Solution biophysics identifies lipid nanoparticle non-sphericity, polydispersity, and dependence on internal ordering for efficacious mRNA delivery.

Lipid nanoparticles (LNPs) are the most advanced delivery system currently available for RNA therapeutics. Their development has accelerated since the success of Patisiran, the first siRNA-LNP therapeutic, and the mRNA vaccines that emerged during the COVID-19 pandemic. Designing LNPs with specific targeting, high potency, and minimal side effects is crucial for their successful clinical use.

Roles for Prlhr/GPR10 and Npffr2/GPR74 in feeding responses to PrRP.

Objective: Several groups of neurons in the NTS suppress food intake, including Prlh-expressing neurons (NTS cells). Not only does the artificial activation of NTS cells decrease feeding, but also the expression of Prlh (which encodes the neuropeptide PrRP) and neurotransmission by NTS neurons contributes to the restraint of food intake and body weight, especially in animals fed a high fat diet (HFD). We set out to determine roles for putative PrRP receptors in the response to NTS PrRP and exogenous PrRP-related peptides.

Efficacy, Safety, and Immunogenicity of the MATISSE (Maternal Immunization Study for Safety and Efficacy) Maternal Respiratory Syncytial Virus Prefusion F Protein Vaccine Trial.

Objective: To evaluate descriptive efficacy data, exploratory immunogenicity data, and safety follow-up through study completion from the global, phase 3 MATISSE (Maternal Immunization Study for Safety and Efficacy) maternal vaccination trial of bivalent respiratory syncytial virus (RSV) prefusion F protein vaccine (RSVpreF).

Methods: MATISSE was a phase 3, randomized, double-blinded, placebo-controlled trial. Healthy pregnant participants aged 49 years or younger at 24-36 weeks of gestation were randomized (1:1) to receive a single RSVpreF 120 micrograms or placebo dose.

Community health promotion and disaster recovery: a PhotoVoice project in Comerío, Puerto Rico.

Background: PhotoVoice - a series of workshops involving participatory photography and narrative-building - was employed in the rural town of Comerío, Puerto Rico (PR) to describe disaster recovery in a rural setting and foster policy dialogue.

Methods: Using PhotoVoice workshops and ethnographic observations, the project describes how women affiliated with a local community-based organization described the priorities for disaster recovery in visual images and narratives. We draw analytically upon theories of intersectionality and coloniality to describe socio-structural and community factors that shape community health in the context of ongoing disasters.

The "Mammograms Available Due to Resources and Education" (MADRE) Study: Rationale and Design.

Background: Latinas suffer disproportionately from breast cancer, partially due to lower uptake of guideline-concordant breast cancer screening. We describe the design of a study to compare two approaches addressing this important public health problem.

Design/methods: We are conducting a 5-year randomized controlled trial.

Cross-Dehydrogenative Coupling of Secondary Amines with Silanes Catalyzed by Agostic Iridium-NSi Species.

An active catalytic system for the cross-dehydrogenative coupling (CDC) of a wide range of secondary amines with silanes is reported. The iridium(III) derivatives [Ir(H)(X)(κ-NSi)(L)] (NSi = {4,8-dimethylquinoline-2-yloxy}dimethylsilyl; L = coe, X = Cl, ; L = coe, X = OTf, ; L = PCy, X = Cl, ; L = PCy X = OTf, ), which are stabilized by a weak yet noticeable Ir···H-C agostic interaction between the iridium and one of the C-H bonds of the 8-Me substituent of the NSi ligand, have been prepared and fully characterized. These species have proven to be effective catalysts for the CDC of secondary amines with hydrosilanes.

Peptide-Functionalized Lipid Nanoparticles for Targeted Systemic mRNA Delivery to the Brain.

Systemic delivery of large nucleic acids, such as mRNA, to the brain remains challenging in part due to the blood-brain barrier (BBB) and the tendency of delivery vehicles to accumulate in the liver. Here, we design a peptide-functionalized lipid nanoparticle (LNP) platform for targeted mRNA delivery to the brain. We utilize click chemistry to functionalize LNPs with peptides that target receptors overexpressed on brain endothelial cells and neurons, namely the RVG29, T7, AP2, and mApoE peptides.

Oxidized mRNA Lipid Nanoparticles for Chimeric Antigen Receptor Monocyte Engineering.

Chimeric antigen receptor (CAR) monocyte and macrophage therapies are promising solid tumor immunotherapies that can overcome the challenges facing conventional CAR T cell therapy. mRNA lipid nanoparticles (mRNA-LNPs) offer a viable platform for engineering of CAR monocytes with transient and tunable CAR expression to reduce off-tumor toxicity and streamline cell manufacturing. However, identifying LNPs with monocyte tropism and intracellular delivery potency is difficult using traditional screening techniques.

Mentoring Early-Career Investigators of HIV/STI Health Disparities Research: A Study Examining the CAPS Visiting Professors Program.

Background: To build research capacity for early-career faculty conducting HIV/STI research with minoritized communities and to enhance diversity in the scientific workforce, the University of California, San Francisco (UCSF) Center for AIDS Prevention (CAPS) conducts a training program for visiting professors (VPs), begun in 1996. VPs are in residence at CAPS for three summers, complete a pilot research project, and prepare National Institutes of Health (NIH) grant proposals. Best practices and key elements for successfully training scholars of color, and others who work with minoritized communities, are identified.

A Qualitative Evidence Synthesis of Continuous Subcutaneous Insulin Infusion: Acceptability, Implementation, Equity.

This work provides a synthesis of the perceptions of people with type 1 diabetes mellitus (T1DM) and healthcare professionals about the acceptability, implementation, and equity of continuous subcutaneous insulin infusion (CSII). A qualitative evidence synthesis was carried out. Three online databases (Medline, Embase, and Web of Science) were searched.

Exploring predictors of COVID-19 precautionary behaviors during the initial rollout of COVID-19 vaccines in a predominately Hispanic sample.

•Precautionary behaviors were lower if primary language in household was Spanish.•Testing positive for COVID-19 was inversely associated with precautionary behaviors.•Healthcare practitioners were the most trusted source of COVID-19 information.

Don't worry, be APPE: Developing and refining a skills-based assessment of student preparedness for advanced pharmacy practice experiences.

Background: The Accreditation Council for Pharmacy Education (ACPE) 2025 Standards charge pharmacy programs to assess student readiness for Advanced Pharmacy Practice Experiences (APPEs), but the method of assessment is not defined. This report describes the process of developing, implementing, and refining an APPE readiness assessment (ARA) that can be adapted to individual institutional needs and learning outcomes.

Educational Activity: The ARA at The University of Texas at El Paso School of Pharmacy, a Hispanic-serving institution, is comprised of two practice areas: drug information and the Pharmacist Patient Care Process, each with multiple objective structured clinical examinations (OSCEs) to mimic how students will apply these skills in required APPE rotations.

Levels of Empathy in Students and Professors with Patients in a Faculty of Dentistry.

Background: Empathy is an attribute that plays an essential role in the dentist-patient therapeutic relationship, clinical care, and treatment adherence, along with providing other benefits. The main objective of this research was to establish the validity, reliability, and invariance of the Jefferson Scale of Empathy and then characterize the empathy levels of students and teachers at a dental school.

Materials And Methods: An observational and cross-sectional study analyzed a sample of undergraduate students and professors from the Universidad Andrés Bello Faculty of Dentistry (Chile) (n = 1727 and n = 267, respectively).

Breaking the final barrier: Evolution of cationic and ionizable lipid structure in lipid nanoparticles to escape the endosome.

In the past decade, nucleic acid therapies have seen a boon in development and clinical translation largely due to advances in nanotechnology that have enabled their safe and targeted delivery. Nanoparticles can protect nucleic acids from degradation by serum enzymes and can facilitate entry into cells. Still, achieving endosomal escape to allow nucleic acids to enter the cytoplasm has remained a significant barrier, where less than 5% of nanoparticles within the endo-lysosomal pathway are able to transfer their cargo to the cytosol.

Lipid nanoparticle-mediated RNA delivery for immune cell modulation.

Lipid nanoparticles (LNPs) have emerged as the preeminent nonviral drug delivery vehicles for nucleic acid therapeutics, as exemplified by their usage in the mRNA COVID-19 vaccines. As a safe and highly modular delivery platform, LNPs are attractive for a wide range of applications. In addition to vaccines, LNPs are being utilized as platforms for other immunoengineering efforts, especially as cancer immunotherapies by modulating immune cells and their functionality via nucleic acid delivery.

Efficient Hydroxyapatite Extraction from Salmon Bone Waste: An Improved Lab-Scaled Physico-Chemico-Biological Process.

The demand for novel tissue grafting and regenerative wound care biomaterials is growing as traditional options often fall short in biocompatibility, functional integration with human tissue, associated cost(s), and sustainability. Salmon aquaculture generates significant volumes of waste, offering a sustainable opportunity for biomaterial production, particularly in osteo-conduction/-induction, and de novo clinical/surgical bone regeneration. Henceforth, this study explores re-purposing salmon waste through a standardized pre-treatment process that minimizes the biological content, followed by a treatment stage to remove proteins, lipids, and other compounds, resulting in a mineral-rich substrate.

Puerto Rican physician's recommendations to mitigate medical migration from Puerto Rico to the mainland United States.

Puerto Rico (PR) is a United States (US) territory with a history of colonial violence, poverty, and government corruption. Due to these sociopolitical factors and natural disasters (e.g.

Investigation of Isobactin Analogues of Teixobactin.

Although teixobactin is a promising antibiotic drug candidate against Gram-positive bacteria, it aggregates to form gels that may limit intravenous administration. We previously reported -acyl isopeptide prodrugs of teixobactin analogues that address the problem of gel formation while retaining antibiotic activity. We termed these compounds .

Fast and facile synthesis of amidine-incorporated degradable lipids for versatile mRNA delivery in vivo.

Lipid nanoparticles (LNPs) are widely used for mRNA delivery, with cationic lipids greatly affecting biodistribution, cellular uptake, endosomal escape and transfection efficiency. However, the laborious synthesis of cationic lipids limits the discovery of efficacious candidates and slows down scale-up manufacturing. Here we develop a one-pot, tandem multi-component reaction based on the rationally designed amine-thiol-acrylate conjugation, which enables fast (1 h) and facile room-temperature synthesis of amidine-incorporated degradable (AID) lipids.