Increasing awareness of healthy eating through the use of performing arts: An evaluation of the StarBites project

This project report discusses an evaluation of StarBites - a joint initiative between the arts for health and foods for health strands of Halton's Healthy Living Programme. StarBites aims to convey healthy eating messages through drama, dance, poetry, and music performed by school children.Halton's Healthy Living programm

Emergency life support training for school children: exploring local implementation and outcomes of the Heartstart UK school programme within the context of the National Healthy School Standard

This project discusses the implementation of Heartstart UK - an initiative co-ordinated by the British Heart Foundation to increase emergency life support training - in a number of schools in Cheshire.British Heart Foundation

Discovery and optimisation of small-molecule ERK5 inhibitors as cancer therapeutics

PhD ThesisExtracellular signal-regulated kinase 5 (ERK5) is a member of the protein kinase superfamily, which plays an essential role in the transduction of extracellular signals to intracellular effectors. Activation of the ERK5 signalling pathway is associated with cell survival, proliferation, and differentiation, and thus ERK5 over-expression may have implications in carcinogenesis. Therefore, the discovery and development of small molecule inhibitors of ERK5 may offer a novel therapeutic intervention for cancer. High throughput screening (HTS) of chemical libraries, conducted by Cancer Research Technology, revealed three distinct chemical series as moderate inhibitors of ERK5. Two of these series are described herein i.e.: 3-cyanopyridines (IC50 = 0.5 – 31.3 μM); and pyrrolecarboxamides (IC50 = 0.66 – 3.5 μM). Two 3-cyanopyridine based hits (2-(2-((3-cyano-4-(4-fluorophenyl)-6-phenylpyridin-2- yl)thio)acetamido)acetic acid, 68 and 2-((3-cyano-4-(4-fluorophenyl)-6-phenylpyridin-2- yl)thio)-N-(2-oxopropyl)acetamide, 67; IC50 values = 1.6 and 0.5 μM, respectively) were resynthesised and were slightly less active at 4.9 and 20.5 μM. The 3-cyanopyridine scaffold was deemed a valid starting point for initiating structure activity relationship (SAR) studies. Three areas were identified for further investigation i.e.: modification to the thioether sidechain; modification to the aryl substituent; and isosteric replacement of the 3-cyano motif. Structure-activity studies did not result in improved potency over the initial hits. Previously, the pyrrole-carboxamide series has been validated successfully. Hit-to-lead studies around the aroyl ring highlighted the importance of substitution pattern for potency, with 2,6-difluoro (or 2,3-dichloro) substituents conferring the greatest potency (4-(2,6- difluorobenzoyl)-N-(pyridin-4-ylmethyl)-1H-pyrrole-2-carboxamide, 144; IC50 = 2.3 μM) initially. Truncation of the carboxamide side-chain resulted in improved activity (IC50 = 0.9 4 μM) and crucially, ≥100-fold selectivity for ERK5 over the closely related kinase p38α was also achieved e.g. 4-(2,6-difluorobenzoyl)-N-(pyridin-4-yl)-1H-pyrrole-2-carboxamide, 256.. Tuning of the aroyl substituents and pyridyl groups resulted in discovery of 4-(2-bromo-6- fluorobenzoyl)-N-(pyridin-3-yl)-1H-pyrrole-2-carboxamide, 278 a potent and selective ERK5 inhibitor with excellent drug-like properties (i.e.: MW = 388; cLogP = 3.2; LE = 0.35; Aqueous solubility = >100 μM; PPB = 94%). Preliminary in vivo studies of lead compound 4-(2-bromo-6-fluorobenzoyl)-N-(pyridin-3-yl)-1H-pyrrole-2-carboxamide have confirmed efficacy in xenograft tumour models, and satisfactory pharmacokinetic properties in mice. The pyrrole-carboxamide series has now entered the lead optimisation phase of drug discovery, focussing on improvement of cellular activity, and eliminating CYP inhibition, with the aim of providing compounds with suitable potency and properties for clinical trials.Cancer Research U

Private Speech and Inner Speech in Typical and Atypical Development

Children often talk themselves through their activities: They produce private speech to regulate their thought and behaviour, which is internalised to form inner speech, or silent verbal thought. Private speech and inner speech can together be referred to as self-directed speech (SDS). SDS is thought to be an important aspect of human cognition. The first chapter of the present thesis explores the theoretical background of research on SDS, and brings the reader up-to-date with current debates in this research area. Chapter 2 consists of empirical work that used the observation of private speech in combination with the dual task paradigm to assess the extent to which the executive function of planning is reliant on SDS in typically developing 7- to 11-year-olds. Chapters 3 and 4 describe studies investigating the SDS of two groups of atypically developing children who show risk factors for SDS impairment—those with autism and those with specific language impairment. The research reported in Chapter 5 tests an important tenet of neoVygotskian theory—that the development of SDS development is domain-general—by looking at cross-task correlations between measures of private speech production in typically developing children. Other psychometric properties of private speech production (longitudinal stability and cross-context consistency) were also investigated. Chapter 6, the General Discussion, first summarises the main body of the thesis, and then goes on to discuss next steps for this research area, in terms of the methods used to study SDS, the issue of domain-general development, and the investigation of SDS in developmental disorders

Organoids, organs-on-chips and other systems, and microbiota

The human gut microbiome is considered an organ in its entirety and has been the subject of extensive research due to its role in physiology, metabolism, digestion, and immune regulation. Disequilibria of the normal microbiome have been associated with the development of several gastrointestinal diseases, but the exact underlying interactions are not well understood. Conventional in vivo and in vitro modelling systems fail to faithfully recapitulate the complexity of the human host–gut microbiome, emphasising the requirement for novel systems that provide a platform to study human host–gut microbiome interactions with a more holistic representation of the human in vivo microenvironment. In this review, we outline the progression and applications of new and old modelling systems with particular focus on their ability to model and to study host–microbiome cross-talk

Berry chemoprevention: do berries decrease the window of opportunity for tumourigenesis

In addition to smoking and UV exposure, lifestyle factors, such as diet, nutrition, and physical activity, have been shown to play a significant role for many cancers. It is estimated that up to 50% of some cancer types are preventable; many through lifestyle and dietary changes with the presence or absence of certain dietary components strongly associated with an increased or decreased risk. Here we summarize the work that has been performed with polyphenols, with a focus on those derived from black raspberries. These have been extensively studied for the prevention and treatment of a variety of conditions and diseases. Here we focus on their use for the prevention or treatment of specific cancer types and the impact they have on biological systems. The aim is to highlight the need to improve our understanding of how the environment impacts upon the normal biological processes that affect health and disease, thereby, enabling us to implement smarter prevention and treatment measures

Preventing long-term risk of obesity for two generations: Prenatal physical activity is part of the puzzle

Background. The period surrounding pregnancy has been identified as a risk period for overweight/obesity in both mother and child because of excessive gestational weight gain (GWG). The promotion of a healthy GWG is therefore of paramount importance in the context of the prevention of obesity in the current and next generations. Objective. To provide a comprehensive overview of the effect of prenatal physical activity interventions, alone or in combination with nutritional counselling, on GWG and to address whether preventing excessive GWG decreases the incidence of infant high birth weight and/or postpartum weight retention. Method. A search of the PubMed database was conducted to identify all relevant studies. Nineteen studies were included in this review: 13 interventions combining physical activity, nutrition, and GWG counselling and 6 interventions including physical activity alone. Results. Prenatal lifestyle interventions promoting healthy eating and physical activity habits appear to be the most effective approach to prevent excessive GWG. Achievement of appropriate GWG may also decrease the incidence of high infant birth weight and postpartum weight retention. Conclusion. Healthy eating habits during pregnancy, combined with an active lifestyle, may be important elements in the prevention of long-term risk of obesity for two generations. © 2012 Stephanie-May Ruchat and Michelle F. Mottola

Reacting to the Past: The French Revolution from the Eyes of History Students

From the Editorial Introduction:Dr. Allison Belzer, Assistant Professor of History, began to utilize the “Rousseau, Burke, and Revolution in France, 1791” text in her Civilization classes and Modern France course. The students accepted the challenge and put forward remarkable work, far more insightful than seen in traditional lecture formats. The students were all assigned roles within the factions Jacobin, Noble, Clergy, Moderates, the crowd, and individual characters like King Louis XVI, Marquis de Lafayette, lawyer, doctor, journalist, and rural delegate. Every group was given delegates and power just as they were historically distributed. The students got a chance to make their mark on the historical debates such as the constitution, slavery, and equal rights. The roles were dynamic and ever changing as back room deals were encouraged. Also crowd riots could shift the number of delegates and therefore the balance of power with moment’s notice. The student experience was unique amongst classroom atmospheres, with feelings of pressure, competition, and excitement all playing a role in their assigned work. Basically, no one wanted to lose their head or be killed in a crowd riot, and their best defense were the writings they published in weekly newspapers hoping to gain approval of the factions and crowd. Every week each group produced newspapers comprised of their individual essays. The newspapers stated the stance and political leanings of the factions and covered details of the fighting and protests. The following pieces are written in first person as though they were published by historical characters in 18th-century France at the height of the debate over the role of the clergy, monarchy, and what equal rights for all really meant to the men and women of France. (Editor, Francis Tannie Arnsdorff