Effect of Cannabis on Memory Consolidation, Learning and Retrieval and Its Current Legal Status in India: A Review.

Cannabis is one of the oldest crops grown, traditionally held religious attachments in various cultures for its medicinal use much before its introduction to Western medicine. Multiple preclinical and clinical investigations have explored the beneficial effects of cannabis in various neurocognitive and neurodegenerative diseases affecting the cognitive domains. Tetrahydrocannabinol (THC), the major psychoactive component, is responsible for cognition-related deficits, while cannabidiol (CBD), a non-psychoactive phytocannabinoid, has been shown to elicit neuroprotective activity. In the present integrative review, the authors focus on the effects of cannabis on the different cognitive domains, including learning, consolidation, and retrieval. The present study is the first attempt in which significant focus has been imparted on all three aspects of cognition, thus linking to its usage. Furthermore, the investigators have also depicted the current legal position of cannabis in India and the requirement for reforms.

Role of Endogenous Lipopolysaccharides in Neurological Disorders.

Lipopolysaccharide (LPS) is a cell-wall immunostimulatory endotoxin component of Gram-negative bacteria. A growing body of evidence reveals that alterations in the bacterial composition of the intestinal microbiota (gut dysbiosis) disrupt host immune homeostasis and the intestinal barrier function. Microbial dysbiosis leads to a proinflammatory milieu and systemic endotoxemia, which contribute to the development of neurodegenerative diseases and metabolic disorders. Two important pathophysiological hallmarks of neurodegenerative diseases (NDDs) are oxidative/nitrative stress and inflammation, which can be initiated by elevated intestinal permeability, with increased abundance of pathobionts. These changes lead to excessive release of LPS and other bacterial products into blood, which in turn induce chronic systemic inflammation, which damages the blood-brain barrier (BBB). An impaired BBB allows the translocation of potentially harmful bacterial products, including LPS, and activated neutrophils/leucocytes into the brain, which results in neuroinflammation and apoptosis. Chronic neuroinflammation causes neuronal damage and synaptic loss, leading to memory impairment. LPS-induced inflammation causes inappropriate activation of microglia, astrocytes, and dendritic cells. Consequently, these alterations negatively affect mitochondrial function and lead to increases in oxidative/nitrative stress and neuronal senescence. These cellular changes in the brain give rise to specific clinical symptoms, such as impairment of locomotor function, muscle weakness, paralysis, learning deficits, and dementia. This review summarizes the contributing role of LPS in the development of neuroinflammation and neuronal cell death in various neurodegenerative diseases.

The Role of a Gut Microbial-Derived Metabolite, Trimethylamine N-Oxide (TMAO), in Neurological Disorders.

Trimethylamine lyases are expressed in a wide range of intestinal microbiota which metabolize dietary nutrients like choline, betaine, and L-carnitine to form trimethylamine (TMA). Trimethylamine N-oxide (TMAO) is an oxidative product of trimethylamine (TMA) catalyzed by the action of flavin monooxygenases (FMO) in the liver. Higher levels of TMAO in the plasma and cerebrospinal fluid (CSF) have been shown to contribute to the development of risk factors and actively promote the pathogenesis of metabolic, cardiovascular, and cerebrovascular diseases. The investigations on the harmful effects of TMAO in the development and progression of neurodegenerative and sleep disorders are summarized in this manuscript. Clinical investigations on the role of TMAO in predicting risk factors and prognostic factors in patients with neurological disorders are also summarized. It is observed that the mechanisms underlying TMAO-mediated pathogenesis include activation of inflammatory signaling pathways such as nuclear factor kappa B (NF-κß), NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, and MAPK/JNK in the periphery and brain. Data suggests that TMAO levels increase with age-related cognitive dysfunction and also induce mitochondrial dysfunction, oxidative stress, neuronal senescence, and synaptic damage in the brain. Further research into the relationships between dietary food consumption and gut microbiota-dependent TMAO levels could provide novel therapeutic options for neurological illnesses.

Mechanistic Insights into the Link between Gut Dysbiosis and Major Depression: An Extensive Review.

Depression is a highly common mental disorder, which is often multifactorial with sex, genetic, environmental, and/or psychological causes. Recent advancements in biomedical research have demonstrated a clear correlation between gut dysbiosis (GD) or gut microbial dysbiosis and the development of anxiety or depressive behaviors. The gut microbiome communicates with the brain through the neural, immune, and metabolic pathways, either directly (via vagal nerves) or indirectly (via gut- and microbial-derived metabolites as well as gut hormones and endocrine peptides, including peptide YY, pancreatic polypeptide, neuropeptide Y, cholecystokinin, corticotropin-releasing factor, glucagon-like peptide, oxytocin, and ghrelin). Maintaining healthy gut microbiota (GM) is now being recognized as important for brain health through the use of probiotics, prebiotics, synbiotics, fecal microbial transplantation (FMT), etc. A few approaches exert antidepressant effects via restoring GM and hypothalamus-pituitary-adrenal (HPA) axis functions. In this review, we have summarized the etiopathogenic link between gut dysbiosis and depression with preclinical and clinical evidence. In addition, we have collated information on the recent therapies and supplements, such as probiotics, prebiotics, short-chain fatty acids, and vitamin B12, omega-3 fatty acids, etc., which target the gut-brain axis (GBA) for the effective management of depressive behavior and anxiety.

Cardiovascular Risk Factors and Outcomes in COVID-19: Hospital-Based Prospective Study in India

Background & ObjectivesPresence of cardiovascular (CV) risk factors enhance adverse outcomes in COVID-19. To determine association of risk factors with clinical outcomes in India we performed a study. MethodsSuccessive virologically confirmed patients of COVID-19 at a government hospital were recruited at admission and in-hospital outcome and other details obtained. The cohort was classified according to age, sex, hypertension, diabetes and tobacco use. To compare intergroup outcomes we performed univariate and multivariate logistic regression. ResultsFrom March-September 2020 we recruited 4645 (men 3386, women 1259) out of 5103 COVID-19 patients (91.0%). Mean age was 46{+/-}18y, hypertension was in 17.8%, diabetes in 16.6% and tobacco-use in 29.5%. Duration of hospital stay was 6.8{+/-}3.7 days, supplemental oxygen was in 18.4%, non-invasive ventilation in 7.1%, mechanical ventilation in 3.6% and 7.3% died. Unadjusted and age-sex adjusted odds ratio and 95% confidence intervals, respectively were, age [≥]50y (4.16, 3.22-5.37 and 4.15,3.21-5.35), men (1.88,1.41-2.51 and 1.26,0.91-1.48); hypertension (2.22,1.74-2.83 and 1.32,1.02-1.70), diabetes (1.88,1.46-2.43 and 1.16,0.89-1.52) and tobacco (1.29,1.02-1.63 and 1.28,1.00-1.63). Need for invasive ventilation was greater in age >50y (3.06,2.18-4.28 and 3.06,2.18-4.29) and diabetes (1.64,1.14-2.35 and 1.12,0.77-1.62). Non-invasive ventilation was more in age [≥]50y (2.27,1.80-2.86 and 2.26,1.79-2.85) and hypertension (1.82,1.41-2.35 and 1.29,0.99-1.69). Multivariate adjustment for presenting factors attenuated the significance. ConclusionCardiovascular risk factors-age, male sex, hypertension, diabetes and tobacco-are associated with greater risk of death and adverse outcomes in COVID-19 patients in India.

Changing Smiles Through Multidisciplinary Approach with Predictable Aesthetics: A Case Report.

This clinical report describes a multidisciplinary approach for the rehabilitation of a young patient with mobile and missing front teeth. The objectives of the treatment were to eliminate tooth mobility and replacing missing tooth, while enhancing aesthetics and restoring masticatory function. Treatment included placement of endodontic stabilizer and rehabilitating missing tooth with fixed partial denture and gingival porcelain to satisfy the patient's aesthetic and functional expectations.