3D Super-Resolution Imaging of PSD95 Reveals an Abundance of Diffuse Protein Supercomplexes in the Mouse Brain.

PSD95 is an abundant scaffolding protein that assembles multiprotein complexes controlling synaptic physiology and behavior. Confocal microscopy has previously shown that PSD95 is enriched in the postsynaptic terminals of excitatory synapses and two-dimensional (2D) super-resolution microscopy further revealed that it forms nanoclusters. In this study, we utilized three-dimensional (3D) super-resolution microscopy to examine the nanoarchitecture of PSD95 in the mouse brain, characterizing the spatial arrangement of over 8 million molecules.

A community-based analysis of security practices regarding over-the-counter skincare products in nationwide retail drug stores.

Access to over-the-counter (OTC) skincare products is critical for managing a wide range of dermatologic conditions, yet recent trends in urban retail stores may jeopardize this accessibility and exacerbate healthcare disparities. However, the emerging trend of securing skincare products behind security glass in urban retail environments poses significant risks to healthcare equity and accessibility. Herein, we aim to quantify the prevalence of skincare products behind security glass in pharmacies within a 25-mile radius of Times Square, New York City.

Characteristics of overnight video-EEG monitoring in infantile epileptic spasms syndrome at 2-week follow-up.

Objective: To determine the optimal duration of electroencephalography (EEG) recording to detect epileptic spasms (ES) based on inpatient overnight video-EEG monitoring in patients with infantile epileptic spasms syndrome (IESS) at the 2-week follow-up.

Methods: Patients with IESS and overnight EEG monitoring between January 2020 and June 2022 were retrospectively reviewed. Time-to-ES, time-to-sleep and time-to-epileptic encephalopathy (EE) per the Burden of Amplitudes and Epileptiform Discharges (BASED 2021) score.

Effects of Coprecipitation Conditions on the Electrochemical Properties of Cobalt-Free LiNiMnAlO Cathodes.

Commercializing high-nickel, cobalt-free cathodes, such as LiNiMnAlO (NMA-90), hinges on effectively incorporating Al during the hydroxide coprecipitation reaction. However, Al coprecipitation is nontrivial as Al possesses unique precipitation properties compared to Ni and Mn, which impact the final precursor morphology and consequently the cathode properties. In this study, the nuance of Al coprecipitation and its influence on the cycling stability of NMA with increasing Al content is elucidated.

Non-Operative Management of Uncomplicated Appendicitis in Children: Can Patients Be Discharged From the Emergency Department?

Introduction: Non-operative management of uncomplicated appendicitis in children is a safe alternative to laparoscopic appendectomy. The purpose of this study is to determine the feasibility of nonoperative outpatient management of uncomplicated appendicitis in pediatric patients.

Methods: A standardized pathway for non-operative outpatient management of uncomplicated appendicitis in children (NOMA-C) was implemented in a university pediatric surgery practice starting October 2021.

Single-molecule digital sizing of proteins in solution.

The physical characterization of proteins in terms of their sizes, interactions, and assembly states is key to understanding their biological function and dysfunction. However, this has remained a difficult task because proteins are often highly polydisperse and present as multicomponent mixtures. Here, we address this challenge by introducing single-molecule microfluidic diffusional sizing (smMDS).

Introduction to Entrustable Professional Activities for Pediatric Surgery.

Background: Entrustable Professional Activities (EPAs) have emerged as a valuable tool in medical education, enabling the assessment of trainee competence in a real-world context. Despite its growing popularity in other medical specialties, the use of EPAs in pediatric surgery is still relatively new.

Methods: This article provides an overview of the development and application of EPAs in pediatric surgery.

Six Years of Quality Improvement in Pectus Excavatum Repair: Implementation of Intercostal Nerve Cryoablation and ERAS Protocols for Patients Undergoing Nuss Procedure.

Background: The Nuss procedure for pectus excavatum is associated with prolonged hospitalizations due to pain. We evaluated implementation of intercostal nerve cryoablation and enhanced recovery after surgery (ERAS) protocols on outcomes of Nuss procedures performed over six years at a single institution.

Methods: This retrospective cohort study included patients who underwent Nuss procedure from 10/2017 to 09/2023.

Disparities in outpatient rural cholecystectomy outcomes.

Background: Previous studies showed comparable outcomes for common in-patient general surgery operations, but it is unknown if this extends to outpatient operations. Our aim was to compare outpatient cholecystectomy outcomes between rural and urban hospitals.

Methods: A retrospective cohort analysis was done using the Nationwide Ambulatory Surgery Sample for patients 20-years-and-older undergoing cholecystectomy between 2016 and 2018 ​at rural and urban hospitals.

An examination of the mechanisms driving the therapeutic effects of an AAV expressing a soluble variant of VEGF receptor-1.

In previous animal model studies, we demonstrated the potential of rAAV2-sVEGFRv-1, which encodes a truncated variant of the alternatively spliced soluble version of VEGF receptor-1 (VEGFR1), as a human gene therapy for age-related macular degeneration (AMD) and diabetic retinopathy (DR). Here, we elucidate in vitro some of the mechanisms by which rAAV2-sVEGFRv-1 exerts its therapeutic effects. Human umbilical vein endothelial cells (HUVECs) were infected with rAAV2-sVEGFRv-1 or a control virus vector in the presence of members of the VEGF family to identify potential binding partners via ELISA, which showed that VEGF-A, VEGF-B, and placental growth factor (PlGF) are all ligands of its transgene product.

Single-Molecule Stoichiometry of Supramolecular Complexes.

The use of single-molecule microscopy is introduced as a method to quantify the photophysical properties of supramolecular complexes rapidly at ultra low concentrations (<1 nM), previously inaccessible. Using a model supramolecular system based on the host-guest complexation of cucurbit[]uril (CB[]) macrocycles together with a fluorescent guest (), we probe fluorescent CB[] host-guest complexes in the single molecule regime. We show quantification and differentiation of host-guest photophysics and stoichiometries, both in aqueous media and noninvasively in hydrogel, by thresholding detected photons.

Responsive neurostimulation of thalamic nuclei for regional and multifocal drug-resistant epilepsy in children and young adults.

Objective: Responsive neurostimulation (RNS) is a US FDA-approved form of neuromodulation to treat patients with focal-onset drug-resistant epilepsy (DRE) who are ineligible for or whose condition is refractory to resection. However, the FDA approval only extends to use in patients with one or two epileptogenic foci. Recent literature has shown possible efficacy of thalamic RNS in patients with Lennox-Gastaut syndrome and multifocal epilepsy.

RASP: Optimal Single Puncta Detection in Complex Cellular Backgrounds.

Super-resolution and single-molecule microscopies have been increasingly applied to complex biological systems. A major challenge of these approaches is that fluorescent puncta must be detected in the low signal, high noise, heterogeneous background environments of cells and tissue. We present RASP, Radiality Analysis of Single Puncta, a bioimaging-segmentation method that solves this problem.

High-density volumetric super-resolution microscopy.

Volumetric super-resolution microscopy typically encodes the 3D position of single-molecule fluorescence into a 2D image by changing the shape of the point spread function (PSF) as a function of depth. However, the resulting large and complex PSF spatial footprints reduce biological throughput and applicability by requiring lower labeling densities to avoid overlapping fluorescent signals. We quantitatively compare the density dependence of single-molecule light field microscopy (SMLFM) to other 3D PSFs (astigmatism, double helix and tetrapod) showing that SMLFM enables an order-of-magnitude speed improvement compared to the double helix PSF by resolving overlapping emitters through parallax.

Targeting the activated microenvironment with endosialin (CD248)-directed CAR-T cells ablates perivascular cells to impair tumor growth and metastasis.

Background: Targeting of solid cancers with chimeric antigen receptor (CAR)-T cells is limited by the lack of suitable tumor-specific antigens and the immunosuppressive, desmoplastic tumor microenvironment that impedes CAR-T cell infiltration, activity and persistence. We hypothesized that targeting the endosialin (CD248) receptor, strongly expressed by tumor-associated pericytes and perivascular cancer-associated fibroblasts, would circumvent these challenges and offer an exciting antigen for CAR-T cell therapy due to the close proximity of target cells to the tumor vasculature, the limited endosialin expression in normal tissues and the lack of phenotype observed in endosialin knockout mice.

Methods: We generated endosialin-directed E3K CAR-T cells from three immunocompetent mouse strains, BALB/c, FVB/N and C57BL/6.

Antibody agonists trigger immune receptor signaling through local exclusion of receptor-type protein tyrosine phosphatases.

Antibodies can block immune receptor engagement or trigger the receptor machinery to initiate signaling. We hypothesized that antibody agonists trigger signaling by sterically excluding large receptor-type protein tyrosine phosphatases (RPTPs) such as CD45 from sites of receptor engagement. An agonist targeting the costimulatory receptor CD28 produced signals that depended on antibody immobilization and were sensitive to the sizes of the receptor, the RPTPs, and the antibody itself.

Role of high-resolution ultrasound and magnetic resonance neurography in the evaluation of peripheral nerves in the upper extremity.

Upper extremity entrapment neuropathies are common conditions in which peripheral nerves are prone to injury at specific anatomical locations, particularly superficial regions or within fibro-osseous tunnels, resulting in pain and potential disability. Although neuropathy is primarily diagnosed clinically by physical examination and electrophysiology, imaging evaluation with ultrasound and magnetic resonance neurography are valuable complementary non-invasive and accurate tools for evaluation and can help define the site and cause of nerve dysfunction which ultimately leads to precise and timely treatment. Ultrasound, which has higher spatial resolution, can quickly and comfortably characterize the peripheral nerves in real time and can evaluate for denervation related muscle atrophy.

The role of high-resolution ultrasound and MRI in the evaluation of peripheral nerves in the lower extremity.

Lower extremity peripheral neuropathy is a commonly encountered neurologic disorder, which can lead to chronic pain, functional disability, and decreased quality of life for a patient. As diagnostic imaging modalities have improved, imaging has started to play an integral role in the detection and characterization of peripheral nerve abnormalities by non-invasively and accurately identifying abnormal nerves as well as potential causes of neuropathy, which ultimately leads to precise and timely treatment. Ultrasound, which has high spatial resolution and can quickly and comfortably characterize peripheral nerves in real time along with associated denervation muscle atrophy, and magnetic resonance neurography, which provides excellent contrast resolution between nerves and other tissues and between pathologic and normal segments of peripheral nerves, in addition to assessing reversible and irreversible muscle denervation changes, are the two mainstay imaging modalities used in peripheral nerve assessment.

scAAV2-Mediated Expression of Thioredoxin 2 and C3 Transferase Prevents Retinal Ganglion Cell Death and Lowers Intraocular Pressure in a Mouse Model of Glaucoma.

Elevated intraocular pressure (IOP) in glaucoma causes retinal ganglion cell (RGC) loss and damage to the optic nerve. Although IOP is controlled pharmacologically, no treatment is available to restore retinal and optic nerve function. In this paper, we aimed to develop a novel gene therapy for glaucoma using an AAV2-based thioredoxin 2 (Trx2)-exoenzyme C3 transferase (C3) fusion protein expression vector (scAAV2-Trx2-C3).

Changes in Self-Reported Adult Health and Household Food Security With the 2021 Expanded Child Tax Credit Monthly Payments.

Importance: The 2021 Expanded Child Tax Credit (ECTC) provided families with children monthly payments from July 2021 to December 2021. The association of this policy with adult health is understudied.

Objective: To examine changes in adult self-reported health and household food security before and during ECTC monthly payments.