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This review explores the complex relationship between social determinants of health and the biology of chronic wounds associated with diabetes mellitus, with an emphasis on racial/ethnic disparities. Chronic wounds pose significant healthcare challenges, often leading to severe complications for millions of people in the United States, and disproportionally affect African American, Hispanic, and Native American individuals. Social determinants of health, including economic stability, access to healthcare, education, and environmental conditions, likely influence stress, weathering, and nutrition, collectively shaping vulnerability to chronic diseases, such as obesity and DM, and an elevated risk of chronic wounds and subsequent lower extremity amputations. Here, we review these issues and discuss the urgent need for further research focusing on understanding the mechanisms underlying racial/ethnic disparities in chronic wounds, particularly social deprivation, weathering, and nutrition, to inform interventions to address these disparities., (© 2024 The Author(s). Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

Background: (1)Sarcopenia, or low skeletal mass index (SMI), contributes to higher lung cancer mortality. The SMI at third lumbar vertebrae (L3) is the reference standard for body composition analysis. However, there is a need to explore the validity of alternative landmarks in this population. We compared the agreement of sarcopenia identification at the first lumbar (L1) and second lumbar (L2) to L3 in non-Hispanic Black (NHB) and White (NHW) individuals with lung cancer., Methods: (2)This retrospective, cross-sectional study included 214 NHB and NHW adults with lung cancer. CT scans were analyzed to calculate the SMI at L1, L2, and L3. T-tests, chi-square, Pearson's correlation, Cohen's kappa, sensitivity, and specificity analysis were used., Results: (3)Subjects presented with a mean age of 68.4 ± 9.9 years and BMI of 26.3 ± 6.0 kg/m 2 . Sarcopenia prevalence varied from 19.6% at L1 to 39.7% at L3. Cohen's kappa coefficient was 0.46 for L1 and 0.64 for L2, indicating weak and moderate agreement for the identification of sarcopenia compared to L3., Conclusions: (4)Sarcopenia prevalence varied greatly depending on the vertebral landmark used for assessment. Using L2 or L1 alone resulted in a 16.8% and 23.8% misclassification of sarcopenia in this cohort of individuals with lung cancer., Competing Interests: Conflicts of Interest: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

African American adults have a higher prevalence of Alzheimer's dementia (AD) than non-Hispanic Whites. The impact of a Mediterranean Diet (Med Diet) and intentional weight loss (IWL) on the gut microbiome may alter AD risk. A post hoc analysis of the Building Research in Diet and Cognition (BRIDGE) trial was performed to determine whether participation in an 8-month Med Diet lifestyle intervention with ( n = 35) or without IWL ( n = 31) was associated with changes in gut microbiota structure, abundance, and function and whether these changes were related to changes in cognitive performance. The results showed that family and genus alpha diversity increased significantly in both groups combined ( p = 0.0075 and p = 0.024, respectively). However, there were no other significant microbially related within- or between-group changes over time. Also, an increase in Med Diet adherence was significantly associated with a decrease in alpha diversity at the phylum level only ( p = 0.049). Increasing alpha diversity was associated with decreasing cognitive performance, but this association was attenuated after controlling for Med Diet adherence. In sum, an 8-month Med Diet lifestyle intervention with or without IWL did not appreciably alter the gut microbiome.

Parkinson's disease (PD), a heterogeneous disease with no disease-modifying treatments available, is the fastest growing neurological disease worldwide. Currently, physical exercise is the most promising treatment to slow disease progression, with evidence suggesting it is neuroprotective in animal models. The onset, progression, and symptom severity of PD are associated with low grade, chronic inflammation which can be quantified by measuring inflammatory biomarkers. In this perspective, we argue that C-reactive protein (CRP) should be used as the primary biomarker for monitoring inflammation and therefore disease progression and severity, particularly in studies examining the impact of an intervention on the signs and symptoms of PD. CRP is the most studied biomarker of inflammation, and it can be detected using relatively well-standardized assays with a wide range of detection, allowing for comparability across studies while generating robust data. An additional advantage of CRP is its ability to detect inflammation irrespective of its origin and specific pathways, an advantageous characteristic when the cause of inflammation remains unknown, such as PD and other chronic, heterogeneous diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mehta, Luthra, Corcos and Fantuzzi.)

This Perspective highlights the work of Dr. Daniela Novick in the field of cytokine biology. Using affinity chromatography to characterize cytokine-binding proteins, she identified soluble forms of the receptors as well as binding proteins for several cytokines, including tumor necrosis factor, interleukin (IL) 6, IL-18 and IL-32. Importantly, her work has been key in the development of monoclonal antibodies against interferons and cytokines. This Perspective discusses her contribution to the field and highlights her recent review on this topic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ghezzi, Fantuzzi and Dinarello.)

Those with mild cognitive impairment (MCI), a precursor to dementia, have a gut microbiome distinct from healthy individuals, but this has only been shown in healthy individuals, not in those exhibiting several risk factors for dementia. Using amplicon 16S rRNA gene sequencing in a case-control study of 60 older (ages 55-76), obese, predominately female, African American adults, those with MCI (cases) had different gut microbiota profiles than controls. While microbial community diversity was similar between cases and controls, the abundances of specific microbial taxa weren't, such as Parabacteroides distasonis (lower in cases) and Dialister invisus (higher in cases). These differences disappeared after adjusting for markers of oxidative stress and systemic inflammation. Cognitive scores were positively correlated with levels of Akkermansia muciniphila, a bacterium associated with reduced inflammation. Our study shows that gut microbial composition may be associated with inflammation, oxidative stress, and MCI in those at high risk for dementia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 McLeod et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Rationale and Objectives: To validate skeletal muscle and adipose tissues cross sectional area (CSA) and densities between a fully automated neural network (test program) and a semi-automated program requiring human correction (reference program) for lumbar 1 (L1) and lumbar 2 (L2) CT scans in patients with lung cancer., Materials and Methods: Agreement between the reference and test programs was measured using Dice-similarity coefficient (DSC) and Bland-Altman plots with limits of agreement within 1.96 standard deviation., Results: A total of 49 L1 and 47 L2 images were analyzed from patients with lung cancer (mean age = 70.51 ± 9.48 years; mean BMI = 27.45 ± 6.06 kg/m 2 ; 71% female, 55% self-identified as Black and 96% as non-Hispanic ethnicity). The DSC indicates excellent overlap (>0.944) or agreement between the two measurement methods for muscle, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) CSA and all tissue densities at L1 and L2. The DSC was lowest for intermuscular adipose tissue (IMAT) CSA at L1 (0.889) and L2 (0.919)., Conclusion: The use of a fully automated neural network to analyze body composition at L1 and L2 in patients with lung cancer is valid for measuring skeletal muscle and adipose tissue CSA and densities when compared to a reference program. Further validation in a more diverse sample and in different disease and health states is warranted to increase the generalizability of the test program at L1 and L2., Competing Interests: The authors declare no competing interests., (© 2022 Published by Elsevier Ltd.)

Background: Lung cancer incidence and mortality rates are higher in Non-Hispanic Black (NHB) compared to Non-Hispanic White (NHW) individuals in the Chicago metropolitan area, which may be related to exposure to chronic stress which may increase inflammation., Specific Aim: We investigated disparities in inflammation as measured by neutrophil to lymphocyte ratio (NLR) in individuals with lung cancer by race and by neighborhood concentrated disadvantage index (CDI)., Methods: This retrospective, cross-sectional study included 263 NHB and NHW adults with lung cancer. We analyzed NLR as a continuous and categorical variable to determine degree and prevalence of inflammation. We used Mann Whitney U, t-tests, Chi square tests, linear and logistic regression models as appropriate., Results: More than 60% of subjects had inflammation (NLR ≥ 3) at lung cancer diagnosis. The degree of inflammation was significantly lower in NHB (NLR 5.50 +/- 7.45) compared to NHW individuals (NLR 6.53 +/- 6.53; p=0.01) but did not differ by neighborhood CDI. The prevalence of inflammation (NLR ≥ 3) was significantly lower in NHB (55.07%) compared to NHW individuals (71.20%; p<0.01) and in those from the most disadvantaged (54.07%) compared to the least disadvantaged (71.88%; p<0.01) neighborhoods., Conclusion: At lung cancer diagnosis, there is a lower degree and prevalence of inflammation in NHB compared to NHW individuals, and lower prevalence in those residing in the most disadvantaged neighborhoods. Further research is needed to determine mechanisms of inflammation that may be contributing to lung cancer disparities as well as whether NLR is an appropriate biomarker when examining racial differences in inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Byrne, Gomez, Kim, Oddo, Koh and Fantuzzi.)

Background: To date, no medication has slowed the progression of Parkinson's disease (PD). Preclinical, epidemiological, and experimental data on humans all support many benefits of endurance exercise among persons with PD. The key question is whether there is a definitive additional benefit of exercising at high intensity, in terms of slowing disease progression, beyond the well-documented benefit of endurance training on a treadmill for fitness, gait, and functional mobility. This study will determine the efficacy of high-intensity endurance exercise as first-line therapy for persons diagnosed with PD within 3 years, and untreated with symptomatic therapy at baseline., Methods: This is a multicenter, randomized, evaluator-blinded study of endurance exercise training. The exercise intervention will be delivered by treadmill at 2 doses over 18 months: moderate intensity (4 days/week for 30 min per session at 60-65% maximum heart rate) and high intensity (4 days/week for 30 min per session at 80-85% maximum heart rate). We will randomize 370 participants and follow them at multiple time points for 24 months. The primary outcome is the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score (Part III) with the primary analysis assessing the change in MDS-UPDRS motor score (Part III) over 12 months, or until initiation of symptomatic antiparkinsonian treatment if before 12 months. Secondary outcomes are striatal dopamine transporter binding, 6-min walk distance, number of daily steps, cognitive function, physical fitness, quality of life, time to initiate dopaminergic medication, circulating levels of C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF). Tertiary outcomes are walking stride length and turning velocity., Discussion: SPARX3 is a Phase 3 clinical trial designed to determine the efficacy of high-intensity, endurance treadmill exercise to slow the progression of PD as measured by the MDS-UPDRS motor score. Establishing whether high-intensity endurance treadmill exercise can slow the progression of PD would mark a significant breakthrough in treating PD. It would have a meaningful impact on the quality of life of people with PD, their caregivers and public health., Trial Registration: ClinicalTrials.gov NCT04284436 . Registered on February 25, 2020., (© 2022. The Author(s).)

The background method is a widely used technique to bound mean properties of turbulent flows rigorously. This work reviews recent advances in the theoretical formulation and numerical implementation of the method. First, we describe how the background method can be formulated systematically within a broader 'auxiliary function' framework for bounding mean quantities, and explain how symmetries of the flow and constraints such as maximum principles can be exploited. All ideas are presented in a general setting and are illustrated on Rayleigh-Bénard convection between stress-free isothermal plates. Second, we review a semidefinite programming approach and a timestepping approach to optimizing bounds computationally, revealing that they are related to each other through convex duality and low-rank matrix factorization. Open questions and promising directions for further numerical analysis of the background method are also outlined. This article is part of the theme issue 'Mathematical problems in physical fluid dynamics (part 1)'.

In the United States, >5.4 million people age 65 and older are affected by cognitive impairment and dementia, including Alzheimer's disease. African Americans are more likely than non-Hispanic whites to suffer from these disorders. Obesity is linked to accelerated age-related cognitive decline, and weight loss through caloric restriction is a potential strategy to prevent this cognitive impairment. Adherence to a healthful dietary pattern, such as the Mediterranean Diet (MedDiet), has also shown positive effects on reducing risk for dementia. African Americans are disproportionately affected by obesity and have less healthful diets than non-Hispanic whites. We present baseline characteristics from a three-arm randomized controlled trial that randomized 185 obese (BMI ≥ 30 kg/m 2 and ≤ 50 kg/m 2 ) healthy older adults (55-85 years of age) to: 1) Typical Diet Control (TDC); 2) MedDiet alone (MedDiet-A) intervention; or 3) MedDiet caloric restricted intervention to promote weight loss (MedDiet-WL). The majority of the sample was African American (91.4%) and female (85.9%). The two active interventions (MedDiet-A and MedDiet-WL) met once weekly for 8 months, and the TDC received weekly general health newsletters. Baseline data were collected between January 2017 and July 2019 in Chicago, IL. In our sample, closer adherence to a MedDiet pattern was associated with higher attention and information processing (AIP) and higher executive functioning (EF). Consistent with the literature, we saw that older participants performed more poorly on the cognitive assessments than younger participants, and women outperformed men across verbally mediated tasks, especially ones related to learning and memory., Competing Interests: 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.

(1) Background: There are currently very few interventions performed within a community setting that compare the effects of physical activity (PA) versus PA plus weight loss on cancer and chronic disease risk in older African Americans. Therefore, we investigated the impact of an 8 week (24 session) PA intervention compared to a PA plus weight loss intervention on fat mass, glucose metabolism, and markers of inflammation in older, overweight and obese African Americans. (2) Methods: Subjects were randomized to a PA ( n = 83) or PA plus weight loss ( n = 72) intervention that met three times weekly for 8 weeks. At baseline and post-intervention, anthropometrics, body composition, systemic inflammation (high-sensitivity C-reactive protein, tumor necrosis factor-α, and interleukin 6), fasting glucose, insulin and homeostasis model assessment-insulin resistance (HOMA-IR) were determined. (3) Results: Subjects had a mean age of 67 years (SD = 5.3) and were mostly women (88%). The PA plus weight loss group lost more total and visceral fat than the PA group (-4.0% vs. +0.6% and -4.1% vs. +3.7%, respectively, p < 0.01 for both). Changes in inflammation and glucose metabolism were similar between groups post-intervention. Within the PA plus weight loss group only, serum insulin and HOMA-IR decreased significantly. (4) Conclusions: PA combined with weight loss can decrease total and visceral fat mass and improve insulin sensitivity, confirming that these cancer- and chronic disease-related risk factors are influenced by relatively modest lifestyle changes in the short term., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Introduction: Acute pancreatitis (AP) is a healthcare challenge with considerable mortality. Treatment is limited to supportive care, highlighting the need to investigate disease drivers and prognostic markers. Activin A is an established mediator of inflammatory responses, and its serum levels correlate with AP severity. We hypothesized that activin A is independent of body mass index (BMI) and is a targetable promoter of the AP inflammatory response., Methods: We assessed whether BMI and serum activin A levels are independent markers to determine disease severity in a cohort of patients with AP. To evaluate activin A inhibition as a therapeutic, we used a cerulein-induced murine model of AP and treated mice with activin A-specific neutralizing antibody or immunoglobulin G control, both before and during the development of AP. We measured the production and release of activin A by pancreas and macrophage cell lines and observed the activation of macrophages after activin A treatment., Results: BMI and activin A independently predicted severe AP in patients. Inhibiting activin A in AP mice reduced disease severity and local immune cell infiltration. Inflammatory stimulation led to activin A production and release by pancreas cells but not by macrophages. Macrophages were activated by activin A, suggesting activin A might promote inflammation in the pancreas in response to injury., Discussion: Activin A provides a promising therapeutic target to interrupt the cycle of inflammation and tissue damage in AP progression. Moreover, assessing activin A and BMI in patients on hospital admission could provide important predictive measures for screening patients likely to develop severe disease.

The purpose of this systematic review is to analyze the available evidence linking short-chain fatty acids (SCFA) to leptin's levels and production. We performed a systematic review using the PubMed/Medline database including primary articles written in English that measured leptin production or levels as well as SCFA used as an intervention, mechanism or outcome. The search yielded a total of 573 citations; 36 studies were included in the final analysis. The quality of the studies was analyzed through two validated tools based on objective criteria. Overall, the studies presented low risk of bias to construct and statistical validity. However, the majority presented a high risk of attrition and detection bias. In vitro studies (n = 8) consistently demonstrated that SCFA stimulate leptin expression in adipocytes through activation of free fatty acid receptor 3 (FFAR3). In animal studies (n = 24), interventions to modulate high-fat diet outcomes predominantly caused a decrease in circulating leptin levels and increased SCFA, associated with suppressed weight gain. Control of dysbiosis through administration of prebiotics and probiotics also played a role in leptin synthesis in animal studies. In human studies (n = 4) leptin was mainly correlated with adiposity but dysbiosis interfered with this relationship. We conclude that the association between SCFA and leptin remains incompletely understood but occurs mainly through the activation of FFAR3 in adipocytes. However, body fat rather than SCFA remains the main driver for leptin synthesis in vivo. Future studies should aim to better clarify the role of SCFA in regulating leptin production in vivo., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Cachexia occurs in individuals affected by chronic diseases in which systemic inflammation leads to fatigue, debilitation, decreased physical activity and sarcopenia. The pathogenesis of cachexia-associated sarcopenia is not fully understood., Objectives: The aim of this systematic review is to summarize the current evidence on genes expressed in the skeletal muscles of humans with chronic disease-associated cachexia and/or sarcopenia (cases) compared to controls and to assess the strength of such evidence., Methods: We searched PubMed, EMBASE and CINAHL using three concepts: cachexia/sarcopenia and associated symptoms, gene expression, and skeletal muscle., Results: Eighteen genes were studied in at least three research articles, for a total of 27 articles analyzed in this review. Participants were approximately 60 years of age and majority male; sample size was highly variable. Use of comparison groups, matching criteria, muscle biopsy location, and definitions of cachexia and sarcopenia were not homogenous. None of the studies fulfilled all four criteria used to assess the quality of molecular analysis, with only one study powered on the outcome of gene expression. FOXO1 was the only gene significantly increased in cases versus healthy controls. No study found a significant decrease in expression of genes involved in autophagy, apoptosis or inflammation in cases versus controls. Inconsistent or non-significant findings were reported for genes involved in protein degradation, muscle differentiation/growth, insulin/insulin growth factor-1 or mitochondrial transcription., Conclusion: Currently available evidence on gene expression in the skeletal muscles of humans with chronic disease-associated cachexia and/or sarcopenia is not powered appropriately and is not homogenous; therefore, it is difficult to compare results across studies and diseases., Competing Interests: The authors have declared that no competing interests exist.

Background: Premature infants are susceptible to oxidative stress, increasing the risk for serious morbidities. High-dose human milk (HM) feedings decrease morbidity risks and may reduce oxidative stress in this population. The purpose of this study was to compare oxidative stress using serial urinary F 2 -isoprostane concentrations in predominantly HM and preterm formula (PF)-fed premature infants over the first 21 days of life (DOL), while controlling for perinatal oxidative stress exposures including bovine-based human milk fortifier (HMF) or PF introduction to predominantly HM-fed infants., Methods: This was a quasi-experimental design that categorized 22 premature infants into mutually exclusive comparison groups based on exposure to HM and PF. Serial urine samples (before and after first feeding, and DOL 7, 14, and 21) were used to determine urine F 2 -isoprostane concentrations measured by enzyme-linked immunosorbent assays. We analyzed data using Mann-Whitney U test, Wilcoxon rank test, and multilevel models., Results: Comparing the predominantly HM-fed and predominantly PF-fed groups over time, median F 2 -isoprostane concentrations decreased significantly in the predominantly HM group (P = .003) and increased significantly in the predominantly PF group (P = .01). Perinatal oxidant exposures and the introduction of HMF did not affect results., Conclusions: Our results demonstrate that predominantly HM feedings were associated with decreased oxidative stress, whereas PF feedings increased oxidative stress in premature infants, even after controlling for perinatal oxidant exposures of HMF or PF introduction., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Objectives: Among critically ill patients, the benefits of nutrition support may vary depending on severity of organ dysfunction. The objective of the current article was to explore the relationship between organ failure and calories exposure with hospital mortality during the first week of acute respiratory distress syndrome., Design: Retrospective observational study., Setting: Single-center ICU., Patients: Adults admitted to the ICU with a diagnosis of acute respiratory distress syndrome., Interventions: Calorie delivery from enteral nutrition, parenteral nutrition, propofol, and dextrose containing fluids were collected for 7 days following intubation. Sequential Organ Failure Assessment score was calculated at ICU admit and for the same 7 days to describe organ dysfunction; four different Sequential Organ Failure Assessment variables were created 1) Sequential Organ Failure Assessment at ICU admit, 2) average Sequential Organ Failure Assessment for the first 7 days following intubation, 3) the highest Sequential Organ Failure Assessment for the first 7 days following intubation, and 4) change in Sequential Organ Failure Assessment from intubation to 7 days later., Measurements and Main Results: A total of 298 patients were included. Sequential Organ Failure Assessment at ICU admit, average Sequential Organ Failure Assessment for the first 7 days following intubation, highest Sequential Organ Failure Assessment for the first 7 days following intubation, change in Sequential Organ Failure Assessment from intubation to 7 days later, and calorie delivery the first 7 days following intubation were all associated with increased likelihood of mortality. Compared with patients with low organ failure and low-calorie delivery, those with high-calorie delivery and low organ failure, low-calorie delivery and high organ failure, and the combination of both high organ failure with high-calorie delivery were associated with an incremental increase in the likelihood or mortality., Conclusions: Organ failure appears to modify the relationship between calorie exposure and ICU outcome. Additional research is needed to identify appropriate thresholds for safe calorie exposure with increased organ failure.

Introduction: Several instruments developed to assess dietary intake of groups or populations have strengths and weaknesses that affect their specific application. No self-administered, closed-ended dietary survey was previously used in Argentina to assess current food and nutrient intake on a daily basis., Objective: To design and validate a self-administered, structured food record (NutriQuid, NQ) representative of the adult Argentine population's food consumption pattern to measure individual energy and nutrient intake., Materials and Methods: Records were loaded onto a database using software that checks a regional nutrition information system (SARA program), automatically quantifying energy and nutrient intake. NQ validation included two phases: (1) NQ construct validity comparing records kept simultaneously by healthy volunteers (45-75 years) and a nutritionist who provided meals (reference), and (2) verification of whether NQ reflected target population consumption (calories and nutrients), week consumption differences, respondent acceptability, and ease of data entry/analysis. Data analysis included descriptive statistics, repeated measures ANOVA, intraclass correlation coefficient, nonparametric regression, and cross-classification into quintiles., Results: The first validation (study group vs. reference) showed an underestimation (10%) of carbohydrate, fat, and energy intake. Second validation: 109 volunteers (91% response) completed the NQ for seven consecutive days. Record completion took about 9min/day, and data entry 3-6min. Mean calorie intake was 2240±119kcal/day (42% carbohydrates, 17% protein, and 41% fat). Intake significantly increased in the weekend., Conclusion: NQ is a simple and efficient tool to assess dietary intake in large samples., (Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

The occurrence of illicit drugs (cocaine, opioids, amphetamines and cannabis derivatives), some of their metabolites and 48 pharmaceuticals, was investigated in pool and source waters in ten Italian indoor swimming pools. The samples were analyzed by highperformance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), after solid phase extraction (SPE). Cocaine and its metabolites were found in nine swimming pools, at concentrations from 0.3 to 4.2 ng/L for cocaine, 1.1 to 48.7 ng/L for norcocaine, 0.7 to 21.4 ng/L for benzoylecgonine and 0.1 to 7.3 ng/L for norbenzoylecgonine. Opioids, amphetamines and cannabis derivatives were never detected. The most frequent pharmaceuticals were anti-inflammatory drugs: ibuprofen was found in all the pool waters, with a maximum 197 ng/L and ketoprofen was detected in 9/10 samples (maximum 127 ng/L). Among anticonvulsants, carbamazepine and its metabolite, 10,11-dihydro-10,11dihydroxycarbamazepine, were frequent in swimming pool water (8/10 samples) at concentrations up to 62 ng/L. The cardiovascular drug valsartan was also found frequently (8/10 samples), but at lower concentrations (up to 9 ng/L). Other pharmaceuticals were detected occasionally and at lower concentrations (atenolol, enalapril, paracetamol, hydroclorothiazide, irbesartan and dehydro-erythromycin). Carbamazepine, irbesartan and dehydroerythromycin were detected at very low levels (up to 5 ng/L) in only one of the four source water samples. A quantitative risk assessment showed that the health risk for humans to these substance in swimming pool waters was generally negligible, even for vulnerable subpopulations such as children and adolescents., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to determine the effect of digested whole human milk (HM; first sample available after birth from mothers of premature infants) on inflammation, oxidative stress, and cytotoxicity in Caco-2 human intestinal epithelial cells stimulated with lipopolysaccharides or tumor necrosis factor (TNF) to mimic the potential in vivo insults facing the premature infant's gastrointestinal tract., Methods: Fully differentiated Caco-2 cells were exposed to digested HM (n = 10; samples from 10 different individuals) before stimulation with lipopolysaccharides, TNF, or no stimulation overnight. Inflammation was determined by production of interleukin-8, oxidative stress by levels of F2-isoprostane, and cytotoxicity by released lactate dehydrogenase., Results: HM significantly suppressed interleukin-8 production and cytotoxicity in TNF-stimulated cells, while also suppressing cell death under baseline conditions. Individual HM samples differed widely in their ability to modulate cellular responses., Conclusions: Results from this study provide evidence that digested HM can reduce both an exaggerated inflammatory response and intestinal damage that contribute to the pathogenesis of necrotizing enterocolitis.

Background: The Intensive Nutrition in Acute Lung Injury: Clinical Trial (INTACT), designed to evaluate outcomes of calorie delivery from acute respiratory distress syndrome (ARDS) diagnosis through hospital discharge, was stopped due to higher mortality in the intervention group. Post hoc analysis found timing and dose of calorie delivery influenced mortality. The objective of this retrospective cohort study was to determine if early vs late calorie exposure changed the hazard of death among a larger sample of patients with ARDS., Methods: Adult patients who met the eligibility criteria for INTACT but did not participate were included. Daily calorie delivery was collected from the date INTACT eligibility was determined to extubation or death. Cox proportional hazards regression was used to model the relationship between hazard of hospital death with average calorie exposure received over increasing study days and after day 7., Results: A total of 298 patients were included; overall mortality was 33%. Among patients who remained intubated at 1 week (n = 202), higher kcal/kg received from intensive care unit (ICU) days 1-6 increased hazards of subsequent death on days 7+ (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.01-1.06); kcal/kg received after ICU day 7 decreased the hazards of death on day 7+ (HR, 0.53; 95% CI, 0.33-0.84)., Conclusions: Higher calorie exposure between ICU days 1 and 7 was associated with higher subsequent hazard of mortality, and provision of high-calorie exposure after day 8 decreased the hazards of death., (© 2017 American Society for Parenteral and Enteral Nutrition.)

Background: Primary Prevention of Diabetes Program in Buenos Aires Province evaluates the effectiveness of adopting healthy lifestyle to prevent type 2 diabetes (T2D) in people at high risk of developing it. We aimed to present preliminary data analysis of FINDRISC and laboratory measurements taken during recruitment of people for the Primary Prevention of Diabetes Program in Buenos Aires Province in the cities of La Plata, Berisso, and Ensenada, Argentina., Methods: People were recruited through population approach (house-to-house survey by FINDRISC in randomized areas) and opportunistic approach (FINDRISC completed by participants during consultations for nonrelated prediabetes/diabetes symptoms in public and private primary care centres of cities involved). In people with FINDRISC score ≥ 13 points, we evaluated blood concentrations of HbA 1c , creatinine, lipids, and an oral glucose tolerance test (OGTT)., Results: Approximately 3415 individuals completed the FINDRISC populational survey and 344 the opportunistic survey; 43% of the 2 groups scored over 13 points; 2.8 and 75.4% of them, respectively, took the prescribed OGTT. Approximately 53.7% of the OGTT showed normal values and 5.2% unknown T2D. The remaining cases showed 69.5% impaired fasting glucose, 13.6% impaired glucose tolerance, and 16.9% both impairments. HbA 1c values showed significant differences compared with normal glucose tolerance (4.96 ± 0.43%), prediabetes (5.28 ± 0.51%), and T2D (5.60 ± 0.51%). Participants with prediabetes and T2D showed a predominant increase in low-density lipoprotein-cholesterol values. In prediabetes, >50% showed insulin resistance., Conclusions: People with prediabetes/T2D had dyslipidemia associated with insulin resistance, which promotes the development of T2D and cardiovascular disease. Thus, it merits its appropriate treatment., (Copyright © 2017 John Wiley & Sons, Ltd.)

Acute Pancreatitis is a substantial health care challenge with increasing incidence. Patients who develop severe disease have considerable mortality. Currently, no reliable predictive marker to identify patients at risk for severe disease exists. Treatment is limited to rehydration and supporting care suggesting an urgent need to develop novel approaches to improve standard care. Activin is a critical modulator of inflammatory responses, but has not been assessed in pancreatitis. Here, we demonstrate that serum activin is elevated and strongly correlates with disease severity in two established murine models of acute pancreatitis induced by either cerulein or IL-12 + IL-18. Furthermore, in mice, inhibition of activin conveys survival benefits in pancreatitis. In addition, serum activin levels were measured from a retrospective clinical cohort of pancreatitis patients and high activin levels in patients at admission are predictive of worse outcomes, indicated by longer overall hospital and intensive care unit stays. Taken together, activin is a novel candidate as a clinical marker to identify those acute pancreatitis patients with severe disease who would benefit from aggressive treatment and activin may be a therapeutic target in severe acute pancreatitis.

Purpose African American women with breast cancer have higher cancer-specific and overall mortality rates. Obesity is common among African American women and contributes to breast cancer progression and numerous chronic conditions. Weight loss interventions among breast cancer survivors positively affect weight, behavior, biomarkers, and psychosocial outcomes, yet few target African Americans. This article examines the effects of Moving Forward, a weight loss intervention for African American breast cancer survivors (AABCS) on weight, body composition, and behavior. Patients and Methods Early-stage (I-III) AABCS were randomly assigned to a 6-month interventionist-guided (n = 125) or self-guided (n = 121) weight loss program supporting behavioral changes to promote a 5% weight loss. Anthropometric, body composition, and behavioral data were collected at baseline, postintervention (6 months), and follow-up (12 months). Descriptive statistics and mixed models analyses assessed differences between groups over time. Results Mean (± standard deviation) age, and body mass index were 57.5 (± 10.1) years and 36.1 (± 6.2) kg/m 2 , respectively, and 82% had stage I or II breast cancer. Both groups lost weight. Mean and percentage of weight loss were greater in the guided versus self-guided group (at 6 months: 3.5 kg v 1.3kg; P < .001; 3.6% v 1.4%; P < .001, respectively; at 12 months: 2.7 kg v 1.6 kg; P < .05; 2.6% v 1.6%; P < .05, respectively); 44% in the guided group and 19% in the self-guided group met the 5% goal. Body composition and behavioral changes were also greater in the interventionist-guided group at both time points. Conclusion The study supports the efficacy of a community-based interventionist-guided weight loss program targeting AABCS. Although mean weight loss did not reach the targeted 5%, the mean loss of > 3% at 6 months is associated with improved health outcomes. Affordable, accessible health promotion programs represent a critical resource for AABCS.

Obesity has been linked to cognitive impairment, cognitive decline and dementia. Given that 38.5% of U.S. adults 60years and older are obese and these numbers are rapidly increasing, strategies to decouple obesity from cognitive decline are needed. Innovative lifestyle strategies that may postpone the onset of subclinical symptoms or even arrest the transition to overt dementia in at-risk individuals are critically needed. Poor diet is central to the development of obesity and diet may affect cognition. Adherence to a Mediterranean Diet (MedDiet) is associated with reduced risk of cognitive impairment and dementia. Furthermore, weight loss through caloric restriction improves cognitive function. This paper describes the Building Research in Diet and CoGnition (BRIDGE) study, a randomized trial examining the effect of the MedDiet, with and without weight loss, on cognitive functioning in obese older adults. Obese (BMI≥30 and ≤50kg/m 2 ) older adults (≥55years) (n=180) will be randomized in a 2:2:1 allocation scheme to: Typical Diet Control; MedDiet alone, without weight loss; or MedDiet lifestyle intervention to promote weight loss and weight loss maintenance. Both MedDiet intervention groups will meet for one individual session and 27 group sessions over an 8-month period. Individuals in the control group will not receive instruction on changing lifestyle habits. Outcomes will be assessed at baseline, 8 and 14months. The primary outcome is cognitive functioning; secondary outcomes will include changes in body weight, diet, cardiovascular, metabolic, and inflammatory biomarkers., (Copyright © 2017. Published by Elsevier Inc.)

Communication among cells (also known as cross-talk) plays a prominent role in the current knowledge of the pathophysiology of cancer and of cancer-associated conditions such as paraneoplastic syndromes and cachexia that are responsible for much of cancer's morbidity and mortality. Yet, biomedical scientists lack an explicit unifying frame that places this exchange of molecular information at the core of their understanding of cancer as a systemic disease. Propaganda is a type of information that aims at misleading, a form of communication intended primarily to serve the messenger. The biased molecular cross-talk between cancer and non-cancer cells can be considered as a form of biological propaganda. I here propose cancer is a propagandist as a metaphor that may serve as a unifying frame to interpret both cancer and cancer-associated syndromes under the same communication-based concept and may thus serve to bring together research that is currently compartmentalized under separate disciplines., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Fatigue is highly prevalent after hematopoietic stem cell transplantation (HCT). It has been described as intense and may last for years following treatment., Objective: The aim of this study is to compare fatigue, physical activity, sleep, emotional distress, cognitive function, and biological measures in HCT survivors with persistent fatigue (n = 25) with age- and gender-matched healthy controls with occasional tiredness (n = 25)., Methods: Data were collected using (a) objective, real-time assessments of physical activity and sleep over 7 days; (b) patient-reported fatigue assessments; (c) computerized objective testing of cognitive functioning; and (d) biological measures. Differences between groups were examined using multivariate analysis of variance., Results: Survivors of HCT reported increased physical (P < .001), mental (P < .001), and overall (P < .001) fatigue as well as increased anxiety (P < .05) and depression (P < .01) compared with healthy controls. Red blood cell (RBC) levels were significantly lower in HCT survivors (P < .001). Levels of RBC for both groups, however, were in the normal range. Tumor necrosis factor-α (P < .001) and interleukin-6 (P < .05) levels were significantly higher in HCT survivors., Conclusions: Persistent fatigue in HCT survivors compared with healthy controls with occasional tiredness is accompanied by increased anxiety and depression along with decreased RBC counts. Elevated tumor necrosis factor-α and interleukin-6 levels may be important biomarkers., Implications for Practice: This study provides preliminary support for the conceptualization of fatigue as existing on a continuum, with tiredness anchoring one end and exhaustion the other. Persistent fatigue experienced by HCT survivors is more severe than the occasional tiredness of everyday life.

Visceral adipose tissue (VAT) but not subcutaneous adipose tissue (SAT) is associated with obesity-related diseases including colorectal cancer (CRC). Superficial SAT (SSAT) and deep SAT (DSAT), components of SAT, also appear to independently influence disease risk. These abdominal adipose tissues (AATs) are not extensively studied in connection with CRC and have not been explored in the United States despite known racial variations in body composition. We conducted a case-control study that compared associations between AAT with CRC risk and race of African-American (AA) and non-Hispanic white (NHW) men with incident CRC matched by age, body mass index, and race (N = 158, 79/group). Cross-sectional computed tomography images were used for assessment of AAT. Overall cases and controls had similar VAT areas (140 ± 192 vs 149 ± 152 cm 2 , P-value = 0.93); however, cases had lower SSAT than controls (88 ± 39 vs 112 ± 65 cm 2 , P < 0.01). Among controls, AA had significantly lower VAT (114 ± 168 vs 180 ± 167, P < 0.01) than NHW. Conditional logistic regression revealed that AA men with greater SSAT had lower odds for CRC (odds ratio [OR]: 0.24, 95% confidence interval [CI] 0.07-0.85). Our findings indicate that VAT does vary between cases and controls by race; however, this variation is not a risk factor for CRC. The negative association between CRC and SSAT in AA men warrants further investigation.

Background: Reduced fat oxidation in hypertrophied hearts coincides with a shift of carnitine palmitoyl transferase I from muscle to increased liver isoforms. Acutely increased carnitine palmitoyl transferase I in normal rodent hearts has been shown to recapitulate the reduced fat oxidation and elevated atrial natriuretic peptide message of cardiac hypertrophy., Methods and Results: Because of the potential for reduced fat oxidation to affect cardiac atrial natriuretic peptide, and thus, induce adipose lipolysis, we studied peripheral and systemic metabolism in male C57BL/6 mice model of transverse aortic constriction in which left ventricular hypertrophy occurred by 2 weeks without functional decline until 16 weeks (ejection fraction, -45.6%; fractional shortening, -22.6%). We report the first evidence for initially improved glucose tolerance and insulin sensitivity in response to 2 weeks transverse aortic constriction versus sham, linked to enhanced insulin signaling in liver and visceral adipose tissue (epididymal white adipose tissue [WAT]), reduced WAT inflammation, elevated adiponectin, mulitilocular subcutaneous adipose tissue (inguinal WAT) with upregulated oxidative/thermogenic gene expression, and downregulated lipolysis and lipogenesis genes in epididymal WAT. By 6 weeks transverse aortic constriction, the metabolic profile reversed with impaired insulin sensitivity and glucose tolerance, reduced insulin signaling in liver, epididymal WAT and heart, and downregulation of oxidative enzymes in brown adipose tissue and oxidative and lipogenic genes in inguinal WAT., Conclusions: Changes in insulin signaling, circulating natriuretic peptides and adipokines, and varied expression of adipose genes associated with altered insulin response/glucose handling and thermogenesis occurred prior to any functional decline in transverse aortic constriction hearts. The findings demonstrate multiphasic responses in extracardiac metabolism to pathogenic cardiac stress, with early iWAT browning providing potential metabolic benefits., (© 2017 American Heart Association, Inc.)

Objective: Studies were performed to uncover the significance of obesity in rheumatoid arthritis (RA) and preclinical models., Methods: Preclinical arthritis models were used to examine the impact of obesity on disease onset and remission. Conditioned media from RA adipose tissues were used to investigate the mechanism contributing to joint neutrophil influx and M1 macrophage differentiation observed in early and remission phases of arthritis., Results: We report that mice fed with high fat diet (HFD) have an earlier onset of collagen-induced arthritis (CIA) compared with mice on regular diet. However, the differences in CIA joint swelling between the two diet groups are lost once disease is established. We found that early arthritis triggered by obesity is due to elevated joint MIP2/interleukin-8 levels detected in CIA as well as in the RA and mouse adipose tissues and the effect of this chemokine on neutrophil recruitment. Although active disease progression is similarly affected in both diet groups, arthritis resolution is accelerated in lean mice while joint inflammation is sustained in obese mice. We document that HFD can prolong toll-like receptor (TLR)4-induced arthritis by increasing joint monocyte migration and further remodelling the recruited cells into M1 macrophages. Consistently, we show that adipose condition media can transform RA and wild-type naïve myeloid cells into M1 macrophages; however, this function is impaired by TLR4 blockade or deficiency., Conclusions: We conclude that despite established disease being unaffected by obesity, the early and the resolution phases of RA are impacted by obesity through different mechanisms., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Gestational weight gain (GWG) is an important modifiable factor known to influence fetal outcomes including birth weight and adiposity. Unlike behaviors such as smoking and alcohol consumption, the effect of GWG throughout pregnancy on fetal development and other outcomes has not been extensively studied. The aim of this study was to investigate the relationship of GWG with endocrine factors such as adiponectin, leptin, and C-reactive protein which may be associated with inflammatory response, fetal growth, and adiposity later in life. Data were obtained from the Ulm Birth Cohort Study (UBCS) and the Ulm SPATZ Health Study, two methodologically similar birth cohort studies including newborns and their mothers recruited from 11/2000-11/2001 and 04/2012-05/2013. In the two included birth cohorts we consistently observed statistically significant positive associations between GWG beginning as early as the second trimester with fetal cord blood leptin and stronger association beginning as early as the first trimester with post-delivery maternal serum leptin. Total weight gain exceeding commonly accepted recommended guidelines was consistently associated with higher leptin levels in both cord blood and post-delivery maternal serum. These results suggest a potential pathomechanistic link between fetal environment and surrogate markers of long-term health., Competing Interests: The authors declare no competing financial interests.

Background: Our trial INTACT (Intensive Nutrition in Acute Lung Injury Trial) was designed to compare the impact of feeding from acute lung injury (ALI) diagnosis to hospital discharge, an interval that, to our knowledge, has not yet been explored. It was stopped early because participants who were randomly assigned to energy intakes at nationally recommended amounts via intensive medical nutrition therapy experienced significantly higher mortality hazards than did those assigned to standard nutrition support care that provided energy at 55% of recommended concentrations., Objective: We assessed the influence of dose and timing of feeding on hospital mortality., Design: Participants (n = 78) were dichotomized as died or discharged alive. Associations between the energy and protein received overall, early (days 1-7), and late (days ≥8) and the hazards of hospital mortality were evaluated between groups with multivariable analysis methods., Results: Higher overall energy intake predicted significantly higher mortality (OR: 1.14, 95% CI: 1.02, 1.27). Among participants enrolled for ≥8 d (n = 66), higher early energy intake significantly increased the HR for mortality (HR: 1.17, 95% CI: 1.07, 1.28), whereas higher late energy intake was significantly protective (HR: 0.91, 95% CI: 0.83, 1.0). Results were similar for early but not late protein (grams per kilogram) exposure (early-exposure HR: 8.9, 95% CI: 2.3, 34.3; late-exposure HR: 0.15, 95% CI: 0.02, 1.1). Threshold analyses indicated early mean intakes ≥18 kcal/kg significantly increased subsequent mortality., Conclusions: Providing kilocalories per kilogram or grams of protein per kilogram early post-ALI diagnosis at recommended levels was associated with significantly higher hazards for mortality, whereas higher late energy intakes reduced mortality hazards. This time-varying effect violated the Cox proportionality assumption, indicating that feeding trials in similar populations should extend beyond 7 d and use time-varying statistical methods. Future trials are required for corroboration. INTACT was registered at clinicaltrials.gov as NCT01921101., (© 2017 American Society for Nutrition.)

Purpose: To evaluate the association of galectin-3 (Gal3) with obesity and inflammatory status in a cohort of metabolically healthy, predominantly African-American women with varying cardiovascular disease (CVD) risk as determined by CRP levels., Methods: We assessed the association between BMI and serum levels of Gal3, IL-6, CRP, and adiponectin in metabolically healthy women (N = 97) to determine the overall association between Gal3, obesity, and inflammation in groups at different CVD risk., Results: Obese women had significantly higher serum Gal3 compared to non-obese participants (P = 0.0016), although Gal3 levels were comparable among different classes of obesity. BMI (R 2  = 0.1406, P = 0.0013), IL-6 (R 2  = 0.0689, P = 0.035), and CRP (R 2  = 0.0468, P = 0.0419), but not adiponectin, positively predicted the variance of Gal3 levels in the total study population. However, the predicting effect of BMI (R 2  = 0.2923, P = 0.0125) and inflammation (R 2  = 0.3138, P = 0.038) on Gal3 was only present in women at low/moderate risk of CVD (CRP ≤ 3 µg/mL)., Conclusions: Gal3 is positively correlated with obesity and inflammation in women, while the presence of elevated CVD risk may disturb the strength of Gal3 as a biomarker of inflammation.

Background: Physical education (PE) can be considered an instrument for active lifestyle promotion, and PE teachers can motivate youths to continue their studies in the field of Movement Sciences (MS)., Methods: To evaluate the role of PE in higher secondary school in promoting physical activity (PA) and MS careers, previous PE experiences and current PA practice were investigated in a sample of Italian freshmen enrolled in different university degree courses., Results: A total of 7033 questionnaires were completed by students from 14 universities (41.3% males, mean age 20 ± 2.76 years). Recreation seemed to be the principal aim (42.2%) pursued during PE lessons, which are based mainly on practical activities (51.7%). Of all respondents, 67.2% were satisfied with the PE received during higher secondary school, and 51.6% participated in extracurricular PA. Current practice of PA was reported by 58.1% of the sample. Extracurricular activities were associated with choice of MS curricula (odds ratio: 2.15; 95% confidence interval, 1.85-2.50) and with current practice of PA (odds ratio: 1.68, 95% confidence interval, 1.51-1.87). Geographical differences concerning lessons organization and satisfaction were registered (P < .01)., Conclusions: To enhance its role in health promotion, PE teaching should be improved by increasing the time allocated to PE and by strengthening the provision of school-based extracurricular PA.

Objective: Insulin signaling plays pivotal roles in the development and metabolism of many tissues and cell types. A previous study demonstrated that ablation of insulin receptor (IR) with aP2-Cre markedly reduced adipose tissues mass and protected mice from obesity. However, multiple studies have demonstrated widespread non-adipocyte recombination of floxed alleles in aP2-Cre mice. These findings underscore the need to re-evaluate the role of IR in adipocyte and systemic metabolism with a more adipose tissue-specific Cre mouse line., Methods: We generated and phenotyped a new adipose tissue-specific IR mouse model using the adipose tissue-specific Adipoq-Cre line., Results: Here we show that the Adipoq-Cre-mediated IR KO in mice leads to lipodystrophy and metabolic dysfunction, which is in stark contrast to the previous study. In contrast to white adipocytes, absence of insulin signaling does not affect development of marrow and brown adipocytes, but instead is required for lipid accumulation particularly for the marrow adipocytes. Lipodystrophic IR KO mice have profound insulin resistance, hyperglycemia, organomegaly, and impaired adipokine secretion., Conclusions: Our results demonstrate differential roles for insulin signaling for white, brown, and marrow adipocyte development and metabolic regulation.

We introduce an innovative numerical technique based on convex optimization to solve a range of infinite-dimensional variational problems arising from the application of the background method to fluid flows. In contrast to most existing schemes, we do not consider the Euler-Lagrange equations for the minimizer. Instead, we use series expansions to formulate a finite-dimensional semidefinite program (SDP) whose solution converges to that of the original variational problem. Our formulation accounts for the influence of all modes in the expansion, and the feasible set of the SDP corresponds to a subset of the feasible set of the original problem. Moreover, SDPs can be easily formulated when the fluid is subject to imposed boundary fluxes, which pose a challenge for the traditional methods. We apply this technique to compute rigorous and near-optimal upper bounds on the dissipation coefficient for flows driven by a surface stress. We improve previous analytical bounds by more than 10 times and show that the bounds become independent of the domain aspect ratio in the limit of vanishing viscosity. We also confirm that the dissipation properties of stress-driven flows are similar to those of flows subject to a body force localized in a narrow layer near the surface. Finally, we show that SDP relaxations are an efficient method to investigate the energy stability of laminar flows driven by a surface stress.

Background: Breast cancer survival rates are significantly lower among African-American women compared to white women. In addition, African-American women with breast cancer are more likely than white women to die from co-morbid conditions. Obesity is common among African-American women, and it contributes to breast cancer progression and the development and exacerbation of many weight-related conditions. Intervening upon obesity may decrease breast cancer and all-cause mortality among African-American breast cancer survivors., Methods/design: Moving Forward is a weight loss intervention being evaluated in a randomized trial with a projected sample of 240 African American breast cancer survivors. Outcomes include body mass index, body composition, waist:hip ratio, and behavioral, psychosocial and physiological measures. Survivors are randomized to either a 6-month guided weight loss intervention that involves twice weekly classes and text messaging or a self-guided weight loss intervention based on the same materials offered in the guided program. The guided intervention is being conducted in partnership with the Chicago Park District at park facilities in predominantly African-American neighborhoods in Chicago. Recruitment strategies include direct contact to women identified in hospital cancer registries, as well as community-based efforts. Data collection occurs at baseline, post-intervention (6 months) and at a 12-month follow-up., Discussion: This study evaluates a community-based, guided lifestyle intervention designed to improve the health of African-American breast cancer survivors. Few studies have addressed behavioral interventions in this high-risk population. If successful, the intervention may help reduce the risk for breast cancer recurrence, secondary cancers, and co-morbid conditions, as well as improve quality of life., Trial Registration: U.S. Clinicaltrials.gov number: NCT02482506, April 2015.

Objective: In this study, the associations between vitamin D, insulin sensitivity, and inflammation and their relationships with adipose tissue expression of vitamin D receptor (VDR) and inflammatory markers in women with morbid obesity were determined., Methods: An oral glucose tolerance test prior to surgery was completed by healthy premenopausal women (n = 76) seeking bariatric surgery. Abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were collected during surgery., Results: Approximately, 70% of our subjects were vitamin D sufficient or optimal, and 80% had normal glucose tolerance. No significant association between serum 25-hydroxyvitamin D [25(OH)D] with circulating inflammatory markers or insulin sensitivity was identified. In subjects with waist circumference of <139 cm (n = 42), log25(OH)D positively predicted VAT logIL-6 mRNA expression (P = 0.003). LogVDR expression was positively correlated with the expression of inflammatory markers in both SAT (logIL-1β mRNA: r = 0.95, P < 0.0001; logTNF mRNA: r = 0.82, P < 0.0001) and VAT (logIL-1β mRNA: r = 0.89, P < 0.0001; logTNF mRNA: r = 0.75, P < 0.0001). VAT logVDR expression positively predicted logHOMA-IR in non-African American subjects (P = 0.05)., Conclusions: The beneficial effects of vitamin D on inflammation and insulin sensitivity were not supported by our findings. VDR does not appear to possess a protective effect in adipose tissue., (© 2015 The Obesity Society.)

Background: Exposure to persistent organic pollutants (POPs) is associated with increased diabetes risk, although the mechanism of action is not well delineated., Methods: We investigated established diabetes biomarkers that could implicate potential mechanistic pathways, including C-reactive protein (CRP), a marker of systemic inflammation; gamma glutamyl transferase (GGT), a liver enzyme associated with oxidative stress; and adiponectin, an adipokine modulating glucose regulation and fatty acid oxidation. These biomarkers as well as hemoglobin A1c (HA1c), and POPs [polychlorinated biphenyls (PCBs), p,p-dichlorodiphenyldichloroethylene (DDE) and polybrominated diphenyl ethers (PBDEs)] were measured in a cohort of Great Lakes sport caught fish (GLSCF) consumers. We examined associations of POPs and fish consumption with HA1c and incident diabetes, and evaluated mediation and moderation by the diabetes biomarkers., Results: Odds of incident diabetes were elevated with exposure to DDE and PCBs. DDE and PCB 118 were positively, and fish meals were inversely, associated with HA1c. CRP was inversely associated with saltwater and total fish meals, particularly in persons with higher adiposity, but did not mediate the associations of fish meals with HA1c. There were few associations of POPs with adiponectin, CRP and GGT, with the exception of positive associations of PCB 118 with GGT, PBDEs with GGT in older persons, and PBDEs with adiponectin. Adiponectin, CRP and GGT did not mediate associations of DDE and PCBs with HA1c or incident diabetes. However, the association of DDE with HA1c was stronger in persons with higher CRP, GGT and BMI, and lower adiponectin, while the association of PCB 118 with HA1c was stronger in persons with higher GGT., Conclusions: These findings suggest that adiponectin, CRP and GGT did not mediate effects of POPs on diabetes or HA1c. However, POPs may have stronger effects on blood glucose in persons at higher risk for diabetes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Despite extensive use of enteral (EN) and parenteral nutrition (PN) in intensive care unit (ICU) populations for 4 decades, evidence to support their efficacy is extremely limited., Methods: A prospective randomized trial was conducted evaluate the impact on outcomes of intensive medical nutrition therapy (IMNT; provision of >75% of estimated energy and protein needs per day via EN and adequate oral diet) from diagnosis of acute lung injury (ALI) to hospital discharge compared with standard nutrition support care (SNSC; standard EN and ad lib feeding). The primary outcome was infections; secondary outcomes included number of days on mechanical ventilation, in the ICU, and in the hospital and mortality., Results: Overall, 78 patients (40 IMNT and 38 SNSC) were recruited. No significant differences between groups for age, body mass index, disease severity, white blood cell count, glucose, C-reactive protein, energy or protein needs occurred. The IMNT group received significantly higher percentage of estimated energy (84.7% vs 55.4%, P < .0001) and protein needs (76.1 vs 54.4%, P < .0001) per day compared with SNSC. No differences occurred in length of mechanical ventilation, hospital or ICU stay, or infections. The trial was stopped early because of significantly greater hospital mortality in IMNT vs SNSC (40% vs 16%, P = .02). Cox proportional hazards models indicated the hazard of death in the IMNT group was 5.67 times higher (P = .001) than in the SNSC group., Conclusions: Provision of IMNT from ALI diagnosis to hospital discharge increases mortality., (© 2014 American Society for Parenteral and Enteral Nutrition.)

Acute pancreatitis (AP), although most often a mild and self-limiting inflammatory disease, worsens to a characteristically necrotic severe acute pancreatitis (SAP) in about 20% of cases. Obesity, affecting more than one-third of American adults, is a risk factor for the development of SAP, but the exact mechanism of this association has not been identified. Coincidental with chronic low-grade inflammation, activation of the nucleotide-binding domain, leucine-rich containing family, pyrin-domain containing 3 (NLRP3) inflammasome increases with obesity. Lean mice genetically deficient in specific components of the NLRP3 inflammasome are protected from experimentally induced AP, indicating a direct involvement of this pathway in AP pathophysiology. We hypothesized that inhibition of the NLRP3 inflammasome with the sulfonylurea drug glyburide would reduce disease severity in obese mice with cerulein-induced SAP. Treatment with glyburide led to significantly reduced relative pancreatic mass and water content and less pancreatic damage and cell death in genetically obese ob/ob mice with SAP compared with vehicle-treated obese SAP mice. Glyburide administration in ob/ob mice with cerulein-induced SAP also resulted in significantly reduced serum levels of interleukin 6, lipase, and amylase and led to lower production of lipopolysaccharide-stimulated interleukin 1β release in cultured peritoneal cells, compared with vehicle-treated ob/ob mice with SAP. Together, these data indicate involvement of the NLRP3 inflammasome in obesity-associated SAP and expose the possible utility of its inhibition in prevention or treatment of SAP in obese individuals., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Currently, there is no therapy for severe acute pancreatitis (AP) except for supportive care. The lipase inhibitor orlistat, the peroxisome proliferator-activated receptor γ agonist rosiglitazone, and the chemokine receptor 2 antagonists attenuate the severity of AP in rodents if administered before or at the time of induction of pancreatitis. However, it is unknown whether these treatments are effective if administered therapeutically after induction of pancreatitis., Methods: Male C57BL6 mice with diet-induced obesity received 2 injections of mrIL-12 (150 ng per mouse) and mrIL-18 (750 ng per mouse) intraperitoneally at 24-hour intervals. The mice were injected 2, 24, and 48 hours after the second injection of IL-12 + IL-18 with orlistat (2 mg per mouse), rosiglitazone (0.4 mg per mouse), RS102895 (0.3 mg per mouse), or vehicle (20 μL of DMSO and 80 μL of canola oil) and euthanized after 72 hours., Results: Orlistat decreased intra-abdominal fat necrosis compared with vehicle (P < 0.05). However, none of the drug treatments produced significant decreases in pancreatic edema, acinar necrosis, or intrapancreatic fat necrosis., Conclusions: Drugs previously shown to improve the severity of AP when given before or at the time of induction of pancreatitis failed to do so when administered therapeutically in the IL-12 + IL-18 model.

Serum samples from 74 obese women were assayed for 25-hydroxyvitamin D [25(OH)D] concentrations using an automated immunoassay [Architect (Abbott)] and ELISA (Alpco Diagnostics), and results were compared with the LC/MS/MS reference method (Quest Diagnostics). The Architect values were significantly lower (mean difference: -13 nmol/L; 95% limits: -54; 28 nmol/L) and the ELISA values were significantly higher (mean difference: 24 nmol/L; 95% limits: -36; 84 nmol/L) than the LC/MSIMS values. The slope of the Passing-Bablok regression line relative to LC/MSIMS was 0.5 [95% confidence interval (CI): 0.41; 0.60] and 1.17 (95% CI: 0.87; 1.56) for Architect and ELISA, respectively, with an intercept of approximately 16 for both assays. Using 50 nmol/L as the cut-point for deficiency, Architect and ELISA misclassified 20 and 27% of the subjects, respectively. In subjects with low circulating 25-hydroxylated ergocalciferol [25(OH)D2] (<10 nmol/L), a Bland-Altman plot and Kappa statistics (Kappa = 0.73; 95% CI: 0.49-0.97) showed good agreement between Architect and LC/MS/MS. However, in subjects with high circulating 25(OH)D2 (>or=10 nmol/L), Architect demonstrated poor agreement (Kappa = 0.40; 95% CI: 0.16-0.65). ELISA demonstrated a higher degree of overestimation in women with minimal 25(OH)D2 than those with high 25(OH)D2, suggesting that ELISA overestimates 25-hydroxylated cholecalciferol [25(OH)D3] but underestimates 25(OH)D2.

Background: Increased cellular iron exposure is associated with colorectal cancer (CRC) risk. Hepcidin, a liver peptide hormone, acts as the primary regulator of systemic iron status by blocking iron release from enterocytes into plasma. Concentrations are decreased during low iron status and increased during inflammation. The role of hepcidin and the factors influencing its regulation in CRC remains largely unknown. This study explored systemic and tumor level iron regulation in men with CRC., Methods: The participants were 20 CRC cases and 20 healthy control subjects. Colonic tissue (adenocarcinoma [cases] healthy mucosa [controls]) was subjected to quantitative PCR (hepcidin, iron transporters and IL-6) and Perls' iron staining. Serum was analyzed using ELISA for hepcidin, iron status (sTfR) and inflammatory markers (CRP, IL-6, TNF-α). Anthropometrics, dietary iron intake and medical history were obtained., Results: Cases and controls were similar in demographics, medication use and dietary iron intake. Systemically, cases compared to controls had lower iron status (sTfR: 21.6 vs 11.8 nmol/L, p < 0.05) and higher marker of inflammation (CRP: 8.3 vs 3.4 μg/mL, p < 0.05). Serum hepcidin was mildly decreased in cases compared to controls; however, it was within the normal range for both groups. Within colonic tissue, 30% of cases (6/20) presented iron accumulation compared to 5% of controls (1/20) (χ(2) = 5.0; p < 0.05) and higher marker of inflammation (IL-6: 9.4-fold higher compared to controls, p < 0.05). Presence of adenocarcinoma iron accumulation was associated with higher serum hepcidin (iron accumulation group 80.8 vs iron absence group 22.0 ng/mL, p < 0.05)., Conclusions: While CRC subjects had serum hepcidin concentrations in the normal range, it was higher given their degree of iron restriction. Inappropriately elevated serum hepcidin may reduce duodenal iron absorption and further increase colonic adenocarcinoma iron exposure. Future clinical studies need to assess the appropriateness of dietary iron intake or iron supplementation in patients with CRC.

Production of Annexin A1 (ANXA1), a protein that mediates the anti-inflammatory action of glucocorticoids, is altered in obesity, but its role in modulation of adiposity has not yet been investigated. The objective of this study was to investigate modulation of ANXA1 in adipose tissue in murine models of obesity and to study the involvement of ANXA1 in diet-induced obesity in mice. Significant induction of ANXA1 mRNA was observed in adipose tissue of both C57BL6 and Balb/c mice with high fat diet (HFD)-induced obesity versus mice on chow diet. Upregulation of ANXA1 mRNA was independent of leptin or IL-6, as demonstrated by use of leptin-deficient ob/ob mice and IL-6 KO mice. Compared to WT mice, female Balb/c ANXA1 KO mice on HFD had increased adiposity, as indicated by significantly elevated body weight, fat mass, leptin levels, and adipocyte size. Whereas Balb/c WT mice upregulated expression of enzymes involved in the lipolytic pathway in response to HFD, this response was absent in ANXA1 KO mice. A significant increase in fasting glucose and insulin levels as well as development of insulin resistance was observed in ANXA1 KO mice on HFD compared to WT mice. Elevated plasma corticosterone levels and blunted downregulation of 11-beta hydroxysteroid dehydrogenase type 1 in adipose tissue was observed in ANXA1 KO mice compared to diet-matched WT mice. However, no differences between WT and KO mice on either chow or HFD were observed in expression of markers of adipose tissue inflammation. These data indicate that ANXA1 is an important modulator of adiposity in mice, with female ANXA1 KO mice on Balb/c background being more susceptible to weight gain and diet-induced insulin resistance compared to WT mice, without significant changes in inflammation.