Comparison of postmenopausal endogenous sex hormones among Japanese, Japanese Brazilians, and non-Japanese Brazilians

<p>Abstract</p> <p>Background</p> <p>Differences in sex hormone levels among populations might contribute to the variation in breast cancer incidence across countries. Previous studies have shown higher breast cancer incidence and mortality among Japanese Brazilians than among Japanese. To clarify the difference in hormone levels among populations, we compared postmenopausal endogenous sex hormone levels among Japanese living in Japan, Japanese Brazilians living in the state of São Paulo, and non-Japanese Brazilians living in the state of São Paulo.</p> <p>Methods</p> <p>A cross-sectional study was conducted using a control group of case-control studies in Nagano, Japan, and São Paulo, Brazil. Participants were postmenopausal women older than 55 years of age who provided blood samples. We measured estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), testosterone and free testosterone by radioimmunoassay; bioavailable estradiol by the ammonium sulfate precipitation method; and sex hormone-binding globulin (SHBG) by immunoradiometric assay. A total of 363 women were included for the present analyses, comprising 185 Japanese, 44 Japanese Brazilians and 134 non-Japanese Brazilians.</p> <p>Results</p> <p>Japanese Brazilians had significantly higher levels of estradiol, bioavailable estradiol, estrone, testosterone and free testosterone levels, and lower SHBG levels, than Japanese. Japanese Brazilians also had significantly higher levels of bioavailable estradiol, estrone and DHEAS and lower levels of SHBG and androstenedione than non-Japanese Brazilians. Levels of estradiol, testosterone and free testosterone, however, did not differ between Japanese Brazilians and non-Japanese Brazilians. These differences were observed even after adjustment for known breast cancer risk factors. We also found an increase in estrogen and androgen levels with increasing body mass index, but no association for most of the other known risk factors.</p> <p>Conclusions</p> <p>We found higher levels of estrogens and androgens in Japanese Brazilians than in Japanese and levels similar to or higher than in non-Japanese Brazilians. Our findings may help explain the increase in the incidence and mortality rate of breast cancer among Japanese Brazilians.</p

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Opção ou desconhecimento?: panorama da prática interpretativa ligada ao repertório vocal existente no Brasil de 1730 a 1850, sob o ponto de vista do registro fonográfico brasileiro realizado entre 1957 e 2005

Esta pesquisa tem como objetivo traçar um panorama da prática interpretativa ligada ao repertório vocal que existiu no Brasil entre 1730 e 1850, sob o ponto de vista das mudanças estéticas e funcionais que esse gênero musical tem sofrido desde suas primeiras execuções na década de 1950. A partir do levantamento por amostragem de registros fonográficos brasileiros realizados entre 1957 e 2005, organizado em discografia e listas, localizamos e comparamos por meio de fichas obras que foram gravadas mais de uma vez por diferentes intérpretes e em épocas distintas. Essa comparação nos revelou uma diversidade de soluções de ordem prática e interpretativa que tem sido adotada por músicos brasileiros para a execução de um repertório que durante décadas foi considerado desconhecido. A escassez de referências histórico-musicais, indispensáveis para uma melhor compreensão da música setecentista e oitocentista, dificulta a prática interpretativa desse repertório e uma tradição musical que se perdeu ao longo do tempo faz com que não exista consenso entre as diferentes gravações de uma mesma obra. Este trabalho conclui que não existe uma escola de interpretação da música praticada no Brasil entre 1730 e 1850, e que nos últimos 50 anos, por opção ou desconhecimento, cada músico tem adotado soluções particulares de acordo com sua realidade musical disponível.This study has as its objective the mapping out of a panorama of interpretative practice linked to the vocal repertoire, which existed in Brazil between 1730 and 1850, as it relates to the aesthetic and functional changes that this music has undergone since its first performances in the 1950's. From the survey carried out with Brazilian recordings done between 1957 and 2005, which have been organized in the discography and repertoire lists, we located and compared those that have been recorded more than once, by different interpreters and at distinct periods of time. This comparison disclosed a variety of solutions, both practical and performatic, which were adopted by Brazilian musicians to perform this repertoire, considered unknown for decades. The scarcity of historic and musical references, as indispensable as they are for the best understanding of the music of the 18th and 19th centuries, makes the interpretative practice of this repertoire more difficult, added to the loss of the musical tradition through time. For these reasons, there does not exist a consensus between the different recordings of the same piece. We conclude that a specific school of musical practice in Brazil between 1730 and 1850 does not exist and that in the last fifty years, as a result of their own option or out of ignorance, each musician or musical group has adopted his own particular solutions in accordance with the musical reality available