Clinical and pathological tools for identifying microsatellite instability in colorectal cancer

Aim To assess practical accuracy of revised Bethesda criteria (BGrev), pathological predictive model (MsPath), and histopathological parameters for detection of high-frequency of microsatellite instability (MSI-H) phenotype in patients with colorectal carcinoma (CRC). Method Tumors from 150 patients with CRC were analyzed for MSI using a fluorescence-based pentaplex polymerase chain reaction technique. For all patients, we evaluated age, sex, family history of cancer, localization, tumor differentiation, mucin production, lymphocytic infiltration (TIL), and Union for International Cancer Control stage. Patients were classified according to the BGrev, and the groups were compared. The utility of the BGrev, MsPath, and clinical and histopathological parameters for predicting microsatellite tumor status were assessed by univariate logistic regression analysis and by calculating the sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. Results Fifteen out of 45 patients who met and 4 of 105 patients who did not meet the BGrev criteria had MSI-H CRC. Sensitivity, specificity, PPV, and NPV for BGrev were 78.9%, 77%, 30%, and 70%, respectively. MSI histology (the third BGrev criterion without age limit) was as sensitive as BGrev, but more specific. MsPath model was more sensitive than BGrev (86%), with similar specificity. Any BGrev criterion fulfillment, mucinous differentiation, and right-sided CRC were singled out as independent factors to identify MSI-H colorectal cancer. Conclusion The BGrev, MsPath model, and MSI histology are useful tools for selecting patients for MSI testing

Clinical and pathological tools for identifying microsatellite instability in colorectal cancer

Aim To assess practical accuracy of revised Bethesda criteria (BGrev), pathological predictive model (MsPath), and histopathological parameters for detection of high-frequency of microsatellite instability (MSI-H) phenotype in patients with colorectal carcinoma (CRC). Method Tumors from 150 patients with CRC were analyzed for MSI using a fluorescence-based pentaplex polymerase chain reaction technique. For all patients, we evaluated age, sex, family history of cancer, localization, tumor differentiation, mucin production, lymphocytic infiltration (TIL), and Union for International Cancer Control stage. Patients were classified according to the BGrev, and the groups were compared. The utility of the BGrev, MsPath, and clinical and histopathological parameters for predicting microsatellite tumor status were assessed by univariate logistic regression analysis and by calculating the sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. Results Fifteen out of 45 patients who met and 4 of 105 patients who did not meet the BGrev criteria had MSI-H CRC. Sensitivity, specificity, PPV, and NPV for BGrev were 78.9%, 77%, 30%, and 70%, respectively. MSI histology (the third BGrev criterion without age limit) was as sensitive as BGrev, but more specific. MsPath model was more sensitive than BGrev (86%), with similar specificity. Any BGrev criterion fulfillment, mucinous differentiation, and right-sided CRC were singled out as independent factors to identify MSI-H colorectal cancer. Conclusion The BGrev, MsPath model, and MSI histology are useful tools for selecting patients for MSI testing

Dynamic transitions in a model of the hypothalamic-pituitary-adrenal axis

Dynamic properties of a nonlinear five-dimensional stoichiometric model of the hypothalamicpituitary-adrenal (HPA) axis were systematically investigated. Conditions under which qualitative transitions between dynamic states occur are determined by independently varying the rate constants of all reactions that constitute the model. Bifurcation types were further characterized using continuation algorithms and scale factor methods. Regions of bistability and transitions through supercritical Andronov-Hopf and saddle loop bifurcations were identified. Dynamic state analysis predicts that the HPA axis operates under basal (healthy) physiological conditions close to an Andronov-Hopf bifurcation. Dynamic properties of the stress-control axis have not been characterized experimentally, but modelling suggests that the proximity to a supercritical Andronov-Hopf bifurcation can give the HPA axis both, flexibility to respond to external stimuli and adjust to new conditions and stability, i.e., the capacity to return to the original dynamic state afterwards, which is essential for maintaining homeostasis. The analysis presented here reflects the properties of a low-dimensional model that succinctly describes neurochemical transformations underlying the HPA axis. However, the model accounts correctly for a number of experimentally observed properties of the stress-response axis. We therefore regard that the presented analysis is meaningful, showing how in silico investigations can be used to guide the experimentalists in understanding how the HPA axis activity changes under chronic disease and/or specific pharmacological manipulations

Proinflammatory Cytokine IL-6 and JAK-STAT Signaling Pathway in Myeloproliferative Neoplasms

The recent JAK1/2 inhibitor trial in myeloproliferative neoplasms (MPNs) showed that reducing inflammation can be more beneficial than targeting gene mutants. We evaluated the proinflammatory IL-6 cytokine and JAK-STAT signaling pathway related genes in circulating CD34(+) cells of MPNs. Regarding laboratory data, leukocytosis has been observed in polycythemia vera (PV) and JAK2V617F mutation positive versus negative primary myelofibrosis (PMF) patients. Moreover, thrombocytosis was reduced by JAK2V617F allele burden in essential thrombocythemia (ET) and PMF. 261 significantly changed genes have been detected in PV, 82 in ET, and 94 genes in PMF. The following JAK-STAT signaling pathway related genes had augmented expression in CD34(+) cells of MPNs: CCND3 and IL23A regardless of JAK2V617F allele burden; CSF3R, IL6ST, and STAT1/2 in ET and PV with JAK2V617F mutation; and AKT2, IFNGR2, PIM1, PTPN11, and STAT3 only in PV. STAT5A gene expression was generally reduced in MPNs. IL-6 cytokine levels were increased in plasma, as well as IL-6 protein levels in bone marrow stroma of MPNs, dependent on JAK2V617F mutation presence in ET and PMF patients. Therefore, the JAK2V617F mutant allele burden participated in inflammation biomarkers induction and related signaling pathways activation in MPNs

Serbia in the East

Title: Srbija na istoku (Serbia in the East) Originally published: Novi Sad, Srpska narodna zadružna Štamparija, 1872 Language: SerbianThe excerpts used are from Svetozar Marković, Srbija na istoku (NiŠ: Gradina, 1972), pp. 172–173. About the author Svetozar Marković [1846, Jagodina (present-day central Serbia) – 1875, Trieste]: the founder of the socialist movement in Serbia. As an exceptional student of the Velika Škola, the first high school and later university in Serbia, he won a state s..

Successful surgical treatment of terminal heart failure in an adolescent - left ventricular assist device implantation and subsequent heart transplantation

Introduction. Implantation of the new-generation left ventricular assist device (LVAD) is an efficient therapeutic option as a bridge to transplantation in adults, as well as in children and adolescents with small body surface. The aim of this work was to present a case of a successful surgical treatment of terminal heart failure in a male adolescent who had an LVAD implanted as a bridge to heart transplantation. Case outline. The patient, a 17-year-old male, was admitted with the end-stage heart failure due to the dilated cardiomyopathy and implanted LVAD. Fourteen months after LVAD implantation, a successful “second stage” surgical procedure was performed – orthotopic heart transplantation preceded by the LVAD explantation. Conclusion. Long-term mechanical circulatory support is an effective and safe method in treatment of the end-stage heart failure as a bridge to transplantation in the adolescent period

Visualization on the Day Night Year Globe

The story about a properly oriented outdoor globe in the hands and minds of Eratosthenes, Jefferson, Milanković and science educators is presented. Having the same orientation in space as the Earth, the Day Night Year Globe (DING) shows in real time the pattern of illumination of the Earth’s surface and its diurnal and seasonal variations. It is an ideal object for the visualization of knowledge and increase in knowledge about: the form of the Earth, Earth’s rotation, Earth’s revolution around the Sun, the length of seasons, solstices, equinoxes, the longitude problem, the distribution of the Sun’s radiation over the Earth, the impact of this radiation on Earth’s climate, and how to use it efficiently. By attaching a movable vane to the poles, or adding pins around the equator to read time, DING becomes a spherical/globe-shaped sundial. So, the DING is simultaneously useful for teaching physics, geophysics, astronomy, use of solar energy and promoting an inquiry-based learning environment for students and the public