Evaluating the toxicity of permeability enhanchers of polyethylene glycol brij ethers surfactants group on cellular membranes and some of their physicochemical properties

The aim of this study is to evaluate the effect of polyethylene glycol brij ethers surfactants group on red blood cells as a model for biological membranes. Also in this study, physicochemical properties including emulsification index (E24), foam producing activity (Fh) and critical micelle concentration (cmc) were studied. Surfactant solutions were prepared in McIvan’s buffer in specific concentrations. 0.2 ml of red blood cells (RBC) was mixed with 0.2 ml of each surfactant solution. The four surfactant solutions had each been incubated differently at two different temperatures for three different times. Each test was done six times. The results were presented as mean absorbance ± the standard deviation. E24, Fh and cmc were also determined for each surfactant solution. All of the surfactant solutions showed hemolytic activity. In comparison with the four studied surfactants, brij 56 had the highest hemolytic effect and brij 72 the lowest. The values of E24 and Fh had good correlation with hydrophilic-lipophilic balance values. According to the results of this study, brijs should be used at concentrations lower than cmc in formulations. Also, according to the results, the use of brijs with low hemolytic effect such as brij 72, is preferred in pharmaceutical preparations.Key words: Brij, biological membrane, hemolysis, hydrophile-lipophile balance (HLB)

‘It is not a quick fix’ structural and contextual issues that affect implementation of integrated health and well-being services: a qualitative study from North East England

Objective The objective of this article is to examine the factors affecting the design, commissioning and delivery of integrated health and well-being services (IHWSs), which seek to address multiple health-related behaviours, improve well-being and tackle health inequalities using holistic approaches. Study design Qualitative studies embedded within iterative process evaluations. Methods Semi-structured interviews conducted with 16 key informants as part of two separate evaluations of IHWSs in North East England, supplemented by informal observations of service delivery. Transcripts and fieldnotes were analysed thematically. Results The study findings identify a challenging organisational context in which to implement innovative service redesign, as a result of budget cuts and changes in NHS and local authority capacity. Pressures to demonstrate outcomes affected the ability to negotiate the practicalities of joint working. Progress is at risk of being undermined by pressures to disinvest before the long-term benefits to population health and well-being are realised. The findings raise important questions about contract management and relationships between commissioners and providers involved in implementing these new ways of working. Conclusions These findings provide useful learning in terms of the delivery and commissioning of similar IHWSs, contributing to understanding of the benefits and challenges of this model of working

Drilling Performance Monitoring and Optimization: A Data-driven Approach

Abstract Drilling performance monitoring and optimization are crucial in increasing the overall NPV of an oil and gas project. Even after rigorous planning, drilling phase of any project can be hindered by unanticipated problems, such as bit balling. The objective of this paper is to implement artifcial intelligence technique to develop a smart model for more accurate and robust real-time drilling performance monitoring and optimization. For this purpose, the back propagation, feed forward neural network model was developed to predict rate of penetration (ROP) using diferent input parameters such as weight on bit, rotations per minute, mud fow (GPM) and diferential pressures. The heavy hitter features identifcation and dimensionality reduction are performed to understand the impacts of each of the drilling parameters on ROP. This will be used to optimize the input parameters for model development and validation and performing the operation optimization when bit is underperforming. The model is frst developed based on the drilling experiments performed in the laboratory and then extended to feld applications. From both laboratory and feld test data provided, we have proved that the data-driven model built using multilayer perceptron technique can be successfully used for drilling performance monitoring and optimization, especially identifying the bit malfunction or failure, i.e., bit balling. We have shown that the ROP has complex relationship with other drilling variables which cannot be captured using conventional statistical approaches or from diferent empirical models. The data-driven approach combined with statistical regression analysis provides better understanding of relationship between variables and prediction of ROP

"It was the whole picture" a mixed methods study of successful components in an integrated wellness service in North East England

Background A growing number of Local Authorities (LAs) have introduced integrated wellness services as part of efforts to deliver cost effective, preventive services that address the social determinants of health. This study examined which elements of an integrated wellness service in the north east of England were effective in improving health and wellbeing (HWB). Methods The study used a mixed-methods approach. In-depth semi-structured interviews (IVs) were conducted with integrated wellness service users (n = 25) and focus groups (FGs) with group based service users (n = 14) and non-service users (n = 23) to gather the views of stakeholders. Findings are presented here alongside analysis of routine monitoring data. The different data were compared to examine what each data source revealed about the effectiveness of the service. Results Findings suggest that integrated wellness services work by addressing the social determinants of health and respond to multiple complex health and social concerns rather than single issues. The paper identifies examples of ‘active ingredients’ at the heart of the programme, such as sustained relationships, peer support and confidence building, as well as the activities through which changes take place, such as sports and leisure opportunities which in turn encourage social interaction. Wider wellbeing outcomes, including reduced social isolation and increased self-efficacy are also reported. Practical and motivational support helped build community capacity by encouraging community groups to access funding, helped navigate bureaucratic systems, and promoted understanding of marginalised communities. Fully integrated wellness services could support progression opportunities through volunteering and mentoring. Conclusions An integrated wellness service that offers a holistic approach was valued by service users and allowed them to address complex issues simultaneously. Few of the reported health gains were captured in routine data. Quantitative and qualitative data each offered a partial view of how effectively services were working

Embedded Research::a promising way to create evidence-informed impact in public health?

Background Embedded research (ER) is recognized as one way to strengthen the integration of evidence into public health (PH) practice. In this paper, we outline a promising example of the co-production of research evidence between Fuse, the UKCRC Centre for Translational Research in Public Health and a local authority (LA) in north east England. Methods We critically examine attempts to share and use research findings to influence decision-making in a LA setting, drawing on insights from PH practitioners, managers, commissioners and academic partners involved in this organizational case study. We highlight what can be achieved as a co-located embedded researcher. Results The benefits and risks of ER are explored, alongside our reflections on the added value of this approach and the institutional prerequisites necessary for it to work. We argue that while this is not a new methodological approach, its application in PH as a way to facilitate evidence use is novel, and raises pragmatic and theoretical questions about the nature of impact and the extent to which it can be engineered. Conclusion With increased situated understanding of organizational culture and norms and greater awareness of the socio-political realities of PH, ER enables new co-produced solutions to become possible

Genomic Instability Is Associated with Natural Life Span Variation in Saccharomyces cerevisiae

Increasing genomic instability is associated with aging in eukaryotes, but the connection between genomic instability and natural variation in life span is unknown. We have quantified chronological life span and loss-of-heterozygosity (LOH) in 11 natural isolates of Saccharomyces cerevisiae. We show that genomic instability increases and mitotic asymmetry breaks down during chronological aging. The age-dependent increase of genomic instability generally lags behind the drop of viability and this delay accounts for ∼50% of the observed natural variation of replicative life span in these yeast isolates. We conclude that the abilities of yeast strains to tolerate genomic instability co-vary with their replicative life spans. To the best of our knowledge, this is the first quantitative evidence that demonstrates a link between genomic instability and natural variation in life span

Ancient goat genomes reveal mosaic domestication in the Fertile Crescent.

Current genetic data are equivocal as to whether goat domestication occurred multiple times or was a singular process. We generated genomic data from 83 ancient goats (51 with genome-wide coverage) from Paleolithic to Medieval contexts throughout the Near East. Our findings demonstrate that multiple divergent ancient wild goat sources were domesticated in a dispersed process that resulted in genetically and geographically distinct Neolithic goat populations, echoing contemporaneous human divergence across the region. These early goat populations contributed differently to modern goats in Asia, Africa, and Europe. We also detect early selection for pigmentation, stature, reproduction, milking, and response to dietary change, providing 8000-year-old evidence for human agency in molding genome variation within a partner species

Deletion of the Mitochondrial Superoxide Dismutase sod-2 Extends Lifespan in Caenorhabditis elegans

The oxidative stress theory of aging postulates that aging results from the accumulation of molecular damage caused by reactive oxygen species (ROS) generated during normal metabolism. Superoxide dismutases (SODs) counteract this process by detoxifying superoxide. It has previously been shown that elimination of either cytoplasmic or mitochondrial SOD in yeast, flies, and mice results in decreased lifespan. In this experiment, we examine the effect of eliminating each of the five individual sod genes present in Caenorhabditis elegans. In contrast to what is observed in other model organisms, none of the sod deletion mutants shows decreased lifespan compared to wild-type worms, despite a clear increase in sensitivity to paraquat- and juglone-induced oxidative stress. In fact, even mutants lacking combinations of two or three sod genes survive at least as long as wild-type worms. Examination of gene expression in these mutants reveals mild compensatory up-regulation of other sod genes. Interestingly, we find that sod-2 mutants are long-lived despite a significant increase in oxidatively damaged proteins. Testing the effect of sod-2 deletion on known pathways of lifespan extension reveals a clear interaction with genes that affect mitochondrial function: sod-2 deletion markedly increases lifespan in clk-1 worms while clearly decreasing the lifespan of isp-1 worms. Combined with the mitochondrial localization of SOD-2 and the fact that sod-2 mutant worms exhibit phenotypes that are characteristic of long-lived mitochondrial mutants—including slow development, low brood size, and slow defecation—this suggests that deletion of sod-2 extends lifespan through a similar mechanism. This conclusion is supported by our demonstration of decreased oxygen consumption in sod-2 mutant worms. Overall, we show that increased oxidative stress caused by deletion of sod genes does not result in decreased lifespan in C. elegans and that deletion of sod-2 extends worm lifespan by altering mitochondrial function

Genome-Wide Association Analysis of Oxidative Stress Resistance in Drosophila melanogaster

Background: Aerobic organisms are susceptible to damage by reactive oxygen species. Oxidative stress resistance is a quantitative trait with population variation attributable to the interplay between genetic and environmental factors. Drosophila melanogaster provides an ideal system to study the genetics of variation for resistance to oxidative stress. Methods and Findings: We used 167 wild-derived inbred lines of the Drosophila Genetic Reference Panel for a genomewide association study of acute oxidative stress resistance to two oxidizing agents, paraquat and menadione sodium bisulfite. We found significant genetic variation for both stressors. Single nucleotide polymorphisms (SNPs) associated with variation in oxidative stress resistance were often sex-specific and agent-dependent, with a small subset common for both sexes or treatments. Associated SNPs had moderately large effects, with an inverse relationship between effect size and allele frequency. Linear models with up to 12 SNPs explained 67–79 % and 56–66 % of the phenotypic variance for resistance to paraquat and menadione sodium bisulfite, respectively. Many genes implicated were novel with no known role in oxidative stress resistance. Bioinformatics analyses revealed a cellular network comprising DNA metabolism and neuronal development, consistent with targets of oxidative stress-inducing agents. We confirmed associations of seven candidate genes associated with natural variation in oxidative stress resistance through mutational analysis. Conclusions: We identified novel candidate genes associated with variation in resistance to oxidative stress that hav

Role of Nrf2 Dysfunction in Uremia-Associated Intestinal Inflammation and Epithelial Barrier Disruption

Aims: To study the expression profile of inflammatory and tight junction proteins in the colon from CKD rats compared to healthy controls, and demonstrate the role of Nrf2 (transcription factor nuclear factor erythroid 2-related factor 2) using a potent Nrf2 activator