A descriptive examination of rurality in the Environmental influences on Child Health Outcomes Cohort: Implications, illustrations, and future directions.

Purpose: The Environmental influences on Child Health Outcomes (ECHO) Cohort has enrolled over 60,000 children to examine how early environmental factors (broadly defined) are associated with key child health outcomes. The ECHO Cohort may be well-positioned to contribute to our understanding of rural environments and contexts, which has implications for rural health disparities research. The present study examined the outcome of child obesity to not only illustrate the suitability of ECHO Cohort data for these purposes but also determine how various definitions of rural and urban populations impact the presentation of findings and their interpretation.

Gene acquisition by giant transposons primes eukaryotes for rapid evolution via horizontal gene transfer.

Horizontal gene transfer (HGT) disseminates genetic information between species and is a powerful mechanism of adaptation. Yet, we know little about its underlying drivers in eukaryotes. Giant transposons have been implicated as agents of fungal HGT, providing an unprecedented opportunity to reveal the evolutionary parameters behind this process.

Gastrointestinal Device-Mediated Delivery of mRNA-Lipid Nanoparticles Achieves Distinct Expression and Biodistribution in Mice and Pigs.

Recent investigations into autonomous ingestible microjet devices have demonstrated the feasibility of delivering many drug modalities directly into the gastrointestinal (GI) wall via the oral route. However, the expression and biodistribution of mRNA after such injections remain unexplored. mRNA-lipid nanoparticles (mRNA-LNPs) are promising therapeutics for treating or vaccinating against many diseases and pathogens.

Enhancing RNA encapsulation quantification in lipid nanoparticles: Sustainable alternatives to Triton X-100 in the RiboGreen assay.

To quantify concentration and encapsulation efficiency (EE) of mRNA in lipid nanoparticles (LNPs) the RiboGreen assay is extensively used. As part of this assay, a surfactant is used to release mRNA from LNPs for detection with the RiboGreen dye. So far, the surfactant of choice has been Triton X-100, which is harmful to human health and the environment.

Identifying biochemical changes in the kidney using proton nuclear magnetic resonance in an adenine diet chronic kidney disease mouse model.

This study aimed to investigate the metabolic changes in the kidneys in a murine adenine-diet model of chronic kidney disease (CKD). Kidney fibrosis is the common pathological manifestation across CKD aetiologies. Sustained inflammation and fibrosis cause changes in preferred energy metabolic pathways in the cells of the kidney.

Fluorescently Tagged to Understand the Infection Process on Cotton () and Weed Plant Species.

Verticillium wilt is a soil-borne disease caused by distinct vegetative compatibility groups (VCG) of the fungus . Defoliating (VCG 1A) and non-defoliating (VCG 2A) pathotypes of have contributed to yield losses of cotton production in Australia. To study the virulence and the infection process of on cotton, two isolates, one representing each VCG, have been transformed with fluorescent protein genes.

Tuning the double lipidation of salmon calcitonin to introduce a pore-like membrane translocation mechanism.

A widespread strategy to increase the transport of therapeutic peptides across cellular membranes has been to attach lipid moieties to the peptide backbone (lipidation) to enhance their intrinsic membrane interaction. Efforts in vitro and in vivo investigating the correlation between lipidation characteristics and peptide membrane translocation efficiency have traditionally relied on end-point read-out assays and trial-and-error-based optimization strategies. Consequently, the molecular details of how therapeutic peptide lipidation affects it's membrane permeation and translocation mechanisms remain unresolved.

Lipid nanoparticles containing labile PEG-lipids transfect primary human skin cells more efficiently in the presence of apoE.

Nucleic acid-based therapeutics encapsulated into lipid nanoparticles (LNPs) can potentially target the root cause of genetic skin diseases. Although nanoparticles are considered impermeable to skin, research and clinical studies have shown that nanoparticles can penetrate into skin with reduced skin barrier function when administered topically. Studies have shown that epidermal keratinocytes express the low-density lipoprotein receptor (LDLR) that mediates endocytosis of apolipoprotein E (apoE)-associated nanoparticles and that dermal fibroblasts express mannose receptors.

Active Transport and Ocular Distribution of Intravitreally Injected Liposomes.

Purpose: Drug delivery to the retina remains a challenge due to ocular barriers and fast clearing mechanisms. Nanocarrier drug delivery systems (NDDSs) hold the promise of prolonging intraocular retention times and increasing drug concentrations in the retina.

Methods: Anionic and cationic PEGylated liposomes, loaded with oxaliplatin (OxPt) to be used as trace element, were prepared from dry lipid powders.

are active eukaryotic transposable elements mobilized by a new family of tyrosine recombinases.

Transposable elements in eukaryotic organisms have historically been considered "selfish," at best conferring indirect benefits to their host organisms. The are a recently discovered feature in fungal genomes that are, in some cases, predicted to confer beneficial traits to their hosts and also have hallmarks of being transposable elements. Here, we provide experimental evidence that are indeed autonomous transposons, using the model , and identify the HhpA "Captain" tyrosine recombinase as essential for their mobilization into genomic sites with a specific target site consensus sequence.

A Polyphasic Approach including Whole Genome Sequencing Reveals sp. nov. as a Cryptic Sister Species to .

Whole genome sequencing is rapidly increasing phylogenetic resolution across many groups of fungi. To improve sequencing coverage in the genus (), we report nine new genomes representing five different species. Phylogenetic comparison between these genomes and those reported previously showed that is a distinct species from its close relative .

Formulation and characterization of insulin nanoclusters for a controlled release.

The growing interest in biopharmaceuticals combined with the challenges regarding formulation and delivery continues to encourage the development of new and improved formulations of this class of therapeutics. Nanoclusters (NCs) represent a type of formulation strategy where the biopharmaceutical is clustered in a reversible manner to function as both the therapeutic and the vehicle. In this study, insulin NCs (INCs) were formulated by a new methodology of first crosslinking proteins followed by desolvation.

hSSB1 (NABP2/OBFC2B) modulates the DNA damage and androgen-induced transcriptional response in prostate cancer.

Background: Activation and regulation of androgen receptor (AR) signaling and the DNA damage response impact the prostate cancer (PCa) treatment modalities of androgen deprivation therapy (ADT) and radiotherapy. Here, we have evaluated a role for human single-strand binding protein 1 (hSSB1/NABP2) in modulation of the cellular response to androgens and ionizing radiation (IR). hSSB1 has defined roles in transcription and maintenance of genome stability, yet little is known about this protein in PCa.

Tibial Post Fracture After Total Knee Arthroplasty: Ultrasound as a Viable Diagnostic Tool: A Case Report.

Case: A 60-year-old woman presented with knee instability and pain that started approximately 13 years after a posterior stabilized total knee arthroplasty. Physical examination revealed significant posterior laxity. Bedside ultrasound (US) documented a free-floating, hyperechoic linear artifact within the posterior knee joint capsule.

A Natural Fungal Gene Drive Enacts Killing via DNA Disruption.

Fungal spore killers are a class of selfish genetic elements that positively bias their own inheritance by killing non-inheriting gametes following meiosis. As killing takes place specifically within the developing fungal ascus, a tissue which is experimentally difficult to isolate, our understanding of the mechanisms underlying spore killers are limited. In particular, how these loci kill other spores within the fungal ascus is largely unknown.

Association Between Initial Prescription Size and Likelihood of Opioid Refill After Total Knee and Hip Arthroplasty.

Background: The present study was designed to test the hypothesis that there was no association between initial opioid prescription size and the likelihood of refill after elective primary total knee (TKA) and hip arthroplasty (THA).

Methods: We retrospectively analyzed large national datasets of commercial and Medicare insurance claims to identify a weighted cohort of 120,889 primary total joint arthroplasties (76,900 TKA and 43,989 THA) comprised of opioid-naive patients aged 18 to 75 years who had surgery between January 2015 and November 2019. The primary outcome was refill of any prescription opioid medication within 30 days after discharge, and the primary predictor variable was the total amount of opioid filled in the initial discharge prescription measured in oral morphine equivalents (OMEs).

Prosthetic Joint Infection Due to Mycobacterium senegalense After Exposure to Zebu Cattle: A Case Report.

Case: A 69-year-old male patient, 5 years after a well-functioning total hip arthroplasty for severe osteoarthritis, presented with a 3-month history of progressive, unrelenting, "burning" pain in his right hip with accompanying fullness of the right thigh. Inflammatory markers were elevated, and imaging revealed a large unilocular fluid collection with communication to the hip joint. Aspiration was positive for Mycobacterium senegalense.

Reactive Oxygen Species-Responsive Polymer Nanoparticles to Improve the Treatment of Inflammatory Skin Diseases.

To improve the quality of life for people living with chronic inflammatory skin diseases, we propose a new treatment strategy by exploring a stimuli-responsive drug delivery system. Formulations designed by exploiting smart materials can be programmed to perform a specific action upon exposure to disease-related stimuli. For instance, increased levels of reactive oxygen species (ROS), especially the accumulation of hydrogen peroxide, can be utilized to differentiate between healthy and inflamed tissues.

Biopharmaceutical nanoclusters: Towards the self-delivery of protein and peptide therapeutics.

Protein and peptide biopharmaceuticals have had a major impact on the treatment of a number of diseases. There is a growing interest in overcoming some of the challenges associated with biopharmaceuticals, such as rapid degradation in physiological fluid, using nanocarrier delivery systems. Biopharmaceutical nanoclusters (BNCs) where the therapeutic protein or peptide is clustered together to form the main constituent of the nanocarrier system have the potential to mimic the benefits of more established nanocarriers (e.

A large transposable element mediates metal resistance in the fungus Paecilomyces variotii.

The horizontal transfer of large gene clusters by mobile elements is a key driver of prokaryotic adaptation in response to environmental stresses. Eukaryotic microbes face similar stresses; however, a parallel role for mobile elements has not been established. A stress faced by many microorganisms is toxic metal ions in their environment.