Pituitary tumor transforming gene-1 haplotypes and risk of pituitary adenoma: a case-control study

<p>Abstract</p> <p>Background</p> <p>It has been suggested that pituitary adenoma results from accumulation of multiple genetic and/or epigenetic aberrations, which may be identified through association studies. As pituitary tumor transforming gene-1 (<it>PTTG1</it>)/securin plays a critical role in promoting genomic instability in pituitary neoplasia, the present study explored the association of <it>PTTG1 </it>haplotypes with the risk of pituitary adenoma.</p> <p>Methods</p> <p>We genotyped five <it>PTTG1 </it>haplotype-tagging SNPs (htSNP) by PCR-RFLP assays in a case-control study, which included 280 Han Chinese patients diagnosed with pituitary adenoma and 280 age-, gender- and geographically matched Han Chinese controls. Haplotypes were reconstructed according to the genotyping data and linkage disequilibrium status of the htSNPs.</p> <p>Results</p> <p>No significant differences in allele and genotype frequencies of the htSNPs were observed between pituitary adenoma patients and controls, indicating that none of the individual <it>PTTG1 </it>SNPs examined in this study is associated with the risk of pituitary adenoma. In addition, no significant association was detected between the reconstructed <it>PTTG1 </it>haplotypes and pituitary adenoma cases or the controls.</p> <p>Conclusions</p> <p>Though no significant association was found between <it>PTTG1 </it>haplotypes and the risk of pituitary adenoma, this is the first report on the association of individual <it>PTTG1 </it>SNPs or <it>PTTG1 </it>haplotypes with the risk of pituitary adenoma based on a solid study; it will provide an important reference for future studies on the association between genetic alterations in <it>PTTG1 </it>and the risk of pituitary adenoma or other tumors.</p

Explainable Recommendations in Intelligent Systems: Delivery Methods, Modalities and Risks

With the increase in data volume, velocity and types, intelligent human-agent systems have become popular and adopted in different application domains, including critical and sensitive areas such as health and security. Humans’ trust, their consent and receptiveness to recommendations are the main requirement for the success of such services. Recently, the demand on explaining the recommendations to humans has increased both from humans interacting with these systems so that they make an informed decision and, also, owners and systems managers to increase transparency and consequently trust and users’ retention. Existing systematic reviews in the area of explainable recommendations focused on the goal of providing explanations, their presentation and informational content. In this paper, we review the literature with a focus on two user experience facets of explanations; delivery methods and modalities. We then focus on the risks of explanation both on user experience and their decision making. Our review revealed that explanations delivery to end-users is mostly designed to be along with the recommendation in a push and pull styles while archiving explanations for later accountability and traceability is still limited. We also found that the emphasis was mainly on the benefits of recommendations while risks and potential concerns, such as over-reliance on machines, is still a new area to explore

Signaling pathway networks mined from human pituitary adenoma proteomics data

Abstract Background We obtained a series of pituitary adenoma proteomic expression data, including protein-mapping data (111 proteins), comparative proteomic data (56 differentially expressed proteins), and nitroproteomic data (17 nitroproteins). There is a pressing need to clarify the significant signaling pathway networks that derive from those proteins in order to clarify and to better understand the molecular basis of pituitary adenoma pathogenesis and to discover biomarkers. Here, we describe the significant signaling pathway networks that were mined from human pituitary adenoma proteomic data with the Ingenuity pathway analysis system. Methods The Ingenuity pathway analysis system was used to analyze signal pathway networks and canonical pathways from protein-mapping data, comparative proteomic data, adenoma nitroproteomic data, and control nitroproteomic data. A Fisher's exact test was used to test the statistical significance with a significance level of 0.05. Statistical significant results were rationalized within the pituitary adenoma biological system with literature-based bioinformatics analyses. Results For the protein-mapping data, the top pathway networks were related to cancer, cell death, and lipid metabolism; the top canonical toxicity pathways included acute-phase response, oxidative-stress response, oxidative stress, and cell-cycle G2/M transition regulation. For the comparative proteomic data, top pathway networks were related to cancer, endocrine system development and function, and lipid metabolism; the top canonical toxicity pathways included mitochondrial dysfunction, oxidative phosphorylation, oxidative-stress response, and ERK/MAPK signaling. The nitroproteomic data from a pituitary adenoma were related to cancer, cell death, lipid metabolism, and reproductive system disease, and the top canonical toxicity pathways mainly related to p38 MAPK signaling and cell-cycle G2/M transition regulation. Nitroproteins from a pituitary control related to gene expression and cellular development, and no canonical toxicity pathways were identified. Conclusions This pathway network analysis demonstrated that mitochondrial dysfunction, oxidative stress, cell-cycle dysregulation, and the MAPK-signaling abnormality are significantly associated with a pituitary adenoma. These pathway-network data provide new insights into the molecular mechanisms of human pituitary adenoma pathogenesis, and new clues for an in-depth investigation of pituitary adenoma and biomarker discovery.</p

Heterophilic antibodies causing falsely high serum calcitonin values

Heterophilic antibodies (HA) may interfere in some immunoassays, causing falsely high hormone values, of wich practitioners should be aware when measuring calcitonin (CT) used as tumor marker for medullary thyroid carcinoma (MTC). We studied four patients with thyroid nodules, three of whom underwent surgical neck exploration, after an erroneous diagnosis of MTC because of falsely high serum CT eventually proved to be due to HA. One patient had a lingual thyroid, two autoimmune thyroiclitis and the fourth a colloid goiter. The minimal incremental CT response to calcium infusion raised our suspicion of possible false high CT values due to HA. There was no linearity of the CT values obtained by testing serial dilutions of the sera in the CT assay, which employs two monoclonal mouse anti-CT antibodies. Addition of normal mouse gamma globulin eliminated the interference by HA in the sera of two patients. Serum assayed in a polyclonal radioimmunoassay using goat anti-CT antibodies gave normal CT values. Finally, incubation of the sera in Heterophilic Blocking Tubes((R)) (HBT) eliminated the false CT immunoreactivity. A spontaneous change of the CT serum concentrations was noticed in three patients over several months, apparently due to changing titles of HA. We suggest that, in patients a) whose CT response to calcium or pentagastrin infusion is minimal despite high basal CT values, b) with autoimmune thyroiditis and c) in whom an unexpected change in serum CT concentrations occurs, the possibility of spuriously high CT values because of circulating HA should be considered

Blood lymphocyte blastogenesis in patients with thyroid dysfunction: Ex vivo response to mitogen activation and cyclosporin A

Objective: To evaluate lymphocyte activation following mitogen and cyclosporin A (CsA) administration in peripheral blood of hyperthyroxinaemic and hypothyroid patients. Materials and methods: Lymphocyte activation was evaluated by determining blastogenesis in 48 h cultured blood lymphocytes obtained from eight hyperthyroxinaemic and eight hypothyroid patients, following phytohaemagglutinin (PHA)-induced stimulation in the absence or presence of CsA. Twelve healthy volunteers served as controls. Results and conclusions: Lymphocytes from hypothyroid patients exhibited reduced response to PHA and lower sensitivity to CsA compared with control, which could be attributed to their reduced activation capability coexisting with hypothyroidism. In hyperthyroxinaemic samples, the actions of high CsA concentrations were mostly targeted toward activated lymphoblasts. Considering the cellular targets that thyroid hormones and CsA may share, the therapeutic implications of their cross-talk need careful consideration. © 2010 Springer Basel AG

Fever and standard monitoring parameters of ICU patients: A descriptive study

Objective: To investigate the effect of fever episodes and fever characteristics on heart rate, arterial blood pressure and arterial oxygen saturation of intensive care unit (ICU) patients. Methods: This was a prospective study conducted in the medical-surgical ICU of General University Hospital of Patras, Greece. All patients who were consecutively admitted from October 2005 to February 2006 and manifested fever during ICU stay were enrolled. A tympanic membrane or an axillary thermometer was used for the measurement of patient temperature. Standard monitoring parameters were recorded by nursing personnel at 1-h intervals. Results: Seventy-five ICU patients manifested fever during the study period. Increase of core temperature during fever episodes was followed by a significant increase in heart rate (p &lt; 0.001) and decreases in arterial blood pressure (p &lt; 0.001) and arterial oxygen saturation (p = 0.002). Alterations of heart rate and arterial blood pressure were significantly affected by magnitude of fever, while alteration of arterial oxygen saturation was affected by etiology of fever. Conclusions: The present findings confirmed the effect of fever episodes on standard monitoring parameters of ICU patients. However, alterations of these parameters, although statistically significant, were not clinically important and cannot guide antipyretic treatment. © 2007 Elsevier Ltd. All rights reserved