Weight History Correlates of Resting Energy Expenditure in Women With Bulimia Nervosa.

OBJECTIVE: Among those with bulimia nervosa, weight suppression has been associated with illness severity and treatment prognosis. Although significant weight loss is known to reduce metabolic rate, the relation between weight suppression and resting energy expenditure (REE) in bulimia nervosa has not been examined. This study tested the hypothesis of an inverse relation between weight suppression and REE in a sample of women with bulimia nervosa (N = 84). METHODS: In primary analyses, linear regressions were conducted between weight suppression and REE, corrected for fat-free mass. In follow-up, exploratory analyses, stepwise linear regressions were conducted to explore the main and interaction effects of weight history and weight suppression on REE. RESULTS: Neither traditional (TWS) nor developmental weight suppression (DWS) correlated with REE. Results from exploratory analyses, however, revealed a medium-to-large inverse relation between several weight history variables and REE (highest past weight, sr2 = 0.05; lowest postmorbid weight, sr2 = 0.07; current weight, sr2 = 0.05). Additionally, DWS interacted with current (sr2 = 0.08) and highest premorbid (sr2 = 0.05) z-BMI to influence REE with a medium-to-large effect. For individuals low in current and premorbid z-BMIs, higher DWS associated with lower REE levels. However, for individuals at higher premorbid z-BMIs, higher DWS unexpectedly associated with greater REE levels. DISCUSSION: In this sample of women with bulimia nervosa, reduced REE associated with higher weights across all timepoints. If the interaction effect between DWS and z-BMI history persists in future studies, this may indicate unique challenges faced by individuals low in z-BMI and high in DWS related to weight gain and normalization of eating.

Physiological, body composition, and body mass measures show that a developmental measure of weight suppression is more valid than the traditional measure.

OBJECTIVE: The traditional measure of weight suppression (TWS; the difference between an individual's highest past weight at adult height and current weight), has been associated with many psychological, behavioral and biological variables in those with eating disorders. A new measure of weight suppression, called developmental weight suppression (DWS), corrects two major problems in the original measure. Initial research indicates that DWS represents a superior operationalization of the construct weight suppression was originally designed to measure (Lowe [1993, Psychol Bull, 114: 100]). This study is the first to examine the relation between both WS measures and weight history, body composition and a variety of metabolic hormones. METHODS: Data were collected in 91 women with bulimia nervosa (BN) or BN-spectrum disorders. RESULTS: Both weight suppression indices were related to multiple hormones. However, multiple regression analyses showed that the independent effects of DWS differed from the independent effects of TWS in that only DWS was negatively related to: (1) current z-BMI, (2) body fat percentage, and (3) insulin, leptin, T3 free, and TSH. This differential pattern also occurred when results were corrected for multiple comparisons. DISCUSSION: Findings provide stronger biological support for the construct validity of DWS than TWS and suggest that: (1) from the perspective of individuals with BN, high DWS embodies success at food restriction and weight loss, (2) elevated DWS may trap individuals with BN in a powerful biobehavioral bind, and (3) DWS is the preferred measure of weight suppression in future research on eating disorders. PUBLIC SIGNIFICANCE: Most individuals with bulimia nervosa lose substantial weight in the process of developing their disorder. Such weight suppression is related to many characteristics of those with the eating disorder bulimia nervosa. This study shows why a new measure of weight suppression, based on an individual's growth during development, is more biologically valid than the traditional measure of weight suppression.

Dietary nitrate intake and net nitrite-generating capacity of the oral microbiome interact to enhance cardiometabolic health: Results from the Oral Infections Glucose Intolerance and Insulin Resistance Study (ORIGINS).

Background: We investigated the association between dietary nitrate intake and early clinical cardiometabolic risk biomarkers, and explored whether the oral microbiome modifies the association between dietary nitrate intake and cardiometabolic biomarkers. Methods: Cross-sectional data from 668 (mean [SD] age 31 [9] years, 73% women) participants was analyzed. Dietary nitrate intakes and alternative healthy eating index (AHEI) scores were calculated from food frequency questionnaire responses and a validated US food database. Subgingival 16S rRNA microbial genes (Illumina, MiSeq) were sequenced, and PICRUSt2 estimated metagenomic content. The Microbiome Induced Nitric oxide Enrichment Score (MINES) was calculated as a microbial gene abundance ratio representing enhanced net capacity for NO generation. Cardiometabolic risk biomarkers included systolic and diastolic blood pressure, HbA1c, glucose, insulin, and insulin resistance (HOMA-IR), and were regressed on nitrate intake tertiles in adjusted multivariable linear models. Results: Mean nitrate intake was 190[171] mg/day. Higher nitrate intake was associated with lower insulin, and HOMA-IR but particularly among participants with low abundance of oral nitrite enriching bacteria. For example, among participants with a low MINES, mean insulin[95%CI] levels in high vs. low dietary nitrate consumers were 5.8[5.3,6.5] vs. 6.8[6.2,7.5] (p=0.004) while respective insulin levels were 6.0[5.4,6.6] vs. 5.9[5.3,6.5] (p=0.76) among partcipants with high MINES (interaction p=0.02). Conclusion: Higher dietary nitrate intake was only associated with lower insulin and insulin resistance among individuals with reduced capacity for oral microbe-induced nitrite enrichment. These findings have implications for future precision medicine-oriented approaches that might consider assessing the oral microbiome prior to enrollment into dietary interventions or making dietary recommendations.

Clinical attachment loss is cross-sectionally associated with elevated glucose among adults without diabetes.

AIM: We investigated whether periodontal measures are cross-sectionally associated with prediabetes and cardiometabolic biomarkers among non-diabetic younger adults. MATERIALS AND METHODS: One thousand seventy-one participants (mean age = 32.2 years [SE = 0.3]; 73% female) from the Oral Infections, Glucose Intolerance and Insulin Resistance Study were enrolled. Full-mouth clinical attachment loss (fm-CAL), probing depth (fm-PD) and bleeding on probing were ascertained. Interproximal CAL (i-CAL) and probing depths (i-PD) served as our primary exposures. Glucose, HbA1c, insulin and insulin resistance (HOMA-IR) outcomes were assessed from fasting blood. Prediabetes was defined per American Diabetes Association guidelines. Prediabetes prevalence ratios (PR [95% CI]) and mean [SE] cardiometabolic biomarkers were regressed on periodontal variables via multivariable robust variance Poisson regression or multivariable linear regression. RESULTS: Prevalence of prediabetes was 12.5%. Fully adjusted prediabetes PR in Tertiles 3 versus 1 of mean i-CAL was 2.42 (1.77, 3.08). Fully adjusted fasting glucose estimates across i-CAL tertiles were 83.29 [0.43], 84.31 [0.37], 86.48 [0.46]; p for trend <.01. Greater percent of sites with i-PD ≥3 mm showed elevated natural-log-HOMA-IR after adjustment (0%-12% of sites = 0.33 [0.03], 13%-26% of sites = 0.39 [0.03], ≥27% of sites = 0.42 [0.03]; p for trend = .04). CONCLUSIONS: i-CAL (vs. fm-CAL) was associated with elevated fasting glucose and prediabetes, whereas i-PD (vs. fm-PD) was associated with insulin resistance. Future studies are needed to examine periodontal disease and incident prediabetes.

Higher Glycemic Index and Glycemic Load Diet Is Associated with Slower Disease Progression in Amyotrophic Lateral Sclerosis.

OBJECTIVE: High-caloric diets may slow the progression of amyotrophic lateral sclerosis; however, key macronutrients have not been identified. We examined whether dietary macronutrients are associated with the rate of progression and length of survival among the prospective cohort study participants. METHODS: Participants with a confirmed diagnosis of sporadic amyotrophic lateral sclerosis enrolled in the Multicenter Cohort Study of Oxidative Stress were included (n = 304). We evaluated baseline macronutrient intake assessed by food frequency questionnaire in relation to change in revised amyotrophic lateral sclerosis functional rating scale total-score, and tracheostomy-free survival using linear regression and Cox proportional hazard models. Baseline age, sex, disease duration, diagnostic certainty, body mass index, bulbar onset, revised amyotrophic lateral sclerosis functional rating scale total-score, and forced vital capacity were included as covariates. RESULTS: Baseline higher glycemic index and load were associated with less decline of revised amyotrophic lateral sclerosis functional rating scale total score at 3-month follow-up (ß = -0.13, 95% CI -0.2, -0.01, p = 0.03) and (ß = -0.01, 95% CI -0.03, -0.0007, p = 0.04), respectively. Glycemic index second-quartile, third-quartile, and fourth-quartile groups were associated with less decline at 3 months by 1.9 (95% CI -3.3, -0.5, p = 0.008), 2.0 (95% CI -3.3, -0.6, p = 0.006), and 1.6 (95% CI -3.0, -0.2, p = 0.03) points compared with the first-quartile group; the glycemic load fourth-quartile group had 1.4 points less decline compared with the first-quartile group (95% CI -2.8, 0.1, p = 0.07). Higher glycemic index was associated with a trend toward longer tracheostomy-free survival (HR 0.97, 95% CI 0.93, 1.00, p = 0.07). INTERPRETATION: Higher dietary glycemic index and load are associated with slower disease progression in amyotrophic lateral sclerosis. ANN NEUROL 2024;95:217-229.

New insights in the mechanisms of weight-loss maintenance: Summary from a Pennington symposium.

Obesity is a chronic disease that affects more than 650 million adults worldwide. Obesity not only is a significant health concern on its own, but predisposes to cardiometabolic comorbidities, including coronary heart disease, dyslipidemia, hypertension, type 2 diabetes, and some cancers. Lifestyle interventions effectively promote weight loss of 5% to 10%, and pharmacological and surgical interventions even more, with some novel approved drugs inducing up to an average of 25% weight loss. Yet, maintaining weight loss over the long-term remains extremely challenging, and subsequent weight gain is typical. The mechanisms underlying weight regain remain to be fully elucidated. The purpose of this Pennington Biomedical Scientific Symposium was to review and highlight the complex interplay between the physiological, behavioral, and environmental systems controlling energy intake and expenditure. Each of these contributions were further discussed in the context of weight-loss maintenance, and systems-level viewpoints were highlighted to interpret gaps in current approaches. The invited speakers built upon the science of obesity and weight loss to collectively propose future research directions that will aid in revealing the complicated mechanisms involved in the weight-reduced state.

Differential mechanisms affecting weight loss and weight loss maintenance.

In most lifestyle, pharmacological and surgical interventions, weight loss occurs over an approximately 6- to 9-month period and is followed by a weight plateau and then weight regain. Overall, only about 15% of individuals can sustain a 10% or greater non-surgical, non-pharmacological, weight loss. A key question is the degree to which the genotypes, phenotypes and environmental correlates of success in weight loss and weight loss maintenance are continuous or dichotomous. This Perspective is a comparison of the interactions of weight loss and maintenance with genetic, behavioural, physiological and environmental homeostatic systems and a discussion of the implications of these findings for research in, and treatment of, obesity. Data suggest that weight loss and weight loss maintenance are physiologically and psychologically different in many ways. Consequently, individuals may require different interventions designed for temporarily sustaining a negative energy balance during weight loss versus permanently maintaining energy balance after weight loss.

Clinical research resource support for off-site research coordinators in intensive and specialty care units.

Clinical Research Coordinators (CRCs) are vital collaborators in a clinical research project. They often are the primary liaisons between investigators and human participants in studies and are involved in every aspect of many protocols, including participant recruitment, care (both usual medical care and specific study-related monitoring and procedures), data collection, specimen processing, and follow-up. The Clinical Translational Science Award program, which was created by the National Institutes of Health in 2006, has significantly expanded the venues in which Clinical Research Resource (CRR) - based CRCs are embedded. CRCs functioning in these areas, outside of the research-focused in-patient environment of the CRR, are designated as "off-site" CRCs. Many of these locations, such as intensive care units and emergency departments, require that CRCs interact regularly with healthcare providers whose primary functions are focused on providing optimal patient care rather than research and often involving very complex patients. These off-site CRCs require additional training and support outside of the usual research-oriented environment of the CRR. They are required to function within the context of the patient-care team while fostering implementation of collaborative research. This is a description of such a program specifically geared to off-site CRCs with the goal of enhancing the quality of research and experiences of CRCs.

Appetite, Energy Expenditure, and the Regulation of Energy Balance.

At usual weight, energy intake and expenditure are coupled and covary to maintain body weight (energy stores). A change in energy balance, especially weight loss, invokes discoordinated effects on energy intake and output that favor return to previous weight. These regulatory systems reflect physiological changes in systems regulating energy intake and expenditure rather than a lack of resolve. The biological and behavioral physiology of dynamic weight change are distinct from those of attempts at static weight maintenance of an altered body weight. This suggests that optimal therapeutic approaches to losing or gaining vs. sustaining weight changes are different for most individuals.

Do referrals improve the representation of women in mobile phone surveys?

Random digit dial surveys with mobile phones risk under-representation of women. To address this, we compare the characteristics of women recruited directly with those of women recruited through referrals from male household members. The referral process improves representation of vulnerable groups, such as young women, the asset poor, and those living in areas with low connectivity. Among mobile phone users, we show a referral (rather than a direct dial) protocol includes more nationally representative proportions of women with these attributes. While seeking intra-household referrals may improve representation, we show that it does so at a higher cost.

Heightened sensitivity to high-calorie foods in children at risk for obesity: insights from behavior, neuroimaging, and genetics.

Pediatric obesity is a major public health concern. Genetic susceptibility and increased availability of energy-dense food are known risk factors for obesity. However, the extent to which these factors jointly bias behavior and neural circuitry towards increased adiposity in children remains unclear. While undergoing fMRI, 108 children (ages 5-11y) performed a food-specific go/no-go task. Participants were instructed to either respond ("go") or inhibit responding ("no-go") to images of food or toys. Half of the runs depicted high-calorie foods (e.g., pizza) whereas the other half depicted low-calorie foods (e.g., salad). Children were also genotyped for a DNA polymorphism associated with energy intake and obesity (FTO rs9939609) to examine the influence of obesity risk on behavioral and brain responses to food. Participants demonstrated differences in behavioral sensitivity to high- and low-calorie food images depending on task demands. Participants were slower but more accurate at detecting high- (relative to low-) calorie foods when responding to a neutral stimulus (i.e., toys) and worse at detecting toys when responding to high-calorie foods. Inhibition failures were accompanied by salience network activity (anterior insula, dorsal anterior cingulate cortex), which was driven by false alarms to food images. Children at a greater genetic risk for obesity (dose-dependent model of the FTO genotype) demonstrated pronounced brain and behavioral relationships such that genetic risk was associated with heightened sensitivity to high-calorie food images and increased anterior insula activity. These findings suggest that high-calorie foods may be particularly salient to children at risk for developing eating habits that promote obesity.

p38 MAPK activation and STIM1-Orai3 association mediate TRPC6 externalization.

Endothelial cell (EC) migration is critical for the repair of monolayer disruption following angioplasties, but migration is inhibited by lipid oxidation products, including lysophosphatidylcholine (lysoPC), which open canonical transient receptor potential 6 (TRPC6) channels. TRPC6 activation requires an increase in intracellular Ca2+ concentration ([Ca2+]i), the source of which is unknown. LysoPC can activate phospholipase A2 to release arachidonic acid (ArA). ArA can activate arachidonic acid-regulated calcium (ARC) channels that are formed by stromal interaction molecule 1 (STIM1) and Orai1 and Orai3 proteins. Both lysoPC and ArA can activate p38 mitogen-activated protein kinase (MAPK) that induces the phosphorylation required for STIM1-Orai3 association. This is accompanied by an increase in [Ca2+]i and TRPC6 externalization. The effect of lysoPC and ArA is not additive, suggesting activation of the same pathway. The increase in [Ca2+]i activates an Src kinase that leads to TRPC6 activation. Downregulation of Orai3 using siRNA blocks the lysoPC- or ArA-induced increase in [Ca2+]i and TRPC6 externalization and preserves EC migration. These data show that lysoPC induces activation of p38 MAPK, which leads to STIM1-Orai3 association and increased [Ca2+]i. This increase in [Ca2+]i activates an Src kinase leading to TRPC6 externalization, which initiates a cascade of events ending in cytoskeletal changes that disrupt EC migration. Blocking this pathway preserves EC migration in the presence of lipid oxidation products.NEW & NOTEWORTHY The major lysophospholipid component in oxidized LDL, lysophosphatidylcholine (lysoPC), can activate p38 MAP kinase, which in turn promotes externalization of Orai3 and STIM1-Orai3 association, suggesting involvement of arachidonic acid-regulated calcium (ARC) channels. The subsequent increase in intracellular calcium activates an Src kinase required for TRPC6 externalization. TRPC6 activation, which has been shown to inhibit endothelial cell migration, is blocked by p38 MAP kinase or Orai3 downregulation, and this partially preserves endothelial migration in lysoPC.

iPLA2 inhibition blocks LysoPC-induced TRPC6 externalization and promotes Re-endothelialization of carotid injuries in hypercholesterolemic mice.

Lipid oxidation products, including lysophosphatidylcholine (lysoPC), accumulate at the site of arterial injury after vascular interventions and hinder re-endothelization. LysoPC activates calcium-permeable channels, specifically canonical transient receptor potential 6 (TRPC6) channels that induce a sustained increase in intracellular calcium ion concentration [Ca2+]i and contribute to dysregulation of the endothelial cell (EC) cytoskeleton. Activation of TRPC6 leads to inhibition of EC migration in vitro and delayed re-endothelization of arterial injuries in vivo. Previously, we demonstrated the role of phospholipase A2 (PLA2), specifically calcium-independent PLA2 (iPLA2), in lysoPC-induced TRPC6 externalization and inhibition of EC migration in vitro. The ability of FKGK11, an iPLA2-specific pharmacological inhibitor, to block TRPC6 externalization and preserve EC migration was assessed in vitro and in a mouse model of carotid injury. Our data suggest that FKGK11 prevents lysoPC-induced PLA2 activity, blocks TRPC6 externalization, attenuates calcium influx, and partially preserves EC migration in vitro. Furthermore, FKGK11 promotes re-endothelization of an electrocautery carotid injury in hypercholesterolemic mice. FKGK11 has similar arterial healing effects in male and female mice on a high-fat diet. This study suggests that iPLA2 is a potential therapeutic target to attenuate calcium influx through TRPC6 channels and promote EC healing in cardiovascular patients undergoing angioplasty.

p85α regulatory subunit isoform controls PI3-kinase and TRPC6 membrane translocation.

Activation of phosphatidylinositol 3-kinase (PI3K) by lipid oxidation products, including lysophosphatidylcholine (lysoPC), increases the externalization of canonical transient receptor potential 6 (TRPC6) channels leading to a subsequent increase in intracellular calcium that contributes to cytoskeletal changes which inhibit endothelial cell (EC) migration in vitro and impair EC healing of arterial injuries in vivo. The PI3K p110α and p110δ catalytic subunit isoforms regulate lysoPC-induced TRPC6 externalization in vitro, but have many other functions. The goal of the current study is to identify the PI3K regulatory subunit isoform involved in TRPC6 externalization to potentially identify a more specific treatment regimen to improve EC migration and arterial healing, while minimizing off-target effects. Decreasing the p85α regulatory subunit isoform protein levels, but not the p85ß and p55γ regulatory subunit isoforms, with small interfering RNA inhibits lysoPC-induced translocation of the PI3K catalytic subunit to the plasma membrane, dramatically decreased phosphatidylinositol (3,4,5)-trisphosphate (PIP3) production and TRPC6 externalization, and significantly improves EC migration in the presence of lysoPC. These results identify the important and specific role of p85α in controlling translocation of PI3K from the cytosol to the plasma membrane and PI3K-mediated TRPC externalization by oxidized lipids. Current PI3K inhibitors block the catalytic subunit, but our data suggest that the regulatory subunit is a novel therapeutic target to promote EC migration and healing after arterial injuries that occur with angioplasty.

Selective targeting of visceral adiposity by polycation nanomedicine.

Obesity is a pandemic health problem with poor solutions, especially for targeted treatment. Here we develop a polycation-based nanomedicine polyamidoamine generation 3 (P-G3) that-when delivered intraperitoneally-selectively targets visceral fat due to its high charge density. Moreover, P-G3 treatment of obese mice inhibits visceral adiposity, increases energy expenditure, prevents obesity and alleviates the associated metabolic dysfunctions. In vitro adipogenesis models and single-cell RNA sequencing revealed that P-G3 uncouples adipocyte lipid synthesis and storage from adipocyte development to create adipocytes that possess normal functions but are deficient in hypertrophic growth, at least through synergistically modulating nutrient-sensing signalling pathways. The visceral fat distribution of P-G3 is enhanced by modifying P-G3 with cholesterol to form lipophilic nanoparticles, which is effective in treating obesity. Our study highlights a strategy to target visceral adiposity and suggests that cationic nanomaterials could be exploited for treating metabolic diseases.

Nitrite Generating and Depleting Capacity of the Oral Microbiome and Cardiometabolic Risk: Results from ORIGINS.

Background The enterosalivary nitrate-nitrite-nitric oxide (NO3-NO2-NO) pathway generates NO following oral microbiota-mediated production of salivary nitrite, potentially linking the oral microbiota to reduced cardiometabolic risk. Nitrite depletion by oral bacteria may also be important for determining the net nitrite available systemically. We examine if higher abundance of oral microbial genes favoring increased oral nitrite generation and decreased nitrite depletion is associated with a better cardiometabolic profile cross-sectionally. Methods and Results This study includes 764 adults (mean [SD] age 32 [9] years, 71% women) enrolled in ORIGINS (Oral Infections, Glucose Intolerance, and Insulin Resistance Study). Microbial DNA from subgingival dental plaques underwent 16S rRNA gene sequencing; PICRUSt2 was used to estimate functional gene profiles. To represent the different components and pathways of nitrogen metabolism in bacteria, predicted gene abundances were operationalized to create summary scores by (1) bacterial nitrogen metabolic pathway or (2) biochemical product (NO2, NO, or ammonia [NH3]) formed by the action of the bacterial reductases encoded. Finally, nitrite generation-to-depletion ratios of gene abundances were created from the above summary scores. A composite cardiometabolic Z score was created from cardiometabolic risk variables, with higher scores associated with worse cardiometabolic health. We performed multivariable linear regression analysis with cardiometabolic Z score as the outcome and the gene abundance summary scores and ratios as predictor variables, adjusting for sex, age, race, and ethnicity in the simple adjusted model. A 1 SD higher NO versus NH3 summary ratio was inversely associated with a -0.10 (false discovery rate q=0.003) lower composite cardiometabolic Z score in simple adjusted models. Higher NH3 summary score (suggestive of nitrite depletion) was associated with higher cardiometabolic risk, with a 0.06 (false discovery rate q=0.04) higher composite cardiometabolic Z score. Conclusions Increased net capacity for nitrite generation versus depletion by oral bacteria, assessed through a metagenome estimation approach, is associated with lower levels of cardiometabolic risk.

Fasting Serum IGFBP-1 as a Marker of Insulin Resistance in Diverse School Age Groups.

Introduction: The known markers of insulin resistance in obese children are well studied. However, they require serial measurements and complicated calculations. The objective is to study IGFBP-1 and its relation with other known risk measures. Materials and Methods: The study included 98 New York City school students of diverse ethnic/racial backgrounds (57 males and 41 females), 11-15 years of age. Subjects were enrolled in a cross-sectional study, and anthropometric measures were collected. They underwent fasting intravenous glucose tolerance tests (IVGTT), and glucose, insulin, lipids, IGFBP-1, adiponectin and inflammatory markers were collected. Results: The subjects were stratified into 3 groups based upon the BMI Z-score. Out of all the subjects, 65.3% were in the group with a BMI Z-score <1 SDS, 16.3% subjects were in the group with a BMI Z-score of 1 to 2 SDS, and 18.4% of the subjects were in the group with a BMI Z-score of more than 2 SDS. The group with a BMI Z-score of more than 2 SDS had increased waist circumference (WC), body fat, increased fasting insulin, and triglycerides (TG). This group had decreased levels of adiponectin and HDL and low IGFBP-1 as compared to the group with BMI <1 SDS. The group with a BMI Z-score of 1 to 2 SDS had a decreased level of IGFBP-1 as compared to the group with a BMI Z-score less than 1 SDS. IGFBP-1 inversely correlated with age, WC, BMI, body fat, TG, and insulin levels. IGFBP-1 positively correlated with adiponectin and HDL levels. Conclusion: IGFBP-1 in children can identify the presence of insulin resistance in the group with BMI 1 to 2 SDS, even before the known markers of insulin resistance such as elevated triglycerides and even before decreased HDL and adiponectin levels are identified.

Traditional versus developmental measures of weight suppression: Exploring their relationships with bulimic psychopathology.

OBJECTIVE: Weight suppression (WS) is related to a wide variety of eating disorder characteristics. However, individuals with eating disorders usually reach their highest premorbid weight while still developing physically. Therefore, a more sensitive index of individual differences in highest premorbid weight may be one that compares highest premorbid z-BMI to current z-BMI (called developmental weight suppression [DWS] here). METHOD: In this exploratory study, we compared the relationships between traditional weight suppression (TWS) and DWS and a variety of measures related to bulimic psychopathology in 91 females (M age, 25.2; 60.5% White), with clinical or sub-clinical bulimia nervosa. RESULTS: TWS and DWS were correlated (r = 0.40, p < 0.001). TWS was only significantly related to a measure of physical activity whereas DWS was related to 14 outcomes. DWS showed consistent positive relations with behavioural outcomes (e.g., binge eating) but consistent negative relations with cognitive/affective outcomes (e.g., weight concerns). CONCLUSIONS: Findings indicated much more consistent relationships between the novel DWS measure and bulimic characteristics than with the TWS measure. DWS showed both positive and negative relations with bulimic symptoms, though these findings require replication to confirm their validity. Consistent evidence indicated that the two WS measures served as mutual suppressor variables.

Early microbial markers of periodontal and cardiometabolic diseases in ORIGINS.

Periodontitis affects up to 50% of individuals worldwide, and 8.5% are diagnosed with diabetes. The high-comorbidity rate of these diseases may suggest, at least in part, a shared etiology and pathophysiology. Changes in oral microbial communities have been documented in the context of severe periodontitis and diabetes, both independently and together. However, much less is known about the early oral microbial markers of these diseases. We used a subset of the ORIGINS project dataset, which collected detailed periodontal and cardiometabolic information from 787 healthy individuals, to identify early microbial markers of periodontitis and its association with markers of cardiometabolic health. Using state-of-the-art compositional data analysis tools, we identified the log-ratio of Treponema to Corynebacterium bacteria to be a novel Microbial Indicator of Periodontitis (MIP), and found that this MIP correlates with poor periodontal health and cardiometabolic markers early in disease pathogenesis in both subgingival plaque and saliva.