Health Equity: The Only Path Forward for Primary Care.

The 2021 National Academies of Sciences, Engineering, and Medicine (NASEM) report on Implementing High-Quality Primary Care identifies 5 high-level objectives regarding payment, access, workforce development, information technology, and implementation. Nine junior primary care leaders (3 internal medicine, 3 family medicine, 3 pediatrics) invited from broad geographies, practice settings, and academic backgrounds used appreciative inquiry to identify priorities for the future of primary care. Highlighting the voices of these early career clinicians, we propose a response to the report from the perspective of early career primary care physicians. Health equity must be the foundation of the future of primary care. Because Barbara Starfield's original 4 Cs (first contact, coordination, comprehensiveness, and continuity) may not be inclusive of the needs of under-resourced communities, we promote an extension to include 5 additional Cs: convenience, cultural humility, structural competency, community engagement, and collaboration. We support the NASEM report's priorities and its focus on achieving health equity. We recommend investing in local communities and preparatory programs to stimulate diverse individuals to serve in health care. Finally, we support a blended value-based care model with risk adjustment for the social complexity of our patients.Appeared as Annals "Online First" article.

Sugars measured enzymatically in a fasting overnight urine sample are not sensitive biomarkers of dietary added sugar intake in postmenopausal women.

BACKGROUND: Restricting dietary sugar is a leading recommendation, but limited biomarkers assessing intake exist. Although 24-h urinary sucrose (U-Suc) and urinary fructose (U-Fruc) excretion has been used with mixed success, collection is burdensome. AIM: This study aimed to test the sensitivity of an enzymatic assay of U-Suc and U-Fruc to detect changing added sugar intake using low-burden overnight urine samples in 30 postmenopausal women. METHODS: Women consumed usual dietary intake during day 1 and usual intake plus a sugar sweetened beverage during day 2. Weighed, photographed food records assessed intake. Enzymatic assay measured U-Suc and U-Fruc from fasting overnight samples; liquid chromatography mass spectrometry (LC-MS) validated U-Suc findings. RESULTS: Dietary added sugars increased significantly during day 2 (p < 0.001), but urinary sugars were not significantly increased. Enzymatic assay detected urinary sugars in 75% (U-Suc) and 35% (U-Fruc) of samples. Dietary sucrose was not associated with U-Suc, however dietary fructose was significantly associated with U-Fruc [ß = 0.031; p < 0.05] among women with detectable urinary sugars. Participants with detectable U-Fruc consumed more energy from added sugars [12.6% kcal day 1; 21.5% kcal day 2] than participants with undetectable U-Fruc [9.3% kcal day 1; 17.4% kcal day 2], p < 0.05. Using LC-MS, U-Suc predicted sucrose and added sugar intake [ß = 0.017, ß = 0.013 respectively; both p < 0.05]. CONCLUSIONS: Urinary sugars measured enzymatically from overnight urine samples were not sensitive biomarkers of changing added sugar intake in postmenopausal women. However, urinary fructose measured by enzymatic assay or LC-MS may differentiate low versus high added sugar consumers.

Application of Comparative Lipidomics to Elucidate Postprandial Metabolic Excursions Following Dairy Milk Ingestion in Individuals with Prediabetes.

Nutrient-dense dairy foods are an important component of a healthy diet. Recommendations, however, advise non- and low-fat dairy foods despite controversy concerning whether full-fat dairy foods adversely impact cardiometabolic health. Therefore, in this study, our objective is to examine the differential plasma lipidomic responses to non-fat or full-fat milk ingestion during postprandial hyperglycemia. Seven adults with prediabetes completed a randomized cross-over study in which glucose was consumed alone or with non-fat or full-fat dairy milk. Plasma samples collected at 90 min and 180 min post milk ingestion were used to perform untargeted lipidomics analysis. A total of 332 lipids from 20 classes and five lipid categories were detected at different time points during the postprandial period. Dairy milk, especially non-fat milk, protected against lipid changes otherwise induced by glucose ingestion. Co-ingestion of dairy milk with glucose, regardless of fat content, significantly altered lipid profiles although full-fat milk more substantially modulated lipid profiles. For the identified lipid biomarkers, 68.0% and 66.7% of the lipids significantly increased at 90 and 180 min, respectively, while phosphatidylcholines (GPs) contributed most for the significant increase. Comparative lipidomics analysis indicated that both types of dairy milk induced significant changes in several lipid pathways, including glycerophospholipid metabolism and α-linolenic acid metabolism, to protect against postprandial hyperglycemia. In summary, our comparative lipidomics results suggested that dairy milk-mediated lipid modulation may be an effective dietary approach to reduce the risk of metabolic diseases among those with prediabetes.

Synthetic α-Tocopherol, Compared with Natural α-Tocopherol, Downregulates Myelin Genes in Cerebella of Adolescent Ttpa-null Mice.

BACKGROUND: Vitamin E (α-tocopherol; α-T) deficiency causes spinocerebellar ataxia. α-T supplementation improves neurological symptoms, but little is known about the differential bioactivities of natural versus synthetic α-T during early life. OBJECTIVE: We assessed the effects of dietary α-T dose and source on tissue α-T accumulation and gene expression in adolescent α-tocopherol transfer protein-null (Ttpa-/-) mice. METHODS: Three-week-old male Ttpa-/- mice (n  = 7/group) were fed 1 of 4 AIN-93G-based diets for 4 wk: vitamin E deficient (VED; below α-T limit of detection); natural α-T, 600 mg/kg diet (NAT); synthetic α-T, 816 mg/kg diet (SYN); or high synthetic α-T, 1200 mg/kg diet (HSYN). Male Ttpa+/+ littermates fed AIN-93G [75 mg synthetic α-T (CON)] served as controls (n  = 7). At 7 wk of age, tissue α-T concentrations and stereoisomer profiles were measured for all groups. RNA-sequencing was performed on cerebella of Ttpa-/- groups. RESULTS: Ttpa-/- mice fed VED had undetectable brain α-T concentrations. Cerebral cortex α-T concentrations were greater in Ttpa-/- mice fed NAT (9.1 ± 0.7 nmol/g), SYN (10.8 ± 1.0 nmol/g), and HSYN (13.9 ± 1.6 nmol/g) compared with the VED group but were significantly lower than in Ttpa+/+ mice fed CON (24.6 ± 1.2 nmol/g) (P < 0.001). RRR-α-T was the predominant stereoisomer in brains of Ttpa+/+ mice (∼40%) and Ttpa-/- mice fed NAT (∼94%). α-T stereoisomer composition was similar in brains of Ttpa-/- mice fed SYN and HSYN (2R: ∼53%; 2S: ∼47%). Very few of the 16,774 genes measured were differentially expressed. However, compared with the NAT diet, HSYN significantly downregulated 20 myelin genes, including 2 transcription factors: SRY-box transcription factor 10 (Sox10) and myelin regulatory factor (Myrf), and several downstream target genes (false discovery rate <0.05). CONCLUSIONS: High-dose synthetic α-T compared with natural α-T alters myelin gene expression in the adolescent mouse cerebellum, which could lead to morphological and functional abnormalities later in life.

Controlled Feeding of an 8-d, High-Dairy Cheese Diet Prevents Sodium-Induced Endothelial Dysfunction in the Cutaneous Microcirculation of Healthy, Older Adults through Reductions in Superoxide.

BACKGROUND: While excess dietary sodium impairs vascular function by increasing oxidative stress, the dietary incorporation of dairy foods improves vascular health. We demonstrated that single-meal cheese consumption ameliorates acute, sodium-induced endothelial dysfunction. However, controlled feeding studies examining the inclusion of cheese, a dairy product that contains both bioactive constituents and sodium, are lacking. OBJECTIVES: We tested the hypothesis that microcirculatory endothelium-dependent dilation (EDD) would be impaired by a high-sodium diet, but a sodium-matched diet high in dairy cheese would preserve EDD through oxidant stress mechanisms. METHODS: We gave 11 adults without salt-sensitive blood pressure (<10 mmHg Δ mean arterial pressure; 64 ± 2 y) 4 separate 8-d controlled dietary interventions in a randomized, crossover design: a low-sodium, no-dairy intervention (LNa; 1500 mg/d sodium); a low-sodium, high-cheese intervention (LNaC; 1500 mg/d sodium, 170 g/d cheese); a high-sodium, no-dairy intervention (HNa; 5500 mg/d sodium); and a high-sodium, high-cheese intervention (HNaC; 5500 mg/d sodium, 170 g/d cheese). On Day 8 of each diet, EDD was assessed through a localized infusion (intradermal microdialysis) of acetylcholine (ACh), both alone and during coinfusion of NG-nitro-L-arginine methyl ester (NO synthase inhibitor), L-ascorbate (nonspecific antioxidant), apocynin [NAD(P)H oxidase inhibitor], or tempol (superoxide scavenger). RESULTS: Compared with LNa, microvascular responsiveness to ACh was attenuated during HNa (LNa: -4.82 ± 0.20 versus HNa: -3.21 ± 0.55 M logEC50; P = 0.03) but not LNaC (-5.44 ± 0.20 M logEC50) or HNaC (-4.46 ± 0.50 M logEC50). Further, ascorbate, apocynin, and tempol administration each increased ACh-induced vasodilation during HNa only (Ringer's: 38.9 ± 2.4; ascorbate: 48.0 ± 2.5; tempol: 45.3 ± 2.7; apocynin: 48.5 ± 2.6% maximum cutaneous vascular conductance; all P values < 0.01). CONCLUSIONS: These results demonstrate that incorporating dairy cheese into a high-sodium diet preserves EDD by decreasing the concentration of superoxide radicals. Consuming sodium in cheese, rather than in nondairy sources of sodium, may be an effective strategy to reduce cardiovascular disease risk in salt-insensitive, older adults. This trial was registered at clinicaltrials.gov as NCT03376555.

Infant Rhesus Macaque Brain α-Tocopherol Stereoisomer Profile Is Differentially Impacted by the Source of α-Tocopherol in Infant Formula.

BACKGROUND: α-Tocopherol (αT) in its natural form [2'R, 4'R, 8'R αT (RRR-αT)] is more bioactive than synthetic α-tocopherol (all rac-αT). All rac-αT is widely used in infant formulas, but its accretion in formula-fed infant brain is unknown. OBJECTIVE: We sought to compare αT and stereoisomer status in infant rhesus macaques (Macaca mulatta) fed infant formula (RRR-αT or all rac-αT) with a reference group fed a mixed diet of breast milk and maternal diet. METHODS: From 1 d after birth until 6 mo of age, infants (n = 23) were either nursery reared and exclusively fed 1 of 2 formulas by staff personnel or were community housed with their mothers and consumed a mixed reference diet of breast milk (69 mL/d at 6 mo) transitioning to monkey diet at ∼2 mo (MF; n = 8). Formulas contained either 21 µmol RRR-αT/L (NAT-F; n = 8) or 30 µmol all rac-αT/L (SYN-F; n = 7). Total αT and αT stereoisomers were analyzed in breast milk at 2, 4, and 6 mo and in monkey plasma and liver and 6 brain regions at 6 mo of age. α-Tocopherol transfer protein (α-TTP), lipoprotein αT, and urinary α-carboxyethyl-hydroxychroman (α-CEHC) were measured. One-way ANOVA with Tukey's post-hoc test was used for analysis. RESULTS: At study termination, plasma, liver, lipoprotein, and brain total αT did not differ between groups. However, the NAT-F-fed group had higher RRR-αT than the SYN-F-fed group (P < 0.01) and the MF group (P < 0.0001) in plasma (1.7- and 2.7-fold) and brain (1.5- and 2.5-fold). Synthetic αT 2R stereoisomers (SYNTH-2R) were generally 3- and 7-fold lower in brain regions of the NAT-F group compared with those of the SYN-F and MF groups (P < 0.05). SYNTH-2R stereoisomers were 2-fold higher in MF than SYN-F (P < 0.0001). The plasma percentage of SYNTH-2R was negatively correlated with the brain percentage of RRR-αT (r = -0.99, P < 0.0001). Brain αT profiles were not explained by α-TTP mRNA or protein expression. Urine α-CEHC was 3 times higher in the NAT-F than in the MF group (P < 0.01). CONCLUSIONS: Consumption of infant formulas with natural (NAT-F) compared with synthetic (SYN-F) αT differentially impacted brain αT stereoisomer profiles in infant rhesus macaques. Future studies should assess the functional implications of αT stereoisomer profiles on brain health.

The National Football League Combine 40-yd Dash: How Important is Maximum Velocity?

Clark, KP, Rieger, RH, Bruno, RF, and Stearne, DJ. The NFL combine 40-yard dash: how important is maximum velocity? J Strength Cond Res 33(6): 1542-1550, 2019-This investigation analyzed the sprint velocity profiles for athletes who completed the 40-yard (36.6 m) dash at the 2016 National Football League (NFL) Combine. The purpose was to evaluate the relationship between maximum velocity and sprint performance, and to compare acceleration patterns for fast and slow athletes. Using freely available online sources, data were collected for body mass and sprint performance (36.6 m time with split intervals at 9.1 and 18.3 m). For each athlete, split times were used to generate modeled curves of distance vs. time, velocity vs. time, and velocity vs. distance using a monoexponential equation. Model parameters were used to quantify acceleration patterns as the ratio of maximum velocity to maximum acceleration (vmax/amax, or τ). Linear regression was used to evaluate the relationship between maximum velocity and sprint performance for the entire sample. In addition, athletes were categorized into fast and slow groups based on maximum velocity, with independent t-tests and effect size statistics used to evaluate between-group differences in sprint performance and acceleration patterns. Results indicated that maximum velocity was strongly correlated with sprint performance across 9.1, 18.3, and 36.6 m (r of 0.72, 0.83, and 0.94, respectively). However, both fast and slow groups accelerated in a similar pattern relative to maximum velocity (τ = 0.768 ± 0.068 seconds for the fast group and τ = 0.773 ± 0.070 seconds for the slow group). We conclude that maximum velocity is of critical importance to 36.6 m time, and inclusion of more maximum velocity training may be warranted for athletes preparing for the NFL Combine.

Unaccompanied homeless youth have extremely poor diet quality and nutritional status.

A lack of in-depth assessment of the nutritional status of homeless youth precludes interventions that achieve nutritional adequacy. We enrolled 118 unaccompanied homeless youth to obtain sociodemographic and health data along with dietary, anthropometric, biochemical, and clinical assessments. As a reference, homeless youth data were compared to a convenience sample of 145 college students. Obesity was prevalent among homeless youth than among college students (29% vs. 8% respectively (CI: 11.2, 29.9). Among homeless youth, 74% of females versus 41% of males were overweight/obese (CI: 14.9, 51.2). Homeless youth also had poor diet quality (44.37 (SD: 12.64)). Over 70% of homeless youth had inadequate intakes of vitamins A, C, D3 and E, as well as calcium and magnesium. Our findings show increased weight, adiposity, and suboptimal intakes of essential nutrients among unaccompanied homeless youth. Further studies are needed to inform evidence-based nutrition interventions that will aid in improving their nutritional health.

Comparative Metabolomics Elucidates Postprandial Metabolic Modifications in Plasma of Obese Individuals with Metabolic Syndrome.

Although higher intakes of dairy milk are associated with a lower risk of metabolic syndrome (MetS), the underlying protective mechanism remains unclear. This study investigated the dynamic metabolic profile shift following the ingestion of low-fat milk or an isocaloric volume of rice milk in obese individuals with metabolic syndrome (MetS). In a randomized, double-blind, crossover study, postprandial plasma samples ( n = 266) were collected from 19 MetS participants. Plasma samples were analyzed by a targeted metabolomics platform which specifically detects 117 metabolites from 25 metabolic pathways. The comprehensive time-course metabolic profiling in MetS participants indicated that the postprandial metabolic profiles distinguish low-fat milk and rice milk consumption in a time-dependent manner. Metabolic biomarkers, such as orotate, leucine/isoleucine and adenine, showed significantly different trends in the two test beverages. Bayesian statistics identified 12 metabolites associated with clinical characteristics of postprandial vascular endothelial function, such as flow-mediated dilation (FMD), postprandial plasma markers of oxidative stress and NO status. Furthermore, metabolic pathway analysis based on these metabolite data indicated the potential utility of metabolomics to provide mechanistic insights of dietary interventions to regulate postprandial metabolic excursions.

Premeal Low-Fat Yogurt Consumption Reduces Postprandial Inflammation and Markers of Endotoxin Exposure in Healthy Premenopausal Women in a Randomized Controlled Trial.

Background: Metabolic endotoxemia is associated with obesity and contributes to postprandial inflammation. Objective: We aimed to determine if low-fat yogurt consumption prevents postprandial inflammation and dysmetabolism in healthy women by inhibiting biomarkers of metabolic endotoxemia. Methods: Premenopausal women defined as obese and nonobese [body mass index (BMI, in kg/m2) 30-40 and 18.5-27, respectively, n = 120] were randomly assigned to consume 339 g of low-fat yogurt (YN, yogurt nonobese; YO, yogurt obese) or 324 g of soy pudding (CN, control nonobese; CO, control obese) for 9 wk (n = 30/group). The intervention foods each supplied 330 kcal with 3 g fat, 66 g carbohydrate, and 4-6 g protein. At weeks 0 and 9, participants ingested 226 g of yogurt or 216 g of soy pudding before a meal providing 56-60 g fat, 82 g carbohydrate, and 28-30 g protein. Plasma soluble CD14 (sCD14), lipopolysaccharide-binding protein (LBP), LPS activity, interleukin-6 (IL-6), glucose, triglyceride, and insulin were measured hourly for 4 h to assess differences in postprandial responses between groups by 2-factor ANOVA. Results: Premeal yogurt consumption prevented the postprandial decrease in sCD14 net incremental area under the curve (net iAUC) by 72% in obese individuals at week 0 (P = 0.0323). YN and YO had ≥40% lower net iAUC of LBP-to-sCD14 ratio and plasma IL-6 concentration than CN and CO, respectively (P < 0.05). CO had postprandial hyperglycemia which was not evident in YO; in contrast YN had 57% less postprandial hypoglycemia than did CN (P-interaction = 0.0013). After 9 wk of yogurt consumption, ΔAUC of LBP-to-sCD14 ratios of YO and YN were less than half of those of the control groups (P = 0.0093). Conclusion: Yogurt consumption improved postprandial metabolism and biomarkers of metabolic endotoxemia in healthy premenopausal women. Premeal yogurt consumption is a feasible strategy to inhibit postprandial dysmetabolism and thus may reduce cardiometabolic risk. This trial was registered at clinicaltrials.gov as NCT01686204.

Higher Primary Care Physician Continuity is Associated With Lower Costs and Hospitalizations.

PURPOSE: Continuity of care is a defining characteristic of primary care associated with lower costs and improved health equity and care quality. However, we lack provider-level measures of primary care continuity amenable to value-based payment, including the Medicare Quality Payment Program (QPP). We created 4 physician-level, claims-based continuity measures and tested their associations with health care expenditures and hospitalizations. METHODS: We used Medicare claims data for 1,448,952 beneficiaries obtaining care from a nationally representative sample of 6,551 primary care physicians to calculate continuity scores by 4 established methods. Patient-level continuity scores attributed to a single physician were averaged to create physician-level scores. We used beneficiary multilevel models, including beneficiary controls, physician characteristics, and practice rurality to estimate associations with total Medicare Part A & B expenditures (allowed charges, logged), and any hospitalization. RESULTS: Our continuity measures were highly correlated (correlation coefficients ranged from 0.86 to 0.99), with greater continuity associated with similar outcomes for each. Adjusted expenditures for beneficiaries cared for by physicians in the highest Bice-Boxerman continuity score quintile were 14.1% lower than for those in the lowest quintile ($8,092 vs $6,958; ß = -0.151; 95% CI, -0.186 to -0.116), and the odds of hospitalization were 16.1% lower between the highest and lowest continuity quintiles (OR = 0.839; 95% CI, 0.787 to 0.893). CONCLUSIONS: All 4 continuity scores tested were significantly associated with lower total expenditures and hospitalization rates. Such indices are potentially useful as QPP measures, and may also serve as proxy resource-use measures, given the strength of association with lower costs and utilization.

Co-ingestion of whole eggs or egg whites with glucose protects against postprandial hyperglycaemia-induced oxidative stress and dysregulated arginine metabolism in association with improved vascular endothelial function in prediabetic men.

Replacing a portion of a glucose challenge with whole eggs (EGG) or egg whites (WHITE) was shown to protect against glucose-induced impairments in vascular function. We hypothesised in the present study that previously observed vasoprotection following co-ingestion of EGG or WHITE with glucose was attributed to limiting postprandial hyperglycaemia-induced oxidative stress that improves NO∙ bioavailability. Prediabetic men completed a randomised, cross-over study in which they ingested isoenergetic meals containing 100 g glucose (GLU), or 75 g glucose with 1·5 EGG, seven WHITE or two egg yolks (YOLK). At 30 min intervals for 3 h, we assessed plasma NO∙ metabolites, the lipid peroxidation biomarker malondialdehyde, antioxidants, arginine and its methylated metabolites (asymmetric dimethylarginine and symmetric dimethylarginine), tetrahydrobiopterin redox status, vasoconstrictors and inflammatory markers. Compared with GLU, malondialdehyde was lower and NO∙ metabolites were greater in EGG and WHITE, but YOLK was not different from GLU. Malondialdehyde was inversely correlated with NO∙ metabolites and vascular function, whereas NO∙ metabolites were positively correlated with vascular function. Compared with GLU, arginine was greater, but asymmetric and symmetric dimethylarginine and angiotensin-II were lower in all egg-based meals. Antioxidants, tetrahydrobiopterin redox status and inflammatory markers did not differ among treatments. Thus, while each egg-based meal improved arginine metabolism, only EGG and WHITE limited lipid peroxidation. This suggests that vasoprotection mediated by EGG and WHITE likely occurs in an NO∙-dependent manner by improving arginine metabolism and attenuating oxidative stress that otherwise limit NO∙ biosynthesis and bioavailability to the vascular endothelium.

Replacing carbohydrate during a glucose challenge with the egg white portion or whole eggs protects against postprandial impairments in vascular endothelial function in prediabetic men by limiting increases in glycaemia and lipid peroxidation.

Eggs attenuate postprandial hyperglycaemia (PPH), which transiently impairs vascular endothelial function (VEF). We hypothesised that co-ingestion of a glucose challenge with egg-based meals would protect against glucose-induced impairments in VEF by attenuating PPH and oxidative stress. A randomised, cross-over study was conducted in prediabetic men (n 20) who ingested isoenegertic meals (1674 kJ (400 kcal)) containing 100 g glucose (GLU), or 75 g glucose with 1·5 whole eggs (EGG), seven egg whites (WHITE) or two egg yolks (YOLK). At 30 min intervals for 3 h, brachial artery flow-mediated dilation (FMD), plasma glucose, insulin, cholecystokinin (CCK), lipids (total, LDL- and HDL-cholesterol; TAG), F2-isoprostanes normalised to arachidonic acid (F2-IsoPs/AA), and methylglyoxal were assessed. In GLU, FMD decreased at 30-60 min and returned to baseline levels by 90 min. GLU-mediated decreases in FMD were attenuated at 30-60 min in EGG and WHITE. Compared with GLU, FMDAUC was higher in EGG and WHITE only. Relative to baseline, glucose increased at 30-120 min in GLU and YOLK but only at 30-90 min in EGG and WHITE. GlucoseAUC and insulinAUC were also lower in EGG and WHITE only. However, CCKAUC was higher in EGG and WHITE compared with GLU. Compared with GLU, F2-IsoPs/AAAUC was lower in EGG and WHITE but unaffected by YOLK. Postprandial lipids and methylglyoxal did not differ between treatments. Thus, replacing a portion of a glucose challenge with whole eggs or egg whites, but not yolks, limits postprandial impairments in VEF by attenuating increases in glycaemia and lipid peroxidation.

Low-fat yogurt consumption reduces biomarkers of chronic inflammation and inhibits markers of endotoxin exposure in healthy premenopausal women: a randomised controlled trial.

The anti-inflammatory mechanisms of low-fat dairy product consumption are largely unknown. The objective of this study was to determine whether low-fat yogurt reduces biomarkers of chronic inflammation and endotoxin exposure in women. Premenopausal women (BMI 18·5-27 and 30-40 kg/m2) were randomised to consume 339 g of low-fat yogurt (yogurt non-obese (YN); yogurt obese (YO)) or 324 g of soya pudding (control non-obese; control obese (CO)) daily for 9 weeks (n 30/group). Fasting blood samples were analysed for IL-6, TNF-α/soluble TNF II (sTNF-RII), high-sensitivity C-reactive protein, 2-arachidonoyl glycerol, anandamide, monocyte gene expression, soluble CD14 (sCD14), lipopolysaccharide (LPS), LPS binding protein (LBP), IgM endotoxin-core antibody (IgM EndoCAb), and zonulin. BMI, waist circumference and blood pressure were also determined. After 9-week yogurt consumption, YO and YN had decreased TNF-α/sTNFR-RII. Yogurt consumption increased plasma IgM EndoCAb regardless of obesity status. sCD14 was not affected by diet, but LBP/sCD14 was lowered by yogurt consumption in both YN and YO. Yogurt intervention increased plasma 2-arachidonoylglycerol in YO but not YN. YO peripheral blood mononuclear cells expression of NF-κB inhibitor α and transforming growth factor ß1 increased relative to CO at 9 weeks. Other biomarkers were unchanged by diet. CO and YO gained approximately 0·9 kg in body weight. YO had 3·6 % lower diastolic blood pressure at week 3. Low-fat yogurt for 9 weeks reduced biomarkers of chronic inflammation and endotoxin exposure in premenopausal women compared with a non-dairy control food. This trial was registered as NCT01686204.

Effects of prior aerobic exercise on sitting-induced vascular dysfunction in healthy men.

INTRODUCTION: Acute aerobic exercise prevents sitting-induced impairment of flow-mediated dilation (FMD). Further, evidence suggests that sitting-induced impairment of FMD occurs via an oxidative stress-dependent mechanism that disrupts endothelial function. PURPOSE: We hypothesized that acute aerobic exercise would prevent impairment of femoral artery FMD by limiting oxidative stress responses that increase endothelin-1 (ET-1) levels and disrupt nitric oxide (NO) status. METHODS: In a randomized, cross-over study, healthy men (n = 11; 21.2 ± 1.9 years) completed two 3 h sitting trials that were preceded by 45 min of either quiet rest (REST) or a single bout of continuous treadmill exercise (65% maximal oxygen consumption) (EX). Superficial femoral artery FMD, plasma glucose, malondialdehyde (MDA), ET-1, arginine (ARG) and its related metabolites [homoarginine (HA), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA)] were assessed at baseline, 1 h following EX (or REST) (0 h), and at 1 h intervals during 3 h of uninterrupted sitting. Data were analyzed using repeated measures ANOVA. RESULTS: During REST, femoral artery FMD declined from baseline (2.6 ± 1.8%) at 1, 2, and 3 h of sitting and resting shear rate decreased at 3 h. In contrast, when sitting was preceded by EX, femoral artery FMD (2.7 ± 2.0%) and resting shear rate responses were unaffected. No between trial differences were detected for plasma glucose, MDA, ET-1, ARG, HA, ADMA, or SDMA. CONCLUSION: Prior aerobic exercise prevented the decline in femoral artery FMD that is otherwise induced by prolonged sitting independent of changes in oxidative stress, ET-1, and NO status.

Zinc status alters growth and oxidative stress responses in rat hepatoma cells.

Zinc deficiency and excess influence cellular homeostasis and are believed to modulate apoptosis. Zinc also regulates cell growth and proliferation. Understanding of the role of zinc in the mechanisms associated with these changes is limited because of its diverse, complex, and cell-specific effects. Therefore, we investigated the oxidative stress responses and the underlying molecular mechanisms associated with the disruption of intracellular zinc homeostasis in H4IIE rat hepatoma cells. We found that zinc excess (100 µM) and DTPA (diethylenetriaminepentaacetic acid; 50-100 µM) induced zinc deficiency both generate reactive oxygen species (ROS) and decrease viability in H4IIE cells. However, cotreatment with the antioxidant, N-acetyl-L-cysteine (NAC) both reduced ROS production and protected cells from death. We additionally observed an increase in Bax mRNA and cytochrome c release from the mitochondria in DTPA-treated cells and an elevated expression of Fas/Fas ligand mRNA with zinc treatment. Both treatments increased p53 and MdM2 protein concentrations along with caspase 3/7 activity. These results suggest that zinc deficiency stimulates mitochondrial-dependent apoptosis whereas zinc activates the extrinsic-apoptotic pathway. Both decreasing and increasing cellular zinc concentrations modulate ROS mediated apoptosis and warrant further research on zinc mediated cancer chemoprevention in this and other cancer cell lines.

Whole milk dairy foods and cardiometabolic health: dairy fat and beyond.

Bovine dairy milk is a nutrient-rich matrix, but consumption of full-fat dairy food varieties has been claimed historically to be associated with poorer cardiometabolic health, a notion often attributed to the saturated fat content. However, continued investigation that includes observational studies and randomized controlled trials (RCTs) provide evidence that favorably supports full-fat dairy foods and their bioactive components on cardiometabolic health. This review addresses this controversy by examining the evidence surrounding full-fat dairy foods and their implications for human health. Dairy foods are heterogeneous, not just in their fat content but also in other compositional aspects within and between fermented (e.g., yogurt, cheese) and nonfermented products (e.g., milk) that could differentially influence cardiometabolic health. Drawing from complementary lines of evidence from epidemiological studies and RCTs, this review describes the health effects of dairy foods regarding their fat content, as well as their polar lipids that are concentrated in the milk fat globule fraction. Observational studies have limitedly supported the consumption of full-fat dairy to protect against cardiometabolic disorders. However, this framework has been disputed by RCTs indicating that dairy foods, regardless of their fat content or fermentation, are not detrimental to cardiometabolic health and may instead alleviate certain cardiometabolic risk factors. As dietary recommendations evolve, which currently indicate to avoid full-fat dairy foods, it is essential to consider the totality of evidence, especially from RCTs, while also recognizing that investigation is needed to evaluate the complexity of dairy foods within diverse dietary patterns and their impacts on cardiometabolic health.

Spinal cord injury-induced metabolic impairment and steatohepatitis develops in non-obese rats and is exacerbated by premorbid obesity.

Impaired sensorimotor functions are prominent complications of spinal cord injury (SCI). A clinically important but less obvious consequence is development of metabolic syndrome (MetS), including increased adiposity, hyperglycemia/insulin resistance, and hyperlipidemia. MetS predisposes SCI individuals to earlier and more severe diabetes and cardiovascular disease compared to the general population, which trigger life-threatening complications (e.g., stroke, myocardial infarcts). Although each comorbidity is known to be a risk factor for diabetes and other health problems in obese individuals, their relative contribution or perceived importance in propagating systemic pathology after SCI has received less attention. This could be explained by an incomplete understanding of MetS promoted by SCI compared with that from the canonical trigger diet-induced obesity (DIO). Thus, here we compared metabolic-related outcomes after SCI in lean rats to those of uninjured rats with DIO. Surprisingly, SCI-induced MetS features were equal to or greater than those in obese uninjured rats, including insulin resistance, endotoxemia, hyperlipidemia, liver inflammation and steatosis. Considering the endemic nature of obesity, we also evaluated the effect of premorbid obesity in rats receiving SCI; the combination of DIO + SCI exacerbated MetS and liver pathology compared to either alone, suggesting that obese individuals that sustain a SCI are especially vulnerable to metabolic dysfunction. Notably, premorbid obesity also exacerbated intraspinal lesion pathology and worsened locomotor recovery after SCI. Overall, these results highlight that normal metabolic function requires intact spinal circuitry and that SCI is not just a sensory-motor disorder, but also has significant metabolic consequences.

A green tea extract confection decreases circulating endotoxin and fasting glucose by improving gut barrier function but without affecting systemic inflammation: A double-blind, placebo-controlled randomized trial in healthy adults and adults with metabolic syndrome.

Anti-inflammatory activities of catechin-rich green tea extract (GTE) in obese rodents protect against metabolic endotoxemia by decreasing intestinal permeability and absorption of gut-derived endotoxin. However, translation to human health has not been established. We hypothesized that GTE would reduce endotoxemia by decreasing gut permeability and intestinal and systemic inflammation in persons with metabolic syndrome (MetS) compared with healthy persons. A randomized, double-blind, placebo-controlled, crossover trial in healthy adults (n = 19, 34 ± 2 years) and adults with MetS (n = 21, 40 ± 3 years) examined 4-week administration of a decaffeinated GTE confection (890 mg/d total catechins) on serum endotoxin, intestinal permeability, gut and systemic inflammation, and cardiometabolic parameters. Compared with the placebo, the GTE confection decreased serum endotoxin (P = .023) in both healthy persons and those with MetS, while increasing concentrations of circulating catechins (P < .0001) and γ-valerolactones (P = .0001). Fecal calprotectin (P = .029) and myeloperoxidase (P = .048) concentrations were decreased by GTE regardless of health status. Following the ingestion of gut permeability probes, urinary lactose/mannitol (P = .043) but not sucralose/erythritol (P > .05) was decreased by GTE regardless of health status. No between-treatment differences (P > .05) were observed for plasma aminotransferases, blood pressure, plasma lipids, or body mass nor were plasma tumor necrosis factor-α, interleukin-6, or the ratio of lipopolysaccharide-binding protein/soluble cluster of differentiation-14 affected. However, fasting glucose in both study groups was decreased (P = .029) by the GTE confection compared with within-treatment arm baseline concentrations. These findings demonstrate that catechin-rich GTE is effective to decrease circulating endotoxin and improve glycemic control in healthy adults and those with MetS, likely by reducing gut inflammation and small intestinal permeability but without affecting systemic inflammation.

Low-fat milk ingestion prevents postprandial hyperglycemia-mediated impairments in vascular endothelial function in obese individuals with metabolic syndrome.

Greater intakes of low-fat dairy foods are associated with a lower risk of cardiovascular disease. The objective of this study was to examine whether acute low-fat milk ingestion would limit postprandial impairments in vascular endothelial function by limiting oxidative stress responses that decrease nitric oxide (NO) bioavailability. A randomized, double-blind, cross-over study was conducted in adults with metabolic syndrome (MetS) who ingested low-fat milk (475 mL) or an isocaloric volume of rice milk after an overnight fast. Brachial artery flow-mediated dilation (FMD), plasma glucose, malondialdehyde (MDA), arginine (ARG), and asymmetric dimethylarginine (ADMA) were assessed at 30-min intervals during the 3-h postprandial period. Participants' (n = 19) postprandial FMD responses were unaffected by low-fat milk but transiently decreased (P < 0.01) from 6.2 ± 0.8% (mean ± SEM) at baseline to 3.3 ± 0.7% at 30 min and 3.9 ± 0.6% at 60 min following rice milk consumption. Glucose and MDA increased to a greater extent in the rice milk trial (P < 0.001). The MDA area under the 3 h postprandial curve (AUC0-3 h) was correlated with glucose AUC0-3 h (r = 0.75; P < 0.01) and inversely related to FMD AUC0-3 h (r = -0.59; P < 0.01). ARG decreased following rice milk and increased with low-fat milk, whereas only rice milk increased ADMA:ARG. The ADMA:ARG AUC0-3 h was correlated with MDA AUC0-3 h (r = 0.55) and was inversely related to FMD AUC0-3 h (r = -0.52) (P < 0.05). These findings suggest that low-fat milk maintains vascular endothelial function in individuals with MetS by limiting postprandial hyperglycemia that otherwise increases lipid peroxidation and reduces NO bioavailability. This trial was registered at clinicaltrials.gov as NCT01411293.