Quantification of proteins in whole blood, plasma and DBS, with element-labelled antibody detection by ICP-MS

Over recent years, quantification of multiple proteins in body fluids has become increasingly prominent, which is beneficial to a number of scientific fields, not least biomedical. Several techniques have been developed based on conventional ELISA; one of these techniques is analysis of proteins labelled with element-tagged antibodies by ICP-MS in serum, allowing quantification of multiple targets within a single sample. This research aimed to quantify albumin and immunoglobulin G (IgG) levels in plasma, whole blood and dried blood spots using NANOGOLD and Europium labelled antibodies analysed by ICP-MS. Before the proteins were quantified simultaneously, albumin and IgG concentrations were measured separately and compared to protein levels obtained by ELISA. It was found that protein concentrations for both albumin and IgG obtained with element-labelled antibody detection correspond to those determined by ELISA. Furthermore, albumin and IgG levels measured simultaneously by ICP-MS correspond to concentrations found when the proteins were analysed separately by ICP-MS. Finally, development of this method has provided a positive indication that it can be extended to quantification of additional proteins, which could be related to a disease or as a minimum provide additional information for a protein profile of an individual. [Abstract copyright: Copyright © 2019. Published by Elsevier Inc.

The Prevalence of Sexual and Gender Minority Youth in the Justice System: A Systematic Review and Meta-Analysis

Theoretical models, such as the minority stress model, suggest that sexual and gender minority (SGM) youth may be overrepresented in the justice system. However, few studies have examined rates of SGM youth in the system, and even fewer have compared them with rates of these youth in the broader community. To obtain a more accurate estimate, we conducted a systematic review and meta-analysis of 31,258 youths and compared rates of SGM youth in the justice system with those in the community. Contrary to claims that SGM youth are overrepresented generally, this review suggests that sexual minority girls, specifically, are disproportionally involved in the justice system. Rates of involvement appeared to differ across ethnic subgroups of sexual minority youth, and evidence is inconclusive regarding the prevalence of gender minority youth in the system. Implications of these findings for researchers and justice system professionals are discussed

Endocrinologic, neurologic, and visual morbidity after treatment for craniopharyngioma

Craniopharyngiomas are locally aggressive tumors which typically are focused in the sellar and suprasellar region near a number of critical neural and vascular structures mediating endocrinologic, behavioral, and visual functions. The present study aims to summarize and compare the published literature regarding morbidity resulting from treatment of craniopharyngioma. We performed a comprehensive search of the published English language literature to identify studies publishing outcome data of patients undergoing surgery for craniopharyngioma. Comparisons of the rates of endocrine, vascular, neurological, and visual complications were performed using Pearson’s chi-squared test, and covariates of interest were fitted into a multivariate logistic regression model. In our data set, 540 patients underwent surgical resection of their tumor. 138 patients received biopsy alone followed by some form of radiotherapy. Mean overall follow-up for all patients in these studies was 54 ± 1.8 months. The overall rate of new endocrinopathy for all patients undergoing surgical resection of their mass was 37% (95% CI = 33–41). Patients receiving GTR had over 2.5 times the rate of developing at least one endocrinopathy compared to patients receiving STR alone or STR + XRT (52 vs. 19 vs. 20%, χ2P < 0.00001). On multivariate analysis, GTR conferred a significant increase in the risk of endocrinopathy compared to STR + XRT (OR = 3.45, 95% CI = 2.05–5.81, P < 0.00001), after controlling for study size and the presence of significant hypothalamic involvement. There was a statistical trend towards worse visual outcomes in patients receiving XRT after STR compared to GTR or STR alone (GTR = 3.5% vs. STR 2.1% vs. STR + XRT 6.4%, P = 0.11). Given the difficulty in obtaining class 1 data regarding the treatment of this tumor, this study can serve as an estimate of expected outcomes for these patients, and guide decision making until these data are available

SPARC: a matricellular regulator of tumorigenesis

Although many clinical studies have found a correlation of SPARC expression with malignant progression and patient survival, the mechanisms for SPARC function in tumorigenesis and metastasis remain elusive. The activity of SPARC is context- and cell-type-dependent, which is highlighted by the fact that SPARC has shown seemingly contradictory effects on tumor progression in both clinical correlative studies and in animal models. The capacity of SPARC to dictate tumorigenic phenotype has been attributed to its effects on the bioavailability and signaling of integrins and growth factors/chemokines. These molecular pathways contribute to many physiological events affecting malignant progression, including extracellular matrix remodeling, angiogenesis, immune modulation and metastasis. Given that SPARC is credited with such varied activities, this review presents a comprehensive account of the divergent effects of SPARC in human cancers and mouse models, as well as a description of the potential mechanisms by which SPARC mediates these effects. We aim to provide insight into how a matricellular protein such as SPARC might generate paradoxical, yet relevant, tumor outcomes in order to unify an apparently incongruent collection of scientific literature

A theoretical and experimental study on the detection of proteins with electrochemical impedance spectroscopy

Breast cancer is one of the deadliest diseases in existence for women in this time and age. Current methods of detection can be slow and often very painful processes. As with most types of cancer, there exists a need to discover biomarkers that would specifically detect the disease. The ability to distinguish between healthy patients and cancer patients through blood sampling would dramatically impact the future of cancer detection and diagnosis. The ultimate goal would be to integrate a type of biosensing scheme that could detect these markers in a quick and quantitative manner. The biosensor platform chosen for this research was electrochemical impedance (EIS). EIS can be used to monitor the adsorption of proteins on the surface of an electrode by following the change in impedance over time at a specific frequency. EIS has historically been applied in the study of corrosion, semiconductors, batteries, and electro-organic synthesis. Classical theory from electrochemistry can also be applied in a biological setting, where the rates of a reaction occurring on the surface of the electrode can be determined. Initial studies were conducted on a model protein system of bovine serum albumin. Here, the adsorption of bovine serum albumin (BSA) from aqueous solutions containing three specific concentrations of BSA onto three different electrode surfaces was studied. The concentrations studied were: 0.25, 0.50, and 1.00 mg/ml BSA; the surfaces studied were: unmodified gold, 16-mercaptodecanoic acid (MHA)-modified gold, and antibody immobilized on MHA-modified gold. After the initial verification studies, antigen detection in solution on a gold rotating disk electrode with immobilized antibody was performed using EIS. The antibody specifically detected the cancer-associated proliferating cell nuclear antigen (caPCNA). This antigen-antibody coupling was investigated by tracking the change in impedance over time at a specific perturbation frequency. This binding was tracked over a range of antigen concentrations in solution. The resulting curves from both sets of studies illustrated the effect of analyte concentration in solution, and the effect of surface characteristics in the system. The observed adsorption curves were described successfully using a composite model that considered both Langmuir adsorption and the multilayer/rearrangement model. Parameters for both Langmuir and the multilayer/rearrangement equations were then extracted and compared for each set of experiments. This research shows that protein interactions on the surface of a gold rotating disk electrode could be successfully monitored by tracking impedance change at a specific frequency over time

Effects of Nutritional Interventions during Pregnancy on Infant and Child Cognitive Outcomes:A Systematic Review and Meta-Analysis

Background: Epidemiological studies have demonstrated that folate, iodine and iron intake during pregnancy impacts on foetal brain development and cognitive function. However, in human studies, the relationship with other dietary nutrients is less clear. Objective: This systematic review aims to critically appraise the current literature and meta-analyses results from nutritional interventions during pregnancy that aimed to optimise infant and child cognitive outcomes. Design: Ten electronic databases were searched for articles published up to August 2017. The search was limited to articles published in English. Randomised controlled trials (RCTs) testing the impact of any nutritional intervention (dietary counselling, education, nutrient supplementation, fortified foods and/or foods) during pregnancy on cognitive outcomes of children (&lt;10 years old). Two independent reviewers assessed study eligibility and quality using the American Dietetic Association quality criteria checklist for primary research. Standardised mean differences were used for nine cognitive domains to measure effects for meta-analyses. Results: A total of 34 RCTs were included (21 studies included children aged less than 35 months, 10 studies included children aged 36–60 months and 3 studies included children aged 61–119 months). The types of nutritional interventions included nutrient supplements, whole foods, fortified foods and nutrition education. The following nine cognition outcomes: attention, behaviour, crystallised intelligence, fluid intelligence, global cognition, memory, motor skills, visual processing, and problem solving were not significantly impacted by nutritional interventions, although 65% of studies conducted post-hoc data analyses and were likely to be underpowered. Although, long chain polyunsaturated fatty acids (LCPUFA) supplementation was associated with a marginal increase in crystallised intelligence (Effect size (ES): 0.25; 95% confidence interval (95% CI): −0.04, 0.53), the effect was not statistically significant (p = 0.09), with significant study heterogeneity (p = 0.00). Conclusions: LCPUFA supplementation may be associated with an improvement in child crystallised intelligence, however further research is warranted. The remaining eight cognition domains were not significantly impacted by maternal nutritional interventions