Cost-Effective Use of Silver Dressings for the Treatment of Hard-to-Heal Chronic Venous Leg Ulcers

Aim To estimate the cost-effectiveness of silver dressings using a health economic model based on time-to-wound-healing in hard-to-heal chronic venous leg ulcers (VLUs). Background Chronic venous ulceration affects 1–3% of the adult population and typically has a protracted course of healing, resulting in considerable costs to the healthcare system. The pathogenesis of VLUs includes excessive and prolonged inflammation which is often related to critical colonisation and early infection. The use of silver dressings to control this bioburden and improve wound healing rates remains controversial. Methods A decision tree was constructed to evaluate the cost-effectiveness of treatment with silver compared with non-silver dressings for four weeks in a primary care setting. The outcomes: ‘Healed ulcer’, ‘Healing ulcer’ or ‘No improvement’ were developed, reflecting the relative reduction in ulcer area from baseline to four weeks of treatment. A data set from a recent meta-analysis, based on four RCTs, was applied to the model. Results Treatment with silver dressings for an initial four weeks was found to give a total cost saving (£141.57) compared with treatment with non-silver dressings. In addition, patients treated with silver dressings had a faster wound closure compared with those who had been treated with non-silver dressings. Conclusion The use of silver dressings improves healing time and can lead to overall cost savings. These results can be used to guide healthcare decision makers in evaluating the economic aspects of treatment with silver dressings in hard-to-heal chronic VLUs

Fluids in cosmology

We review the role of fluids in cosmology by first introducing them in General Relativity and then by applying them to a FRW Universe's model. We describe how relativistic and non-relativistic components evolve in the background dynamics. We also introduce scalar fields to show that they are able to yield an inflationary dynamics at very early times (inflation) and late times (quintessence). Then, we proceed to study the thermodynamical properties of the fluids and, lastly, its perturbed kinematics. We make emphasis in the constrictions of parameters by recent cosmological probes.Comment: 34 pages, 4 figures, version accepted as invited review to the book "Computational and Experimental Fluid Mechanics with Applications to Physics, Engineering and the Environment". Version 2: typos corrected and references expande

A Booster Vaccine Expressing a Latency-Associated Antigen Augments BCG Induced Immunity and Confers Enhanced Protection against Tuberculosis

BACKGROUND: In spite of a consistent protection against tuberculosis (TB) in children, Mycobacterium bovis Bacille Calmette-Guerin (BCG) fails to provide adequate protection against the disease in adults as well as against reactivation of latent infections or exogenous reinfections. It has been speculated that failure to generate adequate memory T cell response, elicitation of inadequate immune response against latency-associated antigens and inability to impart long-term immunity against M. tuberculosis infections are some of the key factors responsible for the limited efficiency of BCG in controlling TB. METHODS/PRINCIPAL FINDINGS: In this study, we evaluated the ability of a DNA vaccine expressing α-crystallin--a key latency antigen of M. tuberculosis to boost the BCG induced immunity. 'BCG prime-DNA boost' regimen (B/D) confers robust protection in guinea pigs along with a reduced pathology in comparison to BCG vaccination (1.37 log(10) and 1.96 log(10) fewer bacilli in lungs and spleen, respectively; p<0.01). In addition, B/D regimen also confers enhanced protection in mice. Further, we show that B/D immunization in mice results in a heightened frequency of PPD and antigen specific multi-functional CD4 T cells (3(+)) simultaneously producing interferon (IFN)γ, tumor necrosis factor (TNF)α and interleukin (IL)2. CONCLUSIONS/SIGNIFICANCE: These results clearly indicate the superiority of α-crystallin based B/D regimen over BCG. Our study, also demonstrates that protection against TB is predictable by an increased frequency of 3(+) Th1 cells with superior effector functions. We anticipate that this study would significantly contribute towards the development of superior booster vaccines for BCG vaccinated individuals. In addition, this regimen can also be expected to reduce the risk of developing active TB due to reactivation of latent infection

CD152 (CTLA-4) Determines CD4 T Cell Migration In Vitro and In Vivo

BACKGROUND:Migration of antigen-experienced T cells to secondary lymphoid organs and the site of antigenic-challenge is a mandatory prerequisite for the precise functioning of adaptive immune responses. The surface molecule CD152 (CTLA-4) is mostly considered as a negative regulator of T cell activation during immune responses. It is currently unknown whether CD152 can also influence chemokine-driven T cell migration. METHODOLOGY/PRINCIPAL FINDINGS:We analyzed the consequences of CD152 signaling on Th cell migration using chemotaxis assays in vitro and radioactive cell tracking in vivo. We show here that the genetic and serological inactivation of CD152 in Th1 cells reduced migration towards CCL4, CXCL12 and CCL19, but not CXCL9, in a G-protein dependent manner. In addition, retroviral transduction of CD152 cDNA into CD152 negative cells restored Th1 cell migration. Crosslinking of CD152 together with CD3 and CD28 stimulation on activated Th1 cells increased expression of the chemokine receptors CCR5 and CCR7, which in turn enhanced cell migration. Using sensitive liposome technology, we show that mature dendritic cells but not activated B cells were potent at inducing surface CD152 expression and the CD152-mediated migration-enhancing signals. Importantly, migration of CD152 positive Th1 lymphocytes in in vivo experiments increased more than 200% as compared to CD152 negative counterparts showing that indeed CD152 orchestrates specific migration of selected Th1 cells to sites of inflammation and antigenic challenge in vivo. CONCLUSIONS/SIGNIFICANCE:We show here, that CD152 signaling does not just silence cells, but selects individual ones for migration. This novel activity of CD152 adds to the already significant role of CD152 in controlling peripheral immune responses by allowing T cells to localize correctly during infection. It also suggests that interference with CD152 signaling provides a tool for altering the cellular composition at sites of inflammation and antigenic challenge

Cytochrome P450 1 genes in birds : evolutionary relationships and transcription profiles in chicken and Japanese quail embryos

© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 6 (2011): e28257, doi:10.1371/journal.pone.0028257.Cytochrome P450 1 (CYP1) genes are biomarkers for aryl hydrocarbon receptor (AHR) agonists and may be involved in some of their toxic effects. CYP1s other than the CYP1As are poorly studied in birds. Here we characterize avian CYP1B and CYP1C genes and the expression of the identified CYP1 genes and AHR1, comparing basal and induced levels in chicken and quail embryos. We cloned cDNAs of chicken CYP1C1 and quail CYP1B1 and AHR1. CYP1Cs occur in several bird genomes, but we found no CYP1C gene in quail. The CYP1C genomic region is highly conserved among vertebrates. This region also shares some synteny with the CYP1B region, consistent with CYP1B and CYP1C genes deriving from duplication of a common ancestor gene. Real-time RT-PCR analyses revealed similar tissue distribution patterns for CYP1A4, CYP1A5, CYP1B1, and AHR1 mRNA in chicken and quail embryos, with the highest basal expression of the CYP1As in liver, and of CYP1B1 in eye, brain, and heart. Chicken CYP1C1 mRNA levels were appreciable in eye and heart but relatively low in other organs. Basal transcript levels of the CYP1As were higher in quail than in chicken, while CYP1B1 levels were similar in the two species. 3,3′,4,5,5′-Pentachlorobiphenyl induced all CYP1s in chicken; in quail a 1000-fold higher dose induced the CYP1As, but not CYP1B1. The apparent absence of CYP1C1 in quail, and weak expression and induction of CYP1C1 in chicken suggest that CYP1Cs have diminishing roles in tetrapods; similar tissue expression suggests that such roles may be met by CYP1B1. Tissue distribution of CYP1B and CYP1C transcripts in birds resembles that previously found in zebrafish, suggesting that these genes serve similar functions in diverse vertebrates. Determining CYP1 catalytic functions in different species should indicate the evolving roles of these duplicated genes in physiological and toxicological processes.Funding to MEJ and BB was from the Carl Tryggers Stiftelse and The Swedish Research Council Formas. Funding for BRW and JJS was from the United States National Institutes of Health (National Institute of Environmental Health Sciences), grants R01ES015912 and P42ES007381 to JJS

Heterosexual couples and prostate cancer support groups: a gender relations analysis.

Introduction: Men diagnosed with prostate cancer (PCa) can receive supportive care from an array of sources including female partners and prostate cancer support groups (PCSGs). However, little is known about how heterosexual gender relations and supportive care play out among couples who attend PCSGs. Distilling such gender relation patterns is a key to understanding and advancing supportive care for men who experience PCa and their families

Do Gene Variants Influencing Adult Adiposity Affect Birth Weight? A Population-Based Study of 24 Loci in 4,744 Danish Individuals

Several obesity risk alleles affecting adult adiposity have been identified by the recent wave of genome wide association studies. We aimed to examine the potential effect of these variants on fetal body composition by investigating the variants in relation to birth weight and ponderal index of the newborn.Midwife records from the Danish State Archives provided information on mother's age, parity, as well as birth weight, birth length and prematurity of the newborn in 4,744 individuals of the population-based Inter99 study. Twenty-four risk alleles showing genome-wide associations with adult BMI and/or waist circumference were genotyped. None of the 24 risk variants tested showed an association with birth weight or ponderal index after correction for multiple testing. Birth weight was divided into three categories low (≤10(th) percentile), normal (10(th)-90(th) percentile) and high birth weight (≥90th percentile) to allow for non-linear associations. There was no difference in the number of risk alleles between the groups (p = 0.57). No interactions between each risk allele and birth weight in the prediction of adult BMI were observed. An obesity risk score was created by summing up risk alleles. The risk score did not associate with fetal body composition. Moreover there was no interaction between the risk score and birth weight/ponderal index in the prediction of adult BMI.24 common variants associated with adult adiposity did not affect or interact with birth weight among Danes suggesting that the effects of these variants predominantly arise in the post-natal life

Regulation of BRCA1 expression and its relationship to sporadic breast cancer

Germ-line mutations in the BRCA1 tumour suppressor gene contribute to familial breast tumour formation, but there is no evidence for direct mutation of the BRCA1 gene in the sporadic form of the disease. In contrast, decreased expression of the BRCA1 gene has been shown to be common in sporadic tumours, and the magnitude of the decrease correlates with disease progression. BRCA1 expression is also tightly regulated during normal breast development. Determining how these developmental regulators of BRCA1 expression are co-opted during breast tumourigenesis could lead to a better understanding of sporadic breast cancer aetiology and the generation of novel therapeutic strategies aimed at preventing sporadic breast tumour progression