Discovery of novel hybrid tryptamine-rivastigmine molecules as potent AChE and BChE inhibitors exhibiting multifunctional properties for the management of Alzheimer's disease.

Contemporary research evidence has corroborated a gradual loss of central cholinergic neurons in Alzheimer's Disease (AD). This progressive deterioration leads to cognitive dysfunction and impaired motor activity, culminating in the brain cell's death in the disease. The approved drugs for AD treatment can only offer relief from symptoms without addressing the underlying pathological hallmarks of the disease.

Predictive Modeling and Drug Repurposing for Type-II Diabetes.

Diabetes mellitus (DM) is a global health concern, and dipeptidyl peptidase-4 (DPP-4) is a key therapeutic target. The study used three machine learning and deep learning models to predict potential DPP-4 inhibitors using a curated data set of 6,750 compounds. The models included support vector machine (SVM), random forest (RF), naive Bayes (NB), and multitask deep neural network (MTDNN).

Unlocking translational machinery for antitubercular drug development.

Targeting translational factor proteins (TFPs) presents significant promise for the development of innovative antitubercular drugs. Previous insights from antibiotic binding mechanisms and recently solved 3D crystal structures of Mycobacterium tuberculosis (Mtb) elongation factor thermo unstable-GDP (EF-Tu-GDP), elongation factor thermo stable-EF-Tu (EF-Ts-EF-Tu), and elongation factor G-GDP (EF-G-GDP) have opened up new avenues for the design and development of potent antituberculosis (anti-TB) therapies.

An update on ATP synthase inhibitors: A unique target for drug development in M. tuberculosis.

ATP synthase is a key protein in the oxidative phosphorylation process, as it aids in the effective production of ATP (Adenosine triphosphate) in all life's of kingdoms. ATP synthases have distinctive properties that contribute to efficient ATP synthesis. The ATP synthase of mycobacterium is of special relevance since it has been identified as a target for potential anti-TB molecules, especially Bedaquiline (BDQ).

Targeting the cytochrome bc complex for drug development in M. tuberculosis: review.

The terminal oxidases of the oxidative phosphorylation pathway play a significant role in the survival and growth of M. tuberculosis, targeting these components lead to inhibition of M. tuberculosis.

Machine learning-enabled predictive modeling to precisely identify the antimicrobial peptides.

The ubiquitous antimicrobial peptides (AMPs), with a broad range of antimicrobial activities, represent a great promise for combating the multi-drug resistant infections. In this study, using a large and diverse set of AMPs (2638) and non-AMPs (3700), we have explored a variety of machine learning classifiers to build in silico models for AMP prediction, including Random Forest (RF), k-Nearest Neighbors (k-NN), Support Vector Machine (SVM), Decision Tree (DT), Naive Bayes (NB), Quadratic Discriminant Analysis (QDA), and ensemble learning. Among the various models generated, the RF classifier-based model top-performed in both the internal [Accuracy: 91.

Qualitative assessment of compost engendered from municipal solid waste and green waste by indexing method.

The present study aims at quantification of the quality of three varieties of composts made from municipal solid waste, green waste and combined waste by critically evaluating their physicochemical attributes, effect on soil fertility and metal pollution risk. Each waste type was treated with effective micro-organisms to compare the compost quality using Quality Control Indices. The effect of microbial consortia on the wastes was prominent resulting in decreased pH levels and increased electrical conductivity.

Management zone delineation and spatial distribution of micronutrients in cold-arid region of India.

The plant health is governed by many factors: soil playing a central role which exhibits huge variability in its characteristics. Micronutrients even though needed in small quantities by plants play an indispensable role in affecting the crop growth and development. The assessment of spatial variability of different soil parameters is incumbent for tackling the loss of crop productivity on account of non-receipt of desirable inputs.

Development and validation of consensus machine learning-based models for the prediction of novel small molecules as potential anti-tubercular agents.

Tuberculosis (TB) is an infectious disease and the leading cause of death globally. The rapidly emerging cases of drug resistance among pathogenic mycobacteria have been a global threat urging the need of new drug discovery and development. However, considering the fact that the new drug discovery and development is commonly lengthy and costly processes, strategic use of the cutting-edge machine learning (ML) algorithms may be very supportive in reducing both the cost and time involved.

Effect of environmental toxicants on neuronal functions.

In the last few years, neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD) have attracted attention due to their high prevalence worldwide. Environmental factors may be one of the biggest reasons for these diseases related to neuronal dysfunctions. Most of neuronal disorders are strongly associated with pre- and postnatal exposure to environmental toxins released from industries.

Denouement of Chemicals on Amyotrophic Lateral Sclerosis: Is Green Chemistry the Answer.

Medicinal Chemistry has played a critical role in evolving new products, resources and processes which inexorably correspond to our high standards of living. Unfortunately, this has also caused deterioration of human health and threats to the global environment, even deaths when highly exposed to certain chemicals, whether due to improper use, mishandling or disposal. There are chemicals, which apart from being carcinogens, endocrine disruptors or neurotoxins, are also responsible for climate change and ozone depletion.

In vitro bactericidal activity of 3-cinnamoyl-4-hydroxy-6-methyl-2-pyrone (CHP) against drug-susceptible, drug-resistant and drug-tolerant isolates of Mycobacterium tuberculosis.

Objectives: Tuberculosis (TB) poses a serious global threat to humans. New bactericidal agents that can shorten treatment duration and target drug resistance still remain a top priority in the discovery of anti-TB drugs. The objective of this study was to investigate the bactericidal potential of 3-cinnamoyl-4-hydroxy-6-methyl-2-pyrone (CHP) against drug-susceptible, drug-resistant clinical isolates and drug-tolerant Mycobacterium tuberculosis.

Emerging opportunities of exploiting mycobacterial electron transport chain pathway for drug-resistant tuberculosis drug discovery.

: Tuberculosis (TB) is a leading infectious disease worldwide whose chemotherapy is challenged by the continued rise of drug resistance. This epidemic urges the need to discover anti-TB drugs with novel modes of action.: The mycobacterial electron transport chain (ETC) pathway represents a hub of anti-TB drug targets.

Early onset cerebral amyloid angiopathy following childhood exposure to cadaveric dura.

Amyloid-β transmission has been described in patients both with and without iatrogenic Creutzfeldt-Jakob disease; however, there is little information regarding the clinical impact of this acquired amyloid-β pathology during life. Here, for the first time, we describe in detail the clinical and neuroimaging findings in 3 patients with early onset symptomatic amyloid-β cerebral amyloid angiopathy following childhood exposure to cadaveric dura (by neurosurgical grafting in 2 patients and tumor embolization in a third). Our observations provide further in vivo evidence that cerebral amyloid angiopathy might be caused by transmission of amyloid-β seeds (prions) present in cadaveric dura and have diagnostic relevance for younger patients presenting with suspected cerebral amyloid angiopathy.

Support and Assessment for Fall Emergency Referrals (SAFER) 2: a cluster randomised trial and systematic review of clinical effectiveness and cost-effectiveness of new protocols for emergency ambulance paramedics to assess older people following a fall with referral to community-based care when appropriate.

Background: Emergency calls are frequently made to ambulance services for older people who have fallen, but ambulance crews often leave patients at the scene without any ongoing care. We evaluated a new clinical protocol which allowed paramedics to assess older people who had fallen and, if appropriate, refer them to community-based falls services.

Objectives: To compare outcomes, processes and costs of care between intervention and control groups; and to understand factors which facilitate or hinder use.

Paramedic Assessment of Older Adults After Falls, Including Community Care Referral Pathway: Cluster Randomized Trial.

Study Objective: We aim to determine clinical and cost-effectiveness of a paramedic protocol for the care of older people who fall.

Methods: We undertook a cluster randomized trial in 3 UK ambulance services between March 2011 and June 2012. We included patients aged 65 years or older after an emergency call for a fall, attended by paramedics based at trial stations.

Intravenous Thrombolysis in Unknown-Onset Stroke: Results From the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry.

Background And Purpose: Stroke patients with unknown onset (UKO) are excluded from thrombolytic therapy. We aim to study the safety and efficacy of intravenous alteplase in ischemic stroke patients with UKO of symptoms compared with those treated within 4.5 hours in a large cohort.

Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study.

Background: There is a link between high on-treatment platelet reactivity (HPR) and adverse vascular events in stroke. This study aimed to compare multiple electrode platelet aggregometry (MEA), in healthy subjects and ischaemic stroke patients, and between patients naive to antiplatelet drugs (AP) and those on regular low dose AP. We also aimed to determine prevalence of HPR at baseline and at 3-5 days after loading doses of aspirin.

Use of Dexmedetomidine and Esmolol for Hypotension in Lumbar Spine Surgery.

Background: The importance of decreasing bleeding in spine surgery is not only important to maintain the patient's hemodynamic balance but also allow a better view of the surgical field.

Objectives: The current study aimed to compare dexmedetomidine and Esmolol™ as agents to induce hypotension in lumbar spine surgeries.

Patients And Methods: A total of 50 patients aged 20 to 65 years belonging to the American society of anaesthesiologist (ASA) class I - II scheduled for decompression and fixation of the lumbar spine were included and divided into two groups namely, Group I, who received Esmolol and group II, who received dexmedetomidine, intravenously.

Association of ACE Gene I/D polymorphism with migraine in Kashmiri population.

Introduction: Migraine is a complex, recurrent headache disorder that is one of the most common complaints in neurology practice. The role of various genes in its pathogenesis is being studied. We did this study to see whether an association exists between ACE gene I/D polymorphism and migraine in our region.

Complete ophthalmoplegia: A rare presentation of idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH) is a disorder defined by clinical criteria that include signs and symptoms isolated to those produced by increased intracranial pressure (ICP; e. g., headache, papilledema, and vision loss), elevated ICP with normal cerebrospinal fluid (CSF) composition, and no other cause of intracranial hypertension evident on neuroimaging or other evaluations.

Clinical relevance of genetic polymorphism in CYP2C9 gene to pharmacodynamics and pharmacokinetics of phenytoin in epileptic patients: validatory pharmacogenomic approach to pharmacovigilance.

Aims And Objectives: Variations in drug metabolizing genes are known to have a clinical impact on AED therapy. We genotyped normal and epileptic patient cohorts of monoethnic population of Kashmir valley for CYP2C9 gene and allelic polymorphism and investigated the effect of CYP2C9*2 and *3 polymorphism on the Pharmacokinetic and therapeutic and/or adverse pharmacodynamic responses to Phenytoin in the idiopathic epilepsy patients.

Methods: PCR-RFLP methods were used for genotyping of 121 normal controls and 92 idiopathic epilepsy patients for CYP2C9*2 and *3 polymorphism, the results were validated by direct sequencing.

The changes in clot microstructure in patients with ischaemic stroke and the effects of therapeutic intervention: a prospective observational study.

Background: Stroke is the second largest cause of death worldwide. Hypercoagulability is a key feature in ischaemic stroke due to the development of an abnormally dense clot structure but techniques assessing the mechanics and quality of clot microstructure have limited clinical use. We have previously validated a new haemorheological technique using three parameters to reflect clot microstructure (Fractal Dimension (d f )) ex-vivo, real-time clot formation time (T GP ) and blood clot strength (elasticity at the gel point (G'GP)).

Prospective evaluation of blood coagulability and effect of treatment in patients with stroke using rotational thromboelastometry.

Background: Stroke is the second largest cause of death worldwide. Abnormalities in hemostasis play an important role in the pathophysiology of ischemic stroke (IS). These hemostatic defects can be detected using rotational thromboelastometry (ROTEM) as a global method of measuring coagulation.