Preventive Treatment with Ketamine attenuates the ischaemia-reperfusion response in a chronic postichaemia pain model

published_or_final_versio

Surprising dissimilarities in a newly formed pair of 'identical twin' stars

The mass and chemical composition of a star are the primary determinants of its basic physical properties--radius, temperature, luminosity--and how those properties evolve with time. Thus, two stars born at the same time, from the same natal material, and with the same mass are 'identical twins,' and as such might be expected to possess identical physical attributes. We have discovered in the Orion Nebula a pair of stellar twins in a newborn binary star system. Each star in the binary has a mass of 0.41 +/- 0.01 solar masses, identical to within 2 percent. Here we report that these twin stars have surface temperatures that differ by ~300K (~10%), and luminosities that differ by ~50%, both at high confidence level. Preliminary results indicate that the stars' radii also differ, by 5-10%. These surprising dissimilarities suggest that one of the twins may have been delayed by several hundred thousand years in its formation relative to its sibling. Such a delay could only have been detected in a very young, definitively equal-mass binary system3 such as that reported here. Our findings reveal cosmic limits on the age synchronisation of young binary stars, often used as tests for the age calibrations of star-formation models.Comment: Published in Nature, 19 June 200

Solar-type dynamo behaviour in fully convective stars without a tachocline

In solar-type stars (with radiative cores and convective envelopes), the magnetic field powers star spots, flares and other solar phenomena, as well as chromospheric and coronal emission at ultraviolet to X-ray wavelengths. The dynamo responsible for generating the field depends on the shearing of internal magnetic fields by differential rotation. The shearing has long been thought to take place in a boundary layer known as the tachocline between the radiative core and the convective envelope. Fully convective stars do not have a tachocline and their dynamo mechanism is expected to be very different, although its exact form and physical dependencies are not known. Here we report observations of four fully convective stars whose X-ray emission correlates with their rotation periods in the same way as in Sun-like stars. As the X-ray activity - rotation relationship is a well-established proxy for the behaviour of the magnetic dynamo, these results imply that fully convective stars also operate a solar-type dynamo. The lack of a tachocline in fully convective stars therefore suggests that this is not a critical ingredient in the solar dynamo and supports models in which the dynamo originates throughout the convection zone.Comment: 6 pages, 1 figure. Accepted for publication in Nature (28 July 2016). Author's version, including Method

Options for early breast cancer follow-up in primary and secondary care : a systematic review

Background Both incidence of breast cancer and survival have increased in recent years and there is a need to review follow up strategies. This study aims to assess the evidence for benefits of follow-up in different settings for women who have had treatment for early breast cancer. Method A systematic review to identify key criteria for follow up and then address research questions. Key criteria were: 1) Risk of second breast cancer over time - incidence compared to general population. 2) Incidence and method of detection of local recurrence and second ipsi and contra-lateral breast cancer. 3) Level 1–4 evidence of the benefits of hospital or alternative setting follow-up for survival and well-being. Data sources to identify criteria were MEDLINE, EMBASE, AMED, CINAHL, PSYCHINFO, ZETOC, Health Management Information Consortium, Science Direct. For the systematic review to address research questions searches were performed using MEDLINE (2011). Studies included were population studies using cancer registry data for incidence of new cancers, cohort studies with long term follow up for recurrence and detection of new primaries and RCTs not restricted to special populations for trials of alternative follow up and lifestyle interventions. Results Women who have had breast cancer have an increased risk of a second primary breast cancer for at least 20 years compared to the general population. Mammographically detected local recurrences or those detected by women themselves gave better survival than those detected by clinical examination. Follow up in alternative settings to the specialist clinic is acceptable to women but trials are underpowered for survival. Conclusions Long term support, surveillance mammography and fast access to medical treatment at point of need may be better than hospital based surveillance limited to five years but further large, randomised controlled trials are needed

The Hordaland Women's Cohort: A prospective cohort study of incontinence, other urinary tract symptoms and related health issues in middle-aged women

<p>Abstract</p> <p>Background</p> <p>Urinary incontinence (UI) is a prevalent symptom in middle-aged women, but data on incidence is limited and rarely reported. In order to analyze incidence, remission, or development patterns of severity and types of UI, we have established a 15-year prospective cohort (1997–2012).</p> <p>Methods</p> <p>The Cohort is based on the national collection of health data gathered from county studies (CONOR). Hordaland Health Study (HUSK) is one of them from Hordaland County. Each of the county studies may have local sub-studies and our Cohort is one of them. The Cohort included women aged 40–45 in order to have a broad approach to women's health including UI and other lower urinary tract symptoms (LUTS). A onefifth random sampling from HUSK was used to create the Cohort in 1997–1999. For the necessary sample size a preliminary power calculation, based on a 70% response rate at inclusion and 5% annual attrition rates was used. The Cohort is planned to collect data through questionnaires every second year for the 15-year period from 1997–2012.</p> <p>Discussion</p> <p>The Cohort represents a relatively large random sample (N = 2,230) of about 15% of the total population of women born between 1953–57 in the county of Hordaland. Our data shows that the cohort population is very similar to the source population. The baseline demographic, social and medical characteristics of the Cohort are compared with the rest of women in HUSK (N = 7,746) and there were no significant differences between them except for the level of education (P = 0.001) and yearly income (P = 0.018), which were higher in the Cohort population. Urological characteristics of participants from the Cohort (N = 1,920) were also compared with the other participants (N = 3,400). There were no significant statistical differences except for somewhat more urinary continence (P = 0.04), more stress incontinence (P = 0.048) and smaller amount of leakage (P = 0.015) in the Cohort. In conclusion, the Cohort ispopulation-based, with little selection bias, and thus is a rather unique study forinvestigating UI and LUTS in comparison with many other projects with similar purposes.</p

Comparison of two methods based on cross-sectional data for correcting corpus uterine cancer incidence and probabilities

BACKGROUND: Two methods are presented for obtaining hysterectomy prevalence corrected estimates of invasive cancer incidence rates and probabilities of the corpus uterine. METHODS: The first method involves cross-sectional hysterectomy data from the Utah Hospital Discharge Data Base and mortality data applied to life-table methods. The second involves hysterectomy prevalence estimates obtained directly from the Utah Behavior Risk Factor Surveillance System (BRFSS) survey. RESULTS: Hysterectomy prevalence estimates based on the first method are lower than those obtained from the second method through age 74, but higher in the remaining ages. Correction for hysterectomy prevalence is greatest among women ages 75–79. In this age group, the uncorrected rate is 125 (per 100,000) and the corrected rate based on the life-table method is 223 using 1995–97 data, 243 using 1992–94 data, and 228 from the survey method. The uncorrected lifetime probability of developing corpus uterine cancer is 2.6%; the corrected probability from the life-table method using 1995–97 data is 4.2%, using 1992–94 data is 4.5%; and based on prevalence data from the survey method is 4.6%. CONCLUSIONS: Both methods provide reasonable hysterectomy prevalence estimates for correcting corpus uterine cancer rates and probabilities. Because of declining trends in hysterectomy in recent decades, corrected estimates from the life-table method are less pronounced than those based on the survey method. These methods may be useful for obtaining corrected uterine cancer rates and probabilities in areas of the world that do not have sufficient years of hysterectomy data to directly compute prevalence

TAp73 is one of the genes responsible for the lack of response to chemotherapy depending on B-Raf mutational status

<p>Abstract</p> <p>Background</p> <p>Although there have been many studies on the p73 gene, some of its functions still remain unclear. There is little research on the relationship between p73 gene transcription and its protein expression and the response to certain drugs such as oxaliplatin and cetuximab, which are drugs currently used in colorectal cancer.</p> <p>The purpose of this study was to evaluate the impact of TAp73 expression on oxaliplatin and cetuximab-based chemotherapy in colorectal cancer cell lines with different K-Ras and B-Raf mutational status.</p> <p>Methods</p> <p>TAp73 was analyzed in three colorectal tumor cell lines HT-29, SW-480 and Caco-2. mRNA TAp73 was determined using Real time PCR; TAp73 protein by immunoblotting and cell viability was analyzed by the MTT method.</p> <p>Results</p> <p>We found that mRNA and TAp73 protein were decreased in cells treated with oxaliplatin (in monotherapy or combined with cetuximab) when B-Raf is mutated. This was statistically significant and was also associated with higher cell viability after the treatment.</p> <p>Conclusions</p> <p>Here, for the first time we report, that there is a signaling loop between B-Raf activation and p73 function.</p> <p>Low expression of TAp73 in colorectal cancer cell lines with mutated B-Raf may be involved in the lack of response to oxaliplatin in monotherapy or combined with cetuximab.</p

Conservation of geosites as a tool to protect geoheritage: the inventory of Ceará Central Domain, Borborema Province - NE/Brazil

The Ceará Central Domain, in the northern Borborema Province/NE Brazil, encompasses important geological records (geosites) which allow understanding a relevant period of the Earth’s evolution, mainly associated to Neoproterozoic Brazilian/Pan-African Cycle and West Gondwana amalgamation, besides Neoarchean to Ordovician records. The presented geoheritage inventory aims to characterise the geosites with scienti c relevance of Ceará Central Domain. By applying a method for large areas, the nal selection resulted in eight geological frameworks represented by 52 geosites documented in a single database. This is the rst step for a geoconservation strategy based on systematic inventories, statutory protection, geoethical behaviour and awareness about scienti c, educational and/or cultural relevance of geosites.We specially thank all experts that helped us with this inventory: Afonso Almeida, Carlos E.G. de Araújo, César Veríssimo, Christiano Magini, Clóvis Vaz Parente, Felipe G. Costa, Irani C. Mattos, Neivaldo de Castro, Otaciel de Melo, Sebástian G. Chiozza, Ticiano Santos and Stefano Zincone. We are also thankful to Kátia Mansur, Ricardo Fraga Pereira and anonymous reviewers for their valuable contributions. PM is grateful to Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for PhD mobility scholarship PDSE Program/Process n 88881.132168/2016-01info:eu-repo/semantics/publishedVersio

Hormonal control of p53 and chemoprevention

Improvements in the detection and treatment of breast cancer have dramatically altered its clinical course and outcome. However, prevention of breast cancer remains an elusive goal. Parity, age of menarche, and age at menopause are major risk factors drawing attention to the important role of the endocrine system in determining the risk of breast cancer, while heritable breast cancer susceptibility syndromes have implicated tumor suppressor genes as important targets. Recent work demonstrating hormonal modulation of the p53 tumor suppressor pathway draws together these established determinants of risk to provide a model of developmental susceptibility to breast cancer. In this model, the mammary epithelium is rendered susceptible due to impaired p53 activity during specific periods of mammary gland development, but specific endocrine stimuli serve to activate p53 function and to mitigate this risk. The results focus attention on p53 as a molecular target for therapies to reduce the risk of breast cancer

E2F-1 induces melanoma cell apoptosis via PUMA up-regulation and Bax translocation

BACKGROUND: PUMA is a pro-apoptotic Bcl-2 family member that has been shown to be involved in apoptosis in many cell types. We sought to ascertain whether induction of PUMA plays a crucial role in E2F-1-induced apoptosis in melanoma cells. METHODS: PUMA gene and protein expression levels were detected by real-time PCR and Western blot in SK-MEL-2 and HCT116 cell lines after Ad-E2F-1 infection. Activation of the PUMA promoter by E2F-1 overexpression was detected by dual luciferase reporter assay. E2F-1-induced Bax translocation was shown by immunocytochemistry. The induction of caspase-9 activity was measured by caspase-9 colorimetric assay kit. RESULTS: Up-regulation of the PUMA gene and protein by E2F-1 overexpression was detected by real-time PCR and Western blot analysis in the SK-MEL-2 melanoma cell line. In support of this finding, we found six putative E2F-1 binding sites within the PUMA promoter. Subsequent dual luciferase reporter assay showed that E2F-1 expression could increase the PUMA gene promoter activity 9.3 fold in SK-MEL-2 cells. The role of PUMA in E2F-1-induced apoptosis was further investigated in a PUMA knockout cell line. Cell viability assay showed that the HCT116 PUMA-/- cell line was more resistant to Ad-E2F-1-mediated cell death than the HCT116 PUMA+/+ cell line. Moreover, a 2.2-fold induction of the PUMA promoter was also noted in the HCT116 PUMA+/+ colon cancer cell line after Ad-E2F-1 infection. Overexpression of a truncated E2F-1 protein that lacks the transactivation domain failed to up-regulate PUMA promoter, suggesting that PUMA may be a transcriptional target of E2F-1. E2F-1-induced cancer cell apoptosis was accompanied by Bax translocation from the cytosol to mitochondria and the induction of caspase-9 activity, suggesting that E2F-1-induced apoptosis is mediated by PUMA through the cytochrome C/Apaf-1-dependent pathway. CONCLUSION: Our studies strongly demonstrated that E2F-1 induces melanoma cell apoptosis via PUMA up-regulation and Bax translocation. The signaling pathways provided here will further enhance insights on the mechanisms of E2F-1-induced cancer cell apoptosis as a strategy for cancer therapy