A Novel Splice Variant Confers Susceptibility to Otitis Media in Humans.

Otitis media is the most frequently diagnosed disease and a leading cause of hearing loss in young children. However, genetic contributors to susceptibility and pathogen-host-environment interactions in otitis media remain to be identified. Such knowledge would help identify at-risk individuals and effectively monitor, diagnose, and treat patients with otitis media.

Determining whether a phosphatic concretion containing a Cretaceous juvenile crocodylian is a coprolite or a non-fecal concretion.

Phosphatic concretions in terrestrial settings are often identified as coprolites based upon their biotic contents and high phosphorus levels. However, recent discoveries have shown that non-fecal origins of fossiliferous phosphatic concretions are more common than originally recognized. Confusion about the taphonomic origin of phosphatic concretions can lead to erroneous paleobiological and paleoenvironmental interpretations, so a set of criteria would be useful to evaluate whether a phosphatic concretion is a coprolite.

Altered relaxation and Mitochondria-Endoplasmic Reticulum Contacts Precede Major (Mal)adaptations in Aging Skeletal Muscle and are Prevented by Exercise.

Sarcopenia, or age-related muscle dysfunction, contributes to morbidity and mortality. Besides decreases in muscle force, sarcopenia is associated with atrophy and fast-to-slow fiber type switching, which is typically secondary to denervation in humans and rodents. However, very little is known about cellular changes preceding these important (mal)adaptations.

Peptides rapidly transport antibiotic across the intact tympanic membrane to treat a middle ear infection.

The tympanic membrane (TM) forms an impenetrable barrier to medical therapies for middle ear (ME) diseases like otitis media. By screening a phage-displayed peptide library, we have previously discovered rare peptides that mediate the active transport of cargo across the intact membrane of animals and humans. Since the M13 filamentous bacteriophage on which the peptides are expressed are large (nearly 1 µm in length), this offers the possibility of noninvasively delivering drugs, large drug packages, or gene therapy to the ME.

Peptide-Mediated Transport Across the Intact Tympanic Membrane Is Intracellular, with the Rate Determined by the Middle Ear Mucosal Epithelium.

The tympanic membrane forms an impenetrable barrier between the ear canal and the air-filled middle ear, protecting it from fluid, pathogens, and foreign material entry. We previously screened a phage display library and discovered peptides that mediate transport across the intact membrane. The route by which transport occurs is not certain, but possibilities include paracellular transport through loosened intercellular junctions and transcellular transport through the cells that comprise the various tympanic membrane layers.

Design and Implementation of Tabletop Cybersecurity Simulation for Health Informatics Graduate Students.

Background:  Experiential learning through simulation allows students to apply didactic knowledge to real-world situations. Tabletop simulation allows for the exploration of a variety of topics, including cybersecurity in health care. Due to its low frequency, yet high-risk nature, simulation is a perfect educational modality to practice responding to a cybersecurity attack.

Highly Effective Biocides against Reveal New Mechanistic Insights Across Gram-Negative Bacteria.

is a major nosocomial pathogen that persists in healthcare settings despite rigorous disinfection protocols due to intrinsic mechanisms conferring resistance. We sought to systematically assess cationic biocide efficacy against this pathogen using a panel of multidrug-resistant clinical isolates. Our studies revealed widespread resistance to commercial cationic disinfectants that are the current standard of care, raising concerns about their efficacy.

Practical considerations for using low-cost sensors to assess wildfire smoke exposure in school and childcare settings.

Background: More frequent and intense wildfires will increase concentrations of smoke in schools and childcare settings. Low-cost sensors can assess fine particulate matter (PM) concentrations with high spatial and temporal resolution.

Objective: We sought to optimize the use of sensors for decision-making in schools and childcare settings during wildfire smoke to reduce children's exposure to PM.

Cumulative housing cost burden exposures and disadvantages to children's well-being and health.

Housing affordability is a growing challenge for households in the United States and other developed countries. Prolonged exposure to housing cost burden can have damaging effects on households, and, in particular, children. These burdens can exacerbate parental stress, reduce investments in children and expose households to greater neighborhood disadvantage.

Immigrant Legal Status among Essential Frontline Workers in the United States during the COVID-19 Pandemic Era.

Emerging evidence suggests that the COVID-19 pandemic has extracted a substantial toll on immigrant communities in the United States, due in part to increased potential risk of exposure for immigrants to COVID-19 in the workplace. In this article, we use federal guidance on which industries in the United States were designated essential during the COVID-19 pandemic, information about the ability to work remotely, and data from the 2019 American Community Survey to estimate the distribution of essential frontline workers by nativity and immigrant legal status. Central to our analysis is a proxy measure of working in the primary or secondary sector of the segmented labor market.

Engineering self-deliverable ribonucleoproteins for genome editing in the brain.

The delivery of CRISPR ribonucleoproteins (RNPs) for genome editing in vitro and in vivo has important advantages over other delivery methods, including reduced off-target and immunogenic effects. However, effective delivery of RNPs remains challenging in certain cell types due to low efficiency and cell toxicity. To address these issues, we engineer self-deliverable RNPs that can promote efficient cellular uptake and carry out robust genome editing without the need for helper materials or biomolecules.

Structural optimization of siRNA conjugates for albumin binding achieves effective MCL1-directed cancer therapy.

The high potential of siRNAs to silence oncogenic drivers remains largely untapped due to the challenges of tumor cell delivery. Here, divalent lipid-conjugated siRNAs are optimized for in situ binding to albumin to improve pharmacokinetics and tumor delivery. Systematic variation of the siRNA conjugate structure reveals that the location of the linker branching site dictates tendency toward albumin association versus self-assembly, while the lipid hydrophobicity and reversibility of albumin binding also contribute to siRNA intracellular delivery.

Genetic architecture distinguishes tinnitus from hearing loss.

Tinnitus is a heritable, highly prevalent auditory disorder treated by multiple medical specialties. Previous GWAS indicated high genetic correlations between tinnitus and hearing loss, with little indication of differentiating signals. We present a GWAS meta-analysis, triple previous sample sizes, and expand to non-European ancestries.

Immunomodulatory Response of the Middle Ear Epithelial Cells in Otitis Media.

Hypothesis: The middle ear (ME) epithelium transforms because of changed immunomodulation during infection.

Introduction: The epithelial cells of the tympanic cavity represent the first line of defense in the context of otitis media. They can convert from a typical mucosal site into a respiratory epithelium and vice versa.

Engineering self-deliverable ribonucleoproteins for genome editing in the brain.

The delivery of CRISPR ribonucleoproteins (RNPs) for genome editing and has important advantages over other delivery methods, including reduced off-target and immunogenic effects . However, effective delivery of RNPs remains challenging in certain cell types due to low efficiency and cell toxicity. To address these issues, we engineered self-deliverable RNPs that can promote efficient cellular uptake and carry out robust genome editing without the need for helper materials or biomolecules.

Identification and Analysis of the Ankle Microbiome Using Next-Generation DNA Sequencing: An Observational Analysis.

Introduction: Next-generation DNA sequencing (NGS) technologies have increased the sensitivity for detecting the bacterial presence and have been used in other areas of orthopaedics to better understand the native microbiome of various joints. This study uses NGS to determine whether (1) a unique microbiome exists in human ankle tissues, (2) if components of the ankle microbiome affect patient outcomes, and (3) whether microbes found on the skin are a normal part of the ankle microbiome.

Methods: A prospective study recruited 32 patients undergoing total ankle arthroplasty (n = 23) or ankle arthrodesis (n = 9) via direct anterior approach between November 2020 and October 2021.

Application of an Ultra-Low-Cost Passive Sampler for Light-Absorbing Carbon in Mongolia.

Low-cost, long-term measures of air pollution concentrations are often needed for epidemiological studies and policy analyses of household air pollution. The Washington passive sampler (WPS), an ultra-low-cost method for measuring the long-term average levels of light-absorbing carbon (LAC) air pollution, uses digital images to measure the changes in the reflectance of a passively exposed paper filter. A prior publication on WPS reported high precision and reproducibility.

Deriving Novel Quaternary Ammonium Compound Disinfectant Scaffolds from a Natural Product: Mechanistic Insights of the Quaternization of Ianthelliformisamine C.

In the search for novel quaternary ammonium compound (QAC) disinfectants that can evade bacterial resistance, we turned to natural products as a source of inspiration. Herein we used natural product ianthelliformisamine C as a scaffold to design a small library of QACs. We first synthesized ianthelliformisamine C via an amide coupling that allowed for facile purification without the need for protecting groups.