Liposomal delivery of glucoCEST and 2-deoxyglucoCEST reagents

Chemical Exchange Saturation Transfer (CEST) is an emerging MRI contrast mechanism that detects the presence of exchangeable protons, enabling natural sugars such as glucose to be used as contrast agents (glucoCEST). GlucoCEST offers a cheaper, safer and higher resolution alternative for the visualisation and staging of tumors than the current standard method, FDG-PET. Section 2 demonstrates that high concentrations of glucose can be encapsulated inside 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (DPPC) liposomes to produce vesicular CEST contrast agents, from which the generated signal was concentration, temperature and pH dependent. The use of paramagnetic metal ions to create paraCEST agents can result in superior imaging sensitivity compared to diaCEST agents. Thus, Section 3 describes work carried out on the incorporation of lanthanide ions into liposomal glucoCEST reagents in an attempt to produce paraCEST signals. The results were largely unsuccessful due to the finding that co-solvation of glucose and lanthanide-DOTA complexes in water does not cause an significantly enhanced shift difference between the hydroxyl proton resonances and the water resonance. The in vivo CEST signal arising from the glucose analogue, 2-DG, is enhanced and prolonged in comparison to glucose due to its poor metabolism. Additionally, 2-DG is a glycolytic inhibitor and is thereby cytotoxic to cancer cells. Section 4 reports the encapsulation of 2-DG inside DPPC liposomes and the characterisation of both lipoglucose and lipo-2-DG agents when exposed to a number of variables: 0-20% PBS buffer was found to have a negligiable effect on CEST signal generation; lipo-2-DG and lipoglucose CEST signal gradually increased across the temperature range 25-37 °C; monosaccharide encapsulating DSPC liposomes were found to generate inferior signal to analogous DPPC liposomes; and smaller 2-DG liposomes appeared to give slightly greater CEST signal but this was offset by the higher internal volume and encapsulation efficiency of larger liposomes, if not corrected for. The advantages of liposomal encapsulation of monosaccharides include prolonged in vivo circulation and the potential for both passive and active tumor targeting. In Section 5, an active EGFR-targeting strategy was constructed which included the synthesis of EGFR-targeting peptides, two novel maleimide lipids and several novel short-chain PEG lipids, with the hydroxyl-capped analogue proving most promising. In addition, 2-DG was found to be a poor radiosensitiser in CRC cell lines as well as in a lung cancer cell line when a successful literature procedure was followed

Examining evidence for behavioural mimicry of parental eating by adolescent females.:An observational study

Behavioural mimicry is a potential mechanism explaining why adolescents appear to be influenced by their parents' eating behaviour. In the current study we examined whether there is evidence that adolescent females mimic their parents when eating. Videos of thirty-eight parent and female adolescent dyads eating a lunchtime meal together were examined. We tested whether a parent placing a food item into their mouth was associated with an increased likelihood that their adolescent child would place any food item (non-specific mimicry) or the same item (specific mimicry) in their mouth at three different time frames, namely, during the same second or within the next fifteen seconds (+15), five seconds (+5) or two second (+2) period. Parents and adolescents' overall food intake was positively correlated, whereby a parent eating a larger amount of food was associated with the adolescent eating a larger meal. Across all of the three time frames adolescents were more likely to place a food item in their mouth if their parent had recently placed that same food item in their mouth (specific food item mimicry); however, there was no evidence of non-specific mimicry. This observational study suggests that when eating in a social context there is evidence that adolescent females may mimic their parental eating behaviour, selecting and eating more of a food item if their parent has just started to eat that food

Co-creating museum robots with people that are autistic and/or have learning disabilities

The integration of robots into everyday life is an increasingly common and mundane phenomena. Understanding how people regard and interact with these robots is a rapidly growing area of study, however, there is limited consideration of the attitudes of people that are autistic and/or have learning disabilities. This poster showcases preliminary findings from two co-creative workshops run with the input and guidance of these communities and their caregivers. Early insights from these workshops offer twofold contributions; first, the outline of a framework for embedding people that are autistic and/or have learning disabilities within research meaningful to them through reflection and iteration. Second, an overview of their attitudes towards robots, with specific insights into robots used in museums. Attitudes are broadly positive, although risk perception is seen to affect trust and therefore contextual engagement

Trichain cationic lipids: the potential of their lipoplexes for gene delivery

Lipoplexes (LDs) have been prepared from DNA and positively charged vesicles composed of the helper lipid, dioleoyl l-α-phosphatidylethanolamine (DOPE) and either a dichain (DC) oxyethylated cationic lipid or their corresponding novel trichain (TC) counterpart. This is the first study using the TC lipids for the preparation of LDs and their application. Here the results of biophysical experiments characterising the LDs have been correlated with the in vitro transfection activity of the complexes. Photon correlation spectroscopy, zeta potential measurements and transmission electron microscopy studies indicated that, regardless of the presence of a third chain, there were little differences between the size and charge of the TC and DC containing LDs. Small angle neutron scattering studies established however that there was a significant conformational re-arrangement of the lipid bilayer when in the form of a LD complex as opposed to the parent vesicles. This re-arrangement was particularly noticeable in LDs containing TC lipids possessing a third chain of C12 or a longer chain. These results suggested that the presence of a third hydrophobic chain had a significant effect on lipid packing in the presence of DNA. Picogreen fluorescence and gel electrophoresis studies showed that the TC lipids containing a third acyl chain of at least C12 were most effective at complexing DNA while the TC lipids containing an octanoyl chain and the DC lipids were least effective. The transfection efficacies of the TC lipids in the form of LDs were found to be higher than for the DC analogues, particularly when the third acyl chain was an octanoyl or oleoyl moeity. Little or no increase in transfection efficiency was observed when the third chain was a methyl, acetyl or dodecanoyl group. The large enhancement in transfection performance of the TC lipids can be attributed to their ability to complex their DNA payload. These studies indicate that presence of a medium or long third acyl chain was especially beneficial for transfection

Interventions to improve health and the determinants of health among sex workers in high-income countries: a systematic review

Many sex worker populations face high morbidity and mortality, but data are scarce on interventions to improve their health. We did a systematic review of health and social interventions to improve the health and wider determinants of health among adult sex workers in high-income countries. We searched MEDLINE, Embase, PsycINFO, CINAHL, the Cochrane Library, Web of Science, EthOS, OpenGrey, and Social Care Online, as well as the Global Network of Sex Work Projects and the Sex Work Research Hub for studies published between Jan 1, 2005 and Dec 16, 2021 (PROSPERO CRD42019158674). Quantitative studies reporting disaggregated data for sex workers were included and no comparators were specified. We assessed rigour using the Quality Assessment Tool for Quantitative Studies. We summarised studies using vote counting and a narrative synthesis. 20 studies were included. Most reported findings exclusively for female sex workers (n=17) and street-based sex workers (n=11). Intervention components were divided into education and empowerment (n=14), drug treatment (n=4), sexual and reproductive health care (n=7), other health care (n=5), and welfare (n=5). Interventions affected a range of mental health, physical health, and health behaviour outcomes. Multicomponent interventions and interventions that were focused on education and empowerment were of benefit. Interventions that used peer design and peer delivery were effective. An outreach or drop-in component might be beneficial in some contexts. Sex workers who were new to working in an area faced greater challenges accessing services. Data were scarce for male, transgender, and indoor-based sex workers. Co-designed and co-delivered interventions that are either multicomponent or focus on education and empowerment are likely to be effective. Policy makers and health-care providers should improve access to services for all genders of sex workers and those new to an area. Future research should develop interventions for a greater diversity of sex worker populations and for wider health and social needs