Serum levels of IL-6 type cytokines and soluble IL-6 receptors in active B-cell chronic lymphocytic leukemia and in cladribine induced remission.

We have investigated the serum concentrations of interleukin-6 (IL-6) and two IL-6 family cytokines-oncostatin M (OSM) and leukemia inhibitory factor (LIF)-in 63 patients with B-cell chronic lymphocytic leukemia (B-CLL) and 17 healthy controls using the enzyme-linked immunosorbent assay (ELISA) method. Simultaneously, we measured the serum levels of the soluble forms of two subunits of the IL-6 receptor complex-ligand binding glycoprotein 80 (sIL-6R) and glycoprotein 130 (sgp130). The cytokines and receptors were evaluated in 25 untreated patients and 38 patients treated with cladribine (2-CdA), as well as in 17 healthy controls. We have correlated the serum levels of these proteins with Rai's clinical stage of the disease, the response to 2-CdA treatment and some hematological parameters. We have also evaluated the correlation of the IL-6 serum level with the concentration of OSM and IL-6 soluble receptors. IL-6 was measurable in 62/63 (98.4%), OSM in 20/25 (80%) of untreated and 14/38 (37.8%) of the treated patients. sIL-6R and sgp130 were detectable in all 63 patients and LIF in none of the CLL patients. IL-6 serum level in untreated patients was not significantly different as compared to its concentration in the control group (P>0.05). However, in the patients treated with 2-CdA the IL-6 level was significantly lower (P<0.02), and the lowest concentration was found in the patients with complete remission (CR; median 1.4pg/ml; P<0.02). The concentration of sIL-6R was significantly higher in untreated (median 61.8 ng/ml) and treated (median 50.1 ng/ml) CLL patients when compared to normal persons (median 41.2 ng/ml; P=0.04; P<0.001, respectively). There was no difference between the sIL-6R levels in the patients with CR and the healthy controls. In non-responders sIL-6R concentration was the highest and similar to its level in the untreated patients. OSM level was higher in the untreated patients (median 1.8pg/ml) than in the normal controls (median 0.0pg/ml; P<0.001) and in the CR patients (median 0.0pg/ml; P<0.03). The serum concentration of sgp130 was similar in the untreated (median 480 pg/ml) and treated (median 470 pg/ml) patients, as well as in the healthy persons (median 420 pg/ml; P>0.05). We have found significant positive correlation between the levels of sIL-6R and the lymphocytes count in CLL patients (p=0.423; P<0.001). In addition, sIL-6R and OSM serum concentrations correlated also with CLL Rai stage. In conclusion, the serum level of IL-6, OSM and sIL-6R, but not LIF and sgp130, are useful indicators of CLL activity

Simulation techniques in the anatomy curriculum: review of literature

Modern medical education faces a problem of combining the latest technology, procedures and information with classic teaching methods. Simulation is a technique, which replaces or amplifies doctor–patient experiences in controlled conditions and therefore evokes or replicates substantial aspects of the real world in a fully interactive manner. The basic course of anatomy in medical education could be recognised as the best example of implementing new educational techniques such as simulation, into the traditional medical curriculum. The PubMed database was searched using specific key words. Finally 72 articles were accepted and were divided into 3 basic categories of teaching methods: Category 1 — cadaveric dissection, Category 2 — simulator based education and Category 3 — other. A state of the art anatomical curriculum offers numerous possibilities and solutions including the oldest like cadaveric dissection and newest like simulators. Different simulation techniques are used with different intensity; however cadaveric dissection is still the most popular method. The second most frequent method is simulation-based training, in which North America is the leading country. The identification of anatomical structures during virtual surgical procedures or laparoscopic robotic procedures can be integrated into the traditional anatomy course. New technologies are supportive and beneficial in anatomy teaching however each excitement of new technologies sometimes should be tempered and evaluated for its usefulness in making the learning process constructive for students and their future practice

Molecular and Clinicopathological Biomarkers in the Neoadjuvant Treatment of Patients with Advanced Resectable Melanoma

Neoadjuvant systemic therapy is emerging as the best medical practice in patients with resectable stage III melanoma. As different regimens are expected to become available in this approach, the improved optimization of treatment strategies is required. Personalization of care in each individual patient—by precisely determining the disease-related risk and the most efficient therapeutic approach—is expected to minimize disease recurrence, but also the incidence of treatment-related adverse events and the extent of surgical intervention. This can be achieved through validation and clinical application of predictive and prognostic biomarkers. For immune checkpoint inhibitors, there are no validated predictive biomarkers until now. Promising predictive molecular biomarkers for neoadjuvant immunotherapy are tumor mutational burden and the interferon-gamma pathway expression signature. Pathological response to neoadjuvant treatment is a biomarker of a favorable prognosis and surrogate endpoint for recurrence-free survival in clinical trials. Despite the reliability of these biomarkers, risk stratification and response prediction in the neoadjuvant setting are still unsatisfactory and represent a critical knowledge gap, limiting the development of optimized personalized strategies in everyday practice

Structure of the hydroxyl groups and adsorbed D2OD_2O sites in the DX zeolite : DFT and experimental NMR data

We report on density functional theory computations combined with the results of measurements of the quadrupole coupling constants for 17O, hydroxyl deuterons, and adsorbed water deuterons in DX zeolite (n(Si)/n(Al) = 1). Calculations are performed for the crystalline periodic model of the DX zeolite. The local structural parameters are found for various oxygen positions at equilibrium. The quadrupole coupling constants for 17O are in the range CQ(17O) = 7.75 ± 0.5 and 3.75 ± 0.5 MHz for (Si–OD–Al) and (Si–O–Al) substructures, respectively. Related values of the asymmetry parameter η fall in the ranges of 0.9 ± 0.5 and 0.15 ± 0.1, respectively. The quadrupole coupling constant for deuterons depends on the OD distance according to the relation CQ(D)[MHz] = −2.732dOD[MHz/Å] + 2.938 MHz. Deuterons are assigned to labeled oxygen positions according to the decreasinng quadrupole coupling constant CQ(D) as O1 ≥ O4 > O2 > O3, with their relative abundances of 54.4, 7.6, 26.6, and 11.4%, respectively. The binding energy of deuteron in hydroxyl groups and for adsorbed water molecules is analyzed. Formation of the water hexamer in the plane of the 12-ring window was confirmed. Results of the calculations are compared with NMR experimental data for 17O and D