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People that Deliver's vision is "a world where health supply chain workforces are empowered and equipped to optimize health outcomes by improving access to health commodities." However, health supply chain management (HSCM) is not a recognized profession in many low- and middle-income countries (LMICs). HSCM professionalization efforts are essential if health outcomes are to be significantly improved in these countries; this means transforming supply chain management into a recognized profession of the highest integrity.The Strategic Training Executive Program (STEP) was created in 2016 to address prevailing leadership style gaps. Since then, STEP has undergone rigorous revisions to improve its applicability, scalability, and usefulness in LMICs. To date, STEP-in all its forms-has been delivered to 30 countries and contributed to building the supply chain capacities of more than 600 health supply chain professionals.This case study discusses the evolution journey of designing and sustaining the second generation of STEP (STEP 2.0). This journey is an innovative illustration of how diverse yet motivated organizations collaborated during a global lockdown and health emergency to reimagine a program recognized by all as essential for post-pandemic supply chain systems., (© Bobo et al.)

Objectives: The current recommended treatment for patients with recurrent episodes of schizophrenia and related conditions is antipsychotic medication. However, many antipsychotic users remain functionally impaired and experience serious physical and mental side effects. This study aims to assess the cost-effectiveness of a gradual antipsychotic reduction and discontinuation strategy compared with maintenance treatment over 24 months from mental health services, health and social care, and societal perspectives., Methods: Nineteen mental health trusts recruited patients to the Research into Antipsychotic Discontinuation and Reduction (RADAR) randomized controlled trial. Quality-adjusted life-years were calculated from patient-reported EQ-5D-5L, with years of full capability calculated from the patient-reported ICECAP-A. Mental health services use and medication was collected from medical records. Other resource use and productivity loss was collected using self-completed questionnaires. Costs were calculated from published sources., Results: A total of 253 participants were randomized: 126 assigned to antipsychotic dose reduction and 127 to maintenance. There were no significant differences between arms in total costs for any perspectives. There were no significant difference in quality-adjusted life-years (-0.035; 95% CI: -0.123 to 0.052), whereas years of full capability were significantly lower in the reduction arm compared with the maintenance arm (baseline-adjusted difference: -0.103; 95% CI: -0.192 to -0.014). The reduction strategy was dominated by maintenance for all analyses and was not likely to be cost-effective., Conclusions: It is unlikely that gradual antipsychotic reduction and discontinuation strategy is cost-effective compared with maintenance over 2-years for patients with schizophrenia and other recurrent psychotic disorders who are on long-term antipsychotics., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Background: Urothelial carcinoma recurrence of an orthotopic neobladder created from bowel segment is a rare occurrence. The usage of bowel segments to create neobladder following cystectomy for urinary diversion is growing yet there still remains a large gap in the literature about recurrence in neobladder. We carry out the first systematic review to outline current details of urothelial cancer recurrences in a neobladder, diagnostic approach, management and long term prognosis., Method: We carried out a systematic review searching databases PubMed (MEDLINE), Scopus and Web of Science. Only studies reporting on urothelial carcinoma recurrence of the neobladder with or without multi-focal disease were reported. A quality assessment tool was utilized to ensure all studies met quality standards., Results: Fifteen studies were included in the systematic review meeting inclusion criteria. Fourteen of these studies were cases in men where pT3 disease was the most prevalent (29%). The most common symptomology was macroscopic haematuria seen in eight patients (53.33%). Management varied among cases and including adjuvant chemotherapy regimens and surgical interventions consisting of endoscopic resection to robotic neocystectomy and nephroureterectomy. Follow up period for these patients was up to 38 months and 55% of patients did not see a recurrence., Conclusion: The nature of recurrence is hypothesised to be due to seeding of urothelial cells into the non-urothelial surfaces compatible for both implantation and growth. We present the first systematic review to report on recurrence rates and details of diagnosis and outcomes of various management regimes for urothelial carcinoma of the neobladder., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The importance of gender diversity is well recognized. Despite promising change in addressing gender disparity, there remains a significant gap in women's representation in urology. Worldwide, a lack of diversity has been observed at scientific meetings. This study analyses the trend in women's representation at the Urological Society of Australia and New Zealand Annual Scientific Meeting (USANZ ASM) over the last nine years., Method: We retrospectively collected data from eight conference programs between 2014 and 2022, evaluating the trend in the proportion of women represented in various sections. A difference of proportions test was performed to determine whether a significant change was seen from year to year., Results: A significant increase in women's representation was observed, the most significant increase was evident in the last three years, chairpersons increased from 5.9% to 44.1% (P = 0.003), international speakers from 11.7% to 39.1% (P ≤ 0.001), expert speakers from 19.1% to 42.0% (P = 0.002), and total speakers from 19.5% to 34.7% (P ≤ 0.001)., Conclusion: Our study shows that a significant increase in the representation of women at the USANZ ASM has been achieved over the last three years. Unfortunately, this increase in representation has not been mirrored in the number of women trainees and training applicants. Additionally, this increase in representation well exceeds the proportion of women who are USANZ members, and is unevenly distributed across topics. A positive change has been observed, the challenge remains in dealing with unconscious bias and balancing the fine line between inclusivity and tokenism., (© 2023 Royal Australasian College of Surgeons.)

Herein, we compared peri-operative and post-operative outcomes between robotic-assisted and laparoscopic partial nephrectomy. Various reviews of the current literature have detailed the lack of single-surgeon studies in this domain. Our study featured a single surgeon experienced in both approaches to reduce this bias seen in other multi-centre studies. We retrospectively analysed data from two hospitals to compare patient demographics, tumour characteristics, peri-operative and post-operative outcomes of all partial nephrectomies undertaken by a single surgeon with extensive experience in both approaches. Statistical analysis was carried out using GraphPad prism software. Warm ischaemia time was significantly reduced in the robotic arm compared to the laparoscopic group. This translated into an improvement in acute renal function. Length of stay was also significantly reduced. This study highlights some benefits of robotic-assisted in comparison to laparoscopic partial nephrectomy. Further large-scale prospective studies would be valuable in confirming these findings and justifying their usage against their financial cost., (© 2023. Crown.)

Background: Studies report that 12%-23% of patients with functional anorectal disorders have a history of sexual abuse (SA). This article aims to assess whether there is a difference in symptom severity, quality of life or anorectal physiology findings in female patients presenting to a colorectal pelvic floor service with and without a history of sexual abuse., Methods: A retrospective analysis of all female patients attending a single tertiary pelvic floor unit for faecal incontinence or constipation between 2017 and 2019 was performed. Patients were divided into two groups depending on the presence or absence of a volunteered history of sexual abuse. Validated quality of life and symptom severity scores, along with anorectal physiology studies were analysed and compared between the two groups., Results: There were 148 patients included in the study period and 17% reported a history of SA. There was no statistically significant difference in symptom severity, quality of life scores or anorectal physiology studies between those with and without a history of SA., Conclusion: In female patients seeking management for defaecatory symptoms, those who have reported a history of SA did not demonstrate any significant difference in symptom severity, quality of life or physiological measures when compared to those without a history of SA., (© 2023 Royal Australasian College of Surgeons.)

Introduction: Salvage stereotactic body radiation therapy (SBRT) for localized prostate cancer recurrence following radiation therapy remains controversial. We performed a systematic review to assess the efficacy and side effect profile of salvage SBRT for locally recurrent prostate cancer to define the role of salvage SBRT in clinical practice., Methods: A systematic review was carried out using Pubmed (MEDLINE) and Scopus databases. Inclusion and exclusion criteria were satisfied if studies reported on patients with prior radiation therapy for prostate cancer who had subsequently had a local recurrence. Those studies included were quality assessed using the ROBINS-I checklist., Results: Five studies in total met criteria for inclusion and included all reportable outcomes. A total of 265 participants are reported on in total. Median doses for SBRT ranged from 30 to 36 Gy delivered over 5-6 fractions. Recurrence free survival ranged from 40% to 76% at 2 years. Genitourinary toxicity was more prevalent than gastrointestinal toxicities. Grade 2 and 3 genitourinary complication rates ranged from 5% to 22% and 0% to 9%, respectively. Gastrointestinal grade 2 complication rates ranged from 0% to 11% and no grade 3 complications were recorded., Discussion: Salvage SBRT appears to be comparable and potentially superior in some aspects to other salvage therapies, taking into account the limitations in cross-study comparisons. This systematic review serves as one of the first to characterize SBRT as a salvage option for locally recurrent prostate cancer., (© 2023 Wiley Periodicals LLC.)

Background: Immune checkpoint inhibitors (ICI) have revolutionised treating advanced cancers. ICI are administered intravenously every 2-6 weeks for up to 2 years, until cancer progression/unacceptable toxicity. Physiological efficacy is observed at lower doses than those used as standard of care (SOC). Pharmacodynamic studies indicate sustained target occupancy, despite a pharmacological half-life of 2-3 weeks. Reducing frequency of administration may be possible without compromising outcomes. The REFINE trial aims to limit individual patient exposure to ICI whilst maintaining efficacy, with potential benefits in quality of life and reduced drug treatment/attendance costs., Methods/design: REFINE is a randomised phase II, multi-arm, multi-stage (MAMS) adaptive basket trial investigating extended interval administration of ICIs. Eligible patients are those responding to conventionally dosed ICI at 12 weeks. In stage I, patients (n = 160 per tumour-specific cohort) will be randomly allocated (1:1) to receive maintenance ICI at SOC vs extended dose interval. REFINE is currently recruiting UK patients with locally advanced or metastatic renal cell carcinoma (RCC) who have tolerated and responded to initial nivolumab/ipilimumab, randomised to receive maintenance nivolumab SOC (480 mg 4 weekly) vs extended interval (480 mg 8 weekly). Additional tumour cohorts are planned. Subject to satisfactory outcomes (progression-free survival) stage II will investigate up to 5 different treatment intervals. Secondary outcome measures include overall survival, quality-of-life, treatment-related toxicity, mean incremental pathway costs and quality-adjusted life-years per patient. REFINE is funded by the Jon Moulton Charity Trust and Medical Research Council, sponsored by University College London (UCL), and coordinated by the MRC CTU at UCL. Trial Registration ISRCTN79455488. NCT04913025 EUDRACT #: 2021-002060-47. CTA 31330/0008/001-0001; MREC approval: 21/LO/0593. REFINE Protocol version 4.0., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The current study aims to compare peri-operative and post-operative outcomes between robotic assisted vs. laparoscopic partial nephrectomy. Multiple reviews of the current literature have detailed the lack of single surgeon studies in this domain. To limit inter-operator bias, we utilise a single surgeon experienced in both approaches to reduce this bias seen in other multi-centre studies., Methods and Materials: We retrospectively compared patient demographics, tumour characteristics, peri-operative and post-operative outcomes of all partial nephrectomies undertaken by a single surgeon between 2014 and 2021 with experience in both laparoscopic and robotic surgery. The Da Vinci surgical system was utilized. Statistical analysis was carried out using GraphPad prism software version 7.03, San Diego, CA, USA., Results: Warm ischemia time was reduced by 2.6 min, length of stay reduced by 1.3 days and acute renal function deterioration was reduced by 55% with all these results being significant with robotic assisted partial nephrectomy compared to laparoscopic partial nephrectomy., Conclusion: This study highlights the benefits of robotic assisted in comparison to laparoscopic partial nephrectomy. Further large-scale prospective studies and cost-benefit analysis of robotic assisted partial nephrectomy would be valuable in confirming these findings and justifying the usage against their financial cost.

Purpose: Body weight and insulin resistance (IR) are closely correlated, and their temporal sequences in affecting blood pressure (BP) remain poorly defined. We examined the temporal sequences of weight loss and IR change, and their relations with BP in the Pounds Lost trial, a randomized weight-loss diet intervention study., Methods: The present study included overweight/obese adults, who were randomized in a 2 × 2 factorial design to low-calorie diets containing 20 or 40% fat and 15 or 25% protein (diets with 65, 55, 45 and 35% carbohydrate). Weight, IR, systolic and diastolic BP levels were measured at baseline, 6 and 24 months. After excluding the subjects who took antihypertensive drugs, cross-lagged path and mediation analyses were performed among 540 participants., Results: After adjusting for age, race, sex, and diet groups, the cross-lagged path coefficient from baseline weight to 24-month IR (β 1  = 0.135, P = 0.04) was significantly greater than the path coefficient (β 2  = 0.022, P > 0.05) from baseline IR to 24-month weight (P < 0.05 for the difference in βs), indicating that weight-loss preceded change of IR. The mediation effects of 24-month IR on the 24-month systolic BP and diastolic BP were estimated at 20.94% (P = 0.004) and 17.03% (P = 0.034), respectively., Conclusions: Our data indicate that weight loss precedes change of IR, which mediates a significant proportion of the effects of weight loss on changes of BP in response to the diet interventions., Trial Registration: NCT00072995 First Posted November 17, 2003 Last Update Posted January 30, 2013 this study was not 'retrospectively registered'., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Recombinant spider silk has the potential to provide a new generation of biomaterial scaffolds as a result of its degree of biocompatibility and lack of immunogenicity. These recombinant biomaterials are, however, reported to exhibit poor cellular adhesion which limits their potential for use in applications such as tissue engineering and regenerative medicine. In this study, a simple chemical functionalization approach is described that specifically addresses this issue and significantly improves the adhesion of human mesenchymal stem cells (CiMSCs) to a recombinant spider silk biomaterial. This utilizes copper-catalyzed or strain-promoted azide-alkyne cycloaddition (CuAAC/SPAAC) "click" chemistry to covalently attach cyclo(RGDfK) peptides to the azide group of l-azidohomoalanine, a methionine analogue previously site specifically incorporated into the primary sequence of a thioredoxin (TRX)-tagged silk fusion protein, TRX-4RepCT, to give TRX 3Aha -4RepCT 3Aha . This method is used to produce cyclo(RGDfK) functionalized films and macroscopic fibers. Over 24 h, cyclo(RGDfK) functionalized TRX 3Aha -4RepCT 3Aha  films and 4RepCT 3Aha  fibers display significantly improved performance in CiMSC culture, yielding far greater cell numbers than the controls. This approach circumvents the previously observed lack of cell adhesion, thus allowing spider silk derived biomaterials to be used where such adhesion is critical, in tissue engineering, regenerative medicine and wound healing., (© The Authors. Published by Wiley-VCH GmbH.)

Purpose: This systematic review evaluates factors influencing breast cancer outcomes for women treated in Australia, facilitating the exploration of disparities in breast cancer outcomes for certain groups of women in Australia., Method: A systematic literature search was performed using MEDLINE and Scopus focusing on breast cancer in Australia with outcome measures being breast cancer survival and recurrence with no restrictions on date. Risk of bias was assessed using Cairns Assessment Scale for Observational studies of Risk factors (CASOR)., Results: Fifteen quantitative studies were included: two were high quality, 11 were intermediate quality, and two were low quality. Traditional risk factors such as invasive tumour type, larger size, higher grade and stage, lymph node involvement and absence of hormone receptors were found to be associated with breast cancer mortality. Being younger (<40 years old) and older (>70 years old), having more comorbidities, being of lower socioeconomic status, identifying as Aboriginal or Torres Strait Islander, living in more rural areas or having a mastectomy were factors found to be associated with poorer breast cancer outcomes., Conclusion: Despite the heterogeneity of the studies, this review identified significant risk factors for breast cancer mortality and recurrence. The use of this data would be most useful in developing evidence-based interventions and in optimising patient care through creation of a prediction model., Prospero Registration: CRD42017072857., (© 2019 John Wiley & Sons Ltd.)

Calories from any food have the potential to increase risk for obesity and cardiometabolic disease because all calories can directly contribute to positive energy balance and fat gain. However, various dietary components or patterns may promote obesity and cardiometabolic disease by additional mechanisms that are not mediated solely by caloric content. Researchers explored this topic at the 2017 CrossFit Foundation Academic Conference 'Diet and Cardiometabolic Health - Beyond Calories', and this paper summarizes the presentations and follow-up discussions. Regarding the health effects of dietary fat, sugar and non-nutritive sweeteners, it is concluded that food-specific saturated fatty acids and sugar-sweetened beverages promote cardiometabolic diseases by mechanisms that are additional to their contribution of calories to positive energy balance and that aspartame does not promote weight gain. The challenges involved in conducting and interpreting clinical nutritional research, which preclude more extensive conclusions, are detailed. Emerging research is presented exploring the possibility that responses to certain dietary components/patterns are influenced by the metabolic status, developmental period or genotype of the individual; by the responsiveness of brain regions associated with reward to food cues; or by the microbiome. More research regarding these potential 'beyond calories' mechanisms may lead to new strategies for attenuating the obesity crisis., (© 2018 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Polymer microparticles are widely used as acellular drug delivery platforms in regenerative medicine, and have emerging potential as cellular scaffolds for therapeutic cell delivery. In the clinic, PLGA microparticles are typically administered intramuscularly or subcutaneously, with the clinician and clinical application site determining the precise needle gauge used for delivery. Here, we explored the role of needle diameter in microparticle delivery yield, and develop a modified viscosity formulation to improve microparticle delivery across a range of clinically relevant needle diameters. We have identified an optimal biocompatible formulation containing 0.25% pluronic F127 and 0.25% carboxymethyl cellulose, which can increase delivery payload to 520% across needle gauges 21-30G, and note that needle diameter impacts delivery efficacy. We use this formulation to increase the delivery yield of PLGA microparticles, and separately, PLGA-cell scaffolds supporting viable mesenchymal stem cells (MSCs), demonstrating the first in vitro delivery of this cell scaffold system. Together, these results highlight an optimal formulation for the delivery of microparticle and microparticle-cell scaffolds, and illustrate how careful choice of delivery formulation and needle size can dramatically impact delivery payload., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Objectives: Few data are available to describe the changes in incidence of pediatric-onset inflammatory bowel disease (IBD). The aim of this study was to describe changes in incidence and phenotypic presentation of pediatric-onset IBD in northern France during a 24-year period., Methods: Pediatric-onset IBD (<17 years) was issued from a population-based IBD study in France between 1988 and 2011. Age groups and digestive location were defined according to the Paris classification., Results: 1,350 incident cases were recorded (8.3% of all IBD) including 990 Crohn's disease (CD), 326 ulcerative colitis (UC) and 34 IBD unclassified (IBDU). Median age at diagnosis was similar in CD (14.4 years (Q1=11.8-Q3=16.0)) and UC (14.0 years (11.0-16.0)) and did not change over time. There were significantly more males with CD (females/males=0.82) than UC (females/males=1.25) (P=0.0042). Median time between onset of symptoms and IBD diagnosis was consistently 3 months (1-6). Mean incidence was 4.4/10 5 for IBD overall (3.2 for CD, 1.1 for UC and 0.1 for IBDU). From 1988-1990 to 2009-2011, a dramatic increase in incidences of both CD and UC were observed in adolescents (10-16 years): for CD from 4.2 to 9.5/10 5 (+126%; P<0.001) and for UC, from 1.6 to 4.1/10 5 (+156%; P<0.001). No modification in age or location at diagnosis was observed in either CD or UC., Conclusions: In this population-based study, CD and UC incidences increased dramatically in adolescents across a 24-year span, suggesting that one or more strong environmental factors may predispose this population to IBD.

Introduction: This study sought to determine whether 10 years of assignment to intensive lifestyle intervention (ILI) relative to diabetes support and education leads to better cognition. We examine intervention effects overall and among clinical subgroups, and report correlations between computer-administered and interviewer-administered cognitive batteries., Methods: The Action for Health in Diabetes (Look AHEAD) was a 16-site randomized controlled trial with overweight/obese individuals (aged 45-76) who had type 2 diabetes. The NIH Toolbox Cognition Battery tests developed to measure cognition across the lifespan were used to evaluate cognition. Results were compared with standard paper-and-pencil tests. The Toolbox and paper-and-pencil tests were administered an average of 10.9 years after randomization to 1002 participants., Results: Toolbox measures significantly correlated with interviewer-administered measures, with the strongest correlations between the Toolbox Fluid Cognition Composite and Trails B ( r  = -0.64, P  < .0001) and Digit Symbol Coding ( r  = 0.63, P  < .0001), and between the Toolbox Dimensional Change Card Sort ( r  = 0.55, P  < .0001) and the Digit Symbol Coding test. Overall, ILI and diabetes support and education groups had similar adjusted mean cognitive outcomes ( P  > .05 for all). Subgroup analyses identified different intervention effects within baseline body mass index groups for Picture Sequence Memory ( P  = .01), within baseline cardiovascular disease groups for Picture Vocabulary ( P  = .01) and Fluid Cognition Composite ( P  = .02) measures, and within baseline age groups for Picture Vocabulary ( P  = .02)., Discussion: Correlations between Toolbox and interviewer-administered outcomes provide a measure of internal validity. Findings suggest no overall effect of the intervention on cognition and that an ILI resulting in weight loss may have negative implications for cognition in individuals aged ≥60, with previous history of cardiovascular disease, and those with body mass index ≥40.

Background: Experimentally establishing a group's body weight maintenance energy requirement is an important component of metabolism research. At present, the reference approach for measuring the metabolizable energy intake (MEI) from foods required for body weight maintenance in non-confined subjects is the doubly-labeled water (DLW)-total energy expenditure (TEE) method. In the current study, we evaluated an energy-intake weight balance method as an alternative to DLW that is more flexible and practical to apply in some settings., Methods: The hypothesis was tested that MEI from foods observed in a group of subjects maintaining a constant energy intake while keeping their weight within ±1 kg over 10 days is non-significantly different from DLW-measured TEE (TEE DLW ). Six non-obese subjects evaluated as part of an earlier study completed the inpatient protocol that included a 3-day initial adjustment period., Results: The group body weight coefficient of variation (X ± SD) during the 10-day balance period was 0.38 ± 0.10% and the slope of the regression line for body weight versus protocol day was non-significant at 1.8 g/day (R 2 , 0.002, p = 0.98). MEI from foods observed during the 10-day balance period (2390 ± 543 kcal/day) was non-significantly different (p = 0.96) from TEE measured by DLW (2373 ± 713 kcal/day); the MEI/TEE DLW ratio was 1.03 ± 0.15 (range 0.87-1.27) and the correlation between MEI from foods and TEE DLW was highly significant (R 2 , 0.88, p = 0.005)., Conclusions: A carefully managed 10-day protocol that includes a constant MEI level from foods with weight stability (±1 kg) will provide a group's body weight maintenance energy requirement similar to that obtained with DLW. This approach opens the possibility of conducting affordable weight balance studies, shorter in duration than those previously reported, that are needed to answer a wide range of questions in clinical nutrition. Trial registration The study is registered at http://www.clinicaltrials.gov (NCT01672632; August 20, 2012).

To assess the association of markers for dietary protein intake, measures of dietary adherence and demographic variables with weight loss in the POUNDS Lost study over the first 6 months and again between 6 and 24 months using data from those who completed each period. This is a secondary analysis of pooled data on completers assigned to one of four diets: 65%C/15%P/20%F (AP/LF), 55%C/25%P/20%F (HP/LF), 45%C/15%P/40%F (AP/HF) or 35%C/25%P40%F (HP/HF) in the POUNDS Lost study. Urinary nitrogen excretion, dietary adherence measured by 24-h recall and attendance at sessions, age (above and below 50 years), gender, race/ethnicity and activity by pedometry were analysed. Increased spread between protein intake at baseline and protein at 6 or 24 months, assessed by urinary nitrogen excretion, was associated with greater weight loss from baseline to 2 years. At 6 and 24 months, older age, male gender, body mass index > 30 kg m -2 and adherence to the fat and protein diets were associated with more weight loss. None of these variables was associated with a regain from 6 to 24 months. Weight regain for women in the highest carbohydrate (65%) group was significantly greater (-4.4 kg [95% CI: -5.9, -3.0]) than for women in the lowest carbohydrate group (-1.8 kg [95% CI: -3.2, -0.4 kg]) (P for interaction = 0.012). An increased spread in the difference between baseline and follow-up protein intake was associated with greater weight loss, consistent with the 'protein spread theory'. Women eating the highest carbohydrate diet regained more weight from 6 to 24 months., (© 2017 World Obesity Federation.)

Background: The role of thyroid hormones in diet-induced weight loss and subsequent weight regain is largely unknown., Objectives: To examine the associations between thyroid hormones and changes in body weight and resting metabolic rate (RMR) in a diet-induced weight loss setting., Subjects/methods: Data analysis was conducted among 569 overweight and obese participants aged 30-70 years with normal thyroid function participating in the 2-year Prevention of Obesity Using Novel Dietary Strategies (POUNDS) LOST randomized clinical trial. Changes in body weight and RMR were assessed during the 2-year intervention. Thyroid hormones (free triiodothyronine (T3), free thyroxine (T4), total T3, total T4 and thyroid-stimulating hormone (TSH)), anthropometric measurements and biochemical parameters were assessed at baseline, 6 months and 24 months., Results: Participants lost an average of 6.6 kg of body weight during the first 6 months and subsequently regained an average of 2.7 kg of body weight over the remaining period from 6 to 24 months. Baseline free T3 and total T3 were positively associated, whereas free T4 was inversely associated, with baseline body weight, body mass index and RMR. Total T4 and TSH were not associated with these parameters. Higher baseline free T3 and free T4 levels were significantly associated with a greater weight loss during the first 6 months (P<0.05) after multivariate adjustments including dietary intervention groups and baseline body weight. Comparing extreme tertiles, the multivariate-adjusted weight loss±s.e. was -3.87±0.9 vs -5.39±0.9 kg for free T3 (P trend =0.02) and -4.09±0.9 vs -5.88±0.9 kg for free T4 (P trend =0.004). The thyroid hormones did not predict weight regain in 6-24 months. A similar pattern of associations was also observed between baseline thyroid hormones and changes in RMR. In addition, changes in free T3 and total T3 levels were positively associated with changes in body weight, RMR, body fat mass, blood pressure, glucose, insulin, triglycerides and leptin at 6 months and 24 months (all P<0.05)., Conclusions: In this diet-induced weight loss setting, higher baseline free T3 and free T4 predicted more weight loss, but not weight regain among overweight and obese adults with normal thyroid function. These findings reveal a novel role of thyroid hormones in body weight regulation and may help identify individuals more responsive to weight loss diets.

Objective: To assess whether an average of 10 years of lifestyle intervention designed to reduce weight and increase physical activity lowers the prevalence of cognitive impairment among adults at increased risk due to type 2 diabetes and obesity or overweight., Methods: Central adjudication of mild cognitive impairment and probable dementia was based on standardized cognitive test battery scores administered to 3,802 individuals who had been randomly assigned, with equal probability, to either the lifestyle intervention or the diabetes support and education control. When scores fell below a prespecified threshold, functional information was obtained through proxy interview., Results: Compared with control, the intensive lifestyle intervention induced and maintained marked differences in weight loss and self-reported physical activity throughout follow-up. At an average (range) of 11.4 (9.5-13.5) years after enrollment, when participants' mean age was 69.6 (54.9-87.2) years, the prevalence of mild cognitive impairment and probable dementia was 6.4% and 1.8%, respectively, in the intervention group, compared with 6.6% and 1.8%, respectively, in the control group ( p = 0.93). The lack of an intervention effect on the prevalence of cognitive impairment was consistent among individuals grouped by cardiovascular disease history, diabetes duration, sex, and APOE ε4 allele status (all p ≥ 0.50). However, there was evidence ( p = 0.03) that the intervention effect ranged from benefit to harm across participants ordered from lowest to highest baseline BMI., Conclusions: Ten years of behavioral weight loss intervention did not result in an overall difference in the prevalence of cognitive impairment among overweight or obese adults with type 2 diabetes., Clinicaltrialsgov Identifier: NCT00017953 (Action for Health in Diabetes)., Level of Evidence: This study provides Class II evidence that for overweight adults with type 2 diabetes, a lifestyle intervention designed to reduce weight and increase physical activity does not lower the risk of cognitive impairment., (© 2017 American Academy of Neurology.)

Background/objectives: Adiponectin has a pivotal role in linking fat distribution with cardiometabolic disorders. We investigated the associations of long-term changes in circulating adiponectin with body composition and fat distribution at different abdominal depots in response to weight-loss dietary interventions, as well as the modification effect of sex., Subjects/methods: In the 2-year Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) Trial, 811 overweight or obese adults were randomly assigned to one of four diets varying in macronutrient intakes. Circulating concentrations of adiponectin were repeatedly measured at baseline, 6 months and 2 years. Body composition and fat distribution were repeatedly measured by dual-energy X-ray absorptiometry scan (n=424) and computed tomography (n=195)., Results: Over the 2-year intervention, after adjustment for age, sex, ethnicity, follow-up time, diet group, baseline body mass index and baseline level of respective outcome trait, increase of adiponectin was significantly associated with reduction of total fat mass (FM), total fat-free mass (FFM), whole body total percentage of fat mass (FM%), percentage of trunk fat (TF%), total adipose tissue (TAT), and adipose tissue mass at different depots including visceral (VAT), deep subcutaneous (DSAT) and superficial subcutaneous (SSAT; P<0.03 for each). The relations with FM, FM%, TF%, VAT and DSAT were significantly modified by sex (P for interaction=0.02, 0.005 and <0.001, 0.002, 0.03, respectively) with greater reductions associated with increase of adiponectin in men than in women., Conclusions: Long-term changes in circulating adiponectin were differentially associated with improvement of body composition and abdominal fat distribution in men and women.

Objective: Weight-loss intervention through diet modification has been widely used to improve obesity-related hyperglycemia; however, little is known about whether genetic variation modifies the intervention effect. We examined the interaction between weight-loss diets and genetic variation of fasting glucose on changes in glycemic traits in a dietary intervention trial., Research Design and Methods: The Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial is a randomized, controlled 2-year weight-loss trial. We assessed overall genetic variation of fasting glucose by calculating a genetic risk score (GRS) based on 14 fasting glucose-associated single nucleotide polymorphisms, and examined the progression in fasting glucose and insulin levels, and insulin resistance and insulin sensitivity in 733 adults from this trial., Results: The GRS was associated with 6-month changes in fasting glucose (P<0.001), fasting insulin (P=0.042), homeostasis model assessment of insulin resistance (HOMA-IR, P=0.009) and insulin sensitivity (HOMA-S, P=0.043). We observed significant interaction between the GRS and dietary fat on 6-month changes in fasting glucose, HOMA-IR and HOMA-S after multivariable adjustment (P-interaction=0.007, 0.045 and 0.028, respectively). After further adjustment for weight loss, the interaction remained significant on change in fasting glucose (P=0.015). In the high-fat diet group, participants in the highest GRS tertile showed increased fasting glucose, whereas participants in the lowest tertile showed decreased fasting glucose (P-trend <0.001); in contrast, the genetic association was not significant in the low-fat diet group (P-trend=0.087)., Conclusions: Our data suggest that participants with a higher genetic risk may benefit more by eating a low-fat diet to improve glucose metabolism.

Objective: In addition to slowing diabetes development among participants in the Diabetes Prevention Program (DPP), intensive lifestyle change and metformin raised HDL-cholesterol (HDL-C) compared to placebo treatment. We investigated the lifestyle and metabolic determinants as well as effects of biomarkers of inflammation, endothelial dysfunction and coagulation and their changes resulting from lifestyle and metformin interventions on the increase in HDL-C in the DPP., Methods: The effects of a 1year period of intensive lifestyle change aimed at achieving 7% weight loss or metformin 850mg twice daily versus placebo on HDL-C were assessed in 3070 participants with impaired glucose tolerance, and on HDL particle concentration (HDL-P) and size in a subgroup of 1645 individuals. Treatment-associated changes in lifestyle and metabolic factors as well as in novel biomarkers were investigated for their associations with change in HDL-C using multiple regression analysis., Results: After adjusting for BMI, insulin resistance, glycemia, dietary saturated fat, alcohol intake, physical activity and nine different biomarkers, only adiponectin accounted for the effect of intensive lifestyle change on HDL-C via an increase in large HDL-P. By contrast baseline and change in BMI and tissue plasminogen activator levels attenuated the effect of metformin on HDL-C, with adiponectin having no specific effect., Conclusion: While both lifestyle and metformin interventions used to prevent diabetes increase HDL-C, the mechanisms involved differ between the two treatments and may have consequences for future risk of cardiovascular disease., Competing Interests: none, (Copyright © 2016. Published by Elsevier Inc.)

Objective: Diabetic nephropathy is characterized at its onset by glomerular hyperfiltration. Prospective studies in humans measuring filtration rates with weight gain are lacking. We investigated renal filtration following weight gain induced by overfeeding., Design: Eight weeks of overfeeding (40% above energy requirements, 44% fat, 15% protein and 41% carbohydrate) as well as a 6-month follow-up after the overfeeding intervention., Subjects: Thirty-five participants (age: 26.7 ±5.3 years; body mass index: 25.5 ± 2.2 kg m(-2) ; 29 m/6f)., Measurements: Creatinine clearance rate (Ccr) from 24-h urine collection, estimated glomerular filtration rate (eGFR) from the modification of diet in renal disease (MDRD), insulin sensitivity/glucose disposal rate (GDR) by a euglycemic-hyperinsulinemic clamp, components from basic metabolic panels and serum lipid panels., Results: Both eGFR and Ccr increased with overfeeding (P = 0.04) and serum lipids (all P < 0.05), along with a decrease in insulin sensitivity (P = 0.003). Fasting glucose concentration was not affected (P = 0.98), but the per cent change in Ccr correlated positively with the change in GDR with overfeeding (r = 0.39, P = 0.02). Six months following overfeeding, serum glucose was maintained, and no evidence of urinary glucose was observed at any time-point., Conclusions: These data suggest that renal hyperfiltration may act as a mechanism to preserve insulin sensitivity through maintenance of systemic glucose homoeostasis with caloric excess., (© 2015 The Association for the Publication of the Journal of Internal Medicine.)

We evaluated weight changes in obese patients at 6-months after they ended participation in a 12-month randomised controlled trial in which they received daily placebo, zonisamide 200 mg or zonisamide 400 mg, in addition to lifestyle counselling. Of the originally randomised 225 patients, 218 completed month-12 when study interventions were discontinued. For the 154 patients who returned for 6-month follow-up off-treatment, weight changes between month-12 and month-18 for placebo (n = 53), zonisamide 200 mg (n = 49) and zonisamide 400 mg groups (n = 52) were 0.5 kg [95% confidence interval (CI), -0.8 to 1.8; 0.7%], 1.5 kg (0.2-2.8; 1.6%; p = 0.26 vs. placebo) and 2.4 kg (1.1-3.7; 2.6%; p = 0.04 vs. placebo), respectively. Our results suggest that although zonisamide 400 mg daily for 12-months resulted in greater weight loss than with placebo, weight regain after discontinuation of interventions was greater in the zonisamide 400 mg group than placebo group., (© 2014 John Wiley & Sons Ltd.)

Aims: This study examined the effects of pioglitazone on body weight and bone mineral density (BMD) prospectively in patients with impaired glucose tolerance as pioglitazone (TZD) increases body weight and body fat in diabetic patients and increases the risk of bone fractures., Methods: A total of 71 men and 163 women aged 49.3 (10.7) years [mean (s.d.)]; body mass index (BMI), 34.5 (5.9) kg/m(2) were recruited at five sites for measurements of body composition by dual energy X-ray absorptiometry at baseline and at conversion to diabetes or study end, if they had not converted., Results: Mean follow-up was 33.6 months in the pioglitazone group and 32.1 months in the placebo group. Body weight increased 4.63 ± 0.60 (m ± s.e.) kg in the pioglitazone group compared to 0.98 ± 0.62 kg in the PIO group (p < 0.0001). Body fat rose 4.89 ± 0.42 kg in the pioglitazone group compared to 1.41 ± 0.44 kg, (p < 0.0001) in placebo-treated subjects. The increase in fat was greater in legs and trunk than in the arms. BMD was higher in all regions in men and significantly so in most. PIO decreased BMD significantly in the pelvis in men and women, decreased BMD in the thoracic spine and ribs of women and the lumbar spine and legs of men. Bone mineral content also decreased significantly in arms, legs, trunk and in the total body., Conclusions: Pioglitazone increased peripheral fat more than truncal fat and decreased BMD in several regions of the body., (© 2013 John Wiley & Sons Ltd.)

Obesity is a serious disease associated with increased patient risk of several comorbidities, including type 2 diabetes mellitus, cardiovascular disease, dyslipidemia, hypertension, some cancers, and greater mortality. Furthermore, obesity has a deleterious impact on quality of life and increases health care costs. Moderate weight loss of 5% to 10% has been shown to significantly improve several patient cardiometabolic risk factors and physical functioning, however, it is often difficult to begin the weight-loss conversation with patients. Primary care providers play a critical role in discussing the health effects of excess weight with patients, managing obesity-related comorbidities, and recommending appropriate weight-loss strategies. Open communication, realistic goal setting, and consistent monitoring are key factors in implementing an effective weight-loss program in the primary care setting. Although diet and lifestyle modifications are the first lines of approach and the foundation of any weight-loss strategy, in many cases, additional interventions may be necessary, including medical or surgical management. Herein, we discuss the approaches that primary care providers should consider when recommending appropriate weight-loss strategies for overweight/obese patients to achieve clinically meaningful weight loss, including pharmacotherapies approved for chronic management of patients with obesity, to be used as adjuncts to diet and lifestyle modifications, and surgical options.

Background: Sugar-sweetened drinks and the fructose they provide are associated with several health problems., Methods: Data from the Nielsen Homescan and product content were analysed for sweetener type using the Gladson Nutrition Database. Meta-analyses and randomized clinical trials were used to evaluate outcomes of beverage and fructose intake., Results: Over 70% of all foods contain some amounts of added sugar, and consumption of soft drinks has increased fivefold since 1950. Meta-analyses suggest that consumption of sugar-sweetened beverages is related to the risk of diabetes, the metabolic syndrome and cardiovascular disease in adults and in children. Drinking two sugar-sweetened beverages per day for 6 months induced features of the metabolic syndrome and fatty liver. Randomized, controlled trials in children and adults lasting from 6 months to 2 years have shown that lowering the intake of soft drinks reduced weight gain. Genetic factors influence the weight gain when drinking soft drinks., Conclusion: Consumption of calorie-sweetened beverages and the fructose they contain has continued to increase and may play a role in the epidemic of obesity, the metabolic syndrome and fatty liver disease. Reducing intake of soft drinks is associated with less weight gain and metabolic improvement as well., (© 2013 The Authors. Pediatric Obesity © 2013 International Association for the Study of Obesity.)

The use of self-monitoring as a tool to facilitate behavioral modification is common in many lifestyle-based weight loss interventions. Electronic tracking programs, including computer-based systems and smart phone applications, have been developed to allow individuals to self-monitor their behavior digitally. These programs offer an advantage over traditional self-report modalities in that they can provide users with direct feedback about dietary and/or physical activity adherence levels and thereby assist them in real-time decision making. This article describes the use of an Internet-based computerized tracking system (CTS) that was developed specifically for the POUNDS LOST study, a 2-year randomized controlled trial designed to test the efficacy of four macronutrient diets for weight and fat reduction in healthy, overweight men and women (body mass index range = 25.0-39.9 kg/m(2)). The CTS served many functions in this study, including data collection, dietary and exercise assessment and feedback, messaging system, and report generation. Across all groups, participants with high usage of the CTS during the initial 8 weeks lost greater amounts of weight than participants with low usage (8.7% versus 5.5% of initial body weight, respectively; p < .001) at week 32. Rates of CTS utilization were highest during the first year of this 2-year intervention, and utilization of the CTS declined steadily over time. The unique features of the CTS combined with technological developments, such as smart phone applications, offer significant potential to improve the user's self-monitoring experience and adherence to health promotion programs designed specifically for individuals with obesity and type 2 diabetes., (© 2012 Diabetes Technology Society.)

Few well-controlled trials have evaluated the effects that macronutrient composition has on changes in food cravings during weight loss treatment. The present study, which was part of the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial, investigated whether the fat and protein content of four different diets affected changes in specific food cravings in overweight and obese adults. A sample of 811 adults were recruited across two clinical sites, and each participant was randomly assigned to one of four macronutrient prescriptions: 1) low fat (20% of energy), average protein (15% of energy); 2) moderate fat (40%), average protein (15%); 3) low fat (20%), high protein (25%); 4) moderate fat (40%), high protein (25%). With few exceptions, the type of diet that participants were assigned did not differentially affect changes in specific food cravings. Participants assigned to the high-fat diets, however, had reduced cravings for carbohydrates at month 12 (p<0.05) and fruits and vegetables at month 24. Also, participants assigned to high-protein diets had increased cravings for sweets at month 6 and month 12 (ps<0.05). Participants in all four dietary conditions reported significant reductions in food cravings for specific types of foods (i.e., high fat foods, fast food fats, sweets, and carbohydrates/starches; all ps<0.05). Cravings for fruits and vegetables, however, were increased at month 24 (p<0.05). Calorically restricted diets (regardless of their macronutrient composition) yielded significant reductions in cravings for fats, sweets, and starches whereas cravings for fruits and vegetables were increased.

Background: Weight loss reduces energy expenditure, but the contribution of different macronutrients to this change is unclear., Hypothesis: We tested the hypothesis that macronutrient composition of the diet might affect the partitioning of energy expenditure during weight loss., Design: A substudy of 99 participants from the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial had total energy expenditure (TEE) measured by doubly labeled water, and resting energy expenditure (REE) measured by indirect calorimetry at baseline and repeated at 6 months in 89 participants. Participants were randomly assigned to one of four diets with either 15 or 25% protein and 20 or 40% fat., Results: TEE and REE were positively correlated with each other and with fat-free mass and body fat, at baseline and 6 months. The average weight loss of 8.1 ± 0.65 kg (least-square mean ± s.e.) reduced TEE by 120 ± 56  kcal per day and REE by 136 ± 18 kcal per day. A greater weight loss at 6 months was associated with a greater decrease in TEE and REE. Participants eating the high-fat diet (HF) lost significantly more fat-free mass (1.52 ± 0.55 kg) than the low-fat (LF) diet group (P<0.05). Participants eating the LF diet had significantly higher measures of physical activity than the HF group., Conclusion: A greater weight loss was associated with a larger decrease in both TEE and REE. The LF diet was associated with significant changes in fat-free body mass and energy expenditure from physical activity compared with the HF diet.

Dopamine (DA) and DA D₂ receptors (D2R) have been implicated in obesity and are thought to be involved in the rewarding properties of food. Osborne-Mendel (OM) rats are susceptible to diet induced obesity (DIO) while S5B/P (S5B) rats are resistant when given a high-fat diet. Here we hypothesized that the two strains would differ in high-fat food self-administration (FSA) and that the D2R agonist bromocriptine (BC) would differently affect their behavior. Ad-libitum fed OM and S5B/P rats were tested in a FSA operant chamber and were trained to lever press for high-fat food pellets under a fixed-ratio (FR1) and a progressive ratio (PR) schedule. After sixteen days of PR sessions, rats were treated with three different doses of BC (1, 10 and 20 mg/kg). No significant differences were found between the two strains in the number of active lever presses. BC treatment (10 mg/kg and 20 mg/kg) increased the number of active lever presses (10 mg/kg having the strongest effect) whereas it decreased rat chow intake in the home cage with equivalent effects in both strains. These effects were not observed on the day of BC administration but on the day following its administration. Our results suggest that these two strains have similar motivation for procuring high fat food using this paradigm. BC increased operant responding for high-fat pellets but decreased chow intake in both strains, suggesting that D2R stimulation may have enhanced the motivational drive to procure the fatty food while correspondingly decreasing the intake of regular food. These findings suggest that susceptibility to dietary obesity (prior to the onset of obesity) may not affect operant motivation for a palatable high fat food and that differential susceptibility to obesity may be related to differential sensitivity to D2R stimulation., (Copyright © 2010. Published by Elsevier B.V.)

Objective: Accumulation of adipose tissue is associated with cardiometabolic risks. Although visceral adipose tissue (VAT) has been strongly implicated in this relationship, there is still some debate regarding the contribution of abdominal subcutaneous adipose tissue (SAT). The purpose of this study was to determine the contribution of abdominal SAT to cardiometabolic risk factors, independent of total and visceral adiposity. These relationships were assessed in Caucasian and African Americans., Design: It is a cross-sectional analysis of the Pennington Center Longitudinal Study., Subjects: Data were extracted from 1246 participants. Total body fat mass (FM) was measured by dual-energy X-ray absorptiometry, whereas abdominal VAT and SAT areas (cm(2)) were measured with computed tomography. The cardiometabolic risk factors included resting blood pressure (BP), fasting blood glucose and triglyceride concentrations and high-density lipoprotein cholesterol (HDL-C)., Results: Positive relationships across tertiles of VAT were seen for the participants with high glucose, high BP and low HDL-C (P<0.043). There was also a significant increase in the percentage of participants with two or more cardiometabolic risk factors across most tertiles of abdominal SAT (P<0.042). Logistic regression analysis showed that in univariate models, all adiposity measures were significantly associated with increased odds of having all risk factors in men and women. In multivariate models, VAT was significantly associated with most risk factors across gender. Abdominal SAT and FM (odds ratios (ORs) 1.3-2.1; all P<0.05) were associated with fewer risk factors after accounting for VAT. VAT (OR=5.9 and 5.3) and SAT (OR=2.0 and 1.8) were both associated with higher odds of the presence of two or more cardiometabolic risk factors in both males and females (P<0.001)., Conclusion: The data suggest that abdominal SAT is not protective against unfavorable cardiometabolic risk profiles. These conclusions were consistent across ethnic groups.

Background: Osborne-Mendel (OM) rats are prone to obesity when fed a high-fat diet, whereas S5B/Pl (S5B) rats are resistant to diet-induced obesity when fed the same diet. OM rats have a decreased satiation response to fatty acids infused in the gastrointestinal tract, compared to S5B rats. One possible explanation is that OM rats are less sensitive to the satiating hormone, glucagon-like peptide 1 (GLP-1). GLP-1 is produced in the small intestine and is released in response to a meal. The current experiments examined the role of GLP-1 in OM and S5B rats., Methods: Experiment 1 examined preproglucagon mRNA expression in the ileum of OM and S5B rats fed a high-fat (55% kcal) or low-fat (10% kcal) diet. Experiment 2 investigated the effects of a 2 h high-fat meal after a 24 h fast in OM and S5B rats on circulating GLP-1 (active) levels. Experiment 3 examined the effects of exendin-4 (GLP-1 receptor agonist) administration on the intake of a high-fat or a low-fat diet in OM and S5B rats., Results: Preproglucagon mRNA levels were increased in the ileum of OM rats compared to S5B rats and were increased by high-fat diet in OM and S5B rats. OM and S5B rats exhibited a similar meal-initiated increase in circulating GLP-1 (active) levels. Exendin-4 dose dependently decreased food intake to a greater extent in S5B rats compared to OM rats. The intake of low-fat diet, compared to the intake of high-fat diet, was more sensitive to the effects of exendin-4 in these strains., Conclusions: These results suggest that though OM and S5B rats have similar preproglucagon mRNA expression in the ileum and circulating GLP-1 levels, OM rats are less sensitive to the satiating effects of GLP-1. Therefore, dysregulation of the GLP-1 system may be a mechanism through which OM rats overeat and gain weight.

Objective: A reduction in glycogen after the switch to an isoenergetic high-fat diet (HFD) might promote a compensatory increase in food intake to reestablish carbohydrate balance. We assessed the effect of an isoenergetic switch from a 49%-carbohydrate to 50%-fat diet on nutrient balance and ad libitum food intake. We hypothesized that carbohydrate balance would be inversely related to ad libitum energy intake., Methods: In 47 men and 11 women (22.6+/-0.4 years; 26.1+/-0.5 kg m(-2)), fuel balance was measured in a respiration chamber over 4 days. During the first day, an isoenergetic, high-carbohydrate diet was provided followed by a 3-day isoenergetic, HFD. At the end of this period and after 16 h of fasting, three options of foods (cookies, fruit salad and turkey sandwich) were offered ad libitum for 4 h. The relationships between post-chamber ad libitum intake and macronutrient oxidation and balance measured day-to-day and over the 4-day respiration chamber stay were studied., Results: After switching to a HFD, 24-h respiratory quotient decreased from 0.87+/-0.02 to 0.83+/-0.02 (P<0.0001) resulting in a 4-day cumulative carbohydrate, fat and protein balances of -183+/-368, 342+/-480 and 65+/-267 kcal, respectively. Cumulative energy balance (224+/-362 kcal per 4 days) did not influence ad libitum energy intake. However, we detected that 4-day carbohydrate balance was a positive and independent predictor of post-chamber ad libitum energy intake (R (2)=0.10; P=0.01), whereas no significant influence of fat and protein balances was found., Conclusion: In response to an isoenergetic change from a high-carbohydrate to HFD, higher carbohydrate balance related to increased energy intake.