Predicting energy intake in adults who are dieting and exercising.

BACKGROUND: When a lifestyle intervention combines caloric restriction and increased physical activity energy expenditure (PAEE), there are two components of energy balance, energy intake (EI) and physical activity energy expenditure (PAEE), that are routinely misreported and expensive to measure. Energy balance models have successfully predicted EI if PAEE is known. Estimating EI from an energy balance model when PAEE is not known remains an open question. OBJECTIVE: The objective was to evaluate the performance of an energy balance differential equation model to predict EI in an intervention that includes both calorie restriction and increases in PAEE. DESIGN: The Antonetti energy balance model that predicts body weight trajectories during weight loss was solved and inverted to estimate EI during weight loss. Using data from a calorie restriction study that included interventions with and without prescribed PAEE, we tested the validity of the Antonetti weight predictions against measured weight and the Antonetti EI model against measured EI using the intake-balance method at 168 days. We then evaluated the predicted EI from the model against measured EI in a study that prescribed both calorie restriction and increased PAEE. RESULTS: Compared with measured body weight at 168 days, the mean (±SD) model error was 1.30 ± 3.58 kg. Compared with measured EI at 168 days, the mean EI (±SD) model error in the intervention that prescribed calorie restriction and did not prescribe increased PAEE, was -84.9 ± 227.4 kcal/d. In the intervention that prescribed calorie restriction combined with increased PAEE, the mean (±SD) EI model error was -155.70 ± 205.70 kcal/d. CONCLUSION: The validity of the newly developed EI model was supported by experimental observations and can be used to determine EI during weight loss.

Technical report: an online international weight control registry to inform precision approaches to healthy weight management.

BACKGROUND: Personalizing approaches to prevention and treatment of obesity will be a crucial aspect of precision health initiatives. However, in considering individual susceptibility to obesity, much remains to be learned about how to support healthy weight management in different population subgroups, environments and geographical locations. SUBJECTS/METHODS: The International Weight Control Registry (IWCR) has been launched to facilitate a deeper and broader understanding of the spectrum of factors contributing to success and challenges in weight loss and weight loss maintenance in individuals and across population groups. The IWCR registry aims to recruit, enroll and follow a diverse cohort of adults with varying rates of success in weight management. Data collection methods include questionnaires of demographic variables, weight history, and behavioral, cultural, economic, psychological, and environmental domains. A subset of participants will provide objective measures of physical activity, weight, and body composition along with detailed reports of dietary intake. Lastly, participants will be able to provide qualitative information in an unstructured format on additional topics they feel are relevant, and environmental data will be obtained from public sources based on participant zip code. CONCLUSIONS: The IWCR will be a resource for researchers to inform improvements in interventions for weight loss and weight loss maintenance in different countries, and to examine environmental and policy-level factors that affect weight management in different population groups. This large scale, multi-level approach aims to inform efforts to reduce the prevalence of obesity worldwide and its associated comorbidities and economic impacts. TRIAL REGISTRATION: NCT04907396 (clinicaltrials.gov) sponsor SB Roberts; Tufts University IRB #13075.

Detection of brain somatic variation in epilepsy-associated developmental lesions.

OBJECTIVE: Epilepsy-associated developmental lesions, including malformations of cortical development and low-grade developmental tumors, represent a major cause of drug-resistant seizures requiring surgical intervention in children. Brain-restricted somatic mosaicism has been implicated in the genetic etiology of these lesions; however, many contributory genes remain unidentified. METHODS: We enrolled 50 children who were undergoing epilepsy surgery into a translational research study. Resected tissue was divided for clinical neuropathologic evaluation and genomic analysis. We performed exome and RNA sequencing to identify somatic variation and we confirmed our findings using high-depth targeted DNA sequencing. RESULTS: We uncovered candidate disease-causing somatic variation affecting 28 patients (56%), as well as candidate germline variants affecting 4 patients (8%). In agreement with previous studies, we identified somatic variation affecting solute carrier family 35 member A2 (SLC35A2) and mechanistic target of rapamycin kinase (MTOR) pathway genes in patients with focal cortical dysplasia. Somatic gains of chromosome 1q were detected in 30% (3 of 10) of patients with Type I focal cortical dysplasia (FCD)s. Somatic variation in mitogen-activated protein kinase (MAPK) pathway genes (i.e., fibroblast growth factor receptor 1 [FGFR1], FGFR2, B-raf proto-oncogene, serine/threonine kinase [BRAF], and KRAS proto-oncogene, GTPase [KRAS]) was associated with low-grade epilepsy-associated developmental tumors. RNA sequencing enabled the detection of somatic structural variation that would have otherwise been missed, and which accounted for more than one-half of epilepsy-associated tumor diagnoses. Sampling across multiple anatomic regions revealed that somatic variant allele fractions vary widely within epileptogenic tissue. Finally, we identified putative disease-causing variants in genes not yet associated with focal cortical dysplasia. SIGNIFICANCE: These results further elucidate the genetic basis of structural brain abnormalities leading to focal epilepsy in children and point to new candidate disease genes.

Alpha thalassemia genotypes in Kuwait.

BACKGROUND: The frequency of the alpha thalassemia trait is approximately 40% in the Kuwaiti population, but there has been no comprehensive study of the prevalent alleles. This is a report of patients who were referred for molecular diagnosis over a 20-year period. METHODS: This is a retrospective study of the α-globin genotypes obtained in the Hemoglobin Research Laboratory of the Department of Pediatrics, Kuwait University from 1994 to 2015. Genotyping was performed by a combination of PCR, allele-specific oligonucleotide hybridization and reverse dot blot hybridization (Vienna Lab Strip Assay). RESULTS: Four hundred samples were characterized and analyzed from individuals aged < 1 month to 80 years, with a median of 6 years from 283 unrelated families. Most (90.8%) were Kuwaiti nationals. The commonest genotype was homozygosity for the polyadenylation-1 mutation (αPA-1α/α PA-1α) in 33.3% of the samples, followed by heterozygosity (αα/α PA-1α) for the same mutation in 32.3%. PA-1 was therefore the most frequent allele (0.59). The frequency of the α0 (--MED) allele was 0.017. Rare alleles that were found in very low frequencies included α0 (--FIL) in a Filipino child, Hb Constant Spring, Hb Adana, and Hb Icaria. CONCLUSION: There is a wide variety of alpha thalassemia alleles among Kuwaitis, but nondeletional PA-1 is by far the most common cause of the moderate to severe HbH (ß4 tetramer) disease phenotype. The α0 (-MED) allele is also encountered, which has implications for premarital counseling, especially for the possibility of having babies with alpha thalassemia major (Barts hydrops fetalis).

Allometric models of adult regional body lengths and circumferences to height: Insights from a three-dimensional body image scanner.

OBJECTIVES: Recent reports on body regional mass scalings to height have advanced understanding differences in adult heights. These studies resulted in conjectures on how regional lengths and circumferences may scale to height. We provide evidence for these conjectures by analyzing a large sample of regional limb, trunk, chest, and head lengths and circumferences in a large sample of US Army basic training recruits. METHODS: Participants consisted of 10 271 males and 2760 females ages 17 to 21 years old who reported for basic training at Fort Jackson, SC. Participants were imaged by a three-dimensional (3D) body scanner for uniform sizing which yielded 159 body measurements of total mass, lengths and circumferences at regional sites of arms, legs, trunk, chest, and head. The allometric model, Body Measur e i = α i H ß i was applied to derive scaling exponents which were applied to estimate regional mass scalings. RESULTS: Body mass scaled to height with powers of ∼2.0 (mean ß ± SE, 1.98 ± 0.04, 1.93 ± 0.06). Arm and leg lengths scaled to exponents larger than 1.0 and head height and circumferences at regional sites scaled to exponents smaller than 1.0. The leg, arm, and trunk mass scaling exponents were all above 2.0. Head mass scaled to powers smaller than 2.0. CONCLUSIONS: The 3D scanner allowed hundreds of anthropometric measurements to be obtained within seconds. The ensuing analysis revealed that greater height yielded disproportional increases in limb lengths, limb mass and trunk mass. These analyses provide evidence that could not be previously measured that further both biomechanical and metabolic conjectures.

Revisiting the United States Army body composition standards: a receiver operating characteristic analysis.

BACKGROUND: The objective for percent body fat standards in the United States Army Body Composition Program (ABCP) is to ensure soldiers maintain optimal well-being and performance under all conditions. However, conducting large-scale experiments within the United States Army to evaluate the efficacy of the thresholds is challenging. METHODS: A receiver operating characteristic (ROC) analysis with corresponding area under the curve (AUC) was performed on body mass index (BMI) and waist circumference to determine optimal gender-specific age cohort thresholds that meet ABCP percent body fat standards in the National Health and Nutrition Examination Survey (NHANES) III. A second dataset consisting of a cohort of basic training recruits (N = 20,896 soldiers, 28% female) with BMI and waist circumference measured using a 3D body image scanner was applied to calculate what percent of basic training recruits meet the ABCP percent body fat standards. Regression models to determine the contribution of different circumference sites to the predictions of percent body fat were developed using a database compiled at the New York Obesity Research Center (N = 500). RESULTS: Optimal BMI thresholds ranged from 23.65 kg/m2 (17-21-year-old cohort) to 26.55 kg/m2 (40 and over age cohort) for males and 21.75 to 24.85 kg/m2 for females. The AUC values were between 0.86 and 0.92. The waist circumference thresholds ranged 81.35 to 97.55 cm for males and 77.05 to 89.35 cm for females with AUC values between 0.90 and 0.91. These BMI thresholds were exceeded by 65% of male and 74% of female basic training recruits and waist circumference thresholds were exceeded by 73% of male and 85% of female recruits. The single circumference that contributed most to prediction of body fat was waist circumference in males and mid-thigh circumference in females. CONCLUSIONS: The ABCP percent body fat thresholds yield BMI thresholds that are below the United States Army BMI standards, especially in females which suggests the ABCP percent body fat standards may be too restrictive. The United States Army percent body fat standards could instead be matched to existing national health guidelines.

Predictive Mathematical Models of Weight Loss.

PURPOSE OF REVIEW: Validated thermodynamic energy balance models that predict weight change are ever more in use today. Delivery of model predictions using web-based applets and/or smart phones has transformed these models into viable clinical tools. Here, we provide the general framework for thermodynamic energy balance model derivation and highlight differences between thermodynamic energy balance models using four representatives. RECENT FINDINGS: Energy balance models have been used to successfully improve dietary adherence, estimate the magnitude of food waste, and predict dropout from clinical weight loss trials. They are also being used to generate hypotheses in nutrition experiments. Applications of thermodynamic energy balance weight change prediction models range from clinical applications to modify behavior to deriving epidemiological conclusions. Novel future applications involve using these models to design experiments and provide support for treatment recommendations.

Risk of avascular necrosis of the femoral head in children with sickle cell disease on hydroxyurea: MRI evaluation.

BACKGROUND: There are conflicting reports on the role of hydroxyurea (HU) in the pathogenesis of avascular necrosis of the femoral head (AVNFH) in patients with sickle cell disease (SCD). PROCEDURE: The present study is a prospective cohort study of Kuwaiti children with SCD who were treated with HU. They had magnetic resonance imaging of the hips before starting HU and at regular intervals during a follow-up period, ranging from 1 to 15 years. RESULTS: There were 40 patients (18 SS, 19 Sß0-thalassemia, and three SD genotypes), aged 6-20 years. Pre-HU, 11 (27.5%) had varying grades of AVNFH, while post HU, the prevalence was 32.5%. Two patients developed new lesions during the study, while five (45.5%) that had lesions pre-HU remained static, another five (45.5%) progressed, and one (9%) improved radiologically. The older patients who had been on HU the longest were more likely to deteriorate. The only hematological parameter that was consistently associated with AVNFH was the reticulocyte count. CONCLUSIONS: The frequency and rate of progression of AVNFH in this study is much less than that previously reported for our patients not treated with HU. There is no evidence that HU therapy is a risk factor for AVNFH. It may, in fact, prevent new lesions and deter the progression of existing AVNFH.

Scaling of adult human bone and skeletal muscle mass to height in the US population.

OBJECTIVES: The scaling of structural components to body size is well studied in mammals, although comparable human observations in a large and diverse sample are lacking. The current study aimed to fill this gap by examining the scaling relationships between total body (TB) and regional bone and skeletal muscle (SM) mass with body size, as defined by stature, in a nationally representative sample of the US population. METHODS: Subjects were 17,126 non-Hispanic (NH) white, NH black, and Mexican American men and women, aged ≥18 years, evaluated in the National Health and Nutrition Examination Survey who had TB and regional bone mineral (BMin) and lean soft tissue (LST) mass measured by dual-energy X-ray absorptiometry. BMin and appendicular LST served as surrogate bone and SM mass measures, respectively. The allometric model, BMin or LST = α(height)ß , in a logarithmic form was used to generate scaling exponents. RESULTS: The findings were similar across all gender and race groups: body mass scaled to height with powers of ~2.0 (mean ß ± SE, 1.94 ± 0.08-2.29 ± 0.09) while TB and appendicular BMin and appendicular LST scaled to height with consistently larger powers than those for body mass (eg, all P < .05 in NH white men and women); the largest BMin and LST scaling powers to height were observed in the lower extremities. CONCLUSIONS: Bone and SM mass, notably those of the lower extremities, increase as proportions of body mass with greater adult height. Metabolic and biomechanical implications emerge from these observations, the first of their kind in a representative adult US population sample.

The Sub-Phenotypes of Sickle Cell Disease in Kuwait.

Kuwaiti patients with sickle cell disease generally have a mild phenotype, but exhibit considerable heterogeneity, in spite of high Hb F levels. We have carried out a cross-sectional study of patients with sickle cell disease in the five major hospitals in Kuwait. Details of their hemoglobin (Hb) genotypes, clinical presentations and complications are presented. The study was over a span of 3 years and involved 396 patients, made up of 351 (88.6%) Kuwaitis and 45 (11.4%) expatriates. They were aged <1 to 73 years. Hb SS (ßS/ßS) was the most common (in 246 patients, i.e. 62.1%) followed by Hb S (HBB: c.20A>T)-ß-thalassemia (Hb S-ß-thal) in 138 (34.8%) and 11 (2.8%) Hb S/Hb D-Punjab (HBB: c.364G>C). Hb F ranged from 1.0 to 55.0%, with a mean of 21.2 ± 9.8%. The most common presentation was vaso-occlusive crises (VOCs), with 230 (54.8%) having had at least one prior to the study with 54 (13.2%) and 74 (18.9%) having between 2-3 and >3 VOCs, respectively. Hydroxyurea (HU) was prescribed to 157 (39.6%) patients. The most common complication was gallstones in 131 (33.1%), followed by acute splenic sequestration in 26.8% and avascular necrosis of the femoral head in 21.2% patients, respectively. Stroke, priapism and leg ulcers were rare. Gallstones, splenic sequestration and osteonecrosis were significantly more common in patients aged >16 years. Patients with Hb S-ß-thal were similar to those with Hb SS in their clinical profiles. The phenotypic expression of sickle cell disease in Kuwaitis is unique in many respects. The role(s) of Hb F and other genetic modifiers require further elucidation.

Acute acinar pancreatitis blocks vesicle-associated membrane protein 8 (VAMP8)-dependent secretion, resulting in intracellular trypsin accumulation.

Zymogen secretory granules in pancreatic acinar cells express two vesicle-associated membrane proteins (VAMP), VAMP2 and -8, each controlling 50% of stimulated secretion. Analysis of secretion kinetics identified a first phase (0-2 min) mediated by VAMP2 and second (2-10 min) and third phases (10-30 min) mediated by VAMP8. Induction of acinar pancreatitis by supramaximal cholecystokinin (CCK-8) stimulation inhibits VAMP8-mediated mid- and late-phase but not VAMP2-mediated early-phase secretion. Elevation of cAMP during supramaximal CCK-8 mitigates third-phase secretory inhibition and acinar damage caused by the accumulation of prematurely activated trypsin. VAMP8-/- acini are resistant to secretory inhibition by supramaximal CCK-8, and despite a 4.5-fold increase in total cellular trypsinogen levels, are fully protected from intracellular trypsin accumulation and acinar damage. VAMP8-mediated secretion is dependent on expression of the early endosomal proteins Rab5, D52, and EEA1. Supramaximal CCK-8 (60 min) caused a 60% reduction in the expression of D52 followed by Rab5 and EEA1 in isolated acini and in in vivo The loss of D52 occurred as a consequence of its entry into autophagic vacuoles and was blocked by lysosomal cathepsin B and L inhibition. Accordingly, adenoviral overexpression of Rab5 or D52 enhanced secretion in response to supramaximal CCK-8 and prevented accumulation of activated trypsin. These data support that acute inhibition of VAMP8-mediated secretion during pancreatitis triggers intracellular trypsin accumulation and loss of the early endosomal compartment. Maintaining anterograde endosomal trafficking during pancreatitis maintains VAMP8-dependent secretion, thereby preventing accumulation of activated trypsin.

Adult energy requirements predicted from doubly labeled water.

BACKGROUND: Estimating energy requirements forms an integral part of developing diet and activity interventions. Current estimates often rely on a product of physical activity level (PAL) and a resting metabolic rate (RMR) prediction. PAL estimates, however, typically depend on subjective self-reported activity or a clinician's best guess. Energy-requirement models that do not depend on an input of PAL may provide an attractive alternative. METHODS: Total daily energy expenditure (TEE) measured by doubly labeled water (DLW) and a metabolic chamber from 119 subjects obtained from a database of pre-intervention measurements measured at Pennington Biomedical Research Center were used to develop a metabolic ward and free-living models that predict energy requirements. Graded models, including different combinations of input variables consisting of age, height, weight, waist circumference, body composition, and the resting metabolic rate were developed. The newly developed models were validated and compared to three independent databases. RESULTS: Sixty-four different linear and nonlinear regression models were developed. The adjusted R2 for models predicting free-living energy requirements ranged from 0.65 with covariates of age, height, and weight to 0.74 in models that included body composition and RMR. Independent validation R2 between actual and predicted TEE varied greatly across studies and between genders with higher coefficients of determination, lower bias, slopes closer to 1, and intercepts closer to zero, associated with inclusion of body composition and RMR covariates. The models were programmed into a user-friendly web-based app available at: http://www.pbrc.edu/research-and-faculty/calculators/energy-requirements/ (Video Demo for Reviewers at: https://www.youtube.com/watch?v=5UKjJeQdODQ ) CONCLUSIONS: Energy-requirement equations that do not require knowledge of activity levels and include all available input variables can provide more accurate baseline estimates. The models are clinically accessible through the web-based application.

Energy Intake Derived from an Energy Balance Equation, Validated Activity Monitors, and Dual X-Ray Absorptiometry Can Provide Acceptable Caloric Intake Data among Young Adults.

Background: Assessments of energy intake (EI) are frequently affected by measurement error. Recently, a simple equation was developed and validated to estimate EI on the basis of the energy balance equation [EI = changed body energy stores + energy expenditure (EE)]. Objective: The purpose of this study was to compare multiple estimates of EI, including 2 calculated from the energy balance equation by using doubly labeled water (DLW) or activity monitors, in free-living adults. Methods: The body composition of participants (n = 195; mean age: 27.9 y; 46% women) was measured at the beginning and end of a 2-wk assessment period with the use of dual-energy X-ray absorptiometry. Resting metabolic rate (RMR) was calculated through indirect calorimetry. EE was assessed with the use of the DLW technique and an arm-based activity monitor [Sensewear Mini Armband (SWA); BodyMedia, Inc.]. Self-reported EI was calculated by using dietitian-administered 24-h dietary recalls. Two estimates of EI were calculated with the use of a validated equation: quantity of energy stores estimated from the changes in fat mass and fat-free mass occurring over the assessment period plus EE from either DLW or the SWA. To compare estimates of EI, reporting bias (estimated EI/EE from DLW × 100) and Goldberg ratios (estimated EI/RMR) were calculated. Results: Mean ± SD EEs from DLW and SWA were 2731 ± 494 and 2729 ± 559 kcal/d, respectively. Self-reported EI was 2113 ± 638 kcal/d, EI derived from DLW was 2723 ± 469 kcal/d, and EI derived from the SWA was 2720 ± 730 kcal/d. Reporting biases for self-reported EI, DLW-derived EI, and SWA-derived EI are as follows: -21.5% ± 22.2%, -0.7% ± 18.5%, and 0.2% ± 20.8%, respectively. Goldberg cutoffs for self-reported EI, DLW EI, and SWA EI are as follows: 1.39 ± 0.39, 1.77 ± 0.38, and 1.77 ± 0.38 kcal/d, respectively. Conclusions: These results indicate that estimates of EI based on the energy balance equation can provide reasonable estimates of group mean EI in young adults. The findings suggest that, when EE derived from DLW is not feasible, an activity monitor that provides a valid estimate of EE can be substituted for EE from DLW.

The Sickle ß-Thalassemia Phenotype.

Sß-thalassemia (Sß-thal) is common among Gulf Arab patients with sickle cell disease, but the phenotype of this group had not been well-documented. We have studied a group of Kuwaiti patients and compared the phenotype in the homozygotes (SS) and Sß-thal patients. Complete blood count, hemoglobin quantitation, serum bilirubin, and lactate dehydrogenase were determined with standard techniques. The patients were screened for α-globin genotype. The Sß-thal patients were also screened for the HBG2 Xmn-1 polymorphism. ß-Thal mutations were determined by arrayed primer extension or direct sequencing. There were 70 SS and 32 Sß-thal patients with mean ages of 14.8±5.9 and 14.2±5.9 years, respectively. The Sß-thal patients had more frequent, severe pain episodes per year compared with the SS, while the patterns among Sß-thal and Sß-thal patients were not significantly different. There were no differences in the frequencies of acute chest syndrome, gallstones, and blood transfusion in the SS and Sß-thal patients. However, none of the Sß-thal patients had been transfused. Among the Sß-thal patients, 25 had ß-thal and 7 had ß-thal mutations, the most common being cd39 (C→T) and IVS-I-110 (G→A), respectively. Sß-thal shows a severe phenotype in Kuwait, even among those with Sß-thal, in whom the IVS-I-110 (G→A) mutation is predominant.

Myths, presumptions, and facts about obesity.

BACKGROUND: Many beliefs about obesity persist in the absence of supporting scientific evidence (presumptions); some persist despite contradicting evidence (myths). The promulgation of unsupported beliefs may yield poorly informed policy decisions, inaccurate clinical and public health recommendations, and an unproductive allocation of research resources and may divert attention away from useful, evidence-based information. METHODS: Using Internet searches of popular media and scientific literature, we identified, reviewed, and classified obesity-related myths and presumptions. We also examined facts that are well supported by evidence, with an emphasis on those that have practical implications for public health, policy, or clinical recommendations. RESULTS: We identified seven obesity-related myths concerning the effects of small sustained increases in energy intake or expenditure, establishment of realistic goals for weight loss, rapid weight loss, weight-loss readiness, physical-education classes, breast-feeding, and energy expended during sexual activity. We also identified six presumptions about the purported effects of regularly eating breakfast, early childhood experiences, eating fruits and vegetables, weight cycling, snacking, and the built (i.e., human-made) environment. Finally, we identified nine evidence-supported facts that are relevant for the formulation of sound public health, policy, or clinical recommendations. CONCLUSIONS: False and scientifically unsupported beliefs about obesity are pervasive in both scientific literature and the popular press. (Funded by the National Institutes of Health.).

First Trimester Detection of Placental Disease: Challenges and Opportunities.

It is generally agreed that placental pathology accounts for the majority of perinatal morbidity and mortality. If a placental prodrome could be diagnosed in vivo, risk for maternal or fetal complications could be estimated and acted upon before clinical symptoms are apparent. This is especially relevant in early diagnoses of gestational diabetes mellitus, which can be controlled through carefully monitored diet and activity changes. To meet this important need, there have been increased efforts to identify early gestation biomarkers of placental dysfunction using innovative imaging technologies. Here we outline innovative quantitative markers of placental shape and their relationship to placental function, clinical implications of these quantifiers, and the most recent mathematical models that utilize placental images to delineate at risk from normal pregnancies. We propose that novel contexts of readily available placental measures and routine collection of in vivo placental images in all pregnancies may be all that are needed to advance the identification of early risk determination of complicated pregnancies from placental images.

Vesicle associated membrane protein 8 (VAMP8)-mediated zymogen granule exocytosis is dependent on endosomal trafficking via the constitutive-like secretory pathway.

Acinar cell zymogen granules (ZG) express 2 isoforms of the vesicle-associated membrane protein family (VAMP2 and -8) thought to regulate exocytosis. Expression of tetanus toxin to cleave VAMP2 in VAMP8 knock-out (-/-) acini confirmed that VAMP2 and -8 are the primary VAMPs for regulated exocytosis, each contributing ∼50% of the response. Analysis of VAMP8(-/-) acini indicated that although stimulated secretion was significantly reduced, a compensatory increase in constitutive secretion maintained total secretion equivalent to wild type (WT). Using a perifusion system to follow secretion over time revealed VAMP2 mediates an early rapid phase peaking and falling within 2-3 min, whereas VAMP8 controls a second prolonged phase that peaks at 4 min and slowly declines over 20 min to support the protracted secretory response. VAMP8(-/-) acini show increased expression of the endosomal proteins Ti-VAMP7 (2-fold) and Rab11a (4-fold) and their redistribution from endosomes to ZGs. Expression of GDP-trapped Rab11a-S25N inhibited secretion exclusively from the VAMP8 but not the VAMP2 pathway. VAMP8(-/-) acini also showed a >90% decrease in the early endosomal proteins Rab5/D52/EEA1, which control anterograde trafficking in the constitutive-like secretory pathway. In WT acini, short term (14-16 h) culture also results in a >90% decrease in Rab5/D52/EEA1 and a complete loss of the VAMP8 pathway, whereas VAMP2-secretion remains intact. Remarkably, rescue of Rab5/D52/EEA1 expression restored the VAMP8 pathway. Expressed D52 shows extensive colocalization with Rab11a and VAMP8 and partially copurifies with ZG fractions. These results indicate that robust trafficking within the constitutive-like secretory pathway is required for VAMP8- but not VAMP2-mediated ZG exocytosis.

Weighing the Evidence of Common Beliefs in Obesity Research.

Obesity is a topic on which many views are strongly held in the absence of scientific evidence to support those views, and some views are strongly held despite evidence to contradict those views. We refer to the former as "presumptions" and the latter as "myths." Here, we present nine myths and 10 presumptions surrounding the effects of rapid weight loss; setting realistic goals in weight loss therapy; stage of change or readiness to lose weight; physical education classes; breastfeeding; daily self-weighing; genetic contribution to obesity; the "Freshman 15"; food deserts; regularly eating (versus skipping) breakfast; eating close to bedtime; eating more fruits and vegetables; weight cycling (i.e., yo-yo dieting); snacking; built environment; reducing screen time in childhood obesity; portion size; participation in family mealtime; and drinking water as a means of weight loss. For each of these, we describe the belief and present evidence that the belief is widely held or stated, reasons to support the conjecture that the belief might be true, evidence to directly support or refute the belief, and findings from randomized controlled trials, if available. We conclude with a discussion of the implications of these determinations, conjecture on why so many myths and presumptions exist, and suggestions for limiting the spread of these and other unsubstantiated beliefs about the obesity domain.

The gap between expectations and reality of exercise-induced weight loss is associated with discouragement.

BACKGROUND: Exercise interventions result in modest weight loss, yet exercise is frequently prescribed for weight loss. PURPOSE: To identify individuals who become discouraged when exercise fails to achieve weight loss. METHODS: Representative samples of U.S. adults were recruited using Google Consumer Surveys in August-October 2014. Respondents were asked about beliefs and potential discouragement regarding the role of exercise and weight loss. An analysis of variance was performed to predict individuals that become discouraged if exercise does not lead to weight loss. RESULTS: The belief that exercise is a very effective way to lose weight was common (71% of respondents). Stronger belief that exercise is an effective way to lose weight (p<0.001) in individuals with higher weight status (p=0.04) positively predicted discouragement with exercise. Higher weight status combined with the belief that exercise reduces weight was a significant positive predictor of discouragement (p=0.01). CONCLUSIONS: Individuals with higher weight status that believe that exercise is an effective way to lose weight are more likely to become discouraged when exercise does not lead to weight loss. Prescribing exercise for weight loss might contribute to discouragement. Future studies should evaluate ways to encourage exercise without promoting the belief that exercise will yield weight loss.