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In the tripartite influence model, appearance-ideal internalization is identified as a prominent risk factor for the development of body dissatisfaction and subsequent eating disorder (ED) behaviors. For men, prior research has emphasized the importance of both thin-ideal internalization and muscular-ideal internalization in explaining later ED behaviors and muscle dysmorphia (MD) symptoms. Previous research in heterosexual men has shown that the associations between muscular-ideal internalization and ED or MD symptoms may depend on whether the individual has also internalized the thin ideal. However, this interaction has not been examined in research with sexual minority men (SMM).The current study collected self-report data from 452 at risk SMM (i.e., endorsed body dissatisfaction), with ages ranging from 18 to 35 years. Linear regression models were conducted to test the interaction effects between thinness and muscularity internalization on ED symptoms, MD behaviors, and general body dissatisfaction. Simple slopes and the Johnson-Neyman technique were used to investigate significant interaction terms.Thin- and muscular-ideal internalization were positively associated with muscular appearance intolerance and dietary restriction with no significant interaction. Muscular drive for size was highest when both muscularity internalization and thinness internalization were high. Muscular-ideal internalization was positively associated with both cognitive restraint and general body dissatisfaction, but only at lower levels of thinness internalization.Given the interacting association between thinness and muscularity internalization and aspects of body dissatisfaction, attitudes, and behavior, prevention and intervention programs for EDs and MDs in SMM should seek to dismantle both thinness and muscularity internalization.Internalizing-or adopting as one's own-the ideal of a body with low body fat and high muscularity has been shown to lead to muscle dysmorphia and eating disorder symptoms in men. The current study examines whether the combination of thin-ideal and muscular-ideal internalization is associated with worse symptoms than either facet alone in sexual minority men. Treatment efforts in sexual minority men should address both types of internalization.

Sexual minority men (SMM) are disproportionately at risk for suicidality. Furthermore, SMM are at elevated risk for appearance-ideal internalization and body dissatisfaction, which are both associated with suicidality. Theoretical recommendations suggest including interaction terms between appearance-ideal internalization and body dissatisfaction when examining deleterious health outcomes. To test these interactions and examine whether appearance-ideal internalization or body dissatisfaction impart greater suicidality, the current study analyzed associations between specific forms of appearance-ideal internalization and suicidality among SMM, and whether body dissatisfaction moderated these associations. Participants were 171 SMM recruited for an eating disorder prevention program. Analyses examined the association between thin and muscular-ideal internalization with count of suicide risk, with body fat and muscularity dissatisfaction moderating these associations. Zero-inflated Poisson regressions revealed that the association between thin-ideal internalization and suicide risk was moderated by body fat dissatisfaction, such that thin-ideal internalization was associated with increased suicide risk at high levels of body fat dissatisfaction. Muscularity concerns were not significantly associated with suicidality, suggesting that thinness concerns may be more salient than muscularity for suicidality among SMM. Future research should replicate findings among larger SMM samples and extend the current design into non-SMM samples to examine if results generalize to other vulnerable populations.

This study examined sexual orientation and gender identity differences in co-occurring depressive symptoms and substance use disorders (SUDs) among young adults in the Growing Up Today Study national cohort (n = 12,347; ages 20-35; 93% non-Hispanic white). Self-administered questionnaires assessed recent co-occurring depressive symptoms and probable nicotine dependence, alcohol use disorder, and drug use disorder. Multinomial logistic regressions with generalized estimating equations quantified differences in prevalences of depressive symptoms only, SUDs only, and co-occurrence, among sexual minorities (mostly heterosexual; lesbian, gay, and bisexual [LGB]) compared to completely heterosexual participants, and gender minorities compared to cisgender participants. Analyses stratified by sex assigned at birth revealed sexual minorities evidenced greater odds of co-occurrence than their completely heterosexual counterparts (assigned female AORs: 3.11-9.80, ps

Long-term topical skin care by traditional anti-melanogenic agents can raise several safety concerns. An understanding of the molecular mechanisms of active compounds on melanogenesis is, therefore, necessary to address pigmentation issues. Here we revealed that stimulation with 1 mM betaine, an abundant component in rice bran, significantly reduced 21% of intracellular melanin content by suppressing tyrosinase activity and microphthalmia-associated transcription factor (MITF) expression in B16-F1 murine melanocytes. The expression of MITF was suppressed at both mRNA and protein levels by 43 and 44%, respectively. Subsequently, the betaine-stimulated melanocytes showed inhibition of PKA-CREB signaling axis but activation of extracellular-signal-regulated kinase and AKT-GSK3β signaling pathways. This inhibition and activation led to downregulation of MITF expression at both the transcriptional and post-translational levels to suppress melanin synthesis. These findings collectively suggested that betaine is a potential anti-melanogenic compound for functional foods and cosmetics.

ObjectiveThe authors qualitatively examined how lesbian, gay, bisexual, transgender, and queer (LGBTQ) young adults with probable substance use disorders conceptualized their substance use vis-à-vis their LGBTQ identities.MethodsIndividual, in-depth, semistructured interviews were conducted with 59 LGBTQ young adults (ages 21-34) who were participants in a larger longitudinal cohort study and who met criteria for a probable substance use disorder. Data were analyzed via iterative, thematic analytic processes.ResultsParticipants' narratives highlighted processes related to minority stress that shape substance use, including proximal LGBTQ stressors (e.g., self-stigma and expectations of rejection) and distal LGBTQ stressors (e.g., interpersonal and structural discrimination) and associated coping. Participants also described sociocultural influences, including the ubiquitous availability of substances within LGBTQ social settings, as salient contributors to their substance use and development of substance use disorders. Participants who considered themselves transgender or other gender minorities, all of whom identified as sexual minorities, described unique stressors and coping at the intersection of their minority identities (e.g., coping with two identity development and disclosure periods), which shaped their substance use over time.ConclusionsMultilevel minority stressors and associated coping via substance use in adolescence and young adulthood, coupled with LGBTQ-specific sociocultural influences, contribute to the development of substance use disorders among some LGBTQ young adults. Treatment providers should address clients' substance use vis-à-vis their LGBTQ identities and experiences with related stressors and sociocultural contexts and adopt culturally humble and LGBTQ-affirming treatment approaches. Efforts to support LGBTQ youths and young adults should focus on identifying ways of socializing outside of substance-saturated environments.

Background We investigated sexual-orientation differences in typologies of self-reported familial and non-familial warmth in childhood (before age 11) and adolescence (ages 11–17); and tested whether warmth explained sexual minority emerging adults’ (ages 18–25) heightened odds of having heavier alcohol use trajectories (AUTs) and heightened risk for past-year alcohol use disorder (AUD) compared to completely heterosexuals. Methods Using self-reported data from the U.S.-based Growing Up Today Study cohort, latent class analyses identified typologies of familial and non-familial warmth during childhood and adolescence. Multivariable regression models tested our objectives. Results Six warmth classes emerged, including: High-High (i.e., high familial and high non-familial warmth, respectively); High-Moderate; Moderate-Moderate; Moderate-Occasional; Occasional-Occasional; and Low-Low. Among women, sexual minorities had higher odds than completely heterosexuals of being in the Moderate-Moderate, Moderate-Occasional, and Occasional-Occasional versus the High-High warmth class. There were not significant associations between sexual orientation and warmth classes for men. Lower warmth classes were generally associated with greater past-year AUD, and mediated heightened disparities in AUD for sexual minority women versus completely heterosexual women (4.3% mediated), but not among men. Warmth classes were generally unassociated with AUTs, and did not mediate sexual-orientation differences in AUTs. Conclusions Lower warmth was associated with greater alcohol-related problems, but not alcohol use itself. Warmth explained a small proportion of AUD disparities for sexual minority women—but not for men.

Lesbian and bisexual women are at greater risk of being obese than heterosexual women; however, there is little research on dietary intake among lesbian and bisexual women.This study estimated differences in dietary quality and intake during adulthood comparing heterosexual women to lesbian and bisexual women.Biennial mailed questionnaires were used to collect data from a cohort between 1991 and 2011. Heterosexual-identified women were the reference group.More than 100,000 female registered nurses in the United States, aged 24 to 44 years, were recruited in 1989 to participate in the Nurses' Health Study II. More than 90% of the original sample are currently active in the study. About 1.3% identified as lesbian or bisexual.Dietary measures were calculated from a 133-item food frequency questionnaire administered every 4 years. Measures included diet quality (Alternative Healthy Eating Index-2010 and Dietary Approaches to Stop Hypertension); calorie, fat, and fiber intake; and glycemic load and index.Multivariable adjusted repeated measures linear regression models were fit.On average, lesbian and bisexual women reported better diet quality (P0.001) and diets lower in glycemic index (P0.001) than heterosexual women. In the whole cohort, diet quality scores increased as participants aged, and were lower among women living in rural compared to urban regions. Comparisons in dietary intake across sexual orientation groups were generally similar across age and rurality status. However, differences between lesbian and heterosexual women in Alternative Healthy Eating Index-2010 were larger during younger compared to older ages, suggesting that diet quality estimates among sexual orientation groups converged as women aged.Lesbian and bisexual women reported higher diet quality than heterosexuals. More research examining how diet affects risk for chronic conditions, such as diabetes, among sexual minorities is needed. Physical activity, sedentary behavior, disordered eating behaviors, and psychosocial and minority stress should be explored as potential contributors to higher rates of obesity among sexual minority women.

Aims To estimate longitudinal associations between self-reported sexual orientation and past-year polysubstance use among youth, and test how gender, age, and early onset of tobacco and alcohol use contributed to variation in polysubstance use. Design Longitudinal community-based cohort of U.S. adolescents from the Growing Up Today Study (GUTS 1) (N = 16,873) followed from ages 12-29 years. Setting United States of America (USA). Participants 13,519 individuals (7,839 females; 5,680 males) who responded to at least one of five self-administered questionnaires from 1999-2010. Ninety-three percent reported their race/ethnicity as non-Hispanic white. Measurements Multivariable repeated measures generalized estimating equations estimated relative risks (RRs) of concurrent polysubstance use (i.e., past 12-month use of three or more substances) comparing sexual orientation minority youth (i.e., mostly heterosexual [MH], bisexual [BI], gay/lesbian [GL]) to their same-gender, completely heterosexual (CH) counterparts. Mediation analyses tested whether early onset of tobacco and/or alcohol use explained relationships between sexual orientation and concurrent polysubstance use. Findings Compared with their same-gender CH peers, sexual minorities evidenced higher risk for concurrent polysubstance use over all repeated measures (RRs for sexual minority subgroups: 1.63-2.91, p-values

Mesenchymal stem cells (MSCs) have been proven to be therapeutically effective against atopic dermatitis (AD) in preclinical studies. However, the safety and efficacy of MSCs against AD have not yet been investigated in a clinical study. To establish the safety and efficacy of human umbilical cord blood-derived MSCs (hUCB-MSCs) in AD, 34 adult patients with moderate-to-severe AD were enrolled in two phase trials with a follow-up for 1 month and 3 months, respectively. Patients were randomly allocated to receive low dose (2.5 × 107) or high dose (5.0 × 107) of hUCB-MSCs subcutaneously. An Eczema Area and Severity Index (EASI) score, Investigator's Global Assessment (IGA) score, Severity Scoring for Atopic Dermatitis (SCORAD) score, adverse effect assessments, and serum biomarker levels were evaluated as end points. A single treatment of hUCB-MSCs resulted in dose-dependent improvements in AD manifestation. Fifty-five percent of patients in high dose hUCB-MSC-treated group showed a 50% reduction in the EASI score. The IGA score and SCORAD score decreased by 33% and 50%, respectively, in high dose-treated group. Particularly, the administration of high dose hUCB-MSCs reduced the pruritus score by 58%. The serum IgE levels and number of blood eosinophils were downregulated by the treatment. No serious adverse events occurred, and none of the patients discontinued the trial due to adverse events. This is the first report to demonstrate a marked improvement of AD features with cell therapeutics. These data suggest that the infusion of hUCB-MSCs might be an effective therapy for patients with moderate-to-severe AD.

Introduction Sexual minority female adolescents have worse reproductive health than heterosexual peers; research into the origins of these disparities is limited. Our objective was to examine whether exposure to structural stigma (e.g., societal-level conditions, cultural norms, institutional policies/practices that constrain the lives of the stigmatized) is associated with sexually transmitted infections (STIs) and teen pregnancy in sexual minority female adolescents. Methods Longitudinal data were utilized from 6581 female adolescents aged 9–14 years at baseline (1996) in the U.S.-based Growing Up Today Study and followed through 2007. We used a previously-validated structural stigma scale composed of four state-level items (e.g., employment non-discrimination policies) with one item added relevant to reproductive health. Risk ratios were generated from multivariate models. Results Sexual minority female adolescents were significantly more likely than heterosexual peers to have an STI diagnosis and teen pregnancy. Sexual minority female adolescents living in states with lower, compared to higher, levels of structural stigma were significantly less likely to have an STI diagnosis, after adjustment for individual- and state-level covariates (relative risk [RR] = 0.70, 95% confidence interval [CI]: 0.51, 0.97). In contrast, among completely heterosexual adolescents, structural stigma was not associated with STI diagnosis. Teen pregnancy risk—a rare outcome—did not vary by level of structural stigma for sexual minority or heterosexual adolescents. Conclusions Structural stigma is a potential risk factor for adverse reproductive health among sexual minority female adolescents. Changing laws and policies to be inclusive of all people, regardless of sexual orientation, can help alleviate entrenched reproductive health disparities.

BACKGROUND: Diet and eating habits during youth have implications on diet and eating habits during adulthood; however, little longitudinal research has examined sexual orientation and gender expression differences in diet. OBJECTIVE: To examine sexual orientation and gender expression differences in diet quality and eating habits from adolescence to young adulthood. DESIGN: Data across multiple time-points from the longitudinal Growing Up Today Study cohorts (1997–2011) were used. PARTICIPANTS/SETTING: Participants (n=12,880; ages 10–23 years) are the children of women from the Nurses’ Health Study II cohort. MAIN OUTCOME MEASURES: Diet quality scores were assessed using the Alternative Healthy Eating Index-2010. Additionally, breakfast consumption (≥5 days/week) and family dinners (≥5 days/week) were assessed. STATISTICAL ANALYSES PERFORMED: Multivariable generalized estimating equations regression models were fit to estimate sexual orientation and gender expression differences in diet quality scores, breakfast consumption, and family dinners, stratified by sex assigned at birth over available repeated measures. RESULTS: “Gender nonconforming” males had significantly higher diet quality scores than “very gender conforming” males (p

OBJECTIVE Lesbian and bisexual (LB) women are more likely than heterosexual women to exhibit risk factors for type 2 diabetes, but studies estimating the burden of type 2 diabetes among LB women are uncommon and limited to cross-sectional designs. This study investigated incidence of type 2 diabetes in LB women and heterosexual women in a large, longitudinal U.S. cohort. RESEARCH DESIGN AND METHODS Women participating in the Nurses’ Health Study II (NHS II) ages 24–44 years in 1989 were prospectively followed through 2013. Self-reported clinician diagnosis of type 2 diabetes was assessed every other year to identify incidence. Of the participants, 1,267 identified as lesbian or bisexual and 92,983 identified as heterosexual. Cox proportional hazards regression was used to model incidence of type 2 diabetes. RESULTS LB women had a 27% higher risk of developing type 2 diabetes than heterosexual women (adjusted incidence rate ratio [IRR] 1.27, 95% CI 1.05, 1.54). Differences between LB women and heterosexual women in risk of type 2 diabetes were greater during younger ages (sexual orientation–by-age interaction, P < 0.001). BMI mediated the relationship between sexual orientation and type 2 diabetes; the IRR was completely attenuated when BMI was added to the model (IRR 0.85, 95% CI 0.70, 1.03). CONCLUSIONS Findings indicate that LB women develop type 2 diabetes at younger ages than heterosexual women. Higher BMI in LB women is an important contributor to this disparity. Public health and clinical efforts to prevent, detect, and manage obesity and type 2 diabetes among LB women are warranted.

AIMS: We estimated sexual-orientation differences in alcohol use trajectories during emerging adulthood, and tested whether alcohol use trajectories mediated sexual-orientation differences in alcohol use disorders (AUDs). DESIGN: Longitudinal self-reported survey data from the Growing Up Today Study. SETTING: United States. PARTICIPANTS: A total of 12 493 participants aged 18–25 during the 2003, 2005, 2007 or 2010 surveys. MEASUREMENTS: Stratified by gender, longitudinal latent class analyses estimated alcohol use trajectories (using past-year frequency, quantity and binge drinking from 2003 to 2010). Multinomial logistic regression tested differences in trajectory class memberships by sexual orientation [comparing completely heterosexual (CH) participants with sexual-minority subgroups: mainly heterosexual (MH), bisexual (BI) and gay/lesbian (GL) participants]. Modified Poisson regression and mediation analyses tested whether trajectories explained sexual-orientation differences in AUDs (past-year DSM-IV abuse/dependence in 2010). FINDINGS: Six alcohol use trajectory classes emerged for women and five for men: these included heavy (23.5/36.9% of women/men), moderate (31.8/26.4% of women/men), escalation to moderately heavy (9.7/12.0% of women/men), light (17.0% for women only), legal (drinking onset at age 21; 11.1/15.7% of women/men) and non-drinkers (7.0/9.1% of women/men). Compared with CH women, MH and BI women had higher odds of being heavy, moderate, escalation to moderately heavy and light drinkers versus non-drinkers (odds ratios = 2.02–3.42; P-values < 0.01–0.04). Compared with CH men, MH men had higher odds of being heavy, moderate and legal drinkers versus non-drinkers (odds ratios = 2.24–3.34; P-values < 0.01–0.01). MH men and women, BI women and GLs had higher risk of AUDs in 2010 than their same-gender CH counterparts (risk ratios = 1.34–2.17; P-values < 0.01). Alcohol use trajectories mediated sexual-orientation differences in AUDs for MH and GL women (proportion of effect mediated = 30.8–31.1%; P-values < 0.01–0.02), but not for men. CONCLUSIONS: In the United States, throughout emerging adulthood, several sexual-minority subgroups appear to have higher odds of belonging to heavier alcohol use trajectories than completely heterosexuals. These differences partially explained the higher risk of alcohol use disorders among mainly heterosexual and gay/lesbian women but not among sexual-minority men.

Although epidemiologic studies have established the existence of large sexual orientation disparities in illicit drug use among adolescents and young adults, the determinants of these disparities remain understudied. This study sought to determine whether sexual orientation disparities in illicit drug use are potentiated in states that are characterized by high levels of stigma surrounding sexual minorities. State-level structural stigma was coded using a previously established measure based on a 4-item composite index: (1) density of same-sex couples; (2) proportion of Gay-Straight Alliances per public high school; (3) 5 policies related to sexual orientation discrimination (e.g., same-sex marriage, employment non-discrimination); and (4) public opinion toward homosexuality (aggregated responses from 41 national polls). The index was linked to individual-level data from the Growing Up Today Study, a prospective community-based study of adolescents (2001-2010). Sexual minorities report greater illicit drug use than their heterosexual peers. However, for both men and women, there were statistically significant interactions between sexual orientation status and structural stigma, such that sexual orientation disparities in marijuana and illicit drug use were more pronounced in high-structural stigma states than in low-structural stigma states, controlling for individual- and state-level confounders. For instance, among men, the risk ratio indicating the association between sexual orientation and marijuana use was 24% greater in high- versus low-structural stigma states, and for women it was 28% greater in high- versus low-structural stigma states. Stigma in the form of social policies and attitudes may contribute to sexual orientation disparities in illicit drug use.

Mechanism of barley sprout extract (BS), which contains policosanols and polyphenols, on cholesterol and glucose metabolism was investigated. BS reduced the intracellular cholesterol concentrations in the HepG2 cells and the plasma cholesterol concentrations in the mice by the activation of AMPK and the subsequent phosphorylation inhibition of HMGCR. BS suppressed the nuclear translocation of SREBP2, reducing the transcription of HMGCR. AMPK activation with BS reduced the fasting glucose and hepatic triglyceride concentrations in mice by repressing the hepatic gluconeogenic genes, including fructose-1, 6-bisphosphatase and pyruvate carboxylase and the plasma levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6. The activation of hepatic autophagy by BS was confirmed by induced protein expressions of LC3-II and LAMP. In conclusion, BS activates AMPK and hepatic autophagy and inhibits SREBP2, resulting in hypocholesterolemic and hypoglycemic activities and improvements in the symptoms of hepatic steatosis.

Evidence indicates that restaurant-based interventions have the potential to promote healthier purchasing and improve the nutrients consumed. This study adds to this body of research by reporting the results of a trial focused on promoting the sale of healthy child menu items in independently owned restaurants. Eight pair-matched restaurants that met the eligibility criteria were randomized to a menu-only versus a menu-plus intervention condition. Both of the conditions implemented new healthy child menu items and received support for implementation for eight weeks. The menu-plus condition also conducted a marketing campaign involving employee trainings and promotional materials. Process evaluation data captured intervention implementation. Sales of new and existing child menu items were tracked for 16 weeks. Results indicated that the interventions were implemented with moderate to high fidelity depending on the component. Sales of new healthy child menu items occurred immediately, but decreased during the post-intervention period in both conditions. Sales of existing child menu items demonstrated a time by condition effect with restaurants in the menu-plus condition observing significant decreases and menu-only restaurants observing significant increases in sales of existing child menu items. Additional efforts are needed to inform sustainable methods for improving access to healthy foods and beverages in restaurants.

The transcriptional coactivator peroxisome proliferator–activated receptor γ coactivator (PGC)-1α and its splice variant N terminal (NT)-PGC-1α regulate adaptive thermogenesis by transcriptional induction of thermogenic and mitochondrial genes involved in energy metabolism. We previously reported that full-length PGC-1α (FL-PGC-1α) is dispensable for cold-induced nonshivering thermogenesis in FL-PGC-1α−/− mice, since a slightly shorter but functionally equivalent form of NT-PGC-1α (NT-PGC-1α254) fully compensates for the loss of FL-PGC-1α in brown and white adipose tissue. In the current study, we challenged FL-PGC-1α−/− mice with a high-fat diet (HFD) to investigate the effects of diet-induced thermogenesis on HFD-induced obesity. Despite a large decrease in locomotor activity, FL-PGC-1α−/− mice exhibited the surprising ability to attenuate HFD-induced obesity. Reduced fat mass in FL-PGC-1α−/− mice was closely associated with an increase in body temperature, energy expenditure, and whole-body fatty acid oxidation (FAO). Mechanistically, FL-PGC-1α−/− brown adipose tissue had an increased capacity to oxidize fatty acids and dissipate energy as heat, in accordance with upregulation of thermogenic genes UCP1 and DIO2. Furthermore, augmented expression of FAO and lipolytic genes in FL-PGC-1α−/− white adipose tissue was highly correlated with decreased fat storage in adipose tissue. Collectively, our data highlight a protective effect of NT-PGC-1α on diet-induced obesity by enhancing diet-induced thermogenesis and FAO.

Intake of dietary aroma compounds may regulate cellular lipid metabolism. We demonstrated that trans-caryophyllene, a flavor compound in plant foods and teas, activates peroxisome proliferator-activated receptor (PPAR)-α through direct interaction with the ligand-binding domain of PPAR-α. The agonistic activity of trans-caryophyllene was investigated by the luciferase reporter assay, surface plasmon resonance, and time-resolved fluorescence resonance energy transfer assay. Following the stimulation of cells with trans-caryophyllene, intracellular triglyceride concentrations were significantly reduced by 17%, and hepatic fatty acid uptake was significantly increased by 31%. The rate of fatty acid oxidation was also significantly increased. The expressions of PPAR-α and its target genes and proteins in fatty acid uptake and oxidation were significantly up-regulated as well. In HepG2 cells transfected with small interfering RNA of PPAR-α, the effects of trans-caryophyllene on PPAR-α responsive gene expressions, intracellular triglyceride, fatty acid uptake and oxidation were disappeared. These results indicate that the aroma compound, trans-caryophyllene, is PPAR-α agonist thus regulates cellular lipid metabolism in PPAR-α dependent manners.

Purpose This research aimed to explain sexual orientation disparities in body mass index (BMI) by examining child abuse history, weight-related behaviors, and sociodemographics. Methods We used data from 7,960 females and 5,992 males from the prospective Growing Up Today Study over nine waves between 1996 (ages 12–14 years) and 2007 (ages 20–25 years). Using repeated measures of BMI (kg/m 2 ) as a continuous outcome, gender-stratified latent quadratic growth models adjusted for child abuse history, weight-related behaviors, and sociodemographics. BMI at age 17 years (intercept) and 1-year change in BMI (slope) are reported. Results Bisexual females had higher BMI at age 17 years (β = 1.59, 95% CI = 1.00–2.18) and displayed greater one-year increases in BMI (β = .09, 95% CI = .03–.14), compared with completely heterosexual females. Gay males displayed smaller 1-year increases in BMI (β = −.19, 95% CI = −.25 to −.12), compared with completely heterosexual males. No sexual orientation differences in BMI at age 17 years were observed for males, but gay males' BMI at age 25 was less than completely heterosexual males' BMI by 2 units. Among females, sexual orientation differences remained but were slightly attenuated after controlling for child abuse history, weight-related behaviors, and sociodemographics. Among males, the addition of child abuse and weight-related behaviors did not change the estimated difference in 1-year BMI increases. Conclusions Sexual orientation differences in BMI were partly explained by child abuse and weight-related behaviors in females. More research is needed to explore additional drivers of these disparities among both females and males.

BACKGROUND: This study examined associations of sexual orientation and gender identity with prevalence of substance use disorders (SUDs) and co-occurring multiple SUDs in the past 12-month during young adulthood in a United States longitudinal cohort. METHODS: Questionnaires self-administered in 2010 and 2015 assessed probable past 12-month nicotine dependence, alcohol abuse and dependence, and drug abuse and dependence among 12,428 participants of an ongoing cohort study when they were ages 20–35 years. Binary or multinomial logistic regressions using generalized estimating equations were used to estimate differences by sexual orientation and gender identity in the odds of SUDs and multiple SUDs, stratified by sex assigned at birth. RESULTS: Compared with completely heterosexuals (CH), sexual minority (SM; i.e., mostly heterosexual, bisexual, lesbian/gay) participants were generally more likely to have a SUD, including multiple SUDs. Among participants assigned female at birth, adjusted odds ratios (AORs) for SUDs comparing SMs to CH ranged from 1.61–6.97 (ps

Flavonoids are abundant in fruits and vegetables and have various biological activities. A rapid, sensitive method for assessing cellular quercetin levels is necessary because cellular levels are often low. A new method for measuring cellular flavonoid levels is proposed using diphenylboric acid 2-aminoethyl ester (DPBA), a fluorescent probe, and quercetin, a representative flavonoid. This spectrofluorometry-based assay is simple and allows rapid quantification of the cellular quercetin content with high sensitivity. CHO-K1 cells were incubated with quercetin for 5 min, and then the cellular quercetin concentration was assayed using DPBA spectrofluorometry. Results, compared with high-performance liquid chromatography (HPLC), thin layer chromatography (TLC), and conventional spectrophotometry measurements, were highly correlated with HPLC data (R>0.99). The method is more sensitive than TLC and conventional spectrophotometry. Spectrofluorometric measurement using DPBA is a simple, rapid, and sensitive method for assessing cellular quercetin levels.

OBJECTIVE We sought to estimate the association between intimate partner violence, a prevalent psychosocial stressor, and the incidence of type 2 diabetes in women. RESEARCH DESIGN AND METHODS In 2001, 68,376 Nurses’ Health Study II participants answered questions on physical, sexual, and psychological intimate partner violence in adulthood (age ≥18 years) and reported the years in which any abuse occurred. We used Cox proportional hazards models to estimate the associations between intimate partner violence exposures and incidence of type 2 diabetes from 2001 to 2007. We also estimated effects of duration and time since intimate partner violence on type 2 diabetes incidence. RESULTS Of 68,376 respondents, 64,732 met inclusion criteria at the 2001 baseline; of these, 23% reported lifetime physical intimate partner violence, 11% reported lifetime sexual intimate partner violence, and 8% reported moderate and CONCLUSIONS Physical intimate partner violence is modestly associated with incidence of type 2 diabetes in this population. Severe psychological violence may substantially increase type 2 diabetes risk.

We investigated the effect of cineole on the expression of genes related to reverse cholesterol transport and hepatic fatty acid metabolism. Cineole, a small aroma compound in teas and herbs, significantly stimulated the transactivation of liver X receptor modulator (LXR)-α and LXR-β. The mRNA and protein expression of LXRs and their target genes, including ABCA1 and ABCG1, was significantly increased in macrophages stimulated with cineole. This led to the subsequent removal of cholesterol from the cells. Interestingly, cineole showed tissue-selective LXR induction: hepatocytes stimulated with cineole showed significantly reduced expression of LXR-α and LXR-α-responsive genes, including FAS and SCD-1 (P

ObjectiveRestaurants are playing an increasingly important role in children’s dietary intake. Interventions to promote healthy ordering in restaurants have primarily targeted adults. Much remains unknown about how to influence ordering for and by children. Using an ecological lens, the present study sought to identify sources of influence on ordering behaviour for and by children in restaurants.DesignA mixed-methods study was conducted using unobtrusive observations of dining parties with children and post-order interviews. Observational data included: child’s gender, person ordering for the child and server interactions with the dining party. Interview data included: child’s age, restaurant visit frequency, timing of child’s decision making, and factors influencing decision making.SettingTen independent, table-service restaurants in San Diego, CA, USA participated.SubjectsComplete observational and interview data were obtained from 102 dining parties with 150 children (aged 3–14 years).ResultsTaste preferences, family influences and menus impacted ordering. However, most children knew what they intended to order before arriving at the restaurant, especially if they dined there at least monthly. Furthermore, about one-third of children shared their meals with others and all shared meals were ordered from adult (v. children’s) menus. Parents placed most orders, although parental involvement in ordering was less frequent with older children. Servers interacted frequently with children but generally did not recommend menu items or prompt use of the children’s menu.ConclusionsInterventions to promote healthy ordering should consider the multiple sources of influence that are operating when ordering for and by children in restaurants.

Scant research exists on the development of mostly heterosexual identity, the largest sexual orientation minority subgroup. We used longitudinal latent class analysis to characterize patterns of identification with lesbian, gay, bisexual [LGB], or mostly heterosexual identities from ages 12-23 years in 13,859 youth (57% female) in a US national cohort. Three classes emerged: Completely Heterosexual (88.2%), Mostly Heterosexual (9.5%), and LGB (2.4%). LGB Class youth generally identified with sexual minority identities by ages 12-17 years. In contrast, Mostly Heterosexual Class youth identified with sexual minority identities gradually, with steady increases in endorsement starting at age 14 years. Developmental implications of these differential patterns are discussed.

Fucosterol, a sterol that is abundant in marine algae, has hypocholesterolemic activity, but the mechanism underlying its effect is not clearly understood. Because data suggest that fucosterol can increase plasma high-density lipoprotein concentrations, we investigated whether it could activate liver X receptors (LXRs), critical transcription factors in reverse cholesterol transport. Fucosterol dose-dependently stimulated the transcriptional activity of both LXR-α and -β in a reporter gene assay, responses that were attenuated by the LXR antagonist As(2)O(3). Fucosterol also activated co-activator recruitment in cell-free time-resolved fluorescence resonance energy transfer analysis. In THP-1-derived macrophages, it induced the transcriptional activation of ABCA1, ABCG1, and ApoE, key genes in reverse cholesterol transport, and thereby significantly increased the efflux of cholesterol. Fucosterol also regulated intestinal NPC1L1 and ABCA1 in Caco-2 cells. Notably, fucosterol did not induce cellular triglyceride accumulation in HepG2 cells, primarily because of its upregulation of Insig-2a, which delays nuclear translocation of SREBP-1c, a key hepatic lipogenic transcription factor. These results suggest that fucosterol is a dual-LXR agonist that regulates the expression of key genes in cholesterol homeostasis in multiple cell lines without inducing hepatic triglyceride accumulation.

We investigated the in vitro effects of p-coumaric acid on melanogenesis. The melanin content in B16F1 cells stimulated with p-coumaric acid significantly decreased (68 % vs. control) through inhibition of tyrosinase enzyme activity assessed using both cell-free and cell-based assays (46 and 27 % compared with control, respectively). In addition, stimulating B16F1 cells with p-coumaric acid reduced cyclic adenosine monophosphate (cAMP)—responsive element-binding protein (CREB) protein phosphorylation (26 % vs. control), which in turn downregulated the expression of the microphthalmia-associated transcription factor (MITF) and its target gene tyrosinase (27 and 20 % vs. control, respectively). p-Coumaric acid has a hypopigmentation effect in melanocytes by both directly inhibiting tyrosinase enzyme activity and reducing CREB phosphorylation, which inhibits MITF and tyrosinase expression.

Background— Although child abuse is widespread and has been associated with cardiovascular disease (CVD) risk factors, its association with CVD events is not established. Methods and Results— We examined associations of child abuse with CVD events among 66 798 women in the Nurses' Health Study 2. Proportional hazards models estimated hazard ratios and 95% confidence intervals (CIs) for myocardial infarction (n=262), stroke (n=251), and total CVD (n=513). Severe physical abuse was reported by 9% and forced sex by 11% of participants. After adjustment for age, race, childhood body type, parental education, and family CVD history, the hazard ratios for CVD events were 0.91 (95% CI, 0.70–1.17) for mild physical abuse, 1.02 (95% CI, 0.82–1.26) for moderate physical abuse, and 1.46 (95% CI, 1.11–1.92) for severe physical abuse compared with no abuse. Compared with women without childhood sexual abuse, the hazard ratio was 1.10 (95% CI, 0.88–1.35) for unwanted sexual touching and 1.56 (95% CI, 1.23–1.99) for forced sex. After adjustment for adult lifestyle and medical risk factors, the hazard ratio for severe physical abuse was 1.13 (95% CI, 0.85–1.51) and that for forced sex was 1.25 (95% CI, 0.98–1.60); these intermediates accounted for much of the association of severe child abuse with CVD. Associations were similar for retrospectively and prospectively reported events. Women with abuse were less likely to release medical records. The associations were stronger for unconfirmed self-reported events than end points that were corroborated with additional information or medical record review. Conclusion— Severe child abuse is a prevalent risk for early adult CVD that is partially mediated by preventable risk factors.

cope A natural carotenoid abundant in seafood, astaxanthin (AX), has hypolipidemic activity, but its underlying mechanisms of action and protein targets are unknown. We investigated the molecular mechanism of action of AX in hepatic hyperlipidemia by measuring peroxisome proliferator-activated receptors (PPAR) activity. Methods and results We examined the binding of AX to PPAR subtypes and its effects on hepatic lipid metabolism. AX binding activated PPAR-α, but inhibited PPAR-γ transactivation activity in reporter gene assay and time-resolved fluorescence energy transfer analyses. AX had no effect on PPARδ/β transactivation. AX bound directly to PPAR-α and PPAR-γ with moderate affinity, as assessed by surface plasmon resonance experiments. The differential effects of AX on PPARs were confirmed by measuring the expression of unique responsive genes for each PPAR subtype. AX significantly reduced cellular lipid accumulation in lipid-loaded hepatocytes. Transcriptome analysis revealed that the net effects of stimulation with AX (100 μM) on lipid metabolic pathways were similar to those elicited by fenofibrate and lovastatin (10 μM each), with AX rewiring the expression of genes involved in lipid metabolic pathways. Conclusion AX is a PPAR-α agonist and PPAR-γ antagonist, reduces hepatic lipid accumulation by rewiring the transcriptome in lipid-loaded hepatocytes.

cope Taurine, which is abundant in seafood, has antiatherogenic activities in both animals and humans; however, its molecular target has been elusive. We examined whether taurine could activate liver X receptor-α (LXR-α), a critical transcription factor in the regulation of reverse cholesterol transport in macrophages. Methods and results Taurine bound directly to LXR-α in a reporter gene assay, time-resolved fluorescence resonance energy transfer analysis, and limited protease digestion experiment. Macrophage cells incubated with taurine showed reduced cellular cholesterol and induced medium cholesterol in a dose-dependent manner with the induction of ATP-binding cassette transporter A1 and G gene and protein expression. In hepatocytes, taurine significantly induced Insig-2a levels and delayed nuclear translocation of the sterol regulatory element-binding protein 1 (SREBP-1) protein, resulting in a dose-dependent reduction in the cellular lipid levels without inducing the expression of fatty acid synthesis genes. Conclusion Taurine is a direct LXR-α ligand, represses cholesterol accumulation, and modulates the expression of genes involved in reverse cholesterol transport in macrophages, without inducing hepatic lipogenesis. The induction of Insig-2a suppressed the nuclear translocation of SREBP-1c.

Youths with a minority sexual orientation (i.e., gay, lesbian, bisexual, and mostly heterosexual) are at high risk for cigarette smoking. We examined sexual-orientation disparities in smoking during adolescence and emerging adulthood and investigated the role of age at first smoking in contributing to smoking disparities.We used data from the Growing Up Today Study, a large longitudinal cohort of adolescents followed from ages 12 to 24 years (N = 13,913). Self-administered questionnaires filled out annually or biennially assessed age at first smoking, current smoking, frequency of smoking, number of cigarettes smoked daily, and nicotine dependence. Proportional hazards survival analysis and repeated measures regression estimated sexual-orientation differences in smoking.Compared with completely heterosexuals, lesbian/gay, bisexual, and mostly heterosexual youths smoked their first cigarette at younger ages, were more likely to be current smokers, and had higher frequency of smoking. Among past-year smokers, sexual-minority females smoked more cigarettes daily and scored higher on nicotine dependence than completely heterosexual females. In some instances, gender and age modified relationships between sexual orientation and smoking, with relative risk accentuated in female sexual minorities and in sexual minorities during younger ages. Younger age of smoking onset contributed to elevated smoking in mostly heterosexuals and bisexuals, and to a lesser extent in lesbians, but not in gay males.Sexual-orientation minorities are at greater risk for smoking during adolescence and emerging adulthood than heterosexuals. Disparities are larger in females and evident in early adolescence. Prevention and cessation efforts should target this population, preferably beginning in early adolescence.

Background Cross-sectional research has documented elevated prevalence of obesity in lesbian and bisexual women relative to heterosexual women, but little is known about disparities in longitudinal patterns in BMI change during adulthood. Purpose To examine sexual orientation–related disparities in individual BMI trajectories throughout adulthood. Methods Data on BMI, sexual orientation, and sociodemographics were gathered prospectively from 1989 through 2005 from 90,713 U.S. women in the Nurses' Health Study II and examined in 2011 using general growth mixture modeling to identify BMI trajectories from ages 25 to 59 years. Multinomial logistic regression was used to determine whether sexual orientation was associated with BMI trajectory group membership. Results Four BMI trajectory groups were identified and labeled based on mean BMI within each group at baseline and final follow-up: Group 1: slow-weight-gain trajectory; Group 2: moderate-weight-gain trajectory; Group 3: rapid-weight-gain trajectory; and Group 4: obese-to-overweight trajectory. Lesbian and bisexual women showed consistently higher odds of membership in Groups 2–4 (adverse-weight-gain trajectories) versus Group 1 (the slow-weight-gain trajectory) relative to heterosexual women. Conclusions Both lesbian and bisexual women were more likely than heterosexual women to experience adverse-weight-gain trajectories in adulthood. New research efforts are needed to understand and eliminate these pronounced disparities.

We investigated the acute metabolic effects of isoflavones from Pueraria lobata (Willd.) Ohwi (IPL) in ovariectomized (OVX) mice. After 4 weeks of IPL feeding at 500 mg/day/kg body weight (OVX500), plasma 17β-estradiol concentrations were significantly higher (+25%, p

Toxicity, antioxidant activity, and biological functionality of Korean black raspberry wine (KBRW) extracts on human ARPE-19 and HepG2 cells were determined using MTT and lipid/malonaldehyde (MA) assays and reverse transcription polymerase chain reaction (RT-PCR) as well as anti-obesity effect of KBRW extracts on various cancer cells. All samples inhibited MA formation by 38.0–88.0%. Bokbunja and Sanmaesu exerted greater inhibitory effect than other wines. Both cell lines were each treated with KBRW for 24 h, and viability was measured by MTT assay. No toxicity was found, even at 500 μg/mL. Changes in gene expression for CYP7A1, low-density-lipoprotein receptor (LDL) receptor, 3-hydrozy-3-methylglutaryl-CoA (HMG-CoA) reductase, and vescular endothelial growth factor (VEGF) were assessed by semiquantitative RT-PCR. CYP7A1 and LDL receptor expressions in ARPE-19 cells were elevated, whereas HMG CoA reductase expression was decreased by Bokbunja and Sanmaesu. Expression of VEGF was decreased by Bokbunja but elevated by Sanmaesu. In HepG2 cells, gene expression was similar after Bokbunja and Sanmaesu treatments. CYP7A1 and HMG CoA expressions were elevated. LDL receptor expression was increased by Bokbunja but decreased by Sanmaesu. Bokbunja and Sanmaesu inhibited VEGF expression but elevated those of CYP7A1 and HMG CoA reductase. Bokbunja and Sanmaesu displayed anti-cholesterol effects that could be attributed to increased gene expression in CYP7A1 and HMG CoA reductase.

We investigated the hypolipidemic effects of Melissa officinalis essential oil (MOEO) in human APOE2 transgenic mice and lipid-loaded HepG2 cells. Plasma TG concentrations were significantly less in APOE2 mice orally administered MOEO (12.5 mg/d) for 2 wk than in the vehicle-treated group. Cellular TG and cholesterol concentrations were also significantly decreased in a dose- (400 and 800 mg/L) and time- (12 and 24 h) dependent manner in HepG2 cells stimulated with MOEO compared with controls. Mouse hepatic transcriptome analysis suggested MOEO feeding altered several lipid metabolic pathways, including bile acid and cholesterol synthesis and fatty acid metabolism. In HepG2 cells, the rate of fatty acid oxidation, as assessed using [1- 14 C]palmitate, was unaltered; however, the rate of fatty acid synthesis quantified with [1- 14 C]acetate was significantly reduced by treatment with 400 and 800 mg/L MOEO compared with untreated controls. This reduction was due to the decreased expression of SREBP-1c and its responsive genes in fatty acid synthesis, including FAS, SCD1, and ACC1. Subsequent chromatin immunoprecipitation analysis further demonstrated that the binding of p300/CBP-associated factor, a coactivator of SREBP-1c, and histone H3 lysine 14 acetylation at the FAS, SCD1, and ACC1 promoters were significantly reduced in the livers of APOE2 mice and HepG2 cells treated with MOEO compared with their controls. Additionally, MOEO stimulation in HepG2 cells induced bile acid synthesis and reduced the nuclear form of SREBP-2, a key transcription factor in hepatic cholesterol synthesis. These findings suggest that the intake of phytochemicals with pleasant scent could have beneficial metabolic effects. J. Nutr. 142: 432‐440, 2012.

PGC-1α is an inducible transcriptional coactivator that regulates cellular energy metabolism and adaptation to environmental and nutritional stimuli. In tissues expressing PGC-1α, alternative splicing produces a truncated protein (NT-PGC-1α) corresponding to the first 267 amino acids of PGC-1α. Brown adipose tissue also expresses two novel exon 1b-derived isoforms of PGC-1α and NT-PGC-1α, which are 4 and 13 amino acids shorter in the N termini than canonical PGC-1α and NT-PGC-1α, respectively. To evaluate the ability of NT-PGC-1α to substitute for PGC-1α and assess the isoform-specific role of NT-PGC-1α, adaptive thermogenic responses of adipose tissue were evaluated in mice lacking full-length PGC-1α (FL-PGC-1(-/-)) but expressing slightly shorter but functionally equivalent forms of NT-PGC-1α (NT-PGC-1α(254)). At room temperature, NT-PGC-1α and NT-PGC-1α(254) were produced from conventional exon 1a-derived transcripts in brown adipose tissue of wild type and FL-PGC-1α(-/-) mice, respectively. However, cold exposure shifted transcription to exon 1b, increasing exon 1b-derived mRNA levels. The resulting transcriptional responses produced comparable increases in energy expenditure and maintenance of core body temperature in WT and FL-PGC-1α(-/-) mice. Moreover, treatment of the two genotypes with a selective β(3)-adrenergic receptor agonist produced similar increases in energy expenditure, mitochondrial DNA, and reductions in adiposity. Collectively, these findings illustrate that the transcriptional and physiological responses to sympathetic input are unabridged in FL-PGC-1α(-/-) mice, and that NT-PGC-1α is sufficient to link β(3)-androgenic receptor activation to adaptive thermogenesis in adipose tissue. Furthermore, the transcriptional shift from exon 1a to 1b supports isoform-specific roles for NT-PGC-1α in basal and adaptive thermogenesis.

Momilactone B (MB) is a terpenoid phytoalexin present in rice bran that exhibits several biological activities. MB reduced the melanin content in B16 melanocytes melanin content and inhibited tyrosinase activities. Using transcriptome analysis, the genes involved in protein kinase A (PKA) signaling were found to be markedly altered. B16 cells stimulated with MB had decreased concentrations of cAMP protein kinase A activity, and cAMP-response element-binding protein which is a key transcription factor for microphthalmia-associated transcription factor (MITF) expression. Accordingly, the expression of MITF and its target genes, which are essential for melanogenesis, were reduced. MB thus exhibits anti-melanogenic effects by repressing tyrosinase enzyme activity and inhibiting the PKA signaling pathway which, in turn, decreases melanogenic gene expression.

We report a rare case of eye complication following botulinum toxin type A (BTA) injection. A 36-year-old healthy woman received BTA injections on the glabella, forehead, and periocular area to improve her wrinkles. Four days after BTA injection, diplopia and esotropia developed on her right eye.

Red yeast (Monascus purpureus) fermented over rice has a limited hypoglycemic activity. To enhance its glucose-lowering effect, we fermented red yeast over waxy barley, a hypoglycemic grain with high levels of fibers and β-glucans, and investigated the metabolic effects of red yeast barley (RYB) in high-fat-fed hyperglycemic db/db mice for 6 weeks. The fasting glucose levels were significantly reduced in the RYB group at 6 weeks by 25% (p

We investigated the effects of puerarin, the major isoflavone in Kudzu roots, on the regulation of autophagy in ethanol-treated hepatocytes. Incubation in ethanol (100 mM) for 24 h reduced cell viability by 20% and increased the cellular concentrations of cholesterol and triglycerides by 40% and 20%, respectively. Puerarin stimulation significantly recovered cell viability and reduced cellular lipid accumulation to a level comparable to that in untreated control cells. Ethanol incubation reduced autophagy significantly as assessed by microtubule-associated protein1 light chain 3 (LC3) expression using immunohistochemistry and immunoblot analysis. The reduced expression of LC3 was restored by puerarin in a dose-dependent manner in ethanol-treated cells. The effect of puerarin on mammalian targets of rapamycin (mTOR), a key regulator of autophagy, was examined in ethanol-treated hepatocytes. Immunoblotting revealed that puerarin significantly induced the phosphorylation of 5'AMP-activated protein kinase (AMPK), thereby suppressing the mTOR target proteins S6 ribosomal protein and 4E-binding protein 1. These data suggest that puerarin restored the viability of cells and reduced lipid accumulation in ethanol-treated hepatocytes by activating autophagy via AMPK/mTOR-mediated signaling.

The effects of wild type and UV-irradiated lemon balm (Melissa officinalis) ethanolic extracts (MOE and UMOE) on melanogenesis in vitro were examined. UMOE showed potent antioxidant activity and significantly inhibited the mushroom and melanocyte tyrosinase activity, and lowered cellular melanin content by 49% at 200 μg/mL in B16-F1 melanocytes. The key gene and protein expression of tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 were reduced (−73% for TRP-1 protein at 200 μg/mL UMOE, p

Department of Biological Science, Konkuk UniversityAbstract We examined the in vitro mutagenic and antimutagenic effects of hexane-extracted hemp (Cannabis sativa L.subsp. sativa var. sativa) seed oil (HO) with and without S9-mediated metabolic activation, using the TA98 and TA100Salmonella Typhimurium strains. The MTT assay revealed no cytotoxicity in HepG2 cells for HO quantities