The Multi-Omic Approach to Newborn Screening: Opportunities and Challenges.

Newborn screening programs have seen significant evolution since their initial implementation more than 60 years ago, with the primary goal of detecting treatable conditions within the earliest possible timeframe to ensure the optimal treatment and outcomes for the newborn. New technologies have driven the expansion of screening programs to cover additional conditions. In the current era, the breadth of screened conditions could be further expanded by integrating omic technologies such as untargeted metabolomics and genomics.

FAST-IT: ind imple est - n IA (transient ischaemic attack): a prospective cohort study to develop a multivariable prediction model for diagnosis of TIA through proteomic discovery and candidate lipid mass spectrometry, neuroimaging and machine learning-study protocol.

Introduction: Transient ischaemic attack (TIA) may be a warning sign of stroke and difficult to differentiate from minor stroke and TIA-mimics. Urgent evaluation and diagnosis is important as treating TIA early can prevent subsequent strokes. Recent improvements in mass spectrometer technology allow quantification of hundreds of plasma proteins and lipids, yielding large datasets that would benefit from different approaches including machine learning.

A rapid method for the screening of fatty acids in lipids in plasma or serum without prior extraction.

Serum or plasma are the commonly used blood fractions to determine the relationship between dietary and circulating fatty acids in health and disease. Most methods available for the measurement of fatty acids in serum or plasma (referred to as serum henceforth) require prior extraction with organic solvents. We have determined that it is possible to directly convert the lipids in aqueous biological samples to fatty acid methyl esters (FAME) without prior extraction, providing that the ratio of serum to transmethylation solvent does not exceed 10%.

Increased inspired oxygen concentration does not adversely affect oxidative stress and the resolution of inflammation during reperfusion in patients undergoing knee replacement surgery.

The level of inspired oxygen during surgery may modify free radical release, and reperfusion injury. This controlled trial examined the effect of inspired oxygen on F-isoprostanes (F-IsoPs), isofurans (IsoFs), and specialized mediators of inflammation resolution (SPM) during knee replacement surgery. Patients received either 30% O (control  = 21), 50% O ( = 20), or 80% O ( = 19) O, in a parallel design.

Effects of antiemetic doses of dexamethasone on plasma mediators of inflammation resolution and pain after surgery in women.

Background: Dexamethasone is commonly given as an antiemetic during surgical procedures. It has immunosuppressive effects and can affect key enzymes involved in the synthesis of specialised lipid mediators of inflammation resolution (SPM) that direct inflammation resolution and have anti-nociceptive actions. This study examined the effect of dexamethasone on plasma SPM, and the relationship between SPM and perceived pain in women undergoing surgery.

Potency test to discriminate between differentially over-inactivated rabies vaccines: Agreement between the NIH assay and a G-protein based ELISA.

The NIH assay is used to assess the potency of rabies vaccine and is currently a key measure required for vaccine release. As this test involves immunization of mice and subsequent viral challenge, efforts are being made to develop alternative analytical methods that do not rely on animal testing. Sanofi Pasteur has reported the development of a G-protein specific ELISA assay that has shown agreement with the NIH test.

Antiemetic doses of dexamethasone and their effects on immune cell populations and plasma mediators of inflammation resolution in healthy volunteers.

Introduction: The synthetic glucocorticoid dexamethasone is a commonly administered antiemetic. It has immunosuppressive effects and may alter postoperative blood glucose concentrations. Dexamethasone can effect key enzymes involved in inflammation resolution that is an active process driven by specialised lipid mediators of inflammation resolution (SPM).

The effects of alcohol on plasma lipid mediators of inflammation resolution in patients with Type 2 diabetes mellitus.

Background: Type 2 diabetes mellitus is characterized by peripheral insulin resistance and low-grade systemic inflammation. Inflammation resolution is recognised as an important process driven by specialised pro-resolving mediators of inflammation (SPMs) and has the potential to moderate chronic inflammation. Alcohol has the potential to affect synthesis of SPMs by altering key enzymes involved in SPM synthesis and may influence ongoing inflammation associated with Type 2 diabetes mellitus.

Effects of prenatal n-3 fatty acid supplementation on offspring resolvins at birth and 12 years of age: a double-blind, randomised controlled clinical trial.

Resolution of inflammation is an active process involving specialised pro-resolving mediators (SPM) generated from the n-3 fatty acids EPA and DHA. n-3 Fatty acid supplementation during pregnancy may provide an intervention strategy to modify these novel SPM. This study aimed to assess the effect of n-3 fatty acid supplementation in pregnancy on offspring SPM at birth and 12 years of age (12 years).

Hyperbaric oxygen therapy is not associated with oxidative stress assessed using plasma F-isoprostanes and isofurans.

Background And Aims: Hyperbaric oxygen (HBO) therapy is increasingly used in medical practice as a means of enhancing the formation of collagen matrix and angiogenesis, thus promoting healing in wounds and necrotic tissue. However, there are concerns that oxygen can also associate with increased production of oxygen free radicals and oxidative stress. F-Isoprostanes (F-IsoPs) formed by non-enzymatic oxidation of arachidonic acid (AA) are reliable measures for assessing oxidative stress in vivo.

A Randomized Trial of Effects of Alcohol on Cytochrome P450 Eicosanoids, Mediators of Inflammation Resolution, and Blood Pressure in Men.

Background: Cardiovascular effects of alcohol consumption may be influenced by both pro- and anti-inflammatory mechanisms. We previously showed that chronic alcohol consumption increased blood pressure (BP), oxidative stress, and 20-hydroxyeicosatetraenoic acid (20-HETE), a vasoconstrictor and pro-inflammatory eicosanoid synthesized by cytochrome P450 (CYP450) enzymes from arachidonic acid. This study in men examined the effect of consuming red wine (RW) on BP in relation to changes in 20-HETE, oxidative stress (F -isoprostanes), markers of inflammation, anti-inflammatory CYP450 epoxyeicosatrienoic acids (EETs), and specialized pro-resolving mediators of inflammation (SPMs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

Does Furosemide Increase Oxidative Stress in Acute Kidney Injury?

Furosemide, a loop diuretic, is used to increase urine output in patients with acute kidney injury (AKI). It remains uncertain whether the benefits of furosemide in AKI outweigh its potential harms. We investigated if furosemide influenced oxidative stress in 30 critically ill patients with AKI by measuring changes in F-isoprostanes (F-IsoPs), markers of in vivo oxidative stress, in plasma and urine following intravenous furosemide.

Controlled moderate hypovolaemia in healthy volunteers is not associated with the development of oxidative stress assessed by plasma F2-isoprostanes and isofurans.

Hypovolaemia can be associated with substantial morbidity, particularly when it occurs in the setting of trauma and in patients with comorbid diseases. Hypovolaemia and inflammation such as occur in the setting of trauma and surgery, are associated with systemic oxidative stress and free-radical injury. Free-radical injury that results from hypovolaemia-induced organ reperfusion may further augment inflammatory processes.

Determinants of Urinary Output Response to IV Furosemide in Acute Kidney Injury: A Pharmacokinetic/Pharmacodynamic Study.

Objectives: This study assessed the determinants of urinary output response to furosemide in acute kidney injury; specifically, whether the response is related to altered pharmacokinetics or pharmacodynamics.

Design: Prospective cohort.

Setting: Tertiary ICU.

Acute effects of quercetin-3-O-glucoside on endothelial function and blood pressure: a randomized dose-response study.

Background: Epidemiologic studies have suggested that a flavonoid-rich diet can reduce the risk of developing cardiovascular disease. Certain flavonoids, in particular quercetin, have been shown to ameliorate endothelial dysfunction and reduce blood pressure (BP), possibly by increasing the bioavailability of the potent vasodilator nitric oxide (NO). Several studies have indicated that improvements in measures of cardiovascular health do not occur linearly, but rather, plateau or decrease with an increasing dose of flavonoids.

Specialised pro-resolving mediators of inflammation in inflammatory arthritis.

Introduction: Specialised pro-resolving mediators (SPM) are derived from n-3 long chain polyunsaturated fatty acids (n-3FA). They promote resolution of inflammation and may contribute to the beneficial effects of n-3FA in patients with arthritis. This study compared SPM in knee effusions and plasma of patients with arthritis taking n-3FA, and plasma of healthy volunteers taking n-3FA.

n-3 Fatty acid supplementation and proresolving mediators of inflammation.

Purpose Of Review: The review presents recent developments in the identification of specialized proresolving mediators (SPMs) of inflammation following supplementation with n-3 fatty acids in humans.

Recent Findings: A number of reports have measured SPMs in human plasma after n-3 fatty acid supplementation. Although studies have shown some variability in plasma SPM levels, there is strong evidence that a number of resolvins are increased after n-3 fatty acids to concentrations that have been shown to have biological activity.

Specialized proresolving lipid mediators in humans with the metabolic syndrome after n-3 fatty acids and aspirin.

Background: The metabolic syndrome (MetS) is associated with a chronic low-grade inflammatory state and may be affected by the ability to resolve inflammation, which is an active process that involves specialized proresolving lipid mediators (SPMs) derived from n-3 (ω-3) fatty acids.

Objective: We compared plasma concentrations of SPMs in men and women with features of the MetS and in healthy matched control subjects in response to intakes of n-3 fatty acids and aspirin.

Design: MetS volunteers (n = 22) and healthy, matched controls (n = 21) were studied in parallel for 4 wk.

Chlorogenic acid improves ex vivo vessel function and protects endothelial cells against HOCl-induced oxidative damage, via increased production of nitric oxide and induction of Hmox-1.

Dietary polyphenols are potential contributors toward improved cardiovascular health. Coffee is one of the richest sources of dietary polyphenols in a coffee-drinking population, the most abundant form being chlorogenic acid (CGA). Endothelial dysfunction is an early and major risk factor for cardiovascular disease.

n-3 fatty acids reduce plasma 20-hydroxyeicosatetraenoic acid and blood pressure in patients with chronic kidney disease.

Background: Metabolism of arachidonic acid by cytochrome P450 ω-hydroxylase leads to the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) that regulates vascular function, sodium homeostasis and blood pressure (BP). Supplementation with n-3 fatty acids is known to alter arachidonic acid metabolism and reduce the formation of the lipid peroxidation products F2-isoprostanes, but the effect of n-3 fatty acids on 20-HETE has not been studied.

Method: We previously reported a significant effect of n-3 fatty acids but not coenzyme Q10 (CoQ) to reduce BP in a double-blind, placebo-controlled intervention, wherein patients with chronic kidney disease (CKD) were randomized to n-3 fatty acids (4 g), CoQ (200 mg), both supplements or control (4 g olive oil), daily for 8 weeks.

A randomized controlled trial of the effects of n-3 fatty acids on resolvins in chronic kidney disease.

Background And Objective: The high incidence of cardiovascular disease (CVD) in chronic kidney disease (CKD) is related partially to chronic inflammation. n-3 Fatty acids have been shown to have anti-inflammatory effects and to reduce the risk of CVD. Specialized Proresolving Lipid Mediators (SPMs) derived from the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) actively promote the resolution of inflammation.

Chronic erythropoietin treatment improves diet-induced glucose intolerance in rats.

Erythropoietin (EPO) ameliorates glucose metabolism through mechanisms not fully understood. In this study, we investigated the effect of EPO on glucose metabolism and insulin signaling in skeletal muscle. A 2-week EPO treatment of rats fed with a high-fat diet (HFD) improved fasting glucose levels and glucose tolerance, without altering total body weight or retroperitoneal fat mass.

Effects of maternal n-3 fatty acid supplementation on placental cytokines, pro-resolving lipid mediators and their precursors.

The aim of this study was to determine whether supplementation with fish oil-derived n-3 polyunsaturated fatty acids (n-3 PUFA) during pregnancy modifies placental PUFA composition, the accumulation of specialised pro-resolving lipid mediators (SPMs, specifically resolvins (Rv), protectins (PD) and upstream precursors) and inflammatory gene expression. Placentas were collected from women (n=51) enrolled in a randomised, placebo controlled trial of n-3 PUFA supplementation from 20-week gestation. Lipids were extracted for fatty acid analysis and SPMs were quantitated by mass spectrometry.

Short-term n-3 fatty acid supplementation but not aspirin increases plasma proresolving mediators of inflammation.

Resolution of inflammation is an active process involving specialized proresolving mediators (SPM) formed from the n-3 fatty acids. This study examined the effect of n-3 fatty acid supplementation and aspirin on plasma SPMs in healthy humans. Healthy volunteers (n = 21) were supplemented with n-3 fatty acids (2.

Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: a randomized trial.

Omega-3 and n-6 fatty acids are biosynthetic precursors to lipid mediators with antinociceptive and pronociceptive properties. We conducted a randomized, single-blinded, parallel-group clinical trial to assess clinical and biochemical effects of targeted alteration in dietary n-3 and n-6 fatty acids for treatment of chronic headaches. After a 4-week preintervention phase, ambulatory patients with chronic daily headache undergoing usual care were randomized to 1 of 2 intensive, food-based 12-week dietary interventions: a high n-3 plus low n-6 (H3-L6) intervention, or a low n-6 (L6) intervention.