Search

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an early-onset inherited small vessel disease. Decreased cerebral blood flow (CBF) may contribute to white matter hyperintensity (WMH) severity in CADASIL, but more evidence is needed to support this hypothesis. This study comprised six patients with CADASIL who harbored mutations in the coding sequence of NOTCH3 and twelve age-matched neurologically healthy controls. We collected clinical and imaging data from patients with CADASIL and divided the brain into four regions: WMH, normal-appearing white matter (NAWM), gray matter (GM), and global brain. We analyzed the relationship between CBF of each region and the WMH volume. Compared with the control group, CBF was significantly decreased in all four regions in the CADASIL group. Lower CBF in these regions was correlated with higher WMH volume in CADASIL. CBF in the NAWM, GM and global regions was positively correlated with that in WMH region. However, after correction tests, only CBF in the WMH region but not in NAWM, GM and global regions was associated with WMH volume. Our findings suggest that CBF in the WMH region is an influencing factor of the WMH severity in CADASIL. [ABSTRACT FROM AUTHOR]

A core proposition in economics is that voluntary exchanges benefit both parties. We show that people often deny the mutually beneficial nature of exchange, instead espousing the belief that one or both parties fail to benefit from the exchange. Across four studies (and 8 further studies in the online supplementary materials), participants read about simple exchanges of goods and services, judging whether each party to the transaction was better off or worse off afterward. These studies revealed that win-win denial is pervasive, with buyers consistently seen as less likely to benefit from transactions than sellers. Several potential psychological mechanisms underlying win-win denial are considered, with the most important influences being mercantilist theories of value (confusing wealth for money) and theory of mind limits (failing to observe that people do not arbitrarily enter exchanges). We argue that these results have widespread implications for politics and society. [ABSTRACT FROM AUTHOR]

Modulators of the sphingosine-1-phosphate receptor (S1PR) have been proposed as a promising strategy for treating stroke. However, the detailed mechanisms and the potential translational value of S1PR modulators for intracerebral hemorrhage (ICH) therapy warrant exploration. Using collagenase VII-S-induced ICH in the left striatum of mice, we investigated the effects of siponimod on cellular and molecular immunoinflammatory responses in the hemorrhagic brain in the presence or absence of anti-CD3 monoclonal antibodies (Abs). We also assessed the severity of short- and long-term brain injury and evaluated the efficacy of siponimod in long-term neurologic function. Siponimod treatment significantly decreased brain lesion volume and brain water content on day 3 and the volume of the residual lesion and brain atrophy on day 28. It also inhibited neuronal degeneration on day 3 and improved long-term neurologic function. These protective effects may be associated with a reduction in the expression of lymphotactin (XCL1) and T-helper 1 (Th1)-type cytokines (interleukin 1β and interferon-γ). It may also be associated with inhibition of neutrophil and lymphocyte infiltration and alleviation of T lymphocyte activation in perihematomal tissues on day 3. However, siponimod did not affect the infiltration of natural killer cells (NK) or the activation of CD3-negative immunocytes in perihematomal tissues. Furthermore, it did not influence the activation or proliferation of microglia or astrocytes around the hematoma on day 3. Siponimod appears to have a profound impact on infiltration and activation of T lymphocytes after ICH. The effects of neutralized anti-CD3 Abs-induced T-lymphocyte tolerance on siponimod immunomodulation further confirmed that siponimod alleviated the cellular and molecular Th1 response in the hemorrhagic brain. This study provides preclinical evidence that encourages future investigation of immunomodulators, including siponimod, which target the lymphocyte-related immunoinflammatory reaction in ICH therapy. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (CSVD) is a leading cause of stroke and dementia. As the most common type of inherited CSVD, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by the NOTCH3 gene mutation which leads to Notch3 ectodomain deposition and extracellular matrix aggregation around the small vessels. It further causes smooth muscle cell degeneration and small vessel arteriopathy in the central nervous system. Compromised cerebral blood flow occurs in the early stage of CADASIL and is associated with white matter hyperintensity, the typical neuroimaging pathology of CADASIL. This suggests that cerebral hypoperfusion may play an important role in the pathogenesis of CADASIL. However, the mechanistic linkage between NOTCH3 mutation and cerebral hypoperfusion remains unknown. Therefore, in this mini-review, it examines the cellular and molecular mechanisms contributing to cerebral hypoperfusion in CADASIL. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of lysosomal and ubiquitin-proteasome system dysfunction on the abnormal aggregation of α-synuclein, and to analyze its role in the pathogenesis of Parkinson's disease (PD). PC12 cells subjected to nerve growth factor-induced differentiation were used as the cell model to study the dopaminergic neurons, and the lysosomal and proteasomal inhibitors trans-epoxysuccinyl-L-leucylamido-(4-guanidino) butane (E64) and, respectively, were used exclusively and in combination to treat the PC12 cells. The viability and metabolic state of the cells was assessed using the MTT assay; flow cytometry was used to measure the rate of cell apoptosis; and the double immunofluorescence method was applied to observe the formation of thioflavin S- and α-synuclein protein-positive aggregates and inclusion bodies in the PC12 cells. In addition, the Hoechst 33258 staining method was used to observe the apoptosis of the α-synuclein protein and thioflavin-S double-labeled cells. Following the administration of the lysosomal and proteasomal pathway inhibitors, the cell viability decreased in a concentration-dependent manner and the cell apoptosis rate increased. The proportion of PC12 cells with α-synuclein protein-positive aggregates and inclusion bodies in the E64 group was 7.94%, compared with 20.33 and 36.77% in the lactacystin and combination treatment groups, respectively. Statistical analysis indicated that the number of inclusion body-positive cells in the treatment groups was significantly higher than that in the control group (3.78%) (P<0.05). Apoptosis was evident in the double-positive cells with α-synuclein protein-positive inclusion bodies (17.29±1.54%). In conclusion, lysosomal and proteasomal dysfunction may play an important role in the pathogenesis of PD through the induction of abnormal α-synuclein protein aggregation in dopaminergic neurons. [ABSTRACT FROM AUTHOR]

Objective: Rare co-existance of disease or pathology Background: Cortical subarachnoid hemorrhage (cSAH) is a rare clinical presentation with different causes, but rarely happens along with acute ischemic stroke. Intracranial high-grade stenosis originated from brain has been regarded as an unusual cause of cSAH, especially in young adults. Case Report: A case of 33-year-old male presented with mild headache and spontaneous left-sided body weakness. Initial brain computed tomography (CT) showed cSAH in the right superior frontal sulcus. Further neuroimaging examinations including magnetic resonance imaging (MRI), digital subtraction angiography (DSA), transesophageal echocardiogram (TEE); in addition, lumbar puncture and blood tests were performed. Diffusion-weighted imaging (DWI) showed an acute infarction in the right frontal lobe and corona radiata of the territory of middle cerebral artery (MCA). The MR angiography (MRA) displayed no flow signal in the right middle cerebral artery M1-segment, while the DSA displayed bloodstream slowness in the right MCA M1-segment which suggested high-grade stenosis of the right MCA. The abnormal laboratory data suggested hyperhomocysteinemia, and excluded causes of thrombosis, infection, or cancer. The mechanism of cSAH may come about in severe atherosclerotic stenosis of MCAs by the broken of expanded tenuous compensatory pial vessels. The patient had good recovered at follow-up. Conclusions: This case demonstrates cSAH with acute ischemic stroke, which is an uncommon complication, in a young adult stroke patient; a high-grade atherosclerotic stenosis of the MCA was identified as the etiology. [ABSTRACT FROM AUTHOR]

Automated cell classification is an important yet a challenging computer vision task with significant benefits to biomedicine. In recent years, there have been several studies attempted to build an artificial intelligence-based cell classifier using label-free cellular images obtained from an optical microscope. Although these studies showed promising results, such classifiers were not able to reflect the biological diversity of different types of cell. While in terms of malignant cell, it is well-known that intracellular actin filaments are altered substantially. This is thought to be closely related to the abnormal growth features of tumor cells, their ability to invade surrounding tissues and also to metastasize. Therefore, being able to classify different types of cell based on their biological behaviors using automated technique is more advantageous. This article reveals the difference in the actin cytoskeleton structures between breast normal and cancer cells, which may provide new information regarding malignant changes and be used as additional diagnostic marker. Since the features cannot be well detected by human eyes, we proposed the application of convolutional neural network (CNN) in cell classification based on actin-labeled fluorescence microscopy images. The CNN was evaluated on a large number of actin-labeled fluorescence microscopy images of one human normal breast epithelial cell line and two types of human breast cancer cell line with different levels of aggressiveness. The study revealed that the CNN performed better in the cell classification task compared to a human expert. [ABSTRACT FROM AUTHOR]

The location and length of the susceptibility vessel sign (SVS) predicts poor outcome for patients having received reperfusion therapy. The aim of the present study was to assess the predictive value of SVS regarding the clinical outcome for patients untreated with thrombolysis. A retrospective study on acute stroke patients who underwent multimodal magnetic resonance imaging within 3 days from the onset of symptoms was performed. None of the patients had received thrombolysis therapy. The presence, location and length of the SVS were assessed. Uni- and multivariate analyses were used to examine the association between SVS and clinical outcome. A total of 43 SVS+ and 73 SVS- patients were included in the study. A modified Rankin Scale (mRS) of =2 at 3 months was determined in 41.9% of patients in the SVS+ group and 79.4% in the SVS- group (P<0.001). Multivariate analysis revealed that the presence of SVS was an independent parameter to predict mRS >2 at 3 months (odds ratio, 3.390; 95% confidence interval, 1.122-10.240; P=0.030). For patients with SVS+ status, the location and length of the SVS were not independent predictors of the clinical outcome. In conclusion, the presence of SVS may predict poor clinical outcome for acute stroke patients untreated with thrombolysis. [ABSTRACT FROM AUTHOR]

Background: In the present study, a novel mutation in exon 46 at codon 2304 (G2304R) of the SYNE1 gene is described in a Chinese family (proband, mother, and sister) with Emery-Dreifuss muscular dystrophy-like, which clinically manifests as muscle weakness, muscle atrophy, joint contracture, and without significant cardiac abnormalities. Methods: Clinical examination and neuroimaging of the captured target region and high-throughput sequencing were performed in a family of four generations. Muscle changes were evaluated using magnetic resonance imaging and muscle biopsies. Results: Target region capture sequencing yielded a novel missense mutation in codon 2304 (G2304R), which is a heterozygous A to G point mutation at position 6910 (c.6910A > G) in exon 46 of SYNE1 leading to a glycine-to-arginine substitution (p.Gly2304Arg). The results were also identified by Sanger sequencing in three family members but not in the other three unaffected family members and 100 control subjects. Conclusions: This mutation is probably pathogenic and is the first of its kind reported in a familial Emery-Dreifuss muscular dystrophy-like. [ABSTRACT FROM AUTHOR]

The autoimmune encephalitis can develop with or without an underlying tumor. For tumor-negative autoimmune encephalitis, the causes are still largely unknown. Here we presented three patients with autoimmune encephalitis accompanied with vitiligo. Among them, two patients suffered from anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis and one patient suffered from anti-IgLON5 encephalopathy. All of them received intravenous immunoglobulin and steroids as immunotherapy. The two patients with anti-LGI1 encephalitis recovered and got a good prognosis. For the patient with anti-IgLON5 encephalopathy, he only got a moderate and transient improvement. Based on the above, we speculate that vitiligo may be a clue to an autoimmune cause for encephalitis. [ABSTRACT FROM AUTHOR]