Role of Omega-3 Fatty Acids in the Treatment of Depressive Disorders: A Comprehensive Meta-Analysis of Randomized Clinical Trials

Background

Despite omega-3 polyunsaturated fatty acids (PUFA) supplementation in depressed patients have been suggested to improve depressive symptomatology, previous findings are not univocal.

Objectives

To conduct an updated meta-analysis of randomized controlled trials (RCTs) of omega-3 PUFA treatment of depressive disorders, taking into account the clinical differences among patients included in the studies.

Methods

A search on MEDLINE, EMBASE, PsycInfo, and the Cochrane Database of RCTs using omega-3 PUFA on patients with depressive symptoms published up to August 2013 was performed. Standardized mean difference in clinical measure of depression severity was primary outcome. Type of omega-3 used (particularly eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and omega-3 as mono- or adjuvant therapy was also examined. Meta-regression analyses assessed the effects of study size, baseline depression severity, trial duration, dose of omega-3, and age of patients.

Results

Meta-analysis of 11 and 8 trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo (standardized difference in random-effects model 0.56 SD [95% CI: 0.20, 0.92] and 0.22 SD [95% CI: 0.01, 0.43], respectively; pooled analysis was 0.38 SD [95% CI: 0.18, 0.59]). Use of mainly EPA within the preparation, rather than DHA, influenced final clinical efficacy. Significant clinical efficacy had the use of omega-3 PUFA as adjuvant rather than mono-therapy. No relation between efficacy and study size, baseline depression severity, trial duration, age of patients, and study quality was found. Omega-3 PUFA resulted effective in RCTs on patients with bipolar disorder, whereas no evidence was found for those exploring their efficacy on depressive symptoms in young populations, perinatal depression, primary disease other than depression and healthy subjects.

Conclusions

The use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD.     

Evaluation of photoacoustic infrared spectroscopy for simultaneous measurement of N2O and CO2 gas concentrations and fluxes at the soil surface

Simultaneous measurement of N₂O and CO₂ flux at the soil surface with photoacoustic infrared spectroscopy (PAS) is gaining popularity due to portability, low maintenance, and ease‐of‐operation. However, the ability of PAS to measure N₂O with accuracy and precision similar to gas chromatography (GC) is uncertain due to overlap in N₂O, CO₂, and H₂O absorbance spectra combined with the large range in analyte concentrations. We tested the ability of six PAS units to simultaneously measure N₂O and CO₂ gas concentrations and fluxes with accuracy and precision similar to two GC units. We also evaluated H₂O vapor and CO₂ interferences with N₂O measurement. The accuracy and precision of standard gas concentration measurements with PAS and GC were similar. High water vapor (~26 600 ppm) and CO₂ concentrations (~4500 ppm) did not interfere with N₂O measurement across the concentration range typically observed in static flux chambers at the soil surface (~0.5–3.0 ppm N₂O). On average, N₂O fluxes measured with the six PAS were 4.7% higher than one GC and 9.9% lower than the second GC.     

High overexpression of CERES,a plant regulator of translation,induces different phenotypical defence responses during TuMV infection

Mutations in the eukaryotic translation initiation factors eIF4E and eIF(iso)4E confer potyvirus resistance in a range of plant hosts. This supports the notion that, in addition to their role in translation of cellular mRNAs, eIF4E isoforms are also essential for the potyvirus cycle. CERES is a plant eIF4E- and eIF(iso)4E-binding protein that, through its binding to the eIF4Es, modulates translation initiation; however, its possible role in potyvirus resistance is unknown. In this article, we analyse if the ectopic expression of AtCERES is able to interfere with turnip mosaic virus replication in plants. Our results demonstrate that, during infection, the ectopic expression of CERES in Nicotiana benthamiana promotes the development of a mosaic phenotype when it is accumulated to moderate levels, but induces veinal necrosis when it is accumulated to higher levels. This necrotic process resembles a hypersensitive response (HR)-like response that occurs with different HR hallmarks. Remarkably, Arabidopsis plants inoculated with a virus clone that promotes high expression of CERES do not show signs of infection. These final phenotypical outcomes are independent of the capacity of CERES to bind to eIF4E. All these data suggest that CERES, most likely due to its leucine-rich repeat nature, could act as a resistance protein, able to promote a range of different defence responses when it is highly overexpressed from viral constructs.     

Air quality indices: a review

National directives on air quality oblige nations to monitor and report on their air quality, allowing the public to be informed on the ambient pollution levels. The last is the reason for the always increasing interest, demonstrated by the number of publications on this topic in recent years, in air quality/pollution indices: since the concentration of individual pollutants can be confusing, concentration measurements are conveniently transformed in terms of an air quality index. In this way, complex situations are summarized in a single figure, letting comparisons in time and space be possible. In this paper we will give an overview about the Air Quality/Pollution Indices proposed in literature and/or adopted by countries, trying also to categorize them into homogeneous groups. For the classification different approaches can be followed. Since in real life exposure to mixtures of chemicals occurs, with additive, synergistic or antagonistic effects, here we will distinguish between indices that consider the conjoint effect of pollutants and indices only based on the actual most dangerous pollutant. This brief review on air pollution indices shows, on one side, the wide interest in the problem, on the other, the lack of a common strategy which allows to compare the state of the air for cities that follow different directives. The main differences between the indices will be also described.     

Cell‐free protein synthesis and purification of human dopamine D2 receptor long isoform

The human dopamine D2 receptor long isoform (D2L) has significant implications in neurological and neuropsychiatric disorders such as Parkinson's disease and schizophrenia. Detailed structural knowledge of this receptor is limited owing to its highly hydrophobic nature, which leads to protein aggregation and host toxicity when expressed in cellular systems. The newly emerging field of cell‐free protein expression presents numerous advantages to overcome these challenges. This system utilizes protein synthesis machinery and exogenous DNA to synthesize functional proteins outside of intact cells. This study utilizes two different cell‐free systems for the synthesis of human dopamine D2L receptor. These include the Escherichia coli lysate‐based system and the wheat‐germ lysate‐based system. The bacterial cell‐free method used pET 100/D‐TOPO vector to synthesize hexa‐histidine‐tagged D2L receptor using a dialysis bag system; the resulting protein was purified using nickel‐nitrilotriacetic acid affinity resin. The wheat germ system used pEU–glutathione‐S‐transferase (GST) vector to synthesize GST‐tagged D2L receptor using a bilayer translation method; the resulting protein was purified using a GST affinity resin. The presence and binding capacity of the synthesized D2L receptor was confirmed by immunoblotting and radioligand competition assays, respectively. Additionally, in‐gel protein sequencing via Nano LC‐MS/MS was used to confirm protein synthesis via the wheat germ system. The results showed both systems to synthesize microgram quantities of the receptor. Improved expression of this highly challenging protein can improve research and understanding of the human dopamine D2L receptor. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:601–608, 2013     

T Cell Activation and Proinflammatory Cytokine Production in Clinically Cured Tuberculosis Are Time-Dependent and Accompanied by Upregulation of IL-10

Background

Th1 cytokines are essential for the control of M. tuberculosis infection. The role of IL-10 in tuberculosis is controversial and there is an increasing body of evidence suggesting that the relationship between Th1 cytokines and IL-10 is not as antagonistic as it was first believed, and that these cytokines may complement each other in infectious diseases.

Methods

The present study evaluated the activating capacity of CD4+ and CD8+ T cell repertoire in response to antigen stimulation through the expression of CD69 using Flow Cytometry, as well as the functionality of PBMCs by determining the cytokine profile in patients with active tuberculosis and in clinically cured patients after in vitro stimulation using ELISA. Treated patients were subdivided according to time after clinical cure (<12 months or >12 months post-treatment).

Results

We observed that T cell activation was higher in TB-treated patients, especially CD8+ T cell activation in TB-Treated >1 year. Th1 cytokines were significantly higher in TB-Treated, and the levels of IFN-γ and TNF-α increased continuously after clinical cure. Moreover, IL-10 production was significantly higher in cured patients and it was also enhanced in cured patients over time after treatment. Th17, Th2 and Th22 cytokines showed no statistically significant differences between Healthy Donors, Active-TB and TB-Treated.

Conclusions

This study describes a scenario in which potentiation of CD4+ and CD8+ T cell activation and increased Th1 cytokine production are associated with the clinical cure of tuberculosis in the absence of significant changes in Th2 cytokine production and is accompanied by increased production of IL-10. In contrast to other infections with intracellular microorganisms, this response occurs later after the end of treatment.     

Bioinspired FeIIICdII and FeIIIHgII complexes: synthesis, characterization and promiscuous catalytic activity evaluation

In this work we report on the synthesis, crystal structure, and physicochemical characterization of the novel dinuclear [Fe^IIICd^II(L)(μ-OAc)₂]ClO₄·0.5H₂O (1) complex containing the unsymmetrical ligand H₂L = 2-bis[{(2-pyridyl-methyl)-aminomethyl}-6-{(2-hydroxy-benzyl)-(2-pyridyl-methyl)}-aminomethyl]-4-methylphenol. Also, with this ligand, the tetranuclear [Fe₂^IIIHg₂^II(L)₂(OH)₂](ClO₄)₂·2CH₃OH (2) and [Fe^IIIHg^II(L)(μ-CO₃)Fe^IIIHg^II(L)](ClO₄)₂·H₂O (3) complexes were synthesized and fully characterized. It is demonstrated that the precursor [Fe^III₂Hg^II₂(L)₂(OH)₂](ClO₄)₂·2CH₃OH (2) can be converted to (3) by the fixation of atmospheric CO₂ since the crystal structure of the tetranuclear organometallic complex [Fe^IIIHg^II(L)(μ-CO₃)Fe^IIIHg^II(L)](ClO₄)₂·H₂O (3) with an unprecedented {Fe^III(μ-O_phenoxo)₂(μ-CO₃)Fe^III} core was obtained through X-ray crystallography. In the reaction 2 → 3 a nucleophilic attack of a Fe^III-bound hydroxo group on the CO₂ molecule is proposed. In addition, it is also demonstrated that complex (3) can regenerate complex (2) in aqueous/MeOH/NaOH solution. Magnetochemical studies reveal that the Fe^III centers in 3 are antiferromagnetically coupled (J = − 7.2 cm^− 1) and that the Fe^III-OR-Fe^III angle has no noticeable influence in the exchange coupling. Phosphatase-like activity studies in the hydrolysis of the model substrate bis(2,4-dinitrophenyl) phosphate (2,4-bdnpp) by 1 and 2 show Michaelis-Menten behavior with 1 being ~ 2.5 times more active than 2. In combination with k_H/k_D isotope effects, the kinetic studies suggest a mechanism in which a terminal Fe^III-bound hydroxide is the hydrolysis-initiating nucleophilic catalyst for 1 and 2. Based on the crystal structures of 1 and 3, it is assumed that the relatively long Fe^III…Hg^II distance could be responsible for the lower catalytic effectiveness of 2.     

The Advertisement Call of the European Treefrogs (Hyla arborea): A Multilevel Study of Variation

In this study, we analysed the patterns of variation of the European treefrog's advertisement call at four levels of organization: within individuals, within populations, among populations of the same species, and among different species of the same clade. At the within-individual level, call acoustic properties are distinguished into static and dynamic properties. At the within-population level, two sources of call variation were analysed: temperature and body size. Temperature affects both temporal and spectral properties of the call. Body size mostly affects spectral properties. At the between-population level, calls do not show significant differences with respect to temporal properties, but they do differ in two spectral (and stereotyped) properties: the fundamental frequency and the difference in amplitude between dominant and fundamental frequencies. Finally, at the between-species level, call differences are much more conspicuous: they involve both spectral and temporal and both static and dynamic properties. At all four levels, body size is associated with call variation, explaining 11% of the differences among populations of the same species and 73% of the differences among species of the same clade. On the basis of these results, we hypothesize that patterns of variation of call acoustic properties, their constraints, and their biological functions are intrinsically associated. We discuss the role that such an association might play in the evolution of acoustic signals.