Agreement between WHO-UMC causality scale and the Naranjo algorithm for causality assessment of adverse drug reactions.

BACKGROUND: The Pharmacovigilance Program of India recommends the use of the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) scale, while many clinicians prefer the Naranjo algorithm for its simplicity. In the present study, we assessed agreement between the two widely used causality assessment scales, that is, the WHO-UMC criteria and the Naranjo algorithm. MATERIALS AND METHODS: In this study, 842 individual case safety reports were randomly selected from 1000 spontaneously reported forms submitted to the ADR Monitoring Center at a tertiary healthcare Institute in Central India between 2016 and 2018. Two well-trained independent groups performed the causality assessment. One group performed a causality assessment of the 842 ADRs using the WHO-UMC criteria and the other group performed the same using the Naranjo algorithm. The agreement between two ADR causality scales was assessed using the weighted kappa (κ) test. RESULTS: Cohen's kappa coefficient (κ) statistical test was applied between the two scales (WHO-UMC scale and Naranjo algorithm) to find out the agreement between these two scales. "No" agreement was found between the two scales {Kappa statistic with 95% confidence interval = 0.048 (P < 0.001)}. CONCLUSION: There was no agreement found between the WHO-UMC criteria and the Naranjo algorithm in our study.

Organoids: An invaluable tool in pharmacology.

Advances in stem cell cultures and human-induced pluripotent stem cells have inculcated interests in a rapidly evolving concept - "organoids." These are three-dimensional (3D) structures mimicking some of the phenomena of the real organs at anatomical, multicellular, and functional levels in vitro. Organoids have been proven to be better than two-dimensional cell culture in replicating the functionality, architectural, and geometrical features of tissues in vivo. Recent advancements have led to the generation of models for organ development and disease, finding applications in the drug discovery, screening of novel compounds, and personalized medicine. Since organoids follow the same natural pathway as the normal tissue or pathology, they can be used to study the expression of various genotypes and phenotypic variations across different species. In the light of these advancements, organoids are now being merged with bioengineering to come up with even better and reliable models to predict the disease progression and effectiveness of precision medicines, few of its important applications. This article discusses the various aspects of this emerging concept along with its uses, both in the present times and near future, with a special focus on pharmacological applications.

High Production of 2,3-butanediol by a Mutant Strain of the Newly Isolated Klebsiella pneumoniae SRP2 with Increased Tolerance Towards Glycerol.

Biodiesel, a renewable fuel produced by transesterification of animal fats and vegetable oils, generates about 10% (v/v) of crude glycerol as a core byproduct. The high volume of this non bio-degradable glycerol is becoming of a great environmental and economical concern due to its worldwide ever-growing surplus. Herein we report a high production of 2,3-butanediol (2,3-BD) from pure and biodiesel derived crude glycerol using a mutant K. pneumoniae SRM2 obtained from a newly isolated strain Klebsiella pneumoniae SRP2. The mutant strain SRM2 with standing high glycerol concentration (220 g L-1 of medium) could rapidly convert glycerol aerobically to 2,3-BD, a versatile product extensively used in chemical, pharmaceutical and fuel industries Our study revealed that an increased GDH activity led to a substantially enhanced production of 2,3-BD. The mutant strain exhibited 1.3-fold higher activity of GDH than that of parent strain (500.08 vs. 638.6 µmol min -1 mg -1 protein), yielding of 32.3 g L-1 and 77.5 g L-1 2,3-BD with glycerol in batch and fed-batch process respectively. However, in batch culture with crude glycerol, cell growth and glycerol consumption were expressively boosted, and 2,3-BD production was 27.7 g L-1 from 75.0 g/L crude glycerol. In this report, the optimal conditions for high production of 2,3-BD were defined in a completely aerobic process, and 0.59 g g-1 product yield of 2,3-BD was attained by the mutated strain K. pneumoniae SRM2, which is the highest amount obtained from batch biotransformation process of glycerol metabolism till today. These results indicated that our newly developed mutant can tolerate high concentration of glycerol, have a high glycerol utilization rate, and high product yield of 2,3-BD. It is demonstrated that the mutant strain K. pneumoniae SRM2 has an ability to produce fewer co-products at trace concentrations at higher glycerol concentrations, and could be a potential candidate for 2,3-DB production in an industrial bioconversion process.