Visualizing lipid nanoparticle trafficking for mRNA vaccine delivery in non-human primates.

mRNA delivered using lipid nanoparticles (LNPs) has become an important subunit vaccine modality, but mechanisms of action for mRNA vaccines remain incompletely understood. Here, we synthesized a metal chelator-lipid conjugate enabling positron emission tomography (PET) tracer labeling of LNP/mRNA vaccines for quantitative visualization of vaccine trafficking in live mice and non-human primates (NHPs). Following i.

Vasoactive Agents in Burn Patients - Perspectives on Angiotensin-II.

Severe burn injury poses significant clinical challenges, often necessitating the use of vasoactive agents to maintain perfusion. This narrative review explores the current landscape of vasoactive agents in acute burn shock resuscitation and severe burn-injured patients who develop septic shock, with a particular focus on the potential role of the novel vasoactive agent, synthetic angiotensin-II (AT-II), in these settings. While catecholamines and vasopressin remain cornerstone therapies, adverse effects, variable patient response, and a new understanding of burn injury pathophysiology highlight the potentially evolving role of vasoactive agents in these clinical scenarios.

Defining methods to improve eSource site start-up practices.

Background: eSource software that transfers patient electronic health record data into a clinical trial electronic case report form holds promise for increasing data quality while reducing data collection, monitoring and source document verification costs. Integrating eSource into multicenter clinical trial start-up procedures could facilitate the use of eSource technologies in clinical trials.

Methods: We conducted a qualitative integrative analysis to identify eSource site start-up key steps, challenges that might occur in executing those steps, and potential solutions to those challenges.

Investigating the Tolerance of Corneal Endothelial Cells to Surgical Fluid Pressure Using Intact Porcine Eyes.

Purpose: It remains unclear if fluid pressures used during cataract surgeries contribute to iatrogenic corneal endothelial cell (CEC) loss.

Methods: A custom experimental platform was used to pressurize the anterior chamber of explanted porcine eyes to surgical fluid pressures of 60 mm Hg or 400 mm Hg for 5 minutes or 60 mm Hg for 45 minutes (n = 8 or 9 per group). The corneal endothelia were stained with a unique combination of nucleic acid viability dyes and were imaged using fluorescence microscopy without removing the cornea from the globe.

Executive control fluctuations underlie behavioral variability in anthropoids.

In complex tasks requiring cognitive control, humans show trial-by-trial alterations in response time (RT), which are evident even when sensory-motor or other contextual aspects of the task remain stable. Exaggerated intra-individual RT variability is associated with brain injuries and frequently seen in aging and neuropsychological disorders. In this opinion, we discuss recent electrophysiology and imaging studies in humans and neurobiological studies in monkeys that indicate RT variability is linked with executive control fluctuation and that prefrontal cortical regions play essential, but dissociable, roles in such fluctuation of control and the resulting behavioral variability.

Cell non-autonomous signaling through the conserved C. elegans glycoprotein hormone receptor FSHR-1 regulates cholinergic neurotransmission.

Modulation of neurotransmission is key for organismal responses to varying physiological contexts such as during infection, injury, or other stresses, as well as in learning and memory and for sensory adaptation. Roles for cell autonomous neuromodulatory mechanisms in these processes have been well described. The importance of cell non-autonomous pathways for inter-tissue signaling, such as gut-to-brain or glia-to-neuron, has emerged more recently, but the cellular mechanisms mediating such regulation remain comparatively unexplored.

Perspectives on Telemedicine Visits Reported by Patients With Cancer.

Importance: The COVID-19 pandemic catalyzed rapid adoption of telemedicine visits for cancer care delivery. However, patients' experiences with telemedicine remain poorly understood.

Objective: To understand patients' satisfaction with telemedicine visits at a comprehensive cancer center.

Comparison of Reference and Biosimilar Medications for Pediatric Noninfectious Uveitis.

Objective/purpose: Compare outcomes and costs of TNF-alpha inhibitor biosimilars to reference medications in the treatment of pediatric NIU.

Methods: Patients 18 years old or below treated with reference or biosimilar TNF-alpha inhibitor for noninfectious uveitis and had a history of active ocular inflammation with at least 1 month of ophthalmology follow-up from January 1, 2013, to June 1, 2023, were included. Retrospective chart review was performed.

The effects of inorganic nitrate supplementation on muscular power and endurance across the menstrual cycle.

Oral inorganic nitrate ([Formula: see text]) supplementation increases nitric oxide (NO) bioavailability and may improve muscular power in males and females, although data in females are limited. Estrogen increases NO bioavailability and fluctuates throughout the menstrual cycle, with low levels in the early follicular (EF) phase and peaking during the late follicular (LF) phase. The purpose of the present study was to examine the effects of [Formula: see text] supplementation on isokinetic peak power, maximal voluntary isometric contraction (MVIC) force, muscular endurance, and recovery from fatigue in healthy young females during the EF and LF phases of the menstrual cycle.

The influence of sex on the effects of inorganic nitrate supplementation on muscular power and endurance.

Inorganic nitrate ([Formula: see text]) supplementation increases nitric oxide (NO) bioavailability and may improve muscular power and endurance, although most studies are in males. Therefore, the present double-blind, randomized, placebo-controlled study examined the effects of [Formula: see text] supplementation on isokinetic peak power, maximal voluntary isometric contraction (MVIC) force, muscular endurance (time-to-task failure; TTF), and recovery from fatigue in young females ( = 12) and males ( = 14). Participants consumed ∼13 mmol [Formula: see text] [beetroot juice (BRJ)], or an identical [Formula: see text]-depleted beverage placebo (PL), for ∼3 days and 2 h before testing visits.

Initial Upper Palaeolithic lithic industry at Cueva Millán in the hinterlands of Iberia.

The extended period of coexistence between Neanderthals and Homo sapiens in Europe coincided with the emergence of regionally distinctive lithic industries, signalling the onset of the Upper Palaeolithic. The Iberian Peninsula was on the periphery of pioneering Upper Palaeolithic developments, with archaeological remains primarily found in northern territories. We report the discovery of an initial Upper Palaeolithic lithic industry at Cueva Millán in the hinterlands of Iberia.

Vaccines combining slow delivery and follicle targeting of antigens increase germinal center B cell clonal diversity and clonal expansion.

Vaccines incorporating slow delivery, multivalent antigen display, or immunomodulation through adjuvants have an important role to play in shaping the humoral immune response. Here we analyzed mechanisms of action of a clinically relevant combination adjuvant strategy, where phosphoserine (pSer)-tagged immunogens bound to aluminum hydroxide (alum) adjuvant (promoting prolonged antigen delivery to draining lymph nodes) are combined with a potent saponin nanoparticle adjuvant termed SMNP (which alters lymph flow and antigen entry into lymph nodes). When employed with a stabilized HIV Env trimer antigen in mice, this combined adjuvant approach promoted substantial enhancements in germinal center (GC) and antibody responses relative to either adjuvant alone.

Mechano-adaptation: Exercise-driven Piezo1 & Piezo2 augmentation and chondroprotection in articular cartilage.

Chondrocytes in adult joints are mechanosensitive post-mitotic quiescent cells with robustly expressed both Piezo1 and Piezo2 ion channels. Here, we examined the mechano-adaptation and Piezo modulations in articular chondrocytes using a mouse exercise model. We first found differential expression patterns of PIEZO1 and PIEZO2 in articular chondrocytes of healthy knee joints; chondrocytes in tibial cartilage (T) exhibit significantly higher PIEZO1 and PIEZO2 than femoral chondrocytes (F).

Protocol for establishing inducible CRISPRd system for blocking transcription factor-binding sites in human pluripotent stem cells.

Transcription factor (TF) gene knockout or knockdown experiments provide comprehensive downstream effects on gene regulation. However, distinguishing primary direct effects from secondary effects remains challenging. To assess the direct effect of TF binding events, we present a protocol for establishing a doxycycline (Dox)-inducible CRISPRd system in human pluripotent stem cells (hPSCs).

Acute physiological effects on macromolecule digestion following oral ingestion of the enzyme blend Elevase® in individuals that had undergone an ileostomy, but were otherwise healthy-a randomized, double blinded, placebo-controlled exploratory study.

Digestive enzymes can selectively degrade proteins, carbohydrates and lipids; and their supplementation alongside food may accelerate the breakdown of complex food matrices, facilitate greater nutrient absorption, decrease food sensitivities and aid in the management of certain disease states. Several intrinsic and extrinsic factors govern food digestion and for every individual this phenomenon is unique. This study was conducted as a randomized, crossover, placebo-controlled design where each participant served as their own control.

Protocol for establishing inducible CRISPR interference system for multiple-gene silencing in human pluripotent stem cells.

Inducible loss-of-function strategies are crucial for understanding gene function. However, creating inducible, multiple-gene knockout models is challenging and time-consuming. Here, we present a protocol for establishing a doxycycline-inducible CRISPR interference (CRISPRi) system to concurrently silence multiple genes in human induced pluripotent stem cells (hPSCs).