T-wave changes in patients with Wellens syndrome are associated with increased myocardial mechanical and electrical dispersion

Some patients with unstable angina and critical stenosis of the left anterior descending coronary artery (LAD) present with Wellens syndrome (WS), i.e., inverted or biphasic T-waves in the anterior precordial leads. We assessed clinical, angiographic, electro- and echocardiographic characteristic of patients with WS. In this retrospective study, clinical, angiographic, electro- and echocardiographic characteristic of 35 patients with WS were compared to 57 patients with critical LAD stenosis and normal resting electrocardiogram (ECG), and 45 subjects with normal coronary angiogram. QTc dispersion was measured from the 12-lead ECG as the difference between longest and shortest QTc intervals. Mechanical dispersion was defined as the time difference between the longest and shortest contraction durations which were measured as the time from the first deflection of the QRS complex to maximum myocardial shortening of each 18 segmental longitudinal strain curves derived by speckle tracking echocardiography. There were no significant differences in the complexity and location of the LAD lesion, anterograde and collateral flow in LAD and coronary artery dominance between patients with WS and normal ECG (P?>?0.05, for all). Patients with WS had lower global longitudinal strain (GLS) and more pronounced both QTc and myocardial mechanical dispersion than patients with critical LAD stenosis and normal ECG, and control subjects (P?<?0.05). T-wave changes in patients with WS are associated with more profound regional myocardial dysfunction and increased QTc and myocardial mechanical dispersion. Similar angiographic characteristics of the LAD lesion were seen in patients with WS and normal ECG.     

Die Bedeutung des sagittalen Profils bei der zervikalen Endoprothetik

We report on the results of 246 Bryan cervical discs, which were implanted between June 2002 and September 2010 in 146 patients. Of the patients 74 (128 prostheses) could be followed up for more than 1 year and the average follow-up period was 2.6 years. Of the patients 18 were operated on at one level (group 1), 77 prostheses were multilevel surgery (group 2) and with 33 patients arthroplasty was combined with fusion (hybrid, group 3). The global lordosis remained unchanged during follow-up and a recurrence of kyphosis was evident in group 3. The overall mobility improved in all 3 subgroups and 2 cases (group 3) fused. With 5 patients the prosthesis had to be removed and the segment had to be fused in the postoperative course. As a conclusion a meticulous preoperative planning as well as a subtle surgical technique is the main prerequisite for long-lasting mobility of the Bryan prosthesis.     

Diabetes-induced epigenetic signature in vascular cells

Vascular dysfunction is a common consequence of diabetes mellitus. Stable propagation of gene expression from cell to cell generation during development of diseases (like diabetes) is regulated by epigenetic mechanisms. These are heritable patterns of gene expression that cannot solely be explained by changes in DNA sequence. Recent evidence shows that diabetes-induced epigenetic changes can affect gene expression in vascular endothelial cells and vascular smooth muscles cells. Such effects further influence inflammatory and insulin production pathways in these cells and thus ensure a long-term memory, whereby epigenetic changes are maintained even long after restoring normo-glycaemic conditions by appropriate therapeutic approaches. This review focuses on the epigenetic marks, which endure on the vascular chromatin under diabetic conditions.     

Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing

Purpose

Multi-drug resistance (MDR) is a major obstacle to successful cancer treatment. Therefore, in vitro models are necessary for the investigation of the phenotypic changes provoked by cytotoxic agents and more importantly for preclinical testing of new anticancer drugs.

Methods

We analyzed chromosomal, numerical, and structural changes after development of MDR, alterations in p53 and PTEN, single nucleotide polymorphisms (SNPs) in the mdr1 gene and corresponding protein expression of P-glycoprotein (P-gp) in three human MDR cancer cell lines: non-small cell lung carcinoma NCI-H460/R, colorectal carcinoma DLD1-TxR, and glioma U87-TxR. In addition, we explored how these molecular and phenotypic alterations influence the anticancer effect of new drugs.

Results

Cytogenetic analysis showed polyploidy reduction after development of MDR in U87-TxR. Losses of 6q in all resistant cancer cell lines and inactivation of p53 in U87-TxR and PTEN in DLD1-TxR were also revealed. Overexpression of P-gp was observed in all MDR cancer cell lines. We evaluated the anticancer activities and MDR reversal potential of Akt inhibitor GSK690693, Ras inhibitor Tipifarnib, and two P-gp inhibitors (jatrophane diterpenoids). Their effects vary due to the cell-type differences, existence of MDR phenotype, presence of mdr1 SNP, and tumor suppressors’ alterations. Tipifarnib and jatrophane diterpenoids significantly sensitized MDR cancer cells to paclitaxel.

Conclusion

In conclusion, investigated MDR cancer cells obtained new molecular and cytogenetic characteristics that may serve as potential clinical prognostic markers. In addition, these MDR cancer cell lines present a valuable model for preclinical evaluation of new anticancer agents.     

Combined immunohistochemistry for thyroid peroxidase, galectin-3, CK19 and HBME-1 in differential diagnosis of thyroid tumors

We evaluated some proposed molecular thyroid tumor markers: thyroid peroxidase (TPO), galectin-3, cytokeratin-19, and HBME-1, individually and in combination, by immunohistochemistry in a total of 242 archival thyroid tissue sections. The expression of each individual marker was most helpful for the diagnosis of papillary carcinoma and its follicular variant. However, none of them was sensitive and specific enough to discriminate between Hürthle adenoma and carcinoma. Galectin-3 and HBME-1 could be used as single discriminators between follicular thyroid adenoma and carcinoma, but HBME-1 is the better choice. As a single test, all analyzed tumor markers had sufficient power to predict differentiated thyroid cancer, with sensitivities ranging from 66.5% to 82.2%. The sensitivity was improved by using combinations of some proposed markers. Only two antigens, HBME-1 and TPO, had distinct predictive values for different diagnostic alternatives i.e. a sequential combination improved diagnostic accuracy between follicular thyroid adenoma and the follicular variant of papillary thyroid carcinoma to 92.6% and consequently, between overall benign and malignant thyroid tumors to 89.1%. HBME-1 is the most accurate ancillary stain in discriminating well-differentiated thyroid carcinomas from benign tumors, although the addition of TPO did improve accuracy and served as a useful confirmatory marker.     

Cancer stem cell niche: the place to be

Tumors are being increasingly perceived as abnormal organs that, in many respects, recapitulate the outgrowth and differentiation patterns of normal tissues. In line with this idea is the observation that only a small fraction of tumor cells is capable of initiating a new tumor. Because of the features that these cells share with somatic stem cells, they have been termed cancer stem cells (CSC). Normal stem cells reside in a "stem cell niche" that maintains them in a stem-like state. Recent data suggest that CSCs also rely on a similar niche, dubbed the "CSC niche," which controls their self-renewal and differentiation. Moreover, CSCs can be generated by the microenvironment through induction of CSC features in more differentiated tumor cells. In addition to a role in CSC maintenance, the microenvironment is hypothesized to be involved in metastasis by induction of the epithelial-mesenchymal transition, leading to dissemination and invasion of tumor cells. The localization of secondary tumors also seems to be orchestrated by the microenvironment, which is suggested to form a premetastatic niche. Thus, the microenvironment seems to be of crucial importance for primary tumor growth as well as metastasis formation. Combined with its role in the protection of CSCs against genotoxic insults, these data strongly put forward the niche as an important target for novel therapies.     

Serbian medical students’ fertility awareness and attitudes towards future parenthood

Objectives: Medical students represent a group particularly at risk of involuntary childlessness due to their highly demanding careers and university curriculum. The aim of this study was to investigate Serbian medical students’ attitudes towards future parenthood and their awareness of fertility issues.

Methods: A cross-sectional study was conducted among fourth year students at the Faculty of Medicine, University of Belgrade, Serbia, between 12 and 16 December 2016. Data were collected through an anonymous 56-item validated questionnaire, translated into the Serbian language. The participation rate was 87.1%.

Results: More than 95% of students, regardless of gender, wanted to have children in the future; most indicated three as the desired number of children. Both genders equally rated the importance of having children. Women rated significantly higher the likelihood of IVF treatment or child adoption if faced with infertility (both p?=?.001). All students wanted to have their first child before the age of 35 years. Knowledge about the age-related decline in female fertility was not satisfactory. Women found it more important to have children when they felt sufficiently mature, were in a stable relationship, were financially secure, had completed their studies, were not too old to have children, and had access to childcare, although these prerequisites were rated highly by both genders.

Conclusion: Serbian medical students greatly value and have a positive perception of future parenthood. Appropriate education is needed, however, because of their inadequate knowledge of the age-related decline in female fertility.     

Thyroid peroxidase and galectin-3 immunostaining in differentiated thyroid carcinoma with clinicopathologic correlation

Thyroperoxidase and galectin-3 have been reported as useful immunohistochemical markers of thyroid malignancy. In this study, we evaluated the relationship between immunohistochemical staining results for these markers and clinicopathologic features of patients with differentiated thyroid cancer. A total of 193 archival thyroid samples including 28 follicular adenomas, 18 follicular carcinomas, and 147 papillary carcinomas with 114 adjacent thyroid tissues were analyzed by immunohistochemistry. Thyroperoxidase was underexpressed (<50% stained thyrocytes), and galectin-3 was expressed (>5% stained thyrocytes) in most carcinomas. The sensitivity for diagnosis of differentiated thyroid carcinoma was 86.1% for thyroperoxidase and 82.4% for galectin-3, whereas the combination of both markers increased the sensitivity up to 94.5%. Thus, the combination of thyroperoxidase and galectin-3 immunohistochemistry may help to ascertain the malignant nature of the lesion. Furthermore, tumor size, nodal involvement, extrathyroidal invasion, and high tumor-node-metastasis stage in patients with papillary carcinoma were related to thyroperoxidase absence and high galectin-3 expression in most cases (P < .05). In patients with follicular carcinoma, the extent of invasiveness was associated with galectin-3 positivity. Thus, expression of these markers is related to more or less aggressive biological behavior of differentiated thyroid carcinomas. Although thyroperoxidase presence may indicate favorable prognosis of papillary cancer, expression of galectin-3 illustrates the potential importance of this protein in the pathogenesis and/or progression of differentiated thyroid carcinomas.     

Application of Semipermanent Cements and Conventional Cement with Modified Cementing Technique in Dental Implantology

ObjectivesThe aim of this study was to evaluate the influence of artificial ageing on the retention force of original semipermanent cements, as well as the possibility of using conventional cements for semipermanent cementation with adequate modification of the cementing protocol.Materials and methodsForty CoCrMo alloy crowns were divided in four groups (each group n=10) and fixed with two semipermanent cements (resin-based and glass ionomer-based cements) and one conventional (zinc phosphate), using conventional and modified cementation techniques on titanium abutments. The samples were stored in humid conditions for 24 hours at 37°C and subjected to thermocycling (500 cycles) and mechanical cyclic loading (7 days, 3, 6, 9 and 12 months function simulation). The cast crowns were removed and the retention force was recorded.ResultsThe highest initial retention force measured was for zinc-phosphate cement - conventional cementing (198,00±61,90 N), followed in descending order by zinc-phosphate cement - modified cementing technique (152,00±45,42 N), long term temporary cement – GC Fuji Temp LT (57,70±20,40 N), and semipermanent cement - Telio CS Cem Implant (56,10±18,68 N). After 12 months, the highest retention force measured was for zinc-phosphate cement - conventional cementing (88, 90±14, 45 N), followed by zinc-phosphate cement – modified cementing (48, 15±14,41N), semipermanent cement GC Fuji Temp LT (16,55±3,88 N) and Telio CS Cem Implant (15,55±5,52 N).ConclusionsZinc-phosphate cement - modified cementing technique and original semipermanent cements can be recommended for conditional permanent cementing of implant supported crowns.Clinical relevanceThe use of semipermanenet cements and zinc-phosphate cement - modified cementing technique provides a predictable retrievability of implant-supported crowns.     

Mast cells: Versatile gatekeepers of pain

Mast cells are important first responders in protective pain responses that provoke withdrawal from intense, noxious environmental stimuli, in part because of their sentinel location in tissue–environment interfaces. In chronic pain disorders, the proximity of mast cells to nerves potentiates critical molecular cross-talk between these two cell types that results in their synergistic contribution to the initiation and propagation of long-term changes in pain responses via intricate signal networks of neurotransmitters, cytokines and adhesion molecules. Both in rodent models of inflammatory pain and chronic pain disorders, as well as in increasing evidence from the clinic, it is abundantly clear that understanding the mast cell-mediated mechanisms underlying protective and maladaptive pain cascades will lead to improved understanding of mast cell biology as well as the development of novel, targeted therapies for the treatment and management of debilitating pain conditions.