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Children have difficulty swallowing capsules. Yet, when presented with liquid formulations, children often reject oral medications due to their intense bitterness. Presently, effective strategies to identify methods, reagents, and tools to block bitterness remain elusive. For a specific bitter-tasting drug, identification of the responsible bitter receptors and discovery of antagonists for those receptors can provide a method to block perceived bitterness. We have identified a compound (6-methylflavone) that can block responses to an intensely bitter-tasting anti–human immunodeficiency virus (HIV) drug, tenofovir alafenamide (TAF), using a primary human taste bud epithelial cell culture as a screening platform. Specifically, TAS2R39 and TAS2R1 are the main type 2 taste receptors responding to TAF observed via heterologously expressing specific TAS2R receptors into HEK293 cells. In this assay, 6-methylflavone blocked the responses of TAS2R39 to TAF. In human sensory testing, 8 of 16 subjects showed reduction in perceived bitterness of TAF after pretreating (or “prerinsing”) with 6-methylflavone and mixing 6-methylflavone with TAF. Bitterness was completely and reliably blocked in two of these subjects. These data demonstrate that a combined approach of human taste cell culture–based screening, receptor-specific assays, and human psychophysical testing can successfully discover molecules for blocking perceived bitterness of pharmaceuticals, such as the HIV therapeutic TAF. Our hope is to use bitter taste blockers to increase medical compliance with these vital medicines.SIGNIFICANCE STATEMENTIdentification of a small molecule that inhibits bitter taste from tenofovir alafenamide may increase the compliance in treating children with human immunodeficiency virus infections.

Previous studies have shown that menstrual cycle length and fertility are affected by a regular pattern of either: (1) intimate contact with men; or (2) contact with extracts from male axillary secretions; and (3) the axillary extracts of women. Experiments utilizing axillary extracts employed a controlled, double-blind research design using either extract or placebo. The study reported here employed quantitative gas chromatography-mass spectrometry (GC-MS) techniques to determine the concentration of several steroids in the male and female axillary secretion extracts. The steroids examined were: androsterone sulfate, dehydroepiandrosterone sulfate, and the volatile steroid androstenol. The results suggest the following: (1) The concentration of androstenol produced by secretion donors varied during the collection period. Males appear to produce more androstenol at certain times; women's secretions show a menstrual variation in androstenol; the highest concentrations of this compound appear to be produced in the midfollicular phase, prior to ovulation. (2) The concentration of dehydroepiandrosterone sulfate is significantly greater in men than in women. (3) In addition to the steroids, a series of aliphatic acids which range from C2 to C18 in chain length were found. The more volatile members of this series may contribute to the odor of the secretions.

Provides advice on how Christian church leaders can strengthen their staff relations and increase tenures in the United States. Recruitment of quality players; Attraction of team players; Realization that not all staff members play the same positions.