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tonergic system. This was the first study confirming the analgesic effect of Styrax japonicus flower, which provided a candidate for the development of non-opioid analgesics.

EE from flowers of Styrax japonicus, and F1, the active part isolated from EE, showed significant antinociceptive activities. The analgesic effect of F1 appeared to be related to the sedative effect, partially mediated by the GABAergic system, and highly involved in the serotonergic system. This was the first study confirming the analgesic effect of Styrax japonicus flower, which provided a candidate for the development of non-opioid analgesics.Non-alcoholic steatohepatitis (NASH), a severe form of non-alcoholic fatty liver disease (NAFLD), can progress to cirrhosis, hepatocellular carcinoma (HCC), and hepatic failure/liver transplantation. Indeed, NASH will soon be the leading cause of HCC and liver transplantation. Lifestyle intervention represents the cornerstone of NASH treatment, but it is difficult to sustain. However, no pharmacotherapies for NASH have been approved. Oxidative stress has been implicated as one of the key factors in the pathogenesis of NASH. Systematic reviews with meta-analyses have confirmed that vitamin E reduces transaminase activities and may resolve NASH histopathology without improving hepatic fibrosis. However, vitamin E is not recommended for the treatment of NASH in diabetes, NAFLD without liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis. Nevertheless, vitamin E supplementation may improve clinical outcomes in patients with NASH and bridging fibrosis or cirrhosis. Further studies are warranted to confirm such effects of vitamin E and that it would reduce overall mortality/morbidity without increasing the incidence of cardiovascular events. Future clinical trials of the use of vitamin E in combination with other anti-fibrotic agents may demonstrate an additive or synergistic therapeutic effect. Vitamin E is the first-line pharmacotherapy for NASH, according to the consensus of global academic societies.As a key organelle in eukaryotic cells, mitochondria play a central role in maintaining normal cellular functions. Mitochondrial dysfunction is reported to be closely related with aging and various diseases. Epigenetic modifications in nuclear genome provide a substantial layer for the modulation of nuclear-encoded gene expression. However, whether mitochondria could also be subjected to such similar epigenetic alterations and the involved mechanisms remain largely obscure and controversial. Recently, accumulating evidence has suggested that mitochondrial epigenetics, also known as mitoepigenetics may serve as an intriguing regulatory layer in mitochondrial DNA (mtDNA)-encoded gene expression. EG011 Given the potential regulatory role of mitoepigenetics, mitochondrial dysfunction derived from mitoepigenetics-induced abnormal gene expression could also be closely associated with aging and disease development. In this review, we summarized the recent advances in mitoepigenetics, with a special focus on mtDNA methylation in aging and metabolic-related diseases as well as the new methods and technologies for the study of mitoepigenetics. Uncovering the regulatory role of mitoepigenetics will help to understand the underlying mechanisms of mitochondrial dysfunction and provide novel strategies for delaying aging and preventing metabolic-related diseases.Hereditary Spastic Paraplegias (HSP) are a group of rare inherited neurological disorders characterized by progressive loss of corticospinal motor-tract function. Numerous patients with HSP remain undiagnosed despite screening for known genetic causes of HSP. Therefore, identification of novel genetic variations related to HSP is needed. In this study, we identified 88 genetic variants in 54 genes from whole-exome data of 82 clinically well-defined Korean HSP families. Fifty-six percent were known HSP genes, and 44% were composed of putative candidate HSP genes involved in the HSPome and originally reported neuron-related genes, not previously diagnosed in HSP patients. Their inheritance modes were 39, de novo; 33, autosomal dominant; and 10, autosomal recessive. Notably, ALDH18A1 showed the second highest frequency. Fourteen known HSP genes were firstly reported in Koreans, with some of their variants being predictive of HSP-causing protein malfunction. SPAST and REEP1 mutants with unknown function induced neurite abnormality. Further, 54 HSP-related genes were closely linked to the HSP progression-related network. Additionally, the genetic spectrum and variation of known HSP genes differed across ethnic groups. These results expand the genetic spectrum for HSP and may contribute to the accurate diagnosis and treatment for rare HSP.

Despite immense progress of imaging and updates in the MacDonald criteria, the diagnosis of multiple sclerosis remains difficult as it must integrate history, clinical presentation, biological markers, and imaging. There is a multitude of syndromes resembling multiple sclerosis both clinically or on imaging. The goal of this review is to help clinicians orient themselves in these various diagnoses. We organized our review in two categories inflammatory and autoimmune diseases that are close or can be confused with multiple sclerosis, and non-inflammatory syndromes that can present with symptoms or imaging mimicking those of multiple sclerosis.

Review of literature CONCLUSION Progress of imaging and biological sciences have drastically changed the approach and management of multiple sclerosis. But these developments have also shined a light on a variety of diseases previously unknown or poorly known, therefore greatly expanding the differential diagnosis of multiple sclerosis. While autoimmune, many of theBien qu'auto-immuns par nature, nombre de ces syndromes obéissent à des mécanismes physiopathologiques différents de la sclérose en plaque. Leur approche thérapeutique est donc radicalement différente. Il est crucial d'approcher ces pathologies avec rigueur, en intégrant histoire de la maladie, examen clinique, et examens complémentaires.It is well established that head motion and physiological processes (e.g. cardiac and breathing activity) should be taken into consideration when analyzing and interpreting results in fMRI studies. However, even though recent studies aimed to evaluate the performance of different preprocessing pipelines there is still no consensus on the optimal strategy. This is partly due to the fact that the quality control (QC) metrics used to evaluate differences in performance across pipelines have often yielded contradictory results. Furthermore, preprocessing techniques based on physiological recordings or data decomposition techniques (e.g. aCompCor) have not been comprehensively examined. Here, to address the aforementioned issues, we propose a framework that summarizes the scores from eight previously proposed and novel QC metrics to a reduced set of two QC metrics that reflect the signal-to-noise ratio and the reduction in motion artifacts and biases in the preprocessed fMRI data. Using this framework, we evaluate the performance of three commonly used practices on the quality of data 1) Removal of nuisance regressors from fMRI data, 2) discarding motion-contaminated volumes (i.e., scrubbing) before regression, and 3) low-pass filtering the data and the nuisance regressors before their removal. Using resting-state fMRI data from the Human Connectome Project, we show that the scores of the examined QC metrics improve the most when the global signal (GS) and about 17% of principal components from white matter (WM) are removed from the data. Finally, we observe a small further improvement with low-pass filtering at 0.20 Hz and milder variants of WM denoising, but not with scrubbing.T2⁎ relaxivity contrast imaging may serve as a potential imaging biomarker for amyotrophic lateral sclerosis (ALS) by noninvasively quantifying the tissue microstructure. In this preliminary longitudinal study, we investigated the Transverse Relaxivity at Tracer Equilibrium (TRATE) in three muscle groups between SOD1-G93A (ALS model) rat and a control population at two different timepoints. The control group was time matched to the ALS group such that the second timepoint was the onset of disease. We observed a statistically significant decrease in TRATE over time in the gastrocnemius, tibialis, and digital flexor muscles in the SOD1-G93A model (p-value = 0.003, 0.008, 0.005; respectively), whereas TRATE did not change over time in the control group (p-value = 0.4777, 0.6837, 0.9682; respectively). Immunofluorescent staining revealed a decrease in minimum fiber area and cell density in the SOD1-G93A model when compared to the control group (p-value = 6.043E-10 and 2.265E-10, respectively). These microstructural changes observed from histology align with the theorized biophysical properties of TRATE. We demonstrate that TRATE can longitudinally differentiate disease associated atrophy from healthy muscle and has potential to serve as a biomarker for disease progression and ultimately therapy response in patients with ALS.Automated brain tumour segmentation from post-operative images is a clinically relevant yet challenging problem. In this study, an automated method for segmenting brain tumour into its subregions has been developed. The dataset consists of multimodal post-operative brain scans (T1 MRI, post-Gadolinium T1 MRI, and T2-FLAIR images) of 15 patients who were treated with post-operative radiation therapy, along with manual annotations of their tumour subregions. A 3D densely-connected U-net was developed for segmentation of brain tumour regions and extensive experiments were conducted to enhance model accuracy. A model was initially developed using the publicly available BraTS dataset consisting of pre-operative brain scans. This model achieved Dice Scores of 0.90, 0.83 and 0.78 for predicting whole tumour, tumour core, and enhancing tumour subregions when tested on BraTS20 blind validation dataset. The acquired knowledge from BraTS was then transferred to the local dataset. For augmentation purpose, the local dataset was registered to a dataset of MRI brain scans of healthy subjects. To improve the robustness of the model and enhance its accuracy, ensemble learning was used to combine the outputs of all the trained models. Even though the size of the dataset is very small, the final model can segment brain tumours with a high Dice Score of 0.83, 0.77 and 0.60 for whole tumour, tumour core and enhancing core respectively.[Background] Magnetic resonance angiography (MRA) is one of the most important sequences to estimate a cerebrovascular disease. We often encounter poor image quality due to slow arterial flow related to aging and motion artifact caused by disturbance of consciousness. We focused on phase contrast angiography (PCA) to overcome these difficulties. PCA can reduce scan time drastically by combining transverse acquisition and partial slab setting covering entire brain arteries. However, transverse acquisition in PCA has a large difference in signal intensity between proximal and distal vessels. Therefore, we apply tilted optimized non-saturated excitation (TONE) to improve image quality. [Purpose] The purpose of this study to investigate the usefulness of TONE for PCA. [Method] We estimated the efficacy of TONE in transverse acquisition PCA using measurement of signal intensity in arteries. We compared image quality among 1 min PCA with/without TONE and time-of flight (TOF)-MRA, by visual. [Result] TONE improved the signal inhomogeneity in entire brain arteries.