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Skeletal muscle energy production is influenced by both lean body mass and adipose tissue but the effect of their distribution on energy metabolism is unclear. This study examined variations in quadriceps muscle energy metabolism in healthy adults with varied relative amounts of lean and adipose tissue. Results suggest increased adiposity is associated with reduced muscle energetic efficiency with more reliance on glycolysis, and when accompanied with reduced lean mass, is associated with reduced maximum oxidative capacity.

Chronic inflammation has been implicated in the pathophysiology of major depressive disorder (MDD). Activating the resolution of inflammation through ω-3 fatty acid supplementation may prove to be a successful therapeutic strategy for the treatment of MDD. Patients with MDD, body mass index >25 kg/m2, and plasma high-sensitivity C-reactive protein ≥3 μg/mL (n = 61) were enrolled in a 12-week randomized trial consisting of 4 parallel arms: EPA 1, 2, and 4 g/d, and placebo. The supplement contained EPA and DHA in a 3.9:1 ratio. Depression symptoms were assessed using the IDS-C30 scale. Plasma fatty acids and pro-resolving lipid mediators (SPMs) were measured in 42 study completers at baseline and at the end of treatment by liquid chromatography/mass spectrometry. The response rate (≥50% reduction in IDS-30 score) was higher in the 4 g/d EPA arm than placebo (Cohen d = 0.53). In the 4 g/d EPA arm, responders had significantly greater increases in 18-hydroxyeicosapentaenoic acid (18-HEPE) and 13-hydroxydocosahexaenoic acid (13-HDHA) than non-responders (p p p

The gut microbiome may be both helpful and harmful, and not only is it affected by diet, it has also been shown to affect mental health including personality, mood, anxiety and depression. In this clinical study we assessed dietary nutrient composition, mood, happiness, and the gut microbiome in order to understand the role of diet in the gut microbiome and how that affects mood and happiness. For this pilot study, we enrolled 20 adults to follow this protocol: recording a 2-day food log, sampling their gut microbiome, and completing five validated surveys of mental health, mood, happiness and well-being, followed by a minimum 1 week diet change and repeating the food log, microbiome sampling and the 5 surveys. The change from a predominantly Western diet to vegetarian, Mediterranean and ketogenic diets led to changes in calorie and fiber intake. After the diet change, we observed significant changes in measures of anxiety, well-being and happiness, and without changes in gut microbiome diversity. We found strong correlations between greater consumption of fat and protein to lower anxiety and depression, while consuming higher percentages of carbohydrates was associated with increased stress, anxiety, and depression. We also found strong negative correlations between total calories and total fiber intake with gut microbiome diversity without correlations to measures of mental health, mood or happiness. We have shown that changing diet affects mood and happiness, that greater fat and carbohydrate intake is directly associated with anxiety and depression and inversely correlated with gut microbiome diversity. This study is an important step towards understanding how our diet affects the gut microbiome and in turn our mood, happiness and mental health.

Background/Objectives: Thiamine plays a pivotal role in energy metabolism. The aim of the study was to determine serial whole blood TPP concentrations in critically ill patients receiving chronic diuretic treatment before ICU admission and to correlate TPP levels with clinically determined serum phosphorus concentrations. Subjects/Methods: This observational study was performed in 15 medical ICUs. Serial whole blood TPP concentrations were measured by HPLC at baseline and at days 2, 5 and 10 after ICU admission. Results: A total of 221 participants were included. Of these, 18% demonstrated low TPP concentrations upon admission to the ICU, while 26% of participants demonstrated low levels at some point during the 10-day study period. Hypophosphatemia was detected in 30% of participants at some point during the 10-day period of observation. TPP levels were significantly and positively correlated with serum phosphorus levels at each time point (P < 0.05 for all). Conclusions: Our results show that 18% of these critically ill patients exhibited low whole blood TPP concentrations on ICU admission and 26% had low levels during the initial 10 ICU days, respectively. The modest correlation between TPP and phosphorus concentrations suggests a possible association due to a refeeding effect in ICU patients requiring chronic diuretic therapy. © 2023 Elsevier Inc.

Objective Calcium is an essential mineral involved in the functioning of nearly every human cell. Calcium levels are regulated by dietary absorption, vitamin D status, and parathyroid hormone (PTH). This report describes a patient in whom childhood bowel resection and partial gastrectomy resulted in malabsorptive hypocalcemia in adulthood. Case Report A 21-year-old man presented with syncope and a fall resulting in a right femoral neck fracture. His medical history included small bowel obstructions at age 9 requiring bowel resection, and at age 12 with gastric perforation and partial gastrectomy. Laboratory values showed calcium level of 4.9 mg/dL (8.9-10.3 mg/dL). PTH level was 273 pg/mL (12.0-88.0 pg/mL), 25-hydroxy-vitamin D was 28 ng/dL (30-100 ng/mL), and 1,25-dihydroxy-vitamin D was 54 pg/dL (18-72 pg/mL). Furthermore, magnesium and phosphorus levels were 2.1 mg/dL (1.5-2.6 mg/dL) and 4.4 mg/dL (2.4-4.7 mg/dL), respectively. Calcium levels improved to 9.5 mg/dL on 10% calcium gluconate drip but could not be maintained above 7 mg/dL on oral calcium carbonate supplementation, despite doses as high as 3750 mg three times daily with calcitriol 0.75 mcg twice daily. After switching from calcium carbonate to calcium citrate 3500 mg three times daily, the calcium level improved and was maintained between 8.3 and 9.0 mg/dL. Discussion High calcium needs, other nutrient deficiencies, and response to calcium citrate versus calcium carbonate suggest malabsorption from achlorhydria and small bowel resection. Conclusion This case emphasizes the gastrointestinal physiology in calcium homeostasis and highlights the recognition of hypocalcemia as a complication of gastric and bowel resection.

Choline is an essential nutrient for brain development and function that is attained through high-protein foods, which are limited in the phenylalanine-restricted diet of people with phenylketonuria (PKU). This study compared choline consumption among individuals with PKU to a reference sample from the National Health and Nutrition Examination Survey (NHANES), and identified treatment and diet-related factors that may modulate choline needs. Participants were individuals with PKU (n = 120, 4–61 years) managed with dietary therapy alone (n = 49), sapropterin dihydrochloride for ≥1 year (n = 38), or pegvaliase for ≥1 year with no medical food (n = 33). NHANES participants were not pregnant or nursing and came from the 2015–2018 cycles (n = 10,681, 4–70 years). Dietary intake data were used to estimate total usual intake distributions for choline, and mean probability of adequacy (MPA) was calculated as a summary index of nutrient adequacy for four methyl-donor/co-factor nutrients that impact choline utilization (folate, vitamin B12, vitamin B6, and methionine). Only 10.8% (SE: 2.98) of the total PKU sample (14.7% [SE: 4.03] of children; 6.8% [SE: 2.89] of adults) achieved the adequate intake (AI) for choline, while 12.2% (SE:0.79) of the NHANES sample met the recommended level. Adults receiving pegvaliase were the most likely to exceed the AI for choline (14.82% [SE: 4.48]), while adults who were on diet therapy alone were the least likely (5.59% [SE: 2.95]). Without fortified medical foods, individuals on diet therapy and sapropterin would not be able to achieve the AI, and MPA for other methyl donor/co-factor nutrients would be reduced. More frequent monitoring of choline intake and increased choline fortification of medical foods could benefit this population.

Correction of nutritional vitamin deficiency is recommended in children with chronic kidney disease (CKD). The optimal daily dose of vitamin D to achieve or maintain vitamin D sufficiency is unknown. We conducted a phase III, double-blind, randomized trial of two doses of vitamin D3 in children ≥ 9 years of age with CKD stages 3–5 or kidney transplant recipients. Patients were randomized to 1000 IU or 4000 IU of daily vitamin D3 orally. We measured 25-hydroxvitamin D (25(OH)D) levels at baseline, 3 months and 6 months. The primary efficacy outcome was the percentage of patients who were vitamin D replete (25(OH)D ≥ 30 ng/mL) at 6 months. Ninety-eight patients were enrolled: 49 randomized into each group. Eighty (81.6%) patients completed the study and were analyzed. Baseline plasma 25(OH)D levels were ≥ 30 ng/mL in 12 (35.3%) and 12 (27.3%) patients in the 1000 IU and 4000 IU treatment groups, respectively. At 6 months, plasma 25(OH)D levels were ≥ 30 ng/mL in 33.3% (95% CI: 18.0–51.8%) and 74.4% (95% CI: 58.8–86.5%) in the 1000 IU and 4000 IU treatment groups, respectively (p = 0.0008). None of the patients developed vitamin D toxicity or hypercalcemia. In children with CKD, 1000 IU of daily vitamin D3 is unlikely to achieve or maintain a plasma 25(OH)D ≥ 30 ng/mL. In children with CKD stages 3–5, a dose of vitamin D3 4000 IU daily was effective in achieving or maintaining vitamin D sufficiency. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT01909115

High resolution of NMR spectroscopic data of biosamples are a rich source of information on the metabolic response to physiological variation or pathological events. There are many advantages of NMR techniques such as the sample preparation is fast, simple and non-invasive. Statistical analysis of NMR spectra usually focuses on differential expression of large resonance intensity corresponding to abundant metabolites and involves several data preprocessing steps. In this paper we estimate functional components of spectra and test their significance using multiscale techniques. We also ex- plore scaling in NMR spectra and use the systematic variability of scaling descriptors to predict the level of cysteine, an important precursor of glu- tathione, a control antioxidant in human body. This is motivated by high cost (in time and resources) of traditional methods for assessing cysteine level by high performance liquid chromatograph (HPLC).

Individuals experiencing socioeconomic deprivation consistently demonstrate poorer physical and mental health. Income alone is inadequate as a measure of socioeconomic status (SES); a better measure for assessing the deprivation status of individuals is needed.The New Zealand Index of Socioeconomic Deprivation for Individuals, a validated, eight-item measure of deprivation, was modified to create the United States Index of Socioeconomic Deprivation for Individuals (USiDep). The questionnaire was administered to patients with major depressive disorder participating in two clinical trials. Spearman's correlation coefficients evaluated associations between USiDep scores with income and other measures associated with deprivation.The USiDep was completed by 118 participants, demonstrating adequate internal consistency (Crohnbach's alpha = 0.766) and strong item-total correlations. USiDep scores were moderately correlated with past-year personal income (Spearman's rho = -0.362, p.001) and several other measures related to deprivation, including body mass index, level of education, quality of life, severity of childhood traumatic events, self-reported physical health, and negative life events. Patients scoring 5 on the USiDep (the highest possible score, indicating greater deprivation) had significantly lower rates of remission after 12 weeks of treatment than those scoring ≤ 4 (1/12, 8.3% vs 40/98, 40.8%, respectively, p = .03), whereas the lowest income group showed no significant associations with outcomes.The USiDep is a valid, brief questionnaire for assessing SES that has utility for clinical research and may serve as a predictor of treatment outcomes in clinical trials. Validation of the USiDep in healthy controls and other medically and psychiatrically ill populations is warranted.

Hospitalized, malnourished older adults with chronic obstructive pulmonary disease (COPD) have an elevated risk of readmission and mortality.Post-hoc, sub-group analysis from the NOURISH study cohort examined the effect of a high-protein oral nutritional supplement (ONS) containing HMB (HP-HMB) in malnourished, hospitalized older adults with COPD and to identify predictors of outcomes.The NOURISH study (n = 652) was a multicenter, randomized, placebo-controlled, double-blind trial. The COPD subgroup (n = 214) included hospitalized, malnourished (based on Subjective Global Assessment), older adults (≥65 y), with admission diagnosis of COPD who received either standard-of-care plus HP-HMB (n = 109) or standard-of-care and a placebo supplement (n = 105) prescribed 2 servings/day from within 3 days of hospital admission (baseline) and up to 90 days after discharge. The primary study outcome was a composite endpoint of incidence of death or non-elective readmission up to 90-day post-discharge, while secondary endpoints included changes in hand-grip strength, body weight, and nutritional biomarkers over time. Categorical outcomes were analyzed using Cochran-Mantel-Haenszel tests, longitudinal data by repeated measures analysis of covariance; and changes from baseline by analysis of covariance. p-values ≤ 0.05 were considered statistically significant. Multivariate logistic regression was used to model predictors of the primary outcome and components.In patients with COPD, 30, 60, and 90-day hospital readmission rate did not differ, but in contrast, 30, 60, and 90-day mortality risk was approximately 71% lower with HP-HMB supplementation relative to placebo (1.83%, 2.75%, 2.75% vs. 6.67%, 9.52% and 10.48%, p = 0.0395, 0.0193, 0.0113, resp.). In patients with COPD, compared to placebo, intake of HP-HMB resulted in a significant increase in handgrip strength (+1.56 kg vs. -0.34 kg, p = 0.0413) from discharge to day 30; increased body weight from baseline to hospital discharge (0.66 kg vs. -0.01 kg, p 0.05) and, improvements in blood nutritional biomarker concentrations. The multivariate logistic regression predictors of the death, readmission or composite endpoints in these COPD patients showed that participants who were severely malnourished (p = 0.0191) and had a Glasgow prognostic score (GPS) Score of 1 or 2 had statistically significant odds of readmission or death (p = 0.0227).Among malnourished, hospitalized patients with COPD, supplementation with HP-HMB was associated with a markedly decreased mortality risk, and improved handgrip strength, body weight, and nutritional biomarkers within a 90-day period after hospital discharge. This post-hoc, subgroup analysis highlights the importance of early identification of nutritional risk and administration of high-protein ONS in older, malnourished patients with COPD after hospital admission and continuing after hospital discharge.

To provide a foundation for mentoring, junior faculty participated in a mentor training workshop informed by the Mentoring Clinical and Translational Researchers curriculum. The goal was to develop skills and behaviors that engender more rewarding and inclusive mentoring practices. Attendees responded to baseline and follow-up surveys assessing perceived mentoring skills. Follow-up surveys included closed- and open-ended questions about the value and satisfaction of the training, and intended behavior changes. Junior faculty respondents (n = 39) reported significantly higher overall mentoring skills after the training (t = −2.6, p = 0.012) with a medium effect size (Cohen’s D = 0.59). Domains with statistically significant improvement from baseline to follow-up included aligning mentor–mentee expectations and assessing understanding. Thirty-eighty (97%) found the training valuable, and 32 (82%) indicated they would change mentoring-related behaviors because of the training. Intended behavior changes described in open-ended responses aligned with mentoring skills assessed (e.g., aligning expectations). An additional competency domain of evaluating mentoring relationships was also described. A mentor training workshop for junior faculty appeared to contribute to changes in mentoring skills and intended behaviors. Mentor training has the potential to enhance mentorship, which is critical to strengthening a diverse pipeline of clinical and translational science researchers.

Background Individuals with cystic fibrosis (CF) have difficulty maintaining optimal vitamin D status due to pancreatic insufficiency-induced malabsorption, inadequate sunlight exposure, and poor intake of vitamin D containing foods. Vitamin D deficiency may increase the risk of pulmonary exacerbations of CF. The objective of this study was to assess factors impacting vitamin D status in patients with CF recently hospitalized for a pulmonary exacerbation of CF. Methods This was a pre-planned analysis of vitamin D intake in patients enrolled in a multi-center, double-blind, randomized controlled study examining vitamin D therapy for pulmonary exacerbation of CF. Demographic information, responses from a habitual sun exposure questionnaire and food frequency questionnaire, and vitamin D supplement usage were queried and compared to serum 25-hydroxyvitamin D (25(OH)D) concentrations. Results A total of 48 subjects were included in this analysis. Subjects were taking approximately 1,200 IU of vitamin D daily. Reported vitamin D intake, age, race, employment, and education were not significantly associated with vitamin D status in this population. However, smoking status, sunlight exposure in the last 3 years, and skin type (in the bivariate model) were all significantly associated with vitamin D status (all p Conclusions Sunlight exposure was the most predictive determinant of vitamin D status in patients with CF prior to pulmonary exacerbation. Subjects reported vitamin D intake below the recommended amounts. The role and mode of optimizing vitamin D status prior to a pulmonary exacerbation needs further investigation.

Background Adiposity and mitochondrial dysfunction are related factors contributing to metabolic disease development. This pilot study examined whether in vivo and ex vivo indices of mitochondrial metabolism were differentially associated with body composition in males and females. Methods Thirty-four participants including 19 females (mean 27 yr) and 15 males (mean 29 yr) had body composition assessed by dual energy x-ray absorptiometry and magnetic resonance (MR) imaging. Monocyte reserve capacity and maximal oxygen consumption rate (OCR) were determined ex vivo using extracellular flux analysis. In vivo quadriceps mitochondrial function was measured using 31P-MR spectroscopy based on post-exercise recovery kinetics (τPCr). The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin levels. Variables were log-transformed, and Pearson correlations and partial correlations were used for analyses. Results Mitochondrial metabolism was similar between sexes (p > 0.05). In males only, higher fat mass percent (FM%) was correlated with lower reserve capacity (r = − 0.73; p = 0.002) and reduced muscle mitochondrial function (r = 0.58, p = 0.02). Thigh subcutaneous adipose tissue was inversely related to reserve capacity in males (r = − 0.75, p = 0.001), but in females was correlated to higher maximal OCR (r = 0.48, p = 0.046), independent of FM. In females, lean mass was related to greater reserve capacity (r = 0.47, p = 0.04). In all participants, insulin (r = 0.35; p = 0.04) and HOMA-IR (r = 0.34; p = 0.05) were associated with a higher τPCr. Conclusions These novel findings demonstrate distinct sex-dependent associations between monocyte and skeletal muscle mitochondrial metabolism with body composition. With further study, increased understanding of these relationships may inform sex-specific interventions to improve mitochondrial function and metabolic health.

© 2022 American Society for Parenteral and Enteral Nutrition.Background: Acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) may deplete micronutrient levels. Patients are also at risk for micronutrient depletion due to underlying illness(s), poor nutrient intake prior to intensive care unit (ICU) admission and/or increased requirements. We determined vitamin and trace element status before, during and after CRRT in critically ill patients. Methods: This prospective observational study performed in mixed medical and surgical ICU patients. Serial serum vitamin B6 and vitamin C concentrations were measured by HPLC and folic acid by ECLIA. Serum chromium, copper, selenium, and zinc were measured using ICP-MS. Serum ceruloplasmin was measured by the Erel method. Results: Fifty adult ICU patients with AKI were recruited. The median APACHE II score on ICU admission was high at 24.0 (6.0-33.0). The median days on CRRT was 2.0 (2.0-4.0) days. At baseline (within 10-15 minutes of CRRT initiation), serum vitamin C, selenium and zinc were below normal. Serum vitamin B6 levels at 72 hours on CRRT were significantly lower than at 24 hours (p = 0.011). Serum vitamin C values fell significantly at 24 and 72 hours during CRRT (p = 0.030 and p = 0.001), respectively, and remained low 24 and 48 hours after CRRT was stopped (p = 0.021). At baseline and during CRRT, 96% of participants had at least two or more micronutrient levels below the normal range. Conclusion: Serum vitamin C, selenium and zinc concentrations were below the normal range at baseline. CRRT was associated with a significant further decrease in levels of vitamin C, selenium and zinc.

Summary Background Nutrients, such as glutamine (GLN), have been shown to effect levels of a family of protective proteins termed heat shock proteins (HSPs) in experimental and clinical critical illness. HSPs are believed to serve as extracellular inflammatory messengers and intracellular cytoprotective molecules. Extracellular HSP70 (eHSP70) has been termed a chaperokine due to ability to modulate the immune response. Altered levels of eHSP70 are associated with various disease states. Larger clinical trial data on GLN effect on eHSP expression and eHSP70's association with inflammatory mediators and clinical outcomes in critical illness are limited. Objective Explore effect of longitudinal change in serum eHSP70, eHSP27 and inflammatory cytokine levels on clinical outcomes such as pneumonia and mortality in adult surgical intensive care unit (SICU) patients. Further, evaluate effect of parenteral nutrition (PN) supplemented with GLN (GLN-PN) versus GLN-free, standard PN (STD-PN) on serum eHSP70 and eHSP27 concentrations. Methods Secondary observational analysis of a multicenter clinical trial in 150 adults after cardiac, vascular, or gastrointestinal surgery requiring PN support and SICU care conducted at five academic medical centers. Patients received isocaloric, isonitrogenous PN, with or without GLN dipeptide. Serum eHSP70 and eHSP27, interleukin-6 (IL-6), and 8 (IL-8) concentrations were analyzed in patient serum at baseline (prior to study PN) and over 28 days of follow up. Results eHSP70 declined over time in survivors during 28 days follow-up, but non-survivors had significantly higher eHSP70 concentrations compared to survivors. In patients developing pneumonia, eHSP70, eHSP27, IL-8, and IL-6 were significantly elevated. Adjusted relative risk for hospital mortality was reduced 75% (RR = 0.25, p = 0.001) for SICU patients with a faster decline in eHSP70. The area under the receiver operating characteristic curve was 0.85 (95% CI: 0.76 to 0.94) for the final model suggesting excellent discrimination between SICU survivors and non-survivors. GLN-PN did not alter eHSP70 or eHSP27 serum concentrations over time compared to STD-PN. Conclusion Our results suggest that serum HSP70 concentration may be an important marker for severity of illness and likelihood of recovery in the SICU. GLN-supplemented-PN did not increase eHSP70.

The electronic health records (EHR) infrastructure offers a tremendous resource for identifying controls who match the characteristics of study participants in a single-arm trial. The objectives are to (1) demonstrate the feasibility of curating a synthetic control group for an existing study cohort through EHR data extraction and (2) evaluate the effect of a lifestyle intervention on selected cardiovascular health metrics. A total of 711 university employees were recruited between 2008 and 2012 to participate in a health partner intervention to improve cardiovascular health and were followed for five years. Data of nearly 8000 eligible subjects were extracted from the EHR to create a synthetic control cohort during the same study period. To minimize confounding, crude comparison, exact matching, propensity score matching, and doubly robust estimation were used to compare the selected cardiovascular health metrics at 1 and 5 years of follow-up. Blood pressure and body mass index improved in the intervention group compared to the EHR synthetic controls. The findings of changes in lipid measurements were somewhat unexpected. When analyzing the subgroup without lipid-lowering medications, the intervention group exhibited better control of cholesterol levels over time than did our synthetic controls. Some measurements in the EHR system may be more robust for synthetic selection than others. EHR synthetic controls can provide an alternative to estimate intervention effects appropriately in single-arm studies for these measurements.

BACKGROUND Rapid loss of lean mass during catabolic states is associated with impaired convalescence and increased mortality rates. An understanding of metabolic pathways related to lean mass is needed to enable future interventions designed to combat malnutrition. This study assessed the plasma metabolome in relation to lean mass in clinically stable working adults in a US cohort. METHODS This cross-sectional study included 180 adults (mean ± SD, aged 49.7 ± 10.0 years; body mass index, 27.3 ± 5.5 kg/m2 ; 64% female [n=116]). Fasting plasma was analyzed using high-resolution metabolomics (HRM) via liquid chromatography/mass spectrometry. Lean mass was assessed by dual-energy x-ray absorptiometry and expressed as lean mass index (LMI, lean mass kg/height m2 ). Multiple linear regression, metabolic pathway enrichment, and module analyses were used to characterize systemic metabolism associated with LMI. RESULTS Of 5360 metabolites used in analyses, 593 were related to LMI, either upregulated or downregulated (P < .05). These were enriched within 11 metabolic pathways, including branched-chain amino acid degradation, metabolism of alanine and aspartate and other amino acids, butyrate, purines, and niacin metabolism. Module analysis revealed central associations between LMI and L-glutamate, L-leucine/L-isoleucine, L-valine, L-phenylalanine, L-methionine, and L-aspartate, among other validated metabolites. CONCLUSION These novel plasma HRM data demonstrate the wide-reaching associations of lean mass with systemic metabolism in a single snapshot. Such data may inform targeted nutrition support interventions designed to mitigate loss of lean mass and promote regaining skeletal muscle mass and function after illness or injury.

OBJECTIVE This study explored underlying metabolism-related dysfunction by examining metabolomic profiles in adults categorized as lean, as having normal weight obesity (NWO), or as having overweight/obesity. METHODS Participants (N = 179) had fasting plasma analyzed by liquid chromatography and high-resolution mass spectrometry for high-resolution metabolomics. Body composition was assessed by dual-energy x-ray absorptiometry. NWO was defined as BMI 30% for women and > 23% for men. Differentiating metabolomic features were determined by using linear regression models and likelihood ratio tests with false discovery rate correction. Mummichog was used for pathway and network analyses. RESULTS A total of 222 metabolites significantly differed between the groups at a false discovery rate of q = 0.2. Linoleic acid, β-alanine, histidine, and aspartate/asparagine metabolism pathways were significantly enriched (all P

BACKGROUND: Body fat distribution and diet quality influence clinical outcomes in general populations but are understudied in patients with cystic fibrosis (CF). The aim of this pilot study was to assess body fat distribution and diet quality in relation to fasting glucose and lung function in adults with CF. METHODS: Subjects were 24 adults (ages 18–50) with CF and 25 age-matched controls. The Healthy Eating Index 2015 (HEI-2015) was calculated from 3-day food records and data were adjusted/1000 kcal intake. Whole and regional body composition, including visceral adipose tissue (VAT), was assessed by dual energy X-ray absorptiometry. RESULTS: Subjects with CF reported more added sugar intake [26.1 (IQR 18.1) vs. 12.9 (12.5) g/1000kcal, p0.05 for all), although subjects with CF had higher VAT than control subjects [0.3 (IQR 0.3) vs 0.1 (0.3) kg, p=0.02]. Among subjects with CF, VAT was positively associated with added sugar intake (p

Correction of nutritional vitamin deficiency is recommended in children with chronic kidney disease (CKD). The optimal daily dose of vitamin D to achieve or maintain vitamin D sufficiency is unknown.We conducted a phase III, double-blind, randomized trial of two doses of vitamin DNinety-eight patients were enrolled: 49 randomized into each group. Eighty (81.6%) patients completed the study and were analyzed. Baseline plasma 25(OH)D levels were ≥ 30 ng/mL in 12 (35.3%) and 12 (27.3%) patients in the 1000 IU and 4000 IU treatment groups, respectively. At 6 months, plasma 25(OH)D levels were ≥ 30 ng/mL in 33.3% (95% CI: 18.0-51.8%) and 74.4% (95% CI: 58.8-86.5%) in the 1000 IU and 4000 IU treatment groups, respectively (p = 0.0008). None of the patients developed vitamin D toxicity or hypercalcemia.In children with CKD, 1000 IU of daily vitamin DClinicalTrials.gov identifier: NCT01909115.

Diet influences, and is influenced by, a wide range of socioeconomic, cultural, geographic, and genetic variables. Here we survey a matrix of such interactions as well as their connection to a variety of health outcomes, in a cohort of 689 diverse adults employed at Emory University and enrolled in the Center for Health Discovery and Well-Being (CHDWB) study. Principal component analysis (PCA) of the Block Food Frequency Questionnaire revealed seven PC cumulatively explaining 25.8% and each individually at least 2% of the proportional consumption of 110 food items. PC1 is strongly correlated with the Healthy Eating Index-2015 measure, and accordingly healthier scores associate with multiple measures of physical and mental health. It, as well as PC2 (likely a measure of food expense) and PC3 (carbohydrate versus protein consumption) show significant geographic structure across the Atlanta metropolitan area, correlating with race and ethnicity, income level, age and sex. Notably, a polygenic score for body mass index (BMI) consisting of 281 SNPs explains 2.8% of the variance in PC5, which is as strong as its association with BMI itself. PC5 appears to differentiate participants with respect to conscious eating behavior related to the choice of diet or comfort foods. Our analysis adds to the growing literature on factor analysis of socio-demographic influences on nutrition and health.

Obesity and obesity-related metabolic disorders are linked to the intestinal microbiome. However, the causality of changes in the microbiome-host interaction affecting energy metabolism remains controversial. Here, we show the microbiome-derived metabolite δ-valerobetaine (VB) is a diet-dependent obesogen that is increased with phenotypic obesity and is correlated with visceral adipose tissue mass in humans. VB is absent in germ-free mice and their mitochondria but present in ex-germ-free conventionalized mice and their mitochondria. Mechanistic studies in vivo and in vitro show VB is produced by diverse bacterial species and inhibits mitochondrial fatty acid oxidation through decreasing cellular carnitine and mitochondrial long-chain acyl-coenzyme As. VB administration to germ-free and conventional mice increases visceral fat mass and exacerbates hepatic steatosis with a western diet but not control diet. Thus, VB provides a molecular target to understand and potentially manage microbiome-host symbiosis or dysbiosis in diet-dependent obesity.

OBJECTIVES: The immunomodulatory effects of eicosapentaenoic acid (EPA) support it as an effective treatment for major depressive disorder (MDD) associated with chronic inflammation. Increased production of specialized pro-resolving mediators (SPM) during EPA supplementation may help reduce inflammation. We compared the effects of different EPA doses on plasma fatty acids and SPM in MDD patients. METHODS: MDD patients with baseline inflammation (N = 61, IDS-C score >25; BMI > 25 kg/m2; serum CRP > 3 mg/L) were enrolled in a 2-site, 12-wk randomized trial comparing EPA 1, 2 and 4 g/d to placebo (soybean oil). Plasma fatty acids (mol%) and SPM (pg/mL) were measured at baseline and 12 wks (n = 8 [10], 12 [11], 11 and 10 in the placebo, EPA 1, 2 and 4 g/d arms, respectively). Dose effects were tested using the Kruskal-Wallis followed by pairwise Wilcoxon rank-sum tests with Benjamini-Hochberg correction. RESULTS: In the placebo arm, plasma EPA and EPA derivatives did not change at 12 wks, relative to baseline. EPA supplementation significantly increased plasma EPA dose-dependently (3-, 3- and 9-fold in the 1, 2 and 4 g/d arms). Similar significant dose-dependent increases in EPA derivatives were observed in the EPA arms, including 18-hydroxy-EPA (18-HEPE, 8-, 7- and 14-fold) and 15-HEPE (4-, 6- and 10-fold). The increase in 18-HEPE, a precursor of EPA-series resolvins (RvE), by 4 g/d EPA was significantly greater than with lower doses. While RvE1 remained undetected in all treatment arms, RvE2 was detected in some subjects at baseline and 12 wks with a dose-dependent median increase (+3, +6 and +8 pg/mL). RvE3, undetectable at baseline, became detectable in more subjects dose-dependently (n = 1, 2, 3 and 6). The reduction in plasma arachidonic acid (AA) by EPA supplementation significantly differed from placebo only at 2 and 4 g/d but not between the two doses. AA derivatives were not affected, except for the pro-resolving lipoxin B4, which was rarely detected at baseline, but became detectable in most subjects after EPA supplementation (median: 46, 59 and 94 pg/mL). CONCLUSIONS: Our results show a robust dose-effect of EPA in increasing plasma EPA and EPA-derived 18-HEPE, which may result in improved conversion to RvE2 and RvE3. Its associations with reduced inflammation and improved IDS-C scores will be further analyzed. FUNDING SOURCES: NCCIH.

OBJECTIVES: Optimal bone health is maintained through a remodeling cycle consisting of resorption followed by formation. Procollagen type I N-terminal propeptide (P1NP) and C-terminal telopeptides of type I collagen (CTX) are biomarkers of bone metabolism that capture changes in bone formation and bone resorption, respectively. This study aimed to identify unique metabolic pathways related to bone turnover markers (BTMs) in healthy young adults. METHODS: This cross-sectional study included 34 healthy, young adults (19 females, average age 27.8 years). Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry. Fasting plasma was analyzed using dual column liquid chromatography and ultra-high-resolution mass spectrometry for metabolomics. Serum levels of P1NP and CTX were measured with ELISA. Linear regression and pathway enrichment analyses were used to identify metabolic pathways related to the BTMs. RESULTS: All participants had a normal whole-body BMD T-score. Metabolites significantly associated with P1NP (at P

OBJECTIVES: There is a considerable degree of variation in bone mineral density (BMD) within populations. Use of plasma metabolomics may provide insight into established and novel determinants of BMD variance, such as nutrition and gut microbiome composition, to inform future prevention and treatment strategies for loss of BMD. Using high-resolution metabolomics (HRM), we examined low-molecular weight plasma metabolites and nutrition-related metabolic pathways associated with BMD. METHODS: This cross-sectional study included 179 adults (mean age 49.5 ± 10.3 yr, 64% female). Fasting plasma was analyzed using ultra-high-resolution mass spectrometry with liquid chromatography. Whole body and spine BMD were assessed by dual energy x-ray absorptiometry and expressed as BMD (g/cm(2)) or Z-scores. Multiple linear regression, pathway enrichment, and module analyses were used to determine key plasma metabolic features associated with bone density. RESULTS: Of 10,210 total detected metabolic features, whole body BMD Z-score was associated with 710 metabolites, which were significantly enriched in seven metabolic pathways, including linoleic acid, fatty acid activation and biosynthesis, and glycerophospholipid metabolism. Spine BMD was associated with 970 metabolites, significantly enriched in pro-inflammatory pathways involved in prostaglandin formation and linoleic acid metabolism. In module analyses, tryptophan- and polyamine-derived metabolites formed a network that was significantly associated with spine BMD, supporting a link with the gut microbiome. CONCLUSIONS: Plasma HRM provides comprehensive information relevant to nutrition and components of the microbiome that influence bone health. This data supports pro-inflammatory fatty acids and the gut microbiome as novel regulators of postnatal bone remodeling. FUNDING SOURCES: Grant support included funds NIH and VA Office of Research and Development.

There is limited understanding of the role of host metabolism in the pathophysiology of human tuberculosis (TB). Using high-resolution metabolomics with an unbiased approach to metabolic pathway analysis, we discovered that the tryptophan pathway is highly regulated throughout the spectrum of TB infection and disease. This regulation is characterized by increased catabolism of tryptophan to kynurenine, which was evident not only in active TB disease but also in latent TB infection (LTBI). Further, we found that tryptophan catabolism is reversed with effective treatment of both active TB disease and LTBI in a manner commensurate with bacterial clearance. Persons with active TB and LTBI also exhibited increased expression of indoleamine 2,3-dioxygenase-1 (IDO-1), suggesting IDO-1 mediates observed increases in tryptophan catabolism. Together, these data indicate IDO-1-mediated tryptophan catabolism is highly preserved in the human response to Mycobacterium tuberculosis and could be a target for biomarker development as well as host-directed therapies.

Background/aim: Adipokines play an important role in the regulation of metabolism. In critical illness, they alter serum levels and are suspected to worsen clinical outcomes. But the effect of the route of nutrition on adipokines is not known. The purpose of this study was to evaluate the association between the route of nutrition and adipokine levels in critically ill patients. Materials and methods: This prospective study was performed in an intensive care unit ICU . Patients admitted to the ICU for least 72 h and receiving either enteral nutrition EN via tube feeding or parenteral nutrition PN were enrolled. Serum was obtained at baseline, 24 h, and 72 h for concentrations of leptin, adiponectin, resistin, glucagon-like peptide 1 GLP-1 , insulin-like growth factors 1 IGF-1 , and ghrelin. Results: A total of 26 patients were included in the study. Thirteen patients received EN and 13 patients received PN. In the PN group, leptin level significantly increased P = 0.037 , adiponectin and ghrelin significantly decreased during follow up P = 0.037, P = 0.008, respectively . There was no significant change between all adipokines in the EN group and resistin, IGF-1 and GLP-1 in the PN group during follow up. Resistin levels were markedly lower in the EN group at both 24 h P = 0.015 and 72 h P = 0.006 while GLP-1 levels were higher in the EN group at baseline, 24 h, and 72 h P = 0.018, P = 0.005, and P = 0.003, respectively . There were no differences in leptin, adiponectin, IGF-1, and ghrelin levels over time. Conclusion: The delivery of EN in critical illness was associated with decreased resistin levels and increased GLP-1 levels. Thus, the route of nutrition may impact the clinical outcome in critical illness due to adipokines.

Summary Severe burn caused hypermetabolism-sustained muscle wasting and other comorbidities. The goal of nutrition support and other care management is to maintain energy homeostasis in burn patients. Due to dramatic changes and other factors that influence over the time course after burn, the plan of nutrition support has to be adjusted continuously with monitoring patient conditions. Inappropriate management of nutrition support adverses patients' status and progress. The current principal of care management has been encouraged in severe burn patients, which includes earlier enteral feeding, 1.5–2 g/kg of protein intake, and others. However, the detail of each territory in nutrition care is still under investigation. Further, nutrition support is more specialized for certain population as the time being.

Background: Enteral nutrition (EN) increases hyperglycemia due to high carbohydrate concentrations while providing insufficient protein. The study tested whether an EN formula with very high‐protein‐ and low‐carbohydrate‐facilitated glucose control delivered higher protein concentrations within a hypocaloric protocol. Methods: This was a multicenter, randomized, open‐label clinical trial with parallel design in overweight/obese mechanically ventilated critically ill patients prescribed 1.5 g protein/kg ideal body weight/day. Patients received either an experimental very high‐protein (37%) and low‐carbohydrate (29%) or control high‐protein (25%) and conventional‐carbohydrate (45%) EN formula. Results: A prespecified interim analysis was performed after enrollment of 105 patients (52 experimental, 53 control). Protein and energy delivery for controls and experimental groups on days 1–5 were 1.2 ± 0.4 and 1.1 ± 0.3 g/kg ideal body weight/day (P = .83), and 18.2 ± 6.0 and 12.5 ± 3.7 kcals/kg ideal body weight/day (P < .0001), respectively. The combined rate of glucose events outside the range of >110 and ≤150 mg/dL were not different (P = .54, primary endpoint); thereby the trial was terminated. The mean blood glucose for the control and the experimental groups were 138 (−SD 108, +SD 177) and 126 (−SD 99, +SD 160) mg/dL (P = .004), respectively. Mean rate of glucose events >150 mg/dL decreased (Δ = −13%, P = .015), whereas that of 80–110 mg/dL increased (Δ = 14%, P = .0007). Insulin administration decreased 10.9% (95% CI, −22% to 0.1%; P = .048) in the experimental group relative to the controls. Glycemic events ≤80 mg/dL and rescue dextrose use were not different (P = .23 and P = .53). Conclusions: A very high‐protein and low‐carbohydrate EN formula in a hypocaloric protocol reduces hyperglycemic events and insulin requirements while increasing glycemic events between 80–110 mg/dL.

IntroductionThe Certificate Program in Translational Research (CPTR) at the Georgia Clinical and Translational Science Alliance provides Ph.D. students, postdoctoral fellows and faculty with didactic, mentored, and experiential training in clinical and translational research.MethodsQuantitative evaluation includes tracking trainee competency, publications, grants and careers in clinical and translational research. Qualitative evaluation includes interviews with trainees about program experiences.ResultsThe CPTR provided knowledge and skills in clinical and translational research through coursework, clinical rotations, and collaboration with interdisciplinary scientists. Trainees reported increased confidence in 22 program competencies. Trainees have published more than 290 peer-reviewed articles and received over $4 million in grants from the NIH, over $15 million from the U.S. Department of Defense, and more than $300,000 from foundations. Trainees who completed the program remained in clinical and translational research.ConclusionsPrograms like the CPTR are needed to train investigators to advance biomedical discoveries into population health.

The metabolic signaling pathways that drive pathologic tissue inflammation and damage in humans with pulmonary tuberculosis (TB) are not well understood. Using combined methods in plasma high-resolution metabolomics, lipidomics and cytokine profiling from a multicohort study of humans with pulmonary TB disease, we discovered that IL-1β-mediated inflammatory signaling was closely associated with TCA cycle remodeling, characterized by accumulation of the proinflammatory metabolite succinate and decreased concentrations of the anti-inflammatory metabolite itaconate. This inflammatory metabolic response was particularly active in persons with multidrug-resistant (MDR)-TB that received at least 2 months of ineffective treatment and was only reversed after 1 year of appropriate anti-TB chemotherapy. Both succinate and IL-1β were significantly associated with proinflammatory lipid signaling, including increases in the products of phospholipase A2, increased arachidonic acid formation, and metabolism of arachidonic acid to proinflammatory eicosanoids. Together, these results indicate that decreased itaconate and accumulation of succinate and other TCA cycle intermediates is associated with IL-1β-mediated proinflammatory eicosanoid signaling in pulmonary TB disease. These findings support host metabolic remodeling as a key driver of pathologic inflammation in human TB disease., Author summary Pulmonary tuberculosis (TB) often results in pathologic lung inflammation that causes tissue damage and does not control bacterial replication. This impairs the host response to antibiotic treatment and can result in long term deficits in lung function. Currently, the role of host metabolism in regulating the inflammatory response in TB disease is not well understood. Here, we use detailed immunometabolic phenotyping to show that metabolic remodeling of the tricarboxylic acid (TCA) cycle is closely associated with pathologic inflammatory signaling in humans with TB disease. Accumulation of TCA cycle intermediates in plasma, including the proinflammatory metabolite succinate, as well as decreased concentrations of the anti-inflammatory metabolite itaconate, were associated with increases in IL-1β and upregulation of proinflammatory lipid signaling cascades. This inflammatory network was upregulated following delays in appropriate anti-TB treatment and was associated with prolonged time to sputum culture clearance of Mycobacterium tuberculosis. Our study provides new insights into the metabolic reprograming that leads to pathologic inflammation in humans with pulmonary TB.

Context Disruption of gut microbiota may exacerbate severity of cystic fibrosis (CF). Vitamin D deficiency is a common comorbidity in patients with CF that may influence composition of the gut microbiota. Objectives Compare microbiota of vitamin D-sufficient and -insufficient CF patients and assess impact of a weekly high-dose vitamin D3 bolus regimen on gut and airway microbiome in adults with CF and vitamin D insufficiency (25-hydroxyvitamin D < 30 ng/mL). Design Forty-one subjects with CF were classified into two groups: vitamin D insufficient (n = 23) and vitamin D sufficient (n = 18). Subjects with vitamin D insufficiency were randomized to receive 50,000 IU of oral vitamin D3 or placebo weekly for 12 weeks. Sputum and stool samples were obtained pre- and postintervention and 16S ribosomal RNA genes sequenced using Illumina MiSeq technology. Results Gut microbiota differed significantly based on vitamin D status with Gammaproteobacteria, which contain numerous, potentially pathogenic species enriched in the vitamin D-insufficient group. Principal coordinates analysis showed differential gut microbiota composition within the vitamin D-insufficient patients following 12 weeks treatment with placebo or vitamin D3 (permutation multivariate analysis of variance = 0.024), with Lactococcus significantly enriched in subjects treated with vitamin D3, whereas Veillonella and Erysipelotrichaceae were significantly enriched in patients treated with placebo. Conclusion This exploratory study suggests that vitamin D insufficiency is associated with alterations in microbiota composition that may promote inflammation and that supplementation with vitamin D has the potential to impact microbiota composition. Additional studies to determine the impact of vitamin D on microbiota benefit clinical outcomes in CF are warranted.

Anemia, iron deficiency, and hypovitaminosis D are well-known comorbidities in inflammatory bowel disease (IBD). Epidemiologic studies have linked vitamin D deficiency with increased risk of anemia, and in vitro studies suggest that vitamin D may improve iron recycling through downregulatory effects on hepcidin and proinflammatory cytokines.We aimed to investigate the association of vitamin D status with inflammation, iron biomarkers, and anemia in pediatric IBD. Cross-sectional data were obtained from N = 69 patients with IBD aged 5 to19 years. Iron biomarkers (ferritin, soluble transferrin receptor), and 25-hydroxyvitamin D (25(OH)D), inflammatory biomarkers (C-reactive protein and α-1-acid glycoprotein), hepcidin, and hemoglobin were collected. Iron biomarkers were regression corrected for inflammation. Multivariable logistic/linear models were used to examine the associations of 25(OH)D with inflammation, iron status, hepcidin, and anemia.Approximately 50% of subjects were inflamed (C-reactive protein5 mg/L or α-1-acid glycoprotein1 g/L). Iron deficiency prevalence (inflammation-corrected ferritin15 μg/L or soluble transferrin receptor8.3 mg/L) was 67%; anemia was 36%, and vitamin D insufficiency (25(OH)D30 ng/mL) was 77%. In linear regression models, vitamin D insufficiency was associated with increased hepcidin levels (β [SE] = 0.6 [0.2], P = 0.01) and reduced hemoglobin (β [SE] = -0.9 [0.5], P = 0.046), controlling for age, sex, race, insurance status, body mass index for age, inflammation, disease diagnosis (ulcerative colitis versus Crohn's disease), and disease duration, compared with 25(OH)D ≥30 ng/mL.Our results suggest that concentrations of 25(OH)D ≥30 ng/mL are associated with lower hepcidin and higher hemoglobin levels. Further research is needed to clarify the association of vitamin D with inflammation, iron status, and anemia in pediatric IBD.

Summary Background & aims In vitro studies suggest that vitamin D may reduce hepcidin expression and pro-inflammatory cytokine release from monocytes. However, data assessing the vitamin D-mediated effects on iron recycling in healthy individuals are lacking. We aimed to examine the effect of high-dose vitamin D3 on plasma hepcidin, inflammatory cytokine, and ferritin concentrations in healthy adults. Methods This was a pilot, double-blind, placebo-controlled trial in healthy adults (N = 28) randomized to receive a one-time oral dose of 250,000 IU of vitamin D3 or placebo. Between- and within-group differences in plasma hepcidin, pro-inflammatory cytokine [interleukin (IL)-1β, IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1)], and ferritin concentrations at baseline and 1 week were determined using two-sample and paired t-tests, respectively. Results At baseline, plasma 25-hydroxyvitamin D [25(OH)D], hepcidin, pro-inflammatory cytokine, and ferritin concentrations did not differ between the two groups, and greater than 70% of subjects in both groups were vitamin D deficient (25(OH)D Conclusions High-dose vitamin D3 significantly reduced plasma hepcidin concentrations in healthy adults 1 week post-dosing, without a change in plasma pro-inflammatory cytokine or ferritin concentrations. These data suggest that vitamin D may have a role in regulating iron recycling by acting independently of changes in pro-inflammatory markers.

Iron deficiency and anemia affect up to 50% to 75% of patients with inflammatory bowel disease (IBD). Iron deficiency in IBD may be difficult to diagnose because of the effect of inflammation on iron status biomarkers. Thus, there is a need for better methods to accurately determine iron status in IBD.The aim of the study was to investigate the association of inflammation with hemoglobin content of reticulocytes (CHr) and the utility of CHr in comparison to standard iron biomarkers.We conducted a cross-sectional study of children with IBD. Iron biomarkers (CHr, ferritin, soluble transferrin receptor [sTfR], hepcidin, hemoglobin) were measured along with systemic biomarkers of inflammation (C-reactive protein, α1-acid glycoprotein]. Spearman correlations were used to evaluate the relation of inflammation and iron biomarkers. The criterion standard for iron deficiency was defined as inflammation-corrected ferritin15 μg/L or sTfR8.3 mg/L. Receiver operating characteristic curves were used to estimate the prognostic values of all iron biomarkers to identify patients with iron deficiency.We analyzed data in 62 children ages 5 to 18 years. Sixty-nine percent of our subjects had Crohn disease and 31% had ulcerative colitis, of which 42% were girls and 53% African American. The prevalence of anemia was 32%, of iron deficiency was 52% using ferritin15 μg/L or sTfR8.3 mg/L, 39% using red blood cell distribution width of14.5%, 26% using body iron stores of0 mg/kg body weight, 25% using CHr of28 pg, and 11% using mean corpuscular volume of75 fL/cell. The prevalence of elevated CRP or AGP was 48%. After correcting ferritin and sTfR levels for inflammation, the prevalence of iron deficiency was 68%. CHr was correlated with C-reactive protein (rs -0.44, P 0.001) and α1-acid glycoprotein (rs -0.37, P 0.05). The optimal prognostic value for inflammation-adjusted CHr to predict iron deficiency was 34 pg (area under the receiver operating characteristic of 0.70), with 88% sensitivity and 30% specificity.Iron deficiency and anemia are common in this pediatric IBD cohort. All explored iron biomarkers, including CHr, were affected by inflammation and should be adjusted. A single iron biomarker is unlikely to best predict iron deficiency in pediatric IBD. Iron intervention studies are needed to examine the response of iron biomarkers to iron supplementation in the setting of inflammation.

Short bowel syndrome (SBS) in neonates is an uncommon but highly morbid condition. As SBS survival increases, physiologic complications become more apparent. Few reports in the literature elucidate outcomes for adults with a pediatric history of SBS. We present a case report of a patient, born with complicated gastroschisis resulting in SBS at birth, who subsequently developed symptoms and pathologic changes of inflammatory bowel disease (IBD) as an adult. The patient lived from age 7, after a Bianchi intestinal lengthening procedure, to age 34 independent of parenteral nutrition (PN), but requiring hydration fluid via G-tube. He was then diagnosed with IBD, after presenting with weight loss, diarrhea, and malabsorption, which required resumption of PN and infliximab treatment. This report adds to a small body of the literature which points to a connection between SBS in neonates and subsequent diagnosis of IBD. Recent evidence suggests that SBS and IBD have shared features of mucosal immune dysfunction and altered intestinal microbiota. We review current treatment options for pediatric SBS as well as multidisciplinary and coordinated transition strategies. We conclude that there may be an etiologic connection between SBS and IBD and that this knowledge may impact outcomes and approaches to care.

A major impediment to improving the health of communities is the lack of qualified clinical and translational research (CTR) investigators. To address this workforce shortage, the National Institutes of Health (NIH) developed mechanisms to enhance the career development of CTR physician, PhD, and other doctoral junior faculty scientists including the CTR-focused K12 program and, subsequently, the KL2-mentored CTR career development program supported through the Clinical and Translational Science Awards (CTSAs). Our evaluation explores the impact of the K12/KL2 program embedded within the Atlanta Clinical and Translational Science Institute (ACTSI), a consortium linking Emory University, Morehouse School of Medicine and the Georgia Institute of Technology. We conducted qualitative interviews with program participants to evaluate the impact of the program on career development and collected data on traditional metrics (number of grants, publications). 46 combined K12/KL2 scholars were supported between 2002 and 2016. 30 (65%) of the 46 K12/KL2 scholars are women; 24 (52%) of the trainees are minorities, including 10 (22%) scholars who are members of an underrepresented minority group. Scholars reported increased research skills, strong mentorship experiences, and positive impact on their career trajectory. Among the 43 scholars who have completed the program, 39 (91%) remain engaged in CTR and received over $89 000 000 as principal investigators on federally funded awards. The K12/KL2 funding provided the training and protected time for successful career development of CTR scientists. These data highlight the need for continued support for CTR training programs for junior faculty.

Highlights • Vitamin D has a stimulatory effect on the mRNA expression of cathelicidin in vitro. • Anti-TB drugs abolish the vitamin D stimulatory effect of cathelicidin in vitro. • Subjects taking anti-TB drugs have no enhanced cathelicidin response to vitamin D. • Anti-TB drugs may alter the vitamin D stimulatory effect on anti-microbial peptides., Tuberculosis (TB) is a major global health problem. Patients with TB have a high rate of vitamin D deficiency, both at diagnosis and during the course of treatment with anti-tuberculosis drugs. Although data on the efficacy of vitamin D supplementation on Mycobacterium tuberculosis (Mtb) clearance are uncertain from randomized controlled trials (RCTs), vitamin D enhances the expression of the anti-microbial peptide human cathelicidin (hCAP18) in cultured macrophages in vitro. One possible explanation for the mixed (primarily negative) results of RCTs examining vitamin D treatment in TB infection is that anti-TB drugs given to enrolled subjects may impact actions of vitamin D to enhance cathelicidin in macrophages. To address this hypothesis, human macrophage-like monocytic (THP-1) cells were treated with varying doses of first-line anti-tuberculosis drugs in the presence of the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). The expression of hCAP18 was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). 1,25(OH)2D3 strongly induced expression of hCAP18 mRNA in THP-1 cells (fold-change from control). The combination of the standard 4-drug TB therapy (isoniazid, rifampicin, pyrazinamide and ethambutol) in the cultured THP-1 cells demonstrated a significant decrease in hCAP18 mRNA at the dosage of 10 µg/mL. In 31 subjects with newly diagnosed drug-sensitive TB randomized to either high-dose vitamin D3 (1.2 million IU over 8 weeks, n = 13) versus placebo (n = 18), there was no change from baseline to week 8 in hCAP18 mRNA levels in peripheral blood mononuclear cells or in plasma concentrations of LL-37, the protein product of hCAP18. These data suggest that first-line anti-TB drugs may alter the vitamin D-dependent increase in hCAP18 and LL-37 human macrophages.