A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Isolation of phytosterols of Dalbergia ecastophyllum (L.) Taub. (Leguminosae) and modulation of antibiotic resistance by a possible membrane effect

AbstractGlobally there are a larger number of strains of microorganisms resistant to multiple drugs mainly due to misuse and indiscriminate, resulting in increased morbidity, costs inherent benefits of health care, as well as mortality rates for infections. As a result of this a large number of researches have been conducted emphasizing the antimicrobial properties of plant products. In this study, the ethanol extract and hexane fraction of Dalbergia ecastophyllum (L.) Taub. (Leguminosae) have been used to evaluate the antibacterial and antifungal activity and for modulating the resistance of antimicrobials against bacterial strains of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans and fungal strains of Candida krusei, Candida tropicalis. The antibacterial and modulatory activity was determined by microdilution. Inhibition of the growth of bacteria and fungi tested extract was ⩾1024. The activity was enhanced when aminoglycosides were associated with sub-inhibitory concentrations of the ethanol extract and hexane fraction of Dalbergia ecastophyllum. Therefore, it is suggested that the ethanol extract and hexane fraction of Dalbergia ecastophyllum (L.) Taub. (Leguminosae) can be used as a source of natural products with a view to changing the resistance of these microorganisms to antimicrobials

Comparação de metodologias para a determinação do pH e do ponto de congelamento do leite bovino cru sob diferentes características de conservação Comparison of methodologies for the determination of pH and freezing point in raw bovine milk under different conservation characteristics

Objetivou-se comparar metodologias de referência com a espectroscopia de infravermelho com transformada de Fourier para análises do pH e do ponto de congelamento sob diferentes condições de conservação em amostras de leite bovino cru. Foram coletadas amostras de leite de tanques de expansão em 57 propriedades. Cada amostra foi subdividida em 45 frascos (40 mL), que foram distribuídos de acordo com a temperatura de armazenamento (-20; 7 e 25ºC), a idade da amostra (0, 3, 6 e 9 dias) e os níveis de adição de água (0, 2, 4 e 6%). Foi adicionado bronopol a 44 frascos e um foi mantido sem adição do conservante para controle. O pH e o ponto de congelamento foram determinados pela metodologia de referência (potenciômetro e crioscópio eletrônico, respectivamente) e pela metodologia alternativa por meio do equipamento MilkoScanTM FT+. Os resultados obtidos em cada metodologia nas diferentes condições de conservação das amostras foram avaliados por análise de variância e comparação de médias. A análise de regressão linear foi realizada para avaliar as metodologias (referência e alternativa) quanto aos resultados do ponto de congelamento em função da idade da amostra. O bronopol não alterou as médias de pH, porém reduziu o ponto de congelamento. Foram calculados fatores de correção para eliminar esse efeito nos resultados do ponto de congelamento. As médias de pH em amostras com três dias, mantidas a -20 e 25ºC foram mais baixas que as amostras a 7ºC. A idade da amostra influenciou os resultados de pH quando as amostras foram submetidas a 25ºC. O aumento da temperatura de armazenamento para 25ºC reduziu as médias do ponto de congelamento em amostras sem adição de água e com nove dias de armazenagem. O aumento na idade da amostra a -20 e 7ºC não tem efeito sobre médias do ponto de congelamento. Há forte correlação entre as metodologias em função da idade da amostra para o ponto de congelamento.<br>The objective of this work was to compare reference methodologies to Fourier transform infrared spectroscopy for analysis of pH and freezing point (FP) under different storage conditions on samples of raw bovine milk. Milk samples were collected from bulk tank milk on 57 farms. Each sample was subdivided into 45 vials (40 mL) which were distributed according to storage temperature (-20ºC, 7ºC and 25ºC), age of the sample (0, 3, 6 and 9 days) and levels of water addition (0, 2, 4 and 6%). Bronopol was added into 44 flasks and one was maintained without addition of preservative for control. Frozen point and pH were determined by the standard methods (thermistor cryoscope and potentiometer, respectively) and by the alternative methodology by using MilkoScanTM FT+. The results from each method, at different conditions of conservation of the samples, were evaluated by analysis of variance and comparison of means. The linear regression analysis was performed to evaluate the methodologies (reference and alternative) for results of the frozen point in function of the age of the sample. Bronopol did not alter pH means, but it reduced frozen point. Correction factors were calculated to eliminate this effect on the results of the frozen point. Means of pH in three-day samples, kept at -20ºC and 25ºC were lower than the samples at 7ºC. The age of the samples affected the results of pH when they were submitted to 25ºC. The increase of storage temperature to 25ºC reduced means of frozen point in samples without addition of water and at nine days of storage. The increase in age of sample at -20ºC and 7ºC does not affect means of frozen point. There is a strong correlation among methodologies in function of age of the sample for frozen point