The effects of nuts on major cardiovascular disease (CVD) risk factors, including dose-responses and potential heterogeneity by nut type or phytosterol content, are not well established.
We examined ...the effects of tree nuts (walnuts, pistachios, macadamia nuts, pecans, cashews, almonds, hazelnuts, and Brazil nuts) on blood lipids total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein, and triglycerides, lipoproteins apolipoprotein A1, apolipoprotein B (ApoB), and apolipoprotein B100, blood pressure, and inflammation (C-reactive protein) in adults aged ≥18 y without prevalent CVD.
We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two investigators screened 1301 potentially eligible PubMed articles in duplicate. We calculated mean differences between nut intervention and control arms, dose-standardized to one 1-oz (28.4 g) serving/d, by using inverse-variance fixed-effects meta-analysis. Dose-response for nut intake was examined by using linear regression and fractional polynomial modeling. Heterogeneity by age, sex, background diet, baseline risk factors, nut type, disease condition, duration, and quality score was assessed with meta-regression. Publication bias was evaluated by using funnel plots and Egger's and Begg's tests.
Sixty-one trials met eligibility criteria (n = 2582). Interventions ranged from 3 to 26 wk. Nut intake (per serving/d) lowered total cholesterol (-4.7 mg/dL; 95% CI: -5.3, -4.0 mg/dL), LDL cholesterol (-4.8 mg/dL; 95% CI: -5.5, -4.2 mg/dL), ApoB (-3.7 mg/dL; 95% CI: -5.2, -2.3 mg/dL), and triglycerides (-2.2 mg/dL; 95% CI: -3.8, -0.5 mg/dL) with no statistically significant effects on other outcomes. The dose-response between nut intake and total cholesterol and LDL cholesterol was nonlinear (P-nonlinearity < 0.001 each); stronger effects were observed for ≥60 g nuts/d. Significant heterogeneity was not observed by nut type or other factors. For ApoB, stronger effects were observed in populations with type 2 diabetes (-11.5 mg/dL; 95% CI: -16.2, -6.8 mg/dL) than in healthy populations (-2.5 mg/dL; 95% CI: -4.7, -0.3 mg/dL) (P-heterogeneity = 0.015). Little evidence of publication bias was found.
Tree nut intake lowers total cholesterol, LDL cholesterol, ApoB, and triglycerides. The major determinant of cholesterol lowering appears to be nut dose rather than nut type. Our findings also highlight the need for investigation of possible stronger effects at high nut doses and among diabetic populations.
Interleukin-17A (IL-17A) is elaborated by the T helper 17 (T(H)17) subset of T(H) cells and exhibits potent proinflammatory properties in animal models of autoimmunity, including collagen-induced ...arthritis, experimental autoimmune encephalomyelitis, and experimental autoimmune uveitis. To determine whether IL-17A mediates human inflammatory diseases, we investigated the efficacy and safety of AIN457, a human antibody to IL-17A, in patients with psoriasis, rheumatoid arthritis, and chronic noninfectious uveitis. Patients with chronic plaque-type psoriasis (n = 36), rheumatoid arthritis (n = 52), or chronic noninfectious uveitis (n = 16) were enrolled in clinical trials to evaluate the effects of neutralizing IL-17A by AIN457 at doses of 3 to 10 mg/kg, given intravenously. We evaluated efficacy by measuring the psoriasis area and severity index (PASI), the American College of Rheumatology 20% response (ACR20) for rheumatoid arthritis, or the number of responders for uveitis, as defined by either vision improvement or reduction in ocular inflammation or corticosteroid dose. AIN457 treatment induced clinically relevant responses of variable magnitude in patients suffering from each of these diverse immune-mediated diseases. Variable response rates may be due to heterogeneity in small patient populations, differential pathogenic roles of IL-17A in these diseases, and the different involvement or activation of IL-17A-producing cells. The rates of adverse events, including infections, were similar in the AIN457 and placebo groups. These results support a role for IL-17A in the pathophysiology of diverse inflammatory diseases including psoriasis, rheumatoid arthritis, and noninfectious uveitis.
Evolution of a Type Ia supernova (SN Ia) progenitor requires formation of a CO white dwarf (WD), which implies a dependence on the C-burning rate (CBR). It can also be affected by the recently ...identified possibility of C-flame quenching by convective boundary mixing. We present first results of our study of the combined effect of these two potential sources of uncertainty on the SN Ia progenitor evolution. We consider the possibility that the CBR is higher than its currently recommended value by as much as a factor of 1000 if unidentified resonances are important, or that it is significantly lower because of the hindrance effect. For stellar models that assume the Schwarzschild boundary for convection, the maximum initial mass for the formation of CO WDs increases from M
i 5.5 M for the CBR factor of 1000 to M
i 7.0 M for the CBR factor of 0.01. For C-flame quenching models, hybrid C-O-Ne WDs form for a range of initial mass of ΔM
i 1 M, which increases a fraction of stars that form WDs capable of igniting C in a thermonuclear runaway. The most extreme case is found for the CBR factor of 0.1 that is supported by the hindrance model. This nuclear physics assumption, combined with C-flame quenching, leads to the formation of a hybrid C-O-Ne WD with a mass of 1.3 M. Such WDs do not need to accrete much mass to reach the Chandrasekhar limit.
The noradrenergic locus coeruleus (LC) is one of the protein pathology epicenters in neurodegenerative diseases. In contrast to PET (positron emission tomography), MRI (magnetic resonance imaging) ...offers the spatial resolution necessary to investigate the 3–4 mm wide and 1.5 cm long LC. However, standard data postprocessing is often too spatially imprecise to allow investigating the structure and function of the LC at the group level. Our analysis pipeline uses a combination of existing toolboxes (SPM12, ANTs, FSL, FreeSurfer), and is tailored towards achieving suitable spatial precision in the brainstem area. Its effectiveness is demonstrated using 2 datasets comprising both younger and older adults. We also suggest quality assessment procedures which allow to quantify the spatial precision obtained. Spatial deviations below 2.5 mm in the LC area are achieved, which is superior to current standard approaches. Relevant for ageing and clinical researchers interested in brainstem imaging, we provide a tool for more reliable analyses of structural and functional LC imaging data which can be also adapted for investigating other nuclei of the brainstem.
The safety of DHA-rich oil from Schizochytrium sp. and ARA-rich oil from Mortierella alpina was separately evaluated by testing for gene mutations, clastogenicity, and aneugenicity, and by conducting ...28-day and 90-day dietary studies in Wistar rats. The results of all genotoxicity tests were negative. The 28-day and 90-day studies involved dietary exposure to 1000, 2500, and 5000 mg per kg bw of the DHA-rich and ARA-rich oils and two control diets: water and corn oil (vehicle control). There were no treatment-related effects of either the DHA-rich or ARA-rich oils on clinical observations, body weight, food consumption, behavior, hematology, clinical chemistry, coagulation, urinalysis parameters, or necropsy findings. Increases in cholesterol and triglyceride levels were considered related to a high oil diet and non-adverse. The no observable adverse effect level (NOAEL) for both the DHA-rich and ARA-rich oils was 5000 mg per kg bw, the highest dose tested. The results confirm that these oils possess toxicity profiles similar to those of other currently marketed oils and support the safety of DHA-rich oil from Schizochytrium sp. and ARA-rich oil from Mortierella alpina for their proposed uses in food.
•DHA-rich oil from Schizochytrium sp. and ARA-rich oil from Mortierella alpina were found safe for use in foods.•Both oils were found non-genotoxic.•No treatment-related effects were found in subchronic oral toxicity testing.•The NOAEL for both oils were 5000 mg per kg body weight, the highest dose tested.
The purpose of this statement is to provide consensus-based recommendations for optimal management and care for patients with primary mitochondrial disease. This statement is intended for physicians ...who are engaged in the diagnosis and management of these patients. Working group members were appointed by the Mitochondrial Medicine Society. The panel included members with several different areas of expertise. The panel members utilized surveys and the Delphi method to reach consensus. We anticipate that this statement will need to be updated as the field continues to evolve. Consensus-based recommendations are provided for the routine care and management of patients with primary genetic mitochondrial disease.
The purpose of this study was to investigate the reproductive and developmental toxicity of dietary exposure to DHA-rich oil from Schizochytrium sp. and ARA-rich oil from Mortierella alpina. In a ...developmental toxicity study, pregnant Wistar rats were untreated (control) or administered corn oil (vehicle control), 1000, 2500, or 5000 mg/kg bw/day of DHA-rich oil or ARA-rich oil via gavage from gestation days 6 through 20. In the reproductive toxicity study, male and female Wistar rats were administered vehicle control (corn oil), or 1000, 2500, or 5000 mg/kg bw/day of DHA- or ARA-rich oil via gavage throughout the mating period, pregnancy, and the nursing and lactation period. Differences in the number of fetuses, fetal skeletal malformations, and external and visceral anomalies in the developmental study and mortality, clinical signs, fertility indices, physical observations, gross necropsy findings, and gestation period length in the reproductive toxicity study were not dose-related or significantly different from control groups, and were not considered to be treatment related. The no observed adverse effect level (NOAEL) for maternal toxicity and embryo/fetal development and for paternal or maternal treatment-related reproductive toxicity for the DHA-rich oil and ARA-rich oil administered by gavage, was 5000 mg/kg bw/day.
•No developmental and reproductive toxicity was observed for DHA- or ARA-rich oil.•DHA- and ARA-rich oil are obtained from Schizochytrium sp. and Mortierella alpin, respectively.•The no adverse effect levels of DHA- and ARA-rich oil were 5 g/kg bw/day, the highest dose tested.
Ethylene glycol is highly toxic and represents an important cause of poisonings worldwide. Toxicity can result in central nervous system dysfunction, cardiovascular compromise, elevated anion gap ...metabolic acidosis and acute kidney injury. Many states have passed laws requiring addition of the bittering agent, denatonium benzoate, to ethylene glycol solutions to reduce severity of exposures. The objectives of this study were to identify differences between unintentional and intentional exposures and to evaluate the utility of denatonium benzoate as a deterrent.
Using the National Poison Data System, we performed a retrospective analysis of reported cases of ethylene glycol exposures from January 2006 to December 2013. Outcome classification was summed for intentionality and used as a basis for comparison of effect groups. There were 45,097 cases of ethylene glycol exposures resulting in 154 deaths. Individuals more likely to experience major effects or death were older, male, and presented with more severe symptoms requiring higher levels of care. Latitude and season did not correlate with increased exposures; however, there were more exposures in rural areas. Denatonium benzoate use appeared to have no effect on exposure severity or number.
Deaths due to ethylene glycol exposure were uncommon; however, there were major clinical effects and more exposures in rural areas. Addition of denatonium benzoate was not associated with a reduction in exposures. Alternative means to deter ingestion are needed. These findings suggest the need to consider replacing ethylene glycol with alternative and less toxic agents.
Neonatal hypertension occurs in up to 2% of neonatal intensive care survivors and in up to 3% of all neonates. Normal blood pressure (BP) measurements are required to diagnose and manage ...appropriately both hypotension and hypertension in the neonate and infant. The aim of this study was to provide normative BP measurements during the first year of life of healthy infants born at term, using an oscillometric method. Neonates were enrolled from August 2003 to August 2005. Exclusion criteria included: infants of mothers with hypertension or diabetes of any type, use of illicit substances, congenital or chromosomal anomaly, admission to the neonatal intensive care unit or possible sepsis. There were 406 infants enrolled, with 150 children followed at 6 months of age and 118 children at 12 months of age. There were no differences in BP measurements at 6 months or 12 months of age by gender, weight or height. A BP measurement above the 90th percentile on day 2 or at 6 months was not predictive of a BP above the 90th percentile at 12 months of age. Higher systolic and diastolic measurements at 6 months and 12 months were found, in comparison to those in previous studies using ultrasonic devices. The findings of this study provide normative BP values for infants during their first year of life, using the oscillometric method, the most frequently used method in paediatric, neonatal intensive care and emergency departments.
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