Dietary fat and not calcium supplementation or dairy product consumption is associated with changes in anthropometrics during a randomized, placebo-controlled energy-restriction trial

Insufficient calcium intake has been proposed to cause unbalanced energy partitioning leading to obesity. However, weight loss interventions including dietary calcium or dairy product consumption have not reported changes in lipid metabolism measured by the plasma lipidome

Effects of sample handling and storage on quantitative lipid analysis in human serum

There is sparse information about specific storage and handling protocols that minimize analytical error and variability in samples evaluated by targeted metabolomics. Variance components that affect quantitative lipid analysis in a set of human serum samples were determined. The effects of freeze-thaw, extraction state, storage temperature, and freeze-thaw prior to density-based lipoprotein fractionation were quantified. The quantification of high abundance metabolites, representing the biologically relevant lipid species in humans, was highly repeatable (with coefficients of variation as low as 0.01 and 0.02) and largely unaffected by 1–3 freeze-thaw cycles (with 0–8% of metabolites affected in each lipid class). Extraction state had effects on total lipid class amounts, including decreased diacylglycerol and increased phosphatidylethanolamine in thawed compared with frozen samples. The effects of storage temperature over 1 week were minimal, with 0–4% of metabolites affected by storage at 4°C, −20°C, or −80°C in most lipid classes, and 19% of metabolites in diacylglycerol affected by storage at −20°C. Freezing prior to lipoprotein fractionation by density ultracentrifugation decreased HDL free cholesterol by 37% and VLDL free fatty acid by 36%, and increased LDL cholesterol ester by 35% compared with fresh samples. These findings suggest that density-based fractionation should preferably be undertaken in fresh serum samples because up to 37% variability in HDL and LDL cholesterol could result from a single freeze-thaw cycle. Conversely, quantitative lipid analysis within unfractionated serum is minimally affected even with repeated freeze-thaw cycles

A Randomized Placebo-Controlled Trial of \u3cem\u3eN\u3c/em\u3e-Acetylcysteine for Cannabis Use Disorder in Adults

Background—Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults. Methods—In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18–50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200 mg (n=153) or placebo (n=149) twice daily. All participants received contingency management (CM) and medical management. The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment, compared between NAC and placebo participants. Results—There was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence (odds ratio = 1.00, 95% confidence interval 0.63 – 1.59; p=0.984). Overall, 22.3% of urine cannabinoid tests in the NAC group were negative, compared with 22.4% in the placebo group. Many participants were medication non-adherent; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group. Conclusions—In contrast with prior findings in adolescents, there is no evidence that NAC 1200 mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM. This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development, cannabis use profiles, responses to embedded behavioral treatment, medication adherence, and other factors

Lipidomic analysis of variation in response to simvastatin in the Cholesterol and Pharmacogenetics Study

Statins are commonly used for reducing cardiovascular disease risk but therapeutic benefit and reductions in levels of low-density lipoprotein cholesterol (LDL-C) vary among individuals. Other effects, including reductions in C-reactive protein (CRP), also contribute to treatment response. Metabolomics provides powerful tools to map pathways implicated in variation in response to statin treatment. This could lead to mechanistic hypotheses that provide insight into the underlying basis for individual variation in drug response. Using a targeted lipidomics platform, we defined lipid changes in blood samples from the upper and lower tails of the LDL-C response distribution in the Cholesterol and Pharmacogenetics study. Metabolic changes in responders are more comprehensive than those seen in non-responders. Baseline cholesterol ester and phospholipid metabolites correlated with LDL-C response to treatment. CRP response to therapy correlated with baseline plasmalogens, lipids involved in inflammation. There was no overlap of lipids whose changes correlated with LDL-C or CRP responses to simvastatin suggesting that distinct metabolic pathways govern statin effects on these two biomarkers. Metabolic signatures could provide insights about variability in response and mechanisms of action of statins

Enteric Microbiome Metabolites Correlate with Response to Simvastatin Treatment

Although statins are widely prescribed medications, there remains considerable variability in therapeutic response. Genetics can explain only part of this variability. Metabolomics is a global biochemical approach that provides powerful tools for mapping pathways implicated in disease and in response to treatment. Metabolomics captures net interactions between genome, microbiome and the environment. In this study, we used a targeted GC-MS metabolomics platform to measure a panel of metabolites within cholesterol synthesis, dietary sterol absorption, and bile acid formation to determine metabolite signatures that may predict variation in statin LDL-C lowering efficacy. Measurements were performed in two subsets of the total study population in the Cholesterol and Pharmacogenetics (CAP) study: Full Range of Response (FR), and Good and Poor Responders (GPR) were 100 individuals randomly selected from across the entire range of LDL-C responses in CAP. GPR were 48 individuals, 24 each from the top and bottom 10% of the LDL-C response distribution matched for body mass index, race, and gender. We identified three secondary, bacterial-derived bile acids that contribute to predicting the magnitude of statin-induced LDL-C lowering in good responders. Bile acids and statins share transporters in the liver and intestine; we observed that increased plasma concentration of simvastatin positively correlates with higher levels of several secondary bile acids. Genetic analysis of these subjects identified associations between levels of seven bile acids and a single nucleotide polymorphism (SNP), rs4149056, in the gene encoding the organic anion transporter SLCO1B1. These findings, along with recently published results that the gut microbiome plays an important role in cardiovascular disease, indicate that interactions between genome, gut microbiome and environmental influences should be considered in the study and management of cardiovascular disease. Metabolic profiles could provide valuable information about treatment outcomes and could contribute to a more personalized approach to therapy

Mobility and Upright Posture Are Associated with Different Aspects of Cognition in Older Adults

Objectives : Aging is associated with cognitive decline, including visuomotor and memory concerns, and with motor system changes, including gait slowing and stooped posture. We investigated the associations of visuomotor performance and episodic memory with motor system characteristics in healthy older adults. Methods : Neurologically healthy older adults ( N = 160, aged 50–89) completed a battery of cognitive and motor tasks. Cognitive variables were grouped by principal components analysis (PCA) into two components: visuomotor performance and verbal episodic memory. Our primary predictor variables were two aspects of motor function: timed-up-and-go (TUG) speed and neck angle. Additional predictor variables included demographic factors (age, sex and education) and indicators of physical fitness (body mass index/BMI and grip strength). All seven predictor variables were entered stepwise into a multiple regression model for each cognitive component. Results : Poor visuomotor performance was best predicted by a combination of advanced age, high BMI and slow TUG, whereas poor verbal memory performance was best predicted by a combination of advanced age, male sex, low education and acute neck angle. Conclusions : Upright posture and mobility were associated with different cognitive processes, suggesting different underlying neural mechanisms. These results provide the first evidence for a link between postural alignment and cognitive functioning in healthy older adults. Possible causal relationships are discussed

Testing unmanned aircraft systems for salmon spawning surveys

Unmanned aircraft systems (UASs) were tested for counting Chinook salmon (Oncorhynchus tshawytscha) redds as a more accurate, safer alternative to manned helicopter flights. Counting redds from the helicopter was less expensive and time consuming, but of the total redds counted at selected sites with a UAS, an average (± SD) of only 77% ± 14% was counted from the helicopter. A river-wide census of redds was not possible with a UAS because the study area was too large for the single field crew to survey. Simulation analyses were used to compare stratified random sampling (STRS) and sampling proportional to size (PPS) for estimating annual total redd counts from data collected with a UAS. The STRS estimates were more accurate and precise, whereas the PPS estimates, though biased, had 95% CIs that included the observed redd count more frequently. We strongly recommend that researchers conduct simulation analyses to evaluate alternative survey sampling methods if they are considering replacing census counts made from manned aircraft with counts estimated from data collected with a UAS. We conclude that UAS application reduces the risk inherent to manned aircraft flights, but the reduction in risk can come at the cost of estimates of population parameters that can sometimes be inaccurate and lack 95% CI coverage

Effects of sample handling and storage on quantitative lipid analysis in human serum

There is sparse information about specific storage and handling protocols that minimize analytical error and variability in samples evaluated by targeted metabolomics. Variance components that affect quantitative lipid analysis in a set of human serum samples were determined. The effects of freeze-thaw, extraction state, storage temperature, and freeze-thaw prior to density-based lipoprotein fractionation were quantified. The quantification of high abundance metabolites, representing the biologically relevant lipid species in humans, was highly repeatable (with coefficients of variation as low as 0.01 and 0.02) and largely unaffected by 1–3 freeze-thaw cycles (with 0–8% of metabolites affected in each lipid class). Extraction state had effects on total lipid class amounts, including decreased diacylglycerol and increased phosphatidylethanolamine in thawed compared with frozen samples. The effects of storage temperature over 1 week were minimal, with 0–4% of metabolites affected by storage at 4°C, −20°C, or −80°C in most lipid classes, and 19% of metabolites in diacylglycerol affected by storage at −20°C. Freezing prior to lipoprotein fractionation by density ultracentrifugation decreased HDL free cholesterol by 37% and VLDL free fatty acid by 36%, and increased LDL cholesterol ester by 35% compared with fresh samples. These findings suggest that density-based fractionation should preferably be undertaken in fresh serum samples because up to 37% variability in HDL and LDL cholesterol could result from a single freeze-thaw cycle. Conversely, quantitative lipid analysis within unfractionated serum is minimally affected even with repeated freeze-thaw cycles

Effect of Omega-3 Dosage on Cardiovascular Outcomes : An Updated Meta-Analysis and Meta-Regression of Interventional Trials

Objectives:To quantify the effect of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids oncardiovascular disease (CVD) prevention and the effect of dosage. Methods:This study is designed as a random effects meta-analysis and meta-regression of ran-domized control trials with EPA/DHA supplementation. This is an update and expanded analysis ofa previously published meta-analysis which covers all randomized control trials with EPA/DHAinterventions and cardiovascular outcomes published before August 2019. The outcomes includedare myocardial infarction (MI), coronary heart disease (CHD) events, CVDevents (a composite ofMI, angina, stroke, heart failure, peripheral arterial disease, sudden death, and non-scheduledcardiovascular surgical interventions), CHD mortality and fatal MI. The strength of evidence wasassessed using the Grading of Recommendations Assessment, Development, and Evaluationframework. Results:A total of 40 studies with a combined 135,267 participants were included. Supplementationwas associated with reduced risk of MI (relative risk [RR], 0.87; 95% CI, 0.80 to 0.96), high certaintynumber needed to treat (NNT) of 272; CHD events (RR, 0.90; 95% CI, 0.84 to 0.97), high certaintyNNT of 192; fatal MI (RR, 0.65; 95% CI, 0.46 to 0.91]), moderate certainty NNT¼128; and CHDmortality (RR, 0.91; 95% CI, 0.85 to 0.98), low certainty NNT¼431, but not CVD events (RR, 0.95;95% CI, 0.90 to 1.00). The effect is dose dependent for CVD events and MI. Conclusion:Cardiovascular disease remains the leading cause of death worldwide. Supplementationwith EPA and DHA is an effective lifestyle strategy for CVD prevention, and the protective effectprobably increases with dosage.peerReviewe

A Proteinaceous Elicitor Sm1 from the Beneficial Fungus Trichoderma virens Is Required for Induced Systemic Resistance in Maize1[W]

We have previously shown that the beneficial filamentous fungus Trichoderma virens secretes the highly effective hydrophobin-like elicitor Sm1 that induces systemic disease resistance in the dicot cotton (Gossypium hirsutum). In this study we tested whether colonization of roots by T. virens can induce systemic protection against a foliar pathogen in the monocot maize (Zea mays), and we further demonstrated the importance of Sm1 during maize-fungal interactions using a functional genomics approach. Maize seedlings were inoculated with T. virens Gv29-8 wild type and transformants in which SM1 was disrupted or constitutively overexpressed in a hydroponic system or in soil-grown maize seedlings challenged with the pathogen Colletotrichum graminicola. We show that similar to dicot plants, colonization of maize roots by T. virens induces systemic protection of the leaves inoculated with C. graminicola. This protection was associated with notable induction of jasmonic acid- and green leaf volatile-biosynthetic genes. Neither deletion nor overexpression of SM1 affected normal growth or development of T. virens, conidial germination, production of gliotoxin, hyphal coiling, hydrophobicity, or the ability to colonize maize roots. Plant bioassays showed that maize grown with SM1-deletion strains exhibited the same levels of systemic protection as non-Trichoderma-treated plants. Moreover, deletion and overexpression of SM1 resulted in significantly reduced and enhanced levels of disease protection, respectively, compared to the wild type. These data together indicate that T. virens is able to effectively activate systemic disease protection in maize and that the functional Sm1 elicitor is required for this activity