A Randomized Controlled Trial of Long-Term (R)-α-Lipoic Acid Supplementation Promotes Weight Loss in Overweight or Obese Adults without Altering Baseline Elevated Plasma Triglyceride Concentrations.

BACKGROUND: α-Lipoic acid (LA) is a dietary supplement for maintaining energy balance, but well-controlled clinical trials in otherwise healthy, overweight adults using LA supplementation are lacking. OBJECTIVES: The primary objective was to evaluate whether LA supplementation decreases elevated plasma triglycerides in overweight or obese adults. Secondary aims examined if LA promotes weight loss and improves oxidative stress and inflammation. METHODS: Overweight adults [n = 81; 57% women; 21-60 y old; BMI (in kg/m2) ≥ 25] with elevated plasma triglycerides ≥100 mg/dL were enrolled in a 24-wk, randomized, double-blind, controlled trial, assigned to either (R)-α-lipoic acid (R-LA; 600 mg/d) or matching placebo, and advised not to change their diet or physical activity. Linear models were used to evaluate treatment effects from baseline for primary and secondary endpoints. RESULTS: R-LA did not decrease triglyceride concentrations, but individuals on R-LA had a greater reduction in BMI at 24 wk than the placebo group (-0.8; P = 0.04). The effect of R-LA on BMI was correlated to changes in plasma triglycerides (r = +0.50, P = 0.004). Improvement in body weight was greater at 24 wk in R-LA subgroups than in placebo subgroups. Women and obese participants (BMI ≥ 35) showed greater weight loss (-5.0% and -4.8%, respectively; both P < 0.001) and loss of body fat (-9.4% and -8.6%, respectively; both P < 0.005). Antioxidant gene expression in mononuclear cells at 24 wk was greater in the R-LA group (Heme oxygenase 1 [HMOX1] : +22%; P = 0.02) than in placebo. Less urinary F2-isoprostanes (-25%; P = 0.005), blood leukocytes (-10.1%; P = 0.01), blood thrombocytes (-5.1%; P = 0.03), and ICAM-1 (-7.4%; P = 0.04) at 24 wk were also observed in the R-LA group than in placebo. CONCLUSIONS: Long-term LA supplementation results in BMI loss, greater antioxidant enzyme synthesis, and less potential for inflammation in overweight adults. Improved cellular bioenergetics is also evident in some individuals given R-LA.This trial was registered at clinicaltrials.gov as NCT00765310.

Mitochondrial membrane protein mitofusin 2 as a potential therapeutic target for treating free fatty acid-induced hepatic inflammation in dairy cows during early lactation.

Inflammation is critical in the progression from benign hepatic lipidosis to pathological hepatic steatosis. The objective of this study was to examine the potential role of the outer mitochondrial membrane protein mitofusin 2 (MFN2) in the etiology of hepatic steatosis in dairy cows during early lactation. Using a nested case-control design, we compared blood and liver samples from 10 healthy cows and 10 age-matched cows with moderate fatty liver. Cows with moderate fatty liver had high liver triacylglycerols, elevated plasma concentrations of free fatty acids (FFA) and ß-hydroxybutyrate, and low concentrations of glucose. Cows with moderate fatty liver had overactivated inflammatory pathways in the liver, as indicated by increased abundance of phosphorylated nuclear factor κB (NF-κB) p65, NLR family pyrin domain containing 3 (NLRP3) and caspase-1 inflammasome protein, and elevated plasma concentrations and hepatic mRNA abundance of their molecular targets IL-1ß, IL-6, and tumor necrosis factor α (TNF-α). In the cell culture model, we were able to replicate our findings in cows with moderate fatty liver: 1.2 mM exogenous FFA decreased the abundance of MFN2 and upregulated phosphorylation levels of the inhibitor of NF-κB (IκB) α and NF-κB p65, the IκB kinase ß activity, and the abundance of NLRP3, caspase-1, IL-1ß, IL-6, and TNF-α. Whereas MFN2 knockdown potentiated the FFA-induced activation of these inflammatory pathways, overexpression of MFN2 attenuated the detrimental effect of excess exogenous FFA by improving mitochondrial function and decreasing the release of reactive oxygen species, suggesting that MFN2 may be a potential therapeutic target for FFA-induced hepatic inflammation in dairy cows during early lactation.

Iatrogenic cartilage injury associated with the use of stainless-steel cannulas and silicone-guarded cannulas for canine stifle arthroscopy.

OBJECTIVE: To determine the ability to reduce iatrogenic cartilage injury (IACI) during canine stifle arthroscopy by using a silicone arthroscope cannula guard. STUDY DESIGN: Ex vivo canine cadaver experimental study. ANIMALS: Paired canine stifles from 14 cadavers (≥20 kg). METHODS: Stifles (N = 28) were assigned to unguarded traditional or silicone-guarded arthroscopy. Stifle arthroscopy and full joint exploration with meniscal probing was performed by a second-year surgery resident (I.C.) in fourteen canine cadavers, alternating between left and right stifles for guarded vs unguarded arthroscopy. After arthroscopy, stifles were disarticulated, and india ink assay was performed to identify IACI. Total IACI number, lesion length and area, duration of procedure, and procedure difficulty score were recorded for each stifle. RESULTS: Unguarded arthroscopy resulted in more total IACI per joint (unguarded 5.2 ± 3.0, guarded 2.4 ± 1.4; P = .02), larger IACI area (unguarded 5.2 ± 4.2 mm2 , guarded 2.3 ± 1.5 mm2 ; P = .02), and IACI length (unguarded 13.6 ± 6.9 mm, guarded 8.6 ± 5.9 mm; P = .03). No difference was identified in duration of procedure (unguarded 11.8 ± 5.2 minutes, guarded 13.8 ± 4.3 minutes; P = .79) or procedure difficulty score (unguarded 1.7 ± 0.6, guarded 1.6 ± 0.6 P = .73). CONCLUSION: Silicone-guarded arthroscope cannulas decreased IACI number and size during canine cadaveric stifle arthroscopy without increasing duration of procedure or surgical difficulty. CLINICAL SIGNIFICANCE: Silicone-guarded arthroscope cannulas may be safer than traditional cannulas for novice veterinary surgeons performing stifle arthroscopy.

Daily Consumption of Oregon Hazelnuts Affects α-Tocopherol Status in Healthy Older Adults: A Pre-Post Intervention Study.

Background: Inadequate vitamin E and magnesium intakes are of concern for older adults owing to the associated incidence of age-related diseases. Objective: This study was designed to determine the extent to which a 16-wk intervention with hazelnuts alters vitamin E and magnesium status in a group of older men and women, and used a pre-post intervention design without a control group to adjust for temporal changes. Methods: Participants (n = 32 including 22 women; mean ± SD age: 63 ± 6 y) consumed hazelnuts (∼57 g/d) for 16 wk. Blood and urine samples and anthropomorphic measures were taken at the start and end of the intervention to determine plasma concentrations of α-tocopherol and serum concentrations of magnesium, lipids, glucose, insulin, and high-sensitivity C-reactive protein along with urinary vitamin E metabolites; several other micronutrients were measured by a lymphocyte proliferation assay. There were 3 primary endpoints, calculated as the mean changes in measurements between baseline and the end of the 16-wk intervention for 1) plasma α-tocopherol, 2) urinary α-carboxyethyl hydroxychromanol (α-CEHC; an α-tocopherol metabolite), and 3) serum magnesium. Results: Hazelnut consumption increased concentrations of the urinary α-tocopherol metabolite α-CEHC (mean ± SD: 0.84 ± 0.45 to 1.14 ± 0.50 µmol/g creatinine; P = 0.0006). In addition, hazelnut consumption increased serum concentrations of magnesium (+2.1%, P = 0.05), decreased concentrations of fasting glucose (-3.4%, P = 0.03) and LDL cholesterol (-6.0%, P = 0.02), and decreased total:HDL cholesterol ratios (-4.5%, P = 0.009). No significant changes were observed in blood pressure, lymphocyte proliferation assays, and serum concentrations of insulin, high-sensitivity C-reactive protein, triglyceride, α-tocopherol, or HDL cholesterol. Conclusions: Consuming hazelnuts improves a biomarker of vitamin E status in older adults. Vitamin E is a shortfall micronutrient, as identified by the Dietary Guidelines for Americans 2015-2020, which frequently is consumed at levels less than the Estimated Average Requirement of 12 mg/d; thus, hazelnuts should be considered as part of a healthy dietary pattern. This trial was registered at clinicaltrials.gov as NCT03485989.

Stability of antioxidant vitamins in whole human blood during overnight storage at 4°C and frozen storage up to 6 months.

To determine optimal conditions for blood collection during clinical trials, where sample handling logistics might preclude prompt separation of erythrocytes from plasma, healthy subjects (n=8, 6 M/2F) were recruited and non-fasting blood samples were collected into tubes containing different anticoagulants (ethylenediaminetetra-acetic acid (EDTA), Li-heparin or Na-heparin). We hypothesized that heparin, but not EDTA, would effectively protect plasma tocopherols, ascorbic acid, and vitamin E catabolites (α- and γ-CEHC) from oxidative damage. To test this hypothesis, one set of tubes was processed immediately and plasma samples were stored at -80°C, while the other set was stored at 4°C and processed the following morning (~30 hours) and analyzed, or the samples were analyzed after 6 months of storage. Plasma ascorbic acid, as measured using HPLC with electrochemical detection (LC-ECD) decreased by 75% with overnight storage using EDTA as an anticoagulant, but was unchanged when heparin was used. Neither time prior to processing, nor anticoagulant, had any significant effects upon plasma α- or γ-tocopherols or α- or γ-CEHC concentrations. α- and γ-tocopherol concentrations remained unchanged after 6 months of storage at -80°C, when measured using either LC-ECD or LC/mass spectrometry. Thus, refrigeration of whole blood at 4°C overnight does not change plasma α- or γ-tocopherol concentrations or their catabolites. Ascorbic acid is unstable in whole blood when EDTA is used as an anticoagulant, but when whole blood is collected with heparin, it can be stored overnight and subsequently processed.

Comparison of iatrogenic articular cartilage injury in canine stifle arthroscopy versus medial parapatellar mini-arthrotomy in a cadaveric model.

OBJECTIVE: To assess iatrogenic articular cartilage injury (IACI) resulting from arthroscopy versus medial parapatellar mini-arthrotomy of the stifle. STUDY DESIGN: Paired comparison of canine cadaver stifles treated with arthroscopy or mini-arthrotomy ANIMALS: Paired canine stifles from 14 cadavers (≥20 kg). METHODS: Stifles (N = 28) were assigned to arthroscopy or arthrotomy. Full stifle joint exploration and meniscal probing were performed. Joints were disarticulated and India ink assay performed. IACI was defined as sharply delineated lesions with India ink uptake. Incidence, number, and lesion area in defects articular cartilage, incision length, surgery duration, and joint structures visualized were recorded. RESULTS: Arthroscopy resulted in greater IACI than mini-arthrotomy, including incidence of IACI (arthroscopy: 13 stifles, mini-arthrotomy: 4 stifles; P = .009), number of IACI per stifle (arthroscopy: 3.4 ± 2.90, mini-arthrotomy: 0.9 ± 1.96; P = .04), and IACI area (arthroscopy: 5.9 ± 7.58 mm2 , mini-arthrotomy: 1.7 ± 4.50 mm2 ; P = .003). Incision length was shorter with arthroscopy (1.0 ± 0.38 cm) versus mini-arthrotomy (5.3 ± 0.61 cm; P < .0001). Surgical duration was not significantly different between groups (arthroscopy: 12.5 ± 3.49 minutes, mini-arthrotomy: 11.05 ± 1.60 minutes; P = .21). Visualization of articular structures was incomplete in 14/14 mini-arthrotomy stifles and 1/14 arthroscopy stifles (P < .001). CONCLUSION: Incidence, number, and area of IACI were greater in the arthroscopy group versus the mini-arthrotomy group. Mini-arthrotomy resulted in a longer incision and incomplete joint visualization. Methods of preventing IACI and clinical significance of IACI warrant further investigation.

COMPUTED TOMOGRAPHIC CHARACTERISTICS OF THE THYROID GLANDS IN EIGHT HYPERTHYROID CATS PRE- AND POSTMETHIMAZOLE TREATMENT COMPARED WITH SEVEN EUTHYROID CATS.

Hyperthyroidism is the most common feline endocrinopathy; thyroid computed tomography (CT) may improve disease detection and methimazole dose selection. Objectives of this experimental pre-post with historical case-control study were to perform thyroid CT imaging in awake or mildly sedated hyperthyroid cats, compare thyroid gland CT appearance in euthyroid and hyperthyroid cats pre- and postmethimazole treatment, and determine whether thyroid size or attenuation correlate with methimazole dose needed for euthyroidism. Premethimazole treatment, eight hyperthyroid cats received CT scans from the head to heart, which were compared to CT of seven euthyroid cats. Total thyroxine levels were monitored every 3-4 weeks. Postmethimazole CT was performed 30 days after achieving euthyroid status. Computed tomography parameters recorded included thyroid length, width, height, attenuation, and heterogeneity. Median time between CT was 70 days (53-213 days). Mild sedation was needed in five hyperthyroid cats premethimazole, and none postmethimazole. Thyroid volume was significantly larger in hyperthyroid cats compared to euthyroid cats (785.0 mm3 vs. 154.9 mm3 ; P = 0.002) and remained unchanged by methimazole treatment (-4.5 mm3; P = 0.50). Thyroid attenuation and heterogeneity decreased with methimazole treatment (96.1 HU vs. 85.9 HU; P = 0.02. 12.4 HU vs. 8.1 HU; P = 0.009). Methimazole dose ranged from 2.5 to 10 mg daily with a positive correlation between pretreatment thyroid gland volume and dose needed to achieve euthyroidism (P = 0.03). Euthyroid and hyperthyroid cats are easily imaged awake or mildly sedated with CT. Methimazole in hyperthyroid cats significantly lowers thyroid attenuation and heterogeneity, but not size.

Evaluation of the Diagnostic Accuracy of Conventional 2-Dimensional and 3-Dimensional Computed Tomography for Assessing Canine Sacral and Pelvic Fractures by Radiologists, Orthopedic Surgeons, and Veterinary Medical Students.

OBJECTIVE: To determine, using 3 groups of evaluators of varying experience reading orthopedic CT studies, if 3-dimensional computed tomography (3D-CT) provides a more accurate and time efficient method for diagnosis of canine sacral and pelvic fractures, and displacements of the sacroiliac and coxofemoral joints compared with 2-dimensional computed tomography (2D-CT). STUDY DESIGN: Retrospective clinical and prospective study. ANIMALS: Dogs (n = 23): 12 dogs with traumatic pelvic fractures, 11 canine cadavers with pelvic trauma induced by a lateral impactor. METHODS: All dogs had a 2D-CT exam of the pelvis and subsequent 3D-CT reconstructions from the 2D-CT images. Both 2D-CT and 3D-CT studies were anonymized and randomly presented to 2 veterinary radiologists, 2 veterinary orthopedic surgeons, and 2 veterinary medical students. Evaluators classified fractures using a confidence scale and recorded the duration of evaluation for each modality and case. RESULTS: 3D-CT was a more time-efficient technique for evaluation of traumatic sacral and pelvic injuries compared with 2D-CT in all evaluator groups irrespective of experience level reading orthopedic CT studies. However, for radiologists and surgeons, 2D-CT was the more accurate technique for evaluating sacral and pelvic fractures. CONCLUSION: 3D-CT improves sacral and pelvic fracture diagnosis when added to 2D-CT; however, 3D-CT has a reduced accuracy for evaluation of sacral and pelvic fractures if used without concurrent evaluation of 2D-CT images.

COMBINATION OF COMPUTED TOMOGRAPHIC IMAGING CHARACTERISTICS OF MEDIAL RETROPHARYNGEAL LYMPH NODES AND NASAL PASSAGES AIDS DISCRIMINATION BETWEEN RHINITIS AND NEOPLASIA IN CATS.

Feline nasal diseases are a diagnostic challenge. The objective of this retrospective, cross-sectional study was to determine whether computed tomography (CT) imaging characteristics of the medial retropharyngeal lymph nodes (MRPLN), alone or in combination with CT imaging characteristics of the nasal passages, could aid in differentiation between rhinitis and nasal neoplasia. Cats were recruited from record archives at two veterinary facilities during the period of 2008-2012. Selection criteria were presentation for chronic nasal discharge, contrast-enhanced CT of the head that included the MRPLN, and rhinoscopic nasal biopsy resulting in diagnosis of rhinitis or neoplasia. For each CT scan, two board-certified veterinary radiologists recorded MRPLN size, attenuation, heterogeneity, contrast-medium enhancement, margination, shape, presence of a lymph node hilus, perinodal fat, turbinate lysis, paranasal bone lysis, and nasal mass. Both readers were unaware of patient information at the time of CT interpretation. Thirty-four cats with rhinitis and 22 cats with neoplasia were included. Computed tomographic characteristics significantly associated with neoplasia included abnormal MRPLN hilus (OR 5.1), paranasal bone lysis (OR 5.6), turbinate lysis (5.6), mass (OR 26.1), MRPLN height asymmetry (OR 4.5), and decreased MRPLN precontrast heterogeneity (OR 7.0). The combined features predictive of neoplasia were a nasal mass with abnormal hilus (OR 47.7); lysis of turbinates/paranasal bones with abnormal MRPLN hilus (OR 16.2). Findings supported the hypothesis that combining CT features of the nasal passages and MRPLN aided in differentiating rhinitis from neoplasia in cats.

Effect of supranutritional maternal and colostral selenium supplementation on passive absorption of immunoglobulin G in selenium-replete dairy calves.

Selenium (Se) is an essential micronutrient for ruminant animals affecting both performance and immune functions. Adding 3 mg of Se/L (in the form of Na selenite) to colostrum has been shown to improve IgG absorption in Se-deficient newborn dairy calves. The objective of our study was to determine the effect of supranutritional maternal and colostral Se supplementation on IgG status of Se-replete dairy calves. The study design was a 2 × 2 × 2 factorial design. During the last 8 wk before calving, dairy cows at a commercial dairy were fed either 0 (control cows) or 105 mg of Se-yeast once weekly (supranutritional Se-yeast-supplemented cows), in addition to Na selenite at 0.3 mg of Se/kg of DM in their ration. After birth, calves were fed pooled colostrum from control or supranutritional Se-yeast-supplemented cows to which 0 or 3 mg of Se/L (in the form of Na selenite) was added. Concentrations of whole-blood (WB) Se and serum Se measured at birth and at 48 h and 14 d of age, and serum IgG concentrations measured at 48 h and 14 and 60 d of age were determined. Calves born to Se-yeast-supplemented cows had higher WB-Se and serum-Se concentrations for the first 2 wk, and higher IgG absorption efficiency (62% at 48 h), resulting in higher serum-IgG concentrations (43% at 48 h and 65% at 14 d) and higher total serum-IgG content (50% at 48 h and 75% at 14 d), compared with calves born to control cows. Calves that received colostrum with added Na selenite had higher WB-Se concentrations for the first 2 wk, but only at 14 d of age were serum-Se concentrations, serum-IgG concentrations (53% higher), and total serum-IgG content (56% higher) higher, compared with calves that were fed colostrum without added Na selenite. Calves born to Se-yeast-supplemented cows that received colostrum from Se-yeast cows without added Na selenite had a higher IgG absorption efficiency compared with all other treatment groups. Our results support that feeding cows supranutritional Se-yeast supplement during the dry period or spiking colostrum with Na selenite both improve IgG status of Se-replete calves.

Reference gene selection for quantitative PCR studies in sheep neutrophils.

Reference genes are essential for studying mRNA expression with quantitative PCR (qPCR). We investigated 11 potential neutrophil reference genes (RPL19, GAPDH, ACTB, B2M, HPRT, G6PD, TFRC, PGK1, YWHAZ, SDHA and GYPC) for sheep under disease conditions of foot rot (FR) and with or without Se supplementation. Initial screening was based on gene expression level (<28 Cq cycles) and variability (SD < 1.5 Cq cycles) and excluded TFRC, GYPC and HPRT from further analysis. Expression stability of the remaining genes was evaluated using four software programs: geNorm, NormFinder, BestKeeper and the comparative delta Cq method. The neutrophil reference genes, G6PD, YWHAZ, GAPDH, RPL19 and SDHA, consistently ranked among the top five most stable genes under these experimental conditions. The SDHA gene expression was not stable in FR-diseased sheep receiving Se treatment and, thus, cannot be recommended as a reference gene. The commonly used genes, PGK1, ACTB and B2M, were not reliable reference genes, underscoring the need to validate neutrophil reference genes under different experimental conditions. Multiple references genes rather than a single gene may provide more robust and reliable results. The best pair of reference genes was SDHA/G6PD in healthy sheep and GADPH/YWHAZ in FR-diseased sheep.

Vegetarian diets and risk of all-cause mortality in a population-based prospective study in the United States.

The popularity of vegetarian diets has increased the need for studies on long-term health outcomes. A limited number of studies, including only one study from a non-vegetarian population, investigated the risk of mortality with self-identified vegetarianism and reported inconsistent results. This study evaluated prospective associations between vegetarian diets and all-cause mortality among 117,673 participants from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial cohort study. Vegetarian diet status was self-identified on the questionnaire. Deaths were ascertained from follow-up questionnaires and the National Death Index database. Multivariable Cox regression models were used to estimate the risk of all-cause mortality in hazard ratio (HR) and 95% confidence intervals (CI). By diet group, there were 116,894 omnivores (whose diet does not exclude animal products), 329 lacto- and/or ovo-vegetarians (whose diet excludes meat, but includes dairy and/or eggs), 310 pesco-vegetarians (whose diet excludes meat except for fish and seafood) and 140 vegans (whose diet excludes all animal products). After an average follow-up of 18 years, 39,763 participants were deceased. The risk of all-cause mortality did not statistically significantly differ among the four diet groups. Comparing with the omnivore group, the HR (95% CI) were 0.81 (0.64-1.03) for pesco-vegetarian group, 0.99 (0.80-1.22) for lacto- and/or ovo-vegetarian group and 1.27 (0.99-1.63) for vegan group, respectively. Similarly, mortality risk did not differ when comparing lacto- and/or ovo-vegetarians plus vegans with meat/fish eaters (omnivores and pesco-vegetarians) (HR [95% CI] = 1.09 [0.93-1.28]). As this study is one of the two studies of vegetarianism and mortality in non-vegetarian populations, further investigation is warranted.

Dairy product consumption and lung cancer risk: A prospective analysis.

BACKGROUND & AIM: Current evidence on prospective associations between dairy product, dairy fat and lactose intakes and lung cancer risk is limited and inconsistent. We conducted a prospective analysis of associations of lung cancer risk with dairy product intakes in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort. METHODS: Pre-diagnostic dairy product intake was assessed through a validated Diet History Questionnaire. All incident lung cancer cases were pathologically verified. Multivariable Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for associations of lung cancer risk with intakes of total, full-fat, low-fat dairy, fermented or non-fermented dairy products; milk fat content preference; and intakes of total and saturated fats and lactose from dairy products. RESULTS: Among 101,709 adults (mean age of 65.5 years), a total of 1583 lung cancer cases were identified during 1,167,239 person-years of follow up. Mean total dairy product intake was 156 g/1000 kilocalories (kcal), including 20 g/1000 kcal from fermented dairy products. Total dairy intake was not associated with lung cancer risk (HR [95% CI] = 1.03 [0.89-1.18]) comparing the highest quartile with the lowest. Fermented dairy intake was inversely associated with lung cancer risk (0.85 [0.72-0.99]). In contrast, there were no statistically significant associations with low-fat, full-fat or non-fermented dairy product intakes. The preference of whole milk when consuming milk as beverage was associated with a higher risk of lung cancer than the preference of <0.5% fat milk (1.24 [1.03-1.49]). Total fat, saturated fat and lactose intakes from dairy products each were not associated with lung cancer risk. CONCLUSIONS: Our results suggest an inverse association of lung cancer risk with fermented dairy intake and a positive association with the whole milk preference in a US population. Future studies exploring underlying molecular mechanisms are warranted.

Effects of Amount and Chemical Form of Selenium Amendments on Forage Selenium Concentrations and Species Profiles.

Selenium (Se) agronomic biofortification of plants is effective for alleviating Se deficiencies in human and livestock populations. Less is known about how higher selenate amendment rates, or how foliar compared with granular selenate amendments affect forage Se concentrations. Therefore, we compared the effects of a higher sodium selenate foliar amendment rate (900 vs. 90 g Se ha-1), and two selenate amendment methods (liquid foliar sodium selenate vs. granular slow-release Selcote Ultra® at 0, 45, and 90 g Se ha-1) on Se concentrations and Se species in forages across Oregon. The 10 × amendment rate (900 g Se ha-1) resulted in 6.4 × higher forage Se concentrations in the first cut (49.19 vs. 7.61 mg Se kg-1 plant DM, respectively) compared with the 90 g ha-1 amendment rate, indicating that forages can tolerate higher selenate amendment rates. Most Se was incorporated as SeMet (75%) in the harvested portion of the forage (37 mg Se kg-1 forage DM of the first cut) and only a limited amount was stored in the selenate reserve pool in the leaves (~ 5 mg Se kg-1 forage DM). Higher application rates of selenate amendment increased forage Se concentrations in first and second cuts, but carry over in subsequent years was negligible. Application of foliar selenate vs. granular Selcote Ultra® amendments, between 0 and 90 g Se ha-1, both resulted in a linear, dose-dependent increase in forage Se concentration. Amendments differed in their Se incorporation pattern (Se%), in that, first cut forage Se concentrations were higher with foliar selenate amendment and second, third, and residual (following spring) cut forage Se concentrations were higher with granular Selcote Ultra® amendment. Given the linear relationship between forage Se concentrations and whole-blood Se concentrations in livestock consuming Se-biofortified forage, we conclude that targeted grazing or other forage feeding strategies will allow producers to adapt to either selenate-amendment form.

Impact of selenium biofortification on production characteristics of forages grown following standard management practices in Oregon.

Introduction: Low selenium (Se) concentrations in soils and plants pose a health risk for ruminants consuming locally-grown forages. Previous studies have shown that Se concentrations in forages can be increased using soil-applied selenate amendments. However, the effects of foliar selenate amendments applied with traditional nitrogen-phosphorus-potassium-sulfur (NPKS) fertilizers on forage yields, and nutrient contents, and agronomic efficiencies are unknown. Methods: Using a split plot design, we determined the effects of springtime sodium selenate foliar amendment rates (0, 45, and 90 g Se ha-1) and NPKS application (none, NPK for grasses/PK for alfalfa, and NPKS/PKS fertilization at amounts adapted to meet local forage and soil requirements) on forage growth and N, S, and Se concentrations, yields, and agronomic efficiencies. This 2-year study was conducted across Oregon on four representative forage fields: orchardgrass (Dactylis glomerata L.) in Terrebonne (central Oregon), grass-clover mixture in Roseburg (southwestern Oregon), and both grass mixture and alfalfa (Medicago sativa L.) fields in Union (eastern Oregon). Results: Grasses grew poorly and were low in N content without NPK fertilization. Fertilization with NPK/PK promoted forage growth, increased forage N concentrations, and had to be co-applied with S when plant available S was low. Without Se amendment, forage Se concentrations were low and further decreased with NPKS/PKS fertilization. Selenate amendment linearly increased forage Se concentration without adversely affecting forage yields, N and S concentrations, or N and S agronomic efficiencies. Discussion: Importantly, S fertilization did not interfere with Se uptake in Se amended plots. In conclusion, co-application of NPKS/PKS fertilizers and foliar sodium selenate in springtime is an effective strategy to increase forage total Se concentrations, while maintaining optimal growth and quality of Oregon forages.

Multivitamin/Multimineral Supplementation Prevents or Reverses Decline in Vitamin Biomarkers and Cellular Energy Metabolism in Healthy Older Men: A Randomized, Double-Blind, Placebo-Controlled Study.

Despite the reported prevalence of micronutrient deficiencies in older adults, it is not yet established whether multivitamin/multimineral (MV/MM) supplements improve blood micronutrient status in individuals over the age of 65. Therefore, a cohort of 35 healthy men (>67 years) was recruited for an MV/MM supplementation trial. The primary endpoint was, as an indicator of micronutrient status, changes in blood micronutrient biomarkers from baseline to at least six months of supplementation with MV/MM or placebo. The secondary endpoint was basal O2 consumption in monocytes as an indicator of cellular metabolism. MV/MM supplementation improved blood concentrations of pyridoxal phosphate, calcifediol, α-tocopherol, and ß-carotene concentrations throughout the cohort. By contrast, those in the placebo group generally showed declines in blood vitamin concentrations and an increased prevalence of suboptimal vitamin status during the study period. On the other hand, MV/MM supplementation did not significantly affect blood mineral concentrations, i.e., calcium, copper, iron, magnesium, and zinc. Interestingly, MV/MM supplementation prevented the decline in monocyte O2 consumption rate. Overall, MV/MM use improves or prevents declines in vitamin, but not mineral, status and limits declines in cellular O2 consumption, which may have important implications for metabolism and immune health in healthy older men.

Effects of photon irradiation in the presence and absence of hindlimb unloading on the behavioral performance and metabolic pathways in the plasma of Fischer rats.

Introduction: The space environment astronauts experience during space missions consists of multiple environmental challenges, including microgravity. In this study, we assessed the behavioral and cognitive performances of male Fisher rats 2 months after sham irradiation or total body irradiation with photons in the absence or presence of simulated microgravity. We analyzed the plasma collected 9 months after sham irradiation or total body irradiation for distinct alterations in metabolic pathways and to determine whether changes to metabolic measures were associated with specific behavioral and cognitive measures. Methods: A total of 344 male Fischer rats were irradiated with photons (6 MeV; 3, 8, or 10 Gy) in the absence or presence of simulated weightlessness achieved using hindlimb unloading (HU). To identify potential plasma biomarkers of photon radiation exposure or the HU condition for behavioral or cognitive performance, we performed regression analyses. Results: The behavioral effects of HU on activity levels in an open field, measures of anxiety in an elevated plus maze, and anhedonia in the M&M consumption test were more pronounced than those of photon irradiation. Phenylalanine, tyrosine, and tryptophan metabolism, and phenylalanine metabolism and biosynthesis showed very strong pathway changes, following photon irradiation and HU in animals irradiated with 3 Gy. Here, 29 out of 101 plasma metabolites were associated with 1 out of 13 behavioral measures. In the absence of HU, 22 metabolites were related to behavioral and cognitive measures. In HU animals that were sham-irradiated or irradiated with 8 Gy, one metabolite was related to behavioral and cognitive measures. In HU animals irradiated with 3 Gy, six metabolites were related to behavioral and cognitive measures. Discussion: These data suggest that it will be possible to develop stable plasma biomarkers of behavioral and cognitive performance, following environmental challenges like HU and radiation exposure.

Dietary lignan and proanthocyanidin consumption and colorectal adenoma recurrence in the Polyp Prevention Trial.

Lignans and proanthocyanidins are plant polyphenols that have shown protective properties against colorectal neoplasms in some human studies. Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to prospectively evaluate the association between lignan and proanthocyanidin intake, estimated from databases linked to a food frequency questionnaire, and adenoma recurrence in 1,859 participants of the Polyp Prevention Trial. Overall, individual or total lignans or proanthocyanidins were not associated with colorectal adenoma recurrence. However, in sex-specific analyses, total lignan intake was positively associated with any adenoma recurrence in women (highest vs. lowest lignan intake quartile OR = 2.07, 95% CI: 1.22-3.52, p trend = 0.004) but not in men (p interaction = 0.04). To conclude, dietary lignan and proanthocyanidin consumption were not generally related to colorectal adenoma recurrence; however, high lignan intake may increase the risk of adenoma recurrence in women.

Plasma cytokines as potential response indicators to dietary freeze-dried black raspberries in colorectal cancer patients.

Oral consumption of freeze-dried black raspberries attenuated neoplastic changes in colorectal tissue markers of apoptosis, cell proliferation, and angiogenesis in colorectal cancer (CRC) patients. To determine whether plasma concentrations of interleukin (IL)-1ß, IL-2, IL-6, IL-8, IL-10, IL-12p70, granulocyte macrophage colony stimulating factor (GM-CSF), interferon-γ, and tumor necrosis factor-α (TNF-α) were associated with berry treatment and changes in colorectal tissue markers of apoptosis, cell proliferation, and angiogenesis, plasma and biopsy samples of adenocarcinoma and adjacent normal-appearing colorectal tissue were collected before and during berry treatment from 24 CRC patients who had not received prior therapy and drank a slurry of black raspberry powder (20 g in 100 ml drinking water) 3 times a day for 1 to 9 wk. Plasma concentrations of GM-CSF (+0.12 ± 0.04 pg/mL; P = 0.01) and IL-8 (-1.61 ± 0.71 pg/mL; P = 0.04) changed in patients receiving berries for more than 10 days. These changes were correlated with beneficial changes in markers of proliferation (r(ΔGM-CSF, ΔKi67 carcinoma - normal) = -0.51) and apoptosis (r(ΔIL-8, ΔTUNEL carcinoma - normal) = -0.52) observed in colorectal tissue taken within the same week. Plasma concentrations of GM-CSF and IL-8 may serve as noninvasive indicators to monitor tissue response to berry-based interventions for CRC.

Supranutritional Selenium-Yeast Supplementation of Beef Cows during the Last Trimester of Pregnancy Results in Higher Whole-Blood Selenium Concentrations in Their Calves at Weaning, but Not Enough to Improve Nasal Microbial Diversity.

We previously reported that feeding Se-biofortified alfalfa hay to weaned beef calves in a preconditioning program increases whole-blood Se (WB-Se) concentrations and nasal microbiome abundance and diversity during the preconditioning period, decreases morbidity and mortality during the feedlot period, and increases carcass weight and quality at slaughter. The objective of the current study was to see whether similar improvements can be achieved through Se supplementation of dams during various pregnancy trimesters. In a two-year experimental study, 80 Angus-cross cows received once-weekly Se-yeast boluses containing 105 mg of Se, during either the first (TR-1), second (TR-2), or third (TR-3) pregnancy trimester, or were not bolused (CTR). Whole-blood Se concentrations were higher from CTR, to TR-1, to TR-2, and to TR-3 in newborn calves (all p < 0.01). At weaning, only calves from TR-3 mothers had higher WB-Se concentrations compared with calves from CTR mothers (p = 0.02), and no significant differences in nasal microbiome abundance and diversity or nasal microbiota were observed. In the feedlot period, morbidity was low, and no differences were observed. At slaughter, no differences in carcass weight and quality were observed. In conclusion, Se supplementation of pregnant cows is effective for increasing WB-Se concentration of newborn calves, and the increase can be sustained until weaning for calves born to TR-3 dams. However, the increase in WB-Se concentrations is small and does not result in beneficial changes in the nasal microbiome. Thus, calves should be fed Se-biofortified forages again at weaning in a preconditioning program in order to diversify the nasal microbiome prior to entering the feedlot.