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Laryngeal squamous cell carcinoma is a common malignancy in men. Bulgaria is one of the countries in Europe with the highest incidence and mortality rates of the aggressive, severe disease of laryngeal cancer. Proven etiological factors are the abuse of tobacco and alcohol beverages. Despite the progress of technologies of multimodal medical treatment, survival rates have not reached satisfactory levels. Over the last few decades, scientific and clinical research data have led to a growing interest in exploring potential biomarkers. In the last years, non-coding RNAs have become promising biomarkers. They are important key regulators in both normal and tumour specific biological processes as well as in the response to environmental factors and treatment, including chemo- and radiotherapy. Studies have shown ectopic expression of a number of ncRNAs in laryngeal cancer. Published data provide evidence of the lncRNAs and miRNAs that could help us better understand complex carcinogenesis in laryngeal cancer and would provide reliable diagnostic, prognostic and predictive biomarkers., (This is an open access article distributed under the terms of the CC0 Public Domain Dedication.)

Purpose: Laryngeal cancer is one of most common and aggressive head and neck cancers with poor prognosis and great necessity for improvement of treatment modalities. MicroRNAs (miRs) are among the most investigated molecules recently due to their potential as diagnostic and prognostic biomarkers in cancer. The purpose of our study was to explore the association of certain clinicopathological features with the expression levels of some known cancer associated non-coding (nc) RNAs: miR-21 and miR-31 in both of their isoforms, miR-145-5p, miR-55-5p, miR-196a-5p, miR-210-3p, miR-221-3p, miR-222-3p, miR-424-5p, lncRNA MALAT1 and lncRNA HOTAIR., Methods: Expression levels of the chosen markers were investigated in laryngeal squamous cell carcinoma (LSCC) and normal samples in 82 Bulgarian patients via RT-qPCR, and the results were analyzed with SPSS v23.0 statistical software., Results: All of the explored ncRNAs were significantly deregulated in LSCC samples, suggesting their involvement in laryngeal carcinogenesis. New significant association were found between the expression levels of miR-21-5p, miR-222-3p, HOTAIR and family history. Moreover, miR-424-5p showed potential as marker for subglottic LSCC location, and "passenger" miR-31-3p was significantly upregulated in well and moderately differentiated LSCC., Conclusion: Our results enrich the knowledge about ncRNA involvement in LSCC tumorigenesis. Further studies are needed to evaluate the clinical utility of the differently expressed ncRNAs as potential diagnostic and prognostic biomarkers in LSCC.

Objective of the study is to assess the prevalence of Connexin 26 (GJB2) mutation in patients with congenital nonsyndromic sensorineural hearing loss in Bulgarian population. Study design is done prospectively. Patient inclusion criteria for this study were diagnosis of congenital nonsyndromic hearing loss, and absence of potential sibling relationships between patients included in the study (anamnestic pedigree for at least three generations). Patients were excluded from the study group if one of the following conditions were present: secondary hearing loss (cytomegalovirus, rubella, meningo-encephalitis, mastoiditis, other infections, posterior fossa tumors, etc.), exposure to drugs or other prenatal or perinatal etiology of deafness, and congenital syndromic hearing loss. Genomic DNA samples from whole blood were tested with sequence analysis for mutations in the coding region of the GJB2. Results state that 51 patients were analyzed for GJB2 mutations. Twenty of the patients (39%) with mutant alleles were homozygous for the c.35delG mutation (c.35delG/c.35delG) and four patients (8%) presented as heterozygotes (c.35delG/WT). In one patient, who carried a heterozygous mutation c.35delG, a second mutation was found-312del114. Additionally, in two other patients were discovered the mutations Trp24X (W24X) and, respectively, Arg127His(R127H), both in heterozygous states. From the whole study group there was only one patient with compound heterozygous genotype-p.Leu90Pro(L90P)/p.Ile121Asn. The latter one has never been reported in the literature so far. In conclusion, this study determines the importance of connexin 26 mutations in Bulgarian children with severe to profound congenital nonsyndromic sensorineural hearing loss, the prevalence of the different mutation variants and their relationship with the ethnical background of the patients. In addition, we report for the first time a novel mutation in the GJB2 gene.

Background: The proportion of patients visiting general practitioners (GPs), otorhinolaryngologists (ORLs), and allergologists (ALRGs) for nasal complaints is unknown but important in estimating the number of subjects with nasal symptoms bothersome enough to warrant physician consultations and assessing nasal pathological conditions' burden on a national health care system., Objective: The Symptoms of Nasal Inconvenience Fact Finding (SNIFF) survey was developed to (1) assess incidence of physician visits attributable to nasal complaints; (2) characterize patients' nasal conditions; and (3) outline differences across physician categories., Methods: The SNIFF survey was completed over 20 days by Bulgarian GPs, ORLs, and ALRGs whom patients consulted for nasal symptoms. Survey forms differentiated type and severity of patients' conditions according to Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines and ranked bothersome symptoms. Smell impairment, comorbidities, and prescription practices were documented., Results: Sixty-nine physicians (30 GPs, 8 ORLs, 31 ALRGs) completed 1,685 surveys. The proportion of patients with nasal symptoms over the total patients seen was 15.7%: ALRGs, 18.0%; GPs, 14.6%; ORLs, 13.1%. Patients were classified as having intermittent (38.8%) or persistent (61.2%) rhinitis, with most having moderate/severe symptoms (94.4%). Congestion was the leading symptom in 59.1%. Smell was impaired in 69.8% of patients, asthma was present in 21.4%, and cough in 62.9%. ALRGs were more likely to diagnose and manage patients per ARIA guidelines than were ORLs or GPs., Conclusion: The SNIFF survey results demonstrate congestion's role as a leading symptom motivating patients to seek medical advice. SNIFF also uncovered differences in practices among different categories of health care providers., (Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The role of pet exposure in early childhood for allergy/ asthma later in life is still controversial. Recently it was shown that 'avoidance behaviour' is an important factor for the pet distribution in the population. The aim of the present work is to study the association between self-reported pet keeping at home and symptoms in airways, nose and skin among children 2-7 years of age, in a country where primary prevention strategies regarding allergies are not common. A cross-sectional survey on the association between allergy and asthma symptoms and home environmental factors was conducted in two towns in Bulgaria in spring 2004 (the ALLHOME-1 study). Data for 4479 out of 12982 children was obtained. 21.3% of the parents reported having pets at the time of the questionnaire, and 23.3% for pet keeping at index child's birth. Parents of 3.3% of the children got rid of some of the pets and 10.6% refrained from having pets, due in both cases to allergic illness in the family. Keeping dogs or cats at the time of the survey or during the child's first years was associated with most of the symptoms (aOR 1.1-2.2).

Human metabolism of benzene involves pathways coded for by polymorphic genes. To determine whether the genotype at these loci might influence susceptibility to the adverse effects of benzene exposure, 208 Bulgarian petrochemical workers and controls, whose exposure to benzene was determined by active personal sampling, were studied. The frequency of DNA single-strand breaks (DNA-SSB) was determined by alkaline elution, and genotype analysis was performed for five metabolic loci. Individuals carrying the NAD(P)H:quinone oxidoreductase 1 (NQO1) variant had significantly twofold increased DNA-SSB levels compared to wild-type individuals. The same result was observed for subjects with microsomal epoxide hydrolase (EPHX) genotypes that predict the fast catalytic phenotype. Deletion of the glutathione S-transferase T1 (GSTT1) gene also showed a consistent quantitative 35-40% rise in DNA-SSB levels. Neither glutathione S-transferase M1 (GSTM1) nor myeloperoxidase (MPO) genetic variants exerted any effect on DNA-SSB levels. Combinations of two genetic polymorphisms showed the same effects on DNA-SSB as expected from the data on single genotypes. The three locus genotype predicted to produce the highest level of toxicity, based on metabolic pathways, produced a significant 5.5-fold higher level of DNA-SSB than did the genotype predicted to yield the least genotoxicity.

S-Phenylmercapturic acid (S-PMA), is a urinary metabolite of benzene, thought to be derived from the condensation product of benzene oxide with glutathione. S-PMA may be determined by GC, HPLC (UV or fluorescence detection), GC-MS, LC-MS/MS or immunoassays. The limit of sensitivities of most of these techniques is 1 microg/l urine or below. It has been suggested that S-PMA may have value as a biomarker for low level human exposure to benzene, in view of the facts that urinary excretion of S-PMA has been found to be related to airborne benzene in occupationally exposed workers, and that only low background levels of S-PMA have been found in control subjects. We have evaluated the use of S-PMA as a biomarker, using a commercially available analytical service, in a multicentre European study of populations exposed to varying levels of benzene, in Italy (Milan, Genoa) and in Bulgaria (Sofia). These were filling station attendants, urban policemen, bus drivers, petrochemical workers and referents (a total of 623 subjects). S-PMA was measured at the end of the work shift by an immunoassay procedure. Urinary benzene (in Milan only) and the benzene metabolite trans,trans-muconic acid (t,t-MA) were measured before and after the work shift. Air-borne benzene was measured as a monitor of exposure. Urinary benzene was the most discriminatory biomarker and showed a relationship with airborne benzene at all levels of exposure studied (including groups exposed to <0.1 ppm benzene), whereas t,t-MA and S-PMA, as determined by immunoassay, were suitable only in the highest exposed workers (petrochemical industry, geometric mean 1765 microg/m3 (0.55 ppm) benzene). All three biomarkers were positively correlated with smoking as measured by urinary cotinine).

Biomarkers of benzene exposure and effect were evaluated in 158 Bulgarian petrochemical workers and 50 matched controls. Air exposures to benzene averaged about 1.8 ppm, for workers and 0.02 ppm for controls. Urinary trans,trans-muconic acid, and S-phenylmuconic acid, showed dose response relationships with benzene air exposure. The dose response curve for DNA single strand breaks (SSB), but not for the metabolites, showed a saturation effect. NQO1 genotype had a significant effect on SSB. We conclude that the pathways for these metabolites may be distinct from those involved in some forms of genotoxic damage induced by benzene.

The aim of the present study was to evaluate the genotoxic effects of hexavalent chromium (Cr(VI)) in vivo in exposed Bulgarian chromium platers by using classical cytogenetic and molecular cytogenetic analyses of peripheral lymphocytes and exfoliated buccal cells. No significant difference was observed between the exposed workers and the controls with regard to the frequency of cells with chromosome aberrations (CAs) using conventional Giemsa staining and in the frequency of sister chromatid exchanges (SCEs). However, there was a significant increase in the number of cells with micronuclei (MN) in peripheral lymphocytes from chromium exposed workers as compared to the controls. In the buccal cells from these workers, this increase was even more pronounced. Cytosine arabinoside (AraC), an inhibitor of DNA synthesis and repair, was found to significantly increase the levels of MN in vitro in the lymphocytes of both groups. The increase was more expressed in the lymphocytes of chromium exposed workers. Both centromere positive (C(+)) as well as centromere negative (C(-)) MN were observed by the fluorescence in situ hybridization (FISH) technique in both of the cell types studied. No difference between C(+) and C(-) MN frequencies was found in the lymphocytes as well as in the buccal cells. Thus, Cr(VI) appears to have both clastogenic as well as aneugenic effects in humans.