Metabolic Reprogramming in Gut Microbiota Exposed to Polystyrene Microplastics.

: Microplastics (MPs) are small plastic fragments with diameters less than 5 mm in size and are prevalent in everyday essentials and consumables. Large global plastic production has now led to a flooding of MPs in our natural environment. Due to their detrimental impacts on the planet's ecosystems and potentially our health, MPs have emerged as a significant public health concern.

FLASH proton reirradiation, with or without hypofractionation, reduces chronic toxicity in the normal murine intestine, skin, and bone.

Background And Purpose: The normal tissue sparing afforded by FLASH radiotherapy is being intensely investigated for potential clinical translation. Here, we studied the effects of FLASH proton radiotherapy (F-PRT) in the reirradiation setting, with or without hypofractionation. Chronic toxicities in three murine models of normal tissue toxicity including the intestine, skin, and bone were investigated.

Low dose threshold for measuring cardiac functional metrics using four-dimensional CT with deep learning.

Background: Four-dimensional CT is increasingly used for functional cardiac imaging, including prognosis for conditions such as heart failure and post myocardial infarction. However, radiation dose from an acquisition spanning the full cardiac cycle remains a concern. This work investigates the possibility of dose reduction in 4DCT using deep learning (DL)-based segmentation techniques as an objective observer.

FLASH proton reirradiation, with or without hypofractionation, mitigates chronic toxicity in the normal murine intestine, skin, and bone.

Background And Purpose: The normal tissue sparing afforded by FLASH radiotherapy (RT) is being intensely investigated for potential clinical translation. Here, we studied the effects of FLASH proton RT (F-PRT) in the reirradiation setting, with or without hypofractionation. Chronic toxicities in three murine models of normal tissue toxicity including the intestine, skin, and bone were investigated.

Ethnic variation and structure-function analysis of tauopathy-associated alleles.

EIF2AK3, also known as PERK, plays a pivotal role in cellular proteostasis, orchestrating the Unfolded Protein Response (UPR) and Integrated Stress Response (ISR) pathways. In addition to its central position in intracellular stress regulation, human GWAS identify EIF2AK3 as a risk factor in tauopathies, neurodegenerative diseases caused by aberrant tau protein accumulation. Guided by these genomic indicators, our investigation systematically analyzed human PERK variants, focusing on those with potential tauopathy linkages.

FLASH Proton Radiation Therapy Mitigates Inflammatory and Fibrotic Pathways and Preserves Cardiac Function in a Preclinical Mouse Model of Radiation-Induced Heart Disease.

Purpose: Studies during the past 9 years suggest that delivering radiation at dose rates exceeding 40 Gy/s, known as "FLASH" radiation therapy, enhances the therapeutic index of radiation therapy (RT) by decreasing normal tissue damage while maintaining tumor response compared with conventional (or standard) RT. This study demonstrates the cardioprotective benefits of FLASH proton RT (F-PRT) compared with standard (conventional) proton RT (S-PRT), as evidenced by reduced acute and chronic cardiac toxicities.

Methods And Materials: Mice were imaged using cone beam computed tomography to precisely determine the heart's apex as the beam isocenter.

In Vivo Tissue Distribution of Microplastics and Systemic Metabolomic Alterations After Gastrointestinal Exposure.

Global plastic use has consistently increased over the past century with several different types of plastics now being produced. Much of these plastics end up in oceans or landfills leading to a substantial accumulation of plastics in the environment. Plastic debris slowly degrades into microplastics (MPs) that can ultimately be inhaled or ingested by both animals and humans.

Neurodegeneration risk factor, EIF2AK3 (PERK), influences tau protein aggregation.

Tauopathies are neurodegenerative diseases caused by pathologic misfolded tau protein aggregation in the nervous system. Population studies implicate EIF2AK3 (eukaryotic translation initiation factor 2 alpha kinase 3), better known as PERK (protein kinase R-like endoplasmic reticulum kinase), as a genetic risk factor in several tauopathies. PERK is a key regulator of intracellular proteostatic mechanisms-unfolded protein response and integrated stress response.

Network biology analysis of P23H rhodopsin interactome identifies protein and mRNA quality control mechanisms.

Rhodopsin is essential for phototransduction, and many rhodopsin mutations cause heritable retinal degenerations. The P23H rhodopsin variant generates a misfolded rhodopsin protein that photoreceptors quickly target for degradation by mechanisms that are incompletely understood. To gain insight into how P23H rhodopsin is removed from rods, we used mass spectrometry to identify protein interaction partners of P23H rhodopsin immunopurified from Rho mice and compared them with protein interaction partners of wild-type rhodopsin from Rho mice.

A stromal Integrated Stress Response activates perivascular cancer-associated fibroblasts to drive angiogenesis and tumour progression.

Bidirectional signalling between the tumour and stroma shapes tumour aggressiveness and metastasis. ATF4 is a major effector of the Integrated Stress Response, a homeostatic mechanism that couples cell growth and survival to bioenergetic demands. Using conditional knockout ATF4 mice, we show that global, or fibroblast-specific loss of host ATF4, results in deficient vascularization and a pronounced growth delay of syngeneic melanoma and pancreatic tumours.

An Overview of Online Resources for Medical Spanish Education for Effective Communication with Spanish-Speaking Patients.

Phenomenon: Despite the rapid development of virtual medical Spanish educational materials, online resources lack transparency and a peer-review process. The purpose of this interdisciplinary study was to provide a critical inventory of virtual resources for medical Spanish education, thereby providing a panorama of the current state of online medical Spanish.

Approach: Research team members conducted iterative searches to identify medical Spanish online resources, which were then screened for predetermined inclusion/exclusion criteria.

ATF6 is required for efficient rhodopsin clearance and retinal homeostasis in the P23H rho retinitis pigmentosa mouse model.

Retinitis Pigmentosa (RP) is a blinding disease that arises from loss of rods and subsequently cones. The P23H rhodopsin knock-in (P23H-KI) mouse develops retinal degeneration that mirrors RP phenotype in patients carrying the orthologous variant. Previously, we found that the P23H rhodopsin protein was degraded in P23H-KI retinas, and the Unfolded Protein Response (UPR) promoted P23H rhodopsin degradation in heterologous cells in vitro.

Elucidating the effect of enzymatic polymerized polysaccharide particle morphology on emulsion properties.

Exploiting the shape of Pickering stabilizers offers the ability to unlock the full potential of nanoparticle-stabilized emulsions for applications in enhanced oil recovery, pharmaceuticals, cosmetics, and coatings. In this work, we utilize engineered polysaccharide particles derived from the enzymatic polymerization of glucose from sucrose with controlled shape for the stabilization of dodecane-in-water emulsions. Altering the particle shape (spherical aggregates, fibrids, or platelets), while maintaining a neutral surface charge allows for a systematic examination of the role of particle shape in the stabilization of emulsions.

Feasibility of measuring pericoronary fat from precontrast scans: Effect of iodinated contrast on pericoronary fat attenuation.

Background: Pericoronary adipose tissue (PCAT) attenuation has been identified as a marker for cardiovascular risk. The effect of contrast enhancement on fat attenuation is unknown. We aim to compare precontrast coronary scans to postcontrast CCTA for quantification of pericoronary fat volume and attenuation.

Multiexon deletion alleles of ATF6 linked to achromatopsia.

Achromatopsia (ACHM) is an autosomal recessive disease that results in severe visual loss. Symptoms of ACHM include impaired visual acuity, nystagmus, and photoaversion starting from infancy; furthermore, ACHM is associated with bilateral foveal hypoplasia and absent or severely reduced cone photoreceptor function on electroretinography. Here, we performed genetic sequencing in 3 patients from 2 families with ACHM, identifying and functionally characterizing 2 mutations in the activating transcription factor 6 (ATF6) gene.

Coarse-grained molecular dynamics simulations of α-1,3-glucan.

In this paper we present a computational study of aggregation in aqueous solutions of α-1,3-glucan captured using a coarse-grained (CG) model that can be extended to other polysaccharides. This CG model captures atomistic geometry (i.e.

Laparoscopically assisted peritoneal shunt insertion for hydrocephalus.

Over the past 50 years, various shunting procedures involving the peritoneum have been performed for the treatment of hydrocephalus. During placement of the peritoneal portion of the catheter, complications may arise secondary to a lack of direct visualization. We describe a reduced complication rate with laparoscopically-assisted placement of the peritoneal portion of the catheter.

Stroke onset time using sodium MRI in rat focal cerebral ischemia.

Background And Purpose: Thrombolytic therapy with intravenous tPA must be administered within 3 hours after stroke onset. However, stroke onset time cannot be established in 20% to 45% of potential patients. We propose that the rate of increase of the brain concentration of sodium ([Na+]br) after stroke, monitored using sodium MRI in a rat model of cortical ischemia, is linear in each individual animal, can locate the ischemic region, and can be used to estimate onset time.

Suramin reduces infarct volume in a model of focal brain ischemia in rats.

Extracellular adenosine 5'-triphosphate (ATP) provides excitatory transmission in the central nervous system. Stimulation by ATP of ionotropic ligand-gated ion channel purinoceptors (P(2X)) leads to increased intracellular calcium levels, and activation of P(2X) receptors may be involved in the process of excitotoxic neuronal injury caused by stroke. Suramin, as an agent that is known to block P(2X) receptors at a specific concentration, was assessed for its neuroprotective potential in a model of experimental stroke in the rat.