Risco cardiovascular em mulheres de meia-idade com câncer de mama: uma comparação entre dois modelos de risco

PURPOSE:It was to assess the risk of cardiovascular disease (CVD) in breast cancer survivors (BCS).METHODS:This cross-sectional study analyzed 67 BCS, aged 45 -65 years, who underwent complete oncological treatment, but had not received hormone therapy, tamoxifen or aromatase inhibitors during the previous 6 months. Lipid profile and CVD risk were evaluated, the latter using the Framingham and Systematic COronary Risk Evaluation (SCORE) models. The agreement between cardiovascular risk models was analyzed by calculating a kappa coefficient and its 95% confidence interval (CI).RESULTS:Mean subject age was 53.2±6.0 years, with rates of obesity, hypertension, and dyslipidemia of 25, 34 and 90%, respectively. The most frequent lipid abnormalities were high total cholesterol (70%), high LDL-C (51%) and high non-HDL-C (48%) concentrations. Based on the Framingham score, 22% of the participants had a high risk for coronary artery disease. According to the SCORE model, 100 and 93% of the participants were at low risk for fatal CVD in populations at low and high risk, respectively, for CVD. The agreement between the Framingham and SCORE risk models was poor (kappa: 0.1; 95%CI 0.01 -0.2) for populations at high risk for CVD.CONCLUSIONS:These findings indicate the need to include lipid profile and CVD risk assessment in the follow-up of BCS, focusing on adequate control of serum lipid concentrations.OBJETIVO:Avaliar o risco de doença cardiovascular (DCV) em mulheres com câncer de mama.MÉTODOS:Foi conduzido estudo de corte transversal, com 67 mulheres com câncer de mama, entre 45 e 65 anos, tratamento oncológico completo, não usuárias de terapia hormonal, tamoxifeno ou inibidores da aromatase nos últimos 6 meses. Foram avaliados o perfil lipídico e o risco de DCV. Para avaliar o risco de DCV, foram utilizados os modelos Framingham e Systematic COronary Risk Evaluation (SCORE). Para investigar a concordância entre os modelos de risco cardiovascular, foi calculado o coeficiente kappa com seu respectivo intervalo de confiança (IC) de 95%.RESULTADOS:A média de idade das participantes foi de 53,2±6,0 anos. A prevalência de obesidade, hipertensão e dislipidemia foi 25, 34 e 90%, respectivamente. A prevalência de dislipidemia foi 90%. As anormalidades mais comuns do perfil lipídico foram: alto colesterol total (70%), alto LDL-C (51%) e alto não HDL-C (48%). Baseado no escore de Framingham, 22% das mulheres com câncer de mama apresentaram alto risco de doença arterial coronariana. De acordo com o modelo SCORE, 100 e 93% das participantes apresentaram baixo risco de DCV fatal, considerando populações de baixo e alto risco de DCV, respectivamente. A concordância entre os modelos de Framingham e SCORE foi ruim (kappa: 0,1; IC95% 0,01 -0,2), considerando populações de alto risco de DCV.CONCLUSÕES:Esses dados indicam a necessidade de incluir a avaliação do perfil lipídico e do risco de DCV na rotina de seguimento de mulheres com câncer de mama, sendo observadoo adequado controle dos níveis séricos de lipídios.15716

Characterization of the striatal extracellular matrix in a mouse model of Parkinson’s disease

Parkinson’s disease’s etiology is unknown, although evidence suggests the involvement of oxidative modifications of intracellular components in disease pathobiology. Despite the known involvement of the extracellular matrix in physiology and disease, the influence of oxidative stress on the matrix has been neglected. The chemical modifications that might accumulate in matrix components due to their long half-live and the low amount of extracellular antioxidants could also contribute to the disease and explain ineffective cellular therapies. The enriched striatal extracellular matrix from a mouse model of Parkinson’s disease was characterized by Raman spectroscopy. We found a matrix fingerprint of increased oxalate content and oxidative modifications. To uncover the effects of these changes on brain cells, we morphologically characterized the primary microglia used to repopulate this matrix and further quantified the effects on cellular mechanical stress by an intracellular fluorescence resonance energy transfer (FRET)-mechanosensor using the U-2 OS cell line. Our data suggest changes in microglia survival and morphology, and a decrease in cytoskeletal tension in response to the modified matrix from both hemispheres of 6-hydroxydopamine (6-OHDA)-lesioned animals. Collectively, these data suggest that the extracellular matrix is modified, and underscore the need for its thorough investigation, which may reveal new ways to improve therapies or may even reveal new therapies.This research was funded by FEDER (Fundo Europeu de Desenvolvimento Regional) funds through the COMPETE 2020 Operational Program for Competitiveness and Internationalization (POCI), Portugal 2020, and Portuguese funds through FCT (ID/BIM/04293/2020), UnIC (UID/IC/00051/2019), iBiMED (UID/BIM/04501/2020 and POCI-01-0145-FEDER-007628), and LAQV/REQUIMTE (UIDB/50006/2020) research units as well as RV’s Fellowship Grant (IF/00286/2015). Ana Freitas acknowledges FCT for her PhD scholarship (SFRH/BD/111423/2015), Miguel Aroso is hired through the Scientific Employment Stimulus from FCT (CEECIND/03415/2017), and M.L. has an FCT RJEC Id 3762 contract.The authors thank Eduardo D Martín Montiel for his support, fruitful discussions, suggestions, and technical and scientific help. The authors also thank Sofia Lamas and all the i3S Animal facility personnel for their support with the animals throughout the study. Raman spectroscopy, together with wide field and confocal microscopy, were performed at the i3S Scientific Platform Bioimaging, member of the PPBI (Plataforma Portuguesa de Bioimagem, POCI-01-0145-FEDER-022122)

Agreement between dual x-ray absorptiometers using pencil beam and fan beam: indicators of bone health and whole-body plus appendicular tissue composition in adult athletes

OBJECTIVE: The current study was aimed to examine intra-individual variation on indicators of bone health in addition to whole-body plus appendicular tissue measurements using two concurrent assessments based on pencil beam and fan beam dual energy X-ray absorptiometry (DXA) systems in adult athletes from several sports. METHOD: Thirty-two male participants (27.6±10.1 years) were measured on anthropometry including multifrequency bioelectric impedance and air-displacement plethysmography. Bone mineral content (BMC), bone area, fat and lean soft tissue were derived using pencil beam (Lunar DPX-MD+) and fan beam (Lunar iDXA) absorptiometry. Bone mineral density (BMD) was obtained for the femoral neck, trochanter and triangle of ward. Finally, the right thigh was defined as a region of interest (ROI). Analyses comprised intra-class correlation (ICC), Effect size (d) from mean differences of repeated measurements, coefficient of variation (CV) RESULTS: ICC were >0.900 for all measurements. Intra-individual differences were large for BMC (d=1,312; CV=2,7%), bone area (d=1,761; CV=2,7%), fat tissue (d=1,612; CV=11%) and all indicators of appendicular lean soft tissue (d=1,237-1687; CV=2,0-4,1%). A very large difference (d=4,014; CV=8.4%) was diagnosed for lean soft tissue of the ROI. CONCLUSION: Although differences among concurrent instruments for BMC and bone area, the effect size of mean differences was negligible for BMD. Fat and lean soft tissue derived from DXA should be interpreted as reference values (not criterion) due to equipment-related variation, more apparently in the ROI values.info:eu-repo/semantics/publishedVersio

Demographic modeling with whole genome data reveals parallel origin of similar Pundamilia cichlid species after hybridization

Modes and mechanisms of speciation are best studied in young species pairs. In older taxa it is increasingly difficult to distinguish what happened during speciation from what happened after speciation. Lake Victoria cichlids in the genus Pundamilia encompass a complex of young species and polymorphic populations. One Pundamilia species pair, P. pundamilia and P. nyererei, is particularly well-suited to study speciation because sympatric population pairs occur with different levels of phenotypic differentiation and reproductive isolation at different rocky islands within the lake. Genetic distances between allopatric island populations of the same nominal species often exceed those between the sympatric species. It thus remained unresolved whether speciation into P. nyererei and P. pundamilia occurred once, followed by geographical range expansion and interspecific gene flow in local sympatry, or if the species pair arose repeatedly by parallel speciation. Here we use genomic data and demographic modeling to test these alternative evolutionary scenarios. We demonstrate that gene flow plays a strong role in shaping the observed patterns of genetic similarity, including both gene flow between sympatric species and gene flow between allopatric populations, as well as recent and early gene flow. The best supported model for the origin of P. pundamilia and P. nyererei population pairs at two different islands is one where speciation happened twice, whereby the second speciation event follows shortly after introgression from an allopatric P. nyererei population that arose earlier. Our findings support the hypothesis that very similar species may arise repeatedly, potentially facilitated by introgressed genetic variation

Body composition, strength static and isokinetic, and bone health: comparative study between active adults and amateur soccer players

The Centro de Investigação do Desporto e Actividade Física (Research Unit for the Study of Sport and Physical Activity, uid/dtp/04213/2019) is being funded by Fundação para a Ciência e a Tecnologia. AOW is supported by São Paulo Research Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) process: 2017/27234-2.Objective: To compare tissue composition, total and regional bone mineral content and bone mineral density, static hand grip and knee joint isokinetic strength between amateur soccer players and Control Group. Methods: Cross-sectional study. Air displacement plethysmography was used to estimate body volume and, in turn, density. Body composition, bone mineral content and bone mineral density were assessed for the whole body and at standardized regions using dual energy X-ray absorptiometry. Static grip strength was assessed with an adjustable dynamometer, and peak torque derived from isokinetic strength dynamometer (concentric muscular knee actions at 60°/s). Magnitude of the differences between groups was examined using d-Cohen. Results: Compared to healthy active adults, soccer players showed larger values of whole body bone mineral content (+651g; d=1.60; p<0.01). In addition, differences between groups were large for whole body bone mineral density (d=1.20 to 1.90; p<0.01): lumbar spine, i.e. L1-L4 (+19.4%), upper limbs (+8.6%) and lower limbs (+16.8%). Soccer players attained larger mean values in strength test given by static hand grip protocol (+5.6kg, d=0.99; p<0.01). Conclusion: Soccer adequately regulates body composition and is associated better bone health parameters (bone mineral content and density at whole-body and at particular sites exposed to mechanical loadings).Objetivo: Comparar a composição de tecidos, o conteúdo mineral ósseo e a densidade mineral óssea totais e por regiões do corpo, a força de preensão manual estática, e força isocinética da articulação do joelho, entre um grupo de jogadores de futebol amadores e um Grupo Controle. Métodos: Estudo transversal utilizando pletismografia de ar deslocado para estimar o volume corporal, para subsequente cálculo da densidade corporal. A composição de tecidos, o conteúdo mineral ósseo e a densidade mineral óssea foram avaliados para o corpo todo e regiões padronizadas através da absorciometria de raios-X de dupla energia. A força de preensão manual estática foi avaliada por um dinamômetro ajustável. Os momentos máximos de força das ações musculares concêntricas para os extensores e flexores do joelho foram avaliados pela dinamometria isocinética (60°/s). Foi calculado o valor d-Cohen para apreciar a magnitude do efeito das diferenças entre grupos. Resultados: Os futebolistas apresentaram níveis superiores de conteúdo mineral ósseo em comparação com os adultos ativos do Grupo Controle (+651g; d=1,60; p<0,01) e obtiveram valores superiores de densidade mineral óssea (d: 1,20 a 1,90; p<0,01) para a coluna lombar, L1-L4 (+19,4%), membros superiores (+8,6%) e membros inferiores (+16,8%). Para a força de preensão (estática) a diferença foi moderada (d=0,99; p<0,01) com valores mais elevados apresentados pelo futebolistas (+5,6kg; d=0,99; p<0,01). Conclusão: A prática de futebol promove uma regulação adequada da composição corporal (tecidos magro e gordo) e ganhos na densidade mineral óssea, mais acentuada em partes do corpo com maior exposição aos impactos mecânicos da atividade motora.info:eu-repo/semantics/publishedVersio

Sampling plan and methodological aspects: a household healthcare survey in Piauí

OBJETIVO Descrever os aspectos metodológicos do Inquérito de Saúde Domiciliar no Piauí (ISAD-PI), bem como avaliar a conformidade do plano amostral em relação à precisão e aos efeitos do desenho, dado que os inquéritos populacionais de saúde constituem instrumentos importantes para o monitoramento da situação de saúde da população. MÉTODOS O ISAD-PI foi um estudo de base populacional, transversal, que analisou as condições de vida e situação de saúde da população residente nas áreas urbanas dos municípios de Teresina e Picos, no Piauí. A amostragem foi realizada por conglomerados, em dois estágios: Unidades Primárias de Amostragem e domicílios. Para o cálculo do tamanho da amostra, considerou-se a estratificação da população de ambas as cidades, de acordo com a idade dos indivíduos, para ambos os sexos. Para avaliação da conformidade do plano amostral, foi avaliada a taxa de “não-resposta” (TNR) e, além disso, as estimativas de proporções segundo sexo e idade, bem como as prevalências de determinantes sociais de saúde, que foram analisadas em relação à precisão por meio do coeficiente de variação da proporção do erro padrão (Cv-pˆ) e do efeito do delineamento (deff). Foram considerados adequados Cv-pˆ menores que 20%, e deff menores que 1,5. A TNR-Total dos domicílios foi de 38,2% em Teresina e de 38,3% em Picos. Foram realizadas 24 estimativas de proporção em relação à idade e ao sexo e 48 estimativas de prevalência de determinantes sociais e de saúde, totalizando 72 estimativas, das quais 71 apresentaram Cv-pˆ menor que 20% e 61 apresentaram deff menor ou igual a 1,5. CONCLUSÃO Dados gerados a partir do ISAD-PI poderão contribuir para a avaliação das condições de saúde e morbidade na população. Ademais, aspectos metodológicos empregados nesta pesquisa poderão servir de base para estudos realizados em outras cidades do Brasil.OBJECTIVE To describe the methodological aspects of the Piauí home healthcare survey (ISAD-PI) and assess the relation between sampling plan, precision, and design effects, assuming that population health surveys are relevant instruments for health monitoring. METHODS ISAD-PI was a population-based cross-sectional study that analyzed the living conditions and health status of the population residing in urban areas in the municipalities of Teresina and Picos, in Piauí. Sampling was carried out by conglomerates in two stages: Primary Sampling Units and households. To calculate the sample size, we considered the stratification of the population in both cities, according to the age of the individuals. We evaluated the “non-response” rate (NRR) and estimated the proportions according to sex and age, as well as the prevalence of social determinants of health in order to assess the compliance of the sampling plan. Analyses related to the precision according to the coefficient of proportion variation of the standard error (Cv-pˆ) and the design effect (deff). Cv-pˆ less than 20% and deff less than 1.5 were considered adequate. The total NRR of households was 38.2% in Teresina and 38.3% in Picos. We carried out twenty-four proportion estimates in relation to age and sex and 48 prevalence of social and health determinants estimates, totaling 72 estimates. Among them, 71 had Cv-pˆ less than 20% and 61 had deff less than or equal to 1.5. CONCLUSION Data generated from the ISAD-PI may contribute to the assessment of health and morbidity conditions in the population. Furthermore, methodological aspects employed in this research may serve as a basis for studies carried out in other cities in Brazil

Effectiveness and safety of obeticholic acid in a Southern European multicenter cohort of patients with primary biliary cholangitis and suboptimal response to ursodeoxycholic acid

Background Obeticholic acid (OCA) was recently approved as the only on-label alternative for patients with primary biliary cholangitis (PBC) with intolerance or suboptimal response to ursodeoxycholic acid (UDCA). However, few data are available outside clinical trials. Aim To assess the effectiveness and safety of OCA in a real-world cohort of patients with non-effective UDCA therapy. Methods Open-label, prospective, real-world, multicentre study, enrolling consecutive patients who did not meet Paris II criteria, from 18 institutions in Spain and Portugal. Effectiveness was assessed by the changes in GLOBE and UK-PBC scores from baseline. POISE and Paris II criteria were evaluated after 12 months of OCA . Liver fibrosis was evaluated by FIB-4 and AST to platelet ratio index (APRI). Results One hundred and twenty patients were eligible, median time since PBC diagnosis 9.3 (4.0-13.8) years, 21.7% had cirrhosis, and 26.7% received had previous or concomitant treatment with fibrates. Seventy-eight patients completed at least 1 year of OCA. The Globe-PBC score decreased to 0.17 (95% CI 0.05 to 0.28; P = 0.005) and the UK-PBC score decreased to 0.81 (95% CI -0.19 to 1.80; P = 0.11). There was a significant decrease in alkaline phosphatase of 81.3 U/L (95% CI 42.5 to 120; P < 0.001), ALT 22.1 U/L (95% CI 10.4 to 33.8; P < 0.001) and bilirubin 0.12 mg/dL (95% CI 0 to 0.24; P = 0.044). FIB-4 and APRI remained stable. According to the POISE criteria, 29.5% (23 out of 78) achieved response. The adverse events rate was 35%; 11.67% discontinued (8.3% due to pruritus). Conclusions This study supports data from phase III trials with significant improvement of PBC-Globe continuous prognostic marker score among OCA-treated patients with good tolerability

Nitric oxide sensing in plants is mediated by proteolytic control of group VII ERF transcription factors

Nitric oxide (NO) is an important signaling compound in prokaryotes and eukaryotes. In plants, NO regulates critical developmental transitions and stress responses. Here, we identify a mechanism for NO sensing that coordinates responses throughout development based on targeted degradation of plant-specific transcriptional regulators, the group VII ethylene response factors (ERFs). We show that the N-end rule pathway of targeted proteolysis targets these proteins for destruction in the presence of NO, and we establish them as critical regulators of diverse NO-regulated processes, including seed germination, stomatal closure, and hypocotyl elongation. Furthermore, we define the molecular mechanism for NO control of germination and crosstalk with abscisic acid (ABA) signaling through ERF-regulated expression of ABSCISIC ACID INSENSITIVE5 (ABI5). Our work demonstrates how NO sensing is integrated across multiple physiological processes by direct modulation of transcription factor stability and identifies group VII ERFs as central hubs for the perception of gaseous signals in plants

Development of a self-administered web-based test for longitudinal cognitive assessment

Sequential testing with brief cognitive tools has been recommended to improve cognitive screening and monitoring, however the few available tools still depend on an external evaluator and periodic visits. We developed a self-administered computerized test intended for longitudinal cognitive testing (Brain on Track). The test can be performed from a home computer and is composed of several subtests, expected to evaluate different cognitive domains, all including random elements to minimize learning effects. An initial (A) and a refined version of the test (B) were applied to patients with mild cognitive impairment or early dementia (n = 88) and age and education-matched controls. A subsample of a population-based cohort (n = 113) performed the test at home every three months to evaluate test-retest reliability. The test’s final version Cronbach’s alpha was 0.90, test scores were significantly different between patients and controls (p = 0.001), the area under the receiver operating characteristic curve was 0.75 and the smallest real difference (43.04) was lower than the clinical relevant difference (56.82). In the test-retest reliability analysis 9/10 subtests showed two-way mixed single intraclass consistency correlation coefficient >0.70. These results imply good internal consistency, discriminative ability and reliability when performed at home, encouraging further longitudinal clinical and population-based studies