in critically ill children, having an incidence of up to 26.9% and is associated with high morbidity and mortality in pediatric intensive care units (PICU). Currently, the decrease in the glomerular filtration rate is calculated using the serum creatinine levels.

In Vitro Anticancer Activity and Oxidative Stress Biomarkers Status Determined by (L.) F.H. Wigg. Dry Extracts.

Lichens represent an important resource for common traditional medicines due to their numerous metabolites that can exert diverse pharmacological activities including anticancer effects. To find new anticancer compounds with fewer side effects and low tumor resistance, a bioprospective study of (L.) F.

Formulations Based on Drug Loaded Aptamer-Conjugated Liposomes as a Viable Strategy for the Topical Treatment of Basal Cell Carcinoma-In Vitro Tests.

Topical liposomal drug formulations containing AS1411-aptamer conjugated liposomes were designed to deliver in a sustained way the 5-fluorouracil to the tumor site but also to increase the compliance of patients with basal cell carcinoma. The 5-fluorouracil penetrability efficiency through the Strat-M membrane and the skin irritation potential of the obtained topical liposomal formulations were evaluated in vitro and the Korsmeyer Peppas equation was considered as the most appropriate to model the drug release. Additionally, the efficiency of cytostatic activity for targeted antitumor therapy and the hemolytic capacity were performed in vitro.

Severe Coronary Artery Disease in a Person Living with HIV.

The pathophysiology of accelerated atherosclerosis in people living with Human Immunofediciency virus (HIV) is complex. Coronary artery disease (CAD) has become an important cause of mortality in these patients. They often have atypical symptoms, leading to frequently missed diagnoses.

Paclitaxel-Loaded Magnetic Nanoparticles Based on Biotinylated -Palmitoyl Chitosan: Synthesis, Characterization and Preliminary In Vitro Studies.

A considerable interest in cancer research is represented by the development of magnetic nanoparticles based on biofunctionalized polymers for controlled-release systems of hydrophobic chemotherapeutic drugs targeted only to the tumor sites, without affecting normal cells. The objective of the paper is to present the synthesis and in vitro evaluation of the nanocomposites that include a magnetic core able to direct the systems to the target, a polymeric surface shell that provides stabilization and multi-functionality, a chemotherapeutic agent, Paclitaxel (PTX), and a biotin tumor recognition layer. To our best knowledge, there are no studies concerning development of magnetic nanoparticles obtained by partial oxidation, based on biotinylated -palmitoyl chitosan loaded with PTX.

Dual mRNA therapy restores metabolic function in long-term studies in mice with propionic acidemia.

Propionic acidemia/aciduria (PA) is an ultra-rare, life-threatening, inherited metabolic disorder caused by deficiency of the mitochondrial enzyme, propionyl-CoA carboxylase (PCC) composed of six alpha (PCCA) and six beta (PCCB) subunits. We herein report an enzyme replacement approach to treat PA using a combination of two messenger RNAs (mRNAs) (dual mRNAs) encoding both human PCCA (hPCCA) and PCCB (hPCCB) encapsulated in biodegradable lipid nanoparticles (LNPs) to produce functional PCC enzyme in liver. In patient fibroblasts, dual mRNAs encoded proteins localize in mitochondria and produce higher PCC enzyme activity vs.

Author Correction: Naturally-occurring cholesterol analogues in lipid nanoparticles induce polymorphic shape and enhance intracellular delivery of mRNA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Evaluation of the Cytotoxic Activity of the (L.) F. H. Wigg Dry Extract.

The secondary metabolites of lichens have proven to be promising sources of anticancer drugs; one of the most important of these is usnic acid, which is a phenolic compound with dibenzofuran structure that is responsible for the numerous biological actions of lichens of genus . As a result, in this study, we related to this phenolic secondary metabolite. The aim of the present study is the evaluation of the cytotoxic activity of (L.

Naturally-occurring cholesterol analogues in lipid nanoparticles induce polymorphic shape and enhance intracellular delivery of mRNA.

Endosomal sequestration of lipid-based nanoparticles (LNPs) remains a formidable barrier to delivery. Herein, structure-activity analysis of cholesterol analogues reveals that incorporation of C-24 alkyl phytosterols into LNPs (eLNPs) enhances gene transfection and the length of alkyl tail, flexibility of sterol ring and polarity due to -OH group is required to maintain high transfection. Cryo-TEM displays a polyhedral shape for eLNPs compared to spherical LNPs, while x-ray scattering shows little disparity in internal structure.

Challenges and Opportunities in Preclinical Research of Synthetic Cannabinoids for Pain Therapy.

Cannabis has been used in pain management since 2900 BC. In the 20th century, synthetic cannabinoids began to emerge, thus opening the way for improved efficacy. The search for new forms of synthetic cannabinoids continues and, as such, the aim of this review is to provide a comprehensive tool for the research and development of this promising class of drugs.

Accelerated Blood Clearance of Lipid Nanoparticles Entails a Biphasic Humoral Response of B-1 Followed by B-2 Lymphocytes to Distinct Antigenic Moieties.

Accelerated blood clearance (ABC) is a phenomenon in which certain pharmaceutical agents are rapidly cleared from the blood upon second and subsequent administrations. ABC has been observed for many lipid-delivery vehicles, including liposomes and lipid nanoparticles (LNP). Previous studies have demonstrated a role for humoral responses against the polyethylene glycol motifs in clearance, but significant gaps remain in our understanding of the mechanism of ABC, and strategies for limiting the impact of ABC in a clinical setting have been elusive.