Electronic Medical Records (EMRs) are wealthy storehouses of patient information, to which data mining techniques can be prudently applied to reveal clinically significant patterns. Detecting patterns in drug-drug interactions, leading to adverse drug reactions is a powerful application of EMR data mining. Adverse effects of drug treatments can be investigated by mining clinical laboratory tests data which are reliable indicators of abnormal physiological functions. We report here the co-medication effects of pravastatin (HMG-CoA reductase inhibitor) and paroxetine (selective serotonin reuptake inhibitor (SSRI) anti-depressant) on significant clinical parameters, identified through a data mining analysis conducted on the Allscripts data warehouse. We found that the concomitant drug treatments of pravastatin and paroxetine increased the mean values of glucose serum from 113.2 to 132.1 mg/dL and international normalized ratio (INR) from 2.18 to 2.52, respectively. It also decreased the mean values of estimated glomerular filtration rate (eGFR) from 43 to 37 mL/min/1.73 m(3) and blood CO2 levels from 24.8 to 23.9 mEq/L respectively. Our findings indicate that co-medication of pravastatin and paroxetine might have significant impact on blood anti-coagulation, kidney function, and glucose homeostasis. Our methodology can be applied to any EMR data set to reveal co-medication effects of any drug pairs.

Crystallizing RNA has been an imperative and challenging task in the world of RNA research. Assistive methods such as chaperone-assisted RNA crystallography (CARC), employing monoclonal antibody fragments (Fabs) as crystallization chaperones have enabled us to obtain RNA crystal structures by forming crystal contacts and providing initial phasing information. Despite the early successes, the crystallization of large RNAFab complex remains a challenge in practice. The possible reason for this difficulty is that the Fab scaffold has not been optimized for crystallization in complex with RNA. Here, we have used the surface entropy reduction (SER) technique for the optimization of "C209 P4P6/Fab2 model system. Protruding lysine and glutamate residues were mutated to a set of alanines or serines to construct Fab2SMA or Fab2SMS. Expression with the shake flask approach was optimized to allow large scale production for crystallization. Crystal screening shows that significantly higher crystal-forming ratio was observed for the mutant complexes. As the chosen SER residues are far away from the CDR regions of the Fab, the same set of mutations can now be directly applied to other Fabs binding to a variety of ribozymes and riboswitches to improve the crystallizability of FabRNA complex.Keywords: chaperone assisted RNA crystallography/ Fab/protein engineering/shake flask expression/ surface entropy reduction.With every new discovery of a functional RNA, there is a sprint to obtain its crystal structure and elucidate the structurefunction relationship. The dynamic RNA research is mired by the difficulty in obtaining RNA crystals due to its structural property. The negatively charged phosphate backbone of RNA disfavours good crystal forming lattices. Compared to proteins, RNAs have fewer functional groups and have weaker tertiary interactions. The flexible tertiary structure adopting elongated shapes and inter-domain movements within RNA makes crystal packing even more difficult (1). Assistive methods for crystallization are constantly pursued to alleviate these complications (2, 3). Chaperone-assisted RNA crystallography (CARC) is one such assistive method which employs a monoclonal antibody fragment to bind RNAs of interest and aid in crystallization. Synthetic antigenbinding fragments (Fabs) selected from a phage display library can bind to large functional RNAs recognizing tertiary structures. These Fabs have large surface area, participate extensively in crystal contacts and provide good initial phasing information (4, 5).YSGX synthetic library is a reduced genetic codon library that generates randomized CDRs using codons enriched in tyrosines, serines and glycines (6). This was used to obtain the first RNAFab complex crystal structure (1.95 Å ) of ÁC209 P4P6 RNA binding to Fab2 (1, 4). ÁC209 P4P6 RNA is a single site mutant form of the P4P6 RNA of the Tetrahymena group I intron which catalyses its own excision from precursor RNA. The single site mutation increases the tertiary stability by reducing the conformational f...

Our study reports an adverse weight gain on co-medication of escitalopram and bupropion, which warrants further validation studies. Considering co-medication effects of antidepressants on weight is important to design robust depression treatment plans.