Evaluating the Relationship Between Olfactory Function and Loneliness in Community-Dwelling Individuals: A Cross-sectional Study.

BACKGROUND: Olfactory dysfunction (OD) has been reported to impact social interactions. However, the relationship between OD and loneliness has received little attention. The purpose of this study was to determine the association between OD and loneliness, controlling for patient factors. METHODS: Subjects without otolaryngic complaints were enrolled and olfactory function was assessed using: Sniffin' Sticks test to measure threshold, discrimination and identification (TDI), Questionnaire of Olfactory Disorders Negative Statements (QOD-NS) and 9 - item Olfactory-Visual Analogue Scale (VAS). Loneliness was assessed using the De Jong Gierveld (DJG) and University of California Los Angeles (UCLA) loneliness scales. Bivariate analysis was performed followed by regression analysis, controlling for confounders. RESULTS: In total, 221 subjects were included with a mean age of 50.5 years (range 20 to 93), 133 (60.2%) females and 161 (72.9%) white. Mean TDI score was 29.3 (7.0) and 49.5% of the cohort was dysosmic. Using DJG, 36.4% of the cohort were classified as lonely, whereas 35.0% were lonely using UCLA. Olfactory measures were significantly associated with DJG, including TDI (ß = -0.03, p = 0.050), olfactory discrimination (ß = -0.111, p = 0.005), QOD-NS (ß = 0.058, p < 0.001) and olfactory-VAS (ß = 0.032, p < 0.001). UCLA scores were significantly associated with QOD-NS (PR 1.061 [CI 1.018-1.107], p = 0.005) and olfactory-VAS scores (PR 1.027, [CI 1.007-1.049], p = 0.009). After controlling for confounders, the association between DJG and olfactory discrimination, as well as DJG and olfactory-VAS remained significant. CONCLUSIONS: In this community-based sample of older adults, both OD and loneliness were common. Those subjects with worse olfactory function were more likely to report loneliness. Further research is necessary to establish causality, as well as explore the role of depression.

A Community-Based Study on the Prevalence of Olfactory Dysfunction.

BACKGROUND: Olfactory dysfunction (OD) is common, affecting an estimated 13 million adults in the United States. Prior studies may underestimate OD prevalence due to use of brief smell identification tests or age-adjusted cutoff values, which concede that it is acceptable for older people to have a decreased sense of smell. OBJECTIVE: To determine OD prevalence in the healthy community when the goal and expectation is ideal olfactory function, rather than age-based population norms. Secondary goals were to explore factors associated with OD. METHODS: Subjects without otolaryngic complaints were recruited from the community surrounding the Medical University of South Carolina. Olfactory-specific information was collected, and olfactory function was assessed using the Sniffin' Sticks test (Burghardt, Wedel, Germany) to measure threshold, discrimination, and identification (TDI). OD was defined as a TDI score < 31. Bivariate analysis and linear regression were used to determine factors associated with OD. RESULTS: In total, 176 subjects were included with mean age of 52 years (range: 20-93), 111 (63%) female, and 127 (72%) white. Mean TDI score was 28.8 (6.9) and OD was present in 94 (53%) subjects. Multivariate linear regression revealed that TDI decreased an average of 1 point every 5 years. TDI was also associated with Mini-Mental Status Examination (MMSE) score, asthma, and gastroesophageal reflux disease. Threshold was associated with age, heart problems, and gastroesophageal reflux disease. Discrimination was associated with age and MMSE scores. Identification was associated with age, heart problems, and anxiety. CONCLUSIONS: In a community-based sample, OD affects greater than 50% of subjects. Aging impacts all aspects of olfaction, while the effects of factors such as asthma, MMSE scores, gastroesophageal reflux disease, heart problems, and anxiety may only be evident in specific olfactory subtests.

Olfactory cleft mucus proteins associated with olfactory dysfunction in a cohort without chronic rhinosinusitis.

BACKGROUND: Olfactory dysfunction (OD) is a common problem, affecting up to 20% of the general population. Previous studies identified olfactory cleft mucus proteins associated with OD in chronic rhinosinusitis (CRS) but not in a healthy population. In this study we aimed to identify olfactory cleft mucus proteins associated with olfaction in individuals without sinus disease. METHODS: Subjects free of sinus disease completed medical history questionnaires that collected data regarding demographics, comorbidities, and past exposures. Olfactory testing was performed using Sniffin' Sticks, evaluating threshold, discrimination, and identification. Olfactory cleft mucus (OC) and, in select cases, inferior turbinate mucus (IT) were collected with Leukosorb paper and assays performed for 17 proteins, including growth factors, cytokines/chemokines, cell-cycle regulators, and odorant-binding protein (OBP). RESULTS: Fifty-six subjects were enrolled in the study, with an average age of 47.8 (standard deviation [SD], 17.6) years, including 33 females (58.9%). The average threshold/discrimination/identification (TDI) score was 30.3 (SD, 6.4). In localization studies, OBP concentrations were significantly higher in OC than IT mucus (p = 0.006). Cyclin-dependent kinase inhibitor 2A (CDKN2A/p16INK4a), basic fibroblast growth factor (bFGF), chemokine ligand 2 (CCL2/MCP-1), granulocyte macrophage colony-stimulating factor (GM-CSF), and chemokine ligand 20 (CCL20/MIP-3a) all inversely correlated with overall TDI (all rho ≥ -0.479, p ≤ 0.004). Stem cell factor (SCF) correlated positively with overall TDI (rho = 0.510, p = 0.002). CONCLUSION: Placement of Leukosorb paper is relatively site-specific for olfactory proteins and it is feasible to collect a variety of olfactory cleft proteins that correlate with olfactory function. Further study is required to determine mechanisms of OD in non-CRS subjects.

Discovering new classes of Brugia malayi asparaginyl-tRNA synthetase inhibitors and relating specificity to conformational change.

SLIDE software, which models the flexibility of protein and ligand side chains while docking, was used to screen several large databases to identify inhibitors of Brugia malayi asparaginyl-tRNA synthetase (AsnRS), a target for anti-parasitic drug design. Seven classes of compounds identified by SLIDE were confirmed as micromolar inhibitors of the enzyme. Analogs of one of these classes of inhibitors, the long side-chain variolins, cannot bind to the adenosyl pocket of the closed conformation of AsnRS due to steric clashes, though the short side-chain variolins identified by SLIDE apparently bind isosterically with adenosine. We hypothesized that an open conformation of the motif 2 loop also permits the long side-chain variolins to bind in the adenosine pocket and that their selectivity for Brugia relative to human AsnRS can be explained by differences in the sequence and conformation of this loop. Loop flexibility sampling using Rigidity Optimized Conformational Kinetics (ROCK) confirms this possibility, while scoring of the relative affinities of the different ligands by SLIDE correlates well with the compounds' ranks in inhibition assays. Combining ROCK and SLIDE provides a promising approach for exploiting conformational flexibility in structure-based screening and design of species selective inhibitors.

Concise total syntheses of variolin B and deoxyvariolin B.

The total synthesis of the marine alkaloid variolin B has been achieved in 8 steps and 17% overall yield, starting from commercially available 4-chloro-2-methylthiopyrimidine. The key reaction involves the tandem deoxygenation and cyclization of a triarylmethanol using a combination of triethylsilane and trifluoroacetic acid. In addition, the deoxygenated analogue was prepared in 6 steps and 23% overall yield, starting from the same starting material.