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Curcumin and inflammatory bowel diseases: From in vitro studies to clinical trials
Inflammatory bowel diseases (IBDs) may result from mutations in genes encoding for innate immunity, which can lead to exacerbated inflammatory response. Although some mono-targeted treatments have developed in recent years, IBDs are caused through several pathway perturbations. Therefore, targeting all these pathways is difficult to be achieved by a single agent. Moreover, those mono-targeted therapies are usually expensive and may cause side-effects. These limitations highlight the significance of an available, inexpensive and multi-targeted dietary agents or natural compounds for the treatment and prevention of IBDs. Curcumin is a multifunctional phenolic compound that is known for its anti-inflammatory and immunomodulatory properties. Over the past decades, mounting experimental investigations have revealed the therapeutic potential of curcumin against a broad spectrum of inflammatory diseases including IBDs. Furthermore, it has been reported that curcumin directly interacts with many signaling mediators implicated in the pathogenesis of IBDs. These preclinical findings have created a solid basis for the assessment of the efficacy of curcumin in clinical practice. In clinical trials, different dosages e.g., 550 mg /three times daily-1month, and 1 g /twice times daily-6month of curcumin were used for patients with IBDs. Taken together, these findings indicated that curcumin could be employed as a therapeutic candidate in the treatment of IBDs. Moreover, it seems that overcome to current limitations of curcumin i.e., poor oral bioavailability, and poor oral absorption with using nanotechnology and others, could improve the efficacy of curcumin both in pre-clinical and clinical studies. © 2020 Elsevier Lt
COVID-19, de novo seizures, and epilepsy: a systematic review
Objective: We discuss the evidence on the occurrence of de novo seizures in patients with COVID-19, the consequences of this catastrophic disease in people with epilepsy (PWE), and the electroencephalographic (EEG) findings in patients with COVID-19. Methods: This systematic review was prepared according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. MEDLINE, Scopus, and Embase from inception to August 15, 2020 were systematically searched. These key words were used: �COVID� AND �seizure� OR �epilepsy� OR �EEG� OR �status epilepticus� OR �electroencephalography�. Results: We could identify 62 related manuscripts. Many studies were case reports or case series of patients with COVID-19 and seizures. PWE showed more psychological distress than healthy controls. Many cases with new-onset focal seizures, serial seizures, and status epilepticus have been reported in the literature. EEG studies have been significantly ignored and underused globally. Conclusion: Many PWE perceived significant disruption in the quality of care to them, and some people reported increase in their seizure frequency since the onset of the pandemic. Telemedicine is a helpful technology that may improve access to the needed care for PWE in these difficult times. De novo seizures may occur in people with COVID-19 and they may happen in a variety of forms. In addition to prolonged EEG monitoring, performing a through metabolic investigation, electrocardiogram, brain imaging, and a careful review of all medications are necessary steps. The susceptibility of PWE to contracting COVID-19 should be investigated further. © 2020, Fondazione Società Italiana di Neurologia
Donepezil attenuates injury following ischaemic stroke by stimulation of neurogenesis, angiogenesis, and inhibition of inflammation and apoptosis
Donepezil has proven to be an effective drug to reduce neuronal death and subsequently injury in neurodegenerative diseases. The current study evaluated the neuroprotective effects of donepezil in a rat model of ischaemic stroke and explored possible mechanisms which by this drug may reduce cell death. Temporary middle cerebral artery occlusion (tMCAO) was exerted for 45 min to induce ischaemic stroke. The animals were assigned into five groups: sham, control, and three groups treated with different doses of donepezil. Donepezil was intraperitoneally (IP) injected 4 h after reperfusion for 10 consecutive days. Infarct size was determined using TTC staining. The expression of proteins was evaluated using immunohistochemistry assays. Compared with the control group, infarct size was significantly reduced in tMCAO rats treated with different doses of donepezil. Moreover, our results showed significant decreased expression levels of apoptotic markers and pro-inflammatory mediators after treatment with different doses of donepezil for 10 days (P < 0.05). Likewise, significant increase of brain-derived neurotrophic factor (BDNF) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) proteins were found in tMCAO rats treated with donepezil compared with the control group (P < 0.05). Collectively, our findings show the validity of donepezil as a new therapeutic agent for attenuation of injury following ischaemic stroke through attenuation of inflammation and improvement of mitochondrial function, neurogenesis, and angiogenesis. © 2020, Springer Nature Switzerland AG
Identification of a novel missense c.386G > A variant in a boy with the POMGNT1-related muscular dystrophy-dystroglycanopathy
Muscular dystrophy-dystroglycanopathies are autosomal recessive neurologic disorders, caused by homozygous or compound heterozygous mutations in the POMGNT1 gene-encoding protein O-mannose beta-1,2-N-acetylglucosaminyl transferase. This type of muscular dystrophy is characterized by early-onset muscle weakness, gait ataxia, microcephaly, and developmental delay.We performed whole-exome sequencing to detect the disease-causing variants in a 4 year-old boy. Afterwards, Sanger sequencing was performed to confirm the detected variant in the patient and his family. We evaluated a 4 year-old Iranian boy presented with delayed speech and language development, gait ataxia, global developmental delay, motor delay, neurodevelopmental delay, postnatal microcephaly and strabismus. His parents were first cousins, and the mother had a history of spontaneous abortion. In this study, we report a novel missense c.386G > A; p.(Arg129Gln) variant in the POMGNT1 gene which was confirmed by Sanger sequencing in the patient and segregated with the disease in the family. © 2020, Belgian Neurological Society
Improving security using SVM-based anomaly detection: issues and challenges
Security is one of the main requirements of the current computer systems, and recently it gains much importance as the number and severity of malicious attacks increase dramatically. Anomaly detection is one of the main branches of the intrusion detection systems which enables to recognize the newer variants of the security attacks. This paper focuses on the anomaly detection schemes (ADS), which have applied support vector machine (SVM) for detecting intrusions and security attacks. For this purpose, it first presents the required concepts about the SVM classifier and intrusion detection systems. It then classifies the ADS approaches and discusses the various machine learning and artificial intelligence techniques that have been applied in combination with the SVM classifier to detect anomalies. Besides, it specifies the primary capabilities, possible limitations, or advantages of the ADS approaches. Furthermore, a comparison of the studied ADS schemes is provided to illuminate their various technical details. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature
Persistent Paraplegia After Sleeve Gastrectomy: a Case Report
Neurological complications secondary to weight loss surgery (WLS) are highly reported and include peripheral nerve injury, Wernicke�s encephalopathy, polyradiculoneuropathy, neuropathy, myelopathy, peripheral neuropathy, and myopathy. Neurological complications may result from mechanical or inflammatory mechanisms, but they result mainly from deficiencies in B vitamins, vitamin D, vitamin E, zinc, and copper occurring in WLS. Herein is reported the case of a 25-year-old woman with complaints of paraplegia after a sleeve gastrectomy probably due to nutritional deficiencies. This case illustrates the necessity for medical nutrition therapy (MNT) before and after bariatric surgery. © 2020, Association of Surgeons of India
Mapping routine measles vaccination in low- and middle-income countries
The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99 of both occurred in low- and middle-income countries (LMICs)1�4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5�8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 � 5-km2 pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80 coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children. © 2020, The Author(s)
Getting closer to our unpleasant previse: Possible rise in suicide rate in Iran during COVID-19 pandemic
A multi-center study of COVID-19 patient prognosis using deep learning-based CT image analysis and electronic health records
Purpose: As of August 30th, there were in total 25.1 million confirmed cases and 845 thousand deaths caused by coronavirus disease of 2019 (COVID-19) worldwide. With overwhelming demands on medical resources, patient stratification based on their risks is essential. In this multi-center study, we built prognosis models to predict severity outcomes, combining patients� electronic health records (EHR), which included vital signs and laboratory data, with deep learning- and CT-based severity prediction. Method: We first developed a CT segmentation network using datasets from multiple institutions worldwide. Two biomarkers were extracted from the CT images: total opacity ratio (TOR) and consolidation ratio (CR). After obtaining TOR and CR, further prognosis analysis was conducted on datasets from INSTITUTE-1, INSTITUTE-2 and INSTITUTE-3. For each data cohort, generalized linear model (GLM) was applied for prognosis prediction. Results: For the deep learning model, the correlation coefficient of the network prediction and manual segmentation was 0.755, 0.919, and 0.824 for the three cohorts, respectively. The AUC (95 CI) of the final prognosis models was 0.85(0.77,0.92), 0.93(0.87,0.98), and 0.86(0.75,0.94) for INSTITUTE-1, INSTITUTE-2 and INSTITUTE-3 cohorts, respectively. Either TOR or CR exist in all three final prognosis models. Age, white blood cell (WBC), and platelet (PLT) were chosen predictors in two cohorts. Oxygen saturation (SpO2) was a chosen predictor in one cohort. Conclusion: The developed deep learning method can segment lung infection regions. Prognosis results indicated that age, SpO2, CT biomarkers, PLT, and WBC were the most important prognostic predictors of COVID-19 in our prognosis model. © 202
17β-Estradiol Reduces Demyelination in Cuprizone-fed Mice by Promoting M2 Microglia Polarity and Regulating NLRP3 Inflammasome
Estrogen produces a beneficial role in animal models of multiple sclerosis (MS). The effect of 17β-estradiol therapy on microglia polarization and neuroinflammation in the corpus callosum of the cuprizone-induced demyelination model has not been elucidated. In this study, mice were given 0.2 cuprizone (CPZ) for 5 weeks to induce demyelination during which they received 50 ng of 17β-estradiol (EST), injected subcutaneously in the neck region, twice weekly. Data revealed that treatment with 17β-estradiol therapy (CPZ+EST) improved neurological behavioral deficits, displayed by a significant reduction in escape latencies, in comparison to untreated CPZ mice. Also, administration of 17β-estradiol caused a decrease in demyelination levels and axonal injury, as demonstrated by staining with Luxol fast blue, immunofluorescence to myelin basic protein, and transmission electron microscopy analysis. In addition, at the transcriptional level in the brain, mice treated with 17β-estradiol (CPZ+EST) showed a decrease in the levels of M1-assosicted microglia markers (CD86, iNOS and MHC-II) whereas M2-associated genes (Arg-1, CD206 and Trem-2) were increased, compared to CPZ mice. Moreover, administration of 17β-estradiol resulted in a significant reduction (�3-fold) in transcript levels of NLRP3 inflammasome and its downstream product IL-18, compared to controls. In summary, this study demonstrated for the first time that exogenous 17β-estradiol therapy robustly leads to the reduction of M1 phenotype, stimulation of polarized M2 microglia, and repression of NLRP3 inflammasome in the corpus callosum of CPZ demyelination model of MS. The positive effects of 17β-estradiol on microglia and inflammasome seems to facilitate and accelerate the remyelination process. © 2021 IBR