Antihypertensive drugs in blood donations in Serbia - Observational study.

INTRODUCTION: Most of the blood banks worldwide do not defer donors for their medication, with the exception of the teratogenic and platelet aggregation-inhibiting drugs use. In Serbia, where around 245.000 units of blood are collected each year, it is not common practice to consider the medication of potential blood donors. Therefore, the aim of this study was to quantify the presence of antihypertensive drugs in blood samples collected from blood donors treated for hypertension and to raise the issue of the recipient risks posed by drug residues in blood products. METHODS: Serum samples were obtained from 450 volunteer blood donors collected during the year 2017 who reported the use of antihypertensive drugs. All blood donors were required to interrupt regular antihypertensive therapy for 24 h before blood donation and LCMS determination of antihypertensive drugs was performed. RESULTS: Beta blockers were detected in 81 out of 203 samples which tested positive for the presence of antihypertensive drugs. Concentrations above the limit of quantification were determined in 58% of samples positive on beta blockers, containing metoprolol and bisoprolol in amounts sufficient to produce a therapeutic effect in the recipient. CONCLUSION: Therefore, the obtained results suggested that the safety of blood donation from individuals with treated hypertension should not be neglected. A solution for this problem might be the establishment of a standard LCMS screening procedure as a tool for testing the blood of donors taking drugs.

Correction to: pH control and the production of extracellular dextransucrase by Leuconostoc mesenteroides.

Unfortunately, M. M. Vrvic name has been published incorrectly in the original publication as M. M. Vrivic, corrected name appears in this erratum.

Assessing and visualising hazard impacts to enhance the resilience of Critical Infrastructures to urban flooding.

The design, construction and maintenance of Critical Infrastructures (CI) is commonly based on standards that are rigorous, so as to withstand any climate or weather-linked pressures. However, due to climate change, climate characteristics may shift, resulting in increased frequency/magnitude of potential failures, or exposure to new unknown risks. As vital components for the normal functioning of modern societies, the resilience of CIs under climate stressors encompasses their structural integrity, their operational elements, and their capacity to maximize business output. In this work, we propose an integrated and participatory methodological approach to enhance the resilience of interconnected CIs to urban flooding under climate change, by assessing the risk and introducing adaptation measures. The main objectives of the proposed methodology and approach are: (i) to provide scientific evidence for better understanding of how future climate regimes might affect normal operation of interconnected CI in urban areas during their lifespan; (ii) to assess the cost-effectiveness of different adaptation measures; (iii) to involve local stakeholders and operators in the co-design of the approach, as well as the assessment and the evaluation of adaptation measures; (iv) to combine computational modelling with advanced 3D visualisation techniques for effectively engaging stakeholders in decision making; (v) to include risk assessment and damage functions co-designed by end-users and local stakeholders; (vi) to integrate all of the aforementioned components in a specifically designed cloud platform as a Decision Support System for end-users, (vii) to validate the DSS by the end users and local stakeholders. The paper presents the computational background and tools. Additionally, it describes a Case Study in Torbay, UK, where the full methodology and the proposed participatory approach have been applied, with all the specifics, i.e., the scenarios of extreme flooding, the numerical and visualisation results, the response of the stakeholders and the evaluation of selected adaptation measures.

The Potassium Channel Kv1.5 Expression Alters During Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is a chronic, inflammatory, neurodegenerative disease with an autoimmune component. It was suggested that potassium channels, which are involved in crucial biological functions may have a role in different diseases, including MS and its animal model, experimental autoimmune encephalomyelitis (EAE). It was shown that voltage-gated potassium channels Kv1.5 are responsible for fine-tuning in the immune physiology and influence proliferation and differentiation in microglia and astrocytes. Here, we explored the cellular distribution of the Kv1.5 channel, together with its transcript and protein expression in the male rat spinal cord during different stages of EAE. Our results reveal a decrease of Kv1.5 transcript and protein level at the peak of disease, where massive infiltration of myeloid cells occurs, together with reactive astrogliosis and demyelination. Also, we revealed that the presence of this channel is not found in infiltrating macrophages/microglia during EAE. It is interesting to note that Kv1.5 channel is expressed only in resting microglia in the naïve animals. Predominant expression of Kv1.5 channel was found in the astrocytes in all experimental groups, while some vimentin+ cells, resembling macrophages, are devoid of Kv1.5 expression. Our results point to the possible link between Kv1.5 channel and the pathophysiological processes in EAE.

Pleiotropic Effects of Epithelial Mesenchymal Crosstalk on Head and Neck Cancer: EMT and beyond.

Epithelial mesenchymal crosstalk (EMC) describes the interaction of the tumor stroma and associated fibroblasts with epithelial cancer cells. In this study we analysed the effects of EMC on head and neck cancer cells. In tumor cell lines EMC was induced using media conditioned from a mix-culture of cancer cells and fibroblasts. Cell proliferation and chemotherapy response were assessed using direct cell counting. Flow cytometry, immunohistochemistry of markers of epithelial-mesenchymal transition (EMT) and subsequent TissueFaxs™ acquisition and quantification and western blot analysis were performed. Holotomographic microscopy imaging was used to visualize the effects of EMC on Cisplatin response of SCC-25 cells. EMC induced a hybrid epithelial-mesenchymal phenotype in SCC-25 cells with co-expression of vimentin and cytokeratin. This hybrid phenotype was associated with chemotherapy resistance and increased proliferation of the cells. The EMC conditioned medium led to an activation of the IL-6/STAT3 pathway with subsequent phosphorylation of STAT3. EMC induced a hybrid epithelial-mesenchymal phenotype in HNSCC cells accompanied by increased therapy resistance and cell proliferation. The IL-6/STAT3 pathway might be one of the major pathways involved in these EMC-related effects.

Can a single lactate value predict adverse outcome in critically ill newborn?

OBJECTIVES: The aim of this study was to investigate the role of the lactic acidosis, as an early predictor of significant consequences and/or a fatal outcome in term neonates after a perinatal asphyxia. BACKGROUND: Severe perinatal asphyxia can generate multiple organ dysfunction and neonatal mortality. METHODS: In routine clinical practice, after an admission to the Intensive Care Unit, lactate concentration was determined in capillary blood samples during the first one to six hours after birth in 55 term newborns with the post-asphyxial hypoxic-ischemic encephalopathy. The control group consisted of 36 healthy term neonates randomly selected in the maternity ward at the Gynecology and Obstetrics Clinic. RESULTS: Significantly higher concentrations of lactate (p 8.7 mmol/L with 80 % sensitivity and 82% specificity indicated the development of the hypoxic-ischemic encephalopathy stage II/III, while the lactate level>9.95 mmol/L was a predictor of death, with 75% sensitivity and 74.4% specificity. CONCLUSION: Determination of lactate concentrations in serum of term newborns associated with risk factors for the perinatal asphyxia is a useful tool in diagnosing metabolic disorders and ischemic damage, particularly severe clinical forms (Tab. 2, Fig. 3, Ref. 34).

Cartilage T1ρ and T2 relaxation times: longitudinal reproducibility and variations using different coils, MR systems and sites.

OBJECTIVE: To evaluate the longitudinal reproducibility and variations of cartilage T1ρ and T2 measurements using different coils, MR systems and sites. METHODS: Single-Site study: Phantom data were collected monthly for up to 29 months on four GE 3T MR systems. Data from phantoms and human subjects were collected on two MR systems using the same model of coil; and were collected on one MR system using two models of coils. Multi-site study: Three participating sites used the same model of MR systems and coils, and identical imaging protocols. Phantom data were collected monthly. Human subjects were scanned and rescanned on the same day at each site. Two traveling human subjects were scanned at all three sites. RESULTS: Single-Site Study: The phantom longitudinal RMS-CVs ranged from 1.8% to 2.7% for T1ρ and 1.8-2.8% for T2. Significant differences were found in T1ρ and T2 values using different MR systems and coils. Multi-Site Study: The phantom longitudinal RMS-CVs ranged from 1.3% to 2.6% for T1ρ and 1.2-2.7% for T2. Across three sites (n = 16), the in vivo scan-rescan RMS-CV was 3.1% and 4.0% for T1ρ and T2, respectively. Phantom T1ρ and T2 values were significantly different between three sites but highly correlated (R > 0.99). No significant difference was found in T1ρ and T2 values of traveling controls, with cross-site RMS-CV as 4.9% and 4.4% for T1ρ and T2, respectively. CONCLUSION: With careful quality control and cross-calibration, quantitative MRI can be readily applied in multi-site studies and clinical trials for evaluating cartilage degeneration.

Survival and prognostic factors of anaplastic thyroid carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is relatively rare and represents one of the most aggressive tumours with poor prognosis, despite therapy. The aim of the study was to analyse demographic and clinical characteristics of ATC patients, and to identify survival rates and prognostic factors. METHODS: In a retrospective study (1995-2005) ATC was found in 150 patients treated at our institution. Survival was calculated by Kaplan-Meier curve and log-rank test. Potential prognostic factors affecting survival were compared by Cox univariate and multivariate analyses. RESULTS: Mean survival time was 56 weeks; median survival time was 16 weeks and 1 and 5-year survival were 17% and 8%. More than 10% died during the first month and 50% died up to the fourth month. Multivariate analysis showed that age, goitre and surgery were independent prognostic factors of survival in all ATC patients. Among operated patients, the extent of tumour resection, distant metastasis and multicentricity were independent prognostic risk factors of survival. Postoperative radiotherapy was a protective factor. CONCLUSIONS: There is still no successful treatment of ATC that can guarantee long term survival. Younger patients with pre-existing goitre, who undergo complete resection of unilocular early stage ATC without distant metastasis and with postoperative external radiotherapy, stand a better chance of long-term survival.

Survival and Prognostic Factors of Anaplastic Thyroid Carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is relatively rare and represents one of the most aggressive tumours with poor prognosis, despite therapy. The aim of the study was to analyse demographic and clinical characteristics of ATC patients, and to identify survival rates and prognostic factors. METHODS: In a retrospective study (1995-2005) ATC was found in 150 patients treated at our institution. Survival was calculated by Kaplan-Meier curve and log-rank test. Potential prognostic factors affecting survival were compared by Cox univariate and multivariate analyses. RESULTS: Mean survival time was 56 weeks; median survival time was 16 weeks and 1 and 5-year survival were 17% and 8%. More than 10% died during the first month and 50% died up to the fourth month. Multivariate analysis showed that age, goitre and surgery were independent prognostic factors of survival in all ATC patients. Among operated patients, the extent of tumour resection, distant metastasis and multicentricity were independent prognostic risk factors of survival. Postoperative radiotherapy was a protective factor. CONCLUSIONS: There is still no successful treatment of ATC that can guarantee long term survival. Younger patients with pre-existing goitre, who undergo complete resection of unilocular early stage ATC without distant metastasis and with postoperative external radiotherapy, stand a better chance of long-term survival.

Laparoscopic management of ovarian benign masses.

PURPOSE: To determine whether the presence of normal ovarian tissue could assist in the diagnosis of large benign ovarian neoplasms in young females and in choosing the laparoscopic treatment. MATERIALS AND METHODS: A prospective study of 25 patients treated surgically for a cystic ovarian neoplasm measuring diameter more than ten cm or volume more than 500 ml and having normal ovarian tissue or ovarian crescent sign (OCS). Ultrasonography was performed at six weeks, then at three, six, nine, and 12 months postoperatively. RESULTS: The mean age of patients was 15.3 +/- 3.6 years, ranging between 6.5 and 19 years. The mean preoperative volume of the ovarian neoplasm was 1,686 +/- 1,380 cm3, ranging between 550 and 6,000 cm3. The presence of OCS was visualized by ultrasonography in all 25 patients and serum tumor markers were negative in 22. No borderline tumors or malignancies were identified. There was a statistically significant difference between the volume of the affected ovary and the contralateral ovary during the first six weeks follow-up, but without significant difference after three months. CONCLUSIONS: Postoperative ultrasound revealed that the affected ovary resumed its normal volume within three months after surgery, despite the thinned appearance of the ovarian cortex present on ultrasound as the OCS. Laparoscopic ovarian preservation should be the preferred surgical approach for adolescents to ensure the conservation of the entire ovarian tissue.

Giant Gartner duct cyst and elevated CA-125.

BACKGROUND: Gartner duct cysts represent vestigial remnants of the caudal end of the mesonephric (Wolffian) ducts. They are often associated with ureteral and renal abnormalities. In most cases they are solitary, less than 2 cm in diameter. Giant Gartner duct cysts are extremely rare. CASE: We present a girl with a giant Gartner duct cyst, without notable associated abnormalities or pathology, successfully treated by surgical excision. Preoperative aspiration revealed elevated level of CA-125 in the cyst fluid, with normal serum level of the same marker. CONCLUSION: Analyzing the aspirated fluid for CA-125 may be a useful tool for evaluation of cystic lesions in this region.

Ovary-preserving tumorectomy for immature teratoma in an adolescent--case report.

The authors present a case of a 14-year-old premenarchal girl with a large solid tumor of the left ovary. The rim of normal ovarian tissue was visible around the tumor on ultrasonography scan. Although the levels of two tumor markers, LDH and CA125, were elevated, the authors performed an organ-sparing tumorectomy. The final pathology report revealed foci of immature neural tissue, with a final diagnosis immature teratoma Stage Ia.

In vitro scan for enhancers at the TCF7L2 locus.

AIMS/HYPOTHESIS: Recent functional characterisations of genome-wide association study (GWAS) loci suggest that cis-regulatory variation may be a common paradigm for complex disease susceptibility. Several studies point to a similar mechanism at the transcription factor 7-like 2 (TCF7L2) GWAS locus for type 2 diabetes. To address this possibility, we carried out an in vitro scan of this diabetes-associated locus to fine-map cis-regulatory sequences within this genomic interval. METHODS: A systematic cell-based enhancer strategy was employed to interrogate all sequences within the 92 kb type-2-diabetes-association interval for cis-regulatory activity in a panel of cell lines (HCT-116, Neuro-2a, C2C12, U2OS, MIN6 and HepG2). We further evaluated chromatin state at a subset of these regions in HCT-116 and U2OS cells and examined allelic-specific enhancer properties at the type-2-diabetes-associated single nucleotide polymorphism (SNP) rs7903146. RESULTS: In total, we assigned cis-regulatory activity to approximately 30% (9/28) of constructs tested. Notably, a subset of enhancers was active across multiple cell lines and overlapped with key epigenetic markers suggestive of cis-regulatory sequences. We further replicated the allelic-specific properties for SNP rs7903146 in pancreatic beta cells and additionally demonstrate identical allelic-specific enhancer effects in other cell lines. CONCLUSIONS: These results provide a detailed map of cis-regulatory elements within the TCF7L2 GWAS locus and support the hypothesis of cis-regulatory variation leading to type 2 diabetes predisposition. The detection of allelic-specific effects for SNP rs7903146 in multiple cell lines further alludes to the likelihood of a peripheral defect in disease aetiology.

The characterisation of lactic acid bacteria during the fermentation of an artisan Serbian sausage (Petrovská Klobása).

Petrovská Klobása is an artisan Serbian sausage made only from meat and spices without any additives or starter cultures. In order to characterise lactic acid bacteria (LAB) microflora, a total number of 404 LAB strains were isolated from 15 samples collected during 90 days of the fermentation and 120 days of storage of one batch of Petrovská Klobása. The isolates were preliminarily identified by phenotypic tests and subjected to (GTG)5-PCR fingerprinting. Representatives of each group were identified by 16S rDNA sequencing. The results showed that among the isolates, Lactobacillus sakei and Leuconostoc mesenteroides predominate with 36.4% and 37.1% of total LAB strains, respectively. Pediococcus pentosaceus was also isolated in high proportion (18.4%) whereas Enterococcus durans and Enterococcus caseliflavus made only 1% and 6% of the total isolates, correspondingly. The analysis of vacuum packed and modified atmosphere packed (MAP) samples showed higher presence of L. mesenteroides and L. sakei in the total microflora.

Calibration of a 1D/1D urban flood model using 1D/2D model results in the absence of field data.

Recently increased flood events have been prompting researchers to improve existing coupled flood-models such as one-dimensional (1D)/1D and 1D/two-dimensional (2D) models. While 1D/1D models simulate sewer and surface networks using a one-dimensional approach, 1D/2D models represent the surface network by a two-dimensional surface grid. However their application raises two issues to urban flood modellers: (1) stormwater systems planning/emergency or risk analysis demands for fast models, and the 1D/2D computational time is prohibitive, (2) and the recognized lack of field data (e.g. Hunter et al. (2008)) causes difficulties for the calibration/validation of 1D/1D models. In this paper we propose to overcome these issues by calibrating a 1D/1D model with the results of a 1D/2D model. The flood-inundation results show that: (1) 1D/2D results can be used to calibrate faster 1D/1D models, (2) the 1D/1D model is able to map the 1D/2D flood maximum extent well, and the flooding limits satisfactorily in each time-step, (3) the 1D/1D model major differences are the instantaneous flow propagation and overestimation of the flood-depths within surface-ponds, (4) the agreement in the volume surcharged by both models is a necessary condition for the 1D surface-network validation and (5) the agreement of the manholes discharge shapes measures the fitness of the calibrated 1D surface-network.

An analysis of the combined consequences of pluvial and fluvial flooding.

Intense rainfall in urban areas often generates both pluvial flooding due to the limited capacity of drainage systems, as well as fluvial flooding caused by deluges from river channels. The concurrence of pluvial and fluvial flooding can aggravate their (individual) potential damages. To analyse the impact caused by individual and composite type of flooding, the SIPSON/UIM model, an integrated 1D sewer and 2D overland flow was applied to numerical modelling. An event matrix of possible pluvial scenarios was combined with hypothetic overtopping and breaching situations to estimate the surface flooding consequences in the Stockbridge area, Keighley (Bradford, UK). The modelling results identified different flooding drivers in different parts of the study area and showed that the worst scenarios resulted from synthesised events.

Value of ultrasonographic detection of normal ovarian tissue in the differential diagnosis of adnexal masses in pediatric patients.

OBJECTIVE: The aim of the study was to evaluate whether the presence of normal ovarian tissue, the 'ovarian crescent sign' (OCS), could assist in the differential diagnosis between benign and malignant adnexal masses in young patients. METHODS: This was a prospective observational study, from March 2004 to January 2006, which included 98 patients younger than 20 years of age (including two with bilateral tumors) with an ultrasonographic diagnosis of an adnexal mass. Morphological assessment using the Ueland index was performed in each case. Patients were also systematically examined for the presence of the OCS and a comparison was made with the Ueland index. All findings in surgically treated patients were compared with the final histological diagnosis. RESULTS: There were 100 adnexal masses: 90 were benign and 10 were malignant. Forty-eight were managed expectantly and 52, including 17 cases of adnexal torsion, underwent surgical treatment. The OCS was found in 65 (72%) benign adnexal masses and in one (10%) non-invasive malignant tumor. A Ueland index score of < 7 was found in 85 (94%) benign masses and in one (10%) non-invasive malignancy. The OCS was seen in 15 (45%) of 33 masses in premenarchal patients and in 51 (76%) of 67 masses in postmenarchal patients. The OCS was absent in 15 (88%) of the torsioned adnexal masses. CONCLUSIONS: The presence of normal ovarian tissue adjacent to an ovarian mass is a useful morphological feature that can assist exclusion of a malignant tumor in pediatric and adolescent patients. When compared with the Ueland index, diagnostic sensitivity of the OCS is similar, but specificity is lower. The presence of the OCS is significantly less frequent in premenarchal patients than in postmenarchal patients.

An effective multi-objective approach to prioritization of sewer pipe inspection.

The first step in the decision making process for proactive sewer rehabilitation is to assess the condition of conduits. In a risk-based decision context the set of sewers to be inspected first should be identified based on the trade-off between the risk of failures and the cost of inspections. In this paper the most effective inspection works are obtained by solving a multi-objective optimization problem where the total cost of the survey programme and the expected cost of emergency repairs subsequent to blockages and collapses are considered simultaneously. A multi-objective genetic algorithm (MOGA) is used to identify a set of Pareto-optimal inspection programmes. Regardless of the proven effectiveness of the genetic-algorithm approach, the scrutiny of MOGA-based inspection strategies shows that they can differ significantly from each other, even when having comparable costs. A post-processing of MOGA solutions is proposed herein, which allows priority to be assigned to each survey intervention. Results are of practical relevance for decision makers, as they represent the most effective sequence of inspection works to be carried out based on the available funds. The proposed approach is demonstrated on a real large sewer system in the UK.

The incidence of familial nonmedullary thyroid cancer in a large case series.

PURPOSES OF THE STUDY: In contrast to familial medullary carcinoma, familial nonmedullary thyroid carcinoma (FNMTC) is less frequent and has been less investigated. The aim of this study was to determine the frequency of FNMTC and analyse the main demographic and clinical characteristics of the patients. MATERIAL AND METHODS: Data on 1411 patients surgically treated for nonmedullary thyroid carcinoma, in the Center for Endocrine Surgery in Belgrade, from 1995 to 2006 were analysed. The possible presence of malignant tumours of the thyroid gland was investigated in their closest relatives in order to identify cases of FNMTC. Only data on first-degree relatives (parents and children) and second-degree relatives (grandparents, grandchildren and siblings) were taken into account in the analysis. RESULTS: Thirteen patients (11 females and 2 males) (0.92% of those with nonmedullary carcinoma of the thyroid gland) had a familial form of the disease. In five families two members had a tumour, and in one family three members. In five out of six families it was a papillary carcinoma and in one family a follicular carcinoma. Patient age varied from 20 to 79 years, with a mean age of 40 years. The tumour size ranged from 5 to 60 mm (mean 25 mm). In two of the thirteen cases the tumour penetrated the capsule of the thyroid gland. In four cases the tumour was multicentric and bilateral, and in a further two metastases were present in regional lymph nodes. During the follow-up period, which lasted from 2 to 12 years (mean 8.5 years), two relapses were detected. CONCLUSION: Familial nonmedullary carcinoma of the thyroid gland occurs very rarely.