Magnetic particle imaging enables nonradioactive quantitative sentinel lymph node identification: feasibility proof in murine models.

Background: Sentinel lymph node biopsy (SLNB) is an important cancer diagnostic staging procedure. Conventional SLNB procedures with Tc radiotracers and scintigraphy are constrained by tracer half-life and, in some cases, insufficient image resolution. Here, we explore an alternative magnetic (nonradioactive) image-guided SLNB procedure.

Carbon Negative Synthesis of Amino Acids Using a Cell-Free-Based Biocatalyst.

Biological systems can directly upgrade carbon dioxide (CO) into chemicals. The CO fixation rate of autotrophic organisms, however, is too slow for industrial utility, and the breadth of engineered metabolic pathways for the synthesis of value-added chemicals is too limited. Biotechnology workhorse organisms with extensively engineered metabolic pathways have recently been engineered for CO fixation.

S100A1ct: A Synthetic Peptide Derived From S100A1 Protein Improves Cardiac Performance and Survival in Preclinical Heart Failure Models.

Background: The EF-hand Ca sensor protein S100A1 has been identified as a molecular regulator and enhancer of cardiac performance. The ability of S100A1 to recognize and modulate the activity of targets such as SERCA2a (sarcoplasmic reticulum Ca ATPase) and RyR2 (ryanodine receptor 2) in cardiomyocytes has mostly been ascribed to its hydrophobic C-terminal α-helix (residues 75-94). We hypothesized that a synthetic peptide consisting of residues 75 through 94 of S100A1 and an N-terminal solubilization tag (S100A1ct) could mimic the performance-enhancing effects of S100A1 and may be suitable as a peptide therapeutic to improve the function of diseased hearts.

Cephalopod-inspired jetting devices for gastrointestinal drug delivery.

Needle-based injections currently enable the administration of a wide range of biomacromolecule therapies across the body, including the gastrointestinal tract, through recent developments in ingestible robotic devices. However, needles generally require training, sharps management and disposal, and pose challenges for autonomous ingestible systems. Here, inspired by the jetting systems of cephalopods, we have developed and evaluated microjet delivery systems that can deliver jets in axial and radial directions into tissue, making them suitable for tubular and globular segments of the gastrointestinal tract.

Embolization of the Middle Meningeal Artery for Chronic Subdural Hematoma.

Background: Patients receiving standard treatment for chronic subdural hematoma have a high risk of treatment failure. The effect of adjunctive middle meningeal artery embolization on the risk of treatment failure in this population remains unknown.

Methods: We randomly assigned patients with symptomatic chronic subdural hematoma to undergo middle meningeal artery embolization as an adjunct to standard treatment (embolization group) or to receive standard treatment alone (control group).

Health Economic Evaluation of Antimicrobial Stewardship, Procalcitonin Testing, and Rapid Blood Culture Identification in Sepsis Care: A 90-Day Model-Based, Cost-Utility Analysis.

Objective: We evaluated the cost-effectiveness of a bundled intervention including an antimicrobial stewardship program (ASP), procalcitonin (PCT) testing, and rapid blood culture identification (BCID), compared with pre-implementation standard care in critically ill adult patients with sepsis.

Methods: We conducted a decision tree model-based cost-effectiveness analysis alongside a previously published pre- and post-implementation quality improvement study. We adopted a public Canadian healthcare payer's perspective.

IL-2/anti-IL-2 antibody complexes augment immune responses to therapeutic cancer vaccines.

One driver of the high failure rates of clinical trials for therapeutic cancer vaccines is likely the inability to sufficiently engage conventional dendritic cells (cDCs), the antigen-presenting cell (APC) subset that is specialized in priming antitumor T cells. Here, we demonstrate that, relative to vaccination with an injectable mesoporous silica rod (MPS) vaccine alone (Vax), combining MPS vaccines with CD122-biased IL-2/anti-IL-2 antibody complexes (IL-2cx) drives ~3-fold expansion of cDCs at the vaccination sites, vaccine-draining lymph nodes, and spleens of treated mice. Furthermore, relative to Vax alone, Vax+IL-2cx led to a ~3-fold increase in the numbers of CD8 T cells and ~15-fold increase in the numbers of NK cells at the vaccination site.

A non-canonical mechanism of GPCR activation.

The goal of designing safer, more effective drugs has led to tremendous interest in molecular mechanisms through which ligands can precisely manipulate the signaling of G-protein-coupled receptors (GPCRs), the largest class of drug targets. Decades of research have led to the widely accepted view that all agonists-ligands that trigger GPCR activation-function by causing rearrangement of the GPCR's transmembrane helices, opening an intracellular pocket for binding of transducer proteins. Here we demonstrate that certain agonists instead trigger activation of free fatty acid receptor 1 by directly rearranging an intracellular loop that interacts with transducers.

Most Athletes Who Fail to Return to Sport After Latarjet Procedure Cite Psychological Factors: A Systematic Review.

Purpose: To identify the return-to-sport (RTS) rate in athletes undergoing a Latarjet procedure while outlining the specific reasons for failure to RTS.

Methods: An electronic literature search was conducted (PubMed/MEDLINE, Scopus, Web of Science). Studies in peer-reviewed journals with Latarjet procedures performed on athletes that reported rates and reasons for failure to RTS were included.

PARP enzyme de novo synthesis of protein-free poly(ADP-ribose).

PARP enzymes transfer ADP-ribose from NAD onto proteins as a covalent modification that regulates multiple aspects of cell biology. Here, we identify an undiscovered catalytic activity for human PARP1: de novo generation of free PAR molecules that are not attached to proteins. Free PAR production arises when a molecule of NAD or ADP-ribose docks in the PARP1 acceptor site and attaches to an NAD molecule bound to the donor site, releasing nicotinamide and initiating ADP-ribose chains that emanate from NAD/ADP-ribose rather than protein.

Neutralizing antibody correlate of protection against severe-critical COVID-19 in the ENSEMBLE single-dose Ad26.COV2.S vaccine efficacy trial.

Assessment of immune correlates of severe COVID-19 has been hampered by the low numbers of severe cases in COVID-19 vaccine efficacy (VE) trials. We assess neutralizing and binding antibody levels at 4 weeks post-Ad26.COV2.

Bilateral Light-Adjustable Lens Implantation in a Patient With 50-Cut Radial Keratotomy.

Purpose: To report a case of Light Adjustable Lens (LAL, RxSight, Aliso Viejo, CA) implantation in a patient with bilateral 50-cut radial keratotomy (RK) and discuss related preoperative, intraoperative, and postoperative considerations.

Methods: A 78-year-old patient with history of bilateral 50-cut RK underwent phacoemulsification with implantation of LALs in both eyes one month apart. Although LAL technology was not approved specifically for addressing limitations in intraocular lens calculation post-RK due to corneal topography irregularity, the patient opted for this lens due to its ability to make post-operative adjustments to its refractive power.

Association of Cerebrovascular Reactivity With 1-Year Imaging and Clinical Outcomes in Small Vessel Disease: An Observational Cohort Study.

Background And Objectives: In patients with cerebral small vessel disease (SVD), impaired cerebrovascular reactivity (CVR) is related to worse concurrent SVD burden, but less is known about cerebrovascular reactivity and long-term SVD lesion progression and clinical outcomes. We investigated associations between cerebrovascular reactivity and 1-year progression of SVD features and clinical outcomes.

Methods: Between 2018 and 2021, we recruited patients from the Edinburgh/Lothian stroke services presenting with minor ischemic stroke and SVD features as part of the Mild Stroke Study 3, a prospective observational cohort study (ISRCTN 12113543).

Inno4Vac Workshop Report Part 1: Controlled Human Influenza Virus Infection Model (CHIVIM) Strain Selection and Immune Assays for CHIVIM Studies, November 2021, MHRA, UK.

Controlled human infection models (CHIMs) are a critical tool for the understanding of infectious disease progression, characterising immune responses to infection and rapid assessment of vaccines or drug treatments. There is increasing interest in using CHIMs for vaccine development and an obvious need for widely available and fit-for-purpose challenge agents. Inno4Vac is a large European consortium working towards accelerating and de-risking the development of new vaccines, including the development of CHIMs for influenza, respiratory syncytial virus and Clostridioides difficile.

Usability and user experience impressions of older adults with cognitive impairment and people with schizophrenia towards GRADIOR, a cognitive rehabilitation program: A cross-sectional study.

Objective: The aim of this study was to evaluate and compare the impressions of older adults with mild dementia/MCI (mild cognitive impairment) and people with schizophrenia towards the usability of GRADIOR (version 4.5) and their user experience (UX) with this computerized cognitive rehabilitation program.

Methods: The impressions towards the usability of GRADIOR and the UX of 41 older adults with mild dementia/MCI and 41 people with schizophrenia were obtained using the User Experience Questionnaire.

On the Cranial Nerves.

The twelve cranial nerves play a crucial role in the nervous system, orchestrating a myriad of functions vital for our everyday life. These nerves are each specialized for particular tasks. Cranial nerve I, known as the olfactory nerve, is responsible for our sense of smell, allowing us to perceive and distinguish various scents.

Leptin-activated hypothalamic BNC2 neurons acutely suppress food intake.

Leptin is an adipose tissue hormone that maintains homeostatic control of adipose tissue mass by regulating the activity of specific neural populations controlling appetite and metabolism. Leptin regulates food intake by inhibiting orexigenic agouti-related protein (AGRP) neurons and activating anorexigenic pro-opiomelanocortin (POMC) neurons. However, whereas AGRP neurons regulate food intake on a rapid time scale, acute activation of POMC neurons has only a minimal effect.