Racial differences between African-American and white women in insulin resistance and visceral adiposity are associated with differences in apoCIII containing apoAI and apoB lipoproteins

Background: African-Americans have higher HDL, less visceral adipose tissue (VAT) and lower triglyceride (TG) and apoCIII concentrations than whites, despite being more insulin-resistant. We studied in African-American and white women the influences of insulin resistance and VAT on the apoAI concentrations of two HDL subspecies, one that contains apoCIII that is associated with increased risk of coronary heart disease (CHD) and one that does not have apoCIII that is associated with decreased CHD; and on the apoCIII concentrations of HDL and of the apoB lipoproteins. Methods: The participants were 32 women (14 African-Americans, 18 white) of similar age (39 ± 12 vs. 42 ± 11y). Mean BMI was 34 kg/m2 in the African-Americans compared to 30 in the whites. A standard diet (33% fat, 52% carbohydrate, 15% protein) was provided for 7 days followed by a test meal (40% fat, 40% carbohydrate, 20% protein) on Day 8. Insulin sensitivity index (SI) was calculated from the minimal model. Results: After controlling for SI, African-Americans have a higher mean apoAI level in HDL with apoCIII compared with whites (12.9 ± 2.8 and 10.9 ± 2.9 mg/dL, respectively, P = 0.05). SI was associated with higher apoAI in HDL with apoCIII, whereas VAT was not associated with this HDL subspecies. This pattern of results was reversed for apoCIII concentrations in apoB lipoproteins. After adjusting for SI, African-Americans had lower apoCIII in apoB lipoproteins. SI was associated with lower apoCIII in total apoB lipoproteins, whereas VAT was associated with higher apoCIII in all the apoB lipoproteins. Additional adjustment for VAT tended to reduce the difference in apoCIII between the groups. Conclusions: African-American women have a higher HDL with apoCIII level than whites when controlled for insulin sensitivity. African-Americans have lower insulin sensitivity. Insulin sensitivity is associated with higher levels of HDL with apoCIII. ApoCIII levels in VLDL are lower in African-American women than whites, also affected by insulin sensitivity which is associated with low apoCIII in VLDL. VAT has a strong association with apoCIII in apoB lipoproteins but not with apoAI in HDL with apoCIII. Trial registration ClinicalTrials.gov Identifier: NCT0048486

ApoC-III and visceral adipose tissue contribute to paradoxically normal triglyceride levels in insulin-resistant African-American women

Background: African-Americans are more insulin-resistant than whites but have lower triglyceride (TG) concentrations. The metabolic basis for this is unknown. Our goal was to determine in a cross-sectional study the effect of insulin resistance, visceral adipose tissue (VAT) and the apolipoproteins, B, C-III and E, on race differences in TG content of very low density lipoproteins (VLDL). Methods: The participants were 31 women (16 African-American, 15 white) of similar age (37 ± 9 vs. 38 ± 11y (mean ± SD), P = 0.72) and BMI (32.4 ± 7.2 vs. 29.3 ± 6.0 kg/m2, P = 0.21). A standard diet (33% fat, 52% carbohydrate, 15% protein) was given for 7 days followed by a test meal (40% fat, 40% carbohydrate, 20% protein) on Day 8. Insulin sensitivity index (SI) was calculated from the minimal model. VAT was measured at L2-3. The influence of race, SI, VAT and apolipoproteins on the TG content of VLDL was determined by random effects models (REM). Results: African-Americans were more insulin-resistant (SI: 3.6 ± 1.3 vs. 5.6 ± 2.6 mU/L-1.min-1, P < 0.01) with less VAT (75 ± 59 vs. 102 ± 71 cm2, P < 0.01). TG, apoB and apoC-III content of light and dense VLDL were lower in African-Americans (all P < 0.05 except for apoC-III in light VLDL, P = 0.11). ApoE content did not vary by race. In REM, VAT but not SI influenced the TG concentration of VLDL. In models with race, SI, VAT and all apolipoproteins entered, race was not significant but apoC-III and VAT remained significant determinants of TG concentration in light and dense VLDL. Conclusions: Low concentrations of apoC-III and VAT in African-Americans contribute to race differences in TG concentrations. Trial registration ClinicalTrials.gov Identifier: NCT0048486

Fatty Acids, Amphiregulin Production, and Lung Function in a Cohort of Midwestern Veterans

RationaleThe relationship between many fatty acids and respiratory outcomes remains unclear, especially with regard to mechanistic actions. Altered regulation of the process of lung repair is a key feature of chronic lung disease and may impact the potential for pulmonary rehabilitation, but underlying mechanisms of lung repair following injury or inflammation are not well-studied. The epidermal growth factor receptor agonist amphiregulin (AREG) has been demonstrated to promote lung repair following occupational dust exposure in animals. Studies suggest the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) may enhance the production of AREG. The objective of this study was to determine the relationship between fatty acids and lung function in a population of veterans and determine if fatty acid status is associated with concentrations of AREG.Materials and MethodsData were collected from a cross-sectional study of veterans within the Nebraska-Western Iowa Health Care System. Whole blood assays were performed to quantify AREG concentrations via a commercially available ELISA kit. Fatty acids from plasma samples from the same patients were measured using gas-liquid chromatography. Intakes of fatty acids were quantified with a validated food frequency questionnaire. Linear regression models were used to determine whether plasma fatty acids or intakes of fatty acids predicted lung function or AREG concentrations. A p &lt; 0.05 was considered statistically significant.ResultsNinety participants were included in this analysis. In fully adjusted models, plasma fatty acids were associated with AREG production, including the PUFA eicosapentaenoic acid (EPA) (β = 0.33, p = 0.03) and the monounsaturated fatty acid octadecenoic acid: (β = −0.56, p = 0.02). The omega-3 PUFA docosapentaenoic acid (DPA) was positively associated with lung function (β = 0.28, p = 0.01; β = 26.5, p = 0.05 for FEV1/FVC ratio and FEV1 % predicted, respectively), as were the omega-6 PUFAs eicosadienoic acid (β = 1.13, p &lt; 0.001; β = 91.2, p = 0.005 for FEV1/FVC ratio and FEV1 % predicted, respectively) and docosadienoic acid (β = 0.29, p = 0.01 for FEV1/FVC ratio). Plasma monounsaturated and saturated fatty acids were inversely associated with lung function.ConclusionOpposing anti- and pro-inflammatory properties of different fatty acids may be associated with lung function in this population, in part by regulating AREG induction

Individual tree and stand-level carbon and nutrient contents across one rotation of loblolly pine plantations on a reclaimed surface mine

While reclaimed loblolly pine (Pinus taeda L.) plantations in east Texas, USA have demonstrated similar aboveground productivity levels relative to unmined forests, there is interest in assessing carbon (C) and nutrients in aboveground components of reclaimed trees. Numerous studies have previously documented aboveground biomass, C, and nutrient contents in loblolly pine plantations; however, similar data have not been collected on mined lands. We investigated C, N, P, K, Ca, and Mg aboveground contents for first-rotation loblolly pine growing on reclaimed mined lands in the Gulf Coastal Plain over a 32-year chronosequence and correlated elemental rates to stand age, stem growth, and similar data for unmined lands. At the individual tree level, we evaluated elemental contents in aboveground biomass components using tree size, age, and site index as predictor variables. At the stand-level, we then scaled individual tree C and nutrients and fit a model to determine the sensitivity of aboveground elemental contents to stand age and site index. Our data suggest that aboveground C and nutrients in loblolly pine on mined lands exceed or follow similar trends to data for unmined pine plantations derived from the literature. Diameter and height were the best predictors of individual tree stem C and nutrient contents (R ≥ 0.9473 and 0.9280, respectively) followed by stand age (R ≥ 0.8660). Foliage produced weaker relationships across all predictor variables compared to stem, though still significant (P ≤ 0.05). The model for estimating stand-level C and nutrients using stand age provided a good fit, indicating that contents aggrade over time predictably. Results of this study show successful modelling of reclaimed loblolly pine aboveground C and nutrients, and suggest elemental cycling is comparable to unmined lands, thus providing applicability of our model to related systems

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Apolipoproteins and their subspecies in human cerebrospinal fluid and plasma

Introduction: Subspecies of apolipoproteins can be defined by fractionating apolipoproteins based on the presence and absence of coexisting apolipoproteins. Methods: We determined age- and sex-adjusted correlations of enzyme-linked immunosorbent assay–measured plasma and cerebrospinal fluid (CSF) apolipoproteins (apoA-I, apoC-III, apoE, and apoJ) or apolipoprotein subspecies (apoA-I with and without apoC-III, ApoE, or apoJ; apoE with and without apoC-III or apoJ) in 22 dementia-free participants. Results: CSF apoE did not correlate with plasma apolipoproteins or their subspecies. CSF apoJ correlated most strongly with plasma apoA-I without apoJ (r = 0.7). CSF apoA-I correlated similarly strong with plasma total apoA-I and all apoA-I subspecies (r ≥ 0.4) except for apoA-I with apoE (r = 0.3) or apoA-I with apoJ (r = 0.3). CSF apoC-III was most strongly correlated with plasma apoA-I with apoC-III (r = 0.7). Discussion CSF levels of some apolipoproteins implicated in the pathophysiology of dementia might be better approximated by specific plasma apolipoprotein subspecies than total plasma concentrations