John E. Hayes - US grants

DESCRIPTION (provided by applicant): Perceptual variation may represent an important aspect of genetic differences in human ingestive behavior (eg why we choose to eat and drink some foods and beverages but not others). This proposal represents a collaborative effort between investigators in chemosensory psychophysics, and molecular and quantitative behavioral genetics to examine how genetic variation in taste and pain receptors in the mouth may alter response to oral irritants that are commonly found in the food supply. Here, we propose a laboratory study to quantify the impact of variation in specific genes on the sensations that arise from capsaicin (the compound responsible for the heat of 'hot'peppers), piperine (the compound responsible for the burn of black pepper) and ethanol. Previously, we found capsaicin and piperine are bitter to some individuals but not others. Now, we ask if genetic variation in bitter taste genes can explain why. Analyses under Specific Aims 1-3 will determine if common polymorphisms (alternative forms of a gene) for the TRPV1 receptor predict differential response to the burning sensations from these irritants. Secondary aims test if certain variants of bitter taste genes can explain differences in the bitterness of these irritants. Important covariates include frequency of spicy food intake, personality factors (novelty seeking, and sensation seeking) and underlying differences in the intensity of oral sensations (supertasting). At the conclusion of this project, we will have produced a body of valuable data addressing the contribution of genetic polymorphisms on the burn and bitterness of oral irritants. Better understanding of the biology behind irritancy and bitterness will inform attempts to develop methods to block or mask these sensations and potentially remove palatability as a barrier to medication compliance. Proposed work may also provide new insight with respect to food choice behavior or causes of oral pathologies that involve burning sensations. PUBLIC HEALTH RELEVANCE: Taste is the main gatekeeper of ingestion: humans generally swallow what they like and reject what they don't, and what is liked may differ with genetics. This research examines whether the burning and bitterness from natural chemicals found in common spices are related to genetic differences in perception. Better understanding of the basic biology behind bitterness and irritancy will help us understand the dietary choices individuals make, and may help us tailor diets that improve health and wellness while remaining enjoyable to eat.

DESCRIPTION (provided by applicant): This year perhaps 2.5 million people will be added to the approximately 35 million already infected with HIV/AIDS, 50% of whom are women. Topical microbicides offer these women a means to prevent sexually transmitted infections (STIs), including HIV. However, in addition to concerns about the biological efficacy of current microbicides, user acceptance of and adherence to their use is suboptimal. It has been estimated that a single microbicide with even limited efficacy could prevent millions of new HIV cases annually. The design of vaginal microbicide dosage forms has challenged formulation scientists. Safe and efficacious products are necessary, but not sufficient to assure adherence. User acceptability depends both on the physical properties of the material and behavioral factors. Constraints that drive acceptance must be identified and addressed early in development. The acceptability of the product to women must be evaluated preclinically. We propose the rational preclinical design and development of a dosage form that delivers an immediate efficacious dose of active pharmaceutical ingredient (API) followed by the slow release of API over a period of 1-3 days to maintain efficacy. This dosage form can be thought of as a temporal vaginal ring/diaphragm that releases API(s) as it slowly erodes away. These products will be an adaptation of current softgel capsule technology. However, unlike current gelatin capsules, we will develop a range of non-gelatin capsules varying in shape and firmness (texture). Human perceptual data will be assessed throughout and guide the design process. Carrageenan will be used for the development of heat-stable softgels that, unlike current gelatin capsules, will not melt in tropical environments. The two-phase nature of softgels ('ovules') will permit the inclusion of a second component. Our R21 goals provide for proof-of-concept of this new delivery system, and the R33 goals will optimize both acceptability and biophysical functionality. The R33 will also explore potential higher-order functionality, like mucoadhesion or delivery of probiotics. Here, we propose a new microbicide delivery system, designed to overcome both biological (insufficient HIV neutralization) and behavioral (poor acceptability and adherence) deficiencies of current products. By designing formulations that function for optimal efficacy and optimal use (acceptability / adherence), microbicides produced via these methods are likely to have a greater impact on the HIV/AIDS pandemic than those currently in the development pipeline. Also, by developing a methodology for design of vaginal products where multiple factors (shape, texture, size, and multi-stage delivery) play a central role, we increase the options women have in microbicide use. Critically, our product type is flexible - allowing for multiple textures, sizes, shapes and antiviral strategies - to accommodate a range of user preferences. PUBLIC HEALTH RELEVANCE: Globally, HIV is a heterosexual disease, so there is a strong demand for women initiated and controlled prevention options. Microbicides have strong potential to meet this need, but only if formulation scientists can make products that effectively prevent HIV transmission while being acceptable to users - if products are sticky or messy, women will not use them, even if they work in the lab. Here, we incorporate user acceptability early in the optimization process to make formulations that maximize drug delivery and user acceptability at the same time, instead of considering acceptability only as an afterthought in the formulation process.

The COVID-19 pandemic is the most devastating infectious disease outbreak in a century, particularly in underserved and minoritized communities. In 2020 alone, it will cost a million lives. It continues to wreak economic havoc worldwide. Therefore, it is critical to develop new tools that can mitigate the spread of SARS- CoV-2, the virus that causes COVID-19. Rapid screening tools can identify potentially infected individuals who can then be isolated/quarantined from the uninfected and directed towards further testing and treatment. Unfortunately, definitive viral testing for SARS-CoV-2 has proven difficult to implement in many countries, including the US, due to technical, financial and governmental hurdles to universal access and timely processing. Symptom-based screening offers a valuable, albeit imperfect, complement to viral testing that can help identify many individuals with the disease for isolation as well as treatment. A major challenge with symptomatic testing is that COVID-19 is highly protean: the heterogeneity of symptoms means no single symptom or constellation of symptoms is definitive diagnostically. Still, there is growing evidence that sudden partial or complete olfactory loss ? even more than other symptoms such as fever or dry cough ? is the single best predictor of COVID-19. In this proposal, we will develop and implement objective, self-administered smell tests for the purpose of identifying individuals with COVID-19 prior to, or in the absence of, viral testing, as well as for use in population-level surveillance of COVID-19 spread. Several kinds of objective tests have been used in clinical or laboratory settings to assess an individual's olfactory ability, including those that test the ability to identify or discriminate odors as well as procedures to determine the lowest concentration an individual can reliably perceive (i.e., odor detection threshold). Each approach has technical and logistical advantages and disadvantages, and each captures different aspects of olfactory dysfunction. Regarding COVID-19, it is unknown what type of measure has the highest specificity or sensitivity. In Aim 1, we will use self-administered objective testing of odor identification and odor detection threshold in SARS-CoV-2-tested individuals to determine which olfactory measure is the best predictor of COVID-19. In Aim 2, we will use objective smell testing to assess whether population monitoring of olfactory loss in university, municipal or other community settings can serve as a sentinel of COVID-19 community spread. Together, our studies will provide a rapid, remote-friendly, cost-effective, scalable, non-intrusive method to screen for COVID-19 at the individual level and to assess prevalence in communities, especially those that have been traditionally underserved by the health care system and public health infrastructure.