Majmaah University

Treatment-resistant depression (TRD) represents a significant therapeutic challenge, as conventional treatments demonstrate limited efficacy. Although ketamine's acute antidepressant effects are well-documented, the role of maintenance therapy remains understudied. We conducted a systematic review to assess the efficacy, safety, and optimal implementation strategies of ketamine maintenance therapy in TRD.

Following PRISMA guidelines, we searched major databases for studies published between January 2020 and November 2024 that examined ketamine maintenance therapy in TRD. Studies were assessed using the Cochrane Risk of Bias 2 tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies.

Eleven studies met inclusion criteria. Regular maintenance dosing showed superior outcomes compared to variable protocols (relapse rates: 27.3 % vs 45.6 %). Younger age (<45 years) and shorter duration of depression (<2 years) predicted better response rates. Concurrent psychotherapy improved treatment maintenance (HR: 0.72 for relapse). Adverse events were generally mild to moderate, resulting in a 7.2 % discontinuation rate.

Ketamine maintenance therapy shows promise as a treatment option for TRD, with regular dosing schedules and early intervention associated with optimal outcomes. While safety profiles are reassuring, standardized protocols and careful patient selection remain essential. Future research should focus on determining the optimal maintenance duration and identifying reliable biomarkers for treatment response.

Tuberculosis (TB) remains a major public health problem with increased incidence of drug-resistant TB due to failure of existing treatments. Current anti-TB drugs are mainly directed at targeting important biochemical pathways in the Mtb with the biotransformation of drugs through hepatic metabolism. However, new proof indicates that Mtb can directly contribute to drug metabolism, therefore determining both the effectiveness and the resistance of a therapeutic agent. This review aims to explore the mechanism of action of Mtb mediated drug biotransformation, the several enzymes it contains and new metabolic pathway by which the pathogen could alter, neutralize or even stimulate antitubercular agents. Static liver-based models of metabolism are then compared to pathogen-based models to give a deeper understanding of how the host and pathogen jointly determine the final outcome and efficacy of the drug. In addition, the Mtb driven biotransformation, causes impact Mtb metabolism on pharmacokinetics, drug half-life, and bioavailability, and the potential to develop new therapeutic approaches are also elaborated. This review also discusses possible directions in drug discovery by identifying Mtb-specific enzymes, using combination therapy, which affects the host and pathogen's metabolism, and using metabolomic and computational analysis for pathway identification. The potential lies in applying pathogen-specific knowledge to TB drug development to address adaptive resistance, improve on drug dosing regimens, and improve treatment outcomes. Additionally, host-directed therapies (HDTs) and the concept of developing drugs with dual activity are suggested as possible new strategies in TB control. Holders of co-culture systems, organoids, and machine learning-driven metabolomics are considered as advanced models for demystifying Mtb drug metabolism. These findings emphasize the need for a shift towards precision medicine approach to TB therapy to consider the kinetic nature and Mtb metabolism patterns in relation to human health.

Dietary manipulations are crucial for enhancing rabbit behavior and performanceAddn. of Berberine-loaded chitosan nanoparticles BER-CNPs to fattened rabbit diets has been shown to alleviate the adverse effects of heat stress.BER-CNPs have been found to improve growth performance, feed efficiency, liver functions, immunity and redox balanceBER-CNPs have been observed to reduce the levels of IL-4, TNF-α, IFN-γ, Amyloid A, and NF-κ B while increasing the levels of NO and LZM