Identification of Substituted Amino Acid Hydrazides as Novel Anti-Tubercular Agents, Using a Scaffold Hopping Approach.

Discovery and development of new therapeutic options for the treatment of () infection, particularly drug-resistant strains, are urgently required to tackle the global burden of this disease. Herein, we reported the synthesis of a novel series of N-substituted amino acid hydrazides, utilising a scaffold hopping approach within a library of anti-tubercular agents. Efficacy and selectivity were evaluated against three strains of (wild-type, isoniazid-resistant and rifampicin-resistant), and cytotoxicity against macrophages .

What are the experiences of therapists using the online Back Skills Training and implementing it within clinical practice?

Introduction: The purpose of the present study was to explore the experiences of physiotherapists using the online Back Skills Training (i-BeST). The aim of the this programme was to enable clinicians to facilitate group-based treatment based on a cognitive behavioural (CB) approach to the treatment of lower back pain (LBP).

Methods: A qualitative, exploratory approach was chosen.

Identification of Novel Benzoxa-[2,1,3]-diazole Substituted Amino Acid Hydrazides as Potential Anti-Tubercular Agents.

Discovery and development of new therapeutic options for the treatment of () infection are desperately needed to tackle the continuing global burden of this disease and the efficacy and cost limitations associated with current medicines. Herein, we report the synthesis of a series of novel benzoxa-[2,1,3]-diazole substituted amino acid hydrazides in a two-step synthesis and evaluate their inhibitory activity against and selected bacterial strains of clinical importance utilising an end point-determined REMA assay. Alongside this, their potential for undesired cytotoxicity against mammalian cells was assessed employing standard MTT assay methodologies.

Testing a chemical series inspired by plant stress oxylipin signalling agents for herbicide safening activity.

Background: Herbicide safening in cereals is linked to a rapid xenobiotic response (XR), involving the induction of glutathione transferases (GSTs). The XR is also invoked by oxidized fatty acids (oxylipins) released during plant stress, suggesting a link between these signalling agents and safening. To examine this relationship, a series of compounds modelled on the oxylipins 12-oxophytodienoic acid and phytoprostane 1, varying in lipophilicity and electrophilicity, were synthesized.

Rational Development of Novel Activity Probes for the Analysis of Human Cytochromes P450.

The identification and quantification of functional cytochromes P450 (CYPs) in biological samples is proving important for robust analyses of drug efficacy and metabolic disposition. In this study, a novel CYP activity-based probe was rationally designed and synthesised, demonstrating selective binding of CYP isoforms. The dependence of probe binding upon the presence of NADPH permits the selective detection of functionally active CYP.

The first intramolecular silene Diels-Alder reactions.

The synthesis of silaheterocycles through the first examples of an intramolecular silene Diels-Alder reaction is described.

Key role for a glutathione transferase in multiple-herbicide resistance in grass weeds.

Multiple-herbicide resistance (MHR) in black-grass (Alopecurus myosuroides) and annual rye-grass (Lolium rigidum) is a global problem leading to a loss of chemical weed control in cereal crops. Although poorly understood, in common with multiple-drug resistance (MDR) in tumors, MHR is associated with an enhanced ability to detoxify xenobiotics. In humans, MDR is linked to the overexpression of a pi class glutathione transferase (GSTP1), which has both detoxification and signaling functions in promoting drug resistance.

Preparation and complete (1) H and (13)C assignment of some pentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecane-8,11-dione (PCUD) derivatives.

The preparation of a number of alkyl and alkoxy derivatives of pentacyclo[5.4.0.

The maize benzoxazinone DIMBOA reacts with glutathione and other thiols to form spirocyclic adducts.

Maize, wheat and other grasses synthesise large quantities of benzoxazinones and their glucosides, which act as antifeedant and allelopathic agents. These activities are probably due to the electrophilic nature of the aglycones, however, the mechanism of their action is unclear. In biological systems, glutathione (GSH) is the major electrophile-reactive compound so the reaction of the major maize benzoxazinone DIMBOA with GSH was studied.

Impact of the Accreditation of Clinical Educators scheme: reflections from one higher education institution.

Objective: To provide a critically reflective account of clinical educators' experiences of the Accreditation of Clinical Educators (ACE) scheme, launched by the Chartered Society of Physiotherapy in 2004, and its impact on practice.

Design: A qualitative methodology with three elements: focus group interviews during the accreditation process, and completion of a questionnaire at its conclusion and 6 months following completion. All data were transcribed and analysed using the constant comparative method.

Transition metal-catalysed cross-coupling reactions of P-activated enols.

Transition metal catalysed cross-coupling reactions are ubiquitous in organic chemistry providing an impressive technique for C-C bond formation. Whilst many electrophilic partners have been described for these reactions, aryl and vinyl phosphates, phosphonates and phosphonites can offer advantages in terms of preparation, stability and reactivity profile. This critical review summarises the advances made to date utilising P-activated enols in metal-catalysed cross-coupling reactions (97 references).

The Arabidopsis phi class glutathione transferase AtGSTF2: binding and regulation by biologically active heterocyclic ligands.

The plant-specific phi class of glutathione transferases (GSTFs) are often highly stress-inducible and expressed in a tissue-specific manner, suggestive of them having important protective roles. To date, these functions remain largely unknown, although activities associated with the binding and transport of reactive metabolites have been proposed. Using a sensitive and selective binding screen, we have probed the Arabidopsis thaliana GSTFs for natural product ligands from bacteria and plants.

Fluorescence quenched quinone methide based activity probes--a cautionary tale.

A carbamate linked quenching group coupled with a pro-quinone methide reactive core provides an effective tool for studying enzyme function without problems associated with background fluorescence from unreacted probe. However, the relatively slow fragmentation of the carbamate linkage in such a strategy may cause problems of loss of signal or a decoupling of enzyme activity and labelling.

The perceptions of Athenian physiotherapists on the referral service in Greece and its impact on professional autonomy.

Background And Purpose: The attainment of professional autonomy is considered a priority of any profession. The development of autonomy in physiotherapy has differed among countries, with some achieving a high degree of autonomy while others have struggled. The current literature reveals little about the autonomy of physiotherapists in Greece, although it would appear they face both external and internal threats to autonomous practice and to the development of their profession.

Silenes in organic synthesis: a concise synthesis of (+/-) -epi-picropodophyllin.

A concise, seven step synthesis of the aryl tetralin lignan lactone epi-picropodophyllin from piperonal is described. The key steps are a silene diene Diels-Alder reaction and the Hosomi-Sakurai reaction of the resultant silacyclohexene.

Hosomi-Sakurai reactions of silacyclohexenes.

Silacyclic allyl silanes, derived from silene-diene Diels-Alder reactions, combine with acetals in the presence of Lewis acids to afford, following oxidation of the intermediate fluorosilane, either butane-1,4-diols or tetrahydronaphthalenes containing four contiguous chiral centres with moderate to good diastereoselectivity.

Silenes in organic synthesis: a short synthesis of prelactone B.

A sequence involving dihydroxylation and acid induced fragmentation of silene generated silacyclohexenes represents the key step in a concise synthetic route to beta-hydroxy-delta-lactones.

Hosomi-Sakurai reactions of silacyclic allyl silanes.

Substituted silacyclohexenes, generated through silene-diene [4 + 2] cycloaddition reactions, undergo Lewis acid promoted Sakurai type reactions with acetals to afford, following oxidation of the resultant fluorosilane, 1,4-diols with four contiguous chiral centres.

Measuring hearing aid outcomes using the Satisfaction with Amplification in Daily Life (SADL) questionnaire: Australian data.

The aims of this study were to investigate hearing aid satisfaction for a group of older Australians fitted with government-funded hearing aids using the Satisfaction with Amplification in Daily Life (SADL) questionnaire; to compare the Australian data gathered with the provisional normative data reported by Cox and Alexander (1999); and to investigate the relationship between SADL satisfaction and several participant variables, hearing aid variables, and other outcome measures. The SADL questionnaire and a Client Satisfaction Survey (CSS) were distributed by mail to 1284 adults fitted with government-funded hearing aids three to six months previously. 1014 surveys were returned.

Reflective practice and clinical supervision: an interprofessional perspective.

Background: In the United Kingdom, the drive to encourage reflective practice through clinical supervision, as a means of ensuring quality of provision in nursing and other health care professions, is now well-embedded, not only in policy but also in practice. However, debate and critique of these concepts is limited.

Aim: The aim of this paper is to draw on research, conducted with undergraduate occupational therapy students and qualified physiotherapists, in order to contribute to the debate about the functions of clinical supervision and reflective practice in nursing and other health care professions.

Parasitic exploitation as an engine of diversity.

Parasitic exploitation occurs within and between a wide variety of taxa in a plethora of diverse contexts. Theoretical and empirical analyses indicate that parasitic exploitation can generate substantial genetic and phenotypic polymorphism within species. Under some circumstances, parasitic exploitation may also be an important factor causing reproductive isolation and promoting speciation.