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Sleep is thought to help consolidate hippocampus-dependent memories by reactivating previously encoded neural representations, promoting both quantitative and qualitative changes in memory representations. However, the qualitative nature of changes to memory representations induced by sleep remains largely uncharacterized. In this study, we investigated how memories are reconstructed by hypothesizing that semantic coherence, defined as conceptual relatedness between statements of free-recall texts and quantified using latent semantic analysis (LSA), is affected by post-encoding sleep. Short naturalistic videos of events featuring six animals were presented to 115 participants who were randomly assigned to either 12- or 24-h delay groups featuring sleep or wakefulness. Participants' free-recall responses were analyzed to test for an effect of sleep on semantic coherence between adjacent statements, and overall. The presence of sleep reduced both forms of semantic coherence, compared to wakefulness. This change was robust and not due to shifts in conciseness or repetitiveness with sleep. These findings support the notion that sleep-dependent consolidation qualitatively changes the features of reconstructed memory representations by reducing semantic coherence.The aim of this study is to perform volumetric and basic radiobiological analyses using the database on prostate patients treated by HDR brachytherapy in our institution during the period 2011-2016. Real-time ultrasound based technique was used, with Oncentra Prostate planning software. The whole period was divided into two sub-periods, according to the 100% dose per fraction, which was 10.5 Gy during the first period (2011-2012), and 11 Gy during the second period (2013-2016), for each of the three fractions. The follow up time varied from 19 to 81 months, with a median of 45 months and a mean of 47 months. The uniformity of the treatment technique for both periods is investigated. Telaprevir cost Tumour Control Probability (TCP) values for the expected local control are calculated according to a population phenomenological TCP model for different values of the α/β ratio. The calculations are based on the obtained averaged Dose Volume Histograms for the two investigated sub-periods. 74 patients were treated in total. Local control failure is observed in 5 cases, which corresponds to an observed TCP = 93.2%. The comparison of the calculated population average DVH with the DVHs of the cases with local control failure shows that in 4 of them, doses higher than average were delivered to the prostate. It is shown that the uniformity of the treatment was improved during the second sub-period. A possible explanation of the observed failures may be that these cases exhibit inherent tumour cell radio-resistance higher than average. Our radiobiological analysis indicates a α/β ratio value somewhat higher than the one currently accepted. The value of the prostate α/β ratio is estimated to be in the range of [3.5-6] Gy.Plasticity of the cerebral cortex following a modification of the sensorimotor experience takes place in several steps that can last from few hours to several months. Among the mechanisms involved in the dynamic modulation of the cerebral cortex in adults, it is commonly proposed that short-term plasticity reflects changes in synaptic connections. Here, we were interested in the time-course of synaptic plasticity taking place in the somatosensory primary cortex all along a 14-day period of sensorimotor perturbation (SMP), as well as during a recovery phase up to 24 h. Activation and expression level of pre- (synapsin 1, synaptophysin, synaptotagmin 1) and postsynaptic (AMPA and NMDA receptors) proteins, postsynaptic density scaffold proteins (PSD-95 and Shank2), and cytoskeletal proteins (neurofilaments-L and M, β3-tubulin, synaptopodin, N-cadherin) were determined in cortical tissue enriched in synaptic proteins. During the SMP period, most changes were observed as soon as D7 in the presynaptic compartment and were followed, at D14, by changes in the postsynaptic compartment. These changes persisted at least until 24 h of recovery. Proteins involved in synapse structure (scaffolding, adhesion, cytoskeletal) were mildly affected and almost exclusively at D14. We concluded that experience-dependent reorganization of somatotopic cortical maps is accompanied by changes in synaptic transmission with a very close time-course.Circular RNAs (circRNAs) have key roles in a variety of neurological diseases, including epilepsy. This objective of this study was to perform the functional exploration and mechanism investigation of circRNA Ubiquilin1 (circUBQLN1) in epilepsy. Epilepsy cell model was established by the treatment of Mg2+-free in human neurons-hippocampal (HN-h) cells. The quantitative real-time polymerase chain reaction (qRT-PCR) was used for the expression analysis of circUBQLN1, linear-UBQLN1, microRNA-155 (miR-155), and sex-determining region Y-box 7 (SOX7). Proliferation detection was completed using Cell Counting Kit-8 (CCK-8) assay. Apoptosis analysis was conducted by flow cytometry and caspase-3 assay. Oxidative stress was assessed through determining the levels of superoxide dismutase (SOD) and malondialdehyde (MDA). Target analysis was performed by dual-luciferase reporter and RNA pull-down assays. SOX7 protein level was examined by Western blot. CircUBQLN1 was downregulated in epilepsy samples and Mg2+-free-induced cell model. Functional analysis in vitro suggested that circUBQLN1 overexpression facilitated proliferation but reduced apoptosis and oxidative stress in Mg2+-free-treated HN-h cells. Target analysis showed that circUBQLN1 acted as a miR-155 sponge and miR-155-targeted SOX7. Moreover, circUBQLN1 could combine with miR-155 to regulate the SOX7 expression. Reverted assays indicated that circUBQLN1 overexpression alleviated the Mg2+-free-induced nerve injury by sponging miR-155, and knockdown of SOX7 abrogated the protective function of in-miR-155 or circUBQLN1 in the Mg2+-free-treated HN-h cells. Our data revealed that circUBQLN1 prevented nerve injury in Mg2+-free-treated HN-h cells by regulating the miR-155/SOX7 axis, showing that circUBQLN1 might be used as a biomolecular target for the treatment of epilepsy.
(Mal-)nutrition of micronutrients, like selenium, has great impact on the human heart and improper micronutrient intake was observed in 30-50% of patients with heart failure. Low selenium levels have been reported in Europe and Asia and thought to be causal for Keshan disease. Selenium is an essential micronutrient that is needed for enzymatic activity of the 25 so-called selenoproteins, which have a broad range of activities. In this review, we aim to summarize the current evidence about selenium in heart failure and to provide insights about the potential mechanisms that can be modulated by selenoproteins.
Suboptimal selenium levels (<100 μg/L) are prevalent in more than 70% of patients with heart failure and were associated with lower exercise capacity, lower quality of life, and worse prognosis. Small clinical trials assessing selenium supplementation in patients with HF showed improvement of clinical symptoms (NYHA class), left ventricular ejection fraction, and lipid profile, while governmental ioprotein N; SELENOP, selenoprotein P; SELENOS, selenoprotein S; SELENOT, selenoprotein T; TXNRD, thioredoxin reductase.
With a worldwide aging population, frailty and heart failure (HF) have become issues that need to be addressed urgently in cardiovascular clinical practice. In this review, we outline the clinical implications of frailty in HF patients and the potential therapeutic strategies to improve the clinical outcomes of frail patients with HF.
Frailty has physical, psychological, and social domains, each of which is a prognostic determinant for patients with HF, and each domain overlaps with the other, although there are no standardized criteria for diagnosing frailty. Frailty can be targeted for treatment with various interventions, and recent studies have suggested that multidisciplinary intervention could be a promising option for frail patients with HF. However, currently, there is limited data, and further research is needed before its clinical implementation. Frailty and HF share a common background and are strongly associated with each other. More comprehensive assessment and therapeutic interventions for frailty need to be developed to further improve the prognosis and quality of life of frail patients with HF.
Frailty has physical, psychological, and social domains, each of which is a prognostic determinant for patients with HF, and each domain overlaps with the other, although there are no standardized criteria for diagnosing frailty. Frailty can be targeted for treatment with various interventions, and recent studies have suggested that multidisciplinary intervention could be a promising option for frail patients with HF. However, currently, there is limited data, and further research is needed before its clinical implementation. Frailty and HF share a common background and are strongly associated with each other. More comprehensive assessment and therapeutic interventions for frailty need to be developed to further improve the prognosis and quality of life of frail patients with HF.
Multiple newer medications benefit patients with heart failure with reduced ejection fraction (HFrEF). While these therapies benefit the broad population with HFrEF, the efficacy and safety of these therapies have been less well characterized in patients with significant comorbidities.
Common comorbidities of high interest in heart failure (HF) include diabetes mellitus, chronic kidney disease (CKD), atrial fibrillation, and obesity, and each has potential implications for clinical management. As the burden of comorbidities increases in HF populations, risk-benefit assessments of HF therapies in the context of different comorbidities are increasingly relevant for clinical practice. This review summarizes data regarding the core HFrEF therapies in the context of comorbidities, with specific attention to sodium-glucose cotransporter 2 inhibitors, sacubitril/valsartan, mineralocorticoid receptor antagonists (MRAs), and beta-blockers. In general, studies support consistent treatment effects with regard to clisporter 2 inhibitors, sacubitril/valsartan, mineralocorticoid receptor antagonists (MRAs), and beta-blockers. In general, studies support consistent treatment effects with regard to clinical outcome benefits in the presence of comorbidities. Likewise, safety profiles are relatively consistent irrespective of comorbidities, with the exception of heightened risk of hyperkalemia with MRA therapy in patients with severe CKD. In conclusion, while HF management is complex in the context of multiple comorbidities, the totality of evidence strongly supports guideline-directed medical therapies as foundational for improving outcomes in these high-risk patients.Linear regression analyses commonly involve two consecutive stages of statistical inquiry. In the first stage, a single 'best' model is defined by a specific selection of relevant predictors; in the second stage, the regression coefficients of the winning model are used for prediction and for inference concerning the importance of the predictors. However, such second-stage inference ignores the model uncertainty from the first stage, resulting in overconfident parameter estimates that generalize poorly. These drawbacks can be overcome by model averaging, a technique that retains all models for inference, weighting each model's contribution by its posterior probability. Although conceptually straightforward, model averaging is rarely used in applied research, possibly due to the lack of easily accessible software. To bridge the gap between theory and practice, we provide a tutorial on linear regression using Bayesian model averaging in JASP, based on the BAS package in R. Firstly, we provide theoretical background on linear regression, Bayesian inference, and Bayesian model averaging.
My Website: https://www.selleckchem.com/products/Telaprevir(VX-950).html
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