Holmedowling5205

Moreover, clinical studies have indicated that decreased circulating miR-132 levels could be used a potential diagnostic biomarker in AD. Here, we review the pathogenic role of miR-132 activity in AD, and the potential of targeting miR-132 for developing future therapeutic strategies.Rbfox1 is a multifunctional RNA binding protein that regulates alternative splicing, transcription, mRNA stability and translation. Its roles in neurogenesis and neuronal functions are well established. Recent studies also implicate Rbfox1 in the regulation of gene networks that support cell survival during stress. We have earlier characterized the expression of Rbfox1 in amacrine and retinal ganglion cells (RGCs) and showed that deletion of Rbfox1 in adult animals results in depth perception deficiency. The current study investigates the effect of Rbfox1 downregulation on survival of RGCs injured by optic nerve crush (ONC). Seven days after ONC, animals sustained severe degeneration of RGC axons in the optic nerve and significant loss of RGC somas. Semi-quantitative grading of optic nerve damage in control + ONC, control + tamoxifen + ONC, and Rbfox1 -/- + ONC groups ranged from 4.6 to 4.8 on a scale of 1 (normal; no degenerated axons were noted) to 5 (total degeneration; all axons showed degenerated organelles, axonal content, and myelin sheath), indicating a severe degeneration. Among these three ONC groups, no statistical significance was observed when any two groups were compared. The number of RGC somas were quantitatively analyzed in superior, inferior, nasal and temporal retinal quadrants at 0.5, 1, and 1.5 mm from the center of the optic disc. The average RGC densities (cells/mm2) were control 6,438 ± 1,203; control + ONC 2,779 ± 573; control + tamoxifen 6,163 ± 861; control + tamoxifen + ONC 2,573 ± 555; Rbfox1 -/- 6,437 ± 893; and Rbfox1 -/- + ONC 2,537 ± 526. The RGC loss in control + ONC, control + tamoxifen + ONC and Rbfox1 -/- + ONC was 57% (P = 1.44954E-42), 58% (P = 1.37543E-57) and 61% (P = 5.552E-59) compared to RGC numbers in the relevant uninjured groups, respectively. No statistically significant difference was observed between any two groups of uninjured animals or between any two ONC groups. Our data indicate that Rbfox1-mediated pathways have no effect on survival of RGCs injured by ONC.Vagus nerve stimulation (VNS) is an effective technique for the treatment of refractory epilepsy and shows potential for the treatment of a range of other serious conditions. However, until now stimulation has generally been supramaximal and non-selective, resulting in a range of side effects. Selective VNS (sVNS) aims to mitigate this by targeting specific fiber types within the nerve to produce functionally specific effects. In recent years, several key paradigms of sVNS have been developed-spatially selective, fiber-selective, anodal block, neural titration, and kilohertz electrical stimulation block-as well as various stimulation pulse parameters and electrode array geometries. selleck chemicals sVNS can significantly reduce the severity of side effects, and in some cases increase efficacy of the treatment. While most studies have focused on fiber-selective sVNS, spatially selective sVNS has demonstrated comparable mitigation of side-effects. It has the potential to achieve greater specificity and provide crucial information about vagal nerve physiology. Anodal block achieves strong side-effect mitigation too, but is much less specific than fiber- and spatially selective paradigms. The major hurdle to achieving better selectivity of VNS is a limited knowledge of functional anatomical organization of vagus nerve. It is also crucial to optimize electrode array geometry and pulse shape, as well as expand the applications of sVNS beyond the current focus on cardiovascular disease.Background The effects of polyphenols on cognitive functions have been extensively studied. Due to the large heterogeneity in the study designs, however, it is often difficult to interpret their efficacy. link2 To address this issue, we conducted a systematic review and meta-analyses to examine whether acute polyphenol intake may have a beneficial effect on cognition and specifically on the accuracy and speed of attention. Methods PubMed and Scopus databases were systematically searched for studies published up to end of August 2020 following PRISMA guidelines (PROSPERO registration number CRD42021232109). Only placebo-controlled human intervention trials that assessed acute effects of polyphenols on accuracy and speed of attention were included in the meta-analyses. When cognitive tasks were repeated over time, pooled means and standard deviations for intervention and placebo over repetitions separately for each task for both speed and accuracy were calculated. link3 We also conducted separate analyses focusing only on the last repetition. Furthermore, confounding effects of age and source of polyphenols were also considered. Results Eighteen studies met the inclusion criteria. The pooled analysis of last task repetitions showed that the acute consumption of polyphenols improved rapid visual information processing speed in young participants (SMD = 0.26; 95%CI = [0.03-0.50]; I 2= 0%; p = 0.02; k = 5). All other analyses did not reach significance. Conclusion The results of the current study indicate that acute polyphenol consumption might improve speed in rapid visual information processing task, a higher order task with elements of vigilance, working memory, and executive function, in young participants; however, as the current literature is inconsistent and limited, further acute intervention studies are warranted to achieve more conclusive results.The identification of neurological diseases in their presymptomatic phase will be a fundamental aim in the coming years. This step is necessary both to optimize early diagnostics and to verify the effectiveness of experimental disease modifying drugs in the early stages of diseases. Among the biomarkers that can detect neurological diseases already in their preclinical phase, neurofilament light chain (NfL) has given the most promising results. Recently, its measurement in serum has enabled the identification of neurodegeneration in diseases such as multiple sclerosis (MS) and Alzheimer's disease (AD) up to 6-10 years before the onset of symptoms. Similar results have been obtained in conditions such as frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), up to 2 years before clinical onset. Study of the longitudinal dynamics of serum NfL has also revealed interesting aspects of the pathophysiology of these diseases in the preclinical phase. This review sought to discuss these very recent findings on serum NfL in the presymptomatic phase of neurological diseases.The effort, focus, and time to collect data and train EMG pattern recognition systems is one of the largest barriers to their widespread adoption in commercial applications. In addition to multiple repetitions of motions, including exemplars of confounding factors during the training protocol has been shown to be critical for robust machine learning models. This added training burden is prohibitive for most regular use cases, so cross-user models have been proposed that could leverage inter-repetition variability supplied by other users. Existing cross-user models have not yet achieved performance levels sufficient for commercialization and require users to closely adhere to a training protocol that is impractical without expert guidance. In this work, we extend a previously reported adaptive domain adversarial neural network (ADANN) to a cross-subject framework that requires very little training data from the end-user. We compare its performance to single-repetition within-user training and the previous state-of-the-art cross-subject technique, canonical correlation analysis (CCA). ADANN significantly outperformed CCA for both intact-limb (86.8-96.2%) and amputee (64.1-84.2%) populations. Moreover, the ADANN adaptation computation time was substantially lower than the time otherwise devoted to conducting a full within-subject training protocol. This study shows that cross-user models, enabled by deep-learned adaptations, may be a viable option for improved generalized pattern recognition-based myoelectric control.How vision guides gaze in realistic settings has been researched for decades. Human gaze behavior is typically measured in laboratory settings that are well controlled but feature-reduced and movement-constrained, in sharp contrast to real-life gaze control that combines eye, head, and body movements. Previous real-world research has shown environmental factors such as terrain difficulty to affect gaze; however, real-world settings are difficult to control or replicate. Virtual reality (VR) offers the experimental control of a laboratory, yet approximates freedom and visual complexity of the real world (RW). We measured gaze data in 8 healthy young adults during walking in the RW and simulated locomotion in VR. Participants walked along a pre-defined path inside an office building, which included different terrains such as long corridors and flights of stairs. In VR, participants followed the same path in a detailed virtual reconstruction of the building. We devised a novel hybrid control strategy for movemen The similar dependence of gaze behavior on terrain in the RW and in VR indicates that our VR captures real-world constraints remarkably well. High-fidelity VR combined with naturalistic movement control therefore has the potential to narrow the gap between the experimental control of a lab and ecologically valid settings.Primary dysmenorrhea (PDM) is a common gynecological disease characterized by lower abdominal pain. Acupuncture is considered a good alternative therapy for PDM. However, the central mechanism of the analgesic effect of acupuncture is largely unknown. In this study, eligible patients were randomized into the real and sham acupuncture groups using a computer-generated, permuted block randomization method. The study cohort comprised 34 patients 19 in the real acupuncture group and 15 in the sham acupuncture group. The clinical characteristics of the patients during their menstrual period were collected, and imaging scans were performed during the first 3 days of the patients' menstrual period. We analyzed task and resting functional magnetic resonance imaging (fMRI) data to investigate the potential central mechanism of the immediate effect of acupuncture intervention on the intensity of PDM pain. The task fMRI study found that the rostral anterior cingulate cortex (rACC) and right supplemental motor area were activated during real acupuncture. Using the resting-state functional connectivity (FC) method, we found a post- versus pre-treatment change in the FC of the rACC and left precentral gyrus in the comparison of real acupuncture versus sham acupuncture. In addition, the FC of the rACC-left precentral gyrus at baseline was negatively correlated with short-term analgesia, while the change in the FC of the rACC-left precentral gyrus was positively correlated with short-term analgesia after acupuncture treatment. These findings support the importance of rACC-left precentral gyrus resting-state FC in the modulation of the intensity of PDM pain through acupuncture, which may shed light on the central mechanism of acupuncture in the treatment of PDM.