The efficacy and mechanism of peripheral opioids in paediatric inflammatory pain.

Background: The management of pain in children is a common but difficult symptom to treat and the use of strong analgesics is often limited, for a variety of reasons, including fear of inducing side effects. Morphine is normally considered to be a centrally acting analgesic but recently, the beneficial effects of peripheral opioids have been demonstrated in adults for a number of painful inflammatory conditions. When administered in this non invasive way, opioids provide analgesia without achieving significant plasma concentrations and therefore it can be assumed that many of the adverse effects associated with oral or systemic opioids are avoided. Methods: A) The first part of the thesis describes the mechanism of action of peripheral opioids through development and particularly their effect during inflammation. This work was conducted using different ages of Sprague Dawley rat pups and skin inflammation was induced using carageenan. B) The second section is a description of a double-blinded, randomised-controlled, placebo-controlled trial with crossover design, to assess the efficacy of peripheral opioids in paediatric inflammatory pain. This was conducted in children with a diagnosis of Epidermolysis Bullosa (EB), as a model for acute and chronic inflammatory pain Results:. The laboratory study demonstrates that mu opioid receptor (MOR) expression is up regulated in neonatal plantar skin and significantly up regulated in neonatal lumbar dorsal root ganglion (DRG) four hours post hind paw inflammation, MOR protein levels in the rat hind paw plantar skin are significantly up regulated post-natally, and MOR protein levels are significantly up regulated in both neonatal and young adult plantar skin four hours post hind paw inflammation. Clinically, pain reduction was most significant with background pain Conclusion: The developmental regulation of peripheral MOR both in naive and inflamed cutaneous tissue may have implications for the use of topically / peripherally applied opioids in infants and children. "I, Gillian Watterson confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis"

Clearcutting and shearing on a saline soil in East Texas: Impacts on soil physical properties

Soil samples, or in-situ measurements, were collected at seven occasions and at six depths to study the Impact of three forest conditions on soil physical properties of a saline soil in E. Texas. Soil bulk density, CW. of silt plus clay at the surface horizons, soil water content, soil water retention, and depth to groundwater Increased following intensive site preparation. Differences in these properties between the commercial clearcuttlng and undisturbed forest were small. The wet soil conditions created in the Intensive preparation site are not likely to be responsible for the failure of artificial pine regeneration. In areas where site preparation may cause standing water on the surface, all plants and stumps should be left intact after marketable timber is removed

Management and pest management considerations on droughty soils: four year results

Four year survival of pines on droughty (Typic Quartzips~mments) soils was best for longleaf pine and Terr-Sorb -treated loblolly pine. Pest considerations include town ants and Nantucket pine tip moths on loblolly pine. Untreated loblolly pine had reduced leader and total height growth anH increased tip moth infestations, compared to Terra-Sorb and clay-slurry treated loblolly pine. Soil texture averaged less than eight percent silt and clay combined in the treatment areas

Forestry Bulletin No. 25: Silviculture of Southern Bottomland Hardwoods

The potential of southern bottomland hardwood types is clear, for they, along with the cypress, occupy about 37 million acres and compromise more than half of the hardwood stumpage in the south.https://scholarworks.sfasu.edu/forestrybulletins/1021/thumbnail.jp

Mr. and Mrs. G. T. Watterson to The Chairman Board of Trustees Ole Miss, 19 September 1962

The Wattersons urge the board to support Governor Barnett.https://egrove.olemiss.edu/west_union_um/1018/thumbnail.jp

Statistics of selectively neutral genetic variation

Random models of evolution are instrumental in extracting rates of microscopic evolutionary mechanisms from empirical observations on genetic variation in genome sequences. In this context it is necessary to know the statistical properties of empirical observables (such as the local homozygosity for instance). Previous work relies on numerical results or assumes Gaussian approximations for the corresponding distributions. In this paper we give an analytical derivation of the statistical properties of the local homozygosity and other empirical observables assuming selective neutrality. We find that such distributions can be very non-Gaussian.Comment: 4 pages, 4 figure

Differential transactivation of sphingosine-1-phosphate receptors modulates NGF-induced neurite extension

The process of neurite extension after activation of the TrkA tyrosine kinase receptor by nerve growth factor (NGF) involves complex signaling pathways. Stimulation of sphingosine kinase 1 (SphK1), the enzyme that phosphorylates sphingosine to form sphingosine-1-phosphate (S1P), is part of the functional TrkA signaling repertoire. In this paper, we report that in PC12 cells and dorsal root ganglion neurons, NGF translocates SphK1 to the plasma membrane and differentially activates the S1P receptors S1P1 and S1P2 in a SphK1-dependent manner, as determined with specific inhibitors and small interfering RNA targeted to SphK1. NGF-induced neurite extension was suppressed by down-regulation of S1P1 expression with antisense RNA. Conversely, when overexpressed in PC12 cells, transactivation of S1P1 by NGF markedly enhanced neurite extension and stimulation of the small GTPase Rac, important for the cytoskeletal changes required for neurite extension. Concomitantly, differentiation down-regulated expression of S1P2 whose activation would stimulate Rho and inhibit neurite extension. Thus, differential transactivation of S1P receptors by NGF regulates antagonistic signaling pathways that modulate neurite extension

Reversal Distances for Strings with Few Blocks or Small Alphabets

International audienceWe study the String Reversal Distance problem, an extension of the well-known Sorting by Reversals problem. String Reversal Distance takes two strings S and T as input, and asks for a minimum number of reversals to obtain T from S. We consider four variants: String Reversal Distance, String Prefix Reversal Distance (in which any reversal must include the first letter of the string), and the signed variants of these problems, namely Signed String Reversal Distance and Signed String Prefix Reversal Distance. We study algorithmic properties of these four problems, in connection with two parameters of the input strings: the number of blocks they contain (a block being maximal substring such that all letters in the substring are equal), and the alphabet size Σ. For instance, we show that Signed String Reversal Distance and Signed String Prefix Reversal Distance are NP-hard even if the input strings have only one letter

Risk Factors for Leg Ulceration in People Who Inject Drugs: A Cross-Sectional Study

Aims and ObjectivesThe aim of this study was to assess, for the first time in a hard-to-reach population, the risk factors for leg ulceration among PWID, with the objective of making improvements to prevention and care. Background An estimated 4.8 million people globally inject drugs with potential for injecting related harm. Skin and vein damage associated with drug injecting is increasing. Leg ulceration is a chronic condition which in the UK has a prevalence of 15% amongst people who have injected drugs (PWID) compared to 1% in the general population. Glasgow has the highest rate of problematic drug use in Scotland with approximately 13,900 individuals, about 50% of whom are thought to inject. However, the reasons for high prevalence of leg ulceration among PWID are unknown. To support improvements in prevention and care, the dearth of evidence around risk factors for leg ulceration in PWID needs to be addressed.Design A cross-sectional survey of 200 current and former injectors recruited from drugs services in Glasgow, Scotland, to measure skin problems, leg ulceration and injecting habits is reported following STROBE guidelines. Logistic regression modelling examined whether demographics and injecting habits predicted leg ulceration. Results: The likelihood of leg ulceration was increased for those who injected in the groin and the leg. Additionally, injecting in the groin and leg were associated with having a DVT.Conclusion The primary risk factors for leg ulceration in PWID are injecting in the groin and the legs and these are clinically linked to deep vein thrombosis. Injecting into the femoral vein is increasingly common practice for PWID and healthcare practitioners should advise injectors of the increased risk of leg ulceration and DVT and discourage injecting into these areas