Evaluation of Anti-Epileptic activity of Ethanolic Extract of Leaves of Cassia Alata Linn. by Maximal Elecroshock (MES) and Isoniazid Induced Convulsions on Mice

Introduction:Epilepsy is a chronic non-communicable disorder of the brain that affects people of all ages. Approximately 50 million people worldwide have epilepsy, making it one of the most common neurological diseases globally. Nearly 80% of the people with epilepsy live in low and middle-income countries. People with epilepsy respond to treatment approximately 70% of the time. About three fourths of people with epilepsy living in low and middle income countries do not get the treatment they need. Epilepsy is the second common neurological disorder in India. In the 70% of the population with epilepsy there is high prevalence in children about 0.8% and it can affect 1 person in 200 of people. According to WHO people with epilepsy disorder in the growing countries, not getting proper treatment. SCOPE: WHO, there are over 50 million suffers in the world today of which 80% live in the developing countries. An estimated 3.2 million new cases occur each year globally, with atleast 55% of the cases begin in childhood. Epilepsy responds to treatment about 75% of the time, some cases show poor treatment due to inadequate medical supply and proper treatment. Epilepsy increases a person’s risk of premature death by about two to three times. It is the most common serious brain disorder worldwide with no boundaries. Management of epilepsy is a global problem and successful treatment is very essential for preventing or at least delaying the onset of long-term complications. Remedies to treat such different types of seizure are available in nature in the form of herbal medicines or drugs with very minimal adverse effects when compared to the available synthetic drugs. Such herbal drugs as therapeutic agents are a boon when compared to the severe adverse effects of the allopathic medical practice for epileptic seizure, though the quest for a complete and permanent cure for the disease is being pursued relentlessly by eluding physicians and researchers. Therefore herbal medicines have been used for the treatment of various disease because of their fewer adverse effects that conventional medicine. It is believed that the traditional medicines used for the treatment of epilepsy and also in progression of complications of the disease. Main objective of the proposed work is to evaluate the beneficial effects of Cassia alata Linn. for its anti-epileptic activity by using MES and INH model. PLAN OF WORK: 1. Collection and Authentification of Cassia alata Linn. 2. Preparation of ethanolic extract of Cassia alata Linn. (EECA) 3. Experimental Animals 4. Preliminary Phytochemical screening 5. Acute toxicity studies (OECD 423guidelines) 6. Effect of EECA on MES induced epilepsy 7. Effect of EECA on INH induced epilepsy 8. Effect of EECA on GABA level in animal 9. Histopathology 10. Statistical analysis by one way ANOVA followed by Dunnet’s test DISCUSSION: Epilepsy is an assortment of different types of seizures originating from several mechanisms that have in common the sudden excessive discharge of cerebral neurons. It may result in a. Loss of consciousness, b. Atypical or odd behaviour, c. distorted perceptions. Seizures can last from a few seconds to a few minutes100. Patients and health care professionals do not always recognize the signs or symptoms, which can include convulsions, a loss of consciousness, blank staring, lip smacking, or jerking movements of the arms and legs101. A seizure has a clear beginning, middle, and end. Epilepsy was one of the first brain disorders to be Described102. Epileptic seizures are manifested by an abnormal, excessive, and hyper synchronous electrical discharge of neurons in the brain103. Each distinct form of epilepsy has its own natural history and response to treatment101. This diversity probably reflects the many different underlying causes of epilepsy and the variety of epilepsy syndromes in which the clinical and pathological characteristics are distinctive and suggest a specific under lying etiologic mechanism104. The International League against Epilepsy (ILAE) published a modified version of the International Classification of Epileptic Seizures (ICES), which has continued to be a very useful system104. This system is based on the clinical features of seizures and associated EEG findings. The etiology or cellular substrate is not considered. There are three main types of seizures: partial, generalized, and unclassified. There are many kinds of seizures, each with characteristic behavioral changes and electrophysiological disturbances that can usually be detected in scalp electroencephalographic recordings103. A seizure is a transient epileptic event, indicating a disturbance in brain function101. Having a single seizure does not necessarily mean that a person has epilepsy103, 104. Ten percent of adul ts experience a seizure sometime during their lifetime105. Globally, an estimated 2.4 million people are diagnosed with epilepsy each year. In highincome countries, annual new cases are between 30 and 50 per 100000 people in the general population. In low and middle-income countries, this figure can be up to two times higher. In many parts of the world, people with epilepsy and their families suffer from stigma and discrimination. CONCLUSION: The leaves of Cassia alata Linn. showed reduction in the flexion, extensor, clonus and stuper duration in MES induced epilepsy model. So the drug can be used in grandmal epilepsy. In INH model latency of epilepsy and lethality of animal was reduced. So the drug can be used in TLE. The histopathology of hippocampal region of brain showed normal architecture and there is increased neuronal density which is comparable with phenytoin. GABA level is increased, so the drug probably acts as GABA mechanism either Inhibition of GABA transaminase enzyme or Inhibition of GABA transporter. Thus, it may be concluded that Cassia alata Linn. produces significant anti-epileptic activity in both MES and INH induced epilepsy in mice, which is comparable with that of phenytoin. Further work is necessary to elucidate the mechanism of action involved in the antiepileptic activity of Cassia alata Linn. with special reference to Phytochemical constituents

A Survey on Decentralized Access Control Strategies for Data Stored in Clouds

ABSTRACT: This paper details about various methods prevailing in literature of anonymous authentication mechanisms for data stored in clouds. It is a Decentralized access of system in which every system have the access control of data . The Cloud which is a Secured storage area where the anonymous authentication is used, so that only the permitted users can be accessed. Decrypting of data can be viewed only by a valid users and can also stored information only by Valid users. This Scheme prevents Replay attack which mean Eaves Dropping can be avoided, Support Creation of data inside storage, Modifying the data by unknown users , and Reading data stored in Cloud. User can revocate the data only by addressing through the cloud. The authentication and accessing the Cloud is Robust, Hence Overall Communication Storage are been developed by comparing to the Centralized approaches. This paper would promote a lot of research in the area of Anonymous Authentication

Enhanced cycling stability of LiNiO₂ cathodes through a Mg/W dual-cation modification strategy

LiNiO2 cathodes for lithium-ion batteries offer the prospect of high specific capacities; however, a plethora of structural and surface instabilities occur during cycling, which can limit their lifetime and impinge on their safety. Structural and surface modification strategies such as cation-doping have been shown to stabilise cycling performance and prolong cathode lifetimes, yet they often tackle either surface or bulk driven degradation processes. Here, we present a dual-cation substitution approach for the LiNiO2 cathode which produces a coat-doped cathode in a single step. Judicious selection of cation substituents enables the targeted stabilisation of both bulk- and surface-originating instabilities, in this case magnesium and tungsten, respectively. While the addition of tungsten as a sole substituent promotes a rock-salt surface layer which typically reduces the observable capacity, we demonstrate that the incorporation of Mg into W-containing compositions can mitigate these structural transformations. These coat-doped Mg/W-LiNiO2 cathodes exhibit superior cycling stabilities compared to unmodified LiNiO2 and singly-substituted Mg- or W-LiNiO2. X-ray diffraction computed tomography methods complement these findings, providing spatially resolved structural information on the location and heterogeneity of the coat-doped cathodes, guiding synthetic pathways to optimised materials that outperform undoped LiNiO2 even in high-mass loading cell environments

Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation. the GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007

Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry

Background and purpose: Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF). Methods: In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3 years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Results: The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0 years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79–2.03), major bleeding 0.59 (0.40–0.88), myocardial infarction 0.68 (0.40–1.16), and all-cause death 0.86 (0.67–1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76–1.78), myocardial infarction 0.84 (0.48–1.46), major bleeding 0.98 (0.63–1.52) and all-cause death 1.01 (0.79–1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52–1.19), myocardial infarction 0.96 (0.63–1.45), major bleeding 1.54 (1.14–2.08), and all-cause death 0.97 (0.80–1.19). Conclusions: Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death. Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013

Patterns of oral anticoagulant use and outcomes in Asian patients with atrial fibrillation: a post-hoc analysis from the GLORIA-AF Registry

Background: Previous studies suggested potential ethnic differences in the management and outcomes of atrial fibrillation (AF). We aim to analyse oral anticoagulant (OAC) prescription, discontinuation, and risk of adverse outcomes in Asian patients with AF, using data from a global prospective cohort study. Methods: From the GLORIA-AF Registry Phase II–III (November 2011–December 2014 for Phase II, and January 2014–December 2016 for Phase III), we analysed patients according to their self-reported ethnicity (Asian vs. non-Asian), as well as according to Asian subgroups (Chinese, Japanese, Korean and other Asian). Logistic regression was used to analyse OAC prescription, while the risk of OAC discontinuation and adverse outcomes were analysed through Cox-regression model. Our primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). The original studies were registered with ClinicalTrials.gov, NCT01468701, NCT01671007, and NCT01937377. Findings: 34,421 patients were included (70.0 ± 10.5 years, 45.1% females, 6900 (20.0%) Asian: 3829 (55.5%) Chinese, 814 (11.8%) Japanese, 1964 (28.5%) Korean and 293 (4.2%) other Asian). Most of the Asian patients were recruited in Asia (n = 6701, 97.1%), while non-Asian patients were mainly recruited in Europe (n = 15,449, 56.1%) and North America (n = 8378, 30.4%). Compared to non-Asian individuals, prescription of OAC and non-vitamin K antagonist oral anticoagulant (NOAC) was lower in Asian patients (Odds Ratio [OR] and 95% Confidence Intervals (CI): 0.23 [0.22–0.25] and 0.66 [0.61–0.71], respectively), but higher in the Japanese subgroup. Asian ethnicity was also associated with higher risk of OAC discontinuation (Hazard Ratio [HR] and [95% CI]: 1.79 [1.67–1.92]), and lower risk of the primary composite outcome (HR [95% CI]: 0.86 [0.76–0.96]). Among the exploratory secondary outcomes, Asian ethnicity was associated with higher risks of thromboembolism and intracranial haemorrhage, and lower risk of major bleeding. Interpretation: Our results showed that Asian patients with AF showed suboptimal thromboembolic risk management and a specific risk profile of adverse outcomes; these differences may also reflect differences in country-specific factors. Ensuring integrated and appropriate treatment of these patients is crucial to improve their prognosis. Funding: The GLORIA-AF Registry was funded by Boehringer Ingelheim GmbH

Assemblathon 2: evaluating de novo methods of genome assembly in three vertebrate species

Background: The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. Results: In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. Conclusions: Many current genome assemblers produced useful assemblies, containing a significant representation of their genes and overall genome structure. However, the high degree of variability between the entries suggests that there is still much room for improvement in the field of genome assembly and that approaches which work well in assembling the genome of one species may not necessarily work well for another

Comparative genomics reveals insights into avian genome evolution and adaptation

Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits