Context matters: Neural processing of food-flavored e-cigarettes and the influence of smoking.

E-cigarettes are harmful, addictive, and popular. In e-cigarettes, nicotine is often paired with food-flavors. How this pairing of nicotine and food cues influences neural processing warrants investigation, as in smokers, both types of cues activate similar brain regions. Additionally, while most e-cigarettes are sweet, savory e-cigarettes are seemingly absent, although savory flavors are commonly liked in food. To understand how smoking status and type of flavor modulate reactions to food-flavored e-cigarettes, in comparison to actual food, neural and subjective responses to food odors were measured in a 2 (sweet vs. savory odor) x2 (food vs. e-cigarette context) x2 (smokers vs. non-smokers) design in 22 occasional/light smokers and 25 non-smokers. During fMRI scanning, participants were exposed to sweet and savory odors and pictures creating the two contexts. Liking and wanting were repeatedly measured on a 100-unit visual-analogue-scale. Results show that sweet e-cigarettes were liked (Δ = 14.2 ± 1.7) and wanted (Δ = 39.5 ± 3.1) more than savory e-cigarettes, and their cues activated the anterior cingulate more (cluster-level qFDR = 0.003). Further, we observed context-dependent variations in insula response to odors (cluster-level qFDR = 0.023, and = 0.030). Savory odors in an e-cigarette context were wanted less than the same odors in a food-context (Δ = 32.8 ± 3.1). Smokers and non-smokers reacted similarly to flavored product cues. Our results indicate that the principles of flavor preference in food cannot directly be applied to e-cigarettes and that it is challenging to design sweet and savory e-cigarettes to appeal to smokers only.

Can humans smell tastants?

Although studies have shown that olfaction may contribute to the perception of tastant, literature is scarce or circumstantial, especially in humans. This study aims to (i) explore whether humans can perceive solutions of basic prototypical tastants through orthonasal and retronasal olfaction and (ii) to examine what volatile odor compounds (VOCs) underlie this ability. Solutions of 5 basic tastants (sucrose, sodium chloride, citric acid, monosodium glutamate [MSG], quinine) dissolved in water, and 2 fatty acids (oleic and linoleic acid) dissolved in mineral oil were prepared. Triangle discrimination tests were performed (n = 41 in duplicate) to assess whether the tastant solutions can be distinguished from blanks (solvents) through ortho- and retronasal olfaction. Participants were able to distinguish all tastant solutions from blank through orthonasal olfaction. Only sucrose, sodium chloride, oleic acid, and linoleic acid were distinguished from blank by retronasal olfaction. Ethyl dichloroacetate, methylene chloride, and/or acetone were identified in the headspace of sucrose, MSG, and quinine solutions but not in the headspace of water, sodium chloride, and citric acid solutions. Fat oxidation compounds such as alcohols and aldehydes were detected in the headspace of the oleic and linoleic acid solutions but not the mineral oil. We conclude that prototypical tastant solutions can be discriminated from water and fatty acid solutions from mineral oil through orthonasal olfaction. Differences in the volatile headspace composition between blanks and tastant solutions may have facilitated the olfactory discrimination. These findings can have methodological implications for future studies assessing gustatory perception using these prototypical taste compounds.

An ingredient co-occurrence network gives insight into e-liquid flavor complexity.

INTRODUCTION: Part of the appeal of e-cigarettes lies in their available flavors. To achieve attractive flavors, e-liquids contain many different flavoring agents, which allow many flavoring combinations. To advance our knowledge of e-liquid flavors and compositions and to evaluate the effect of legislation, we determined whether there are ingredient combinations that are frequently used together. METHODS: We used e-cigarette ingredient data from the European Common Entry Gate system (EU-CEG) as available on 31 December 2022. RESULTS: In e-liquids, we found 214 ingredient pairs with a co-occurrence odds ratio greater than 10. Together, these consisted of 62 unique ingredients. Network analysis revealed that ingredients were grouped together based on their flavor and/or chemical structure. We identified two densely connected regions (clusters) in the network. One consisted of six ingredients with sweet-vanilla-creamy flavors. The second cluster consisted of 13 ingredients. While some of these have fruity flavors, others, such as alkyl carboxylic acids and dimethyl sulfide, are known to have unpleasant flavors. Additional data and literature analyses indicated that alkyl carboxylic acids can contribute to a creamy and sweet-fruity taste, whereas dimethyl sulfide can contribute to a more refined fruity taste. CONCLUSIONS: These results exemplify that the flavor of e-liquids is not just the sum of its parts. Big data analyses on product data can be used to detect such patterns, but expert knowledge and additional data are needed for further interpretation. Monitoring of e-liquid flavors as well as ingredients will remain important to regulate e-liquid product attractiveness.

Dietary taste patterns and diet quality of female nurses around the night shift.

PURPOSE: Night shift workers are at risk of making poor food choices: e.g. sleep deprivation may lead to higher food intake with innate preferred tastes, such as sweet, savoury and fatty foods. Therefore, better insight in dietary taste patterns of night shift workers may improve the understanding of their food choices. METHODS: This observational study assessed dietary taste patterns of 120 female night shift working nurses and compared them to 307 women of a reference population. Dietary intake, assessed with 24-h dietary recalls, was combined with a taste intensity database, including taste profiles of 557 foods. The contribution to the daily intake of 6 taste clusters was assessed: fat, neutral, sweet/fat, sweet/sour, salt/umami/fat and bitter. RESULTS: During night shifts, nurses consumed a significantly higher energy percentage (en%) of 'neutral' (5.9 en%), 'sweet/sour' (8.1 en%) and 'sweet/fat' (6.5 en%) tasting foods and a lower en% of 'fat' (- 17.1 en%) and 'bitter' (- 2.1 en%) tasting foods than outside the night shift. They consumed a larger en% from foods with a 'sweet/sour' (1.9 en%) taste and a lower en% from foods with a 'bitter' (- 2.1 en%) taste than the reference population, irrespective of age, BMI and smoking status. A higher en% and gram% of 'fat' tasting foods and a higher gram% 'fat/salt/umami' tasting foods were associated with lower diet quality. CONCLUSION: Our results only partly support our hypothesis that nurses would select foods with more innate taste preferences. In addition, fat and savoury tasting foods were negatively associated with their diet quality.

One-year psychophysical evaluation of COVID-19-induced olfactory disorders: a prospective cohort study.

BACKGROUND: Olfactory disorders are common in COVID-19. While many patients recover within weeks, a notable number of patients suffer from prolonged olfactory disorders. Much research has focused on the acute phase of olfactory disorders in COVID-19; however, there is still inconsistency regarding the prognosis. We aim to assess both objective and subjective olfactory function in patients with persisting olfactory disorders following COVID-19, 1 year after diagnosis. METHODS: We objectively measured olfactory function in 77 patients who initially had COVID-19-induced smell disorders, 1 year after confirmed diagnosis. These patients previously underwent two objective measurements at approximately 3 and 6 months after COVID-19, in the context of the COCOS trial (COrticosteroids for COvid-19-induced loss of Smell). The main outcome measurement was TDI score (threshold-discrimination-identification) on Sniffin' Sticks Test (SST). Secondary outcomes included objective gustatory function on Taste Strip Test (TST), self-reported olfactory, gustatory and trigeminal function on a visual analogue scale (VAS) and outcomes on questionnaires about quality of life, and nasal symptoms. RESULTS: The findings of this study show that 1 year following COVID-19, the median TDI score increased to 30.75 (IQR 27.38-33.5), regarded as normosmia. The median TDI score started at 21.25 (IQR 18.25-24.75) at baseline and increased to 27.5 (IQR 23.63-30.0) at 6 months following COVID-19. The increase of 9.5 points on the TDI score between baseline and 1 year after COVID-19 marks a clinically relevant improvement. Regarding the self-reported VAS score (1-10) on sense of smell, it increased from 1.2 (IQR 0.4-3.0) at baseline to 3.2 (IQR 1.4-6.0) at 6 months and further improved up to 6.1 (IQR 2.7-7.5) after 1 year. Objective gustatory function increased with 2 points on TST a year after diagnosis. Self-reported olfactory, gustatory, and trigeminal functions also improved over time, as did quality of life. CONCLUSIONS: Objective and self-reported olfactory function continued to improve 1 year after COVID-19. The median TDI score of 30.75 (IQR 27.38-33.5) is regarded as normosmia, which is a favorable outcome. However, the rate of improvement on TDI score reduces over time.

Lifelong olfactory deprivation-dependent cortical reorganization restricted to orbitofrontal cortex.

Prolonged sensory deprivation has repeatedly been linked to cortical reorganization. We recently demonstrated that individuals with congenital anosmia (CA, complete olfactory deprivation since birth) have seemingly normal morphology in piriform (olfactory) cortex despite profound morphological deviations in the orbitofrontal cortex (OFC), a finding contradictory to both the known effects of blindness on visual cortex and to the sparse literature on brain morphology in anosmia. To establish whether these unexpected findings reflect the true brain morphology in CA, we first performed a direct replication of our previous study to determine if lack of results was due to a deviant control group, a confound in cross sectional studies. Individuals with CA (n = 30) were compared to age and sex matched controls (n = 30) using voxel- and surface-based morphometry. The replication results were near identical to the original study: bilateral clusters of group differences in the OFC, including CA atrophy around the olfactory sulci and volume increases in the medial orbital gyri. Importantly, no group differences in piriform cortex were detected. Subsequently, to assess any subtle patterns of group differences not detectable by our mass-univariate analysis, we explored the data from a multivariate perspective. Combining the newly collected data with data from the replicated study (CA = 49, control = 49), we performed support vector machine classification based on gray matter volume. In line with the mass-univariate analyses, the multivariate analysis could accurately differentiate between the groups in bilateral OFC, whereas the classification accuracy in piriform cortex was at chance level. Our results suggest that despite lifelong olfactory deprivation, piriform (olfactory) cortex is morphologically unaltered and the morphological deviations in CA are confined to the OFC.

How volatile composition facilitates olfactory discrimination of fat content in beef and pork.

Foods differing in fat content can be distinguished through olfaction alone. The mechanisms underlying the ability of humans to discriminate between foods differing in fat content through olfaction are underexplored. In this study, beef and pork samples were prepared (raw and roasted) with low (muscle tissue; raw: 2-5%; roasted: 5%), medium (muscle tissue with lard; raw: 25-30%; roasted: 36-44%), and high (lard; raw: 40-42%; roasted: 69-70%) fat content. Olfactory triangle discrimination tests and ranking tests were performed to explore whether humans can discriminate and rank fat content of the samples through orthonasal olfaction. Headspace-Solid Phase Micro Extraction-Gas Chromatography-Mass Spectrometry (SPME-GC-MS) was used to characterize the volatile compound composition of the headspace of samples differing in fat content. Partial least-squares regression and partial least squares-discriminant analysis were performed to determine the volatile compounds that were responsible for olfactory fat content discrimination. We found that fat content in both raw and roasted samples can be distinguished through orthonasal olfaction. Perceived odor differences did not always contribute to olfactory identification of fat content. Roasted beef and pork meats with higher fat content had more abundant fatty acids, aldehydes, and ketones. Phthalic acid, isobutyl 2-ropylpentyl ester, and carbon disulfide facilitated the olfactory discrimination of fat content in raw pork and beef samples. 2-Methyl-propanal, benzaldehyde, 1-hydroxy-2-propanone, 2,3-pentanedione, 2,5-octanedione, and 2-butanone contributed to odor differences of roasted beef samples differing in fat content. We conclude that beef and pork samples differing in fat content differ in volatile compound composition of the headspace, and that these differences facilitate discrimination between samples differing in fat content based on olfaction alone.

Macronutrient intake and alertness during night shifts - the time interval matters.

Background: Working night shifts is associated with higher safety risks due to shift work-related fatigue. Nutrition, especially certain (macro) nutrient compositions, has been suggested to reduce fatigue, however, results of studies are contradictory. This could be explained by differences in the time interval investigated between the consumption of a meal and measurement of cognitive performance. Therefore, this observational study investigated the association between macronutrient intake and objective alertness at different time intervals during the night shift in nurses. Methods: 128 nurses, aged 20-61 years, completed an alertness test (Psychomotor Vigilance Task) during the night shift and a 24-h dietary recall after the night shift. This was repeated three times, always on the first night shift in a night shift series. The associations between macronutrient intake 0 to 1, 1 to 2, and 2 to 3 h before the PVT with alertness during the night shift were analyzed through Linear Mixed Models. The basic model was adjusted for age and gender and the adjusted model additionally for BMI, start time of PVT and energy and caffeine intake during the relevant time interval. Results: Protein intake was not associated with objective alertness levels, while fat and carbohydrates intake had opposite associations with objective alertness levels over similar time intervals. Fat intake up to 1 h prior to the PVT was borderline associated with a longer median reaction time (RT) (ß = 9.00 ms/10 g fat, 95% CI: -0.21, 18.20), while a higher carbohydrate intake up to 1 h prior to the PVT was borderline associated with shorter median RTs (ß = -3.89, 95% CI: -7.85, 0.06). A higher fat intake 2 to 3 h prior to the PVT was associated with less lapses (log transformed ß = -0.16; 95% CI: -0.31, -0.02), while a higher carbohydrate intake 2 to 3 h prior to the PVT was associated with more lapses (ß = 0.06, 95% CI: 0.01, 0.12). Conclusion: Our results contribute to understanding the association between macronutrient intake, as part of a mixed meal, and alertness levels. Conflicting results from previous studies may probably be due to time differences between macronutrient intake and alertness testing.

Covid-19 affects taste independent of taste-smell confusions: results from a combined chemosensory home test and online survey from a large global cohort.

People often confuse smell loss with taste loss, so it is unclear how much gustatory function is reduced in patients self-reporting taste loss. Our pre-registered cross-sectional study design included an online survey in 12 languages with instructions for self-administering chemosensory tests with 10 household items. Between June 2020 and March 2021, 10,953 individuals participated. Of these, 5,225 self-reported a respiratory illness and were grouped based on their reported COVID test results: COVID-positive (COVID+, N = 3,356), COVID-negative (COVID-, N = 602), and COVID unknown for those waiting for a test result (COVID?, N = 1,267). The participants who reported no respiratory illness were grouped by symptoms: sudden smell/taste changes (STC, N = 4,445), other symptoms excluding smell or taste changes (OthS, N = 832), and no symptoms (NoS, N = 416). Taste, smell, and oral irritation intensities and self-assessed abilities were rated on visual analog scales. Compared to the NoS group, COVID+ was associated with a 21% reduction in taste (95% confidence interval (CI): 15-28%), 47% in smell (95% CI: 37-56%), and 17% in oral irritation (95% CI: 10-25%) intensity. There were medium to strong correlations between perceived intensities and self-reported abilities (r = 0.84 for smell, r = 0.68 for taste, and r = 0.37 for oral irritation). Our study demonstrates that COVID-19-positive individuals report taste dysfunction when self-tested with stimuli that have little to none olfactory components. Assessing the smell and taste intensity of household items is a promising, cost-effective screening tool that complements self-reports and may help to disentangle taste loss from smell loss. However, it does not replace standardized validated psychophysical tests.

The potential for clinical application of automatic quantification of olfactory bulb volume in MRI scans using convolutional neural networks.

The olfactory bulbs (OBs) play a key role in olfactory processing; their volume is important for diagnosis, prognosis and treatment of patients with olfactory loss. Until now, measurements of OB volumes have been limited to quantification of manually segmented OBs, which is a cumbersome task and makes evaluation of OB volumes in large scale clinical studies infeasible. Hence, the aim of this study was to evaluate the potential of our previously developed automatic OB segmentation method for application in clinical practice and to relate the results to clinical outcome measures. To evaluate utilization potential of the automatic segmentation method, three data sets containing MR scans of patients with olfactory loss were included. Dataset 1 (N = 66) and 3 (N = 181) were collected at the Smell and Taste Center in Ede (NL) on a 3 T scanner; dataset 2 (N = 42) was collected at the Smell and Taste Clinic in Dresden (DE) on a 1.5 T scanner. To define the reference standard, manual annotation of the OBs was performed in Dataset 1 and 2. OBs were segmented with a method that employs two consecutive convolutional neural networks (CNNs) that the first localize the OBs in an MRI scan and subsequently segment them. In Dataset 1 and 2, the method accurately segmented the OBs, resulting in a Dice coefficient above 0.7 and average symmetrical surface distance below 0.3 mm. Volumes determined from manual and automatic segmentations showed a strong correlation (Dataset 1: r = 0.79, p < 0.001; Dataset 2: r = 0.72, p = 0.004). In addition, the method was able to recognize the absence of an OB. In Dataset 3, OB volumes computed from automatic segmentations obtained with our method were related to clinical outcome measures, i.e. duration and etiology of olfactory loss, and olfactory ability. We found that OB volume was significantly related to age of the patient, duration and etiology of olfactory loss, and olfactory ability (F(5, 172) = 11.348, p < 0.001, R2 = 0.248). In conclusion, the results demonstrate that automatic segmentation of the OBs and subsequent computation of their volumes in MRI scans can be performed accurately and can be applied in clinical and research population studies. Automatic evaluation may lead to more insight in the role of OB volume in diagnosis, prognosis and treatment of olfactory loss.

Sensory appeal and puffing intensity of e-cigarette use: Influence of nicotine salts versus free-base nicotine in e-liquids.

BACKGROUND: In the US, nicotine salts (with protonated nicotine instead of free-based nicotine) have been reported to lower the harshness and bitterness of e-cigarette aerosols, making it easier to inhale high levels of nicotine. This study aimed to determine whether nicotine salts also increase sensory appeal at lower concentrations (< 20mg/mL). Moreover, and novel, inhalation intensity of both types of e-liquids was compared. METHODS: In a randomized, double-blinded, within-participants design, healthy adults who use e-cigarettes (n=68) vaped tobacco-flavored e-liquids containing 12mg/mL of free-based nicotine or nicotine salt ad libitum, using their own device, during two online sessions (June-July 2021, Utrecht, The Netherlands). The sensory parameters perceived liking, nicotine intensity, harshness, and pleasantness were rated on a 100-unit visual analog scale. The intensity of use was determined by the recorded puff number, duration and interval. RESULTS: Test scores on appeal, harshness and puffing behavior parameters showed no significant differences between the nicotine salt and the free-base condition. The average inhalation time was 2.5seconds. Additional analyses found no significant effect of liquid order, age, gender, smoking status, vaping frequency and familiarity with nicotine salts. Significant positive correlations were found between the sensory parameters except for harshness. CONCLUSIONS: Contrary to a previous study that used higher nicotine concentrations and standardized puffing conditions in a laboratory setting, we did not observe the effects of nicotine salts on sensory appeal in our real-life study paradigm. Moreover, we did not see effects on study parameters related to puffing intensity.

Covid-19 affects taste independently of smell: results from a combined chemosensory home test and online survey from a global cohort (N=10,953).

People often confuse smell loss with taste loss, so it is unclear how much gustatory function is reduced in patients self-reporting taste loss. Our pre-registered cross-sectional study design included an online survey in 12 languages with instructions for self-administering chemosensory tests with ten household items. Between June 2020 and March 2021, 10,953 individuals participated. Of these, 3,356 self-reported a positive and 602 a negative COVID-19 diagnosis (COVID+ and COVID-, respectively); 1,267 were awaiting test results (COVID?). The rest reported no respiratory illness and were grouped by symptoms: sudden smell/taste changes (STC, N=4,445), other symptoms excluding smell or taste loss (OthS, N=832), and no symptoms (NoS, N=416). Taste, smell, and oral irritation intensities and self-assessed abilities were rated on visual analog scales. Compared to the NoS group, COVID+ was associated with a 21% reduction in taste (95% Confidence Interval (CI): 15-28%), 47% in smell (95%-CI: 37-56%), and 17% in oral irritation (95%-CI: 10-25%) intensity. In all groups, perceived intensity of smell (r=0.84), taste (r=0.68), and oral irritation (r=0.37) was correlated. Our findings suggest most reports of taste dysfunction with COVID-19 were genuine and not due to misinterpreting smell loss as taste loss (i.e., a classical taste-flavor confusion). Assessing smell and taste intensity of household items is a promising, cost-effective screening tool that complements self-reports and helps to disentangle taste loss from smell loss. However, it does not replace standardized validated psychophysical tests.

Sensory methods to evaluate perception of flavours in tobacco and other nicotine-containing products: a review.

OBJECTIVES: Sensory methods use human senses to evaluate product attributes. This review provides an overview of the types of sensory methods used to evaluate the perception of flavour in tobacco and other nicotine-containing (ToNic) products and to discuss how sensory data could inform flavoured ToNic product policy. DATA SOURCES: PubMed, Embase and Web of Science. STUDY SELECTION: All peer-reviewed studies evaluating ToNic products using a sensory method published before 23 May 2020. DATA EXTRACTION: Two independent coders completed title/abstract and full-text screening to choose articles for inclusion (Cohen's kappa=0.85, strong agreement). Each coder completed data extraction on half the articles, recording relevant information (eg, sensory methods used, results). The coders categorised sensory methods and generated overarching themes. DATA SYNTHESIS: Of 110 articles identified, we included 29 articles containing 35 studies that used sensory methods to investigate ToNic products. The sensory methods included analytic methods such as discrimination and descriptive tests and hedonic methods such as liking tests. Six themes emerged regarding how sensory methods can be used to understand consumer perception and liking of ToNic products and to inform ToNic product policy. CONCLUSIONS: The identified studies highlight that sensory data can inform ToNic product policy. Analytic and sensory hedonic ratings can be used to assess a ToNic product's ability to promote addiction in the user (ie, abuse liability). Lastly, hedonic ratings can provide information to assess potential use behaviours.

Subjective Mouthfeel and Temperature Alterations in COVID-19 Patients Six to Ten Months After Diagnosis.

Introduction: The characteristics and impact of mouthfeel, temperature, smell, and taste alterations in patients with COVID-19 at a long term are yet not well known. In this study, these characteristics and their impact on daily life and quality of life (QoL) were assessed, six to ten months after infection, in patients with COVID-19 searching for peer support on Facebook. Methods: Between December 2020 and January 2021, members of two COVID-19 Facebook groups were invited to complete a questionnaire. Participants were asked to report their perception of mouthfeel, temperature, smell, and taste alterations and their impact. Results: The questionnaire was completed by 157/216 respondents (73%), with 92% being women. Alterations in mouthfeel, temperature, smell, and taste were reported by respectively 66, 40, 148, and 133 participants. The most frequently reported mouthfeel alterations were "a different feeling" and "dry mouth" in 38 and 30 participants, respectively. Preferences for food temperature were equally changed to "freezing", "cool", "room temperature", "a bit warmer", and "warmer". An impact on daily life and QoL was reported by most patients with alterations in mouthfeel (91% and 79%), temperature (78% and 60%), smell (98% and 93%), and taste (93% and 88%), respectively. Conclusions: Patients with COVID-19 searching for peer support on Facebook experienced, next to smell and taste alterations, mouthfeel and temperature disturbances, six to ten months after infection. These alterations have an impact on daily life and QoL. Implications: Health professionals should, next to smell and taste alterations, be aware of mouthfeel and temperature alterations in patients with COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1007/s12078-022-09304-y.

Prednisolone does not improve olfactory function after COVID-19: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Prednisolone has been suggested as a treatment for olfactory disorders after COVID-19, but evidence is scarce. Hence, we aimed to determine the efficacy of a short oral prednisolone treatment on patients with persistent olfactory disorders after COVID-19. METHODS: We performed a randomized, double-blind, placebo-controlled, single-centered trial in the Netherlands. Patients were included if they were > 18 years old and if they had persistent (> 4 weeks) olfactory disorders within 12 weeks after a confirmed COVID-19 test. The treatment group received oral prednisolone 40 mg once daily for 10 days and the placebo group received matching placebo. In addition, all patients performed olfactory training. The primary outcome was the objective olfactory function on Sniffin' Sticks Test (SST) 12 weeks after the start of treatment, measured in Threshold-Discrimination-Identification (TDI) score. Secondary outcomes were objective gustatory function assessed by the Taste Strip Test (TST) and subjective self-reported outcomes on questionnaires about olfactory, gustatory and trigeminal function, quality of life, and nasal symptoms. The CONSORT 2010 guideline was performed. RESULTS: Between November 2021 and February 2022, we included 115 eligible patients, randomly assigned to the treatment (n = 58) or placebo group (n = 57). No difference in olfactory function between groups was obtained after 12 weeks. Median TDI score on SST was 26.8 (IQR 23.6-29.3) in the placebo group and 28.8 (IQR 24.0-30.9) in the prednisolone group, with a median difference of 2.0 (95% CI 0.75 to 1.5). There was similar improvement on olfactory function in both groups after 12 weeks. Furthermore, on secondary outcomes, we obtained no differences between groups. CONCLUSIONS: This trial shows that prednisolone does not improve olfactory function after COVID-19. Therefore, we recommend not prescribing prednisolone for patients with persistent olfactory disorders after COVID-19. TRIAL REGISTRATION: This trial is registered on the ISRCTN registry with trial ID ISRCTN70794078.

COCOS trial: COrticosteroids for COVID-19-induced loss of Smell-protocol for a single-centred, double-blind, randomised, placebo-controlled trial.

INTRODUCTION: Hyposmia and anosmia are common in COVID-19. Most patients regain normal smell within 4 weeks, but severe loss of smell persists roughly in 20% after 2 months and may last up to a year or longer. These persistent smell disorders greatly influence daily life. It is hypothesised that COVID-19 induces inflammation around the olfactory nerve and in the olfactory pathway, leading to smell disorders. Corticosteroids might reduce this local inflammatory response and improve smell. METHODS AND ANALYSIS: We will conduct a single-centre, randomised, placebo-controlled trial to determine the efficacy of a short high-dose treatment of oral prednisolone for persistent loss of smell after COVID-19 in the early phase. We will include 116 patients with persistent (>4 weeks) loss of smell within 12 weeks of COVID-19 diagnosis, based on a positive PCR/antigen test. One group receives 40 mg of prednisolone for 10 days and the other group receives matching placebo treatment. In addition, all patients will perform smell training for 12 weeks. The primary outcome is objective olfactory function measured by means of sniffin' sticks test. Secondary outcomes are objective gustatory function by means of taste strips test and subjective taste and smell ability, trigeminal sensations, quality of life and nasal symptoms, measured by three questionnaires. These outcomes will be measured at inclusion before treatment and 12 weeks later. ETHICS AND DISSEMINATION: The Institutional Review Board of the University Medical Center Utrecht approved the research protocol (21-635/G-D, October 2021). The trial results will be shared in peer-reviewed medical journals and scientific conferences. TRIAL REGISTRATION NUMBER: NL9635. EUCTR2021-004021-71-NL.

Olfactory discrimination of fat content in milks is facilitated by differences in volatile compound composition rather than odor intensity.

The mechanisms underlying the ability of humans to olfactorily discriminate fat content in milks remain unknown. In this study, we found that fat contents (0.5, 1.5 and 3.5% fat) can be discriminated by olfaction in commercially available pasteurized milks (p < 0.05) but not in ultra-high temperature processed (UHT) milks. The composition of volatile compounds of pasteurized milks differed with fat content, whereas that of UHT milks differing in fat content was similar. Principal component analysis revealed that differences in volatile compound composition of pasteurized milks differing in fat content contribute to olfactory discrimination. In UHT milks, acetoin and 2-heptanone may mask odor differences leading to indistinguishable odors. No differences were observed regarding perceived odor intensity of pasteurized milks or UHT milks differing in fat content. We conclude that the olfactory discrimination of fat content in pasteurized milks is facilitated by differences in volatile compound composition rather than odor intensity.

Human spatial memory is biased towards high-calorie foods: a cross-cultural online experiment.

BACKGROUND: Human memory appears to prioritise locations of high-calorie foods, likely as an adaptation for foraging within fluctuating ancestral food environments. Importantly, this "high-calorie bias" in human spatial memory seems to yield consequences for individual eating behaviour in modern food-abundant settings. However, as studies have mainly been conducted in European (Dutch) populations to date, we investigated whether the existence of the cognitive bias can be reasonably generalised across countries that vary on culturally-relevant domains, such as that of the USA and Japan. Furthermore, we investigated whether sociodemographic factors moderate the expression of the high-calorie spatial memory bias in different populations. METHODS: In a cross-cultural online experiment, we measured the food location memory of diverse participants from the USA (N = 72; 44.4% Male; 54 ± 15.99 years) and Japan (N = 74; 56.8% Male; 50.85 ± 17.32 years), using a validated computer-based spatial memory task with standardised images of high-calorie and low-calorie foods. To directly compare the magnitude of the high-calorie spatial memory bias in a broader cultural scope, we also included data from a previous online experiment that identically tested the food spatial memory of a Dutch sample (N = 405; 56.7% Male; 47.57 ± 17.48 years). RESULTS: In the US sample, individuals more accurately recalled (i.e. had lower pointing errors for) locations of high-calorie foods versus that of low-calorie alternatives (Mean difference = -99.23 pixels, 95% CI = [-197.19, -1.28]) - regardless of one's hedonic preferences, familiarity with foods, and encoding times. Likewise, individuals in the Japanese sample displayed an enhanced memory for locations of high-calorie (savoury-tasting) foods (Mean difference = -40.41 pixels, 95% CI = [-76.14, -4.68]), while controlling for the same set of potential confounders. The magnitude of the high-calorie bias in spatial memory was similar across populations (i.e. the USA, Japan, and the Netherlands), as well as across diverse sociodemographic groups within a population. CONCLUSIONS: Our results demonstrate that the high-calorie bias in spatial memory transcends sociocultural boundaries. Since the cognitive bias may negatively impact on our dietary decisions, it would be wise to invest in strategies that intervene on our seemingly universal ability to efficiently locate calorie-rich foods.