Human erythroleukemia genetics and transcriptomes identify master transcription factors as functional disease drivers.

Acute erythroleukemia (AEL or acute myeloid leukemia [AML]-M6) is a rare but aggressive hematologic malignancy. Previous studies showed that AEL leukemic cells often carry complex karyotypes and mutations in known AML-associated oncogenes. To better define the underlying molecular mechanisms driving the erythroid phenotype, we studied a series of 33 AEL samples representing 3 genetic AEL subgroups including TP53-mutated, epigenetic regulator-mutated (eg, DNMT3A, TET2, or IDH2), and undefined cases with low mutational burden. We established an erythroid vs myeloid transcriptome-based space in which, independently of the molecular subgroup, the majority of the AEL samples exhibited a unique mapping different from both non-M6 AML and myelodysplastic syndrome samples. Notably, >25% of AEL patients, including in the genetically undefined subgroup, showed aberrant expression of key transcriptional regulators, including SKI, ERG, and ETO2. Ectopic expression of these factors in murine erythroid progenitors blocked in vitro erythroid differentiation and led to immortalization associated with decreased chromatin accessibility at GATA1-binding sites and functional interference with GATA1 activity. In vivo models showed development of lethal erythroid, mixed erythroid/myeloid, or other malignancies depending on the cell population in which AEL-associated alterations were expressed. Collectively, our data indicate that AEL is a molecularly heterogeneous disease with an erythroid identity that results in part from the aberrant activity of key erythroid transcription factors in hematopoietic stem or progenitor cells.

KANK1-NTRK3 fusions define a subset of BRAF mutation negative renal metanephric adenomas.

BACKGROUND: Metanephric adenoma (MA) is a rare benign renal neoplasm. On occasion, MA can be difficult to differentiate from renal malignancies such as papillary renal cell carcinoma in adults and Wilms̕ tumor in children. Despite recent advancements in tumor genomics, there is limited data available regarding the genetic alterations characteristic of MA. The purpose of this study is to determine the frequency of metanephric adenoma cases exhibiting cytogenetic aberration t (9;15)(p24;q24), and to investigate the association between t (9,15) and BRAF mutation in metanephric adenoma. METHODS: This study was conducted on 28 archival formalin fixed paraffin-embedded (FFPE) specimens from patients with pathologically confirmed MA. Tissue blocks were selected for BRAF sequencing and fluorescent in situ hybridization (FISH) analysis for chromosomal rearrangement between KANK1 on chromosome 9 (9p24.3) and NTRK3 on chromosome 15 (15q25.3), which was previously characterized and described in two MA cases. RESULTS: BRAFV600E mutation was identified in 62% of our cases, 9 (38%) cases were BRAFWT, and 4 cases were uninformative. Of the 20 tumors with FISH results, two (10%) were positive for KANK1-NTRK3 fusion. Both cases were BRAFWT suggesting mutual exclusivity of BRAFV600E and KANK1-NTRK3 fusion, the first such observation in the literature. CONCLUSIONS: Our data shows that BRAF mutation in MA may not be as frequent as suggested in the literature and KANK-NTRK3 fusions may account for a subset of BRAFWT cases in younger patients. FISH analysis for KANK1-NTRK3 fusion or conventional cytogenetic analysis may be warranted to establish the diagnosis of MA in morphologically and immunohistochemically ambiguous MA cases lacking BRAF mutations.

Dopamine neurons modulate pheromone responses in Drosophila courtship learning.

Learning through trial-and-error interactions allows animals to adapt innate behavioural 'rules of thumb' to the local environment, improving their prospects for survival and reproduction. Naive Drosophila melanogaster males, for example, court both virgin and mated females, but learn through experience to selectively suppress futile courtship towards females that have already mated. Here we show that courtship learning reflects an enhanced response to the male pheromone cis-vaccenyl acetate (cVA), which is deposited on females during mating and thus distinguishes mated females from virgins. Dissociation experiments suggest a simple learning rule in which unsuccessful courtship enhances sensitivity to cVA. The learning experience can be mimicked by artificial activation of dopaminergic neurons, and we identify a specific class of dopaminergic neuron that is critical for courtship learning. These neurons provide input to the mushroom body (MB) γ lobe, and the DopR1 dopamine receptor is required in MBγ neurons for both natural and artificial courtship learning. Our work thus reveals critical behavioural, cellular and molecular components of the learning rule by which Drosophila adjusts its innate mating strategy according to experience.

Evaluation of periodontal ligament cell viability in different storage media based on human PDL cell culture experiments-A systematic review.

BACKGROUND/AIMS: The best treatment for an avulsed tooth is immediate replantation. If this is not possible, a proper transport medium is required for the maintenance of viability of the periodontal ligament cells (PDL). The aim was to systematically review the efficacy of different storage media used for the survival of PDL cells of avulsed teeth in the in vitro setting. METHODS: The search strategy was based on the MeSH keywords in PubMed/MEDLINE: "Transport media for avulsed teeth," "Storage media for avulsed teeth," "Knocked out teeth," "Tooth avulsion," "Biological transport of avulsed tooth," "Cell survival of avulsed tooth," "Cell viability of avulsed tooth," "Tooth replantation," and "Periodontal ligament in avulsed teeth." The "AND" and "OR" Boolean operators were applied to combine keywords. Each study was evaluated for eight criteria, including use of human PDL, in vitro cell culture models, the number of passages, types of storage media, percentages of surviving PDL cells, pH and osmolality of storage media, and the type of test used to asses PDL viability. RESULTS: In 15 selected studies, nine storage media (HBSS, tap water, DMEM, milk, saliva, 10% and 20% propolis, Gatorade, and Viaspan) were analyzed at six time points. For storage up to 2 hours, HBSS, DMEM, milk, 10% propolis, 20% propolis, and Viaspan conserved more than 80% of PDL viability. For storage at 24 hours, Viaspan showed best cell survival at 88.4%, followed by DMEM (70.9%) and 10% propolis (68.3%). Milk and HBSS showed similar PDL survival at 24 hours (57.2% and 57.3%, respectively). CONCLUSIONS: Milk remains the most convenient, cheapest, and readily available solution in most situations while also being capable of keeping PDL cells alive. Further studies are required to evaluate the efficacy of more commonly found storage media besides milk.

Chemical toxicity and radioactivity of depleted uranium: The evidence from in vivo and in vitro studies.

The main aim of this review is to summarize and discuss the current state of knowledge on chemical toxicity and radioactivity of depleted uranium (DU) and their effect on living systems and cell lines. This was done by presenting a summary of previous investigations conducted on different mammalian body systems and cell cultures in terms of potential changes caused by either chemical toxicity or radioactivity of DU. In addition, the authors aimed to point out the limitations of those studies and possible future directions. The majority of both in vitro and in vivo studies performed using animal models regarding possible effects caused by acute or chronic DU exposure has been reviewed. Furthermore, exposure time and dose, DU particle solubility, and uranium isotopes as factors affecting the extent of DU effects have been discussed. Special attention has been dedicated to chromosomal aberrations, DNA damage and DNA breaks, as well as micronuclei formation and epigenetic changes, as DU has recently been considered a possible causative factor of all these processes. Therefore, this approach might represent a novel area of study of DU-related irradiation effects on health. Since different studies offer contradictory results, the main aim of this review is to summarize and briefly discuss previously obtained results in order to identify the current opinion on DU toxicity and radioactivity effects in relation to exposure type and duration, as well as DU properties.

The reality of cancer treatment in a developing country: the effects of delayed TKI treatment on survival, cytogenetic and molecular responses in chronic myeloid leukaemia patients.

Cancer patients in developing and low-income countries have limited access to target therapies. For example, tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukaemia patients (CML) is often delayed. In Bosnia, 16% of patients received immediate TKI treatment (<3 months of diagnosis), while 66% of patients received therapy after a median 14-month wait period. To assess the effect of delayed treatment on outcome, three patient groups were studied according to the time they received TKI treatment (0-5 months, 6-12 months and >13 months delay). The primary endpoints were complete cytogenetic (CCyR) and major molecular response (MMR) at 12 months. At 12 months of therapy, CCyR and MMR rates on imatinib decreased significantly: CCyR was achieved in 67% of patients in the immediate imatinib treatment group, 18% of patients in 6-12 months group and 15% of patients in >13 months wait group. MMR rates at 12 months occurred in 10% of patients with immediate treatment, 6% of those in 6-12 months group and 0% of patients in >13 months wait group. However, CCyR and MMR rates in patients on nilotinib were not associated with duration of treatment delay. Our data suggests that the deleterious effect of a prolonged TKI therapy delay may be ameliorated by the more active TKI nilotinib.

Gene-expression analysis of matrix metalloproteinases 1 and 2 and their tissue inhibitors in chronic periapical inflammatory lesions.

BACKGROUND: Periapical inflammatory lesions have been investigated previously, but understanding of pathogenesis of these lesions (granulomas and radicular cysts) at the molecular level is still questionable. Matrix metalloproteinases (MMPs) are enzymes involved in the development of periapical pathology, specifically inflammation and tissue destruction. To elucidate pathogenesis of periapical granulomas and radicular cysts, we undertook a detailed analysis of gene expression of MMP-1, MMP-2 and their tissue inhibitors, TIMP-1 and TIMP-2. METHODS: A total of 149 samples were analyzed using real-time PCR (59 radicular cysts, 50 periapical granulomas and 40 healthy gingiva samples as controls) for expression of MMP-1, MMP-2, TIMP-1 and TIMP-2 genes. The determination of best reference gene for expression analysis of periapical lesions was done using a panel of 12 genes. RESULTS: We have shown that ß-actin and GAPDH are not the most stable reference controls for gene expression analysis of inflammatory periapical tissues and healthy gingiva. The most suitable reference gene was determined to be SDHA (a succinate dehydrogenase complex, subunit A, flavoprotein [Fp]). We found that granulomas (n = 50) and radicular cysts (n = 59) exhibited significantly higher expression of all four examined genes, MMP-1, MMP-2, TIMP-1, and TIMP-2, when compared to healthy gingiva (n = 40; P < 0.05). CONCLUSION: This study has confirmed that the expression of MMP-1, MMP-2, TIMP-1, and TIMP-2 genes is important for the pathogenesis of periapical inflammatory lesions. Since the abovementioned markers were not differentially expressed in periapical granulomas and radicular cysts, the challenge of finding the genetic differences between the two lesions still remains.

Clinical trials in Bosnia and Herzegovina: Challenges and future perspectives.

Background: Clinical trials (CTs) are research investigations in which participants receive medical treatments, interventions, or tests to assess their safety and efficacy. Each planned clinical is registered through local or national medical agencies, which may differ in the amount of administrative and legal procedures. The objective of this study was to systematically analyze the registration process for clinical trials in Bosnia and Herzegovina in comparison to other Balkan countries. Methods: The search strategy was based using two online databases: Clinicaltrials.gov (CTGR) and Cortellis Clinical Trials Intelligence (cTi). Search engines included studies until 26th April 2021 and countries were compared in terms of the number of studies, status, type, funding, clinical phases and demographic data. Results: The total number of clinical trials from Bosnia and Herzegovina recorded in the CTGR database was 219, while the cTi database comprised 254 registered studies. The total number of reported clinical trials in CTGR and cTi databases were highest in Serbia (n = 1229, n = 1438), followed by Croatia (n = 1142, n = 1300), and Slovenia (n = 801, n = 948), respectively. However, the highest number of clinical trials per capita is in Slovenia (3.85e-4 in CTGR; 4.56e-4 in cTi), followed by Croatia (2.78e-4 in CTGR; 3.17e-4 in cTi), Serbia (1.41e-4 in CTGR; 1.65e-4 in cTi), and Bosnia and Herzegovina (0.67e-4 CTGR; 0.78e-4 cTi). Conclusion: Our analysis showed that Bosnia has the lowest number of clinical trials in the Balkans. Furthermore, the registration process is complex and longer than in developed countries. Since the healthcare system has been in a transition in the past decade, clinical trials are underutilized as a tool for the improvement of patient care. The clinical trial registration process could be improved by establishing an ethical committee at the state level and by enabling a parallel submission process to ethical committees and databases.

COVID-19 vaccine acceptance and rejection in an adult population in Bosnia and Herzegovina.

BACKGROUND: Bosnia and Herzegovina is among ten countries in the world with the highest mortality rate due to COVID-19. Lack of lockdown, open borders, high mortality rate, no vaccination plan, and strong domestic anti-vaccination movement present serious COVID-19 concerns in Bosnia and Herzegovina. In such circumstances, we set out to study 1) the willingness of general public to receive the vaccine, 2) factors that affect vaccine rejection, and 3) motivation for vaccine acceptance. METHODS: A cross-sectional study was conducted among 10471 adults in Bosnia and Herzegovina to assess the acceptance or rejection of participants toward COVID-19 vaccination. Using a logistic regression model, we examined the associations of sociodemographic characteristics with vaccine rejection, reasons for vaccine hesitancy, preferred vaccine manufacturer, and information sources. RESULTS: Surprisingly, only 25.7% of respondents indicated they would like to get a COVID-19 vaccine, while 74.3% of respondents were either hesitant or completely rejected vaccination. The vaccine acceptance increased with increasing age, education, and income level. Major motivation of pro-vaccination behavior was intention to achieve collective immunity (30.1%), while the leading incentive for vaccine refusal was deficiency of clinical data (30.2%). The Pfizer-BioNTech vaccine is shown to be eightfold more preferred vaccine compared to the other manufacturers. For the first time in Bosnia, vaccine acceptance among health care professionals has been reported, where only 39.4% of healthcare professionals expressed willingness to get vaccinated. CONCLUSION: With the high share of the population unwilling to vaccinate, governmental impotence in securing the vaccines supplies, combined with the lack of any lockdown measures suggests that Bosnia and Herzegovina is unlikely to put COVID-19 pandemic under control in near future.

A Review of Molecular and Genetic Diagnostics of Myeloid Malignancies with Emphasis on Diagnostics in Bosnia and Herzegovina.

Here we describe the major genetic and genomic aberrations found in myeloid malignancies and how those markers are used in patients' diagnosis, prognosis, and targeted treatment. In Bosnia and Herzegovina, cytogenetic and molecular diagnostics for myeloid malignancies have been established and continually improved since 2005. We report the current state of available diagnostic tools for myeloid malignancies in Bosnia and Herzegovina. Myeloid malignancies are a heterogeneous group of clonal blood diseases characterized by defects in hematopoietic stem cells and myeloid progenitors that lead to abnormal proliferation, differentiation, localization, and self-renewal. Most common myeloid malignancies include myeloproliferative neoplasms (MPNs), myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). Molecular diagnostics of myeloid malignancies have significantly expanded in the last decade with new genetic and genomic markers for diagnosis, prognosis, and treatment. CONCLUSION: In the last decade, several new genomic markers important for patient diagnosis, prognosis, and therapy have been discovered that need to be implemented in routine molecular diagnostics not only in developed nations but also in developing nations such as Bosnia and Herzegovina.

Multiplexed detection of SARS-CoV-2 and other respiratory infections in high throughput by SARSeq.

The COVID-19 pandemic has demonstrated the need for massively-parallel, cost-effective tests monitoring viral spread. Here we present SARSeq, saliva analysis by RNA sequencing, a method to detect SARS-CoV-2 and other respiratory viruses on tens of thousands of samples in parallel. SARSeq relies on next generation sequencing of multiple amplicons generated in a multiplexed RT-PCR reaction. Two-dimensional, unique dual indexing, using four indices per sample, enables unambiguous and scalable assignment of reads to individual samples. We calibrate SARSeq on SARS-CoV-2 synthetic RNA, virions, and hundreds of human samples of various types. Robustness and sensitivity were virtually identical to quantitative RT-PCR. Double-blinded benchmarking to gold standard quantitative-RT-PCR performed by human diagnostics laboratories confirms this high sensitivity. SARSeq can be used to detect Influenza A and B viruses and human rhinovirus in parallel, and can be expanded for detection of other pathogens. Thus, SARSeq is ideally suited for differential diagnostic of infections during a pandemic.

Intercellular Mitochondrial Transfer in the Tumor Microenvironment.

Cell-to-cell communication is a fundamental process in every multicellular organism. In addition to membrane-bound and released factors, the sharing of cytosolic components represents a new, poorly explored signaling route. An extraordinary example of this communication channel is the direct transport of mitochondria between cells. In this review, we discuss how intercellular mitochondrial transfer can be used by cancer cells to sustain their high metabolic requirements and promote drug resistance and describe relevant molecular players in the context of current and future cancer therapy.

Lifestyle risk factors and comorbidities of cancer patients in a country with limited resources.

Aim To investigate quality of life and exposure to lifestyle risk factors of cancer patients in Bosnia and Herzegovina and a correlation of cancer type with lifestyle risk factors. Methods This was a cross-sectional study conducted on 200 cancer patients from the Clinical Centre of the University of Sarajevo. The respondents completed an anonymous questionnaire consisting of seven sections: basic patient information, physical activity, dietary habits including alternative medicine, tobacco use, alcohol consumption, anxiety, and comorbidities. Results A total of 150 (75%) patients were overweight with 113 (56%) of them being less physically active after the confirmed diagnosis. After the diagnosis, 79 (40%) patients ate less food, and 154 (77%) healthier; 130 (65%) reported consumption of alternative medicine and food supplements, 39 (30%) spent >1/4 of average monthly salary on these products. Majority never consumed alcohol, 135 (68%) and 101 (51%) patients reported history of tobacco use. Being obese was an independent predictor for colorectal carcinoma; being less obese was linked to a decreased risk of breast cancer diagnosis. Physical activity was linked to a decreased risk of lung cancer diagnosis. Many patients (122; 61%) reported having chronic comorbidities, mostly hypertension, while 44 (22%) patients were proven to be clinically anxious. Conclusion Our data suggest lack of public awareness of the consequences of unhealthy lifestyles. Risk factors such as alcohol consumption and tobacco use differed from other European countries. Significance of lifestyle changes after the diagnosis for reducing mortality and cancer recurrence requires further research. Prevention programs and more data are needed.

The effects of mutational profiles on phenotypic presentation of myeloproliferative neoplasm subtypes in Bosnia: 18 year follow-up.

The identification of mutually exclusive somatic mutations shared among myeloproliferative neoplasm (MPN) subtypes has provided a powerful tool for studying disease evolution. Clinical features, gene mutations, and survival over 18 years were analyzed in MPN patients. One hundred thirty-eight MPN patients were subcategorized according to MPN subtypes: essential thrombocythemia (ET, n = 41), polycythemia vera (PV, n = 56), primary myelofibrosis (PMF, n = 10), and MPN unclassified (MPN-U, n = 31). Patient characteristics included clinical parameters, overall survival (OS), and mutational status of the Janus kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL) genes. We compared hematologic and clinical features of JAK2V617F-ET vs. CALR-mutated ET vs. JAK2V617F-PV patients. JAK2V617F-patients had higher values of erythrocytes, hemoglobin, and hematocrit compared to CALR-mutated patients (p < 0.05). The mutant allele burden in JAK2V617F-PV and JAK2V617F-ET patients directly correlated with erythrocyte, hemoglobin, and hematocrit values, but it inversely correlated with platelet count. Thus, mutant allele burden was an indicator of the clinical phenotype in JAK2V617F-MPN patients. OS was not affected by the mutational status. In general, mutated JAK2, CALR, and MPL genes left specific hematological signatures.

Quantitative Analysis of CCL5 and ep300 in Periapical Inflammatory Lesions.

OBJECTIVES: In silico bioinformatical analysis suggested that the expression of two genes, CCL5 (C-C Motif Chemokine Receptor 5) and ep300 (Histone acetyltransferase p300), could be used as potential new biomarkers in differentiation between periapical granulomas and radicular cysts. Thus, we hypothesized that gene expression of CCL5 and ep300 in periapical lesions would classify the lesions as either granuloma or cyst. MATERIALS: Patient samples (n=122) included 46 periapical granulomas, 38 radicular cysts and 38 healthy gingival samples as controls. Real-time PCR analysis of CCL5 and ep300 transcripts was compared to SDHA (Succinate dehydrogenase complex, subunit A) as the reference. Clinical parameters (e.g., intensity of inflammation and lesion size) were measured and correlated with CCL5 and ep300 expression. ROC (Receiver operating characteristic) and logistic regression analyses were used to establish the diagnostic character of ΔCt values. RESULTS: Granulomas and radicular cysts had significantly higher expression of CCL5 and ep300 compared to controls (P<0.05). However, no differences were observed when comparing granulomas and radicular cysts. ROC analyses showed that CCL5 and ep300 have good diagnostic accuracy, but low accuracy for distinguishing between the lesions. CONCLUSIONS: This study confirmed that expression of CCL5 and ep300 is relevant for the pathogenesis of periapical inflammatory lesions but cannot be used as a distinctive marker between these lesions.

Nonsyndromic Examples of Odontogenic Keratocysts: Presentation of Interesting Cases with a Literature Review.

The odontogenic keratocyst (OKC) may occur at any age. However, it mostly occurs during the second and third decades of life. Compared to other odontogenic cysts, this type occurs with a frequency of 5-15%. It is more common in the mandible region and in the male sex. Histologically, odontogenic keratocysts are characterized by the presence of an external connective tissue capsule, with keratinizing lining of the epithelium consisting of 5-8 cell layers with marked palisadisation of polarized basal cells and a corrugated parakeratin layer. The objective of this study is to present cases of odontogenic keratocysts, with reference to the latest classification and dilemmas in therapeutic doctrine. This project was realized in the form of descriptive studies, specifically in a series of cases. A collection of four individual cases was found at the Department of Oral Surgery. Due to the proper approach towards diagnosis, adequate and detailed histopathological analysis, and suitable therapeutic procedures, all cases of odontogenic keratocysts were successfully treated without complications. Enucleation of OKC, with a regular follow-up, proved to be the effective therapeutic choice for the patients described in this paper. Only in the case of recurrence would we consider other therapeutic options, primarily enucleation in combination with Carnoy's solution.

Application of Neural Networks for classification of Patau, Edwards, Down, Turner and Klinefelter Syndrome based on first trimester maternal serum screening data, ultrasonographic findings and patient demographics.

BACKGROUND: The usage of Artificial Neural Networks (ANNs) for genome-enabled classifications and establishing genome-phenotype correlations have been investigated more extensively over the past few years. The reason for this is that ANNs are good approximates of complex functions, so classification can be performed without the need for explicitly defined input-output model. This engineering tool can be applied for optimization of existing methods for disease/syndrome classification. Cytogenetic and molecular analyses are the most frequent tests used in prenatal diagnostic for the early detection of Turner, Klinefelter, Patau, Edwards and Down syndrome. These procedures can be lengthy, repetitive; and often employ invasive techniques so a robust automated method for classifying and reporting prenatal diagnostics would greatly help the clinicians with their routine work. METHODS: The database consisted of data collected from 2500 pregnant woman that came to the Institute of Gynecology, Infertility and Perinatology "Mehmedbasic" for routine antenatal care between January 2000 and December 2016. During first trimester all women were subject to screening test where values of maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (ß-hCG) were measured. Also, fetal nuchal translucency thickness and the presence or absence of the nasal bone was observed using ultrasound. RESULTS: The architectures of linear feedforward and feedback neural networks were investigated for various training data distributions and number of neurons in hidden layer. Feedback neural network architecture out performed feedforward neural network architecture in predictive ability for all five aneuploidy prenatal syndrome classes. Feedforward neural network with 15 neurons in hidden layer achieved classification sensitivity of 92.00%. Classification sensitivity of feedback (Elman's) neural network was 99.00%. Average accuracy of feedforward neural network was 89.6% and for feedback was 98.8%. CONCLUSION: The results presented in this paper prove that an expert diagnostic system based on neural networks can be efficiently used for classification of five aneuploidy syndromes, covered with this study, based on first trimester maternal serum screening data, ultrasonographic findings and patient demographics. Developed Expert System proved to be simple, robust, and powerful in properly classifying prenatal aneuploidy syndromes.

Meta-analysis of depleted uranium levels in the Middle East region.

Since the first widespread use of depleted uranium in military in the 1991 Gulf War, the so-called "Gulf War Syndrome" has been a topic of ongoing debate. However, a low number of reliable scientific papers demonstrating the extent of possible contamination as well as its connection to the health status of residents and deployed veterans has been published. The authors of this study have therefore aimed to make a selection of data based on strict inclusion and exclusion criteria. With the goal of clarifying the extent of DU contamination after the Gulf Wars, previously published data regarding the levels of DU in the Middle East region were analyzed and presented in the form of a meta-analysis. In addition, the authors attempted to make a correlation between the DU levels and their possible effects on afflicted populations. According to results observed by comparing 234U/238U and 235U/238U isotopic activity ratios, as well as 235U/238U mass ratios in air, water, soil and food samples among the countries in the Middle East region, areas indicating contamination with DU were Al Doha, Manageesh and Um Al Kwaty in Kuwait, Al-Salman, Al-Nukhaib and Karbala in Iraq, Beirut in Lebanon and Sinai in Egypt. According to these data, no DU contamination was observed in Algeria, Israel, Afghanistan, Oman, Qatar, Iran, and Yemen. Due to the limited number of reliable data on the health status of afflicted populations, it was not possible to make a correlation between DU levels and health effects in the Middle East region.

Evaluation of Diagnostic Efficiency of Alpha-Fetoprotein in Patients with Liver Cirrhosis and Hepatocellular Carcinoma: Single-Center Experience.

BACKGROUND: AFP serum levels are considered as diagnostic and specific for hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC). AIM: This study aimed to examine the diagnostic value of AFP in the distinguishing of patients with HCC from patients with LC, and to analyse the potential correlation between AFP levels and liver disease stages. MATERIAL AND METHODS: Fifty patients with LC and fifty patients with HCC were included in this study. The majority of the patients were males, while the HBV aetiology was dominant. RESULTS: Significant differences between LC and HCC patients were detected for AST, ALT, GGT, bilirubin, AFP and AP. Patients with HCC had higher AFP values compared to LC. There was no significant correlation between the size of the tumour lesion and serum AFP levels. A positive correlation between AFP concentration and GGT activity was determined, as was the negative correlation between AFP and age of the subjects. The AFP value of 23.34 ng/m showed high sensitivity (84%) and specificity (82%). CONCLUSION: The size of the surface below the ROC curve (AUC) was 0.877 (0.80-0.95), which makes AFP a good biomarker and this diagnostic test is sufficient to separate patients with HCC and LC.

Meta-analysis of depleted uranium levels in the Balkan region.

In recent years, contradicting data has been published on the connection between the presence of depleted uranium and an increased cancer incidence among military personnel deployed in the Balkans during the 1992-1999 wars. This has led to numerous research articles investigating possible depleted uranium contamination of the afflicted regions of the Balkan Peninsula, namely Bosnia & Herzegovina, Serbia, Kosovo and Montenegro. The aim of this study was to collect data from previously published reports investigating the levels of depleted uranium in the Balkans and to present the data in the form of a meta-analysis. This would provide a clear image of the extent of depleted uranium contamination after the Balkan conflict. In addition, we tested the hypothesis that there is a correlation between the levels of depleted uranium and the assumed depleted uranium-related health effects. Our results suggest that the majority of the examined sites contain natural uranium, while the area of Kosovo appears to be most heavily afflicted by depleted uranium pollution, followed by Bosnia & Herzegovina. Furthermore, the results indicate that it is not possible to make a valid correlation between the health effects and depleted uranium-contaminated areas. We therefore suggest a structured collaborative plan of action where long-term monitoring of the residents of depleted uranium-afflicted areas would be performed. In conclusion, while the possibility of depleted uranium toxicity in post-conflict regions appears to exist, there currently exists no definitive proof of such effects, due to insufficient studies of potentially afflicted populations, in addition to the lack of a common epidemiological approach in the reviewed literature.