BackgroundAbout 3885 women are diagnosed with breast cancer and 1285 die from the disease each year in Bulgaria. However no genetic testing to identify the mutations in high-risk families has been provided so far.MethodsWe evaluated 200 Bulgarian women with primary invasive breast cancer and with personal/ family history of breast cancer for the presence of unequivocally damaging germline mutations in BRCA1/2 using Sanger sequencing.ResultsOf the 200 patients, 39 (19.5 %) carried a disease predisposing mutation, including 28 (14 %) with a BRCA1 mutation and 11 (5.5 %) with a BRCA2 mutation. At BRCA1, 6 different mutations were identified, including 2 frameshifts, 1 nonsense and 1 missense that had been previously reported (c.5030_5033delCTAA, c.5263_5264insC, c.4603G > T, c.181 T > G), and 2 frameshifts, which were novel to this study (c.464delA, c.5397_5403delCCCTTGG). At BRCA2, 7 different frameshift mutations were identified, including 5 previously reported (5851_5854delAGTT, c.5946delT, c.5718_5719delCT, c.7910_7914delCCTTT,c.9098_9099insA) and 2 novel (c.8532_8533delAA, c.9682delA).A BRCA1 mutation was found in 18.4 % of women diagnosed with breast cancer at/or under the age of 40 compared to 11.2 % of women diagnosed at a later age; a BRCA2 mutation was found in 4 % of women diagnosed at/or under the age of 40 compared to 6.5 % of women diagnosed at a later age. A mutation was present in 26.8 % patients with a positive family history and in 14.4 % of women with a negative family history.The most prevalent mutation observed in 22 patients (11 %) was BRCA1 c.5263_5264insC, a known Slavic mutation with founder effect in Eastern European and AJ communities. Other recurrent mutations were BRCA2 c.9098-9099insA (2 %), BRCA1 c.181T > G (1 %) and BRCA2 c.5851_5854delAGTT (1 %). Notably, BRCA1 c.5263_5264insC represented 56 % of all mutations identified in this series. Of the 22 patients with BRCA1 c.5263_5264insC, 9 were diagnosed with early onset breast cancer, 11 with TNBCs, 4 with bilateral breast cancer, and 6 with both breast and ovarian cancer.ConclusionsThis is the first comprehensive study of the BRCA1/2 mutation spectrum in Bulgaria and will assist the establishment of efficient protocols for genetic testing and individualized risk assessment for Bulgarian breast/ovarian cancer patients and healthy individuals at a high-risk.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1516-2) contains supplementary material, which is available to authorized users.

Citation: Georgieva KN, Hadjieva MS, Doseva MS, Terzieva DD, Georgiev NG, Andreev GG, Tchekalarova JD. Eff ect of training at lactate threshold intensity on maximal time to exhaustion, depression and anxiety behaviour of spontaneously hypertensive rats after kainate-induced status epilepticus.Folia Medica 2017;59(1): 91-97. doi: 10.1515/folmed-2017-0004 Aim: The objective of the present study was to investigate the eff ect of treadmill training at lactate threshold intensity on maximum time to exhaustion (MTE) and heart rate (HR) as well as behavioral changes after kainate (KA)-induced status epilepticus (SE) of spontaneously hypertensive rats (SHRs). Materials and methods: Male SHRs were divided in four groups: two sedentary (vehicle-and KA-treated) and two exercised (vehicle-and KA-treated), respectively. The exercised rats were trained on a treadmill at a speed of 20 m.min -1 and 0º elevation for 40 min.d -1 , for 4 wk. Maximal time to exhaustion and HR was measured at the beginning and at the end of the training period. Status epilepticus was evoked in half of the sedentary and trained rats by a repetitive intraperitoneal injection of KA in low subconvulsive doses. The other half of the groups received saline. Sucrose preference test (SPT) for depression-like behavior and hole board test (HBT) for impulsivity were performed a month after KA/veh injection. Results:The maximum time of exhaustion was elongated in the SHRs at the end of the training period in comparison with the beginning. However, no eff ect on HR was detected in trained rats. Kainate treatment after one month of training alleviated the SE-induced anhedonia in SPT and stereotyped behavior in HBT, respectively. Conclusions: Taken together, these results demonstrate that exercise exerts a benefi cial infl uence on physical working capacity, depression and impulsive behavior in a co-morbid model of essential hypertension and SE.

INTRODUCTION: The European Society of Cardiology classifies arterial pressure bellow 140/90 mmHg as optimal(below 120/80 mmHg), normal (120-129 mmHg for systolic and/or 80-84 mmHg for diastolic) and high normal (130-139 mmHg for systolic and/or 85-89 mmHg for diastolic). The argument is concerned with different cardiovascular risk. The possibility of arterial hypertension (AH) to appear is higher in individuals with high normal arterial pressure (HNAP). Such individuals could be treated with non-drug therapy as the idea is the appearance of AH to be delayed and the cardiovascular risk to be reduced. The aim of the study was the risk and hemodynamic profile of the students of medicine with HNAP to be examined. MATERIAL AND METHODS: The object of the investigation is focused on students of medicine with HNAP. The two followed-up groups-with HNAP and with optimal arterial blood pressure (OBP) assumed this pattern on the base of inquiry and screening among 116 students (60 men and 56 women). Inquiry and anthropometric methods, arterial pressure monitoring and impedance cardiography were carried up. RESULTS: The dominance of some factors, predisposing hypertension appearance as overweight, increased salt consumption, family history was registered in HNAP group. Hemodynamic evaluation manifested hyperkinetic type of circulation. CONCLUSION: Medical students' risk and hemodynamic profile within HNAP group is close to that of the hypertensive individuals. That makes them a special risk group and there is a necessity of non-drug therapy means application in order for AH expression to be delayed.

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