Increased rates of chromosome breakage in BRCA1 carriers are normalized by oral selenium supplementation.

Women who are born with constitutional heterozygous mutations of the BRCA1 gene face greatly increased risks of breast and ovarian cancer. The product of the BRCA1 gene is involved in the repair of double-stranded DNA breaks and it is believed that increased susceptibility to DNA breakage contributes to the cancer phenotype. It is hoped therefore that preventive strategies designed to reduce chromosome damage will also reduce the rate of cancer in these women. To test for increased mutagenicity of cells from BRCA1 carriers, the frequency of chromosome breaks was measured in cultured blood lymphocytes following in vitro exposure to bleomycin in female BRCA1 carriers and was compared with noncarrier relatives. The frequency of chromosome breaks was also measured in BRCA1 carriers following oral selenium supplementation. Carriers of BRCA1 mutations showed significantly greater mean frequencies of induced chromosome breaks per cell than did healthy noncarrier relatives (0.58 versus 0.39; P < 10(-4)). The frequency of chromosome breaks was greatly reduced following 1 to 3 months of oral selenium supplementation (mean, 0.63 breaks per cell versus 0.40; P < 10(-10)). The mean level of chromosome breaks in carriers following supplementation was similar to that of the noncarrier controls (0.40 versus 0.39). Oral selenium is a good candidate for chemoprevention in women who carry a mutation in the BRCA1 gene.     

Effect of variable annular reduction on functional tricuspid regurgitation and right ventricular dynamics in an ovine model of tachycardia-induced cardiomyopathy

ObjectiveTo investigate the effect of variable tricuspid annular reduction (TAR) on functional tricuspid regurgitation (FTR) and right ventricular (RV) dynamics in ovine tachycardia-induced cardiomyopathy.MethodsNine adult sheep underwent implantation of a pacemaker with an epicardial lead and were paced at 200 to 240 bpm until the development of biventricular dysfunction and functional TR was noted. During reoperation on cardiopulmonary bypass, 6 sonomicrometry crystals were placed around the tricuspid annulus (TA) and 14 were placed on the RV epicardium. Annuloplasty suture was placed around the TA and externalized to an epicardial tourniquet. After weaning from cardiopulmonary bypass, echocardiographic, hemodynamic, and sonomicrometry data were acquired at baseline and during 5 progressive TARs achieved with suture cinching. TA area and RV free wall strains and function were calculated from crystal coordinates.ResultsAfter pacing, changes in left ventricular (LV) ejection fraction and RV fractional area decreased significantly. Mean TA diameter increased from 25.1 ± 2.9 mm to 31.5 ± 3.3 mm (P = .005), and median TR (range, 0-3+) increased from 0 (0) to 3 (2) (P = .004). Progressive suture cinching reduced the TA area by 18 ± 6%, 38 ± 11%, 56 ± 10%, 67 ± 9%, and 76 ± 8%. Only aggressive annular reductions (67% and 76%) decreased TR significantly, but these were associated with deterioration of RV function and strain. A moderate annular reduction of 56% led to a substantial reduction of TR with little deleterious effect on regional RV function.ConclusionsA moderate TAR of approximately 50% may be most advantageous for correction of functional TR and simultaneous maintenance of regional RV performance. Additional subvalvular interventions may be needed to achieve complete valvular competence.     

Evaluation of depression in patients with alzheimer's disease according to the location of medical care

The objective of the study was to assess the severity of depression and to assess the level of self-sufficiency of patients with Alzheimer's disease, with particular emphasis on the place of residence and level of education. The study covered 90 people diagnosed with Alzheimer's disease. All respondents were persons over 65?years of age and residents of cities with a population over one-hundred thousand. The research method based on this work is the author's own questionnaire, the Zung Self-Rating Depression Scale (ZSDS) about depression and the Karnofsky Performance Scale Index (KPSI) for assessment of a patient's self-sufficiency. Regardless of residence, patients with Alzheimer's disease displayed signs of mild or moderate depression (100% in social welfare homes and hospital patients and 60% in those with caregivers at home). Patients with Alzheimer's disease have an unsatisfactory salary in social-economic terms. In those with Alzheimer's disease, quality of life is best for those in family homes under the care of their immediate family. People with a vocational education were the largest group of people diagnosed with Alzheimer's. Patients at home and in the hospital had a higher level of physical activity, but most patients in the hospital needed regular medical care, as did patients in social welfare homes.     

Static and Dynamic Stiffness of Reinforced Concrete Beams Strengthened with Externally Bonded CFRP Strips

This paper presents experimental investigations of reinforced concrete (RC) beams flexurally strengthened with carbon fiber reinforced polymer (CFRP) strips. Seven 3300 mm × 250 mm × 150 mm beams of the same design, with the tension reinforcement ratio of 1.01%, were tested. The beams differed in the way they were strengthened: one of the beams was the reference, two beams were passively strengthened as precracked (series B-I), two beams were passively strengthened as unprecracked (series B-II) and two beams were actively strengthened as unprecracked (series B-III). Moreover, the strengthening parameters differed between the particular series. The parameters were: CFRP strip cross-sectional areas (series B-I, B-II) or prestressing forces (series B-III). The beams were statically loaded, up to the assumed force value, in the three-point bending test and deflections at midspan were registered. After unloading the beams were suspended on flexible ropes (the free-free beam system) and their eigenfrequencies were measured using operational modal analysis (OMA). The static measurements (deflections) and the dynamic measurements (eigenfrequencies) were conducted for the adopted loading steps until failure. Static stiffnesses and dynamic stiffnesses were calculated on the basis of respectively the deflections and the eigenfrequencies. The qualitative and quantitative differences between the parameters are described.     

Contemporary use of P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction referred to primary percutaneous coronary interventions in Poland: Data from ORPKI national registry

Journal of Thrombosis and Thrombolysis - According to guidelines, it is recommended to give P2Y12 inhibitors (preferably ticagrelor or prasugrel) at the time of first medical contact in patients...