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In this review, we will discuss the mechanisms that are involved in the activation of the NLRP3 inflammasome and its crucial role in the pathology of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and multiple sclerosis. We will also review various treatments that target the NLRP3 inflammasome pathway and alleviate neuroinflammation. Finally, we will summarize the novel treatment strategies for neurodegenerative disorders.Dichlorvos is a known risk factor for organ toxicity. The liver and kidney are essential metabolic tissues but it is unclear whether or not there is associated redox dyshomeostasis in both organs in physiological and pathological states. Uric acid accumulation and glutathione dysregulation have been implicated in the aetiopathogenesis of organ damage. https://www.selleckchem.com/ The antioxidant potentials of L-arginine have been shown in various conditions. The present study was thus designed to investigate the synchrony in hepatic and renal uric acid and glutathione status in dichlorvos-induced hepatorenal damage and to probe the possible therapeutic role of L-arginine. Twenty-one male Wistar rats were treated with standard rat diet and water, dichlorvos, or dichlorvos and L-arginine. Our findings revealed that dichlorvos significantly impaired hepatic and renal functions, increased hepatic and renal malondialdehyde, but reduced glutathione and activities of superoxide dismutase, catalase, and glutathione peroxidase. These events were accompanied by increased accumulation of plasma, hepatic, and renal uric acid as well as reduced body weight gain, and hepatic and renal weights. Histopathological examinations revealed hepatic and renal architectural derangement and cellular necrosis and degeneration in dichlorvos-exposed rats. Interestingly, L-arginine reversed dichlorvos-induced systemic, hepatic and renal synchronous redox dyshomeostasis. L-arginine administration also improved hepatic and renal cytoarchitecture. It is thus concluded that dichlorvos triggered synchronous uric acid generation and glutathione alterations in the liver and kidney. L-arginine confers protection against dichlorvos-induced hepatorenal damage via suppression of uric acid generation and blockade of glutathione dysregulation.

Since the introduction of the National Medical Cannabis Programme in The Netherlands, many other countries in Europe have made medical cannabis (MC) and cannabis-based medicines (CBMs) available. However, each of them has implemented a unique legal framework and reimbursement strategy for these products. Therefore, it is vital to study healthcare professionals' knowledge level (HCP) and HCPs in-training regarding both medical uses and indications and understand their safety concerns and potential barriers for MC use in clinical practice.

A comprehensive, systematic literature review was performed using PubMed/MEDLINE, EMBASE, and Google Scholar databases, as well as PsychINFO. Grey literature was also included. Due to the high diversity in the questionnaires used in the studies, a narrative synthesis was performed.

From 6995 studies retrieved, ten studies, all of them being quantitative survey-based studies, were included in the review. In most studies, the majority of participants were in favor of MC and CBMs use for medical reasons. Other common findings were the necessity to provide additional training regarding medical applications of cannabinoids, lack of awareness about the legal status of and regulations regarding MC among both certified physicians, as well as prospective doctors and students of other medicals sciences (e.g., nursing, pharmacy).

For most European countries, we could not identify any studies evaluating HCPs' knowledge and attitudes towards medicinal cannabis. Therefore, similar investigations are highly encouraged. Available evidence demonstrates a need to provide medical training to the HCPs in Europe regarding medical applications of cannabinoids.

For most European countries, we could not identify any studies evaluating HCPs' knowledge and attitudes towards medicinal cannabis. Therefore, similar investigations are highly encouraged. Available evidence demonstrates a need to provide medical training to the HCPs in Europe regarding medical applications of cannabinoids.

The study objective was to compare psychiatric comorbidity among patients seeking treatment for chronic pain and opioid use disorder (OUD) by order of condition onset (i.e., "Pain First," "OUD First," "Same Time").

Data from 170 patients entering two clinical trials of treatments for current comorbid chronic pain and OUD conducted between March 2009 and July 2013 were compared by order of condition onset. The Structured Clinical Interview for DSM-IV-TR Axis I Disorders and the Diagnostic Interview for DSM-IV Personality Disorders (Axis II) were performed by doctoral-level providers using a standardized training protocol. Age of onset group differences on specific diagnostic variables were examined using multinomial logistic regression.

Fifty-two percent were in the "Pain First" group (n = 89), 35 % in the "OUD First" group (n = 59), and 13 % in the "Same Time" group (n = 22). Compared with the Pain First group, the Same Time group was less likely to report heroin (vs. prescription opioids) as the primary drug used (OR = 0.20, 95 % CI = 0.06-0.72) or meet criteria for an Axis II disorder (OR = 0.24, 95 % CI = 0.07-0.83). Compared with the Pain First group, the OUD First group was more likely to meet criteria for a current nonopioid substance use disorder (OR = 3.20, 95 % CI = 1.22-8.40).

Our findings regarding differences in psychiatric comorbidity associated with order of condition onset indicate that varying pathways may exist for the emergence of chronic pain and OUD; further research should investigate potential treatment implications.

Our findings regarding differences in psychiatric comorbidity associated with order of condition onset indicate that varying pathways may exist for the emergence of chronic pain and OUD; further research should investigate potential treatment implications.

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