Design of the PACIFIC study: A randomized controlled trial evaluating a novel treatment for adults with overweight and obesity.

The majority of adults in the United States have overweight or obesity which is associated with significant health and psychological consequences. Behavioral Weight Loss (BWL) is the current gold-standard weight-loss program for adults but recidivism rates continue to be disturbingly high. Given the health consequences of excess weight and the lack of long-term effectiveness of BWL, it is important to identify novel weight-loss programs. We developed the ROC (Regulation of Cues) program to reduce overeating through improvement in sensitivity to appetitive cues and decreased responsivity to external food cues. This study is a 4-arm randomized control trial designed to evaluate the efficacy of ROC, ROC combined with BWL, BWL alone and an active comparator over 24 months. Study recruitment completed in November 2017. Two hundred and seventy-one participants were randomized (mean age = 46.97 years; 82% female, mean BMI = 34.59; 20% Hispanic) and assessments were conducted at baseline, mid-treatment (6 months) and post-treatment (12 months). At this time, participants are completing 6- (18 months) and 12-month (24 months) follow-ups. Targeting novel mechanisms is critically important to improve weight-loss programs. Through this trial, we hope to identify treatments for adults with overweight and obesity to facilitate long-term weight loss and improved health

Screening for eating disorders in adolescents with chronic pain: the Eating Attitudes Test– 16–Chronic Pain

Background Few measures have been validated to screen for eating disorders (ED) in youth with chronic pain. We conducted confirmatory (CFA) of two established factor structures of the Eating Attitudes Test-26 (EAT-26) in a sample of youth with chronic pain attending an intensive interdisciplinary pain treatment (IIPT) program and examined the validity of the best-fitting model in predicting ED diagnoses in this sample. Methods Participants were 880 adolescents (M age = 16.1, SD = 2.1) consecutively admitted into an IIPT program who completed the EAT-26 upon admission. CFA was conducted and in the case of inadequate fit, EFA was planned to identify alternative models. Factors of the best-fitting model were included in a logistic regression analysis to predict ED diagnoses. Results The TLIs (0.70; 0.90), RMSEAs (0.09; 0.07) and CFIs (0.73; 0.92) suggested poor fit of one model and adequate of the second model. Goodness of fit indices from EFA (TLI:0.85, RMSEA:0.06) did not outperform the fit of the second CFA. As such, the second model was retained with the exception of one factor. The items loaded onto a 16-item, five factor model: Fear of Getting Fat, Social Pressure to Gain Weight, Eating-Related Control, Eating-Related Guilt and Food Preoccupation. Based on chart review, 19.1% of the participants were diagnosed with an eating disorder. Logistic regression analyses indicated the new 16-item measure and Fear of Getting Fat, significantly predicted an ED diagnosis that did not include avoidant restrictive food intake disorder (ARFID) and Social Pressure to Gain Weight significantly predicted a diagnosis of ARFID

Attributes of children and adolescents with avoidant/restrictive food intake disorder.

BackgroundAvoidant/Restrictive Food Intake Disorder (ARFID) is a comparatively new DSM-5 diagnosis. In an effort to better understand this heterogeneous patient group, this study aimed to describe the physical and psychological attributes of children and adolescents with ARFID, and to compare them to patients with full-threshold or atypical anorexia nervosa (AN).MethodsChildren and adolescents aged 7-to-19 years (N = 193) were examined upon presenting at a pediatric eating disorder center between July 2015 and December 2017. Data included diagnosis assessed via the semi-structured Eating Disorder Examination interview along with measures of anthropometrics, depression, anxiety, self-esteem, perfectionism and clinical impairment.ResultsCompared to AN and atypical AN (n = 87), patients with ARFID (n = 106) were significantly younger (12.4 vs. 15.1 years, p < .0001), male (41% vs. 15%, p < .0002), and were more likely to be diagnosed with at least one co-morbid DSM-5 diagnosis (75% vs. 61%, p = .04). Patients with ARFID were less likely to be bradycardic (4.7% vs. 24.1%, p < .0001), amenorrheic (11.1 and 34.7%, p = .001), admitted to the hospital (14.2% vs. 27.6%, p = .02), and have a diagnosis of depression (18.9% vs. 48.3%, p < .0001). Patients with ARFID were significantly less likely to experience acute weight loss vs. chronic weight loss as compared with those with AN or atypical AN (p = .0001). On self-report measures, patients with ARFID reported significantly fewer symptoms of depression, anxiety, perfectionism, clinical impairment, concerns about weight and shape, and higher self-esteem than patients with AN or atypical AN (all ps < .0001). No differences were observed by race, anxiety disorder, orthostatic instability, suicidal ideation, and history of eating disorder treatment.ConclusionsStudy results highlight the clinical significance of ARFID as a distinct DSM-5 diagnosis and the physical and psychological differences between ARFID and AN/atypical AN. The novel finding that ARFID patients are more likely than those diagnosed with AN to experience chronic, rather than acute, weight loss suggests important related treatment considerations

Structure–activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors

A structure–activity relationship study of dorsomorphin, a previously identified inhibitor of SMAD 1/5/8 phosphorylation by bone morphogenetic protein (BMP) type 1 receptors ALK2, 3, and 6, revealed that increased inhibitory activity could be accomplished by replacing the pendent 4-pyridine ring with 4-quinoline. The activity contributions of various nitrogen atoms in the core pyrazolo[1,5-a]pyrimidine ring were also examined by preparing and evaluating pyrrolo[1,2-a]pyrimidine and pyrazolo[1,5-a]pyridine derivatives. In addition, increased mouse liver microsome stability was achieved by replacing the ether substituent on the pendent phenyl ring with piperazine. Finally, an optimized compound 13 (LDN-193189 or DM-3189) demonstrated moderate pharmacokinetic characteristics (e.g., plasma t1/2 = 1.6 h) following intraperitoneal administration in mice. These studies provide useful molecular probes for examining the in vivo pharmacology of BMP signaling inhibition

The role of interpersonal personality traits and reassurance seeking in eating disorder symptoms and depressive symptoms among women with bulimia nervosa

The role of interpersonal factors has been proposed in various models of eating disorder (ED) psychopathology and treatment. We examined the independent and interactive contributions of two interpersonal-focused personality traits (i.e., social avoidance and insecure attachment) and reassurance seeking in relation to global ED psychopathology and depressive symptoms among women with bulimia nervosa (BN)

Is childhood trauma associated with lifetime suicide attempts in women with bulimia nervosa?

The purpose of this study was to explore the association between specific forms of childhood abuse and neglect with lifetime suicide attempts in women with bulimia nervosa (BN)

Pretreatment dietary intake is associated with tumor suppressor DNA methylation in head and neck squamous cell carcinomas

Diet is associated with cancer prognosis, including head and neck cancer (HNC), and has been hypothesized to influence epigenetic state by determining the availability of functional groups involved in the modification of DNA and histone proteins. The goal of this study was to describe the association between pretreatment diet and HNC tumor DNA methylation. Information on usual pretreatment food and nutrient intake was estimated via food frequency questionnaire (FFQ) on 49 HNC cases. Tumor DNA methylation patterns were assessed using the Illumina Goldengate Methylation Cancer Panel. First, a methylation score, the sum of individual hypermethylated tumor suppressor associated CpG sites, was calculated and associated with dietary intake of micronutrients involved in one-carbon metabolism and antioxidant activity, and food groups abundant in these nutrients. Second, gene specific analyses using linear modeling with empirical Bayesian variance estimation were conducted to identify if methylation at individual CpG sites was associated with diet. All models were controlled for age, sex, smoking, alcohol and HPV status. Individuals reporting in the highest quartile of folate, vitamin B12 and vitamin A intake, compared with those in the lowest quartile, showed significantly less tumor suppressor gene methylation, as did patients reporting the highest cruciferous vegetable intake. Gene specific analyses identified differential associations between DNA methylation and vitamin B12 and vitamin A intake when stratifying by HPV status. These preliminary results suggest that intake of folate, vitamin A and vitamin B12 may be associated with the tumor DNA methylation profile in HNC and enhance tumor suppression

Pretreatment dietary intake is associated with tumor suppressor DNA methylation in head and neck squamous cell carcinomas

Diet is associated with cancer prognosis, including head and neck cancer (HNC), and has been hypothesized to influence epigenetic state by determining the availability of functional groups involved in the modification of DNA and histone proteins. The goal of this study was to describe the association between pretreatment diet and HNC tumor DNA methylation. Information on usual pretreatment food and nutrient intake was estimated via food frequency questionnaire (FFQ) on 49 HNC cases. Tumor DNA methylation patterns were assessed using the Illumina Goldengate Methylation Cancer Panel. First, a methylation score, the sum of individual hypermethylated tumor suppressor associated CpG sites, was calculated and associated with dietary intake of micronutrients involved in one-carbon metabolism and antioxidant activity, and food groups abundant in these nutrients. Second, gene specific analyses using linear modeling with empirical Bayesian variance estimation were conducted to identify if methylation at individual CpG sites was associated with diet. All models were controlled for age, sex, smoking, alcohol and HPV status. Individuals reporting in the highest quartile of folate, vitamin B12 and vitamin A intake, compared with those in the lowest quartile, showed significantly less tumor suppressor gene methylation, as did patients reporting the highest cruciferous vegetable intake. Gene specific analyses identified differential associations between DNA methylation and vitamin B12 and vitamin A intake when stratifying by HPV status. These preliminary results suggest that intake of folate, vitamin A and vitamin B12 may be associated with the tumor DNA methylation profile in HNC and enhance tumor suppression