RESUMEN
SCENTinel, a rapid smell test designed to screen for olfactory disorders, including anosmia (no ability to smell an odor) and parosmia (distorted sense of smell), measures 4 components of olfactory function: detection, intensity, identification, and pleasantness. Each test card contains one of 9 odorant mixtures. Some people born with genetic insensitivities to specific odorants (i.e. specific anosmia) may fail the test if they cannot smell an odorant but otherwise have a normal sense of smell. However, using odorant mixtures has largely been found to prevent this from happening. To better understand whether genetic differences affect SCENTinel test results, we asked genetically informative adult participants (twins or triplets, Nâ =â 630; singletons, Nâ =â 370) to complete the SCENTinel test. A subset of twins (nâ =â 304) also provided a saliva sample for genotyping. We examined data for differences between the 9 possible SCENTinel odors; effects of age, sex, and race on SCENTinel performance, test-retest variability; and heritability using both structured equation modeling and SNP-based statistical methods. None of these strategies provided evidence for specific anosmia for any of the odors, but ratings of pleasantness were, in part, genetically determined (h2â =â 0.40) and were nominally associated with alleles of odorant receptors (e.g. OR2T33 and OR1G1; Pâ <â 0.001). These results provide evidence that using odorant mixtures protected against effects of specific anosmia for ratings of intensity but that ratings of pleasantness showed effects of inheritance, possibly informed by olfactory receptor genotypes.
Asunto(s)
Odorantes , Olfato , Humanos , Femenino , Masculino , Adulto , Odorantes/análisis , Olfato/fisiología , Persona de Mediana Edad , Trastornos del Olfato/diagnóstico , Trastornos del Olfato/genética , Adulto Joven , Percepción Olfatoria , Anciano , Genotipo , Anosmia/diagnóstico , Anosmia/genéticaRESUMEN
The bitter taste of medicines hinders patient compliance, but not everyone experiences these difficulties because people worldwide differ in their bitterness perception. To better understand how people from diverse ancestries perceive medicines and taste modifiers, 338 adults, European and recent US and Canada immigrants from Asia, South Asia, and Africa, rated the bitterness intensity of taste solutions on a 100-point generalized visual analog scale and provided a saliva sample for genotyping. The taste solutions were five medicines, tenofovir alafenamide (TAF), moxifloxacin, praziquantel, amodiaquine, and propylthiouracil (PROP), and four other solutions, TAF mixed with sucralose (sweet, reduces bitterness) or 6-methylflavone (tasteless, reduces bitterness), sucralose alone, and sodium chloride alone. Bitterness ratings differed by ancestry for two of the five drugs (amodiaquine and PROP) and for TAF mixed with sucralose. Genetic analysis showed that people with variants in one bitter receptor variant gene (TAS2R38) reported PROP was more bitter than did those with a different variant (p= 7.6e-19) and that people with either an RIMS2 or a THSD4 genotype found sucralose more bitter than did others (p=2.6e-8, p=7.9e-11, resp.). Our findings may help guide the formulation of bad-tasting medicines to meet the needs of those most sensitive to them.
RESUMEN
BACKGROUND: The liking for sweet taste is a powerful driver for consuming added sugars, and therefore, understanding how sweet liking is formed is a critical step in devising strategies to lower added sugars consumption. However, current research on the influence of genetic and environmental factors on sweet liking is mostly based on research conducted with individuals of European ancestry. Whether these results can be generalized to people of other ancestry groups warrants investigation. METHODS: We will determine the differences in allele frequencies in sweet-related genetic variants and their effects on sweet liking in 426 adults of either African or East Asian ancestry, who have the highest and lowest average added sugars intake, respectively, among ancestry groups in the U.S. We will collect information on participants' sweet-liking phenotype, added sugars intake (sweetness exposure), anthropometric measures, place-of-birth, and for immigrants, duration of time living in the U.S. and age when immigrated. Ancestry-specific polygenic scores of sweet liking will be computed based on the effect sizes of the sweet-related genetic variants on the sweet-liking phenotype for each ancestry group. The predictive validity of the polygenic scores will be tested using individuals of African and East Asian ancestry from the UK Biobank. We will also compare sweet liking between U.S.-born individuals and immigrants within each ancestry group to test whether differences in environmental sweetness exposure during childhood affect sweet liking in adulthood. DISCUSSION: Expanding genetic research on taste to individuals from ancestry groups traditionally underrepresented in such research is consistent with equity goals in sensory and nutrition science. Findings from this study will help in the development of a more personalized nutrition approach for diverse populations. TRIAL REGISTRATION: This protocol has been preregistered with the Center for Open Science (https://doi.org/10.17605/OSF.IO/WPR9E).
Asunto(s)
Asiático , Negro o Afroamericano , Preferencias Alimentarias , Gusto , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Frecuencia de los Genes , Polimorfismo de Nucleótido Simple , Gusto/genética , Gusto/fisiología , Estados Unidos , Asiático/genética , Negro o Afroamericano/genética , Proyectos de InvestigaciónRESUMEN
Introduction: Based on a large body of previous research suggesting that smell loss was a predictor of COVID-19, we investigated the ability of SCENTinel®, a newly validated rapid olfactory test that assesses odor detection, intensity, and identification, to predict SARS-CoV-2 infection in a community sample. Methods: Between April 5, 2021, and July 5, 2022, 1,979 individuals took one SCENTinel® test, completed at least one physician-ordered SARS-CoV-2 PCR test, and endorsed a list of self-reported symptoms. Results: Among the of SCENTinel® subtests, the self-rated odor intensity score, especially when dichotomized using a previously established threshold, was the strongest predictor of SARS-CoV-2 infection. SCENTinel® had high specificity and negative predictive value, indicating that those who passed SCENTinel® likely did not have a SARS-CoV-2 infection. Predictability of the SCENTinel® performance was stronger when the SARS-CoV-2 Delta variant was dominant rather than when the SARS-CoV-2 Omicron variant was dominant. Additionally, SCENTinel® predicted SARS-CoV-2 positivity better than using a self-reported symptom checklist alone. Discussion: These results indicate that SCENTinel® is a rapid assessment tool that can be used for population-level screening to monitor abrupt changes in olfactory function, and to evaluate spread of viral infections like SARS-CoV-2 that often have smell loss as a symptom.
Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Anciano , Sensibilidad y Especificidad , Odorantes , Trastornos del Olfato/diagnóstico , Trastornos del Olfato/virología , Adulto JovenRESUMEN
PURPOSE: The bad bitter taste of some medicines is a barrier to overcoming noncompliance with medication use, especially life-saving drugs given to children and the elderly. Here, we evaluated a new class of bitter blockers (thiazolidinediones, TZDs). METHODS: In this study, 2 TZDs were tested, rosiglitazone (ROSI) and a simpler form of TZD, using a high-potency sweetener as a positive control (neohesperidin dihydrochalcone, NHDC). We tested bitter-blocking effects using the bitter drugs tenofovir alafenamide fumarate (TAF), a treatment for HIV and hepatitis B infection, and praziquantel (PRAZ), a treatment for schistosomiasis, by conducting taste testing with 2 separate taste panels: a general panel (N = 97, 20-23 years, 82.5% female, all Eastern European) and a genetically informative panel (N = 158, including 68 twin pairs, 18-82 years, 76% female, 87% European ancestry). Participants rated the bitterness intensity of the solutions on a 100-point generalized visual analog scale. FINDINGS: Person-to-person differences in drug bitterness were striking; TAF and PRAZ were weakly or not bitter for some people but moderately to highly bitter for others. Participants in both taste panels rated the bitter drugs TAF and PRAZ as less bitter on average when mixed with NHDC than when sampled alone. ROSI partially suppressed the bitterness of TAF and PRAZ, but effectiveness differed between the 2 panels: bitterness was significantly reduced for PRAZ but not TAF in the general panel and for TAF but not PRAZ in the genetically informative panel. ROSI was a more effective blocker than the other TZD. IMPLICATIONS: These results suggest that TZDs are partially effective bitter blockers and the suppression efficacy differs from drug to drug, from person to person, and from panel to panel, suggesting other TZDs should be designed and tested with more drugs and on diverse populations to define which ones work best with which drugs and for whom. The discovery of bitter receptor blockers can improve compliance with medication use.
Asunto(s)
Gusto , Tiazolidinedionas , Humanos , Femenino , Masculino , Gusto/efectos de los fármacos , Adulto , Anciano , Persona de Mediana Edad , Adulto Joven , Adolescente , Anciano de 80 o más Años , Tiazolidinedionas/uso terapéutico , Tenofovir/uso terapéutico , Tenofovir/análogos & derivados , Rosiglitazona/farmacología , Rosiglitazona/uso terapéutico , AlaninaRESUMEN
Host defense at the mucosal interface requires collaborative interactions between diverse cell lineages. Epithelial cells damaged by microbial invaders release reparative proteins such as the Trefoil factor family (TFF) peptides that functionally restore barrier integrity. However, whether TFF peptides and their receptors also serve instructive roles for immune cell function during infection is incompletely understood. Here, we demonstrate that the intestinal trefoil factor, TFF3, restrains (T cell helper) TH1 cell proliferation and promotes host-protective type 2 immunity against the gastrointestinal parasitic nematode Trichuris muris. Accordingly, T cell-specific deletion of the TFF3 receptor, leucine-rich repeat and immunoglobulin containing nogo receptor 2 (LINGO2), impairs TH2 cell commitment, allows proliferative expansion of interferon (IFN)g+ cluster of differentiation (CD)4+ TH1 cells and blocks normal worm expulsion through an IFNg-dependent mechanism. This study indicates that TFF3, in addition to its known tissue reparative functions, drives anti-helminth immunity by controlling the balance between TH1/TH2 subsets.
Asunto(s)
Enfermedades Transmisibles , Enfermedades Gastrointestinales , Nematodos , Infecciones por Nematodos , Tricuriasis , Animales , Factor Trefoil-3 , Células TH1 , Linfocitos T Colaboradores-InductoresAsunto(s)
Salas de Parto , Cardiopatías Congénitas , Recién Nacido , Embarazo , Humanos , Femenino , Cardiopatías Congénitas/terapiaRESUMEN
Background: The liking for sweet taste is a powerful driver for consuming added sugars, and therefore, understanding how sweet liking is formed is a critical step in devising strategies to lower added sugars consumption. However, current research on the influence of genetic and environmental factors on sweet liking is mostly based on research conducted with individuals of European ancestry. Whether these results can be generalized to people of other ancestry groups warrants investigation. Methods: We will determine the differences in allele frequencies in sweet-related genetic variants and their effects on sweet liking in 426 adults of either African or East Asian ancestry, who have the highest and lowest average added sugars intake, respectively, among ancestry groups in the U.S. We will collect information on participants' sweet-liking phenotype, added sugars intake (sweetness exposure), anthropometric measures, place-of-birth, and for immigrants, duration of time living in the U.S. and age when immigrated. Ancestry-specific polygenic scores of sweet liking will be computed based on the effect sizes of the sweet-related genetic variants on the sweet-liking phenotype for each ancestry group. The predictive validity of the polygenic scores will be tested using individuals of African and East Asian ancestry from the UK Biobank. We will also compare sweet liking between U.S.-born individuals and immigrants within each ancestry group to test whether differences in environmental sweetness exposure during childhood affect sweet liking in adulthood. Discussion: Expanding genetic research on taste to individuals from ancestry groups traditionally underrepresented in such research is consistent with equity goals in sensory and nutrition science. Findings from this study will help in the development of a more personalized nutrition approach for diverse populations. Trial registration: This protocol has been preregistered with the Center for Open Science (https://doi.org/10.17605/OSF.IO/WPR9E) and is approved by the City University of New York Human Research Protection Program (IRB#: 2023-0064-Brooklyn).
RESUMEN
Skin employs interdependent cellular networks to facilitate barrier integrity and host immunity through ill-defined mechanisms. This study demonstrates that manipulation of itch-sensing neurons bearing the Mas-related G protein-coupled receptor A3 (MrgprA3) drives IL-17+ γδ T cell expansion, epidermal thickening, and resistance to the human pathogen Schistosoma mansoni through mechanisms that require myeloid antigen presenting cells (APC). Activated MrgprA3 neurons instruct myeloid APCs to downregulate interleukin 33 (IL-33) and up-regulate TNFα partially through the neuropeptide calcitonin gene related peptide (CGRP). Strikingly, cell-intrinsic deletion of IL-33 in myeloid APC basally alters chromatin accessibility at inflammatory cytokine loci and promotes IL-17/23-dependent epidermal thickening, keratinocyte hyperplasia, and resistance to helminth infection. Our findings reveal a previously undescribed mechanism of intercellular cross-talk wherein "itch" neuron activation reshapes myeloid cytokine expression patterns to alter skin composition for cutaneous immunity against invasive pathogens.
RESUMEN
Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19 taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020-2021, with 235 meeting all inclusion criteria. Drawing on previous studies and guided by early meta-analyses, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct measures of taste are at least as sensitive as those obtained by self-report and that the preponderance of evidence confirms taste loss is a symptom of COVID-19. The meta-analysis showed that, among 138,015 COVID-19-positive patients, 36.62% reported taste dysfunction (95% confidence interval: 33.02%-40.39%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 15) versus self-report (n = 220) methodologies (Q = 1.73, df = 1, P = 0.1889). Generally, males reported lower rates of taste loss than did females, and taste loss was highest among middle-aged adults. Thus, taste loss is likely a bona fide symptom of COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms.
Asunto(s)
Ageusia , COVID-19 , Trastornos del Olfato , Masculino , Adulto , Persona de Mediana Edad , Femenino , Humanos , COVID-19/complicaciones , Ageusia/etiología , Ageusia/epidemiología , SARS-CoV-2 , Trastornos del Gusto/diagnóstico , Trastornos del Gusto/etiología , Trastornos del Gusto/epidemiología , Olfato , GustoRESUMEN
OBJECTIVES: To compare taste changes after transoral robotic surgery (TORS) to taste changes in healthy controls. METHODS: Oropharyngeal cancer patients receiving TORS and healthy controls were recruited. Participants underwent posterolateral and whole-mouth psychophysical taste testing (identification, intensity, and hedonics) at baseline and at 2 weeks postoperatively (patients) or follow-up (controls). Surgeons reported suspension time and glossopharyngeal nerve injury (GNI) based on the identification and sacrifice of the nerve. A Clinical Global Impression (CGI) of taste symptoms was completed at each session ("My sense of taste bothers me" on a 5-point scale from Never [1] to Always [5]). A taste disorder (TD) was a CGI of 3 (Sometimes) or worse. Within-subject changes in CGI and psychophysical scores were computed. "Worsened taste" was a CGI increase by ≥1 point at follow-up. RESULTS: Of 69 participants, most (33/37 tumor, 31/32 controls) had normal baseline taste (CGI < 3). 14/33 (42%) TORS patients and no controls developed new TDs at follow-up. More smokers (7/9) had worsened taste than nonsmokers (19/60, difference = 46% [95% CI 16%-76%]). More patients without GNI (6/22) than with GNI (0/15) had postoperative phantogeusia (difference = 27% [95% CI 9-45%]). Tumor-ipsilateral taste identification (TI) decreased more in patients (-11.3%) than controls (0.8%, difference = 12.2% [95% CI 5.0-19.3%]). Suspension time was not associated with worsened taste symptoms or psychophysical changes. CONCLUSIONS: Patient-reported taste changes after TORS are frequent. Compared to healthy controls, TORS patients have decreased tumor-ipsilateral TI. Suspension time and GNI are unlikely to cause symptomatic TDs. Further investigations of the etiology and long-term symptom burden of TORS-associated TDs will aid in the management of oropharyngeal cancer patients. LEVEL OF EVIDENCE: 3 (non-randomized controlled cohort study) Laryngoscope, 133:3520-3528, 2023.
Asunto(s)
Neoplasias Orofaríngeas , Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Estudios de Cohortes , Neoplasias Orofaríngeas/cirugía , Neoplasias Orofaríngeas/patología , Boca/patología , Trastornos del Gusto/etiologíaRESUMEN
Purpose: The bad bitter taste of some medicines is a barrier to overcoming non-compliance with medication use, especially life-saving drugs given to children and the elderly. Here we evaluated a new class of bitter blockers (thiazolidinediones; TZDs). Methods: In this study, two TZDs were tested, rosiglitazone (ROSI) and a simpler form of TZD, using a high-potency sweetener as a positive control (neohesperidin dihydrochalcone, NHDC). We tested bitter-blocking effects using the bitter drugs tenofovir alafenamide fumarate (TAF), a treatment for HIV and hepatitis B infection, and praziquantel (PRAZ), a treatment for schistosomiasis, by conducting taste testing with two separate taste panels: a general panel (N=97, 20-23 yrs, 82.5% female, all Eastern European) and a genetically informative panel (N=158, including 68 twin pairs, 18-82 yrs, 76% female, 87% European ancestry). Participants rated the bitterness intensity of the solutions on a 100-point generalized visual analog scale. Findings: Participants in both taste panels rated the bitter drugs TAF and PRAZ as less bitter on average when mixed with NHDC than when sampled alone. ROSI partially suppressed the bitterness of TAF and PRAZ, but effectiveness differed between the two panels: bitterness was significantly reduced for PRAZ but not TAF in the general panel and for TAF but not PRAZ in the genetically informative panel. ROSI was a more effective blocker than the other TZD. Implications: These results suggest that TZDs are partially effective bitter blockers, suggesting other TZDs should be designed and tested with more drugs and on diverse populations to define which ones work best with which drugs and for whom. The discovery of bitter receptor blockers can improve compliance with medication use.
RESUMEN
BACKGROUND: Youth identifying as lesbian, gay, bisexual (LGB) and/or transgender/gender nonconforming (TGNC) are at increased risk of violence. School policies and practices may mitigate this risk. METHODS: Researchers merged data from the 2016 New Mexico School Health Profiles and the 2017 New Mexico Youth Risk and Resiliency Survey. Researchers employed multivariable logistic regression to test the associations between school-level measures and violence outcomes. RESULTS: Genders and sexualities alliances (GSAs) were associated with reduced odds of lifetime forced sex among all, heterosexual cisgender, and LGB students, reduced odds of sexual violence among heterosexual cisgender students, and reduced odds of dating violence among LGB students. Inclusive sexual health education was associated with reduced odds of lifetime forced sex among LGB and TGNC students, reduced odds of sexual violence among LGB students, and increased odds of dating violence among heterosexual cisgender students. Inclusive teacher training was associated with increased odds of lifetime forced sex among TGNC students. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: Inclusive sexual health education and the presence of active GSAs may have the greatest potential for reducing violence, especially among LGB and TGNC students. CONCLUSIONS: Findings highlight the important role of school policies and practices in addressing violence.
Asunto(s)
Minorías Sexuales y de Género , Adolescente , Humanos , Masculino , Femenino , Conducta Sexual , Violencia , Estudiantes , PolíticasRESUMEN
SCENTinel™ - a rapid, inexpensive smell test that measures odor detection, intensity, identification, and pleasantness - was developed for population-wide screening of smell function. SCENTinel™ was previously found to screen for multiple types of smell disorders. However, the effect of genetic variability on SCENTinel™ test performance is unknown, which could affect the test's validity. This study assessed performance of SCENTinel™ in a large group of individuals with a normal sense of smell to determine the test-retest reliability and the heritability of SCENTinel™ test performance. One thousand participants (36 [IQR 26-52] years old, 72% female, 80% white) completed a SCENTinel™ test at the 2021 and 2022 Twins Days Festivals in Twinsburg, OH, and 118 of those completed a SCENTinel™ test on each of the festival's two days. Participants comprised 55% percent monozygotic twins, 13% dizygotic twins, 0.4% triplets, and 36% singletons. We found that 97% of participants passed the SCENTinel™ test. Test-retest reliability ranged from 0.57 to 0.71 for SCENTinel™ subtests. Broad-sense heritability, based on 246 monozygotic and 62 dizygotic twin dyads, was low for odor intensity (r=0.03) and moderate for odor pleasantness (r=0.4). Together, this study suggests that SCENTinel™ is a reliable smell test with only moderate heritability effects, which further supports its utility for population-wide screening for smell function.
RESUMEN
T2R bitter receptors, encoded by Tas2r genes, are not only critical for bitter taste signal transduction but also important for defense against bacteria and parasites. However, little is known about whether and how Tas2r gene expression are regulated. Here, we show that in an inflammation model mimicking bacterial infection using lipopolysaccharide, the expression of many Tas2rs was significantly upregulated and mice displayed markedly increased neural and behavioral responses to bitter compounds. Using single-cell assays for transposase-accessible chromatin with sequencing (scATAC-seq), we found that the chromatin accessibility of Tas2rs was highly celltype specific and lipopolysaccharide increased the accessibility of many Tas2rs. scATAC-seq also revealed substantial chromatin remodeling in immune response genes in taste tissue stem cells, suggesting potential long-lasting effects. Together, our results suggest an epigenetic mechanism connecting inflammation, Tas2r gene regulation, and altered bitter taste, which may explain heightened bitter taste that can occur with infections and cancer treatments.
RESUMEN
INTRODUCTION: Infants born with critical congenital heart defects (CCHDs) have unique transitional pathophysiology that often requires special resuscitation and management considerations in the delivery room (DR). While much is known about neonatal resuscitation of infants with CCHDs, current neonatal resuscitation guidelines such as the neonatal resuscitation programme (NRP) do not include algorithm modifications or education specific to CCHDs. The implementation of CCHD specific neonatal resuscitation education is further hampered by the large number of healthcare providers (HCPs) that need to be reached. Online learning modules (eLearning) may provide a solution but have not been designed or tested for this specific learning need. Our objective in this study is to design targeted eLearning modules for DR resuscitation of infants with specific CCHDs and compare HCP knowledge and team performance in simulated resuscitations among HCPs exposed to these modules compared with directed CCHD readings. METHODS AND ANALYSIS: In a prospective multicentre trial, HCP proficient in standard NRP education curriculum are randomised to either (a) directed CCHD readings or (b) CCHD eLearning modules developed by the study team. The efficacy of these modules will be evaluated using (a) individual preknowledge/postknowledge testing and (b) team-based resuscitation simulations. ETHICS AND DISSEMINATION: This study protocol is approved by nine participating sites: the Boston Children's Hospital Institutional Review Board (IRB-P00042003), University of Alberta Research Ethics Board (Pro00114424), the Children's Wisconsin IRB (1760009-1), Nationwide Children's Hospital IRB (STUDY00001518), Milwaukee Children's IRB (1760009-1) and University of Texas Southwestern IRB (STU-2021-0457) and is under review at following sites: University of Cincinnati, Children's Healthcare of Atlanta, Children's Hospital of Los Angeles and Children's Mercy-Kansas City. Study results will be disseminated to participating individuals in a lay format and presented to the scientific community at paediatric and critical care conferences and published in relevant peer-reviewed journals.
Asunto(s)
Cardiopatías Congénitas , Resucitación , Lactante , Embarazo , Recién Nacido , Humanos , Niño , Femenino , Resucitación/métodos , Estudios Prospectivos , Salas de Parto , Aprendizaje , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
Importance: Racial and ethnic differences in skin cancer outcomes are understudied. Delineating these differences in Merkel cell carcinoma (MCC) is needed to better understand this rare disease. Objective: To determine how MCC presentation and outcomes differ across racial and ethnic groups. Design, Setting, and Participants: This retrospective cohort study included patients diagnosed with MCC and followed up from 2000 through 2018 in the 18 population-based cancer registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Patients without follow-up data were excluded. Data analysis occurred from March 12 to November 30, 2022. Main Outcomes and Measures: A Cox proportional hazards regression was conducted to determine associations between demographic variables (race and ethnicity, age, sex, and income) and clinical variables (stage at diagnosis, primary site, and diagnosis year) with MCC-specific survival. Results: Of the 9557 patients with MCC identified (6758 [70.7%] aged ≥70 years; 6008 [62.9%] male), 222 (2.3%) were Asian American or Pacific Islander, 146 (1.5%) Black, 541 (5.7%) Hispanic, and 8590 (89.9%) White. Hispanic patients had improved MCC-specific survival compared with White patients (hazard ratio, 0.82; 95% CI, 0.67-0.99; P = .04). Black patients had the lowest MCC-specific survival, but it was not statistically different from White patients (hazard ratio, 1.19; 95% CI, 0.86-1.60; P = .28). Hispanic and Black patients were less likely to present with a primary site of the head and neck than White patients (183 of 541 [33.8%] Hispanic patients and 45 of 146 [30.8%] Black patients vs 3736 of 8590 [43.5%] White patients; P < .001 and P = .002, respectively). Black patients presented more often than White patients with advanced disease at diagnosis (59 of 146 [40.4%] vs 2510 of 8590 [29.2%]; P = .004). Conclusions and Relevance: In this cohort study, there were differences between racial and ethnic groups in observed MCC outcomes and disease characteristics. Further investigations are warranted into the findings that, compared with White patients, Hispanic patients with MCC had improved outcomes and Black patients did not have worse outcomes despite presenting with more advanced disease.
Asunto(s)
Carcinoma de Células de Merkel , Neoplasias Cutáneas , Humanos , Masculino , Femenino , Etnicidad , Estudios de Cohortes , Estudios Retrospectivos , Carcinoma de Células de Merkel/terapiaRESUMEN
T2R bitter receptors, encoded by Tas2r genes, are not only critical for bitter taste signal transduction but also important for defense against bacteria and parasites. However, little is known about whether and how Tas2r gene expression are regulated. Here we show that, in an inflammation model mimicking bacterial infection, the expression of many Tas2rs are significantly up-regulated and mice displayed markedly increased neural and behavioral responses to bitter compounds. Using single-cell assays for transposase-accessible chromatin with sequencing (scATAC-seq), we found that the chromatin accessibility of Tas2rs was highly cell type specific and inflammation increased the accessibility of many Tas2rs . scATAC-seq also revealed substantial chromatin remodeling in immune response genes in taste tissue stem cells, suggesting potential long-term effects. Together, our results suggest an epigenetic mechanism connecting inflammation, Tas2r gene regulation, and altered bitter taste, which may explain heightened bitter taste that can occur with infections and cancer treatments.