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Background The aim of obesity treatment is to promote loss of fat relative to lean mass. However, body composition changes with calorie restriction differ among individuals. Objectives The goal of this study was to test the hypothesis that insulin secretion predicts body composition changes among young and middle-age adults with high BMI (in kg/m2) following major weight loss. Methods Exploratory analyses were conducted with pre-randomization data from 2 large feeding trials: the Framingham, Boston, Bloomington, Birmingham, and Baylor study (FB4; n = 82, 43.9% women, BMI ≥27) and the Framingham State Food Study [(FS)2; n = 161, 69.6% women, BMI ≥25]. Participants in the 2 trials consumed calorie-restricted moderate-carbohydrate or very-low-carbohydrate diets to produce 12-18% weight loss in ∼14 wk or 10-14% in ∼10 wk, respectively. We determined insulin concentration 30 min after a 75-g oral glucose load (insulin-30) as a measure of insulin secretion and HOMA-IR as a measure of insulin resistance at baseline. Body composition was determined by DXA at baseline and post-weight loss. Associations were analyzed using general linear models with adjustment for covariates. Results In FB4, higher insulin-30 was associated with a smaller decrease in fat mass (0.441 kg per 100 μIU/mL increment in baseline insulin-30; P = 0.005; -1.20-kg mean difference between the first compared with the fifth group of insulin-30) and a larger decrease in lean mass (-0.465 kg per 100 μIU/mL; P = 0.004; 1.27-kg difference). Participants with higher insulin-30 lost a smaller proportion of weight loss as fat (-3.37% per 100 μIU/mL; P = 0.003; 9.20% difference). Greater HOMA-IR was also significantly associated with adverse body composition changes. Results from (FS)2 were qualitatively similar but of a smaller magnitude. Conclusions Baseline insulin dynamics predict substantial individual differences in body composition following weight loss. These findings may inform understanding of the pathophysiological basis for weight regain and the design of more effective obesity treatment. Registered at clinicaltrials.gov as NCT03394664 and NCT02068885.

Background Carbohydrate restriction shows promise for diabetes, but concerns regarding high saturated fat content of low-carbohydrate diets limit widespread adoption. Objectives This preplanned ancillary study aimed to determine how diets varying widely in carbohydrate and saturated fat affect cardiovascular disease (CVD) risk factors during weight-loss maintenance. Methods After 10–14% weight loss on a run-in diet, 164 participants (70% female; BMI = 32.4 ± 4.8 kg/m2) were randomly assigned to 3 weight-loss maintenance diets for 20 wk. The prepared diets contained 20% protein and differed 3-fold in carbohydrate (Carb) and saturated fat as a proportion of energy (Low-Carb: 20% carbohydrate, 21% saturated fat; Moderate-Carb: 40%, 14%; High-Carb: 60%, 7%). Fasting plasma samples were collected prerandomization and at 20 wk. Lipoprotein insulin resistance (LPIR) score was calculated from triglyceride-rich, high-density, and low-density lipoprotein particle (TRL-P, HDL-P, LDL-P) sizes and subfraction concentrations (large/very large TRL-P, large HDL-P, small LDL-P). Other outcomes included lipoprotein(a), triglycerides, HDL cholesterol, LDL cholesterol, adiponectin, and inflammatory markers. Repeated measures ANOVA was used for intention-to-treat analysis. Results Retention was 90%. Mean change in LPIR (scale 0–100) differed by diet in a dose-dependent fashion: Low-Carb (–5.3; 95% CI: –9.2, –1.5), Moderate-Carb (–0.02; 95% CI: –4.1, 4.1), High-Carb (3.6; 95% CI: –0.6, 7.7), P = 0.009. Low-Carb also favorably affected lipoprotein(a) [–14.7% (95% CI: –19.5, –9.5), –2.1 (95% CI: –8.2, 4.3), and 0.2 (95% CI: –6.0, 6.8), respectively; P = 0.0005], triglycerides, HDL cholesterol, large/very large TRL-P, large HDL-P, and adiponectin. LDL cholesterol, LDL-P, and inflammatory markers did not differ by diet. Conclusions A low-carbohydrate diet, high in saturated fat, improved insulin-resistant dyslipoproteinemia and lipoprotein(a), without adverse effect on LDL cholesterol. Carbohydrate restriction might lower CVD risk independently of body weight, a possibility that warrants study in major multicentered trials powered on hard outcomes. The registry is available through ClinicialTrials.gov: https://clinicaltrials.gov/ct2/show/NCT02068885.

Background Longer-term feeding studies suggest that a low-carbohydrate diet increases energy expenditure, consistent with the carbohydrate-insulin model of obesity. However, the validity of methodology utilized in these studies, involving doubly labeled water (DLW), has been questioned. Objective The aim of this study was to determine whether dietary energy requirement for weight-loss maintenance is higher on a low- compared with high-carbohydrate diet. Methods The study reports secondary outcomes from a feeding study in which the primary outcome was total energy expenditure (TEE). After attaining a mean Run-in weight loss of 10.5%, 164 adults (BMI ≥25 kg/m2; 70.1% women) were randomly assigned to Low-Carbohydrate (percentage of total energy from carbohydrate, fat, protein: 20/60/20), Moderate-Carbohydrate (40/40/20), or High-Carbohydrate (60/20/20) Test diets for 20 wk. Calorie content was adjusted to maintain individual body weight within ± 2 kg of the postweight-loss value. In analyses by intention-to-treat (ITT, completers, n = 148) and per protocol (PP, completers also achieving weight-loss maintenance, n = 110), we compared the estimated energy requirement (EER) from 10 to 20 wk of the Test diets using ANCOVA. Results Mean EER was higher in the Low- versus High-Carbohydrate group in models of varying covariate structure involving ITT [ranging from 181 (95% CI: 8–353) to 246 (64–427) kcal/d; P ≤0.04] and PP [ranging from 245 (43–446) to 323 (122–525) kcal/d; P ≤0.02]. This difference remained significant in sensitivity analyses accounting for change in adiposity and possible nonadherence. Conclusions Energy requirement was higher on a low- versus high-carbohydrate diet during weight-loss maintenance in adults, commensurate with TEE. These data are consistent with the carbohydrate-insulin model and lend qualified support for the validity of the DLW method with diets varying in macronutrient composition. This trial was registered at clinicaltrials.gov as NCT02068885.

In this paper, we first show that every bounded linear operator T from $$ L^{p_{1}}({\mathbb S}^1) $$ into $$ L^{p_{2}}({\mathbb S}^1) $$ for $$1< p_{1}, p_{2}

First, using the uniform decomposition in both physical and frequency spaces, we obtain an equivalent norm on modulation spaces. Secondly, we consider the Cauchy problem for the dissipative evolutionary pseudo-differential equation \partial_t u + A(x,D) u = F\big((\partial^\alpha_x u)_{|\alpha|\leq \kappa}\big), \ \ u(0,x)= u_0(x), where $A(x,D)$ is a dissipative pseudo-differential operator and $F(z)$ is a multi-polynomial. We will develop the uniform decomposition techniques in both physical and frequency spaces to study its local well posedness in modulation spaces $M^s_{p,q}$ and in Sobolev spaces $H^s$. Moreover, the local solution can be extended to a global one in $L^2$ and in $H^s$ ($s>\kappa+d/2$) for certain nonlinearities., Comment: 39 Pages

Background GEMINI trials and real-world studies in Western population have demonstrated the effectiveness and safety of vedolizumab (VDZ) for IBD. However, long-term real-world evidence of VDZ in Asian populations remains limited. This study aimed to investigate the effectiveness and safety of VDZ in Taiwan CD and UC patients, and the IBD relapse after VDZ discontinuation. Methods Data were prospectively collected (January 2018-May 2020) from the Taiwan Society of IBD (TSIBD) registry, one of the largest real-world Asian IBD cohorts. Patients (>18 years old) receiving ≥1 dose of VDZ with up to a 1-year follow-up period were analyzed. Effectiveness at 6 month and 1 year including clinical response (CRS), clinical remission (CRM), steroid-free remission (SRM) and mucosal healing (MH);and safety outcome were analyzed descriptively. IBD relapse after VDZ treatment discontinuation was assessed since the reimbursement period in Taiwan is limited due to drug holiday required by government. Results A total of 274 patients (CD:127, UC:147) were included. At VDZ initiation, average [SD] age (year): 33.4 [14.6] in CD and 42.4 [14.3] in UC; median disease duration (years): 3.1 in CD and 3.9 in UC; 50.4% of CD and 70.7% of UC patients were biologics (bio)-naïve. Treatment effectiveness was analyzed (Figure 1-4). At 6 months, effectiveness in the CD bio-naïve group was significantly higher than the bio-exposed patients in CRS (67.4% vs 43.9%, p=0.047), CRM (62.8% vs 39.0%, p=0.025), and SRM (43.3% vs 4.3%, p=0.001), respectively. At 1 year, the CD bio-naïve group had higher CRS (82.1% vs 60.7%, p=0.026) than the bio-exposed group. There was no difference in effectiveness between bio-naïve and bio-exposed groups in UC at both 6 months and 1 year. Three patients (1.1%) reported serious infections (respiratory infection, intractable infection with underlying myelodysplastic syndrome and intestinal perforation due to endoscopy) and two (0.7%) had infusion-related reactions. No malignancies or hepatic injuries were reported. After limited treatment up to one year due to reimbursement, 58% (54/93) of patients had IBD relapse (CD: 27 [62.8%], UC: 27 [54%]). After cessation of VDZ, the mean [SD] time to IBD relapse was 5.5 [4.0] months in CD, and 5.8 [5.7] months for UC. Conclusion This study has shown the effectiveness and safety of VDZ therapy for Taiwan IBD patients. Better outcomes were observed in bio-naïve CD patients, whereas bio-naïve and bio-exposed UC patients have comparable outcomes. After a limited VDZ treatment duration, over one-half of patients had IBD relapse, with the majority occurring within 5 months of VDZ discontinuation. These data suggest that continued VDZ therapy would benefit the majority of IBD patients in Taiwan.

Accurate and precise body composition estimates, notably of total body adiposity, are a vital component of in vivo physiology and metabolic studies. The reference against which other body composition approaches are usually validated or calibrated is the family of methods referred to as multicomponent "body density" models. These models quantify three to six components by combining measurements of body mass, body volume, total body water, and osseous mineral mass. Body mass is measured with calibrated scales, volume with underwater weighing or air-displacement plethysmography, total body water with isotope dilution, and osseous mineral mass by dual-energy X-ray absorptiometry. Body density is then calculated for use in model as body mass/volume. Studies over the past decade introduced a new approach to quantifying body volume that relies on dual-energy X-ray absorptiometry measurements, an advance that simplifies multicomponent density model development by eliminating the need for underwater weighing or air-displacement plethysmography systems when these technologies are unavailable and makes these methods more accessible to research and clinical programs. This review critically examines these new dual-energy X-ray approaches for quantifying body volume and density, explores their shortcomings, suggests alternative derivation approaches, and introduces ideas for potential future research studies.

We define pseudo-differential operators on a locally compact, Hausdorff and abelian group G as natural extensions of pseudo-differential operators on $${\mathbb {R}}^n$$. In particular, for pseudo-differential operators with symbols in $$L^2(G\times \widehat{G})$$, where $$\widehat{G}$$ is the dual group of G, we give explicit formulas for the products and adjoints, characterize them as Hilbert–Schmidt operators on $$L^2(G)$$ and prove that they form a $$C^*$$-algebra, which is also a $$H^*$$-algebra. We give a characterization of trace class pseudo-differential operators in terms of symbols lying in a subspace of $$L^1(G\times \widehat{G})\cap L^2(G\times \widehat{G})$$.

We give necessary and sufficient conditions on the symbols for which the corresponding pseudo-differential operators on the affine group are Hilbert–Schimdt operators. We also give a characterization of trace class pseudo-differential operators on the affine group. A trace formula for these trace class operators is also obtained. We have also obtained the $$L^2$$ boundedness of the Weyl transforms on the affine group.

ObjectiveTo determine the effects of diets varying in carbohydrate to fat ratio on total energy expenditure.DesignRandomized trial.SettingMulticenter collaboration at US two sites, August 2014 to May 2017.Participants164 adults aged 18-65 years with a body mass index of 25 or more.InterventionsAfter 12% (within 2%) weight loss on a run-in diet, participants were randomly assigned to one of three test diets according to carbohydrate content (high, 60%, n=54; moderate, 40%, n=53; or low, 20%, n=57) for 20 weeks. Test diets were controlled for protein and were energy adjusted to maintain weight loss within 2 kg. To test for effect modification predicted by the carbohydrate-insulin model, the sample was divided into thirds of pre-weight loss insulin secretion (insulin concentration 30 minutes after oral glucose).Main outcome measuresThe primary outcome was total energy expenditure, measured with doubly labeled water, by intention-to-treat analysis. Per protocol analysis included participants who maintained target weight loss, potentially providing a more precise effect estimate. Secondary outcomes were resting energy expenditure, measures of physical activity, and levels of the metabolic hormones leptin and ghrelin.ResultsTotal energy expenditure differed by diet in the intention-to-treat analysis (n=162, P=0.002), with a linear trend of 52 kcal/d (95% confidence interval 23 to 82) for every 10% decrease in the contribution of carbohydrate to total energy intake (1 kcal=4.18 kJ=0.00418 MJ). Change in total energy expenditure was 91 kcal/d (95% confidence interval −29 to 210) greater in participants assigned to the moderate carbohydrate diet and 209 kcal/d (91 to 326) greater in those assigned to the low carbohydrate diet compared with the high carbohydrate diet. In the per protocol analysis (n=120, PConclusionsConsistent with the carbohydrate-insulin model, lowering dietary carbohydrate increased energy expenditure during weight loss maintenance. This metabolic effect may improve the success of obesity treatment, especially among those with high insulin secretion.Trial registrationClinicalTrials.govNCT02068885.

Chronic Granulomatous Mastitis (CGM) is a rare disorder and this generally occurs in young women with a recent history of lactation. Development of this disease in nulliparous women are rare with an incidence of 10%. Axillary lymphadenopathy is seen in 15% of cases diagnosed with CGM. We present a case of CGM in a 23- year-old nulliparous woman presenting with a breast mass and multiple axillary lymphadenopathy. To the best of our knowledge there are no documented cases of both these rare clinical features occurring simultaneously. The use of oral steroids prevented surgery and effectively induced remission.

We give the normality, self-adjointness and spectral invariance of pseudo-differential operators on finite abelian groups. We also give a formula for the determinant of every element in a g...

Background While many people with overweight or obesity can lose weight temporarily, most have difficulty maintaining weight loss over the long term. Studies of dietary composition typically focus on weight loss, rather than weight-loss maintenance, and rely on nutrition education and dietary counseling, rather than controlled feeding protocols. Variation in initial weight loss and insufficient differentiation among treatments confound interpretation of results and compromise conclusions regarding the weight-independent effects of dietary composition. The aim of the present study was to evaluate three test diets differing in carbohydrate-to-fat ratio during weight-loss maintenance. Design and dietary interventions Following weight loss corresponding to 12 ± 2% of baseline body weight on a standard run-in diet, 164 participants aged 18 to 65 years were randomly assigned to one of three test diets for weight-loss maintenance through 20 weeks (test phase). We fed them high-carbohydrate (60% of energy from carbohydrate, 20% fat), moderate-carbohydrate (40% carbohydrate, 40% fat), and low-carbohydrate (20% carbohydrate, 60% fat) diets, controlled for protein content (20% of energy). During a 2-week ad libitum feeding phase following the test phase, we assessed the effect of the test diets on body weight. Outcomes The primary outcome was total energy expenditure, assessed by doubly-labeled water methodology. Secondary outcomes included resting energy expenditure and physical activity, chronic disease risk factors, and variables to inform an understanding of physiological mechanisms by which dietary carbohydrate-to-fat ratio might influence metabolism. Weight change during the ad libitum feeding phase was conceptualized as a proxy measure of hunger.

We give necessary and sufficient conditions on the symbols to guarantee that the corresponding pseudo-differential operators are nuclear from \(L^{p_1}({\mathbb {S}}^1)\) into \(L^{p_2}({\mathbb {S}}^1)\) for \(1\le p_1,p_2

We give the determinants and upper bounds for the condition numbers of matrices of pseudo-differential operators $$T_\sigma $$ on $${\mathbb Z}_N$$ with separable symbols $$\sigma $$ on $${\mathbb Z}_N\times {\mathbb Z}_N.$$ For a time series z of size N, we give the computational complexity of $$T_\sigma z$$ . Numerical experiments are also given.

OBJECTIVES: To compare effects of diets varying in carbohydrate (carb) and fat on plasma lipids and lipoprotein subfractions. METHODS: Participants (N = 164, 70% female, 18–65 y, BMI ≥ 25 kg/m(2)) achieved 10–14% weight loss on a run-in diet and then were randomized to 3 test diets for 20 weeks of weight-loss maintenance. Percentages of total energy from carb-fat-protein for high-, moderate-, and low-carb diets were 60-20-20 (HI), 40-40-20 (MOD), and 20–60-20 (LO). Relative amounts of added sugar (15% total carb) and saturated fat (35% total fat) were fixed across diets. Plasma was collected at START (post-weight loss) and END of trial. The primary outcome for this ancillary study was lipoprotein insulin resistance (LPIR) – a 6-component weighted score of triglyceride-rich, high-density, and low-density lipoprotein particle (TRL-P, HDL-P, LDL-P) sizes and subfraction concentrations (large/very large TRL-P, large HDL-P, small LDL-P) (NMR spectroscopy, LabCorp). Other outcomes included large LDL-P concentration, triglycerides (TG), and cholesterol (HDL-C, LDL-C). Means (±SE) and END–START changes (mean [95% CI]) were constructed and compared from repeated measures ANOVA. RESULTS: Retention was 90% and 147 participants provided evaluable data, with no difference in body weight by diet after randomization. LPIR was 32.6 ± 1.5 at START. Change in LPIR differed by diet (P = 0.009): LO (−5.3 [−9.2, −1.5]), MOD (−0.02 [−4.1, 4.1]), HI (3.6 [−0.6, 7.7]). Diet effects favoring LO compared to HI were observed for large/very large TRL-P (P = 0.005), large HDL-P (P = 0.045), TG (P = 0.006), and HDL-C (P = 0.04). There were no mean differences between diets for particle sizes, LDL-P subfraction concentrations, and LDL-C (START: 79.3 ± 1.8 mg/dL; END–START: HI, 8.2 [4.2, 12.2]; MOD, 11.7 [7.8, 15.7]; LO, 10.0 [6.3, 13.7]). CONCLUSIONS: With 3-fold higher saturated fat content (21% vs 7% total energy), a low- vs high-carb diet improved LPIR, a biomarker of diabetes risk, and several other components of the metabolic syndrome, with no adverse effects on LDL-P or LDL-C. These results from a large feeding study suggest that carb restriction may help prevent cardiometabolic disease independent of body weight. FUNDING SOURCES: Nutrition Science Initiative (gifts from Arnold Ventures and Robert Lloyd Corkin Charitable Foundation), New Balance Foundation, Many Voices Foundation, Blue Cross Blue Shield.

Weyl transforms for \(\mathrm{H}\)-type groups are introduced and shown to be the classical Weyl transforms on \({\mathbb R}^n\).

Importance Health care professionals commonly recommend increased water consumption, typically to 8 cups per day, as part of a weight-reducing diet. However, this recommendation is based on limited evidence and virtually no experimental data from the pediatric population. Objective To compare 2 standardized weight-loss diets among adolescents with overweight or obesity, either with or without additional advice and behavioral support to increase habitual water intake to 8 cups per day. Design, Setting, and Participants A randomized clinical, parallel-group trial was conducted between February 2, 2011, and June 26, 2014, at Boston Children’s Hospital, Boston, Massachusetts, among 38 adolescents with overweight or obesity who reported drinking 4 cups or less of water per day. Interventions All participants in both groups received similar weight-reducing interventions, differentiated by advice about water intake (the water group received advice to increase water intake to 8 cups per day; the control group did not receive such advice) but controlled for other dietary recommendations and treatment intensity. The interventions included dietary counseling, daily text messages, and a cookbook with health guides. To support adherence to 8 cups of water per day, the water group received well-defined messages about water through counseling and daily text messages, a water bottle, and a water pitcher with filters. Main Outcomes and Measures The primary outcome was 6-month change in body mass index z score. Data analyses followed the intention-to-treat principle. Results All 38 participants (27 girls and 11 boys; mean [SD] age, 14.9 [1.7] years) completed the study. Both groups reported drinking approximately 2 cups of water per day at baseline. Self-reported change in water intake at 6 months was greater in the water group (difference from baseline, 2.8 cups per day [95% CI, 1.8 to 3.8]; P P = .02) (difference between groups, 1.6 cups per day [95% CI, 0.2 to 3.0 cups per day]; P = .03). The 6-month change in body mass index z score did not differ between the water group (difference from baseline, –0.1 [95% CI, –0.2 to –0.0]; P = .005) and the control group (difference from baseline, –0.1 [95% CI, –0.2 to –0.0]; P = .008) (difference between groups, –0.0 [95% CI, −0.1 to 0.1]; P = .88). Conclusions and Relevance Advice and behavioral supports to consume 8 cups of water per day in the context of a weight-reducing diet did not affect body weight among adolescents with overweight or obesity. Despite intensive behavior supports, few adolescents achieved the target of 8 cups of water per day. Environmental interventions to reduce barriers to water consumption at school may be necessary in future research of the feasibility and effectiveness to achieve the target of an intake of 8 cups of water per day in adolescents. Trial Registration clinicaltrials.gov Identifier:NCT01044134

Diets that have been shown to reduce chronic disease risk focus on increasing intake of foods naturally high in fiber with minimal processing including fruits, vegetables, legumes, and whole grains. Despite evidence for reduced disease burden from both epidemiological and clinical trials, current intake levels of such foods are well below dietary recommendations. Consequently, low intakes of dietary fiber significantly reduce the amount of fermentable substrate available to the gut microbiota as a source of metabolic fuel and likely lead to a less than favorable gut microbial profile. Major end products of gut microbial fermentation of nondigestible and undigested carbohydrates are short chain fatty acids (SCFAs), which have been associated with decreasing the risk of gastrointestinal disorders, cardiovascular disease, and cancer. The ratio of the major SCFAs (acetate, propionate, and butyrate) produced is highly dependent on the chemical composition of the substrate source. A mismatch exists between our archaic genome and gut microbiota, which has evolved primarily on plant-based diets that are high in dietary fiber and fermentable substrate, and our modern diets that contain low intakes of plant-based foods. This deficiency may provide some explanation for the rise in chronic diseases in Western nations. Emerging evidence suggests that interindividual differences in the gut microbiota are influenced by diet (probiotics, prebiotics) or antibiotics and may be linked to variations in physiology, including lipid metabolism that may predispose an individual to risk of certain chronic diseases. Diet is one of the key modulators of gut microbial communities and may provide a tailored approach for optimizing human health.