Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives

Nuclear Translocation of Jacob in Hippocampal Neurons after Stimuli Inducing Long-Term Potentiation but Not Long-Term Depression

Background: In recent years a number of potential synapto-nuclear protein messengers have been characterized that are thought to be involved in plasticity-related gene expression, and that have the capacity of importin- mediated and activity-dependent nuclear import. However, there is a surprising paucity of data showing the nuclear import of such proteins in cellular models of learning and memory. Only recently it was found that the transcription factor cyclic AMP response element binding protein 2 (CREB2) transits to the nucleus during long-term depression (LTD), but not during long-term potentiation (LTP) of synaptic transmission in hippocampal primary neurons. Jacob is another messenger that couples NMDA-receptor-activity to nuclear gene expression. We therefore aimed to study whether Jacob accumulates in the nucleus in physiological relevant models of activity-dependent synaptic plasticity. Methodology/Principal Findings: We have analyzed the dynamics of Jacob’s nuclear import following induction of NMDA-receptor dependent LTP or LTD at Schaffer collateral-CA1 synapses in rat hippocampal slices. Using time-lapse imaging of neurons expressing a Jacob-Green-Fluorescent-Protein we found that Jacob rapidly translocates from dendrites to the nucleus already during the tetanization period of LTP, but not after induction of LTD. Immunocytochemical stainings confirmed the nuclear accumulation of endogenous Jacob in comparison to apical dendrites after induction of LTP but not LTD. Complementary findings were obtained after induction of NMDA-receptor dependent chemical LTP and LTD i

Molecular characterization of hepatitis B virus X gene in chronic hepatitis B patients

BACKGROUND: HBV-X protein is associated with the pathogenesis of HBV related diseases, specially in hepatocellular carcinomas of chronic patients. Genetic variability of the X gene includes genotypic specific variations and mutations emerging during chronic infection. Its coding sequence overlaps important regions for virus replication, including the basal core promoter. Differences in the X gene may have implications in biological functions of the protein and thus, affect the evolution of the disease. There are controversial results about the consequences of mutations in this region and their relationship with pathogenesis. The purpose of this work was to describe the diversity of HBV-X gene in chronic hepatitis patients infected with different genotypes, according to liver disease. METHODS: HBV-X gene was sequenced from chronic hepatitis B patient samples, analyzed by phylogeny and genotyped. Nucleotide and aminoacid diversity was determined calculating intragenetic distances. Mutations at 127, 130 and 131 aminoacids were considered in relation to liver disease. RESULTS: The most prevalent genotype detected in this cohort was F (F1 and F4), followed by D and A. Most of the samples corresponding to genotypes A and F1 were HBeAg(+) and for genotypes D and F4, HBeAg(−) samples were represented in a higher percentage. Intragenetic distance values were higher in HBeAg(−) than in positive samples for all genotypes, and lower in overlapped regions, compared to single codification ones. Nucleotide and aminoacid diversities were higher in HBeAg(−), than in HBeAg(+) samples. CONCLUSIONS: Independently of the infecting genotypes, mutations at any of 127, 130 and/or 131 aminoacid positions and HBeAg(−) status were associated with mild liver disease in this cohort

Plasma ACE2 predicts outcome of COVID-19 in hospitalized patients

AimsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin converting enzyme 2 (ACE2) enabling entrance of the virus into cells and causing the infection termed coronavirus disease of 2019 (COVID-19). Here, we investigate associations between plasma ACE2 and outcome of COVID-19.Methods and resultsThis analysis used data from a large longitudinal study of 306 COVID-19 positive patients and 78 COVID-19 negative patients (MGH Emergency Department COVID-19 Cohort). Comprehensive clinical data were collected on this cohort, including 28-day outcomes. The samples were run on the Olink® Explore 1536 platform which includes measurement of the ACE2 protein. High admission plasma ACE2 in COVID-19 patients was associated with increased maximal illness severity within 28 days with OR = 1.8, 95%-CI: 1.4-2.3 (P ConclusionThis study suggests that measuring plasma ACE2 is potentially valuable in predicting COVID-19 outcomes. Further, ACE2 could be a link between COVID-19 illness severity and its established risk factors hypertension, pre-existing heart disease and pre-existing kidney disease

"Tava morta e revivi": significado de maternidade para adolescentes com experiência de vida nas ruas "I was dead, but came back to life": the meaning of motherhood for adolescent girls with a history of living in the streets

A descoberta da sexualidade entre as adolescentes que fazem das ruas seu espaço de sobrevivência geralmente é permeada pelo desconhecimento do próprio corpo, o que resulta, muitas vezes, em comportamentos de risco para a contaminação por doenças sexualmente transmissíveis e para a gravidez. O objetivo desta pesquisa foi identificar os significados atribuídos à maternidade por adolescentes com experiência de vida nas ruas que optaram por assumir o cuidado dos filhos fora das ruas. Com base na abordagem de pesquisa qualitativa, os dados foram coletados junto a adolescentes-mães abrigadas em uma instituição não-governamental, e analisados segundo a modalidade temática da análise de conteúdo. Os resultados foram discutidos por meio da categoria "a nova vida: mãe & filho", mostrando que a experiência da maternidade é significada de forma positiva pelas adolescentes, sendo o filho entendido como o "salvador" de uma morte certa nas ruas, depositando nele as expectativas de um futuro melhor. A título de considerações finais, observamos no exercício da maternidade uma oportunidade de estabelecimento de novas formas de estar e se relacionar no mundo, sendo o processo de construção dessa maternidade terreno fértil para a intervenção de profissionais da saúde.<br>The discovery of sexuality by adolescent girls living in the streets generally involves lack of knowledge about their own bodies, often resulting in risk behaviors for sexually transmitted diseases and pregnancy. This study aimed to identify the meanings ascribed to motherhood by teenage girls with a history of living in the streets and who chose to assume the care for their children, off the streets. Based on a qualitative methodology, data were collected from the adolescent mothers at a nongovernmental shelter and analyzed according to the content analysis modality. The results were discussed using the category "new life: mother & child", showing that the adolescents ascribed a positive meaning to motherhood, with the child seen as both a "savior" from the mother's certain death on the streets and a repository for the mother's expectations for a better future. The article concludes by analyzing motherhood as an opportunity for establishing new ways of being in (and relating to) the world, with the construction of this motherhood process as a potentially fertile ground for intervention by health professionals

A Mathematical Model for Enhancer Activation Kinetics During Cell Differentiation

Cell differentiation and development are for a great part steered by cell type specific enhancers. Transcription factor (TF) binding to an enhancer together with DNA looping result in transcription initiation. In addition to binding motifs for TFs, enhancer regions typically contain specific histone modifications. This information has been used to detect enhancer regions and classify them into different subgroups. However, it is poorly understood how TF binding and histone modifications are causally connected and what kind of molecular dynamics steer the activation process. Contrary to previous studies, we do not treat the activation events as static epigenetic marks but consider the enhancer activation as a dynamic process. We develop a mathematical model to describe the dynamic mechanisms between TF binding and histone modifications known to characterize an active enhancer. We estimate model parameters from time-course data and infer the causal relationships between TF binding and different histone modifications. We benchmark the performance of this framework using simulated data and survey the ability of our method to identify the correct model structures for a variety of system dynamics, noise levels and the number of measurement time points.Peer reviewe