Diet-Induced Obesity Induces Transcriptomic Changes in Neuroimmunometabolic-Related Genes in the Striatum and Olfactory Bulb.

The incidence of obesity has markedly increased globally over the last several decades and is believed to be associated with the easier availability of energy-dense foods, including high-fat foods. The reinforcing hedonic properties of high-fat foods, including olfactory cues, activate reward centers in the brain, motivating eating behavior. Thus, there is a growing interest in the understanding of the genetic changes that occur in the brain that are associated with obesity and eating behavior. This growing interest has paralleled advances in genomic methods that enable transcriptomic-wide analyses. Here, we examined the transcriptomic-level differences in the olfactory bulb and striatum, regions of the brain associated with olfaction and hedonic food-seeking, respectively, in high-fat-diet (HFD)-fed obese mice. To isolate the dietary effects from obesity, we also examined transcriptomic changes in normal-chow-fed and limited-HFD-fed groups, with the latter being pair-fed with an HFD isocaloric to the consumption of the normal-chow-fed mice. Using RNA sequencing, we identified 274 differentially expressed genes (DEGs) in the striatum and 11 in the olfactory bulb of ad libitum HFD-fed mice compared to the chow-fed group, and thirty-eight DEGs in the striatum between the ad libitum HFD and limited-HFD-fed groups. The DEGs in both tissues were associated with inflammation and immune-related pathways, including oxidative stress and immune function, and with mitochondrial dysfunction and reward pathways in the striatum. These results shed light on potential obesity-associated genes in these regions of the brain.

Brain dopamine responses to ultra-processed milkshakes are highly variable and not significantly related to adiposity in humans.

Ultra-processed foods high in fat and sugar may be addictive, in part, due to their purported ability to induce an exaggerated postingestive brain dopamine response akin to drugs of abuse. Using standard [11C]raclopride positron emission tomography (PET) displacement methods used to measure brain dopamine responses to addictive drugs, we measured postingestive striatal dopamine responses to an ultra-processed milkshake high in fat and sugar in 50 young, healthy adults over a wide body mass index range (BMI 20-45 kg/m2). Surprisingly, milkshake consumption did not result in significant postingestive dopamine response in the striatum (p=0.62) nor any striatal subregion (p>0.33) and the highly variable interindividual responses were not significantly related to adiposity (BMI: r=0.076, p=0.51; %body fat: r=0.16, p=0.28). Thus, postingestive striatal dopamine responses to an ultra-processed milkshake were likely substantially smaller than many addictive drugs and below the limits of detection using standard PET methods.

Possible roles of phytochemicals with bioactive properties in the prevention of and recovery from COVID-19.

Introduction: There have been large geographical differences in the infection and death rates of COVID-19. Foods and beverages containing high amounts of phytochemicals with bioactive properties were suggested to prevent contracting and to facilitate recovery from COVID-19. The goal of our study was to determine the correlation of the type of foods/beverages people consumed and the risk reduction of contracting COVID-19 and the recovery from COVID-19. Methods: We developed an online survey that asked the participants whether they contracted COVID-19, their symptoms, time to recover, and their frequency of eating various types of foods/beverages. The survey was developed in 10 different languages. Results: The participants who did not contract COVID-19 consumed vegetables, herbs/spices, and fermented foods/beverages significantly more than the participants who contracted COVID-19. Among the six countries (India/Iran/Italy/Japan/Russia/Spain) with over 100 participants and high correspondence between the location of the participants and the language of the survey, in India and Japan the people who contracted COVID-19 showed significantly shorter recovery time, and greater daily intake of vegetables, herbs/spices, and fermented foods/beverages was associated with faster recovery. Conclusions: Our results suggest that phytochemical compounds included in the vegetables may have contributed in not only preventing contraction of COVID-19, but also accelerating their recovery.

Recovery rates of persistent post-COVID-19 olfactory dysfunction using psychophysical assessment: A longitudinal cohort study.

Objectives: Persistent olfactory dysfunction (OD) following loss of smell associated with SARS-CoV-2 infection is a major feature of long COVID. Perspectives on the prevalence of persistent OD predominantly rely on self-reported olfactory function. Few studies have tracked longitudinal rates of recovery using psychophysical assessment among patients presenting for evaluation of persistent OD beyond a window of acute recovery. Data anchored in standardized testing methods are needed to counsel patients who fail to acutely regain their sense of smell. This study aims to quantify the degree of persistent OD in post-COVID-19 patients who experience subjective and psychophysical OD. Methods: We grouped participants presenting for OD evaluation into cohorts based on both subjective and psychophysical olfactory status at a baseline assessment and assessed their olfactory abilities with a visual analogue scale and the Sniffin' Sticks extended test at baseline and 1-year time points. Participants had confirmed a history of COVID-19 by lab evaluation or clinical diagnosis if lab evaluation was not available. Results: Baseline olfactory evaluation was completed by 122 participants, 53 of whom completed the 1-year follow-up assessment. Among participants presenting with perceived OD, 74.5% had confirmed psychophysical OD at baseline, with 55.1% at 1-year follow-up. Participants had reliable trends in self-rated versus psychophysically tested olfactory function at both time points. The total threshold, discrimination, and identification (TDI) score improved by +3.25 points in the cohort with psychophysical OD (p = 0.0005), with this improvement largely attributable to an increase in median threshold scores (+2.75 points; p = 0.0004). Conclusions: OD persists in a significant number of patients who fail to acutely recovery their sense of smell after COVID-19, with many demonstrating lingering deficits at 1-year. Improvements in threshold, but not discrimination or identification, most significantly mediate improvement of total TDI score at follow-up.

Effects of genetics on odor perception: Can a quick smell test effectively screen everyone?

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, N = 630; singletons, N = 370) to complete the SCENTinel test. A subset of twins (n = 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 (h2 = 0.40) and were nominally associated with alleles of odorant receptors (e.g. OR2T33 and OR1G1; P < 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.

Integrating the patient's voice into the research agenda for treatment of chemosensory disorders.

World-wide some 658 million people were infected with coronavirus disease 2019 (COVID-19) and millions suffer from chemosensory impairment associated with long COVID. Current treatments for taste and smell disorders are limited. Involving patients has the potential to catalyze the dynamic exchange and development of new ideas and approaches to facilitate biomedical research and therapeutics. We assessed patients' perceptions of the efficacy of treatments for chemosensory impairment using an online questionnaire completed by 5,815 people in the US Logistic regression determined variables predictive of reported treatment efficacy for patients aged 18 to 24, 25 to 39, 40 to 60, and 60+ yrs. who were treated with nasal steroids, oral steroids, zinc, nasal rinse, smell training, theophylline, platelet-rich plasma, and Omega 3. The most consistent predictor was age, with the majority of those 40 to 60 and 60+ reporting that nasal steroids, oral steroids, zinc, nasal rinse, and smell training were only slightly effective or not effective at all. Many of these treatment strategies target regeneration and immune response, processes compromised by age. Only those under 40 reported more than slight efficacy of steroids or smell training. Findings emphasize the need to include patients of all ages in clinical trials. Older adults with olfactory impairment are at increased risk for Alzheimer's disease (AD). We speculate that olfactory impairment associated with long COVID introduces the potential for a significant rise in AD. Long COVID-associated chemosensory impairment increases the urgency for translational and clinical research on novel treatment strategies. Suggestions for high-priority areas for epidemiological, basic, and clinical research on chemosensory impairment follow.

Parosmia Is Positively Associated With Problematic Drinking, as Is Phantosmia With Depressive Symptoms.

OBJECTIVES: Alcohol use disorder (AUD) is a global health problem with significant negative consequences, including preventable deaths. Although olfactory dysfunction is associated with chronic alcohol drinking, the relationship among specific types of olfactory deficits, depressive symptoms, and problematic drinking remains to be explored. Here, we examined the prevalence of olfactory distortion (parosmia) and hallucination (phantosmia) and assessed their associations with problematic drinking and depressive symptoms. METHODS: In April-June 2022, 250 participants across the spectrum of AUD were recruited for assessment in the National Institute on Alcohol Abuse and Alcoholism COVID-19 Pandemic Impact on Alcohol study. Surveys covered self-reported olfactory function, depressive symptoms, and problematic drinking, with key measures assessed, including the Alcohol Use Disorders Identification Test and the Patient Health Questionnaire. Predictors in the analysis included parosmia and phantosmia, with covariates comprising age, sex, socioeconomic status, race, ethnicity, COVID-19 infection status, and smoking status. RESULTS: Among 250 individuals, 5.2% experienced parosmia and 4.4% reported phantosmia. Parosmia was associated with higher Alcohol Use Disorders Identification Test scores (ß = 7.14; 95% confidence interval = 3.31, 10.96; P < 0.001), whereas phantosmia was linked to higher Patient Health Questionnaire scores (ß = 3.32; 95% confidence interval = 0.22, 6.42; P = 0.03). These associations persisted in both the full sample and the subset of participants without COVID-19. CONCLUSIONS: Our study highlights strong existing links among olfactory deficits, problem drinking, and depressive symptoms, underscoring the need to assess smell impairments in clinical settings. Future research should explore these connections further to develop new treatments for individuals with AUD and depression.

Subjective versus Psychophysical Measures of Chemosensory Alterations following COVID-19.

INTRODUCTION: Olfactory dysfunction is a common symptom of COVID-19. However, subjective perception of olfactory function does not always correlate well with more objective measures. This study seeks to clarify associations between subjective and psychophysical measures of olfaction and gustation in patients with subjective chemosensory dysfunction following COVID-19. METHODS: Adults with persistent COVID-19-associated chemosensory disturbance were recruited for a prospective, longitudinal cohort study at a tertiary care institution. Participants provided subjective measures of olfactory and gustatory function and underwent psychophysical assessment using Sniffin' Sticks olfactory and Monell gustatory tests. RESULTS: Data analysis (n = 65) showed a statistically significant association between subjective and psychophysical measures of olfaction (p < 0.001). For each one-point increase in subjectively-reported olfactory ability, there is, on average, a 0.11 (95% CI: 0.06, 0.16; p < 0.001) point increase in TDI score while adjusting for age at baseline assessment, sex, and follow-up time. For each one-point increase in subjectively-reported olfactory ability, there is, on average, a 0.04 (95% CI: 0.02, 0.06; p < 0.001) point and 0.05 (95% CI: 0.03, 0.07; p < 0.001) point increase in discrimination and identification scores, respectively, when adjusting for age at baseline assessment, sex, and follow-up time. CONCLUSION: Subjective olfaction shows a mild to moderate association with psychophysical measures, but it fails to comprehensively assess persistent COVID-19-associated chemosensory deficits. The lack of significant association between subjective olfaction and threshold limits the utility of subjective olfaction in tracking recovery. These findings support the push for more widespread psychophysical chemosensory testing.

Detection of colinear blocks and synteny and evolutionary analyses based on utilization of MCScanX.

As different taxa evolve, gene order often changes slowly enough that chromosomal 'blocks' with conserved gene orders (synteny) are discernible. The MCScanX toolkit ( https://github.com/wyp1125/MCScanX ) was published in 2012 as freely available software for the detection of such 'colinear blocks' and subsequent synteny and evolutionary analyses based on genome-wide gene location and protein sequence information. Owing to its simplicity and high efficiency for colinear block detection, MCScanX provides a powerful tool for conducting diverse synteny and evolutionary analyses. Moreover, the detection of colinear blocks has been embraced as an integral step for pangenome graph construction. Here, new application trends of MCScanX are explored, striving to better connect this increasingly used tool to other tools and accelerate insight generation from exponentially growing sequence data. We provide a detailed protocol that covers how to install MCScanX on diverse platforms, tune parameters, prepare input files from data from the National Center for Biotechnology Information, run MCScanX and its visualization and evolutionary analysis tools, and connect MCScanX with external tools, including MCScanX-transposed, Circos and SynVisio. This protocol is easily implemented by users with minimal computational background and is adaptable to new data of interest to them. The data and utility programs for this protocol can be obtained from http://bdx-consulting.com/mcscanx-protocol .

Exercising healthy behaviors: A latent class analysis of positive coping during the COVID-19 pandemic and associations with alcohol-related and mental health outcomes.

OBJECTIVE: To identify latent classes of positive coping behaviors during the COVID-19 pandemic and examine associations with alcohol-related and mental health outcomes across participants with and without a history of alcohol use disorder (AUD). METHODS: Baseline data from 463 participants who were enrolled in the NIAAA COVID-19 Pandemic Impact on Alcohol (C19-PIA) Study were analyzed. Latent class analysis (LCA) was applied to five positive coping behaviors during COVID-19: taking media breaks, taking care of their body, engaging in healthy behaviors, making time to relax, and connecting with others. Latent class differences and the moderating role of history of AUD on six alcohol-related and mental health outcomes were examined using multiple regression models. RESULTS: LCA revealed two latent classes: 83.4% High Positive Coping and 16.6% Low Positive Coping. Low Positive Coping was associated with higher levels of perceived stress, anxiety symptoms, and loneliness. A history of AUD was consistently associated with higher levels of alcohol-related and mental health outcomes. Significant interactions between Coping Latent Classes and history of AUD indicated that the associations of Low Positive Coping with problematic alcohol use, depressive symptoms, and drinking to cope motives were either stronger or only significant among individuals with a history of AUD. CONCLUSIONS: Individuals with a history of AUD may be particularly vulnerable to depressive symptoms and alcohol-related outcomes, especially when they do not utilize positive coping strategies. The promotion of positive coping strategies is a promising avenue to address alcohol-related and mental health problems during a public health crisis and warrants future research.

Early life stress and body-mass-index modulate brain connectivity in alcohol use disorder.

Early life stress (ELS) significantly increases susceptibility to alcohol use disorder (AUD) by affecting the interplay between the executive and the salience networks (SNs). The link between AUD and higher body-mass index (BMI) is known, but we lack understanding of how BMI impacts the relationship between ELS and brain connectivity in individuals with AUD. To bridge this gap, we investigated the main and interaction effects of ELS and BMI on brain connectivity in individuals with AUD compared to non-AUD participants (n = 77 sex-matched individuals per group). All participants underwent resting-state functional magnetic resonance imaging, revealing intriguing positive functional connectivity between SN seeds and brain regions involved in somatosensory processing, motor coordination and executive control. Examining the relationship of brain connectivity with ELS and BMI, we observed positive associations with the correlations of SN seeds, right anterior insula (RAIns) and supramarginal gyrus (SMG) with clusters in motor [occipital cortex, supplementary motor cortex]; anterior cingulate cortex (ACC) with clusters in frontal, or executive, control regions (middle frontal gyrus; MFG, precentral gyrus) that reportedly are involved in processing of emotionally salient stimuli (all |ß | > 0.001, |p | < 0.05). Interestingly, a negative association of the interaction effect of ELS events and BMI measures with the functional connectivity of SN seeds ACC with decision-making (MFG, precentral gyrus), RAIns and RSMG with visuo-motor control regions (occipital cortex and supplementary motor cortex) (all |ß | = -0.001, |p | < 0.05). These findings emphasize the moderating effect of BMI on ELS-associated SN seed brain connectivity in AUD. Understanding the neural mechanisms linking BMI, ELS and AUD can guide targeted interventions for this population.

Taste loss as a distinct symptom of COVID-19: a systematic review and meta-analysis.

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.

BMI Increases in Individuals with COVID-19-Associated Olfactory Dysfunction.

(1) Background: Reports suggest COVID-19-associated olfactory dysfunction (OD) may result in alterations in dietary behaviors and perceived weight change, but few studies using psychophysical evaluation of post-COVID-19-associated chemosensory dysfunction and body mass index (BMI) exist. The purpose of this study is to assess the impact of both quantitative and qualitative features of COVID-19-associated OD on BMI; (2) Methods: Recruitment of thirty-one participants with self-reported OD in the form of quantitative loss with and without qualitative features. Surveys with questions specific to qualitative olfactory function, Sniffin' Sticks tests, and BMI measures were completed at two visits, one year apart. Group differences were assessed with Wilcoxon signed-rank tests and the Holm-Bonferroni method; (3) Results: Individuals with persistent quantitative OD (n = 15) and self-reported parosmia (n = 19) showed statistically significant increases in BMI after 1 year (p = 0.004, adjusted α = 0.0125; p = 0.011, adjusted α = 0.0167). Controls with transient quantitative OD (n = 16) and participants without self-reported parosmia (n = 12) showed no statistically significant changes in BMI over the same time period (p = 0.079, adjusted α = 0.05; p = 0.028, adjusted α = 0.025); (4) Conclusions: This study shows an association between COVID-19-associated OD and BMI, suggesting olfaction may play a role in altering dietary habits and nutrition in this population. Larger study cohorts are needed to further evaluate this relationship.

Examination of newborn DNA methylation among women with polycystic ovary syndrome/hirsutism.

Research suggests that polycystic ovary syndrome (PCOS) traits (e.g., hyperandrogenism) may create a suboptimal intrauterine environment and induce epigenetic modifications. Therefore, we assessed the associations of PCOS traits with neonatal DNA methylation (DNAm) using two independent cohorts. DNAm was measured in both cohorts using the Infinium MethylationEPIC array. Multivariable robust linear regression was used to determine associations of maternal PCOS exposure or preconception testosterone with methylation ß-values at each CpG probe and corrected for multiple testing by false-discovery rate (FDR). In the birth cohort, 12% (102/849) had a PCOS diagnosis (8.1% PCOS without hirsutism; 3.9% PCOS with hirsutism). Infants exposed to maternal PCOS with hirsutism compared to no PCOS had differential DNAm at cg02372539 [ß(SE): -0.080 (0.010); FDR p = 0.009], cg08471713 [ß(SE):0.077 (0.014); FDR p = 0.016] and cg17897916 [ß(SE):0.050 (0.009); FDR p = 0.009] with adjustment for maternal characteristics including pre-pregnancy BMI. PCOS with hirsutism was also associated with 8 differentially methylated regions (DMRs). PCOS without hirsutism was not associated with individual CpGs. In an independent preconception cohort, total testosterone concentrations were associated with 3 DMRs but not with individual CpGs, though the top quartile of testosterone compared to the lowest was marginally associated with increased DNAm at cg21472377 near an uncharacterized locus (FDR p = 0.09). Examination of these probes and DMRs indicate they may be under foetal genetic control. Overall, we found several associations among newborns exposed to PCOS, specifically when hirsutism was reported, and among newborns of women with relatively higher testosterone around conception.

Risk Assessment of Maladaptive Behaviors in Adolescents: Nutrition, Screen Time, Prenatal Exposure, Childhood Adversities - Adolescent Brain Cognitive Development Study.

PURPOSE: We aimed to identify significant contributing factors to the risk of maladaptive behaviors, such as alcohol use disorder or obesity, in children. To achieve this, we utilized the extensive adolescent brain cognitive development data set, which encompasses a wide range of environmental, social, and nutritional factors. METHODS: We divided our sample into equal sets (test, validation; n = 3,415 each). On exploratory factor analysis, six factor domains were identified as most significant (fat/sugar intake, screen time, and prenatal alcohol exposure, parental aggressiveness, hyperactivity, family violence, parental education, and family income) and used to stratify the children into low- (n = 975), medium- (n = 967), high- (n = 977) risk groups. Regression models were used to analyze the relationship between identified risk groups, and differences in reward sensitivity, and behavioral problems at 2-year follow-up. RESULTS: The functional magnetic resonance imaging analyses showed reduced activation in several brain regions during reward or loss anticipation in high/medium-risk (vs. low-risk) children on a monetary incentive delay task. High-risk children exhibited heightened middle frontal cortex activity when receiving large rewards. They also displayed increased impulsive and motivated reward-seeking behaviors, along with behavioral problems. These findings replicated in our validation set, and a negative correlation between middle frontal cortexthickness and impulsivity behavior was observed in high-risk children. DISCUSSION: Our findings show altered reward function and increased impulsiveness in high-risk adolescents. This study has implications for early risk identification and the development of prevention strategies for maladaptive behaviors in children, particularly those at high risk.

Patient Insights into the Diagnosis of Smell and Taste Disorders in the United States.

OBJECTIVES: Diagnosis of smell/taste dysfunction is necessary for appropriate medical care. This study examines factors affecting testing and diagnosis of smell/taste disorders . METHODS: The online USA Smell and Taste Patient Survey was made available to US patients with smell/taste disorders between April 6-20, 2022. 4,728 respondents were included. RESULTS: 1,791 (38%) patients reported a documented diagnosis. Patients most often saw family practitioners (34%), otolaryngologists (20%), and Taste/Smell clinics (6%) for smell/taste dysfunction. 64% of patients who went to Taste/Smell clinics received smell testing, followed by 39% of patients who saw otolaryngologists, and 31% of patients who saw family practitioners. Factors associated with increased odds of diagnosis included age (25-39 years (OR 2.97, 95% CI [2.25, 3.95]), 40-60 (OR 3.3, 95% CI [2.56, 4.52]), and >60 (OR 4.25, 95% CI [3.21, 5.67]) vs. 18-24 years), male gender (OR 1.26, 95% CI [1.07, 1.48]), insurance status (private (OR 1.61, 95% CI [1.15, 2.30]) or public (OR 2.03, 95% CI [1.42, 2.95]) vs. uninsured), perception of their family practitioner to be knowledgeable (OR 2.12, 95% CI [1.16, 3.90]), otolaryngologic evaluation (OR 6.17, 95% CI [5.16, 7.38]), and psychophysical smell testing (OR 1.77, 95% CI [1.42, 2.22]). CONCLUSION: Psychophysical testing, otolaryngologic evaluation, patient assessment of family practitioner knowledge level, insurance, age, and gender are significant factors in obtaining smell/taste dysfunction diagnosis. This study identifies barriers to diagnosis including lack of insurance or access to specialist evaluation and highlights the importance of educating family practitioners in diagnosis and management of patients with smell/taste disorders.

Association of inflammation biomarkers with food cravings and appetite changes across the menstrual cycle.

IMPORTANCE: Premenstrual symptoms, including food cravings, are often a regular complaint among menstruating women. However, existing evidence regarding the biological mechanisms by which these food cravings occur remains unclear. Inflammation may play an essential role in the occurrence of these food cravings before menstruation. OBJECTIVE: The purpose of the present study was to examine the associations between inflammatory markers and the risk of moderate/severe food cravings while accounting for changes in hormone levels and stress across the menstrual cycle. DESIGN, SETTING, AND PARTICIPANTS: The BioCycle Study followed women (n = 259) aged 18-44 for two menstrual cycles. Food cravings (via questionnaire) were assessed up to four times per cycle. Each assessment corresponded to menses and mid-follicular, ovulation, and luteal phases of the menstrual cycle. A wide range of cytokine and chemokine levels (hsCRP, GCSF, GMCSF, IL-4, IL-6, RANTES, MIP1B, etc.) were assessed in blood samples collected at up to 8 visits per cycle, with visits timed using fertility monitors. MAIN OUTCOMES AND MEASURES: Cravings for chocolate, sweets, salty, and other foods, and changes in appetite were determined to estimate the odds of moderate or severe cravings. Associations between inflammatory markers and risk of reporting a moderate/severe craving symptom at each cycle visit was determined using weighted generalized linear models (e.g., marginal structural models). Models were adjusted for age, BMI, and race, as well as time-varying covariates such as estradiol, stress, leptin, and total energy intake, and accounted for repeated measures (i.e., multiple cycles per woman). Both inflammatory markers and reports of cravings were modeled to account for variation at each visit. RESULTS: An association between higher inflammatory biomarkers such as hsCRP, GCSF, GMCSF, IL-4, IL-6, RANTES, MIP, and increased risk of moderate/severe cravings were identified across the menstrual cycle all risk ratio>1, all CIs range 0.71-2.38. hsCRP retained statistical significance after false discovery rate correction with chocolate, sweet, and salty cravings, while GCSF, GMCSF, IL-6, and RANTES retained significance with chocolate and sweet cravings only. CONCLUSION: and Relevance: The results suggest a potential role of inflammation in food cravings and appetite changes across the menstrual cycle.

Administration of Bifidobacterium animalis subsp. lactis strain BB-12® in healthy children: characterization, functional composition, and metabolism of the gut microbiome.

Introduction: The consumption of probiotics may influence children's gut microbiome and metabolome, which may reflect shifts in gut microbial diversity composition and metabolism. These potential changes might have a beneficial impact on health. However, there is a lack of evidence investigating the effect of probiotics on the gut microbiome and metabolome of children. We aimed to examine the potential impact of a two (Streptococcus thermophilus and Lactobacillus delbrueckii; S2) vs. three (S2 + Bifidobacterium animalis subsp. lactis strain BB-12) strain-supplemented yogurt. Methods: Included in this study were 59 participants, aged one to five years old, recruited to phase I of a double-blinded, randomized controlled trial. Fecal samples were collected at baseline, after the intervention, and at twenty days post-intervention discontinuation, and untargeted metabolomics and shotgun metagenomics were performed. Results: Shotgun metagenomics and metabolomic analyses showed no global changes in either intervention group's gut microbiome alpha or beta diversity indices, except for a lower microbial diversity in the S2 + BB12 group at Day 30. The relative abundance of the two and three intervention bacteria increased in the S2 and S2 + BB12 groups, respectively, from Day 0 to Day 10. In the S2 + BB12 group, the abundance of several fecal metabolites increased at Day 10, including alanine, glycine, lysine, phenylalanine, serine, and valine. These fecal metabolite changes did not occur in the S2 group. Discussion: In conclusion, there were were no significant differences in the global metagenomic or metabolomic profiles between healthy children receiving two (S2) vs. three (S2 + BB12) probiotic strains for 10 days. Nevertheless, we observed a significant increase (Day 0 to Day 10) in the relative abundance of the two and three probiotics administered in the S2 and S2 + BB12 groups, respectively, indicating the intervention had a measurable impact on the bacteria of interest in the gut microbiome. Future research using longer probiotic intervention durations and in children at risk for gastrointestinal disorders may elucidate if functional metabolite changes confer a protective gastrointestinal effect.

Low to moderate genetic influences on the rapid smell test SCENTinel™.

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.