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.

Ageing alters the severity of Sunitinib-induced cardiotoxicity: Investigating the mitogen activated kinase kinase 7 pathway association.

Anti-cancer drug Sunitinib is linked to adverse cardiovascular events, which have shown to involve mitogen activated kinase kinase 7 (MKK7) pathway. Sunitinib-induced cardiotoxicity in 3, 12 and 24 months old male Sprague-Dawley rats and MKK7 expression and activation was investigated using the Langendorff perfused heart model followed by Western blot analysis. Cardiac function and infarct size were measured during/after 125 min of Sunitinib treatment.

Hearing tests are just child's play: the sound scouts game for children entering school.

Objective: To create a hearing test useable without the involvement of a clinician or calibrated equipment, suitable for children aged 5 or older.

Design: The tablet-based app (Sound Scouts) includes tests of speech in quiet, speech in noise and tones in noise, all embedded in game designed to maintain attention. Data were collected to intelligibility-equalize the stimuli, establish normative performance, and evaluate the sensitivity with which Sound Scouts detected known hearing problems and identified their type.

Involvement of mitogen activated kinase kinase 7 intracellular signalling pathway in Sunitinib-induced cardiotoxicity.

The tyrosine kinase inhibitor Sunitinib is used to treat cancer and is linked to severe adverse cardiovascular events. Mitogen activated kinase kinase 7 (MKK7) is involved in the development of cardiac injury and is a component of the c-Jun N-terminal kinase (JNK) signal transduction pathway. Apoptosis signal-regulating kinase 1 (ASK1) is the upstream activator of MKK7 and is specifically inhibited by 2,7-dihydro-2,7-dioxo-3H-naphtho[1,2,3-de]quinoline-1-carboxylic acid ethyl ester (NQDI-1).

Cytotoxicity Study of Textile Fabrics Impregnated With CuO Nanoparticles in Mammalian Cells.

Copper and copper compounds have multifunctional properties (antibacterial, antiviral, and antifungal) with promising applications. Copper in its nanoparticle (Cu NPs) forms has been widely used in various industrial and commercial applications. In the current research, the cytotoxic effects of textile fabrics impregnated with copper oxide nanoparticles (CuO NPs) were studied in mammalian cell lines.

Attenuation of Sunitinib-induced cardiotoxicity through the A3 adenosine receptor activation.

Sunitinib is an anti-cancer tyrosine kinase inhibitor associated with severe cardiotoxic adverse effects. Using rat Langendorff heart model and human acute myeloid leukaemia 60 (HL60) cell line we detected the involvement of protein kinase C (PKC) α during Sunitinib-induced cardiotoxicity and the effect of Sunitinib on cancer progression. The cardioprotective and anti-cancer properties of the A adenosine receptor agonist 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) were investigated.

What Is the Molecular Signature of Mind-Body Interventions? A Systematic Review of Gene Expression Changes Induced by Meditation and Related Practices.

There is considerable evidence for the effectiveness of mind-body interventions (MBIs) in improving mental and physical health, but the molecular mechanisms of these benefits remain poorly understood. One hypothesis is that MBIs reverse expression of genes involved in inflammatory reactions that are induced by stress. This systematic review was conducted to examine changes in gene expression that occur after MBIs and to explore how these molecular changes are related to health.

Selecting Standardized Tests in Nursing Education.

Nursing faculty frequently utilize or consider the use of nationally standardized tests to evaluate nursing student performance and their potential to pass the National Council Licensure Examination (NCLEX)(©) after graduation. There is little literature available to advise and guide nursing faculty in criteria to consider when selecting a standardized testing company to assess student readiness for NCLEX. The intent of this article is to share criteria to consider when evaluating a standardized test or testing program that has been gathered through an informal survey of faculty who are currently using standardized tests.

The Tameside and Glossop Early Attachment Service: Meeting the emotional needs of parents and their babies.

Parent-infant emotional health is probably one of the most complex arenas in which mental health, maternity and health visiting services operate. This critical period can be highly emotionally charged, not only for the infant but also be for the parent. While most parents essentially get it right, severe ruptures in the parent-infant relationship can occur, and can have serious consequences.

WWOSC 2014: research needs for better health resilience to weather hazards.

The first World Weather Open Science Conference (WWOSC, held from 17-21 August 2014 in Montreal, Québec), provided an open forum where the experience and perspective of a variety of weather information providers and users was combined with the latest application advances in social sciences. A special session devoted to health focused on how best the most recent weather information and communication technologies (ICT) could improve the health emergency responses to disasters resulting from natural hazards. Speakers from a plenary presentation and its corresponding panel shared lessons learnt from different international multidisciplinary initiatives against weather-related epidemics, such as malaria, leptospirosis and meningitis and from public health responses to floods and heat waves such as in Ontario and Quebec, Canada.

Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody.

Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and cancer. Cell entry of HCV and other pathogens is mediated by tight junction (TJ) proteins, but successful therapeutic targeting of TJ proteins has not been reported yet. Using a human liver-chimeric mouse model, we show that a monoclonal antibody specific for the TJ protein claudin-1 (ref.

Evaluating the impact of environmental interventions across 2 countries: the International Bikeshare Impacts on Cycling and Collisions Study (IBICCS) Study protocol.

Background: Few international studies examine public bicycle share programs (PBSP) health impacts. We describe the protocol for the International Bikeshare Impacts on Cycling and Collisions Study (IBICCS).

Methods: A quasi-experimental non-equivalent groups design was used.

Development of a guide to applying precaution in local public health.

Purpose: The precautionary principle (PP) urges actions to prevent harm even in the face of scientific uncertainty. Members of Toronto Public Health (TPH) sought guidance on applying precaution.

Methods: We searched five bibliographic databases (yield 60 articles from 1996 to 2009 and 8 from 2009 to 2011) and Google (yield 11 gray literature sources) for material relevant to local public health.

Theoretical studies of the mechanism of N-hydroxylation of primary aromatic amines by cytochrome P450 1A2: radicaloid or anionic?

Primary aromatic and heteroaromatic amines are notoriously known as potential mutagens and carcinogens. The major event of the mechanism of their mutagenicity is N-hydroxylation by P450 enzymes, primarily P450 1A2 (CYP1A2), which leads to the formation of nitrenium ions that covalently modify nucleobases of DNA. Energy profiles of the NH bond activation steps of two possible mechanisms of N-hydroxylation of a number of aromatic amines by CYP1A2, radicaloid and anionic, are studied by dispersion-corrected DFT calculations.

Getting it right from the start: evaluation of a DVD and booklet for new parents.

Early universal preventive interventions have the potential to improve the parent-infant relationship. Getting it Right from the Start is a DVD and booklet given free to new parents to promote sensitive and responsive early parenting and infant communication. Parents in the local area were canvassed for their views and opinions as to what their needs and feelings were about infant mental health.

Experimental testing of quantum mechanical predictions of mutagenicity: aminopyrazoles.

A computational method for predicting the likelihood of aromatic amines being active in the Ames test for mutagenicity was trialed on a set of aminopyrazoles. A virtual array of compounds was generated from the available sets of hydrazines and α-cyanoaldehydes (or ketones) and quantum mechanical calculations used to compute a probability of being active in the Ames test. The compounds selected for synthesis and testing were not based on the predictions and so spanned the range of predicted probabilities.

Theoretical studies of chemical reactivity of metabolically activated forms of aromatic amines toward DNA.

The metabolism of aromatic and heteroaromatic amines (ArNH₂) results in nitrenium ions (ArNH⁺) that modify nucleobases of DNA, primarily deoxyguanosine (dG), by forming dG-C8 adducts. The activated amine nitrogen in ArNH⁺ reacts with the C8 of dG, which gives rise to mutations in DNA. For the most mutagenic ArNH₂, including the majority of known genotoxic carcinogens, the stability of ArNH⁺ is of intermediate magnitude.

Rationally designing safer anilines: the challenging case of 4-aminobiphenyls.

We describe how we have been able to design 4-aminobiphenyls that are nonmutagenic (inactive in the Ames test). No such 4-aminobiphenyls were known to us, but insights provided by quantum mechanical calculations have permitted us to design and synthesize some examples. Importantly, the quantum mechanical calculations could be combined with predictions of other properties of the compounds that contained the 4-aminobiphenyls so that these remained druglike.

A dual role for hypoxia inducible factor-1α in the hepatitis C virus lifecycle and hepatoma migration.

Background & Aims: Hepatitis C virus (HCV) causes progressive liver disease and is a major risk factor for the development of hepatocellular carcinoma (HCC). However, the role of infection in HCC pathogenesis is poorly understood. We investigated the effect(s) of HCV infection and viral glycoprotein expression on hepatoma biology to gain insights into the development of HCV associated HCC.