MRI‐visible perivascular space volume: An in vivo marker of post‐mortem vascular pathology.

Background: MR‐visible perivascular space (PVS) burden is associated with clinical and MRI features of cerebrovascular disease. Its utility as an in vivo biomarker of post‐mortem pathology is uncertain.

Method: Eighteen older adults (age at death 98.

DETECT‐AD ‐ Digital Evaluations and Technologies Enabling Clinical Translation for Alzheimer’s Disease: Results of amyloid screening methodologies in a simulated anti‐amyloid clinical trial using digital biomarkers as primary outcome measures.

Background: With the advent of anti‐amyloid therapies, identifying those with underlying amyloid burdens and detecting subsequent clinical effects of this AD pathology is critical. The DETECT‐AD study (ClinicalTrials.gov, NCT05385913) is a simulated secondary prevention anti‐amyloid clinical trial testing digital biomarkers as more sensitive and meaningful primary outcome measures.

Streptomyces secretes a siderophore that sensitizes competitor bacteria to phage infection.

To overtake competitors, microbes produce and secrete secondary metabolites that kill neighbouring cells and sequester nutrients. This metabolite-mediated competition probably evolved in complex microbial communities in the presence of viral pathogens. We therefore hypothesized that microbes secrete natural products that make competitors sensitive to phage infection.

Enhancing the Self-Propelled Motion of Hydrogen Peroxide Fueled Active Particles with Formic Acid and Other Oxygen Scavengers.

We report enhanced active particle motion in hydrogen peroxide-fueled self-diffusiophoretic active particle systems of up to 400% via addition of low concentrations of oxygen scavenging agents such as formic acid (as well as other organic acids, hydrazine, and citric acid), whereas active motion was inhibited at higher concentrations. Control experiments showed that enhanced motion was decoupled from catalytic hydrogen peroxide decomposition rate and insensitive to particle surface chemistry. Experimental results point to bulk oxygen scavenging as the cause for the enhanced active motion, representing a realization of recently predicted promotional effects of product sinks on self-diffusiophoretic motion.

Bridging Macroscopic Diffusion and Microscopic Cavity Escape of Brownian and Active Particles in Irregular Porous Networks.

While irregular and geometrically complex pore networks are ubiquitous in nature and industrial processes, there is no universal model describing nanoparticle transport in these environments. 3D super-resolution nanoparticle tracking was employed to study the motion of passive (Brownian) and active (self-propelled) species within complex networks, and universally identified a mechanism involving successive cavity exploration and escape. In all cases, the long-time ensemble-averaged diffusion coefficient was proportional to a quantity involving the characteristic length scale and time scale associated with microscopic cavity exploration and escape ( ∼ /), where the proportionality coefficient reflected the apparent porous network connectivity.

Effectiveness of alcohol warning labels for at-risk groups and the general public: A policy-informing randomized experiment in Chile.

Objective: The World Health Organization recommends using health-risk warnings on alcoholic beverages. This study examines the impact of separate or combined warning labels for at-risk groups and the general population on alcohol purchase decisions.

Methods: In 2022, 7758 adults who consumed alcohol or were pregnant/lactating women (54.

In-vivo characterization of scleral rigidity in myopic eyes using fundus-pulsation optical coherence elastography.

The sclera plays an important role in the structural integrity of the eye. However, as myopia progresses, the elongation of the eyeball exerts stretching forces on the posterior sclera, which typically happens in conjunction with scleral remodeling that causes rigidity loss. These biomechanical alterations can cause localized eyeball deformation and vision impairment.

Pathways for Diagnosing and Treating CKD-Associated Pruritus: A Narrative Review.

Purpose Of Review: Chronic kidney disease (CKD)-associated pruritus is a common, persistent, and distressing itch experienced by patients across the CKD spectrum. Although the disorder is associated with adverse outcomes and poor health-related quality of life, it remains underdiagnosed and undertreated. The purpose of this narrative review is to offer health care providers guidance on how to effectively identify, assess, and treat patients with CKD-associated pruritus, with the goal of reducing symptom burden and improving patient-important outcomes, such as quality of life (QoL).

Cost-Effectiveness of Sleep Apnea Diagnosis and Treatment in Hospitalized Persons With Moderate to Severe Traumatic Brain Injury.

Objective: To assess the cost-effectiveness of alternative approaches to diagnose and treat obstructive sleep apnea (OSA) in patients with traumatic brain injury (TBI) during inpatient rehabilitation.

Setting: Data collected during the Comparison of Sleep Apnea Assessment Strategies to Maximize TBI Rehabilitation Participation and Outcome (C-SAS) clinical trial (NCT03033901) on an inpatient rehabilitation TBI cohort were used in this study.

Study Design: Decision tree analysis was used to determine the cost-effectiveness of approaches to diagnosing and treating sleep apnea.

Stabilization of an Infectious Enveloped Virus by Spray-Drying and Lyophilization.

Enveloped viruses are attractive candidates for use as gene- and immunotherapeutic agents due to their efficacy at infecting host cells and delivering genetic information. They have also been used in vaccines as potent antigens to generate strong immune responses, often requiring fewer doses than other vaccine platforms as well as eliminating the need for adjuvants. However, virus instability in liquid formulations may limit their shelf life and require that these products be transported and stored under stringently controlled temperature conditions, contributing to high cost and limiting patient access.

White matter hyperintensities and the surrounding normal appearing white matter are associated with water channel disruption in the oldest old.

Introduction: Age-related magnetic resonance imaging (MRI) T2 white matter hyperintensities (WMHs) are common and associated with neurological decline. We investigated the histopathological underpinnings of MRI WMH and surrounding normal appearing white matter (NAWM), with a focus on astroglial phenotypes.

Methods: Brain samples from 51 oldest old Oregon Alzheimer's Disease Research Center participants who came to autopsy underwent post mortem (PM) 7 tesla MRI with targeted histopathological sampling of WMHs and NAWM.

Combinatorial High-Throughput Screening of Complex Polymeric Enzyme Immobilization Supports.

Recent advances have demonstrated the promise of complex multicomponent polymeric supports to enable supra-biological enzyme performance. However, the discovery of such supports has been limited by time-consuming, low-throughput synthesis and screening. Here, we describe a novel combinatorial and high-throughput platform that enables rapid screening of complex and heterogeneous copolymer brushes as enzyme immobilization supports, named combinatorial high-throughput enzyme support screening (CHESS).

Enlarged perivascular spaces are associated with white matter injury, cognition and inflammation in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Enlarged perivascular spaces have been previously reported in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, but their significance and pathophysiology remains unclear. We investigated associations of white matter enlarged perivascular spaces with classical imaging measures, cognitive measures and plasma proteins to better understand what enlarged perivascular spaces represent in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and whether radiographic measures of enlarged perivascular spaces would be of value in future therapeutic discovery studies for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Twenty-four individuals with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and 24 age- and sex-matched controls were included.

Supra-biological performance of immobilized enzymes enabled by chaperone-like specific non-covalent interactions.

Designing complex synthetic materials for enzyme immobilization could unlock the utility of biocatalysis in extreme environments. Inspired by biology, we investigate the use of random copolymer brushes as dynamic immobilization supports that enable supra-biological catalytic performance of immobilized enzymes. This is demonstrated by immobilizing Bacillus subtilis Lipase A on brushes doped with aromatic moieties, which can interact with the lipase through multiple non-covalent interactions.

Bacterium secretes chemical inhibitor that sensitizes competitor to bacteriophage infection.

To overtake competitors, microbes produce and secrete secondary metabolites that kill neighboring cells and sequester nutrients. This natural product-mediated competition likely evolved in complex microbial communities that included viral pathogens. From this ecological context, we hypothesized that microbes secrete metabolites that "weaponize" natural pathogens (i.

Impact of stalling events on microcirculatory hemodynamics in the aged brain.

Objective: The role of cerebral microvasculature in cognitive dysfunction can be investigated by identifying the impact of blood flow on cortical tissue oxygenation. In this paper, the impact of capillary stalls on microcirculatory characteristics such as flow and hematocrit (Ht) in the cortical angioarchitecture is studied.

Methods: Using a deterministic mathematical model to simulate blood flow in a realistic mouse cortex, hemodynamics parameters, including pressure, flow, vessel diameter-adjustable hematocrit, and transit time are calculated as a function of stalling events.

Computational and experimental approaches to quantify protein binding interactions under confinement.

Crowded environments and confinement alter the interactions of adhesion proteins confined to membranes or narrow, crowded gaps at adhesive contacts. Experimental approaches and theoretical frameworks were developed to quantify protein binding constants in these environments. However, recent predictions and the complexity of some protein interactions proved challenging to address with prior experimental or theoretical approaches.

Classification of traumatic injury to the dural venous sinus using CT venography.

Background And Purpose: Cerebral venous sinus thrombosis (CVST) is an underrecognized cause of morbidity in acute traumatic brain injury (TBI). Radiologic diagnosis is challenging in the setting of concurrent extra-axial injury and a lack of standardized diagnostic criteria. The prevalence of traumatic thrombosis versus compression is unknown.

Nanomotor-enhanced transport of passive Brownian particles in porous media.

Artificial micro/nanomotors are expected to perform tasks in interface-rich and species-rich environments for biomedical and environmental applications. In these highly confined and interconnected pore spaces, active species may influence the motion of coexisting passive participants in unexpected ways. Using three-dimensional super-resolution single-nanoparticle tracking, we observed enhanced motion of passive nanoparticles due to the presence of dilute well-separated nanomotors in an interconnected pore space.

Effect of mechanical stresses on viral capsid disruption during droplet formation and drying.

Identification of the mechanisms by which viruses lose activity during droplet formation and drying is of great importance to understanding the spread of infectious diseases by virus-containing respiratory droplets and to developing thermally stable spray dried live or inactivated viral vaccines. In this study, we exposed suspensions of baculovirus, an enveloped virus, to isolated mechanical stresses similar to those experienced during respiratory droplet formation and spray drying: fluid shear forces, osmotic pressure forces, and surface tension forces at interfaces. DNA released from mechanically stressed virions was measured by SYBR Gold staining to quantify viral capsid disruption.