Dietary Macronutrient Imbalances Lead to Compensatory Changes in Peripheral Taste via Independent Signaling Pathways.

Food choice, in animals, has been known to change with internal nutritional state and also with variable dietary conditions. To better characterize mechanisms of diet-induced plasticity of food preference in Drosophila melanogaster, we synthesized diets with macronutrient imbalances and examined how food choice and taste sensitivity were modified in flies that fed on these diets. We found that dietary macronutrient imbalances caused compensatory behavioral shifts in both sexes to increase preference for the macronutrient that was scant in the food source, and simultaneously reduce preference for the macronutrient that was enriched. Further analysis with females revealed analogous changes in sweet taste responses in labellar neurons, with increased sensitivity on sugar-reduced diet and decreased sensitivity on sugar-enriched diet. Interestingly, we found differences in the onset of changes in taste sensitivity and behavior, which occur over 1-4 d, in response to dietary sugar reduction or enrichment. To investigate molecular mechanisms responsible for diet-induced taste modulation, we used candidate gene and transcriptome analyses. Our results indicate that signaling via Dop2R is involved in increasing cellular and behavioral sensitivity to sugar as well as in decreasing behavioral sensitivity to amino acids on dietary sugar reduction. On the other hand, cellular and behavioral sensitivity to sugar relies on dilp5 and a decrease in sugar preference following dietary sugar abundance was correlated with downregulation of dilp5 Together, our results suggest that feeding preference for sugar and amino acid can be modulated independently to facilitate food choice that accounts for prior dietary experience.SIGNIFICANCE STATEMENT Animals adjust their feeding preferences based on prior dietary experiences. Here, we find that upon dietary macronutrient deprivation, flies undergo compensatory changes in food preference. The altered preference correlates with changes in peripheral taste sensitivity. While Dop2R mediates changes following dietary sugar reduction, downregulation of dilp5 is associated with changes caused by a sugar-enriched diet. This study contributes to a better understanding of neurophysiological plasticity of the taste system in flies, and its role in facilitating adjustment of foraging behavior based on nutritional requirements.

Description of Vaginal Laxity and Prolapse and Correlation With Sexual Function (DeVeLoPS).

INTRODUCTION: Vaginal laxity (VL) is a sensation of vaginal looseness which may develop after pregnancy and vaginal delivery and may be affected by prior pelvic surgery, menopause and aging. Pelvic organ prolapse (POP) is a disorder in which pelvic organs descend from the normal position. VL has attracted recent attention due to the advent of energy-based treatments for this symptom. AIM: To determine the correlation between VL symptoms and physical exam findings of POP, specifically the introital measurement of genital hiatus. METHODS: This was a multi-center cross-sectional study of sexually active women over 18 years of age with a parity of one or greater. Subjects completed the Vaginal Laxity Questionnaire (VLQ), the Pelvic Floor Distress Inventory-20, and the Female Sexual Function Index (FSFI), and were asked if a sexual partner had commented on laxity. Subjects underwent pelvic exam, including the pelvic organ prolapse quantification (POP-Q). MAIN OUTCOMES MEASURES: Correlation between VL symptoms as measured by the VLQ and POP as measured by elements of the POP-Q. RESULTS: A total of 95 subjects with an average age was 54.3 ± 13.18 years were included. Sixty-three percent of patients were postmenopausal. The average VLQ score was 4.2 ± 1.35 and the average FSFI score was 23.42 out of 36. There was no significant correlation between VLQ score and POP or mid-vaginal caliber. Sensation of vaginal tightness was significantly associated with age (P=0.03) and menopausal status (P=0.04). Only 28% of partners commented on laxity and the majority commented on the vagina being tight (21%) rather than loose (7%). CONCLUSION: VL was not correlated with physical exam findings quantifying POP or sexual function. This study emphasizes the need to develop a more standardized definition of VL and a better assessment tool for VL symptoms. Polland A, Duong V, Furuya R, et al. Description of Vaginal Laxity and Prolapse and Correlation With Sexual Function (DeVeLoPS). Sex Med 2021;9:100443.

A systematic review of neurocognitive dysfunction with overactive bladder medications.

INTRODUCTION AND HYPOTHESIS: The aim of this study is to report cognitive dysfunction with commonly used antimuscarinic overactive bladder medications in patients suffering from overactive bladder disorder with and without baseline neurologic conditions. METHODS: We conducted an Ovid MEDLINE, Embase, and PsycINFO search from January 1998 to December 2018 using PRISMA guidelines. Eighteen studies met the inclusion criteria, including 5 randomized controlled trials and 13 observational studies. RESULTS: Cognitive decline was reported with oxybutynin use (5 of 8 studies) and tolterodine use (4 of 7 studies) among patients with and without baseline cognitive impairment. Oxybutynin use was linked to functional, mental, and behavioral decline among patients with Alzheimer's disease (2 studies). No cognitive decline was detected among patients with and without baseline cognitive impairment taking trospium (6 studies), darifenacin (3 studies), imidafenacin (2 studies), and fesoterodine (1 study). Solifenacin was not associated with cognitive decline (2 studies) but was linked to an increased risk of dementia among patients with diabetes (1 study). CONCLUSION: In this review, cognitive decline was reported with oxybutynin and tolterodine use and should be used with caution in adults over 65 years of age. Solifenacin, fesoterodine, and imidafenacin showed mixed results related to central nervous system effect. Trospium and darifenacin were not associated with cognitive decline among patients with and without baseline cognitive impairment.

A Molecular and Cellular Context-Dependent Role for Ir76b in Detection of Amino Acid Taste.

Amino acid taste is expected to be a universal property among animals. Although sweet, bitter, salt, and water tastes have been well characterized in insects, the mechanisms underlying amino acid taste remain elusive. From a Drosophila RNAi screen, we identify an ionotropic receptor, Ir76b, as necessary for yeast preference. Using calcium imaging, we identify Ir76b+ amino acid taste neurons in legs, overlapping partially with sweet neurons but not those that sense other tastants. Ir76b mutants have reduced responses to amino acids, which are rescued by transgenic expression of Ir76b and a mosquito ortholog AgIr76b. Co-expression of Ir20a with Ir76b is sufficient for conferring amino acid responses in sweet-taste neurons. Notably, Ir20a also serves to block salt response of Ir76b. Our study establishes the role of a highly conserved receptor in amino acid taste and suggests a mechanism for mutually exclusive roles of Ir76b in salt- and amino-acid-sensing neurons.