关键词： Alzheimer disease   Deep transfer learning   ImageNet   ADNI dataset  

摘要： Alzheimer's disease is becoming common in the world with the time. It is an irreversible and progressive brain disorder that slowly destroys the memory and thinking skills and, eventually, the ability to perform the simplest tasks. It becomes severe before the noticeable symptoms appear and causes brain disorder which cannot be cured by any medicines and therapies, however its progression can be slow down through early diagnosis. In this paper, we employed different CNN based transfer learning methods for Alzheimer disease classification. We have applied different parameters, and achieved remarkable accuracy on benchmark ADNI dataset. We have tested 13 differnt flavours of different pre-trained CNN models using a fine-tuned approach of transfer learning across two different domain on ADNI dataset (94 AD, 138 MCI and 146 NC). Comparatively, DenseNet showed better performance by achieving a maximal average accuracy of % 99.05. Significant improvement in accuracy has been observed as compared to previously reported works in terms of specificity, sensitivity and accuracy. The source code of propose framework is publicly available.

摘要： Inflammasomes are multimeric protein complexes that can sense a plethora of microbe- and damage-associated molecular signals. They play important roles in innate immunity and are key regulators of inflammation in health and disease. Inflammasome-mediated processing and secretion of proinflammatory cytokines such as interleukin (IL) 1 beta and IL-18 and induction of pyroptosis, a proinflammatory form of cell death, have been associated with the development and progression of common immune-mediated and degenerative central nervous system (CNS) diseases such as Alzheimer disease, multiple sclerosis, brain injury, stroke, epilepsy, Parkinson disease, and amyotrophic lateral sclerosis. A growing number of pharmacological compounds inhibiting inflammasome activation and signaling show therapeutic efficacy in preclinical models of the aforementioned disease conditions. Here, we illustrate regulatory mechanisms of inflammasome activation during CNS homeostasis and tissue injury. We highlight the evidence for inflammasome activation as a mechanistic underpinning in a wide range of CNS diseases and critically discuss the promise and potential limitations of therapeutic strategies that aim to inhibit the inflammasome components in neurological disorders. ANN NEUROL 2021

关键词： Neuritin   Intracerebral hemorrhage   PERK   ATF4   Akt   mTOR   sEPSCs  

摘要： Stroke is one of the leading causes of death worldwide, with intracerebral hemorrhage (ICH) being the most lethal subtype. Neuritin (Nrn) is a neurotropic factor that has been reported to have neuroprotective effects in acute brain and spinal cord injury. However, whether Nrn has a protective role in ICH has not been investigated. In this study, ICH was induced in C57BL/6 J mice by injection of collagenase VII, while the overexpression of Nrn in the striatum was induced by an adeno-associated virus serotype 9 (AAV9) vector. We found that compared with GFP-ICH mice, Nrn-ICH mice showed improved performance in the corner, cylinder and forelimb tests after ICH, and showed less weight loss and more rapid weight recovery. Overexpression of Nrn reduced brain lesions, edema, neuronal death and white matter and synaptic integrity dysfunction caused by ICH. Western blot results showed that phosphorylated PERK and ATF4 were significantly inhibited, while phosphorylation of Akt/ mammalian target of rapamycin was increased in the Nrn-ICH group, compared with the GFP-ICH group. Whole cell recording from motor neurons indicated that overexpression of Nrn reversed the decrease of spontaneous excitatory postsynaptic currents (sEPSCs) and action potential frequencies induced by ICH. These data show that Nrn improves neurological deficits in mice with ICH by reducing brain lesions and edema, inhibiting neuronal death, and possibly by increasing neuronal connections.

关键词： Attachment styles   Functional movement disorders   Functional neurological disorders   Identification of feelings   PNES   Psychogenic non-epileptic seizures  

摘要： Objective: The contribution of psychological and psychiatric symptoms in the development of Functional Neurological Disorders (FND) is unclear. We therefore aimed to investigate the role of different attachment styles (AS) and their relationship with psychiatric symptoms in FND patients as compared with both subjects with neurological disorders (ND) and healthy controls (HC);and the possible differences between patients with functional movement disorders (FMD) and with functional seizures. Methods: In this case-control study, forty-six patients with FND were compared to 34 with ND and 30 HC, by means of an extensive battery to investigate the presence of alexithymia, depression, anxiety, dissociation and to explore their AS using the Revised Experiences in Close Relationships instrument (ECR-R). Results: Patients with FND had higher depression and alexithymia as well as an avoidant pattern on the ECR-R than patients with ND. In the FND group, ECR-R avoidance was an independent predictor of psychiatric symptoms and, altogether, ECR-R avoidance, the somatic-affective component of depression and difficulty identifying feelings were independent predictors of FND. Gender, anxiety and difficulty identifying feelings predicted the presence of functional seizures. Conclusion: The avoidant AS may be an important psychological factor influencing the presence of mood disorders and alexithymia. Their co-occurence might drive maladaptive responses underlying the presence of FND. Although we demonstrated a large overlap between FND phenotypes, patients with functional seizures might have higher alexithymia, which in turn could explain a defensive response less anchored to body reactions and physical symptoms.

关键词： Neurological lower urinary tract dysfunction   Congenital Zika syndrome   Congenital Zika virus syndrome   Zika virus   Urinary tract infection   Microcephaly  

摘要： Introduction We have previously reported on neurogenic bladder dysfunction among Congenital Zika Virus Syndrome (CZS) patients, but it is unknown how they will respond to treatment. Objective To assess whether children with neurological lower urinary tract dysfunction and CZS will respond to Standard therapies. Methodology A prospective observational cohort study of children with CZS referred for urological assessment between 2016 and 2020 to our quaternary center in Brazil. Urological protocol included clinical history, urinalysis and culture, renal and bladder ultrasonography and urodynamic study. Patients were treated based on findings from the first evaluation, with oxybutynin chloride for overactive bladder and low bladder compliance, clean intermittent catheterization for ineffective bladder emptying, or dual therapy when both were observed. Urological outcomes were evaluated between the first and second visits considering patient's adherence. Outcomes measured included clinical, imaging, and urodynamic variables. Data was analyzed using the IBM SPSS 22 software. Results From the cohort of 90 patients, 56 completed the second urodynamic assessment and were included. One presented underactive bladder and 55 overactive bladder. Among these 55, 39 were adherent and 16 non-adherents to the prescribed treatment. Among the 39 adherents, 8 adhered regularly to oxybutynin and clean intermittent catheterization (CIC), 29 to oxybutynin alone, and two to catheterization alone. During follow-up, the number of patients with urinary tract infection and postvoid residual increased, but all other parameters had improved. Renal and bladder ultrasonography improved in 10, maximum bladder pressure decreased in 22 and maximum cystometric capacity and compliance increased in 14 patients. Sixteen patients did not adhere regularly to the prescribed treatment and although the number of patients with urinary tract infection reduced with antibiotic therapy, their bladder capacity and c

关键词： Piperazine   Chalcone   Monoamine oxidase   Acetylcholinesterase  

摘要： Eleven piperazine-containing 1,3-diphenylprop-2-en-1-one derivatives (PC1-PC11) were evaluated for their inhibitory activities against monoamine oxidases (MAOs), cholinesterases (ChEs), and beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1) with a view toward developing new treatments for neurological disorders. Compounds PC10 and PC11 remarkably inhibited MAO-B with IC50 values of 0.65 and 0.71 mu M, respectively. Ten of the eleven compounds weakly inhibited AChE and BChE with > 50% of residual activities at 10 mu M, although PC4 inhibited AChE by 56.6% (IC50 = 8.77 mu M). Compound PC3 effectively inhibited BACE-1 (IC50 = 6.72 mu M), and PC10 and PC11 moderately inhibited BACE-1 (IC50 =14.9 and 15.3 mu M, respectively). Reversibility and kinetic studies showed that PC10 and PC11 were reversible and competitive inhibitors of MAO-B with K-i values of 0.63 +/- 0.13 and 0.53 +/- 0.068 mu M, respectively. ADME predictions for lead compounds revealed that PC10 and PC11 have central nervous system (CNS) drug-likeness. Molecular docking simulations showed that fluorine atom and trifluoromethyl group on PC10 and PC11, respectively, interacted with the substrate cavity of the MAO-B active site. Our results suggested that PC10 and PC11 can be considered potential candidates for the treatment of neurological disorders such as Alzheimer's disease and Parkinson's disease.

关键词： Multiple sclerosis   Demyelination   Biologics   Tumor necrosis factor alpha inhibitors  

摘要： Previous studies have reported an association between anti-tumor necrosis factor alpha (anti-TNF alpha) treatment and central nervous system (CNS) events. We described eight patients presenting with demyelinating CNS events while on treatment with anti-TNF alpha for autoimmune diseases and followed up for a medium period of 4 years. Four patients presented with isolated demyelinating events, three patients fulfilled the criteria for multiple sclerosis (MS), and one patient showed worsening of pre-existing MS after anti-TNF therapy initiation. All patients except one, showed a good medium-term prognosis. Our observation supports an association between anti-TNF alpha treatment and demyelinating events and suggests that a prompt discontinuation of the drug may lead to a favorable demyelinating disease outcome.

关键词： HLA-E   HLA-F   Arbovirus   PSD   ESD   Pernambuco  

摘要： Introduction: Non-classical class I human leukocyte antigens (HLA) molecules are known to modulate the function of cytotoxic cells (NK and T CD8+) during viral infection by interacting with inhibitory/activating receptors. However, little is known about the HLA-E/-F genetic variability on arbovirus infections. Methods: We evaluated by massive parallel sequencing the full HLA-E/-F genetic diversity among patients infected during the arbovirus (ZIKV, DENV, and CHIKV) outbreak leading to a broad range of neurological complications in the Brazilian State of Pernambuco. In parallel, healthy blood donors from the same area were also studied. Plink and R software were used for genetic association study. To limit the false-positive results and enhance the reliability of the results, we adopted P-values < 0.01 as significant levels. Results: Compared to controls, the HLA-F alleles: -1610 C (rs17875375), +1383 G (rs17178385), and +3537 A (rs17875384), all in complete linkage disequilibrium with each other (r2 = 1), were overrepresented in patients presenting peripheral spectrum disorders (PSD). The HLA-F*Distal-D haplotype that harbored the -1610 C allele exhibited a trend increase in PSD group. No associations were found for HLA-E. Conclusions: Our findings showed that the HLA-F genetic background seems to be more important than HLA-E on the susceptibility to PSD complications.

摘要： [...]stroke is common in elderly people who are at high risk of malignant cancer. Since the lymphocytic immune response participates both in tumor progression and brain injuries produced by ischemia, there might be a noteworthy reciprocal interaction between stroke and cancer. [...]the ischemic brain could induce an immunosuppressive response that may promote cancer progression and trigger fetal infections which seriously affect the prognosis and survival of stroke patients. [...]we need more precise indicators to maintain the balance of the post-stroke immunity and predict the outcome of cancer-bearing stroke patients receiving immunotherapies. Recent evidence suggests that in cancer-bearing stroke mice, CD4+ Tregs could be recruited into the tumor, thus attenuate their protection of the blood-brain barrier after stroke. 10 Importantly, with the aging of the population, the number of cancer patients is continuously rising. [...]cancer-related immune response is emerging as a noteworthy clinical issue for stroke patients.