Serotonin Transporter Genomic Biomarker for Quantitative Assessment of Ondansetron Treatment Response in Alcoholics

Paucity of sensitive biomarkers to quantify transient changes in alcohol consumption level remains a critical barrier for the development of efficacious therapeutic agents to treat alcoholism. Recently, in an 11-week, randomized, placebo-controlled, double-blind trial of 283 alcohol-dependent individuals, we demonstrated that ondansetron was efficacious at reducing the severity of drinking (measured as drinks per drinking day; DDD) in alcoholics carrying the LL compared with the LS/SS genotype of the serotonin transporter gene, 5′-HTTLPR. Using peripheral blood samples from a cohort of 41 of these subjects, we determined whether there was a relationship between mRNA expression level of the 5′-HTTLPR genotypes (measured at weeks 0, 4, and 11) and self-reported alcohol consumption following treatment with either ondansetron (4 μg/kg twice daily; N = 19) or placebo (N = 22). Using a mixed-effects linear regression model, we analyzed the effects of DDD and 5′-HTTLPR genotypes on mRNA expression levels within and between the ondansetron and placebo groups. We found a significant three-way interaction effect of DDD, 5′-HTTLPR genotypes, and treatment on mRNA expression levels (p = 0.0396). Among ondansetron but not placebo recipients, there was a significant interaction between DDD and 5′-HTTLPR genotype (p = 0.0385 and p = 0.7938, respectively). In the ondansetron group, DDD was associated positively with mRNA levels at a greater rate of expression alteration per standard drink in those with the LL genotype (slope = +1.1698 in ln scale). We suggest that the combination of the LL genotype and 5′-HTTLPR mRNA expression levels might be a promising and novel biomarker to quantify drinking severity in alcoholics treated with ondansetron

Challenge-response trust assessment model for personal space IoT

© 2016 IEEE. Internet of Things (IoT) embraces the interconnection of identifiable devices that are capable of providing services through their cooperation. The cooperation among devices in such an IoT environment often requires reliable and trusted participating members in order to provide useful services to the end user. Consequently, an IoT environment or space needs to evaluate the trust levels of all devices in contact before admitting them as members of the space. Existing trust evaluation models are based on resources such as historical observations or recommendations information to evaluate the trust level of a device. However, these methods fail if there is no existing trust resource. This paper introduces a specific IoT environment called personal space IoT and proposes a novel trust evaluation model that performs a challenge-response trust assessment to evaluate the trust level of a device before allowing it to participate in the space. This novel challenge-response trust assessment model does not require the historical observation or previous encounter with the device or any existing trusted recommendation. The proposed challenge-response trust assessment model provides a reliable trust resource that can be used along with other resources such as direct trust, recommendation trust to get a comprehensive trust opinion on a specific device. It can also be considered as a new method for evaluating the trust value on a device

Initial trust establishment for personal space IoT systems

© 2017 IEEE. Increasingly, trust has played a crucial role in the security of an IoT system from its inception to the end of its lifecycle. A device has to earn some level of trust even before it is authenticated for admission to the system. Furthermore, once the device is admitted to the system, it may behave maliciously over time; hence its behavior must be evaluated constantly in the form of trust to ensure the integrity of the system. Currently, no mechanism exists to establish an initial trust on a device, without prior knowledge, before its admission to an IoT system. Even when trust is applicable, trust evaluation models require direct/indirect observations over time, historical data on past encounters, or third party recommendations. However, this type of past data is not available in the first encounter between the system and the device. The question is how to establish whether a device can be trusted to a level that merits further evaluation for admission into a mobile and dynamic IoT system when it encounters the system for the first time? This paper addresses this challenge by proposing a challenge-response method and a trust assessment model to establish, without prior knowledge, the initial trust that a device places on another in a mobile and dynamic environment called personal space IoT. The initial trust is established before further interaction can take place and under the assumption that only a limited window of time is available for the trust assessment. The paper describes and evaluates the proposed model theoretically and by simulation. It also describes a practical scheme for realizing the proposed solution

Tip enhanced laser ablation sample transfer for mass spectrometry

© 2015 Materials Research Society. Mass spectrometry is one of the primary analysis techniques for biological analysis but there are technological barriers in sampling scale that must be overcome for it to be used to its full potential on the size scale of single cells. Current mass spectrometry imaging methods are limited in spatial resolution when analyzing large biomolecules. The goal of this project is to use atomic force microscope (AFM) tip enhanced laser ablation to remove material from cells and tissue and capture it for subsequent mass spectrometry analysis. The laser ablation sample transfer system uses an AFM stage to hold the metal-coated tip at a distance of approximately 10 nm from a sample surface. The metal tip acts as an antenna for the electromagnetic radiation and enables the ablation of the sample with a spot size much smaller than a laser focused with a conventional lens system. A pulsed nanosecond UV or visible wavelength laser is focused onto the gold-coated silicon tip at an angle nearly parallel with the surface, which results in the removal of material from a spot between 500 nm and 1 um in diameter and 200 and 500 nm deep. This corresponds to a few picograms of ablated material, which can be captured on a metal surface for MALDI analysis. We have used this approach to transfer small peptides and proteins from a thin film for analysis by mass spectrometry as a first step toward high spatial resolution imaging

Prevalence of Occupational Stress among Secondary School Teachers in Public Schools in the District of Colombo, Sri Lanka

Teacher occupational stress is increasing globally. We aimed to determine the prevalence of occupational stress among secondary teachers, to advocate policies for prevention of occupational stress among teachers in Sri Lanka. A cross-sectional study included 1426 secondary teachers, selected using multistage cluster sampling from public schools of Colombo, Sri Lanka. Validated Teacher Stress Inventory-Sinhala (TSI-Sinhala) assessed occupational stress. Prevalence of high [15.9% (95% CI: 14.0%-17.8%)] and moderate [67.5% (95% CI: 65.1%-69.9%)] occupational stress among secondary teachers, resulted an overall high prevalence of 83.4% (95%CI: 81.4%-85.3%). Moderate occupational stress among female teachers (68.6%, 95% CI: 65.7-71.5%) was significantly higher than males (61.9%. 95% CI: 58.9-64.9%). Urgent attention to preventative interventions for occupational stress among teachers in Sri Lanka is recommended

Investigating microenvironmental regulation of human chordoma cell behaviour

The tumour microenvironment is complex and composed of many different constituents, including matricellular proteins such as connective tissue growth factor (CCN2), and is characterized by gradients in oxygen levels. In various cancers, hypoxia and CCN2 promote stem and progenitor cell properties, and regulate the proliferation, migration and phenotype of cancer cells. Our study was aimed at investigating the effects of hypoxia and CCN2 on chordoma cells, using the human U-CH1 cell line. We demonstrate that under basal conditions, U-CH1 cells express multiple CCN family members including CCN1, CCN2, CCN3 and CCN5. Culture of U-CH1 cells in either hypoxia or in the presence of recombinant CCN2 peptide promoted progenitor cell-like characteristics specific to the notochordal tissue of origin. Specifically, hypoxia induced the most robust increase in progenitor-like characteristics in U-CH1 cells, including increased expression of the notochord-associated markers T, CD24, FOXA1, ACAN and CA12, increased cell growth and tumour-sphere formation, and a decrease in the percentage of vacuolated cells present in the heterogeneous population. Interestingly, the effects of recombinant CCN2 peptide on U-CH1 cells were more pronounced under normoxia than hypoxia, promoting increased expression of CCN1, CCN2, CCN3 and CCN5, the notochord-associated markers SOX5, SOX6, T, CD24, and FOXA1 as well as increased tumour-sphere formation. Overall, this study highlights the importance of multiple factors within the tumour microenvironment and how hypoxia and CCN2 may regulate human chordoma cell behaviour

Inhibitory Effect of Gold Nanoparticles on the D-ribose Glycation of Bovine Serum Albumin

Formation of advanced glycation end products (AGEs) by nonenzymatic glycation of proteins is a major contributory factor to the pathophysiology of diabetic conditions including senile dementia and atherosclerosis. This study describes the inhibitory effect of gold nanoparticles (GNPs) on the D-ribose glycation of bovine serum albumin (BSA). A combination of analytical methods including ultraviolet–visible spectrometry, high performance liquid chromatography, circular dichroism, and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were used to determine the extent of BSA glycation in the presence of citrate reduced spherical GNPs of various sizes and concentrations. GNPs of particle diameters ranging from 2 nm to 20 nm inhibited BSA’s AGE formation. The extent of inhibition correlated with the total surface area of the nanoparticles. GNPs of highest total surface area yielded the most inhibition whereas those with the lowest total surface area inhibited the formation of AGEs the least. Additionally, when GNPs’ total surface areas were set the same, their antiglycation activities were similar. This inhibitory effect of GNPs on BSA’s glycation by D-ribose suggests that colloidal particles may have a therapeutic application for the treatment of diabetes and conditions that promote hyperglycemia

A comparison of automatic protocol generation techniques

Due to the increasing complexity of applications and the availability of high speed networks classical protocols have become the main bottleneck in communication systems. Although tailored protocols are able to respond to the needs of a given application their development is expensive in terms of time and effort. An automatic protocogeneration environment is most desirable. Two approaches currently used are the stub compilation and the runtime adaptive techniques. We have studied these two approaches and the behaviour of the resulting tailored transport protocols. Relative performance comparisons and discussions about these two approaches are presented in this paper

C1 inhibitor deficiency: 2014 United Kingdom consensus document

C1 inhibitor deficiency is a rare disorder manifesting with recurrent attacks of disabling and potentially life-threatening angioedema. Here we present an updated 2014 United Kingdom consensus document for the management of C1 inhibitor-deficient patients, representing a joint venture between the United Kingdom Primary Immunodeficiency Network and Hereditary Angioedema UK. To develop the consensus, we assembled a multi-disciplinary steering group of clinicians, nurses and a patient representative. This steering group first met in 2012, developing a total of 48 recommendations across 11 themes. The statements were distributed to relevant clinicians and a representative group of patients to be scored for agreement on a Likert scale. All 48 statements achieved a high degree of consensus, indicating strong alignment of opinion. The recommendations have evolved significantly since the 2005 document, with particularly notable developments including an improved evidence base to guide dosing and indications for acute treatment, greater emphasis on home therapy for acute attacks and a strong focus on service organisation. This article is protected by copyright. All rights reserved