Notes

Chromatin-mediated alternative splicing regulates cocaine-reward habits.
DPPH radical scavenging capacity, reducing power, ferrous ion chelating ability and inhibition of lipid peroxidation of fermented wheat were significantly stronger than control (P less then 0.05).Sulforaphane (SFN) is a sulfur-containing isothiocyanate found in cruciferous vegetables (Brassicaceae) and a well-known activator of nuclear factor-erythroid 2-related factor 2 (Nrf2), considered a master regulator of cellular antioxidant responses. Patients with chronic diseases, such as diabetes, cardiovascular disease, cancer, and chronic kidney disease (CKD) present with high levels of oxidative stress and a massive inflammatory burden associated with diminished Nrf2 and elevated nuclear transcription factor-κB-κB expression. Because it is a common constituent of dietary vegetables, the salutogenic properties of sulforaphane, especially it's antioxidative and anti-inflammatory properties, have been explored as a nutritional intervention in a range of diseases of ageing, though data on CKD remain scarce. In this brief review, the effects of SFN as a senotherapeutic agent are described and a rationale is provided for studies that aim to explore the potential benefits of SFN-rich foods in patients with CKD.Congenital blindness has been shown to result in behavioral adaptation and neuronal reorganization, but the underlying neuronal mechanisms are largely unknown. Brain rhythms are characteristic for anatomically defined brain regions and provide a putative mechanistic link to cognitive processes. In a novel approach, using magnetoencephalography resting state data of congenitally blind and sighted humans, deprivation-related changes in spectral profiles were mapped to the cortex using clustering and classification procedures. Altered spectral profiles in visual areas suggest changes in visual alpha-gamma band inhibitory-excitatory circuits. Remarkably, spectral profiles were also altered in auditory and right frontal areas showing increased power in theta-to-beta frequency bands in blind compared with sighted individuals, possibly related to adaptive auditory and higher cognitive processing. Moreover, occipital alpha correlated with microstructural white matter properties extending bilaterally across posterior parts of the brain. We provide evidence that visual deprivation selectively modulates spectral profiles, possibly reflecting structural and functional adaptation.An high performance liquid chromatography (HPLC) method, applying diode array (DAD) and coulometric array detection simultaneously, was developed to determine monomeric phenolic compounds in lignin hydrolysates. To allow for additional mass spectrometric detection, a formic acid gradient was designed as an alternative to the non-volatile phosphate buffer gradient. Within a total run time of 28 min, 10 out of 14 analytes were baseline separated by the formic acid gradient, and 8 compounds were completely resolved by the phosphate gradient. The dependence of the coulometric detection on cell potential, potential step width, eluent pH and eluent composition was comprehensively tested. Detection limits ≤20 μg/L were achieved by DAD detection for nine analytes and by coulometric array detection for all analytes, demonstrating the superior sensitivity of electrochemical detection. DAD offered better linearity and reproducibility. Inter-day precision of peak heights spanned from 0.26 to 2.00% (formic acid gradient) and from 0.75 to 2.85% (phosphate buffer gradient) operating the DAD detector, but it exceeded 10% for several compounds applying the coulometric array detector. The simultaneous operation of both detectors offered an enhanced certainty of substance identification. The appropriateness of the method was confirmed by the analysis of various hydrolysates of lignin-containing materials.
dance is a mind-body activity that stimulates neuroplasticity. We explored the effect of dance on cognitive function in older adults.

we searched MEDLINE, EMBASE, CENTRAL and PsycInfo databases from inception to August 2020 (PROSPEROCRD42017057138). Inclusion criteria were (i) randomised controlled trials (ii) older adults (aged ≥ 55years), (iii) intervention-dance and (iv) outcome-cognitive function. Cognitive domains were classified with the Diagnostic and Statistical Manual of Mental Disorders-5 Neurocognitive Framework. Meta-analyses were performed in RevMan5.3 and certainty of evidence with GradePro.

we reviewed 3,997 records and included 11 studies (N = 1,412 participants). Seven studies included only healthy older adults and four included those with mild cognitive impairment (MCI). Dance interventions varied in frequency (1-3×/week), time (35-60minutes), duration (3-12months) and type. We found a mean difference (MD) = 1.58 (95% confidence interval [CI) = 0.21-2.95) on the Mini Mental State Examid executive function. However, there is little difference in complex attention, and evidence also suggests little effect on learning and memory. Future research is needed to determine the optimal dose and if dance results in greater cognitive benefits than other types of physical activity and exercise.
Myocardial infarction (MI) accelerates atherosclerosis and greatly increases the risk of recurrent cardiovascular events for many years, in particular, strokes and MIs. Because B cell-derived autoantibodies produced in response to MI also persist for years, we investigated the role of B cells in adaptive immune responses to MI.

We used an apolipoprotein-E-deficient (ApoE-/-) mouse model of MI-accelerated atherosclerosis to assess the importance of B cells. One week after inducing MI in atherosclerotic mice, we depleted B cells using an anti-CD20 antibody. This treatment prevented subsequent immunoglobulin G accumulation in plaques and MI-induced accelerated atherosclerosis. In gain of function experiments, we purified spleen B cells from mice 1 week after inducing MI and transferred these cells into atherosclerotic ApoE-/- mice, which greatly increasedimmunoglobulin G (IgG) accumulation in plaque and accelerated atherosclerosis. These B cells expressed many cytokines that promote humoural immunity and in urrent cardiovascular events such as MI and stroke.
To measure the variability in carbapenem susceptibility conferred by different OxaAb variants, characterize the molecular evolution of oxaAb and elucidate the contribution of OxaAb and other possible carbapenem resistance factors in the clinical isolates using WGS and LC-MS/MS.

Antimicrobial susceptibility tests were performed on 10 clinical Acinetobacter baumannii isolates. Carbapenem MICs were evaluated for all oxaAb variants cloned into A. baumannii CIP70.10 and BM4547, with and without their natural promoters. Molecular evolution analysis of the oxaAb variants was performed using FastTree and SplitsTree4. Resistance determinants were studied in the clinical isolates using WGS and LC-MS/MS.

Only the OxaAb variants with I129L and L167V substitutions, OxaAb(82), OxaAb(83), OxaAb(107) and OxaAb(110) increased carbapenem MICs when expressed in susceptible A. baumannii backgrounds without an upstream IS element. Carbapenem resistance was conferred with the addition of their natural upstream ISAba1 promotemonstrates that a combination of IS-driven overexpression of oxaAb and the presence of particular amino acid substitutions in the active site to improve carbapenem capture is key in conferring carbapenem resistance in A. baumannii and other mechanisms are not required.
There is debate around the composition of life years gained from smoking elimination. The aim of this study was to conduct a systematic review of the literature to synthesize existing evidence on the effect of smoking status on health expectancy and to examine whether smoking elimination leads to compression of morbidity.

Five databases were systematically searched for peer-reviewed articles. Studies that presented quantitative estimates of health expectancy for smokers and non-/never-smokers were eligible for inclusion. Studies were searched, selected and reviewed by two reviewers who extracted the relevant data and assessed the risk of bias of the included articles independently.

The search identified 2491 unique records, whereof 20 articles were eligible for inclusion (including 26 cohorts). The indicators used to measure health included disability/activity limitations (n=9), health-related quality of life (EQ-5D) (n=2), weighted disabilities (n=1), self-rated health (n=9), chronic diseases (n=6), ca to be harmonized.MuscleAtlasExplorer is a freely available web application that allows for the exploration of gene expression data from human skeletal muscle. It draws from an extensive publicly available dataset of 1654 skeletal muscle expression microarray samples. Detailed, manually curated, patient phenotype data, with information such as age, sex, BMI and disease status, are combined with skeletal muscle gene expression to provide insights into gene function in skeletal muscle. It aims to facilitate easy exploration of the data using powerful data visualization functions, while allowing for sample selection, in-depth inspection and further analysis using external tools. Selleckchem BAY-218 Availability MuscleAtlasExplorer is available at https//mae.crc.med.lu.se/mae2 (username 'muscle' and password 'explorer' pre-publication).The clinical outcome of BRAF-mutated advanced melanoma has been improved by both molecular targeted therapies and immune checkpoint inhibitors. Long-term follow-up data reveal durable clinical responses in patients receiving first-line combinations of BRAF inhibitors plus MEK inhibitors, particularly those showing a complete response. Clinical outcomes are also associated with the lactate dehydrogenase levels and the number of metastatic organs. Although brain metastasis is frequently difficult to control, systemic therapy is preferred in cases with small and asymptomatic brain metastases associated with progressive extra-cranial disease. Control of intra-cranial disease with BRAF inhibitors plus MEK inhibitors is comparable with that of immune checkpoint inhibitors, although immune checkpoint inhibitors are superior to targeted therapies with respect to survival. The BRAF inhibitors plus MEK inhibitors regimen is well-tolerated, and toxicities are usually manageable and reversible, but differ according to the specific regimen used. Guidelines in the United States, Europe, and Japan recommend targeted therapy for patients who need early tumor responses. A meta-analysis of retrospective data shows that the baseline lactate dehydrogenase level is significantly higher in patients treated with BRAF inhibitors plus MEK inhibitors than in those treated with immune checkpoint inhibitors, suggesting that clinicians tend to use BRAF inhibitors plus MEK inhibitors for more advanced disease. Since there is insufficient efficacy and safety data on the use of targeted therapies for acral and mucosal melanoma, a retrospective analysis may be useful. The combination of molecular targeted therapy plus immune checkpoint inhibitors is expected to elicit further improvement. The results of several trials using combination or sequential therapies will be available in the next few years.
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