Mechanisms underlying leptininduced cardioprotection

BACKGROUND: The tissue damage resulting from myocardial ischaemia/reperfusion (I/R) leads to a large proportion of the deaths in the developed world. Even if patients survive a myocardial infarction, I/R injury is associated with decreased cardiac function and a higher incidence of morbidity, and consequently, a reduced quality of life. Leptin is a cytokine produced by white adipose tissue that has been shown to activate the PI3K-Akt and p44/42 MAPK signalling cascades and protect the murine myocardium. The studies described in this thesis focused on the molecular mechanisms underlying leptin-induced cardioprotection with particular reference to cell signalling. METHODS & RESULTS: Using an isolated rat heart model of I/R injury, it was confirmed that leptin given at reperfusion protects the myocardium. This protection was abolished by the administration of specific blockers of the survival kinases PI3K, JAK and p44/42 MAPK. The time-points at which maximal phosphorylation of Akt, p44/42 MAPK and STAT3 occur in response to leptin given at reperfusion were identified. The key role played by the leptin receptor in leptin-induced cardioprotection was established by employing the Zucker obese rat (fa/fa), which has a mutation in the leptin receptor, and its Zucker lean (fa/+) counterpart that possesses a functional OB-R. It was found that the Zucker fatty rats were non-responsive to leptin-induced cardioprotection. Furthermore, it was shown that whilst leptin inhibited mitochondrial permeability transition pore (MPTP) opening in cardiomyocytes from Wistar and Zucker lean rats, MPTP opening in OB-R deficient Zucker fatty rats was unaffected. Finally, leptin was shown to protect against ischaemia-reperfusion injury in an in vivo rat model of I/R injury. CONCLUSION: The present study has yielded information concerning the mechanisms underlying the cardioprotective actions of leptin; including the importance of the OB-R. Extending the studies employing in vivo models of I/R injury will assist in establishing the potential of leptin as a therapeutic agent

An assessment of the antibacterial activity in larval excretion/secretion of four species of insects recorded in association with corpses, using Lucilia sericata Meigen as the marker species

The relative antibacterial activities of excretion/secretion (ES) from two carrion-feeding insects, Calliphora vicina Robineau-Desvoidy and Dermestes maculatus DeGeer, and a detritivore, Tenebrio molitor Linnaeus, were compared to that of Lucilia sericata Meigen, a species with ES of known antibacterial capacity, in order to explore the antimicrobial potential of other carrion and detritivore species. Viable counts were used to assess time-kill of ES against five bacterial species, Staphylococcus aureus, Escherichia coli, Bacillus cereus, Pseudomonas aeruginosa and Proteus mirabilis. Antibacterial activity was recorded in all four insect species although T. molitor and D. maculatus were the most effective in controlling growth of P. mirabilis. The blowflies were more effective in controlling a wider range of both Gram-positive and Gram-negative bacteria. The larval ES from all species was shown to reduce bacterial growth rate although differences in antibacterial spectrum were noted and the degree of potency varied between the four species. These differences may be explained ecologically by the different colonisation times of each insect species on the corpse. Overall, this study demonstrates that research into other carrion-feeding insect species has potential to provide an increased source of antimicrobial chemicals to broaden the range of bacterial species beyond that currently controlled using L. sericata

Double burden of malnutrition: evidence from a selected Nigerian population

Open Access JournalIndices reflecting the double burden of malnutrition in sub-Saharan Africa are increasing. Evidence to support this claim in households of Africa’s most populous country—Nigeria—is scant. This study, therefore, presents results from a study of mother-child pairs sampled from Akwa Ibom State in the southern region of Nigeria. Anthropometric measures for 660 mother-child pairs were collected according to standard procedures. Indices were expressed as the standard deviation of units from the median for the reference group. Chi-square analysis was used to test significant differences in proportion, and was taken as significant. A total of 37.4% of the children were stunted out of which 19.8% were moderately stunted, and 17.6% were severely stunted. Prevalence of wasting was 13.1%, 6.2% were moderately wasted, and 6.9% were severely wasted. Mean maternal body mass index was (23.54 ± 4.60) kgm2. 9.0% were underweight mothers, 23.2% were overweight, and 9.3% were obese. The co-existence of undernutrition among children and overnutrition in women of child-bearing age is prevalent in this population. We recommend that more effort be placed on active nutrition surveillance to ascertain malnutrition prevalence and periodically reassess priority challenges

Detection of Atmospheric Cherenkov Radiation Using Solar Heliostat Mirrors

The gamma-ray energy region between 20 and 250 GeV is largely unexplored. Ground-based atmospheric Cherenkov detectors offer a possible way to explore this region, but large Cherenkov photon collection areas are needed to achieve low energy thresholds. This paper discusses the development of a Cherenkov detector using the heliostat mirrors of a solar power plant as the primary collector. As part of this development, we built a prototype detector consisting of four heliostat mirrors and used it to record atmospheric Cherenkov radiation produced in extensive air showers created by cosmic ray particles.Comment: 16 latex pages, 8 postscript figures, uses psfig.sty, to be published in Astroparticle Physic

Very high energy observations of the BL Lac objects 3C 66A and OJ 287

Using the Solar Tower Atmospheric Cherenkov Effect Experiment (STACEE), we have observed the BL Lac objects 3C 66A and OJ 287. These are members of the class of low-frequency-peaked BL Lac objects (LBLs) and are two of the three LBLs predicted by Costamante and Ghisellini to be potential sources of very high energy (>100 GeV) gamma-ray emission. The third candidate, BL Lacertae, has recently been detected by the MAGIC collaboration. Our observations have not produced detections; we calculate a 99% CL upper limit of flux from 3C 66A of 0.15 Crab flux units and from OJ 287 our limit is 0.52 Crab. These limits assume a Crab-like energy spectrum with an effective energy threshold of 185 GeV.Comment: 24 pages, 15 figures, Accepted for publication in Astroparticle Physic

Tidal friction in close-in satellites and exoplanets. The Darwin theory re-visited

This report is a review of Darwin's classical theory of bodily tides in which we present the analytical expressions for the orbital and rotational evolution of the bodies and for the energy dissipation rates due to their tidal interaction. General formulas are given which do not depend on any assumption linking the tidal lags to the frequencies of the corresponding tidal waves (except that equal frequency harmonics are assumed to span equal lags). Emphasis is given to the cases of companions having reached one of the two possible final states: (1) the super-synchronous stationary rotation resulting from the vanishing of the average tidal torque; (2) the capture into a 1:1 spin-orbit resonance (true synchronization). In these cases, the energy dissipation is controlled by the tidal harmonic with period equal to the orbital period (instead of the semi-diurnal tide) and the singularity due to the vanishing of the geometric phase lag does not exist. It is also shown that the true synchronization with non-zero eccentricity is only possible if an extra torque exists opposite to the tidal torque. The theory is developed assuming that this additional torque is produced by an equatorial permanent asymmetry in the companion. The results are model-dependent and the theory is developed only to the second degree in eccentricity and inclination (obliquity). It can easily be extended to higher orders, but formal accuracy will not be a real improvement as long as the physics of the processes leading to tidal lags is not better known.Comment: 30 pages, 7 figures, corrected typo

Interprofessional education and practice guide: designing ethics-orientated interprofessional education for health and social care students

Health and social care professionals are required to work together to deliver person-centered care. Professionals therefore find themselves making decisions within multidisciplinary teams. For educators, there has been a call to bring students from differing professions together to learn to enable more effective teamwork, interprofessional communication, and collaborative practice. This multidisciplinary working is complicated by the increasingly complex nature of ethical dilemmas that health and social care professionals face. It is therefore widely recognized that the teaching and learning of ethics within health and social care courses is valuable. In this paper, we briefly make the case in support of teaching and learning health and social care ethics through the medium of interprofessional education (IPE). The purpose of this paper is to provide guidance to educators intending to design ethics-orientated IPE for health and social care students. The guidance is based on the ongoing experiences of designing and implementing ethics-orientated IPE across five departments within two universities located in the North of England over a five-year period. Descriptions of the ethics-orientated IPE activities are included in the guide, along with key resources recommended

A self-optimised approach to synthesising DEHiBA for advanced nuclear reprocessing, exploiting the power of machine-learning

In an effort to advance the development of hydrometallurgical reprocessing of used nuclear fuel across the globe, this work sets out to explore and identify an optimised, cost effective pathway to synthesise the ligand DEHiBA (N,N-di-(2-ethylhexyl)isobutyramide). Currently, very few chemical suppliers stock and distribute this specialist ligand, designed for selective uranium chelation and extraction from nuclear fuel. The current high cost of DEHiBA therefore restricts access to essential large-scale testing of this promising ligand designed to advance nuclear reprocessing. This work utilises an automated flow reactor platform for the efficient optimisation of four synthetic routes to DEHiBA. These optimisations focus on optimising cost, reagent efficiency, yield, and productivity target functions by exploiting the power of machine-learning algorithms for rapid process development. Ultimately, we have identified an efficient and cost-effective solvent-free route to DEHiBA from isobutyric anhydride and di-2-ethylhexylamine for 99%, at a purity of 76%, and a process mass intensity of 1.29 g g−1, whilst alternative conditions demonstrated productivities >75 kg L−1 h−1, all whilst maintaining a high level of process control with outlet temperatures not exceeding 35 °C