Rapid brain responses to affective pictures indicate dimensions of trauma-related psychopathology in adolescents

A variety of mental disorders are related to deviant brain activity, but these neural alterations do not validate psychiatric diagnostic categories. High symptom overlap and variable symptom patterns encourage a dimensional approach. Following the logic of the Research Domain Criteria (RDoC), we investigated trauma survivors for symptom clusters that might be associated with characteristics of ERPs, in particular with the early posterior negativity (EPN) elicited during affective picture processing. In rapid serial visual presentation, 90 adolescents (40 male/50 female, age M = 15.0 ± 2.5 years) who had been exposed to varying amounts of traumatic stress passively viewed a stream of high-arousing positive and low-arousing neutral pictures taken from the International Affective Picture System (IAPS). Using standardized interviews, symptoms of trauma-related mental disorders were assessed (including those for PTSD, depression, borderline personality disorder, and behavioral problems). A principal component analysis was performed to derive potential dimensions of psychopathology. Multiple regression analysis confirmed a factor comprising problems concentrating, sleeping difficulties, and mistrust as a predictor of a larger EPN difference between high-arousing positive and low-arousing neutral IAPS pictures (β = 0.19, p < 0.05). Sex predicted the magnitude of the EPN (β = 0.45, p < 0.001). Male adolescents displayed a stronger EPN suppression than female adolescents. The result suggests that problems concentrating, sleeping difficulties, and mistrust seem to be trans-diagnostic elements related to diminished early emotional discrimination represented by the EPN. Furthermore, our findings indicate that the EPN in response to emotional processing is modulated by sex.     

Left ventricular systolic and diastolic function after total correction of tetralogy of Fallot

Left ventricular (LV) systolic and diastolic function was assessed in 12 patients after total correction of tetralogy of Fallot (age range 5 to 18 years, mean 10) and compared with 10 control patients. Only 1 patient had a shunt before total correction that was performed at a mean age of 3.5 years, (range 0.3 to 8). At cardiac catheterization the following indexed LV parameters were measured: end-diastolic and end-systolic volumes, wall mass, ejection fraction, stroke volume and end-diastolic and end-systolic pressures and stresses. The rate-corrected mean velocity of fiber shortening was calculated. LV diastolic operant chamber stiffness and myocardial stiffness were calculated from simultaneous diastolic pressures and volumes in mid- and late diastole using monoexponential formulas. The 2 groups were compared by unpaired t tests. The tetralogy group had higher mean end-diastolic (93 vs 74 ml/m2), end-systolic (29 vs 19 ml/m2) and stroke (64 vs 55 ml/m2) volumes than controls. Rate-corrected mean velocity of fiber shortening was lower in the tetralogy group (1.07 vs 1.24). Myocardial stiffness was higher in the tetralogy group (16 vs 11). Other indexes were not significantly different. Thus, LV function after total correction of tetralogy of Fallot may be abnormal with larger than normal LV size, decreased contractile function and increased myocardial stiffness.     

Systemic treatment of colorectal cancer in Serbia: what have we done and what can we offer in the new century?

The treatment of patients with metastatic colorectal cancer (mCRC) has changed dramatically over recent years in Serbia. The more optimal use of 5-fluorouracil (5-FU) in association with leucovorin (LV), the development of new drugs such as oxaliplatin and irinotecan and of the oral fluoropyrimidines, such as capecitabine, have increased therapeutic options and to the improved outcome of patients with mCRC. Throughout our 10-years published papers in international journals, we presented development of chemotherapy for mCRC and improvement in treatment outcome in Serbia. It is shown that combination therapy with 5-FU/LV and oxaliplatin or irinotecan is more active than 5-FU/LV in first line treatment of mCRC. Sequential therapy with FOLFIRI+FOLFOX was the most efficacious combination in comparison to any other 2 drugs combinations. The combination protocols in second line were superior to mono irinotecan and equal to LV5FU2 in terms of time to progression. The oral fluoropyrimidines seems to have an activity comparable to that of i.v. 5-FU/LV. New agents acting on novel targets are under development. Angiogenesis inhibitors, epidermal growth factor inhibitors, COX-2 inhibitors and farnesyl transferase inhibitors might play a role in the future in the treatment of CRC. We will present our first experience with bevacizumab, vascular endothelial growth factor inhibitor.     

Apolipoprotein CIII overexpressing mice are predisposed to diet-induced hepatic steatosis and hepatic insulin resistance

Nonalcoholic fatty liver disease (NAFLD) and insulin resistance have recently been found to be associated with increased plasma concentrations of apolipoprotein CIII (APOC3) in humans carrying single nucleotide polymorphisms within the insulin response element of the APOC3 gene. To examine whether increased expression of APOC3 would predispose mice to NAFLD and hepatic insulin resistance, human APOC3 overexpressing (ApoC3Tg) mice were metabolically phenotyped following either a regular chow or high-fat diet (HFD). After HFD feeding, ApoC3Tg mice had increased hepatic triglyceride accumulation, which was associated with cellular ballooning and inflammatory changes. ApoC3Tg mice also manifested severe hepatic insulin resistance assessed by a hyperinsulinemic-euglycemic clamp, which could mostly be attributed to increased hepatic diacylglycerol content, protein kinase C-? activation, and decreased insulin-stimulated Akt2 activity. Increased hepatic triglyceride content in the HFD-fed ApoC3Tg mice could be attributed to a ≈ 70% increase in hepatic triglyceride uptake and ≈ 50% reduction hepatic triglyceride secretion. CONCLUSION: These data demonstrate that increase plasma APOC3 concentrations predispose mice to diet-induced NAFLD and hepatic insulin resistance.     

Minimal residual disease monitoring by flow cytometry in children with acute lymphoblastic leukemia

The cells that have avoided the action of antitumor drugs may be retained after remission achievement during induction therapy and consolidation. A combination of these cells is given the name minimal residual disease (MRD). Multicolor flow cytometry has recently attracted considerable interest as the most promising method for measuring the content of residual tumor blasts. This technique is based on the detection of the so-called leukemia-associated immunophenotype (LAIP), i.e., a tumor-specific combination of the expression of membrane and cytoplasmic markers. Flow cytometry may be successfully used to monitor MRD in 90-95% cases of acute lymphoblastic leukemia (ALL) and in 80-85% of patients with acute myelocytic leukemia. The sensitivity of flow cytometry, which is real for routine flow techniques, is a possibility of identifying one cell among 10(4)-10(5) cells. Multicolor flow cytometry (that involves the simultaneous analysis of the expression of a few markers) is the most reasonable tool for MRD monitoring. The monoclonal antibody panels recommended by different groups of investigators for MRD monitoring in B-lineage ALL include antibodies to the pan-B-cell antigen CD19, markers of different stages of differentiation of B-lineage precursors of CD10, CD34, and CD20 and leukemia-associated markers different for each panel, such as CD22, CD38, CD58, CD45, TdT, CD13, CD33. The hyperexpression of CD10, CD34, CD19, TdT, the decreased expression of CD38, CD45, CD22, CD19, the simultaneous expression of markers of different stages of differentiation of B lymphocytes, such as CD10 and CD20, and the lymphoblast coexpression of myeloid markers of CD13, CD33, CDS15 are the most frequently described immunophenotype aberrations in B-lineage ALL. The selection of combinations of markers for MRD monitoring in children with T-ALL is based on the simultaneous expression of combinations of the antigens characteristic for early stages of differentiation of normal T lymphocytes, namely TdT and cytoplasmic CD3. Some authors consider the use of CD99 versus TdT to be most appropriate. There is recent evidence that MRD-positive patients have a higher cumulative risk for recurrences as compared with those without residual blasts. Moreover, the longer the tumor cells are retained during therapy, the worse the prognosis is. Thus, for choice of the adequate intensity of antitumor therapy, it is necessary to qualitatively and quantitatively assess MRD by multicolor flow cytometry at different stages of therapy.     

Extracorporeal life support in pediatric cardiac dysfunction

Background  

Low cardiac output (LCO) after corrective surgery remains a serious complication in pediatric congenital heart diseases (CHD). In the case of refractory LCO, extra corporeal life support (ECLS) extra corporeal membrane oxygenation (ECMO) or ventricle assist devices (VAD) is the final therapeutic option. In the present study we have reviewed the outcomes of pediatric patients after corrective surgery necessitating ECLS and compared outcomes with pediatric patients necessitating ECLS because of dilatated cardiomyopathy (DCM).     

Genomic polymorphism of strains of basic subspecies of plague causative agent

Genomic fingerprinting analysis of strains of the basic subspecies of plague causative agent extracted from different types of hotbeds in the Russian Federation and neighboring countries was performed. This analysis has enabled us to demonstrate their significant genetic polymorphism, as well as the similarity of their phenotypic characteristics. Strains of basic subspecies Y. pestis subsp. pestis are distributed into four genetic variants, each of which has its specific host organism. The conservatism of gene fingerprinting profiles of every genetic variant of Y. pestis subsp. pestis strains underlines the prospects of the proposed methodical approach in the case of the intraspecific differentiation of plague-agent strains (including those with atypical characteristics). The correlation of genovars with the host species gives one the opportunity to use them in the analysis of enzootic territories in during changes in hosts.     

In vitro screening for antitumour activity of Clinopodium vulgare L. (Lamiaceae) extracts

Aqueous extract of Clinopodium vulgare L. showed strong antitumour activity when tested in vitro on A2058 (human metastatic melanoma), HEp-2 (epidermoid carcinoma, larynx, human) and L5178Y (mouse lymphoma) cell lines-6 h after treatment disintegration of the nuclei and cell lysis started. Applied at a concentration of 80 microg/ml it reduced the cell survival to 1.0, 5.6 and 6.6%, respectively. The concentrations of aqueous extract inhibiting the growth of A2058, HEp-2 and L5178Y cells by 50% (IC50 values) were calculated to be 20, 10 and 17.8 microg/ml respectively. Two groups of active substances were detected: the first one, probably combining glycosides, influenced adhesion, while the second one caused massive cell vacuolisation. The chloroform extract, which contained ursolic acid and gentriacontan had also cytotoxic, however a little bit weaker effect. All changes observed were irreversible.