Med. Sci.2014, 2(3), 140-152; doi:10.3390/medsci2030140 - published online 11 July 2014 Show/Hide Abstract
Abstract: Metabolic syndrome (MetS) is chronic inflammatory epidemic state contributing to total and cardiovascular mortality. The current study planned to assess and screen risk factors for MetS and its components. A cross-sectional study conducted to assess age, gender, social status, employment, education, family history, physical activity, dietary habits, alcohol, sleep, body mass index and stress as determinants of MetS. The results were analyzed by Chi Square test with statistical significance of p value <0.05. The frequency of MetS was 17.38% as per modified National Cholesterol Education Program–Adult Treatment Panel III criteria. Females (57.38%), age >50 years (86.90%; p < 0.05), middle socioeconomic status (70.50%), illiteracy (39.35%), and unemployment (81.97%; p < 0.05) were found contributing though to different extents. Subjects with a sedentary lifestyle (72.14%), positive family history (42.63%), omnivore diet (47.55%), stress (78.69%; p < 0.05), insomnia (29.51%) and increased BMI (83.62%; p < 0.001) had shown predisposition to MetS. However, the protective role of alcohol (38.28%), an active lifestyle (36.21%), vegetarian diet (62.07%) and adequate sleep (73.11%) was observed. A significant hypertension (98.37%; p < 0.001), dyslipidemia (77.05%; p < 0.001), dysglycemia (75.41%; p < 0.001) and obesity (59.02%; p < 0.001) was reported in MetS. Common concerns of female gender, increasing age and BMI, sedentary lifestyle, stress and positive family history should be considered for early identification and appropriate intervention to fight the growing MetS epidemic.
Med. Sci.2014, 2(3), 127-139; doi:10.3390/medsci2030127 - published online 1 July 2014 Show/Hide Abstract
Abstract: Drosophila segmentation as a model organism is one of the most highly studied. Among many maternal segmentation coordinate genes, bicoid protein pattern plays a significant role during Drosophila embryogenesis, since this gradient determines most aspects of head and thorax development. Despite the fact that several models have been proposed to describe the bicoid gradient, due to its association with considerable error, each can only partially explain bicoid characteristics. In this paper, a modified version of singular spectrum analysis is examined for filtering and extracting the bicoid gene expression signal. The results with strong evidence indicate that the proposed technique is able to remove noise more effectively and can be considered as a promising method for filtering gene expression measurements for other applications.
Med. Sci.2014, 2(2), 98-126; doi:10.3390/medsci2020098 - published online 13 June 2014 Show/Hide Abstract
Abstract: Sudden cardiac death in people between the ages of 1–40 years is a devastating event and is frequently caused by several heritable cardiac disorders. These disorders include cardiac ion channelopathies, such as long QT syndrome, catecholaminergic polymorphic ventricular tachycardia and Brugada syndrome and cardiomyopathies, such as hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. Through careful molecular genetic evaluation of DNA from sudden death victims, the causative gene mutation can be uncovered, and the rest of the family can be screened and preventative measures implemented in at-risk individuals. The current screening approach in most diagnostic laboratories uses Sanger-based sequencing; however, this method is time consuming and labour intensive. The development of massively parallel sequencing has made it possible to produce millions of sequence reads simultaneously and is potentially an ideal approach to screen for mutations in genes that are associated with sudden cardiac death. This approach offers mutation screening at reduced cost and turnaround time. Here, we will review the current commercially available enrichment kits, massively parallel sequencing (MPS) platforms, downstream data analysis and its application to sudden cardiac death in a diagnostic environment.
Med. Sci.2014, 2(2), 82-97; doi:10.3390/medsci2020082 - published online 14 April 2014 Show/Hide Abstract
Abstract: Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic. In this study, we sought to investigate NKT cell responses to B cell lymphoma. In the presence of exogenous antigen, both mouse and human NKT cell lines produce cytokines following stimulation by B cell lymphoma lines. NKT cell populations were examined ex vivo in mouse models of spontaneous B cell lymphoma, and it was found that during early stages, NKT cell responses were enhanced in lymphoma-bearing animals compared to disease-free animals. In contrast, in lymphoma-bearing animals with splenomegaly and lymphadenopathy, NKT cells were functionally impaired. In a mouse model of blastoid variant mantle cell lymphoma, treatment of tumor-bearing mice with a potent NKT cell agonist, α-galactosylceramide (α-GalCer), resulted in a significant decrease in disease pathology. Ex vivo studies demonstrated that NKT cells from α-GalCer treated mice produced IFN-γ following α-GalCer restimulation, unlike NKT cells from vehicle-control treated mice. These data demonstrate an important role for NKT cells in the immune response to an aggressive hematologic malignancy like mantle cell lymphoma.
Med. Sci.2014, 2(2), 70-81; doi:10.3390/medsci2020070 - published online 26 March 2014 Show/Hide Abstract
Abstract: Obtaining human tumor cell lines from fresh tumors is essential to advance our understanding of antitumor immune surveillance mechanisms and to develop new ex vivo strategies to generate an efficient anti-tumor response. The present study delineates a simple and rapid method for efficiently establishing primary cultures starting from tumor samples of different types, while maintaining the immuno-histochemical characteristics of the original tumor. We compared two different strategies to disaggregate tumor specimens. After short or long term in vitro expansion, cells analyzed for the presence of malignant cells demonstrated their neoplastic origin. Considering that tumor cells may be isolated in a closed system with high efficiency, we propose this methodology for the ex vivo expansion of tumor cells to be used to evaluate suitable new drugs or to generate tumor-specific cytotoxic T lymphocytes or vaccines.
Med. Sci.2014, 2(1), 51-69; doi:10.3390/medsci2010051 - published online 20 February 2014 Show/Hide Abstract
Abstract: Tracking vaccine components from the site of injection to their destination in lymphatic tissue, and simultaneously monitoring immune effects, sheds light on the influence of vaccine components on particle and immune cell trafficking and therapeutic efficacy. In this study, we create a hybrid particle vaccine platform comprised of porous silicon (pSi) and superparamagnetic iron oxide nanoparticles (SPIONs). The impact of nanoparticle size and mode of presentation on magnetic resonance contrast enhancement are examined. SPION-enhanced relaxivity increased as the core diameter of the nanoparticle increased, while encapsulation of SPIONs within a pSi matrix had only minor effects on T2 and no significant effect on T2* relaxation. Following intravenous injection of single and hybrid particles, there was an increase in negative contrast in the spleen, with changes in contrast being slightly greater for free compared to silicon encapsulated SPIONs. Incubation of bone marrow-derived dendritic cells (BMDC) with pSi microparticles loaded with SPIONs, SIINFEKL peptide, and lipopolysaccharide stimulated immune cell interactions and interferon gamma production in OT-1 TCR transgenic CD8+ T cells. Overall, the hybrid particle platform enabled presentation of a complex payload that was traceable, stimulated functional T cell and BMDC interactions, and resolved in cellular activation of T cells in response to a specific antigen.