We compared transcranial direct-current stimulation (tDCS) with a selective serotonin-reuptake inhibitor for the treatment of depression.
In a single-center, double-blind, noninferiority trial ...involving adults with unipolar depression, we randomly assigned patients to receive tDCS plus oral placebo, sham tDCS plus escitalopram, or sham tDCS plus oral placebo. The tDCS was administered in 30-minute, 2-mA prefrontal stimulation sessions for 15 consecutive weekdays, followed by 7 weekly treatments. Escitalopram was given at a dose of 10 mg per day for 3 weeks and 20 mg per day thereafter. The primary outcome measure was the change in the 17-item Hamilton Depression Rating Scale (HDRS-17) score (range, 0 to 52, with higher scores indicating more depression). Noninferiority of tDCS versus escitalopram was defined by a lower boundary of the confidence interval for the difference in the decreased score that was at least 50% of the difference in the scores with placebo versus escitalopram.
A total of 245 patients underwent randomization, with 91 being assigned to escitalopram, 94 to tDCS, and 60 to placebo. In the intention-to-treat analysis, the mean (±SD) decrease in the score from baseline was 11.3±6.5 points in the escitalopram group, 9.0±7.1 points in the tDCS group, and 5.8±7.9 points in the placebo group. The lower boundary of the confidence interval for the difference in the decrease for tDCS versus escitalopram (difference, -2.3 points; 95% confidence interval CI, -4.3 to -0.4; P=0.69) was lower than the noninferiority margin of -2.75 (50% of placebo minus escitalopram), so noninferiority could not be claimed. Escitalopram and tDCS were both superior to placebo (difference vs. placebo, 5.5 points 95% CI, 3.1 to 7.8; P<0.001 and 3.2 points 95% CI, 0.7 to 5.5; P=0.01, respectively). Patients receiving tDCS had higher rates of skin redness, tinnitus, and nervousness than did those in the other two groups, and new-onset mania developed in 2 patients in the tDCS group. Patients receiving escitalopram had more frequent sleepiness and obstipation than did those in the other two groups.
In a single-center trial, tDCS for the treatment of depression did not show noninferiority to escitalopram over a 10-week period and was associated with more adverse events. (Funded by Fundação de Amparo à Pesquisa do Estado de São Paulo and others; ELECT-TDCS ClinicalTrials.gov number, NCT01894815 .).
► Antioxidants tested would be beneficial for reducing the velocity of lipid oxidation. ► Herbs and honey exhibited great efficacy on preventing formation of hexanal. ► The sensory evaluation ...indicated that herbs and honey resulted in a pleasant flavour.
The effect of combinations of sage, oregano and honey on lipid oxidation in cooked chicken meat during refrigeration at 4°C for 96h was determined. Chicken samples (thigh and breast) were then separated into five groups: control; butylated hydroxytoluene; oregano+sage; oregano+sage+5%honey and oregano+sage+10%honey. Quantitative measurements of thiobarbituric acid reactive substances, conjugated dienes, hexanal, fatty acids, cholesterol and cholesterol oxides were used as indicators of lipid oxidation. Acceptability and preference were also evaluated. The effectiveness of the natural antioxidants for reducing the velocity of lipid oxidation in cooked chicken thigh and breast was demonstrated after 48 and 96h of refrigeration at 4°C. The treatments that presented the lowest hexanal values after 96h of refrigeration were oregano+sage+5%honey and oregano+sage+10%honey. Only traces of free cholesterol oxides were found (25-OH, 7-k, 7α-OH and 7β-OH). The natural antioxidants protected cooked chicken meat from oxidation processes and resulted in great acceptability.
We give an introduction to several regularization schemes that deal with ultraviolet and infrared singularities appearing in higher-order computations in quantum field theories. Comparing the ...computation of simple quantities in the various schemes, we point out similarities and differences between them.
Short chain fatty acids (SCFAs) are fermentation products of anaerobic bacteria. More than just being an important energy source for intestinal epithelial cells, these compounds are modulators of ...leukocyte function and potential targets for the development of new drugs. The aim of this study was to evaluate the effects of SCFAs (acetate, propionate and butyrate) on production of nitric oxide (NO) and proinflammatory cytokines tumor necrosis factor α (TNF-α) and cytokine-induced neutrophil chemoattractant-2 (CINC-2αβ) by rat neutrophils. The involvement of nuclear factor κB (NF-κB) and histone deacetylase (HDAC) was examined. The effect of butyrate was also investigated in vivo after oral administration of tributyrin (a pro-drug of butyrate). Propionate and butyrate diminished TNF-α, CINC-2αβ and NO production by LPS-stimulated neutrophils. We also observed that these fatty acids inhibit HDAC activity and NF-κB activation, which might be involved in the attenuation of the LPS response. Products of cyclooxygenase and 5-lipoxygenase are not involved in the effects of SCFAs as indicated by the results obtained with the inhibitors of these enzymes. The recruitment of neutrophils to the peritonium after intraperitoneal administration of a glycogen solution (1%) and the ex vivo production of cytokines and NO by neutrophils were attenuated in rats that previously received tributyrin. These results argue that this triglyceride may be effective in the treatment of inflammatory conditions.
•Digested guaraná inhibited carbohydrate enzymes activity.•Guaraná may be useful to modulate postprandial hyperglycemia.•The polyphenols of guaraná are unstable throughout the in vitro digestion ...process.
Guaraná (Paullinia cupana) is a typical product from Amazon biota that exerts antioxidant capacity due to the presence of phenolic compounds, such as catechin, epicatechin and proanthocyanidins. The objective of this study was to evaluate the potential inhibitory activity of guaraná extracts, after digestion in vitro, on carbohydrates-metabolism enzymes and to assess the bioacessibility of guaraná polyphenols. The guaraná samples before and after enzymatic digestion, were compared for total phenolic content and phenolic profile. Furthermore, we investigated the uptake of polyphenols from guarana, using Caco-2 cells, and the effect of digested guaraná on carbohydrate metabolism enzymes. The amount of total phenolic compounds extracted from guaraná decreased after digestion in vitro, and native phenolics were not identified after cell permeation. On the other hand, polyphenols from guaraná were able to inhibit α-glucosidase and α-amylase activities. In conclusion, guaraná can be considered as a dietary source with anti-hyperglycemic potential.
Copper was continuously and selectively precipitated with Na
2S to concentrations below 0.3
ppb from water containing around 600
ppm of both Cu and Zn in a Continuously Stirred Tank Reactor. The pH ...was controlled at 3 and the pS at 25 (pS
=
−log(S
2−)) by means of an Ag
2S sulfide selective electrode. Copper's recovery and purity were about 100%, whereas the total soluble sulfide concentration was below 0.02
ppm. X-ray diffraction (XRD) analysis showed that copper precipitated as hexagonal CuS (covellite). The mode of the particle size distribution (PSD) of the CuS precipitates was around 36
μm. The PSD increased by high pS values and by the presence of Zn. Depending on the turbulence, the CuS precipitates can grow up to 200
μm or fragment in particles smaller than 3
μm in a few seconds. Zn precipitation with Na
2S at pH 3 and 4, in batch, always lead to Zn concentrations above 1
ppm. Zn precipitated as cubic ZnS (spharelite).
A body mass index (BMI) below morbid obesity range is often a requirement for kidney transplant wait‐listing, but data linking BMI changes to mortality during the waitlist period are lacking. By ...linking the 6‐year (7/2001–6/2007) national databases of a large dialysis organization and the Scientific Registry of Transplant Recipients, we identified 14 632 waitlisted hemodialysis patients without kidney transplantation. Time‐dependent survival models examined the mortality predictability of 13‐week‐averaged BMI, pretransplant serum creatinine as a muscle mass surrogate and their changes over time. The patients were on average 52 ± 13 years old, 40% women and had a BMI of 26.9 ± 6.3 kg/m2. Each kg/m2 increase of BMI was associated with a death hazard ratio (HR) of 0.96 (95%CI: 0.95–0.97). Compared to the lowest creatinine quintile, the 4th and 5th quintiles had death HRs of 0.75 (0.66–0.86) and 0.57 (0.49–0.66), respectively. Compared to minimal (< ± 1 kg) weight change over 6 months, those with 3 kg–<5 kg and ≥5 kg weight loss had death HRs of 1.31 (1.14–1.52) and 1.51 (1.30–1.75), respectively. Similar associations were observed with creatinine changes over time. Transplant‐waitlisted hemodialysis patients with lower BMI or muscle mass and/or unintentional weight or muscle loss have higher mortality in this observational study. Impact of intentional weight change remains unclear.
The authors examined the association of changes in pretransplant BMI or muscle mass with mortality in 14,632 hemodialysis patients over 6 years of kidney transplant waitlisting period (2001–2007) and found that lower BMI or muscle mass and/or unintentional weight or muscle loss were associated with higher mortality. See editorial by Segev et al on page 652.
Zika virus (ZIKV) infection has been associated with severe complications both in the developing and adult nervous system. To investigate the deleterious effects of ZIKV infection, we used human ...neural progenitor cells (NPC), derived from induced pluripotent stem cells (iPSC). We found that NPC are highly susceptible to ZIKV and the infection results in cell death. ZIKV infection led to a marked reduction in cell proliferation, ultrastructural alterations and induction of autophagy. Induction of apoptosis of Sox2
cells was demonstrated by activation of caspases 3/7, 8 and 9, and by ultrastructural and flow cytometry analyses. ZIKV-induced death of Sox2
cells was prevented by incubation with the pan-caspase inhibitor, Z-VAD-FMK. By confocal microscopy analysis we found an increased number of cells with supernumerary centrosomes. Live imaging showed a significant increase in mitosis abnormalities, including multipolar spindle, chromosome laggards, micronuclei and death of progeny after cell division. FISH analysis for chromosomes 12 and 17 showed increased frequency of aneuploidy, such as monosomy, trisomy and polyploidy. Our study reinforces the link between ZIKV and abnormalities in the developing human brain, including microcephaly.
Background and Purpose
The function of the endocannabinoid system (ECS) in renal tissue is not completely understood. Kidney function is closely related to ion reabsorption in the proximal tubule, ...the nephron segment responsible for the re‐absorption of 70–80% of the filtrate. We studied the effect of compounds modulating the activity of cannabinoid (CB) receptors on the active re‐absorption of Na+ in LLC‐PK1 cells.
Experimental Approach
Changes in Na+/K+‐ATPase activity were assessed after treatment with WIN55,212‐2 (WIN), a non‐selective lipid agonist, and haemopressin (HP), an inverse peptide agonist at CB1 receptors. Pharmacological tools were used to investigate the signalling pathways involved in the modulation of Na+ transport.
Key Results
In addition to CB1 and CB2 receptors and TRPV1 channels, the mRNAs encoding for enzymes of the ECS were also expressed in LLC‐PK1. WIN (10−7 M) and HP (10−6 M) altered Na+ re‐absorption in LLC‐PK1 in a dual manner. They both acutely (after 1 min) increased Na+/K+‐ATPase activity in a TRPV1 antagonist‐sensitive way. WIN's stimulating effect persisted for 30 min, and this effect was partially blocked by a CB1 antagonist or a PKC inhibitor. In contrast, HP inhibited Na+/K+‐ATPase after 30 min incubation, and this effect was attenuated by a CB1 antagonist or a PKA inhibitor.
Conclusion and Implications
The ECS is expressed in LLC‐PK1 cells. Both CB1 receptors and TRPV1 channels regulate Na+/K+‐ATPase activity in these cells, and are modulated by lipid and peptide CB1 receptor ligands, which act via different signalling pathways.
We compute the two-loop
β
-function of scalar and spinorial quantum electrodynamics as well as pure Yang–Mills and quantum chromodynamics using the background field method in a fully ...quadridimensional setup using implicit regularization (IREG). Moreover, a thorough comparison with dimensional approaches such as conventional dimensional regularization (CDR) and dimensional reduction (DRED) is presented. Subtleties related to Lorentz algebra contractions/symmetric integrations inside divergent integrals as well as renormalisation schemes are carefully discussed within IREG where the renormalisation constants are fully defined as basic divergent integrals to arbitrary loop order. Moreover, we confirm the hypothesis that momentum routing invariance in the loops of Feynman diagrams implemented via setting well-defined surface terms to zero deliver non-abelian gauge invariant amplitudes within IREG just as it has been proven for abelian theories.
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