Generation and dietary modulation of anti-inflammatory electrophilic omega-3 fatty acid derivatives

Dietary ω-3 polyunsaturated fatty acids (PUFAs) decrease cardiovascular risk via suppression of inflammation. The generation of electrophilic α,β-unsaturated ketone derivatives of the ω-3 PUFAs docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) in activated human macrophages is catalyzed by cyclooxygenase-2 (Cox-2). These derivatives are potent pleiotropic anti-inflammatory signaling mediators that act via mechanisms including the activation of Nrf2- dependent phase 2 gene expression and suppression of pro-inflammatory NF-κB-driven gene expression. Herein, the endogenous generation of ω-3 PUFAs electrophilic ketone derivatives and their hydroxy precursors was evaluated in human neutrophils. In addition, their dietary modulation was assessed through a randomized clinical trial. Methods: Endogenous generation of electrophilic omega-3 PUFAs and their hydroxy precursors was evaluated by mass spectrometry in neutrophils isolated from healthy subjects, both at baseline and upon stimulation with calcium ionophore. For the clinical trial, participants were healthy adults 30-55 years of age with a reported EPA+DHA consumption of ≤ 300 mg/day randomly assigned to parallel groups receiving daily oil capsule supplements for a period of 4 months containing either 1.4 g of EPA+DHA (active condition, n = 24) or identical appearing soybean oil (control condition, n = 21). Participants and laboratory technicians remained blinded to treatment assignments. Results: 5-lypoxygenase-dependent endogenous generation of 7-oxo-DHA, 7-oxo-DPA and 5-oxo-EPA and their hydroxy precursors is reported in human neutrophils stimulated with calcium ionophore and phorbol 12-myristate 13-acetate (PMA). Dietary EPA+DHA supplementation significantly increased the formation of 7-oxo-DHA and 5-oxo-EPA, with no significant modulation of arachidonic acid (AA) metabolite levels. Conclusions: The endogenous detection of these electro.©2014 Cipollina et al

Polypharmacy among anabolic-androgenic steroid users: A descriptive metasynthesis

Background: As far as we are aware, no previous systematic review and synthesis of the qualitative/descriptive literature on polypharmacy in anabolic-androgenic steroid(s) (AAS) users has been published. Method: We systematically reviewed and synthesized qualitative/descriptive literature gathered from searches in electronic databases and by inspecting reference lists of relevant literature to investigate AAS users' polypharmacy. We adhered to the recommendations of the UK Economic and Social Research Council's qualitative research synthesis manual and the PRISMA guidelines. Results: A total of 50 studies published between 1985 and 2014 were included in the analysis. Studies originated from 10 countries although most originated from United States (n = 22), followed by Sweden (n = 7), England only (n = 5), and the United Kingdom (n = 4). It was evident that prior to their debut, AAS users often used other licit and illicit substances. The main ancillary/supplementary substances used were alcohol, and cannabis/cannabinoids followed by cocaine, growth hormone, and human chorionic gonadotropin (hCG), amphetamine/meth, clenbuterol, ephedra/ephedrine, insulin, and thyroxine. Other popular substance classes were analgesics/opioids, dietary/nutritional supplements, and diuretics. Our classification of the various substances used by AAS users resulted in 13 main groups. These non-AAS substances were used mainly to enhance the effects of AAS, combat the side effects of AAS, and for recreational or relaxation purposes, as well as sexual enhancement. Conclusions: Our findings corroborate previous suggestions of associations between AAS use and the use of other licit and illicit substances. Efforts must be intensified to combat the debilitating effects of AAS-associated polypharmacy

Rare coding variants in ten genes confer substantial risk for schizophrenia

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3–50, P < 2.14 × 10−6) and 32 genes at a false discovery rate of <5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular functions that include the formation, structure and function of the synapse. The associations of the NMDA (N-methyl-d-aspartate) receptor subunit GRIN2A and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subunit GRIA3 provide support for dysfunction of the glutamatergic system as a mechanistic hypothesis in the pathogenesis of schizophrenia. We observe an overlap of rare variant risk among schizophrenia, autism spectrum disorders1, epilepsy and severe neurodevelopmental disorders2, although different mutation types are implicated in some shared genes. Most genes described here, however, are not implicated in neurodevelopment. We demonstrate that genes prioritized from common variant analyses of schizophrenia are enriched in rare variant risk3, suggesting that common and rare genetic risk factors converge at least partially on the same underlying pathogenic biological processes. Even after excluding significantly associated genes, schizophrenia cases still carry a substantial excess of URVs, which indicates that more risk genes await discovery using this approach

EPR and optical studies on as grown polycrystalline diamond and diamond films annealed between 1100 and 1900 K

We report a systematic study by electron paramagnetic resonance (EPR), and infrared absorption of as grown and annealed free standing polycrystalline diamond films. In all CVD diamond films studied an EPR resonance is observed at g=2.0028(2). Comparison of the local and bulk concentrations indicated that these centres are inhomogeneously distributed in the films, where as the single substitutional nitrogen centres appear homogeneously distributed throughout the CVD diamond. The strength of the total EPR absorption at g=2.0028 correlates with the total infrared absorption in the CH region. Upon annealing to 1900 K in vacuum the intensity of the resonance at g=2.0028 decreases significantly in intensity and narrows slightly. During this treatment the sharp infrared absorption line at 2820 cm(-1) increased and then decreased in intensity, but besides this there were no significant changes in the infrared absorption The results suggest that the dangling bonds responsible for the g=2.0028 EPR absorption are not located in the diamond lattice but are to be found on grain boundaries or in non-diamond intergranular material and are compensated during annealing when hydrogen on the grain boundaries, or in intergranular material becomes mobile. New unidentified EPR centres are produced when the samples are annealed in vacuum above 1800 K

Cognitive distortions and self-regulatory personality traits associated with proactive and reactive aggression in early adolescence

Contains fulltext : 102379.pdf (publisher's version ) (Open Access)This study investigated mechanisms behind proactive and reactive aggression, by examining whether four types of self-serving cognitive distortions and the personality traits agreeableness and conscientiousness differently predicted proactive and reactive aggression. Self-report questionnaires and a peer nominations method were administered to 173 sixth grade children (age 10-13) of regular elementary schools in the Netherlands. Negative binomial regression analyses showed that proactive aggression was predicted by self-centered and disagreeable tendencies, whereas reactive aggression was predicted by the misattribution of blame to others and the self-regulatory aspects of agreeableness and conscientiousness. Findings emphasize the need to differentiate proactive and reactive aggression in order to accurately predict, prevent and treat aggressive behaviors in childhood.12 p

The Role of Peer Rejection in the Link between Reactive Aggression and Academic Performance

There is substantial evidence to suggest that aggressive behavior is associated with poor academic performance in school-aged children. However, less is known about how different subtypes of aggression are related to academic performance and what variables may account for this association. The current study examined unique associations between reactive (aggression in response to provocation) and proactive (goal-oriented calculated aggression) subtypes of aggression and academic performance. Further, the study evaluated whether peer rejection accounted for the link between these aggression subtypes and academic problems. Study questions were examined using a sample of 147 school-age children (M = 8.22, SD = 1.99, 54.4 % male) who attended a community-based after school program. Path models were used to estimate the proposed associations using Mplus 6.12 statistical software. As expected, findings indicated that high levels of reactive, not proactive, aggression were uniquely associated with low levels of academic performance, and peer rejection accounted for this association. Results advance the literature linking aggression and academic difficulties by indicating that reactive aggression, but not proactive aggression, is associated with academic difficulties. Findings also support previous literature suggesting that peer relationships are an important target of prevention and intervention efforts aimed at improving school performance, particularly for individuals who exhibit reactively aggressive behavior