Towards understanding the design of dual-modal MR/fluorescent probes to sense zinc ions

A series of gadolinium complexes were synthesised in order to test the design of dual-modal probes that display a change in fluorescence or relaxivity response upon binding of zinc. A dansyl-DO3ATA gadolinium complex [GdL1] displayed an increase and a slight blue-shift in fluorescence in the presence of zinc; however, a decrease in relaxation rate was observed. Consequently, the ability of the well-known zinc chelator, BPEN, was assessed for relaxivity response when conjugated to the gadolinium chelate. The success of this probe [GdL2], lead to the inclusion of the same zinc-probing moiety alongside a longer wavelength emitting fluorophore, rhodamine [GdL3], to arrive at the final iteration of these first generation dual-modal zinc-sensing probes. The compounds give insight into the design protocols required for the successful imaging of zinc ions

Cultivating nutrition

"Over the past decade, donor-funded policies and programs designed to address undernutrition in the Global South have shifted away from agriculture-based strategies toward nutrient supplementation and food fortification programs. Given the potential benefits resulting from agriculture-based nutrition interventions, this study uses Q methodology to explore the views of a range of stakeholders from both developed and developing countries on the value of—and constraints related to—gender-sensitive, nutrition-oriented agricultural projects. The three distinct viewpoints that emerge from this exercise all support the use of agricultural strategies to improve nutrition and underline the importance of gender-sensitive approaches. The viewpoints differ, however, on the relative importance of nutrition education, the strategic use of nutrient supplementation and food fortification, and the degree to which agriculture-based approaches have an impact on nutrition. The findings indicate that there is common ground among a range of stakeholders—donors, researchers, policymakers, and program practitioners—on the benefits of agriculture and gender-sensitive strategies to improve nutrition. These areas of agreement can serve as a foundation for forging an effective integrative strategy to improve nutrition that includes gender-sensitive agricultural approaches." Authors' AbstractNutrition ,malnutrition ,Agriculture ,stakeholders ,Gender ,

Cultivating nutrition

"Over the past decade, donor-funded policies and programs designed to address undernutrition in the Global South have shifted away from agriculture-based strategies toward nutrient supplementation and food fortification programs. Given the potential benefits resulting from agriculture-based nutrition interventions, this study uses Q methodology to explore the views of a range of stakeholders from both developed and developing countries on the value of—and constraints related to—gender-sensitive, nutrition-oriented agricultural projects. The three distinct viewpoints that emerge from this exercise all support the use of agricultural strategies to improve nutrition and underline the importance of gender-sensitive approaches. The viewpoints differ, however, on the relative importance of nutrition education, the strategic use of nutrient supplementation and food fortification, and the degree to which agriculture-based approaches have an impact on nutrition. The findings indicate that there is common ground among a range of stakeholders—donors, researchers, policymakers, and program practitioners—on the benefits of agriculture and gender-sensitive strategies to improve nutrition. These areas of agreement can serve as a foundation for forging an effective integrative strategy to improve nutrition that includes gender-sensitive agricultural approaches." Authors' AbstractNutrition ,malnutrition ,Agriculture ,stakeholders ,Gender ,

Lanthanide(III) complexes of rhodamine-DO3A conjugates as agents for dual-modal imaging

Two novel dual-modal MRI/optical probes based on a rhodamine-DO3A conjugate have been prepared. The bis aqua-Gd(III) complex Gd.L1 and mono aqua-Gd(III) complex Gd.L2 behave as dual-modal imaging probes (r1 = 8.5 and 3.8 mM-1s-1 for Gd.L1 and Gd.L2 respectively; λex = 560 nm and λem = 580 nm for both complexes). The rhodamine fragment is pH sensitive and upon lowering of pH an increase in fluorescence intensity is observed as the spirolactam ring opens to give the highly fluorescent form of the molecule. The ligands are bimodal when coordinated to Tb(III) ions, inducing fluorescence from both the lanthanide center and the rhodamine fluorophore, on two independent time-frames. Confocal imaging experiments were carried out to establish the localization of Gd.L2 in HEK cells. Co-localisation with MitoTracker® Green confirmed that Gd.L2 compartmentalizes in the mitochondria. Gd.L2 was also evaluated as an MRI probe for imaging tumors in BALB/c nude mice bearing M21 xenografts. A 36.5% decrease in T1 within the tumor was observed 30 minutes post injection showing that Gd.L2 is preferentially up taken in the tumor. Gd.L2 is the first small molecule MR/fluorescent dual-modal imaging agent to display an off-on pH switch upon its preferential uptake within the more acidic micro-environment of tumor cells

⁹⁹ᵐTc SPECT imaging agent based on cFLFLFK for the detection of FPR1 in inflammation

Non-invasive imaging of the inflammatory process can provide a great deal of insight into a wide variety of diseases states, aiding diagnosis, evaluation and effective targeted treatment. During inflammation, blood borne leukocytes are recruited, through a series of activation and adhesion steps, to the site of injury or infection where they migrate across the blood vessel wall into the tissue. Thus, tracking leukocyte recruitment and accumulation provides a dynamic and localised read out of inflammatory events. Current leukocyte imaging techniques require ex vivo labelling of patient blood, involving laborious processing and potential risks to both patient and laboratory staff. Utilising high affinity ligands for leukocyte specific receptors may allow for injectable tracers that label leukocytes in situ, omitting potentially hazardous ex vivo handling. Formyl peptide receptors (FPRs) are a group of G-protein coupled receptors involved in the chemotaxis and inflammatory functioning of leukocytes. Highly expressed on leukocytes, and up regulated during inflammation, these receptors provide a potential target for imaging inflammatory events. Herein we present the synthesis and initial in vitro testing of a potential Single Photon Emission Computed Tomography (SPECT) leukocyte tracer. The FPR1 antagonist cFLFLFK-NH₂, which displays high affinity with little physiological effect, has been linked via a PEG motif to a ⁹⁹ᵐTc chelate. This tracer shows in vitro binding to human embryonic kidney cells expressing the FPR1 receptor, and functional in vitro tests reveal cFLFLFK-NH₂ compounds to have no effect on inflammatory cell functioning. Overall, these data show that ⁹⁹ᵐTc.cFLFLFK-NH₂ may be a useful tool for non-invasive imaging of leukocyte accumulation in inflammatory disease states

Attitudes to ageing : a systematic review of attitudes to ageing and mental health, and a cross-sectional analysis of attitudes to ageing and quality of life in older adults

This thesis portfolio examines attitudes to ageing in older adults, and explores the impact that attitudes to ageing have on mental health status and quality of life. Attitudes to ageing are becoming more widely measured in older adults, particularly with the ageing population but also due the recent development of the Attitudes to Ageing Questionnaire. There is growing evidence to suggest a relationship between attitudes to ageing and mental health status in older adults. However, no study has explored the association between attitudes to ageing and quality of life in older adults, incorporating the Attitudes to Ageing Questionnaire and the World Health Organisation Quality of Life measures. Firstly a systematic search of studies exploring the relationship between attitudes to ageing and mental health in older adults (≥55 years) was undertaken. All potentially relevant studies were screened against inclusion and exclusion criteria. Variables related to attitudes to ageing, ageism, age stereotypes, depression and anxiety were considered in this review. Twelve papers met inclusion criteria for the systematic review. The setting, culture and measures incorporated varied across the studies. A negative attitude to ageing was associated with poorer mental health status in older adults across all 12 studies. The second part of this portfolio was an international cross-sectional analysis of attitudes to ageing and quality of life in older adults (≥57 years). Correlation and regression analyses explored the relationship between attitudes to ageing and QOL and investigated the impact of socio-demographic variables, depression and attitudes to ageing on two quality of life measures. The two constructs were positively related; a more positive attitude to ageing was associated with a better quality of life. Further, positive attitudes to ageing was a significant predictor of a better QOL. The sample was then divided into two age groups (57-79 years and 80+ years) and attitudes to ageing and quality of life ratings were compared. Results revealed more negative ratings in attitudes to ageing and quality of life in the over 80 year old age group. Correlation and regression analyses were then explored across both age groups. More positive attitudes to ageing was a significant predictor of better quality of life across both age groups. Overall, the two studies in this thesis portfolio highlight the need to better recognise and target older adults’ negative attitudes to ageing. Appropriate psychological interventions could be provided to challenge negative attitudes and promote attitude change in an attempt to improve mental health difficulties and quality of life in older adults. Continued use of the Attitudes to Ageing Questionnaire and quality of life psychometric measures in clinical practice and research is encouraged

THE EFFECTS OF TEACHERS’ ATTITUDES, BEHAVIORS, AND SKILLS ON CULTURALLY RESPONSIVE TEACHING AND THE MULTICULTURAL CURRICULUM: AN ACTION RESEARCH STUDY OF A CULTURALLY RESPONSIVE TEACHING PROFESSIONAL DEVELOPMENT GUIDE IN AN ELEMENTARY CLASSROOM

Today’s students are more ethnically diverse than ever, but are taught by teachers who are a majority white. In response to this cultural mismatch, teachers are adopting innovative practices such as culturally responsive teaching. This qualitative research study utilized participatory action research to examine the perceived culturally responsive attitudes, behaviors, and skills of teachers. Next, this research study examined how teachers operationalized culturally responsive teaching and how the culturally responsive teaching professional development guide informed teachers of their culturally responsive practice. Specifically, through three observations of each participant using the theoretical culturally responsive teaching professional development guide individual participant interviews, culturally responsive attitudes, behaviors, and skills were observed and discussed. The theoretical culturally responsive teaching professional development guide was developed from a synthesis of scholarly culturally responsive literature and research. During two focus group meetings the participants revised the theoretical culturally responsive teaching professional development guide into a teacher-friendly culturally responsive teaching tool. Then a semantic analysis was conducted to ensure the participants’ revisions maintained the integrity of the theoretical culturally responsive teaching professional development guide. Resulting from this research study are findings that teachers’ voices should be utilized to create culturally responsive teaching tools, and there is a need for culturally responsive professional development for teachers and administrators

Maternal fructose and/or salt intake and reproductive outcome in the rat: effects on growth, fertility, sex ratio, and birth order

Maternal diet can significantly skew the secondary sex ratio away from the expected value of 0.5 (proportion males), but the details of how diet may do this are unclear. Here, we altered dietary levels of salt (4% salt in the feed) and/or fructose (10% in the drinking water) of pregnant rats to model potential effects that consumption of a "Western diet" might have on maternofetal growth, development, and sex ratio. We demonstrate that excess fructose consumption before and during pregnancy lead to a marked skew in the secondary sex ratio (proportion of males, 0.60; P < 0.006). The effect was not mediated by selective developmental arrest of female embryos or influenced by fetal position in the uterine horn or sex-specific effects on sperm motility, suggesting a direct effect of glycolyzable monosaccharide on the maternal ovary and/or ovulated oocyte. Furthermore, combined excess maternal consumption of salt and fructose-sweetened beverage significantly reduced fertility, reflected as a 50% reduction in preimplantation and term litter size. In addition, we also noted birth order effects in the rat, with sequential implantation sites tending to be occupied by the same sex

The cognitive footprint of medication: a review of cognitive assessments in clinical trials

What is known and objective: Polypharmacy is common, and many medications have cognitive side effects. Such effects can be transient and subside when the drug in question is discontinued or can be long-lasting with effects present for years afterwards. Although formal assessment of cognition is feasible and often undertaken in neuropsychiatric trials, these effects are usually neglected in the evaluation of any non-neuropsychiatric health intervention. Medication effects can be assessed within a cognitive footprint framework, to account for the magnitude and the duration of cognitive side effects, with some likely to have a greater and more lasting effect than others. Comment: Adverse event reporting suggests that many medications may be indirectly associated with cognitive effects, for example due to headaches, somnolence and ‘dizziness’; however, inferring causation from adverse event reporting can be problematic. In order to better understand the impact of investigational drug and concomitant medications effect on cognition, it would be essential to ensure cognition is prioritized in drug development evaluation. It is suggested that simple instruments that can be easily incorporated into existing trial designs are used to assess the cognitive footprint of medication. What is new and conclusion: We present an overview of existing measures of cognition that can be integrated into drug trials in order to provide a cognitive footprint. Like quality of life testing, such tests should be administered as a standard throughout the key assessment stages of the design of the trial to ensure that any effects on this equally important outcome are also documented. Furthermore, employing routine cognition testing may also enable researchers to identify unanticipated beneficial and non-beneficial effects on cognition. Provision of such a cognitive footprint profile of drugs may provide the necessary evidence to enable decision-makers to make informed decisions on risk-benefit analysis that can subsequently make trade-offs between different drug regimens