A novel frequent BRCA1 recurrent variant c.5117G > A (p.Gly1206Glu) identified after 20 years of BRCA1/2 research in the Baltic region: cohort study and literature review.

BACKGROUND: Several recent studies in the Baltic region have found extended spectrum of pathogenic variants (PV) of the BRCA1/2 genes. The aim of current study is to analyze the spectrum of the BRCA1/2 PV in population of Latvia and to compare common PV between populations of the Baltic region. METHODS: We present a cohort of 9543 unrelated individuals including ones with cancer and unaffected individuals from population of Latvia, who were tested for three most common BRCA1 founder PV. In second line testing, 164 founder negative high-risk individuals were tested for PV of the BRCA1/2 using next generation sequencing (NGS). Local spectrum of the BRCA1/2 PV was compared with the Baltic region by performing a literature review. RESULTS: Founder PV c.5266dupC, c.4035delA or c.181 T > G was detected in 369/9543 (3.9%) cases. Other BRCA1/2 PV were found in 44/164 (26.8%) of NGS cases. Four recurrent BRCA1 variants c.5117G > A (p.Gly1706Glu), c.4675G > A (p.Glu1559Lys), c.5503C > T (p.Arg1835*) and c.1961delA (p.Lys654fs) were detected in 18/44 (41.0%), 5/44 (11.4%), 2/44 (4.5%) and 2/44 (4.5%) cases respectively. Additionally, 11 BRCA1 PV and six BRCA2 PV were each found in single family. CONCLUSIONS: By combining three studies by our group of the same cohort in Latvia, frequency of the BRCA1/2 PV for unselected breast and ovarian cancer cases is 241/5060 (4.8%) and 162/1067 (15.2%) respectively. The frequency of three "historical" founder PV is up to 87.0% (369/424). Other non-founder PV contribute to at least 13.0% (55/424) and this proportion probably will rise by increasing numbers of the BRCA1/2 sequencing. In relative numbers, c.5117G > A is currently the third most frequent PV of the BRCA1 in population of Latvia, overcoming previously known third most common founder variant c.181 T > G. In addition to three BRCA1 founder PV, a total of five recurrent BRCA1 and two recurrent BRCA2 PV have been reported in population of Latvia so far. Many of the BRCA1/2 PV reported in Latvia are shared among other populations of the Baltic region.

Effect of feeding combinations of wet distillers grains and wet corn gluten feed to feedlot cattle.

Three experiments were conducted to evaluate the use of combinations of wet corn gluten feed (WCGF) and wet distillers grain plus solubles (WDGS) in dry-rolled and high-moisture corn-based finishing diets for beef cattle. In Exp. 1, 250 steers (BW = 343 +/- 13.5 kg) were fed 5 treatments consisting of a corn-based, control diet with 0% coproducts, and diets including 30% WCGF, 30% WDGS, 15% WCGF plus 15% WDGS, or 30% WCGF plus 30% WDGS. No associative effects resulted from feeding 15% WCGF plus 15% WDGS; DMI, ADG, and G:F were intermediate between steers fed WCGF or WDGS at 30% of diet DM. Feeding coproducts in combinations at 30 and 60% of diet DM increased ADG, G:F, and final BW (P < 0.05) compared with the corn-based diet. In Exp. 2, 280 yearling steers (BW = 370 +/- 0.45 kg) were used to evaluate feeding 0, 25, 50, or 75% coproducts as a combination of 50% WCGF:50% WDGS (DM basis). Additional diets were fed containing decreased alfalfa hay at 5, 2.5, and 0% (DM basis) as coproduct blend inclusions increased at 25, 50, and 75% (DM basis), respectively. No interactions were observed between alfalfa hay and coproduct blend levels, and no effects on ADG or G:F (P > 0.21) were observed due to alfalfa hay. Intake, ADG, and G:F responded quadratically (P < 0.05) across coproduct levels, with the greatest ADG and G:F at 25 and 50% blend, and similar ADG and G:F for the 0 and 75% blend levels. In Exp. 3, 504 steers (BW = 376 +/- 16 kg) were fed to evaluate 0, 10, 15, 20, 25, and 30% (DM basis) WDGS in diets containing 30% WCGF (DM basis) as well as a control diet with no coproducts. The inclusion of 30% WCGF in the diets increased DMI, ADG, and G:F (P < 0.05) when compared with control. Response to inclusion level of WDGS tended to be quadratic for DMI (P = 0.12), quadratic for ADG (P = 0.05), and no effect for G:F (P = 0.96). Greatest ADG was achieved with 15 to 20% WDGS inclusion in diets containing 30% WCGF. The use of combinations of WCGF and WDGS in finishing diets resulted in similar or improved steer performance compared with corn, suggesting replacement of corn with coproduct combinations up to 75% diet DM is possible if a roughage source is fed.

Functional effects and molecular mechanisms of subtype-selective ERalpha and ERbeta agonists in the cardiovascular system.

Gender differences in the development of cardiovascular disease suggested for a protective function of estrogens in heart disease. The negative or neutral outcome of clinical trials on hormone replacement therapy provides clear evidence that the role of female sex hormones in the cardiovascular system is more complex than previously thought. In particular, the function of estrogens can not be understood without detailed knowledge on the specific function of both estrogen receptor subtypes in the heart and in the vasculature. In here, we review recent studies on subtype selective ERalpha and ERbeta agonists in different animal models of hypertension, cardiac hypertrophy and vascular inflammation. The results indicate that the activation of specific ER subtypes confers specific as well as redundant protective effects in hypertensive heart disease that might ultimately translate into novel treatment options for hypertensive heart disease.

Temperature distribution in a uniform medium heated by linear absorption of a Gaussian light beam.

The linear-diffusion equation is considered for a positive half-space with heat sources represented by Gaussian functions in the transverse plane and by exponential decay along the longitudinal axis. The exact solution is presented as a single quadrature of the complementary error function (erfc). The approximate solution is suggested in the form of the product of two Gaussian functions and the hyperbolic secant function. Comparison with the exact solution shows that the error of this approximation is near 10%. The approximation may be used in different medical applications, e.g., laser angioplasty.

[Ontogeny of cardiac antigens in chickens]. / Ontogenia de los antígenos del corazón de pollo.

The embryonic development of the heart is a complex process in which molecular events take place during the cellular recognition, growth regulation and morphogenesis. In this work, the stage in which cardiac antigens are produced in the chick embryo was established by the use of sera directed against cockerel's heart antigens. Chick embryos were studied in different stages of development, classified according to the Hamburger and Hamilton system. Soluble and insoluble fraction of the cockerel's heart were obtained and used to immunize rabbits; the presence of anti-heart antibodies was tested by double microimmunodiffusion. Antisera to yolk and albumin envelopment, serum and cockerel erythocytes were also produced in order to recognize other molecules in the embryos. Anticockerel red cells antibodies were determined by direct hemaglutination. It was shown that heart antigens appear since the second stage of embryonic development and remain during the whole development, although in some stages it seems that the concentration of some antigens decreases. It is possible that the molecular changes in the heart tissue are manifested as variations in concentration of the cardiac substances.

Características clínicas de los niños asmáticos hospitalizados en un Servicio de Pediatría / Clinical characteristics of asthmatic children hospitalized in a pediatric unit

Introducción:El asma es una enfermedad heterogénea con prevalencia descrita en aumento. En Chile, existen escasos estudios en que se describa las características clínicas de los pacientes pediátricos hospitalizados. Objetivos: Describir las características clínicas de los niños hospitalizados por episodios de crisis asmáticas. Pacientes y Método: Estudio descriptivo, restrospectivo en niños con asma entre 6 y 15 años, hospitalizados en el Servicio de Pediatría del Hospital Clínico de la Pontificia Universidad Católica de Chile, entre los años 1998 y 2004. Resultados: De un total de 317 fichas clínicas que correspondían a pacientes asmáticos hospitalizados, se pudo acceder sólo a 188, de las cuales 113 cumplían con los criterios de inclusión. Sesenta y ocho fichas correspondían a niños (61 por ciento), setenta y cinco niños iniciaron cuadros obstructivos antes de los 3 años (66 por ciento), el desencadenante más frecuente fueron los virus respiratorios en 53 casos (47 por ciento), el 93 por ciento (105 casos) requirió FiO2 < 0,5 por ciento, y 60 pacientes (53 por ciento) tenían antecedentes de atopía. Conclusión: La mayoría de los pacientes hospitalizados presentó crisis leves o moderadas, sin requerir ingreso a la unidad de paciente crítico. La atopía fue un antecedente frecuente. Es importante realizar un estudio prospectivo que evalúe el tipo y adherencia a tratamiento en relación a la evolución clínica del asma en niños.