A Mendelian Trait for Olfactory Sensitivity Affects Odor Experience and Food Selection

SummaryHumans vary in acuity to many odors [1–4], with variation within olfactory receptor (OR) genes contributing to these differences [5–9]. How such variation also affects odor experience and food selection remains uncertain [10], given that such effects occur for taste [11–15]. Here we investigate β-ionone, which shows extreme sensitivity differences [4, 16, 17]. β-ionone is a key aroma in foods and beverages [18–21] and is added to products in order to give a pleasant floral note [22, 23]. Genome-wide and in vitro assays demonstrate rs6591536 as the causal variant for β-ionone odor sensitivity. rs6591536 encodes a N183D substitution in the second extracellular loop of OR5A1 and explains >96% of the observed phenotypic variation, resembling a monogenic Mendelian trait. Individuals carrying genotypes for β-ionone sensitivity can more easily differentiate between food and beverage stimuli with and without added β-ionone. Sensitive individuals typically describe β-ionone in foods and beverages as “fragrant” and “floral,” whereas less-sensitive individuals describe these stimuli differently. rs6591536 genotype also influences emotional associations and explains differences in food and product choices. These studies demonstrate that an OR variant that influences olfactory sensitivity can affect how people experience and respond to foods, beverages, and other products

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Low-Fat Dietary Pattern Intervention and Health-Related Quality of Life: The Women\u27s Health Initiative Randomized Controlled Dietary Modification Trial

BACKGROUND: Intensive dietary intervention programs may lead to benefits in vitality and other components of health quality. The Women\u27s Health Initiative Dietary Modification (DM) intervention includes a large randomized controlled trial of an intensive intervention. OBJECTIVE: To evaluate whether the intervention is associated with improved health-related quality of life (HRQoL) subscales, overall self-reported health, depression symptoms, cognitive functioning, and sleep quality. DESIGN: This randomized controlled trial was analyzed as intent to treat. PARTICIPANTS: Between 1993 and 1998, 48,835 women aged 50 to 79 years were recruited by 40 clinical centers across the United States. Eligibility included having fat intake at baseline \u3e /=32% of total calories, and excluded women with any prior colorectal or breast cancer, recent other cancers, type 1 diabetes, or medical conditions with predicted survival \u3c 3 years. INTERVENTION: Goals were to reduce calories from fat to 20%, increase vegetables and fruit to 5+ servings, and increase grain servings to 6+ servings a day. During the first year, 18 group sessions were held, with quarterly sessions thereafter. MAIN OUTCOME MEASURES: The RAND 36-Item Health Survey was used to assess HRQoL at baseline, Year 1, and close-out (about 8 years postrandomization), and estimate differential HRQoL subscale change scores. STATISTICAL ANALYSES PERFORMED: Mean change in HRQoL scores (Year 1 minus baseline) were compared by randomization group using linear models. RESULTS: At 1 year, there was a differential change between intervention and comparison group of 1.7 units (95% CI 1.5, 2.0) in general health associated with the intervention. DM intervention improved physical functioning by 2.0 units (95% CI 1.7, 2.3), vitality by 1.9 units (95% CI 1.6, 2.2), and global quality of life by 0.09 units (95% CI 0.07, 0.12). With the exception of global quality of life, these effects were significantly modified by body mass index at baseline. CONCLUSIONS: DM intervention was associated with small, but significant improvements in three HRQoL subscales: general health, physical functioning, and vitality at 1 year follow-up, with the largest improvements seen in the women with the greatest baseline body mass index

Comparison of check-all-that-apply and forced-choice Yes/No question formats for sensory characterisation

The application of check-all-that-apply (CATA) questions for sensory product characterisation is gaining acceptance and popularity. This question format has been reported to be a quick and reliable means of gathering sensory profiles from consumers, concurrently with hedonic assessment. However, a limitation of CATA questions is that they do not encourage deep processing by respondents. Forced-choice questions, where respondents answer ‘‘yes’’ or ‘‘no’’ for each term, may encourage systematic processing and be useful when consumers undertake sensory profiling tasks. This research compared sensory profiles elicited by consumers using CATA questions or forced-choice Yes/No questions and contribute to ongoing investigations of CATA questions and related question formats with a view to developing guidelines for best practise. Across seven consumer studies with 600+ consumers and multiple product categories, consistent evidence was obtained that forced-choice Yes/No questions are associated with higher term citation frequencies. However, this did not consistently translate into greater product discrimination. Conclusions regarding similarities and differences amongst samples and the stability of sample and term configurations were generally independent of question format (i.e., whether the sensory data were elicited by CATA or forced-choice Yes/No questions). Overall, the comparison of CATA and forcedchoice Yes/No questions for sensory characterisation suggested parity of the two question formats. This extended to consumers’ perceived difficulty and tediousness for completing the test. Regardless of question format, consumers, on average, perceived the tests as easy and not tedious

Prodrugs available on the Brazilian pharmaceutical market and their corresponding bioactivation pathways

The aim of this paper was to emphasize the importance of prodrug design to therapy, by examining examples available on the Brazilian pharmaceutical market. The principles of prodrug design are briefly discussed herein. Examples of prodrugs from many important therapeutic classes are shown and their advantages relative to the drugs they are derived from are also discussed. Considering the importance of these therapeutic classes, from both therapy and economic standpoints, prodrug design is a very valuable aspect in the research of new drugs and for the pharmaceutical industry as a whole.<br>O objetivo do trabalho foi ressaltar a importância do planejamento de pró-fármacos para a terapia, por meio de exemplos disponíveis no mercado farmacêutico brasileiro. Os princípios da latenciação são sucintamente discutidos. Apresentam-se exemplos de pró-fármacos de muitas classes terapêuticas importantes e as vantagens relativas aos fármacos dos quais derivam são, também, discutidas. Considerando-se a importância dessas classes terapêuticas, tanto do aspecto terapêutico quanto do econômico, o planejamento de pró-fármacos representa aspecto de grande valor na busca de novos fármacos e na indústria farmacêutica como um todo