Extensive representation of sensory deviance in the responses to auditory gaps in unanesthetized rats.

Unexpected changes in incoming sensory streams are associated with large errors in predicting the deviant stimulus relative to a memory trace of past stimuli. Mismatch negativity (MMN) in human studies and the release from stimulus-specific adaptation (SSA) in animal models correlate with prediction errors and deviance detection.1 In human studies, violation of expectations elicited by an unexpected stimulus omission resulted in an omission MMN.2,3,4,5 These responses are evoked after the expected occurrence time of the omitted stimulus, implying that they reflect the violation of a temporal expectancy.6 Because they are often time locked to the end of the omitted stimulus,4,6,7 they resemble off responses. Indeed, suppression of cortical activity after the termination of the gap disrupts gap detection, suggesting an essential role for offset responses.8 Here, we demonstrate that brief gaps in short noise bursts in the auditory cortex of unanesthetized rats frequently evoke offset responses. Importantly, we show that omission responses are elicited when these gaps are expected but are omitted. These omission responses, together with the release from SSA of both onset and offset responses to rare gaps, form a rich and varied representation of prediction-related signals in the auditory cortex of unanesthetized rats, extending substantially and refining the representations described previously in anesthetized rats.

Oral Coenzyme Q10 supplementation leads to better preservation of kidney function in steroid-resistant nephrotic syndrome due to primary Coenzyme Q10 deficiency.

Primary Coenzyme Q10 (CoQ10) deficiency is an ultra-rare disorder caused by defects in genes involved in CoQ10 biosynthesis leading to multidrug-resistant nephrotic syndrome as the hallmark kidney manifestation. Promising early results have been reported anecdotally with oral CoQ10 supplementation. However, the long-term efficacy and optimal prescription remain to be established. In a global effort, we collected and analyzed information from 116 patients who received CoQ10 supplements for primary CoQ10 deficiency due to biallelic pathogenic variants in either the COQ2, COQ6 or COQ8B genes. Median duration of follow up on treatment was two years. The effect of treatment on proteinuria was assessed, and kidney survival was analyzed in 41 patients younger than 18 years with chronic kidney disease stage 1-4 at the start of treatment compared with that of an untreated cohort matched by genotype, age, kidney function, and proteinuria. CoQ10 supplementation was associated with a substantial and significant sustained reduction of proteinuria by 88% at 12 months. Complete remission of proteinuria was more frequently observed in COQ6 disease. CoQ10 supplementation led to significantly better preservation of kidney function (5-year kidney failure-free survival 62% vs. 19%) with an improvement in general condition and neurological manifestations. Side effects of treatment were uncommon and mild. Thus, our findings indicate that all patients diagnosed with primary CoQ10 deficiency should receive early and life-long CoQ10 supplementation to decelerate the progression of kidney disease and prevent further damage to other organs.

Real-Time Multiscale Monitoring and Tailoring of Graphene Growth on Liquid Copper.

The synthesis of large, defect-free two-dimensional materials (2DMs) such as graphene is a major challenge toward industrial applications. Chemical vapor deposition (CVD) on liquid metal catalysts (LMCats) is a recently developed process for the fast synthesis of high-quality single crystals of 2DMs. However, up to now, the lack of in situ techniques enabling direct feedback on the growth has limited our understanding of the process dynamics and primarily led to empirical growth recipes. Thus, an in situ multiscale monitoring of the 2DMs structure, coupled with a real-time control of the growth parameters, is necessary for efficient synthesis. Here we report real-time monitoring of graphene growth on liquid copper (at 1370 K under atmospheric pressure CVD conditions) via four complementary in situ methods: synchrotron X-ray diffraction and reflectivity, Raman spectroscopy, and radiation-mode optical microscopy. This has allowed us to control graphene growth parameters such as shape, dispersion, and the hexagonal supra-organization with very high accuracy. Furthermore, the switch from continuous polycrystalline film to the growth of millimeter-sized defect-free single crystals could also be accomplished. The presented results have far-reaching consequences for studying and tailoring 2D material formation processes on LMCats under CVD growth conditions. Finally, the experimental observations are supported by multiscale modeling that has thrown light into the underlying mechanisms of graphene growth.

The effect of Cistus incanus herbal tea supplementation on oxidative stress markers and lipid profile in healthy adults.

BACKGROUND: Oxidative stress and dyslipidemia play a critical role in the development of cardiovascular disease (CVD). Regular intake of polyphenol-rich diets is associated with a reduced risk of CVDs. METHODS: The present study was a pilot study with 24 healthy volunteers and was designed to determine if a 12-week administration of Cistus incanus herbal tea, containing phenolic acids and flavonoids, reduces cardiovascular risk factors including oxidative stress and dyslipidemia in healthy adults. Phenolic compounds profile and antibacterial activity of Cistus incanus infusion were also measured. RESULTS: Herbal infusion led to improvement in lipid profile by increase (D4%, p = 0.033) high-density lipoprotein cholesterol concentration and decrease triglyceride (D14%, p = 0.013) concentrations. In addition, the Cistus incanus diet was associated with decreased serum concentrations of malondialdehyde (D16%, p < 0.01) and advanced oxidation protein products (D18%, p < 0.001). CONCLUSIONS: Cistus incanus administration decreases cardiovascular risk factors including oxidative stress and dyslipidemia and this action supports the idea of using Cistus incanus tea on a daily basis as an effective dietary component for prevention of atherosclerotic CVD.

Flaxseed (Linum Usitatissimum L.) Supplementation in Patients Undergoing Lipoprotein Apheresis for Severe Hyperlipidemia-A Pilot Study.

Being rich in polyunsaturated fatty acids, flaxseed (Linum usitatissimum L.) is thought to be able to decrease lipid levels and dampen inflammation. In this pilot study, we aimed to determine whether flaxseed supplementation could improve the profiles of lipids and inflammatory mediators in patients with severe hyperlipidemia resistant to conventional lipid-lowering pharmacotherapy and requiring lipoprotein apheresis. To this end, six patients received, blindly-in addition to their normal lipoprotein apheresis regimen-a 10-week dietary supplementation with flaxseed (28 g/d) administered in biscuits. This was followed by a 10-week washed out-period and a 10-week supplementation phase with whole wheat placebo. Blood samples were collected at the end of each phase, before the lipoprotein apheresis session. The primary endpoint was the lipid profile and the secondary endpoints were the concentrations of inflammatory mediators and tolerability. Flaxseed supplementation was well-tolerated and resulted in a consistent and significant decrease in total cholesterol and low-density lipoprotein (LDL) levels. The median (and range) percentage decrease was 11.5% (0-18.8) and 7.3% (4.4-26.6), for cholesterol (p = 0.015) and LDL-C (p = 0.003), respectively. On the other hand, there was no significant effect of flaxseed on lipoprotein(a) (Lp(a)), C-reactive protein (CRP), and interleukin 6 (IL-6) concentrations. These observations indicate that flaxseed can produce a cholesterol- and LDL-lowering effect in patients treated with lipoprotein apheresis. Thus, flaxseed supplementation may help to control cholesterol in this patient population. The flaxseed supplementation protocol applied may be of use for further adequately-powered studies to validate and extend our findings.