Chemical SensesPub Date : 2023-01-01DOI: 10.1093/chemse/bjad039
Yao Zhao, Surabhi Bhutani, Thorsten Kahnt
{"title":"Appetite-regulating hormones modulate odor perception and odor-evoked activity in hypothalamus and olfactory cortices.","authors":"Yao Zhao, Surabhi Bhutani, Thorsten Kahnt","doi":"10.1093/chemse/bjad039","DOIUrl":"10.1093/chemse/bjad039","url":null,"abstract":"<p><p>Odors guide food seeking, and food intake modulates olfactory function. This interaction is mediated by appetite-regulating hormones like ghrelin, insulin, and leptin, which alter activity in the rodent olfactory bulb, but their effects on downstream olfactory cortices have not yet been established in humans. The olfactory tract connects the olfactory bulb to the cortex through 3 main striae, terminating in the piriform cortex (PirC), amygdala (AMY), olfactory tubercule (OT), and anterior olfactory nucleus (AON). Here, we test the hypothesis that appetite-regulating hormones modulate olfactory processing in the endpoints of the olfactory tract and the hypothalamus. We collected odor-evoked functional magnetic resonance imaging (fMRI) responses and plasma levels of ghrelin, insulin, and leptin from human subjects (n = 25) after a standardized meal. We found that a hormonal composite measure, capturing variance relating positively to insulin and negatively to ghrelin, correlated inversely with odor intensity ratings and fMRI responses to odorized vs. clean air in the hypothalamus, OT, and AON. No significant correlations were found with activity in PirC or AMY, the endpoints of the lateral stria. Exploratory whole-brain analyses revealed significant correlations near the diagonal band of Broca and parahippocampal gyrus. These results demonstrate that high (low) blood plasma concentrations of insulin (ghrelin) decrease perceived odor intensity and odor-evoked activity in the cortical targets of the medial and intermediate striae of the olfactory tract, as well as the hypothalamus. These findings expand our understanding of the cortical mechanisms by which metabolic hormones in humans modulate olfactory processing after a meal.</p>","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10590159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41109788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical SensesPub Date : 2023-01-01DOI: 10.1093/chemse/bjad042
Cecilia G Bouaichi, Katherine E Odegaard, Camden Neese, Roberto Vincis
{"title":"Oral thermal processing in the gustatory cortex of awake mice.","authors":"Cecilia G Bouaichi, Katherine E Odegaard, Camden Neese, Roberto Vincis","doi":"10.1093/chemse/bjad042","DOIUrl":"10.1093/chemse/bjad042","url":null,"abstract":"<p><p>Oral temperature is a sensory cue relevant to food preference and nutrition. To understand how orally sourced thermal inputs are represented in the gustatory cortex (GC), we recorded neural responses from the GC of male and female mice presented with deionized water at different innocuous temperatures (14 °C, 25 °C, and 36 °C) and taste stimuli (room temperature). Our results demonstrate that GC neurons encode orally sourced thermal information in the absence of classical taste qualities at the single neuron and population levels, as confirmed through additional experiments comparing GC neuron responses to water and artificial saliva. Analysis of thermal-evoked responses showed broadly tuned neurons that responded to temperature in a mostly monotonic manner. Spatial location may play a minor role regarding thermosensory activity; aside from the most ventral GC, neurons reliably responded to and encoded thermal information across the dorso-ventral and antero-postero cortical axes. Additional analysis revealed that more than half of the GC neurons that encoded chemosensory taste stimuli also accurately discriminated thermal information, providing additional evidence of the GC's involvement in processing thermosensory information important for ingestive behaviors. In terms of convergence, we found that GC neurons encoding information about both taste and temperature were broadly tuned and carried more information than taste-selective-only neurons; both groups encoded similar information about the palatability of stimuli. Altogether, our data reveal new details of the cortical code for the mammalian oral thermosensory system in behaving mice and pave the way for future investigations on GC functions and operational principles with respect to thermogustation.</p>","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10630187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical SensesPub Date : 2023-01-01DOI: 10.1093/chemse/bjad005
Nitzan Dubovski, Yaron Ben-Shoshan Galezcki, Einav Malach, Masha Y Niv
{"title":"Sensitivity of human sweet taste receptor subunits T1R2 and T1R3 to activation by glucose enantiomers.","authors":"Nitzan Dubovski, Yaron Ben-Shoshan Galezcki, Einav Malach, Masha Y Niv","doi":"10.1093/chemse/bjad005","DOIUrl":"https://doi.org/10.1093/chemse/bjad005","url":null,"abstract":"<p><p>We have previously shown that l-glucose, the non-caloric enantiomer of d-glucose, activates the human sweet taste receptor T1R2/T1R3 transiently expressed in HEK293T cells. Here, we show that d- and l-glucose can also activate T1R2 and T1R3 expressed without the counterpart monomer. Serine mutation to alanine in residue 147 in the binding site of T1R3 VFT domain, completely abolishes T1R3S147A activation by either l- or d-glucose, while T1R2/T1R3S147A responds in the same way as T1R2 expressed without its counterpart. We further show that the original T1R2 reference sequence (NM_152232.1) is less sensitive by almost an order of magnitude than the reference sequence at the time this study was performed (NM_152232.4). We find that out of the four differing positions, it is the R317G in the VFT domain of T1R2, that is responsible for this effect in vitro. It is significant for both practical assay sensitivity and because glycine is found in this position in ~20% of the world population. While the effects of the mutations and the partial transfections were similar for d and l enantiomers, their dose-response curves remained distinct, with l-glucose reaching an early plateau.</p>","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":"48 ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9472762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical SensesPub Date : 2023-01-01DOI: 10.1093/chemse/bjad024
{"title":"Correction to: Reply: taste loss as a distinct symptom of COVID-19: a systematic review and meta-analysis.","authors":"","doi":"10.1093/chemse/bjad024","DOIUrl":"10.1093/chemse/bjad024","url":null,"abstract":"","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":"48 ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10893958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10523571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical SensesPub Date : 2023-01-01DOI: 10.1093/chemse/bjad033
Cindy Levesque-Boissonneault, Nicholas Bussière, Frédérique Roy-Côté, Frank Cloutier, Marie-Ève Caty, Johannes Frasnelli
{"title":"A quick test to objectify smell and taste dysfunction at home: a proof of concept for the validation of the chemosensory perception test.","authors":"Cindy Levesque-Boissonneault, Nicholas Bussière, Frédérique Roy-Côté, Frank Cloutier, Marie-Ève Caty, Johannes Frasnelli","doi":"10.1093/chemse/bjad033","DOIUrl":"10.1093/chemse/bjad033","url":null,"abstract":"<p><p>Recent studies have shown the efficacy of a home test for the self-evaluation of olfactory and gustatory functions in quarantined coronavirus disease-2019 (COVID-19) patients. However, testing was often limited to COVID-19 participants, and the accuracy of home test kits was rarely compared to standardized testing. This study aims at providing proof of concept for the validation of the new Chemosensory Perception Test (CPT) developed to remotely assess orthonasal olfactory, retronasal olfactory, and gustatory functions in various populations using common North American household items. In the 2 experiments, a total of 121 participants irrespective of having olfactory and/or gustatory complaints from various causes (COVID-19, sinunasal, post-viral, idiopathic) were tested first, with one or many of the following tests: (i) a brief chemosensory questionnaire, (ii) an olfactory test-Sniffin' Sticks Test (SST) or University of Pennsylvania Smell Identification Test (UPSIT), and/or (iii) a gustatory test-Brief Waterless Empirical Taste Test (B-WETT). We then applied the CPT which yielded 3 different subscores, namely orthonasal, retronasal, and gustatory CPT scores. The orthonasal CPT score was significantly correlated with SST (ρ = 0.837, P < 0.001) and UPSIT (ρ = 0.364, P < 0.001) scores, and exhibited an excellent accuracy to identify olfactory dysfunction (OD) as compared to SST (area under the curve [AUC]: 0.923 [95% confidence interval {CI}, 0.822-1.000], P < 0.001). The retronasal CPT score but not the gustatory CPT score allowed to distinguish between participants with or without subjective gustatory complaint (AUC: 0.818 [95% CI, 0.726-0.909], P < 0.001). The CPT has the ability to identify OD and to quantify subjective gustatory complaints.</p>","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10746307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10011242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical SensesPub Date : 2023-01-01DOI: 10.1093/chemse/bjad044
{"title":"Retraction and replacement of: Taste loss as a distinct symptom of COVID-19: a systematic review and meta-analysis.","authors":"","doi":"10.1093/chemse/bjad044","DOIUrl":"https://doi.org/10.1093/chemse/bjad044","url":null,"abstract":"","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":"48 ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10723633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138796198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical SensesPub Date : 2023-01-01DOI: 10.1093/chemse/bjad007
Rosario B Jaime-Lara, Alexis T Franks, Khushbu Agarwal, Nafisa Nawal, Amber B Courville, Juen Guo, Shanna Yang, Brianna E Brooks, Abhrarup Roy, Karen Taylor, Valerie L Darcey, James D LeCheminant, Stephanie Chung, Ciarán G Forde, Kevin D Hall, Paule V Joseph
{"title":"No significant salt or sweet taste preference or sensitivity differences following ad libitum consumption of ultra-processed and unprocessed diets: a randomized controlled pilot study.","authors":"Rosario B Jaime-Lara, Alexis T Franks, Khushbu Agarwal, Nafisa Nawal, Amber B Courville, Juen Guo, Shanna Yang, Brianna E Brooks, Abhrarup Roy, Karen Taylor, Valerie L Darcey, James D LeCheminant, Stephanie Chung, Ciarán G Forde, Kevin D Hall, Paule V Joseph","doi":"10.1093/chemse/bjad007","DOIUrl":"https://doi.org/10.1093/chemse/bjad007","url":null,"abstract":"<p><p>Ultra-processed food consumption has increased worldwide, yet little is known about the potential links with taste preference and sensitivity. This exploratory study aimed to (i) compare sweet and salty taste detection thresholds and preferences following consumption of ultra-processed and unprocessed diets, (ii) investigate whether sweet and salty taste sensitivity and preference were associated with taste substrates (i.e. sodium and sugar) and ad libitum nutrient intake, and (iii) examine associations of taste detection thresholds and preferences with blood pressure (BP) and anthropometric measures following consumption of ultra-processed and unprocessed diets. In a randomized crossover study, participants (N = 20) received ultra-processed or unprocessed foods for 2 weeks, followed by the alternate diet. Baseline food intake data were collected prior to admission. Taste detection thresholds and preferences were measured at the end of each diet arm. Taste-substrate/nutrient intake, body mass index (BMI), and body weight (BW) were measured daily. No significant differences were observed in participant salt and sweet detection thresholds or preferences after 2 weeks on ultra-processed or unprocessed diets. There was no significant association between salt and sweet taste detection thresholds, preferences, and nutrient intakes on either diet arm. A positive correlation was observed between salt taste preference and systolic BP (r = 0.59; P = 0.01), BW (r = 0.47, P = 0.04), and BMI (r = 0.50; P = 0.03) following consumption of the ultra-processed diet. Thus, a 2-week consumption of an ultra-processed diet does not appear to acutely impact sweet or salty taste sensitivity or preference. Trial Registration: ClinicalTrials.gov Identifier NCT03407053.</p>","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":"48 ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10066841/pdf/bjad007.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9843890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical SensesPub Date : 2023-01-01DOI: 10.1093/chemse/bjad002
Stephanie R Hunter, Mackenzie E Hannum, Robert Pellegrino, Maureen A O'Leary, Nancy E Rawson, Danielle R Reed, Pamela H Dalton, Valentina Parma
{"title":"Proof-of-concept: SCENTinel 1.1 rapidly discriminates COVID-19-related olfactory disorders.","authors":"Stephanie R Hunter, Mackenzie E Hannum, Robert Pellegrino, Maureen A O'Leary, Nancy E Rawson, Danielle R Reed, Pamela H Dalton, Valentina Parma","doi":"10.1093/chemse/bjad002","DOIUrl":"10.1093/chemse/bjad002","url":null,"abstract":"<p><p>It is estimated that 20%-67% of those with COVID-19 develop olfactory disorders, depending on the SARS-CoV-2 variant. However, there is an absence of quick, population-wide olfactory tests to screen for olfactory disorders. The purpose of this study was to provide a proof-of-concept that SCENTinel 1.1, a rapid, inexpensive, population-wide olfactory test, can discriminate between anosmia (total smell loss), hyposmia (reduced sense of smell), parosmia (distorted odor perception), and phantosmia (odor sensation without a source). Participants were mailed a SCENTinel 1.1 test, which measures odor detection, intensity, identification, and pleasantness, using one of 4 possible odors. Those who completed the test (N = 287) were divided into groups based on their self-reported olfactory function: quantitative olfactory disorder only (anosmia or hyposmia, N = 135), qualitative olfactory disorder only (parosmia and/or phantosmia; N = 86), and normosmia (normal sense of smell; N = 66). SCENTinel 1.1 accurately discriminates quantitative olfactory disorders, qualitative olfactory disorders, and normosmia groups. When olfactory disorders were assessed individually, SCENTinel 1.1 discriminates between hyposmia, parosmia, and anosmia. Participants with parosmia rated common odors less pleasant than those without parosmia. We provide proof-of-concept that SCENTinel 1.1, a rapid smell test, can discriminate quantitative and qualitative olfactory disorders, and is the only direct test to rapidly discriminate parosmia.</p>","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":"48 ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9935080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9143203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical SensesPub Date : 2023-01-01DOI: 10.1093/chemse/bjac037
Narumi Sato-Akuhara, Casey Trimmer, Andreas Keller, Yoshihito Niimura, Mika Shirasu, Joel D Mainland, Kazushige Touhara
{"title":"Genetic variation in the human olfactory receptor OR5AN1 associates with the perception of musks.","authors":"Narumi Sato-Akuhara, Casey Trimmer, Andreas Keller, Yoshihito Niimura, Mika Shirasu, Joel D Mainland, Kazushige Touhara","doi":"10.1093/chemse/bjac037","DOIUrl":"10.1093/chemse/bjac037","url":null,"abstract":"<p><p>Humans have significant individual variations in odor perception, derived from their experience or sometimes from differences in the olfactory receptor (OR) gene repertoire. In several cases, the genetic variation of a single OR affects the perception of its cognate odor ligand. Musks are widely used for fragrance and are known to demonstrate specific anosmia. It, however, remains to be elucidated whether the OR polymorphism contributes to individual variations in musk odor perception. Previous studies reported that responses of the human musk receptor OR5AN1 to a variety of musks in vitro correlated well with perceptual sensitivity to those odors in humans and that the mouse ortholog, Olfr1440 (MOR215-1), plays a critical role in muscone perception. Here, we took advantage of genetic variation in OR5AN1 to examine how changes in receptor sensitivity are associated with human musk perception. We investigated the functional differences between OR5AN1 variants in an in vitro assay and measured both perceived intensity and detection threshold in human subjects with different OR5AN1 genotypes. Human subjects homozygous for the more sensitive L289F allele had a lower detection threshold for muscone and found macrocyclic musks to be more intense than subjects homozygous for the reference allele. These results demonstrate that the genetic variation in OR5AN1 contributes to perceptual differences for some musks. In addition, we found that the more functional variant of OR5A1, a receptor involved in β-ionone perception, is associated with the less functional variant of OR5AN1, suggesting that the perceived intensities of macrocyclic musks and β-ionone are inversely correlated.</p>","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":"48 ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9874024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9511019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemical SensesPub Date : 2023-01-01DOI: 10.1093/chemse/bjad038
Celeste Ferraris, Christopher J Scarlett, Tamara Bucher, Emma L Beckett
{"title":"Liking of salt is associated with depression, anxiety, and stress.","authors":"Celeste Ferraris, Christopher J Scarlett, Tamara Bucher, Emma L Beckett","doi":"10.1093/chemse/bjad038","DOIUrl":"10.1093/chemse/bjad038","url":null,"abstract":"<p><p>Early research has shown variations in salt taste qualities in depression, anxiety, and stress. These studies evaluated changes to salt taste intensity and liking (pleasantness) of salt solutions but not of salty foods. Therefore, an Australian population survey (n = 424) was conducted where participants rated recalled intensity and liking of salt index foods and completed the Depression, Anxiety, and Stress Scale (DASS-21) to measure these states. Standard least squares regression (post hoc Tukey's HSD) compared means between groups, and nominal logistic regression assessed differences in distributions between categories. Higher salt liking was found in participants with DASS-21 scores indicative of severe depression (68.3 vs. 60.0, P = 0.005) and severe anxiety (68.4 vs. 60.0, P = 0.001) in comparison to those with normal scores, in all models. Higher salt liking was found in participants with DASS-21 scores indicative of moderate stress (67.7 vs. 60.2, P = 0.009) in the unadjusted model only. Higher salt liking was found in females with DASS-21 scores indicative of anxiety and stress, and in males with indicative depression and anxiety. No relationships between salt taste intensity ratings and the mood states were found. Results indicate that liking salty foods is positively correlated with depression, anxiety, and stress scores. Further research on the relationships between salt liking and intake of salt and salty foods, and the biological mechanisms of these mood states are needed to direct the application of findings toward potential new risk assessment measures, dietary interventions, or therapeutics.</p>","PeriodicalId":9771,"journal":{"name":"Chemical Senses","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41112348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}