Escaping the cohort of concern: in vitro experimental evidence supports non-mutagenicity of N-nitroso-hydrochlorothiazide.

In recent years, nitrosamine impurities in pharmaceuticals have been subject to intense regulatory scrutiny, with nitrosamine drug substance-related impurities (NDSRIs) treated as cohort of concern impurities, regardless of predicted mutagenic potential. Here, we describe a case study of the NDSRI N-nitroso-hydrochlorothiazide (NO-HCTZ), which was positive in the bacterial reverse mutation (Ames) test but is unstable under the test conditions, generating formaldehyde among other products. The mutagenic profile of NO-HCTZ was inconsistent with that expected of a mutagenic nitrosamine, exhibiting mutagenicity in the absence of metabolic activation, and instead aligned well with that of formaldehyde.

NCLEX-RN readiness: HESI Exit Exam validity and nursing program policies.

Background: The HESI® Exit Exam (E2) has been used to assess student readiness for the NCLEX-RN® examination for over two decades.

Purpose: In this study, we examined the relationship between students' average E2 scores and their first time NCLEX-RN pass or fail outcomes to understand the validity of the E2 as a predictor of NCLEX-RN readiness. In addition, we examined the relationship between policies governing E2 use in programs and success on the NCLEX-RN.

Developing a harmonized heat warning and information system for Ontario: a case study in collaboration.

Background: Heat wave early warning systems help alert decision-makers and the public to prepare for hot weather and implement preventive actions to protect health. Prior to harmonization, public health units across Ontario either used independent systems with varying methodologies for triggering and issuing public heat warnings or did not use any system. The federal government also issued heat warnings based on different criteria.

Tiotropium bromide, a long acting muscarinic receptor antagonist triggers intracellular calcium signalling in the heart.

Background And Purpose: Tiotropium bromide (TB) is a long acting muscarinic receptor antagonist used to manage chronic obstructive pulmonary disease (COPD). Recent meta-analyses suggest an increased risk of cardiovascular events with TB. Ca/calmodulin dependent kinase II (CaMKII) and L-type Ca channels regulate Ca concentrations allowing management of Ca across membranes.

mRNA levels are buffered upon knockdown of RNA decay and translation factors via adjustment of transcription rates in human HepG2 cells.

Evidence from yeast and mammals argues the existence of cross-talk between transcription and mRNA decay. Stabilization of transcripts upon depletion of mRNA decay factors generally leads to no changes in mRNA abundance, attributing this to decreased transcription rates. We show that knockdown of human XRN1, CNOT6 and ETF1 genes in HepG2 cells led to significant alteration in stability of specific mRNAs, alterations in half-life were inversely associated with transcription rates, mostly not resulting in changes in abundance.