Gastrointestinal toxicity (GIT) is a debilitating side effect of Irinotecan (CPT-11) and limits its clinical utility. Gut dysbiosis has been shown to mediate this side effect of CPT-11 by increasing ...gut bacterial β-glucuronidase (GUSB) activity and impairing the intestinal mucosal barrier (IMB). We have recently shown the opposing effects of omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) on the gut microbiome. We hypothesized that elevated levels of tissue n-3 PUFA with a decreased n-6/n-3 PUFA ratio would reduce CPT-11-induced GIT and associated changes in the gut microbiome. Using a unique transgenic mouse (FAT-1) model combined with dietary supplementation experiments, we demonstrate that an elevated tissue n-3 PUFA status with a decreased n-6/n-3 PUFA ratio significantly reduces CPT-11-induced weight loss, bloody diarrhea, gut pathological changes, and mortality. Gut microbiome analysis by 16S rRNA gene sequencing and QIIME2 revealed that improvements in GIT were associated with the reduction in the CPT-11-induced increase in both GUSB-producing bacteria (e.g.,
) and GUSB enzyme activity, decrease in IMB-maintaining bacteria (e.g.,
), IMB dysfunction and systemic endotoxemia. These results uncover a host-microbiome interaction approach to the management of drug-induced gut toxicity. The prevention of CPT-11-induced gut microbiome changes by decreasing the tissue n-6/n-3 PUFA ratio could be a novel strategy to prevent chemotherapy-induced GIT.
A novel scaling theory for fully depleted omega-gate (ΩG) MOSFETs, including rectangular-shaped ΩG (RΩG) and cylindrical-shaped ΩG (CΩG) MOSFETs, is presented. The natural length for the ΩG MOSFET is ...obtained by solving the equation of equivalent number of gates (ENG), where the ENG of the ΩG device working in the x-y-z space can be the sum of the ENGs for both the double-gate (DG) and single-gate transistors working in the y-z and x-z planes based on the perimeter-weighted-sum method. Numerical device simulation data for drain-induced-barrier-lowered effects (DIBL) were compared with the model to validate the theory. Among the RΩG devices with the same perimeters, one with a square cross section and a large oxide-to-gate underlap coverage factor (OUCF) will show the worst immunity to the DIBL due to the largest natural length. For equivalent short-channel controlling capability, the RΩG MOSFET with the OUCF=0.7 illustrates an improvement of up to 25% in the minimum effective channel length Lmin when compared with the DG MOSFET.
Interest in the potential cardiovascular (CV) benefits of omega-3 polyunsaturated fatty acids (Ω-3) began in the 1940s and was amplified by a subsequent landmark trial showing reduced CV disease ...(CVD) risk following acute myocardial infarction. Since that time, however, much controversy has circulated due to discordant results among several studies and even meta-analyses. Then, in 2018, three more large, randomized trials were released-these too with discordant findings regarding the overall benefits of Ω-3 therapy. Interestingly, the trial that used a higher dose (4 g/day highly purified eicosapentaenoic acid (EPA)) found a remarkable, statistically significant reduction in CVD events. It was proposed that insufficient Ω-3 dosing (<1 g/day EPA and docosahexaenoic acid (DHA)), as well as patients aggressively treated with multiple other effective medical therapies, may explain the conflicting results of Ω-3 therapy in controlled trials. We have thus reviewed the current evidence regarding Ω-3 and CV health, put forth potential reasoning for discrepant results in the literature, highlighted critical concepts such as measuring blood levels of Ω-3 with a dedicated Ω-3 index and addressed current recommendations as suggested by health care professional societies and recent significant scientific data.
Clustal Omega is a widely used package for carrying out multiple sequence alignment. Here, we describe some recent additions to the package and benchmark some alternative ways of making alignments. ...These benchmarks are based on protein structure comparisons or predictions and include a recently described method based on secondary structure prediction. In general, Clustal Omega is fast enough to make very large alignments and the accuracy of protein alignments is high when compared to alternative packages. The package is freely available as executables or source code from www.clustal.org or can be run on‐line from a variety of sites, especially the EBI www.ebi.ac.uk.
Swine production has focused its efforts to reduce the amount and improve the quality of fat deposited on carcass. Due to the association of the lipid profile with cardiovascular diseases, researches ...have been developed to understand how the deposition occurs and to improve the fatty acid profile of swine fat. Among the factors that affect the fat composition, race, sex, and diet, the third one has the greatest impact. Lipid inclusion seems to be a promising way to modulate the lipid profile of fat in pig carcass, with an effect on saturated, monounsaturated and polyunsaturated fatty acids. The effect is greater in that fatty acid with the highest concentration in the source used. Soybean oil can double the value of linoleic acid, a by-product of olive oil increases oleic acid by 4%, and flaxseed oil has the ability to increase α-linolenic acid from less than 1% to over 18% in total fatty acids. In addition to the source, the duration and concentration influence the modulation of the fatty acid profile.
RESUMO: A cadeia produtiva de suínos tem concentrado esforços para reduzir a quantidade e melhorar a qualidade da gordura depositada na carcaça. Devido a associação do perfil lipídico com doenças cardiovasculares, pesquisas têm sido desenvolvidas para entender como ocorre a deposição e para melhorar o perfil de ácidos graxos na carcaça. Dentre os fatores que afetam a composição dessa gordura estão a raça, o sexo e a dieta dos suínos, sendo que este último é o de maior impacto. A inclusão de ingredientes lipídicos parece uma promissora forma de modular o perfil lipídico da gordura na carcaça dos suínos, sendo observado efeito nos ácidos graxos saturados, monoinsaturados e poli-insaturados. O efeito é maior naquele ácido graxo de maior concentração na fonte utilizada. O óleo de soja pode dobrar o valor do ácido linoleico. Um subproduto do óleo de oliva incrementa em 4% o ácido oleico. E o óleo de linhaça tem a capacidade de aumentar o α-linolênico de menos de 1% para mais de 18% no total de ácidos graxos. Além da fonte, o período e a concentração influenciam na modulação do perfil de ácidos graxos.
Background
Omega‐3 polyunsaturated fatty acids (omega‐3 PUFAs) from fish and plant sources are commonly considered as a promising non‐medical alternative to improve brain functions and slow down the ...progression of dementia. This assumption is mostly based on findings of preclinical studies and epidemiological research. Resulting explanatory models aim at the role omega‐3 PUFAs play in the development and integrity of the brain's neurons, their protective antioxidative effect on cell membranes and potential neurochemical mechanisms directly related to Alzheimer‐specific pathology. Epidemiological research also found evidence of malnutrition in people with dementia. Considering this and the fact that omega‐3 PUFA cannot be synthesised by humans, omega‐3 PUFAs might be a promising treatment option for dementia.
Objectives
To assess the efficacy and safety of omega‐3 polyunsaturated fatty acid (PUFA) supplementation for the treatment of people with dementia.
Search methods
We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), MEDLINE, EMBASE, PsycINFO, CINAHL, ClinicalTrials.gov and the World Health Organization (WHO) portal/ICTRP on 10 December 2015. We contacted manufacturers of omega‐3 supplements and scanned reference lists of landmark papers and included articles.
Selection criteria
We included randomised controlled trials (RCTs) in which omega‐3 PUFA in the form of supplements or enriched diets were administered to people with Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD) or frontotemporal dementia (FTD).
Data collection and analysis
The primary outcome measures of interest were changes in global and specific cognitive functions, functional performance, dementia severity and adverse effects. Two review authors independently selected studies, extracted data and assessed the quality of trials according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of the evidence using the GRADE approach. We received unpublished data from the trial authors and collected adverse effects information from the published articles. We conducted meta‐analyses for available outcome measures at six months.
Main results
We included three comparable randomised, placebo‐controlled trials investigating omega‐3 PUFA supplements in 632 participants with mild to moderate AD over six, 12 and 18 months. We found no studies investigating other types of dementia. All trials were of high methodological quality. The overall quality of evidence for most of the outcomes was high.
There was no evidence of a benefit from omega‐3 PUFAs on cognitive function when measured at six months with the Alzheimer's Disease Assessment Scale ‐ Cognitive subscale (standardised mean difference (SMD) ‐0.02, 95% confidence interval (CI) ‐0.19 to 0.15; 566 participants; 3 studies; high quality evidence) or Mini‐Mental State Examination (mean difference (MD) 0.18, 95% CI ‐1.05 to 1.41; 202 participants; 2 studies; high quality evidence) or on activities of daily living (SMD ‐0.02, 95% CI ‐0.19 to 0.16; 544 participants; 2 studies; high quality evidence). There was also no effect at six months of treatment on severity of dementia measured with the Clinical Dementia Rating ‐ Sum of Boxes (MD ‐0.00, 95% CI ‐0.58 to 0.57; 542 participants; 2 studies; high quality evidence) or on quality of life measured with the Quality of Life Alzheimer's Disease scale (MD ‐0.10, 95% CI ‐1.28 to 1.08; 322 participants; 1 study; high quality evidence). There was no difference at six months on mental health measured with the Montgomery‐Åsberg Depression Rating Scale (MD ‐0.10, 95% CI ‐0.74 to 0.54; 178 participants: 1 study; high quality of evidence) or the Neuropsychiatric Inventory (SMD 0.10, 95% CI ‐0.07 to 0.27; 543 participants; 2 studies; high quality of evidence). One very small study showed a benefit for omega‐3 PUFAs in instrumental activities of daily living after 12 months of treatment (MD ‐3.50, 95% CI ‐4.30 to ‐2.70; 22 participants; moderate quality evidence). The included studies did not measure specific cognitive function. The studies did not report adverse events well. Two studies stated that all adverse events were mild and that they did not differ in overall frequency between omega‐3 PUFA and placebo groups. Data from one study showed no difference between groups in frequency of any adverse event (risk ratio (RR) 1.02, 95% CI 0.95 to 1.10; 402 participants; 1 study; moderate quality evidence) or any serious adverse event (RR 1.05, 95% CI 0.78 to 1.41; 402 participants; 1 study; high quality evidence) at 18 months of treatment.
Authors' conclusions
We found no convincing evidence for the efficacy of omega‐3 PUFA supplements in the treatment of mild to moderate AD. This result was consistent for all outcomes relevant for people with dementia. Adverse effects of omega‐3 PUFAs seemed to be low, but based on the evidence synthesised in this review, we cannot make a final statement on tolerability. The effects on other populations remain unclear.
•Soil moisture retrieval using tau–omega algorithm.•Evaluation of soil moisture retrieval parameters for SMOS soil moisture estimation.•Integration of WRF–NOAH Land Surface Model and MODIS based LST ...in soil moisture retrieval algorithms.•Assessment of SMOS retrieved soil moisture from different approaches for SMD prediction.•Highest performance is shown by WRF-NOAH Land Surface Model based LST.
Soil Moisture and Ocean Salinity (SMOS) is the latest mission which provides flow of coarse resolution soil moisture data for land applications. However, the efficient retrieval of soil moisture for hydrological applications depends on optimally choosing the soil and vegetation parameters. The first stage of this work involves the evaluation of SMOS Level 2 products and then several approaches for soil moisture retrieval from SMOS brightness temperature are performed to estimate Soil Moisture Deficit (SMD). The most widely applied algorithm i.e. Single channel algorithm (SCA), based on τ–ω is used in this study for the soil moisture retrieval. In τ–ω, the soil moisture is retrieved using the Horizontal (H) polarisation following Hallikainen dielectric model, roughness parameters, Fresnel’s equation and estimated Vegetation Optical Depth (τ). The roughness parameters are empirically calibrated using the numerical optimization techniques. Further to explore the improvement in retrieval models, modifications have been incorporated in the algorithms with respect to the sources of the parameters, which include effective temperatures derived from the European Center for Medium-Range Weather Forecasts (ECMWF) downscaled using the Weather Research and Forecasting (WRF)–NOAH Land Surface Model and Moderate Resolution Imaging Spectroradiometer (MODIS) land surface temperature (LST) while the τ is derived from MODIS Leaf Area Index (LAI). All the evaluations are performed against SMD, which is estimated using the Probability Distributed Model following a careful calibration and validation integrated with sensitivity and uncertainty analysis. The performance obtained after all those changes indicate that SCA-H using WRF–NOAH LSM downscaled ECMWF LST produces an improved performance for SMD estimation at a catchment scale.
A
bstract
We present a detailed analysis of
e
+
e
−
→
π
+
π
−
data up to
s
=
1
GeV in the framework of dispersion relations. Starting from a family of
ππ P
-wave phase shifts, as derived from a ...previous Roy-equation analysis of
ππ
scattering, we write down an extended Omnès representation of the pion vector form factor in terms of a few free parameters and study to which extent the modern high-statistics data sets can be described by the resulting fit function that follows from general principles of QCD. We find that statistically acceptable fits do become possible as soon as potential uncertainties in the energy calibration are taken into account, providing a strong cross check on the internal consistency of the data sets, but preferring a mass of the
ω
meson significantly lower than the current PDG average. In addition to a complete treatment of statistical and systematic errors propagated from the data, we perform a comprehensive analysis of the systematic errors in the dispersive representation and derive the consequences for the two-pion contribution to hadronic vacuum polarization. In a global fit to both time- and space-like data sets we find
a
μ
ππ
|
≤ 1 GeV
= 495.0(1.5)(2.1) × 10
− 10
and
a
μ
ππ
|
≤ 0.63 GeV
= 132.8(0.4)(1.0) × 10
− 10
. While the constraints are thus most stringent for low energies, we obtain uncertainty estimates throughout the whole energy range that should prove valuable in corroborating the corresponding contribution to the anomalous magnetic moment of the muon. As side products, we obtain improved constraints on the
ππ P
-wave, valuable input for future global analyses of low-energy
ππ
scattering, as well as a determination of the pion charge radius, 〈
r
π
2
〉 = 0
.
429(1)(4) fm
2
.
Macrophages are central in coordinating the host response to both sterile and infective insults. Clearance of apoptotic cells and cellular debris is a key biological action preformed by macrophages ...that paves the way to the resolution of local inflammation, repair and regeneration of damaged tissues, and re-establishment of function. The essential fatty acid-derived autacoids termed specialized pro-resolving mediators (SPM) play central roles in promoting these processes. In the present article, we will review the role of microvesicles in controlling macrophage efferocytosis and SPM production. We will also discuss the role of both apoptotic cells and microvesicles in providing substrate for transcellular biosynthesis of several SPM families during efferocyotsis. In addition, this article will discuss the biological actions of the recently uncovered macrophage-derived SPM termed maresins. These mediators are produced via 14-lipoxygenation of docosahexaenoic acid that is either enzymatically converted to mediators carrying two hydroxyl groups or to autacoids that are peptide-lipid conjugates, coined maresin conjugates in tissue regeneration. The formation of these mediators is temporally regulated during acute self-limited infectious-inflammation where they promote the uptake and clearance of apoptotic cells, regulate several aspects of the tissue repair and regeneration, and display potent anti-nociceptive actions.
We tested the hypothesis that administration of omega (o)-9, rn-3, and rn-6 to mice can prevent oxidative alterations responsible for behavioral and cognitive alterations related with aging. ...Twenty-eight-day- old mice received skim milk (SM group), SM enriched with omega oil mixture (EM group), or water (control group) for 10 and 14 months, equivalent to middle age. Mice were evaluated for behavioral alterations related to depression and memory and oxidative status brain levels of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and myeloperoxidase (MPO). The 10-month EM group increased immobility time during the forced swimming test compared with control, indicating increased stress response. The 14-month SM- and EM-treated groups increased sucrose consumption compared with control, showing an expanded motivational state. The 14-month SM group decreased the number of rearings compared with the 14- month control and EM groups. The number of entries and time spent in the central square of the open field was higher in the 10-month EM group than in the control, revealing an anxiolytic-like behavior. TBARS decreased in the hippocampus and striatum of the 10-month EM group compared with the control. A similar decrease was observed in the striatum of the 10-month SM group. GSH levels were higher in all 14-month treated groups compared with 10-month groups. MPO activity was higher in the 14- month EM group compared with the 14-month control and SM groups, revealing a possible pro-inflammatory status. In conclusion, omega oils induced conflicting alterations in middle-aged mice, contributing to enhanced behavior and anxiolytic and expanded motivational state, but also to increased stress response and pro-inflammatory alterations. Key words: Aging; Nutraceuticals; Omega 3 fatty acids; Omega 6 fatty acids; Omega 9 fatty acids; Oxidative stress markers
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