Nanotechnology‐Based Rapid Diagnostic Tests

Recently, various nanomaterials are used in order to develop nanotechnology‐based rapid diagnostic tests, such as metallic nanoparticles, quantum dots (QDs), silica nanospheres, magnetic nanoparticles, carbon nanotubes (CNTs), silicon nanowires (SiNWs), nanopores, graphene, nanostructured surfaces, and metal films. This novel nanodiagnostic approach will further develop point‐of‐care (POC) diagnostics and monitoring technologies. Nanobiosensors and microarrays of biosensors can create biochip systems and microfluidic platforms that are the most used nanofabrications for rapid diagnostic tests. These nanoplatforms are constructed for the rapid detection of various diseases or pathogen‐specific biomolecules/markers, such as DNA, proteins, whole cells (e.g., circulating tumor cells), and others. The fabrication of small‐scale portable devices with the incorporation of nanostructures will offer many advantages in the early detection of various diseases and health‐threatening infections by pathogens and in the treatment selection and treatment monitoring. The use of nanostructures in in vitro diagnostics gives the opportunity to augment the sensitivity and specificity required in clinical practice, lowers the cost and test time of the assays, and enables portable microfluidic platforms suitable for resource‐constrained settings. In this chapter, all the state‐of‐the‐art advantages in this field are discussed, starting with the nanostructures used for the fabrication of nanobiosensors, nanobiosensors arrays, and nanofluidic platforms and the nanodiagnostic use of rapid tests in the detection of pathogens, in cancer management, and glucose monitoring for the management of diabetes disease

Current insights in to the pathophysiology of Irritable Bowel Syndrome

Irritable Bowel Syndrome (IBS) represents a functional disorder of gastrointestinal tract without the presence of an anatomic defect, in which abdominal pain is relieved with defecation and is associated with altered bowel habits

Power-law scaling in intratumoral microbiota of colorectal cancer

It has recently been proposed that the study of microbial dynamics in humans may gain insights from island biogeographical theory. Here, we test whether the diversity of the intratumoral microbiota of colorectal cancer tumors (CRC) follows a power law with tumor size akin to the island species-area relationship. We confirm a direct correlation between the quantity of Amplicon Sequence Variants (ASVs) within CRC tumors and tumor sizes, following a (log)power model, explaining 47% of the variation. Understanding the processes involved, potentially through the analogy of tumors and islands, may ultimately contribute to future clinical and therapeutic strategies

Power-law scaling in intratumoral microbiota of colorectal cancer

It has recently been proposed that the study of microbial dynamics in humans may gain insights from island biogeographical theory. Here, we test whether the diversity of the intratumoral microbiota of colorectal cancer tumors (CRC) follows a power law with tumor size akin to the island species-area relationship. We confirm a direct correlation between the quantity of Amplicon Sequence Variants (ASVs) within CRC tumors and tumor sizes, following a (log)power model, explaining 47% of the variation. Understanding the processes involved, potentially through the analogy of tumors and islands, may ultimately contribute to future clinical and therapeutic strategies

Inflammatory pseudotumor associated with Mycobacterium tuberculosis infection

SummaryBackgroundInflammatory pseudotumor is a relatively rare entity; originally identified in the lung, it has been described in multiple extrapulmonary anatomic locations.Case reportWe report on the unusual case of an inflammatory pseudotumor associated with Mycobacterium tuberculosis infection, which was initially mistaken for a renal malignancy both in clinical and radiological settings. We additionally present three brief reviews concerning: (1) infectious agents postulated to induce morphological changes of an inflammatory pseudotumor; (2) mycobacterial pseudotumors; and (3) distinction from inflammatory myofibroblastic tumors of the renal pelvis.ConclusionsThe present case highlights the diagnostic importance of PCR-based detection of mycobacterial DNA in granulomatous tissue responses. It is of crucial importance that clinicians are aware of this unusual manifestation of mycobacterial infection to ensure that pertinent laboratory evaluation is employed and appropriate treatment is administered in order to avoid potential clinical implications

Lessons learned - resolving the enigma of genetic factors in IBS

IBS is the most prevalent functional gastrointestinal disorder and phenotypically characterized by chronic abdominal discomfort, pain and altered defecation patterns. The pathophysiology of IBS is multifactorial, albeit with a substantial genetic component. To date, studies using various methodologies, ranging from family and twin studies to candidate gene approaches and genome-wide association studies, have identified several genetic variants in the context of IBS. Yet, despite enlarged sample sizes, increased statistical power and meta-analyses in the past 7 years, positive associations are still scarce and/or have not been reproduced. In addition, epigenetic and pharmacogenetic approaches remain in their infancy. A major hurdle is the lack of large homogenized case-control cohorts recruited according to standardized and harmonized criteria. The COST Action BM1106 GENIEUR (GENes in Irritable Bowel Syndrome Research Network EURope) has been established to address these obstacles. In this Review, the (epi)genetic working group of GENIEUR reports on the current state-of-the-art in the field, highlights fundamental flaws and pitfalls in current IBS (epi) genetic research and provides a vision on how to address and improve (epi) genetic approaches in this complex disorder in the future.This is the peer reviewed version of the paper: Gazouli, M., Wouters, M. M., Kapur-Pojskić, L., Bengtson, M.-B., Friedman, E., Nikčević, G., Demetriou, C. A., Mulak, A., Santos, J., & Niesler, B. (2016). Lessons learned—Resolving the enigma of genetic factors in IBS. Nature Reviews Gastroenterology & Hepatology, 13(2), 77–87. [https://doi.org/10.1038/nrgastro.2015.206]Published version: [https://imagine.imgge.bg.ac.rs/handle/123456789/977

Detection of Pathogenic Mycobacteria Based on Functionalized Quantum Dots Coupled with Immunomagnetic Separation

Mycobacteria have always proven difficult to identify due to their low growth rate and fastidious nature. Therefore molecular biology and more recently nanotechnology, have been exploited from early on for the detection of these pathogens. Here we present the first stage of development of an assay incorporating cadmium selenide quantum dots (QDs) for the detection of mycobacterial surface antigens. The principle of the assay is the separation of bacterial cells using magnetic beads coupled with genus-specific polyclonal antibodies and monoclonal antibodies for heparin-binding hemagglutinin. These complexes are then tagged with anti-mouse biotinylated antibody and finally streptavidin-conjugated QDs which leads to the detection of a fluorescent signal. For the evaluation of performance, the method under study was applied on Mycobacterium bovis BCG and Mycobacterium tuberculosis (positive controls), as well as E. coli and Salmonella spp. that constituted the negative controls. The direct observation of the latter category of samples did not reveal fluorescence as opposed to the mycobacteria mentioned above. The minimum detection limit of the assay was defined to 104 bacteria/ml, which could be further decreased by a 1 log when fluorescence was measured with a spectrofluorometer. The method described here can be easily adjusted for any other protein target of either the pathogen or the host, and once fully developed it will be directly applicable on clinical samples

Guidelines to Analyze Preclinical Studies Using Perinatal Derivatives.

The last 18 years have brought an increasing interest in the therapeutic use of perinatal derivatives (PnD). Preclinical studies used to assess the potential of PnD therapy include a broad range of study designs. The COST SPRINT Action (CA17116) aims to provide systematic and comprehensive reviews of preclinical studies for the understanding of the therapeutic potential and mechanisms of PnD in diseases and injuries that benefit from PnD therapy. Here we describe the publication search and data mining, extraction, and synthesis strategies employed to collect and prepare the published data selected for meta-analyses and reviews of the efficacy of PnD therapies for different diseases and injuries. A coordinated effort was made to prepare the data suitable to make statements for the treatment efficacy of the different types of PnD, routes, time points, and frequencies of administration, and the dosage based on clinically relevant effects resulting in clear increase, recovery or amelioration of the specific tissue or organ function. According to recently proposed guidelines, the harmonization of the nomenclature of PnD types will allow for the assessment of the most efficient treatments in various disease models. Experts within the COST SPRINT Action (CA17116), together with external collaborators, are doing the meta-analyses and reviews using the data prepared with the strategies presented here in the relevant disease or research fields. Our final aim is to provide standards to assess the safety and clinical benefit of PnD and to minimize redundancy in the use of animal models following the 3R principles for animal experimentation

Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk

Although 21 pancreatic cancer susceptibility loci have been identified in individuals of European ancestry through genome-wide association studies (GWASs), much of the heritability of pancreatic cancer risk remains unidentified. A recessive genetic model could be a powerful tool for identifying additional risk variants. To discover recessively inherited pancreatic cancer risk loci, we performed a re-analysis of the largest pancreatic cancer GWAS, the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including 8,769 cases and 7,055 controls of European ancestry. Six single nucleotide polymorphisms (SNPs) showed associations with pancreatic cancer risk according to a recessive model of inheritance. We replicated these variants in 3,212 cases and 3,470 controls collected from the PANcreatic Disease ReseArch (PANDoRA) consortium. The results of the meta-analyses confirmed that rs4626538 (7q32.2), rs7008921 (8p23.2) and rs147904962 (17q21.31) showed specific recessive effects (p10-3), although none of the six SNPs reached the conventional threshold for genome-wide significance (p < 5×10-8). Additional bioinformatic analysis explored the functional annotations of the SNPs and indicated a possible relationship between rs36018702 and expression of the BCL2L11 and BUB1 genes, which are known to be involved in pancreatic biology. Our findings, while not conclusive, indicate the importance of considering non-additive genetic models when performing GWAS analysis. The SNPs associated with pancreatic cancer in this study could be used for further meta-analysis for recessive association of SNPs and pancreatic cancer risk and might be a useful addiction to improve the performance of polygenic risk scores