Efficacy and Safety of Bococizumab (RN316/PF-04950615), a Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9, in Hypercholesterolemic Japanese Subjects Receiving a Stable Dose of Atorvastatin or Treatment-Naive　- Results From a Randomized, Placebo-Controlled, Dose-Ranging Study.

BACKGROUND: A Phase 2, dose-ranging study of bococizumab, a monoclonal anti-proprotein convertase subtilisin/kexin type 9 antibody, was conducted in Japanese subjects to assess its efficacy, safety, and tolerability in this population.Methods and Results:Two different hypercholesterolemic study populations were enrolled concurrently: Japanese subjects with uncontrolled low-density lipoprotein cholesterol (LDL-C) despite atorvastatin treatment (LDL-C ≥100 mg/dL; n=121), and Japanese subjects naive to lipid-lowering agents and with LDL-C ≥130 mg/dL (n=97). Subjects within each study population were randomized to bococizumab 50, 100, or 150 mg, or placebo, q14D for 16 weeks; an open-label ezetimibe 10 mg daily arm was also included for the atorvastatin-treated population. Significant, dose-dependent reductions in fasting LDL-C levels were observed in all bococizumab arms of both study populations at Weeks 12 and 16 (adjusted mean percent changes from baseline: 54.1-76.7% for atorvastatin-treated subjects and 47.7-66.8% for treatment-naive subjects; P<0.001 vs. placebo for all). Bococizumab also caused dose-dependent changes in other lipid parameters in both study populations at Weeks 12 and 16. No serious adverse events (AEs) related to bococizumab treatment occurred and all treatment-emergent AEs were mild or moderate in severity. No dose-dependent relationship between bococizumab treatment and development of anti-drug antibodies was observed. CONCLUSIONS: Bococizumab was well tolerated and significantly reduced fasting LDL-C in atorvastatin-treated and treatment-naive hypercholesterolemic Japanese subjects. (Clinicaltrials.gov identifier: NCT02055976.).

Genomic dataset of a multiple-drug resistant Pseudomonas sp. strain RAC1 isolated from a flacherie infected Nistari race of Bombyx mori L.

Species belonging to the genus Pseudomonas is a rod shaped Gram-negative bacteria emerged as an important silkworm pathogen with broad-level multi-drug resistance. The extensive usage of antimicrobials in sericulture farming is gradually leading to the emergence of multi-drug resistance (MDR) strains, posing a significant threat to the well-being of both Bombyx mori L. and serifarmers. Pseudomonas spp. with MDR level may gets transmitted from the infected silkworm to human handlers either via direct contact or through contaminated feces. To understand the emerging concern of antimicrobial resistance (AMR) in Pseudomonas spp. provides insights into their genomic information. Here, we present the draft genome sequence data of Pseudomonas sp. strain RAC1 isolated from a flacherie infected Nistari race of Bombyx mori L. from the silkworm rearing house of Raiganj University, India and sequenced using the Illumina NovaSeq 6000 platform. The estimated genome size of the strain was 4494347 bp with a G + C content of 63.5%. The de novo assembly of the genome generated 38 contigs with an N50 of 200 kb. Our data might help to reveal the genetic diversity, underlying mechanisms of AMR and virulence potential of Pseudomonas spp. This draft-genome shotgun project has been deposited under the NCBI GenBank accession number NZ_JAUTXS000000000.