UC San Diego

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. To evaluate this possibility, EDC chemistry was employed to covalently attach amoxicillin, or neomycin molecules to phage bearing a trans-TM peptide, as a model for large drug packages. Eight hours after application of antibiotic-phage to the TM of infected rats, ME bacterial titers were substantially reduced compared to untreated animals. As a control, antibiotic was linked to wild-type phage, not bearing any peptide, and application to the TM did not affect ME bacteria. The results support the ability of rare peptides to actively deliver pharmacologically relevant amounts of drugs through the intact TM and into the ME. Moreover, since bacteriophage engineered to express peptides are viral vectors, the trans-TM peptides could also transport other viral vectors into the ME.

The burden of cirrhosis and chronic liver disease is growing, yet there is a projected worsening deficit in hepatology providers. As such, cirrhosis and liver disease have been important inclusions within the core curricula of Internal Medicine. Formal assessments of provider preparedness resulting from the curriculum are lacking though. Prior studies have demonstrated that exposure to cirrhosis in undergraduate medical education is insufficient, as are learner comfort and self-reported knowledge levels. These findings are further corroborated by a multicenter survey of incoming Internal Medicine interns showing that subjective comfort with and objective knowledge of various liver disease topics are lacking compared to other common Internal Medicine topics. This paper also demonstrates how similar surveys may be used to identify additional topics that may require adjustments for curricular improvement.

RATIONALE: Stable isotope analysis of growth layer groups (GLGs) in mammal dentin is an increasingly prevalent and noninvasive approach to study animal foraging ecology. However, empirical evidence to support assumed proper methodologies for sampling GLGs is lacking. Here, we examine the effects of intratooth and intertooth variations with respect to targeted GLGs, as well as the effects of common pretreatments (e.g., formic acid and graphite) to enhance GLG visibility, on stable isotope values (δ13C and δ15N) from dentin. METHODS: We measured the δ13C and δ15N values of killer whale (Orcinus orca) dentin. We used dentin from 37 teeth to compare stable carbon (δ13C) and nitrogen (δ15N) isotope values from multiple locations within a GLG (intratooth variation), from corresponding GLGs among teeth of an individual (intertooth variation), and from treated and untreated teeth. RESULTS: We observed no significant differences in the δ13C or δ15N values when sampling a single GLG from multiple locations (intratooth variation) or when comparing the same GLG across duplicate teeth of individuals (intertooth variation). One tooth in a triplicate set showed a significantly different but likely biologically inconsequential δ13C value. Lastly, formic acid and graphite highlighting to accentuate GLGs did not significantly influence measured stable isotope values. CONCLUSIONS: We validate several previous assumptions in this field of study. First, dentin samples for stable isotope analysis can be sampled from different locations across a GLG. Second, researchers can compare stable isotope values from the same GLGs of different teeth collected from the same individual in most cases, as the δ13C and δ15N values did not vary with the sampled tooth. Third, a common protocol of formic acid and graphite treatment to enhance GLG visibility does not bias the δ13C and δ15N values from dentin. We also describe factors to consider and cautions associated with these conclusions.

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This study compared the processing of non-binary morphemes in Spanish (e.g., todxs, todes) with the processing of canonical grammatical gender violations in Spanish pronouns (e.g., Los maestros… todas…). Using self-paced reading, the study examined how individual differences in working memory and gender/sex diversity beliefs affected language processing at three regions of interest (ROI): the pronoun, the pronoun +1, and the pronoun +2. Seventy-eight Spanish-English bilinguals completed two self-paced reading tasks, one with non-binary pronouns and another with grammatical gender violations, as well as a working memory task, a language dominance questionnaire, and a gender/sex diversity beliefs questionnaire. Processing costs were operationalized as longer reaction times (RTs) or inaccurate responses. Results showed overall processing costs for non-binary morphemes at all 3 ROIs, but no processing costs were observed in terms of accuracy or response times to the comprehension question. The results suggest that processing non-binary pronouns results in a small processing cost that does not affect overall sentence comprehension. The small observed processing cost was moderated by gender/sex diversity beliefs, with gender normative beliefs increasing RTs at the pronoun and affirmation of diverse gender identities beliefs reducing the RTs at the second spillover region. In contrast, grammatical gender violations only showed a processing cost at the first spillover region and were not moderated by working memory nor gender/sex diversity beliefs. Taken together, the results suggest that non-binary pronouns are processed differently than grammatical gender violations and that the small processing cost they impose can lead to good enough comprehension.

The two-times higher prevalence of Alzheimer's disease (AD) in females versus males is well-known; however, there are also sex/gender differences in clinical presentation and diagnostic accuracy that are less examined but equally important to understand in terms of improving early detection, intervention and disease tracking in each sex/gender. This review explores how these disparities in clinical presentation manifest across the AD continuum, with a focus on the earlier stages of preclinical AD and mild cognitive impairment (MCI). We summarize evidence indicating that female's verbal memory advantage may mask early cognitive decline, leading to delayed MCI diagnosis and limiting opportunities for early intervention. Conversely, females demonstrate steeper cognitive decline at later disease stages compared to males. These patterns align with the cognitive reserve theory, suggesting female's verbal memory strength may act as a domain-specific resilience factor. Lastly, this review emphasizes the need for sex-sensitive diagnostic tools to improve early detection accuracy and equity in clinical practice.