Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms.

In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19-; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: -82.5 ± 27.2 points; C19-: -59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.

Taste Perception of Antidesma bunius Fruit and Its Relationships to Bitter Taste Receptor Gene Haplotypes.

It was shown more than 40 years ago that the ability to perceive the bitterness of the fruit of the Antidesma bunius tree is inversely correlated with the ability to perceive the well-studied bitter tastant phenylthiocarbamide (PTC). To determine if variants of the TAS2R38 gene, which encodes the PTC taste receptor, or variants in any of the other TAS2R bitter or TAS1R sweet receptor genes account for Antidesma taste perception, we recruited an independent subject sample and examined associations between these taste receptor gene haplotypes and Antidesma perception. Consistent with previous findings, almost none of our subjects who reported Antidesma juice as bitter was a PTC "responder" by previous definitions (i.e. a PTC taster). In our study, of the 132 individuals who perceived PTC as bitter, 15 perceived Antidesma as bitter, although these 15 subjects had very weak bitterness perception scores. Examination of TAS2R38 gene haplotypes showed that, of the subjects who perceive Antidesma as bitter, all carried at least one copy of the TAS2R38 AVI (PTC non-taster) haplotype. However, 86 subjects carried at least one AVI haplotype and failed to perceive Antidesma as bitter. No other TAS2R or TAS1R gene variants showed an association with Antidesma bitter, sweet, or sour perception. Our results show that TAS2R38 haplotypes are associated with differential perception of Antidesma berry juice bitterness, and that all those who perceive this bitterness carry at least one AVI haplotype. This indicates that the AVI haplotype is necessary for this perception, but that additional variable factors are involved.

A bio-cultural approach to the study of food choice: The contribution of taste genetics, population and culture.

The study of food choice, one of the most complex human traits, requires an integrated approach that takes into account environmental, socio-cultural and biological diversity. We recruited 183 volunteers from four geo-linguistic groups and highly diversified in terms of both genetic background and food habits from whom we collected genotypes and phenotypes tightly linked to taste perception. We confirmed previous genetic associations, in particular with stevioside perception, and noted significant differences in food consumption: in particular, broccoli, mustard and beer consumption scores were significantly higher (Adjusted P = 0.02, Adjusted P < 0.0001 and Adjusted P = 0.01, respectively) in North Europeans, when compared to the other groups. Licorice and Parmesan cheese showed lower consumption and liking scores in the Sri Lankan group (Adjusted P = 0.001 and Adjusted P < 0.001, respectively). We also highlighted how rs860170 (TAS2R16) strongly differentiated populations and was associated to salicin bitterness perception. Identifying genetic variants on chemosensory receptors that vary across populations and show associations with taste perception and food habits represents a step towards a better comprehension of this complex trait, aimed at improving the individual health status. This is the first study that concurrently explores the contribution of genetics, population diversity and cultural aspects in taste perception and food consumption.

Comparison of reduced sugar high quality chocolates sweetened with stevioside and crude stevia 'green' extract.

BACKGROUND: The demand for zero and reduced-sugar food products containing cocoa is expanding continuously. The present study was designed to evaluate the feasibility of producing high-quality chocolate sweetened with a crude extract of Stevia rebaudiana (Bertoni) prepared by a green microwave-assisted water-steam extraction procedure. Seven approximately isosweet chocolate formulations were developed, mixing cocoa paste, sucrose, commercial stevioside, crude green extract and maltitol in different proportions. All samples were analyzed for the determination of polyphenol and flavonoid content, antioxidant activity, and sensory acceptability. RESULTS: The use of a crude stevia extract allowed low-sugar, high-quality chocolates to be obtained that were also acceptable by consumers and had a significant increased antioxidant activity. Moreover, consumers' segmentation revealed a cluster of consumers showing the same overall liking for the sample with 50% sucrose replaced by the stevia crude extract as that obtained with the commercial stevioside and the control sample (without sucrose replacement). CONCLUSION: The results provide information that can contribute to promoting the development of sweet food products, with advantages in terms of an improved nutritional value (reduced sugar content and increased antioxidant activity) and a reduced impact of the production process on the environment. © 2016 Society of Chemical Industry.

Genetic variation in taste receptor pseudogenes provides evidence for a dynamic role in human evolution.

BACKGROUND: Human bitter taste receptors are encoded by a gene family consisting of 25 functional TAS2R loci. In addition, humans carry 11 TAS2R pseudogenes, some of which display evidence for substantial diversification among species, showing lineage-specific loss of function. Since bitter taste is thought to help prevent the intake of toxic substances, diversity at TAS2R genes could reflect the action of natural selection on the ability to recognize some bitter compounds rather than others. Whether species-specific variation in TAS2R pseudogenes is solely the result of genetic drift or whether it may have been influenced by selection due to different feeding behaviors has been an open question. RESULTS: In this study, we analyzed patterns of variation at human TAS2R pseudogenes in both African and non-African populations, and compared them to those observable in nonhuman primates and archaic human species. Our results showed a similar worldwide distribution of allelic variation for most of the pseudogenes, with the exception of the TAS2R6P and TAS2R18P loci, both of which presented an unexpected higher frequency of derived alleles outside Africa. At the TAS2R6P locus, two SNPs were found in strong linkage disequilibrium (r2 > 0.9) with variants in the functional TAS2R5 gene, which showed signatures of selection. The human TAS2R18P carried a species-specific stop-codon upstream of four polymorphic insertions in the reading frame. SNPs at this locus showed significant positive values in a number of neutrality statistics, and age estimates indicated that they arose after the homo-chimp divergence. CONCLUSIONS: The similar distribution of variation of many human bitter receptor pseudogenes among human populations suggests that they arose from the ancestral forms by a unidirectional loss of function. However we explain the higher frequency of TAS2R6P derived alleles outside Africa as the effect of the balancing selection acting on the closely linked TAS2R5 gene. In contrast, TAS2R18P displayed a more complex history, suggesting an acquired function followed by a recent pseudogenization that predated the divergence of human modern and archaic species, which we hypothesize was associated with adaptions to dietary changes.

The taste for health: the role of taste receptors and their ligands in the complex food/health relationship.

Taste, food, and health are terms that have since always accompanied the act of eating, but the association was simple: taste serves to classify a food as good or bad and therefore influences food choices, which determine the nutritional status and therefore health. The identification of taste receptors, particularly, the G protein-coupled receptors that mediate sweet, umami, and bitter tastes, in the gastrointestinal tract has assigned them much more relevant tasks, from nutrient sensing and hormone release to microbiota composition and immune response and finally to a rationale for the gut-brain axis. Particularly interesting are bitter taste receptors since most of the times they do not mediate macronutrients (energy). The relevant roles of bitter taste receptors in the gut indicate that they could become new drug targets and their ligands new medications or components in nutraceutical formulations. Traditional knowledge from different cultures reported that bitterness intensity was an indicator for distinguishing plants used as food from those used as medicine, and many non-cultivated plants were used to control glucose level and treat diabetes, modulate hunger, and heal gastrointestinal disorders caused by pathogens and parasites. This concept represents a means for the scientific integration of ancient wisdom with advanced medicine, constituting a possible boost for more sustainable food and functional food innovation and design.

Association between Variants of the TRPV1 Gene and Body Composition in Sub-Saharan Africans.

In humans, the transient receptor potential vanilloid 1 (TRPV1) gene is activated by exogenous (e.g., high temperatures, irritating compounds such as capsaicin) and endogenous (e.g., endocannabinoids, inflammatory factors, fatty acid metabolites, low pH) stimuli. It has been shown to be involved in several processes including nociception, thermosensation, and energy homeostasis. In this study, we investigated the association between TRPV1 gene variants, sensory perception (to capsaicin and PROP), and body composition (BMI and bioimpedance variables) in human populations. By comparing sequences deposited in worldwide databases, we identified two haplotype blocks (herein referred to as H1 and H2) that show strong stabilizing selection signals (MAF approaching 0.50, Tajima's D > +4.5) only in individuals with sub-Saharan African ancestry. We therefore studied the genetic variants of these two regions in 46 volunteers of sub-Saharan descent and 45 Italian volunteers (both sexes). Linear regression analyses showed significant associations between TRPV1 diplotypes and body composition, but not with capsaicin perception. Specifically, in African women carrying the H1-b and H2-b haplotypes, a higher percentage of fat mass and lower extracellular fluid retention was observed, whereas no significant association was found in men. Our results suggest the possible action of sex-driven balancing selection at the non-coding sequences of the TRPV1 gene, with adaptive effects on water balance and lipid deposition.

Bitter Is Better: Wild Greens Used in the Blue Zone of Ikaria, Greece.

The current study reports an ethnobotanical field investigation of traditionally gathered and consumed wild greens (Chorta) in one of the five so-called Blue Zones in the world: Ikaria Isle, Greece. Through 31 semi-structured interviews, a total of 56 wild green plants were documented along with their culinary uses, linguistic labels, and locally perceived tastes. Most of the gathered greens were described as bitter and associated with members of Asteraceae and Brassicaceae botanical families (31%), while among the top-quoted wild greens, species belonging to these two plant families accounted for 50% of the wild vegetables, which were consumed mostly cooked. Cross-cultural comparison with foraging in other areas of the central-eastern Mediterranean and the Near East demonstrated a remarkable overlapping of Ikarian greens with Cretan and Sicilian, as well as in the prevalence of bitter-tasting botanical genera. Important differences with other wild greens-related food heritage were found, most notably with the Armenian and Kurdish ones, which do not commonly feature many bitter greens. The proven role of extra-oral bitter taste receptors in the modulation of gastric emptying, glucose absorption and crosstalk with microbiota opens new ways of looking at these differences, in particular with regard to possible health implications. The present study is also an important attempt to preserve and document the bio-cultural gastronomic heritage of Chorta as a quintessential part of the Mediterranean diet. The study recommends that nutritionists, food scientists, and historians, as well as policymakers and practitioners, pay the required attention to traditional rural dietary systems as models of sustainable health.

Taste perception and food choices.

OBJECTIVES: The extent to which variation in taste perception influences food preferences is, to date, controversial. Bitterness in food triggers an innate aversion that is responsible for dietary restriction in children. We investigated the association among genetic variations in bitter receptor TAS2R38 and food choices in healthy children in the Mediterranean area, to develop appropriate tools to evaluate the relation among genetic predisposition, dietary habits, and feeding disorders. The aims of the study were to get a first baseline picture of taste sensitivity in healthy adults and their children and to explore taste sensitivity in a preliminary sample of obese children and in samples affected by functional gastrointestinal diseases. METHODS: Individuals (98 children, 87 parents, 120 adults) were recruited from the general population in southern Italy. Bitterness sensitivity was assessed by means of a suprathreshold method with 6-propyl-2-thiouracil. Genomic DNA from saliva was used to genotype individuals for 3 polymorphisms of TAS2R38 receptor, A49P, A262 V, and V296I. Food intake was assessed by a food frequency questionnaire. RESULTS: Children's taste sensation differed from that of adults: we observed a higher frequency of supertasters among children even in the mother-child dyads with the same diplotypes. Among adults, supertaster status was related with proline-alanine-valine (taster allele) homozygous haplotype, whereas supertaster children were mainly heterozygous. Regarding the food choices, we found that a higher percentage of taster children avoided bitter vegetables or greens altogether compared with taster adults. Taster status was also associated with body mass index in boys. CONCLUSIONS: Greater sensitivity to 6-propyl-2-thiouracil predicts lower preferences for vegetables in children, showing an appreciable effect of the genetic predisposition on food choices. None of the obese boys was a supertaster.

From the tongue to the gut.

The physiology of human taste experienced an unprecedented expansion of knowledge brought forward by modern genetics and molecular biology. In the last 10 years, the cellular organization of taste receptors from taste buds distributed in the various papillae of the tongue and the soft palate was enlightened. This molecular revolution rapidly expanded over and above the tongue because several papers reporting the presence of taste receptors in nongustatory tissues (eg, gut, brain) appeared. Hence, the issue of perception of food molecules is no longer confined to the field of nutrition and food preferences, but is rapidly expanding to gastrointestinal (GI) function and, possibly, to gut dysfunction. In children, functional GI diseases are strictly correlated to food preference and food aversion and up to now, the tools to address these kinds of problems were basic nutritional requirements, familial good sense, and a lot of patience: blunt tools to face extremely common and disturbing complaints. The fact that taste receptors are expressed down the whole of the intestinal tract is of particular interest because of their possible role in digestive behavior and absorption of nutrients; therefore, recent and future discoveries in this field will make possible the fine-tuning of new, sharper tools to treat children with functional GI diseases.

Vanillin Activates Human Bitter Taste Receptors TAS2R14, TAS2R20, and TAS2R39.

Vanilla is widely used in food preparation worldwide for its sensory properties, mainly related to its fragrance, being vanillin the major compound present in the processed vanilla. Vanillin is also known to elicit bitterness as a secondary sensory sensation, but the molecular mechanism of its bitterness has never been reported. Assay buffers of vanillin were tested in vitro on all known 25 human bitter taste receptors TAS2Rs. Three receptors, TAS2R14, TAS2R20, and TAS2R39, were activated, showing that these receptors are mediating the bitterness of vanillin. The result could be useful to improve the overall sensory profile of this broadly used food ingredient, but even more could represent the starting point for further studies to investigate the potential of vanillin in sensory nutrition and other pharmaceutical applications.

Chemoinformatics View on Bitter Taste Receptor Agonists in Food.

Food compounds with a bitter taste have a role in human health, both for their capability to influence food choice and preferences and for their possible systemic effect due to the modulation of extra-oral bitter taste receptors (TAS2Rs). Investigating the interaction of bitter food compounds with TAS2Rs is a key step to unravel their complex effects on health and to pave the way to rationally design new additives for food formulation or drugs. Here, we propose a collection of food bitter compounds, for which in vitro activity data against TAS2Rs are available. The patterns of TAS2R subtype-specific agonists were analyzed using scaffold decomposition and chemical space analysis, providing a detailed characterization of the associations between food bitter tastants and TAS2Rs.

Alteration, Reduction and Taste Loss: Main Causes and Potential Implications on Dietary Habits.

Our sense of taste arises from the sensory information generated after compounds in the oral cavity and oropharynx activate taste receptor cells situated on taste buds. This produces the perception of sweet, bitter, salty, sour, or umami stimuli, depending on the chemical nature of the tastant. Taste impairments (dysgeusia) are alterations of this normal gustatory functioning that may result in complete taste losses (ageusia), partial reductions (hypogeusia), or over-acuteness of the sense of taste (hypergeusia). Taste impairments are not life-threatening conditions, but they can cause sufficient discomfort and lead to appetite loss and changes in eating habits, with possible effects on health. Determinants of such alterations are multiple and consist of both genetic and environmental factors, including aging, exposure to chemicals, drugs, trauma, high alcohol consumption, cigarette smoking, poor oral health, malnutrition, and viral upper respiratory infections including influenza. Disturbances or loss of smell, taste, and chemesthesis have also emerged as predominant neurological symptoms of infection by the recent Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus strain 2 (SARS-CoV-2), as well as by previous both endemic and pandemic coronaviruses such as Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and SARS-CoV. This review is focused on the main causes of alteration, reduction, and loss of taste and their potential repercussion on dietary habits and health, with a special focus on the recently developed hypotheses regarding the mechanisms through which SARS-CoV-2 might alter taste perception.

The best COVID-19 predictor is recent smell loss: a cross-sectional study.

BACKGROUND: COVID-19 has heterogeneous manifestations, though one of the most common symptoms is a sudden loss of smell (anosmia or hyposmia). We investigated whether olfactory loss is a reliable predictor of COVID-19. METHODS: This preregistered, cross-sectional study used a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n=4148) or negative (C19-; n=546) COVID-19 laboratory test outcome. Logistic regression models identified singular and cumulative predictors of COVID-19 status and post-COVID-19 olfactory recovery. RESULTS: Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean±SD, C19+: -82.5±27.2 points; C19-: -59.8±37.7). Smell loss during illness was the best predictor of COVID-19 in both single and cumulative feature models (ROC AUC=0.72), with additional features providing no significant model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms, such as fever or cough. Olfactory recovery within 40 days was reported for ~50% of participants and was best predicted by time since illness onset. CONCLUSIONS: As smell loss is the best predictor of COVID-19, we developed the ODoR-19 tool, a 0-10 scale to screen for recent olfactory loss. Numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (10

Taste-guided identification of high potency TRPA1 agonists from Perilla frutescens.

Perilla frutescens is a food plant widely used in Asian cuisine. This plant was investigated for its interesting taste and somatosensory properties. Perillaldehyde and perillaketone are among the components of the aromatic extracts from P. Frutescens. These compounds were shown here to activate the cloned TRPA1 channel when expressed in an heterologous cell system and are therefore suggested to be responsible for the chemesthetic properties of this plant.

Preclinical profile of antitumor activity of a novel hydrophilic camptothecin, ST1968.

ST1968 is a novel hydrophilic camptothecin (CPT) derivative of the 7-oxyiminomethyl series. Because ST1968 retained ability to form remarkably stable cleavable complexes, this study was done to investigate its preclinical profile of antitumor activity in a large panel of human tumor models, including irinotecan-resistant tumors. Although less potent than SN38 in vitro, i.v. administered ST1968 caused a marked tumor inhibition, superior to that of irinotecan, in most tested models. ST1968 exhibited an impressive activity against several tumors including models of ovarian and colon carcinoma in which a high rate of cures was observed. In the most responsive tumors, complete and persistent tumor regressions were achieved even with low suboptimal doses. Even tumors derived from intrinsically resistant cells exhibited a significant responsiveness. Histologic analysis of treated tumors supports a contribution of both proapoptotic and antiangiogenic effects to ST1968 antitumor efficacy. A study done in yeast cells transformed with CPT-resistant mutant forms of topoisomerase I documented that, in contrast to other tested CPT, ST1968 was active against yeasts expressing the mutant K720E enzyme. Based on its outstanding efficacy superior to that of irinotecan and of its good therapeutic index, ST1968 has been selected for clinical development.

Development of Perilla seed oil and extra virgin olive oil blends for nutritional, oxidative stability and consumer acceptance improvements.

This study reports the blending at different levels (25, 30, 35, 40 and 45%) of Perilla seed oil (PO) with extra virgin olive oil (EVOO). Pure oils and blends were evaluated in terms of free acidity, peroxide value, fatty acid composition, sterols, tocopherols and biophenols content, oxidation stability, sensory acceptability and food pairing. Blends with high content of ω - 3 and ω - 6 fatty acids, biophenols, tocopherols, sterols and satisfying oxidation stability were obtained, representing products with improved nutritional properties. All blends resulted acceptable by consumers. Two groups of consumers with opposite preferences for samples with low (25-35%) and high (40-45%) levels of PO were identified. Blends containing 40-45% of PO were mainly paired to strong-flavour and cooked foods, while blends with less PO were preferably matched with raw meat and vegetables. Consequently, PO and EVOO blends showed promising potential as innovative vegetable oils with improved nutritional properties and versatile gastronomic use.

Synthesis and cytotoxic activity of new 9-substituted camptothecins.

A series of novel 9-substituted camptothecins derived from 9-formylcamptothecin were synthesized. The aldehyde was obtained from 10-hydroxycamptothecin or, better, by total synthesis. The compounds showed antiproliferative activity higher than that of the reference compound topotecan. Modelling suggested the possibility of a favourable interaction of small and polar 9-substituents with the topoisomerase I-DNA complex, which is consistent with the higher activity of these derivatives with respect to the corresponding 7-substituted camptothecins.

Taste-active compounds in a traditional Italian food: 'lampascioni'.

Nature is a rich source of taste-active compounds, in particular of plant origin, many of which have unusual tastes. Many of these are found in traditional food, where spontaneous plants are used as ingredients. Some taste-active compounds were identified in the bulbs of Muscari comosum, a spontaneous plant belonging to the family of the Liliaceae, very common in the Mediterranean area, and used in traditional gastronomy (called 'lampascioni' in South Italy). The bulbs were extracted with a series of solvents of different polarity. The different fractions were submitted to a preliminary sensory evaluation, and the most interesting ones, characterized by a strong bitter taste and some chemestetic properties, were submitted to further purification and structural analysis. From the ethereal extract, several 3-benzyl-4-chromanones and one stilbene derivative were isolated. Pure compounds were examined for their taste activity by means of sensory evaluation, and proved to be responsible for the characteristic taste of this food. Some of these compounds have been synthesized de novo to confirm their structure.

Consumer perception of balsamic vinegar: A cross-cultural study between Korea and Italy.

Understanding cross-cultural differences in food perception is a key issue of food research in order to understand consumer behaviour in different countries. The objective of this study was to explore potential cultural differences of balsamic vinegar perception between Korean and Italian consumers using the sorted napping method. Nine balsamic vinegars different in terms of ingredients, aging time, and origin were evaluated by Korean (n=50) and Italian (n=49) consumers using sorted napping. Familiarity and food matching were also examined. Descriptive analysis was performed to verify the attitude of the consumers in product description. The results obtained from two groups of consumers in Korea and Italy revealed a higher description attitude of the Italians (higher number of total elicited attributes, of attributes in common with the trained panel, of attributes shared with the vocabulary reported in literature, of significant specific positive product-attribute associations). Italian subjects generated various descriptors associated with the European gastronomic culture (aromatic herbs, fortified wine, dried figs, Indian fig, Parmigiano-Reggiano cheese), whereas Korean consumers used more terms related to the Asian food culture (red ginseng, Chinese medicine, Japanese apricot, teriyaki sauce, persimmon vinegar, balloon flower roots). Moreover, cultural differences of food matching were also observed: the Italians would pair the balsamic vinegars mainly with vegetables, fruits and cheese, while Koreans would combine the balsamic vinegars preferably with bread, vegetables and meat. In conclusion, familiarity resulted the main factors for cross-cultural differentiation.