STABILITY STUDY: REGULATORY REQUIRENMENT

Stability is an essential factor of quality, safety and efficacy of a drug product. The objective of stability study is to determine the shelf life, the time period of storage at a specified condition within which the drug product still meets its established specifications. Stability study is of three types that is physical, chemical and microbial stability. Various factors like oxygen, water, temperature, pH, moisture, light and concentration affect the stability. Present work aims to represent the stability testing (ST) requirements of International Conference on Harmonization (ICH), different regulatory agencies like, World Health Organization (WHO), Association of South East Asian Nations (ASEAN) and European Agency for Evaluation of Medicinal and Health Products (EMEA) and difference of those agencies with respect to ICH guideline. Most of the stability requirements for WHO, ASEAN, and EMEA are similar to the ICH guideline, except for the parameters like selection of batches and storage conditions

STABILITY STUDY: REGULATORY REQUIREMENT

Stability is an essential factor of quality, safety and efficacy of a drug product. The objective of stability study is to determine the shelf life, the time period of storage at a specified condition within which the drug product still meets its established specifications. Stability study is of three types that is physical, chemical and microbial stability. Various factors like oxygen, water, temperature, pH, moisture, light and concentration affect the stability. Present work aims to represent the stability testing (ST) requirements of International Conference on Harmonization (ICH), different regulatory agencies like, World Health Organization (WHO), Association of South East Asian Nations (ASEAN) and European Agency for Evaluation of Medicinal and Health Products (EMEA) and difference of those agencies with respect to ICH guideline. Most of the stability requirements for WHO, ASEAN, and EMEA are similar to the ICH guideline, except for the parameters like selection of batches and storage conditions

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology

Publisher Correction: Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

This corrects the article DOI: 10.1038/ncomms5999

Comparative evaluation of DFDBA versus PRF with DFDBA in treatment of grade-II furcation defects – A clinical trial

Background: In order to determine whether a method is more successful for treating a grade-II furcation deficiency, this randomized trial will compare demineralized freeze-dried bone allograft (DFDBA) to platelet-rich fibrin with DFDBA. Materials and Methods: Twenty systematically healthy patients between the ages of 30 and 60 with a grade-II furcation were evaluated pre and postoperatively for changes in the modified plaque index, probing depth, relative vertical and horizontal clinical attachment level, gingival marginal level, and radiographic bone defect. Results: The test group significantly outperformed the control group on all clinical and radiological measures. Conclusion: The experimental group improved at both clinical attachment levels and had a higher decrease in probing depth than the control group did

MLL5 Orchestrates a Cancer Self-Renewal State by Repressing the Histone Variant H3.3 and Globally Reorganizing Chromatin

Mutations in the histone 3 variant H3.3 have been identified in one-third of pediatric glioblastomas (GBMs), but not in adult tumors. Here we show that H3.3 is a dynamic determinant of functional properties in adult GBM. H3.3 is repressed by mixed lineage leukemia 5 (MLL5) in self-renewing GBM cells. MLL5 is a global epigenetic repressor that orchestrates reorganization of chromatin structure by punctuating chromosomes with foci of compacted chromatin, favoring tumorigenic and self-renewing properties. Conversely, H3.3 antagonizes self-renewal and promotes differentiation. We exploited these epigenetic states to rationally identify two small molecules that effectively curb cancer stem cell properties in a preclinical model. Our work uncovers a role for MLL5 and H3.3 in maintaining self-renewal hierarchies in adult GBM