Epidemiological And Molecular Mechanisms Aspects Linking Obesity And Cancer [mecanismos Epidemiológicos E Moleculares Que Associam Obesidade E Câncer]

About 25% of cancer cases globally are due to excess weight and a sedentary lifestyle. These results are alarming, as the world knows a pandemy of obesity and, in consequence, insulin resistance. Obesity may increase risk for various cancers by several mechanisms, including increasing sex and metabolic hormones, and inflammation. Here, we present a review of epidemiological and molecular evidences linking obesity and cancer - particularly colorectal, post-menopausal breast, endometrial, pancreatic, high grade prostate, hepatocellular, gallbladder, kidney and esophageal adenocarcinoma. 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By using images taken with WFCAM on UKIRT and SofI on the NTT and combining them with 2MASS we have measured proper motions for 126 L and T dwarfs in the dwarf archive. Two of these L dwarfs appear to have M dwarf common proper motion companions, and 2 also appear to be high velocity dwarfs, indicating possible membership of the thick disc. We have also compared the motion of these 126 objects to that of numerous moving groups, and have identified new members of the Hyades, Ursa Major and Pleiades moving groups. These new objects, as well as those identified in Jameson et al. (2008) have allowed us to refine the L dwarf sequence for Ursa Major that was defined by Jameson et al. (2008).Comment: Accepted for publication in MNRAS. 10 pages, 3 figure

Extracellular vesicles from pancreatic cancer stem cells lead an intratumor communication network (EVNet) to fuel tumour progression

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.Objective: Intratumor heterogeneity drives cancer progression and therapy resistance. However, it has yet to be determined whether and how subpopulations of cancer cells interact and how this interaction affects the tumour. Design: We have studied the spontaneous flow of extracellular vesicles (EVs) between subpopulations of cancer cells: cancer stem cells (CSC) and non-stem cancer cells (NSCC). To determine the biological significance of the most frequent communication route, we used pancreatic ductal adenocarcinoma (PDAC) orthotopic models, patient-derived xenografts (PDXs) and genetically engineered mouse models (GEMMs). Results: We demonstrate that PDAC tumours establish an organised communication network between subpopulations of cancer cells using EVs called the EVNet). The EVNet is plastic and reshapes in response to its environment. Communication within the EVNet occurs preferentially from CSC to NSCC. Inhibition of this communication route by impairing Rab27a function in orthotopic xenographs, GEMMs and PDXs is sufficient to hamper tumour growth and phenocopies the inhibition of communication in the whole tumour. Mechanistically, we provide evidence that CSC EVs use agrin protein to promote Yes1 associated transcriptional regulator (YAP) activation via LDL receptor related protein 4 (LRP-4). Ex vivo treatment of PDXs with antiagrin significantly impairs proliferation and decreases the levels of activated YAP.Patients with high levels of agrin and low inactive YAP show worse disease-free survival. In addition, patients with a higher number of circulating agrin+ EVs show a significant increased risk of disease progression. Conclusion: PDAC tumours establish a cooperation network mediated by EVs that is led by CSC and agrin, which allows tumours to adapt and thrive. Targeting agrin could make targeted therapy possible for patients with PDAC and has a significant impact on CSC that feeds the tumour and is at the centre of therapy resistance.The work was supported by NORTE-01–0145-FEDER-000029, Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund and national funds through FCT—Foundation for Science and Technology POCI-01–0145-FEDER-32189. Programa Operacional Regional do Norte and co-financed by European Regional Development Fund under the project "The Porto Comprehensive Cancer Center" with the reference NORTE-01-0145-FEDER-072678 - Consórcio PORTO.CCC – Porto.Comprehensive Cancer Center. CFR is supported by FCT (SFRH/BD/131461/2017), NB by (SFRH/BD/130801/2017), IB by FCT (SFRH/BD/144854/2019), and BA by FCT (PD/BD/135546/2018). DG’s contribution was supported by the NCI (R21 CA179907). We acknowledge the support of the i3S Scientific Platforms: Translational Cytometry, Animal Facility, Bioimaging and Histology and Electron Microscopy are members of the national infrastructure PPBI - Portuguese Platform of Bioimaging (PPBI-POCI-01–0145-FEDER-022122). Proteomics was performed at the Proteomics Facility of The Spanish National Center for Biotechnology (CNB-CSIC), ProteoRed, PRB3-ISCIII, supported by grant PT17/0019.info:eu-repo/semantics/publishedVersio

The extraordinarily bright optical afterglow of GRB 991208 and its host galaxy

Observations of the extraordinarily bright optical afterglow (OA) of GRB 991208 started 2.1 d after the event. The flux decay constant of the OA in the R-band is -2.30 +/- 0.07 up to 5 d, which is very likely due to the jet effect, and after that it is followed by a much steeper decay with constant -3.2 +/- 0.2, the fastest one ever seen in a GRB OA. A negative detection in several all-sky films taken simultaneously to the event implies either a previous additional break prior to 2 d after the occurrence of the GRB (as expected from the jet effect). The existence of a second break might indicate a steepening in the electron spectrum or the superposition of two events. Once the afterglow emission vanished, contribution of a bright underlying SN is found, but the light curve is not sufficiently well sampled to rule out a dust echo explanation. Our determination of z = 0.706 indicates that GRB 991208 is at 3.7 Gpc, implying an isotropic energy release of 1.15 x 10E53 erg which may be relaxed by beaming by a factor > 100. Precise astrometry indicates that the GRB coincides within 0.2" with the host galaxy, thus given support to a massive star origin. The absolute magnitude is M_B = -18.2, well below the knee of the galaxy luminosity function and we derive a star-forming rate of 11.5 +/- 7.1 Mo/yr. The quasi-simultaneous broad-band photometric spectral energy distribution of the afterglow is determined 3.5 day after the burst (Dec 12.0) implying a cooling frequency below the optical band, i.e. supporting a jet model with p = -2.30 as the index of the power-law electron distribution.Comment: Accepted for publication in Astronomy and Astrophysics, 9 pages, 6 figures (Fig. 3 and Fig. 4 have been updated

History of Spinal Neurosurgery and Spine Societies

info:eu-repo/semantics/publishedVersio

Importance of TP53 codon 72 and intron 3 duplication 16bp polymorphisms in prediction of susceptibility on breast cancer

<p>Abstract</p> <p>Background</p> <p><it>TP53 </it>is one of major tumour suppressor genes being essential in preservation of genome integrity. Two very common polymorphisms have been demonstrated to contribute to cancer susceptibility and tumour behaviour. The purpose of this study was to evaluate the role of <it>Arg72Pro </it>and <it>PIN3 Ins16bp </it>polymorphisms in <it>TP53 </it>gene as genetic susceptibility and predictive markers to breast cancer.</p> <p>Methods</p> <p>We analysed DNA samples from 264 breast cancer patients and 440 controls, for <it>TP53 Arg72Pro </it>and <it>PIN3 Ins16bp </it>polymorphisms using PCR-RFLP.</p> <p>Results</p> <p>We observed that women with <it>A2A2 </it>genotype have increased risk for developing breast cancer, either in women with or without familial history (FH) of the disease (OR = 4.40, 95% CI 1.60–12.0; p = 0.004; OR = 3.88, 95% CI 1.18–12.8; p = 0.026, respectively). In haplotype analysis, statistically significant differences were found between <it>TP53 Arg-A2 </it>haplotype frequencies and familial breast cancer cases and the respective control group (OR = 2.10, 95% CI 1.08–4.06; p = 0.028). Furthermore, both <it>TP53 </it>polymorphisms are associated with higher incidence of lymph node metastases.</p> <p>Conclusion</p> <p>Our findings suggest <it>TP53 PIN3 Ins16bp </it>polymorphism as a real risk modifier in breast cancer disease, either in sporadic and familial breast cancer. Furthermore, both TP53 polymorphisms are associated with higher incidence of lymph node metastases.</p

Impact of the Covid-19 pandemic on perinatal mental health (Riseup-PPD-COVID-19): protocol for an international prospective cohort study

Background: Corona Virus Disease 19 (COVID-19) is a new pandemic, declared a public health emergency by the World Health Organization, which could have negative consequences for pregnant and postpartum women. The scarce evidence published to date suggests that perinatal mental health has deteriorated since the COVID-19 outbreak. However, the few studies published so far have some limitations, such as a cross-sectional design and the omission of important factors for the understanding of perinatal mental health, including governmental restriction measures and healthcare practices implemented at the maternity hospitals. Within the Riseup-PPD COST Action, a study is underway to assess the impact of COVID-19 in perinatal mental health. The primary objectives are to (1) evaluate changes in perinatal mental health outcomes; and (2) determine the risk and protective factors for perinatal mental health during the COVID-19 pandemic. Additionally, we will compare the results between the countries participating in the study. Methods: This is an international prospective cohort study, with a baseline and three follow-up assessments over a six-month period. It is being carried out in 11 European countries (Albania, Bulgaria, Cyprus, France, Greece, Israel, Malta, Portugal, Spain, Turkey, and the United Kingdom), Argentina, Brazil and Chile. The sample consists of adult pregnant and postpartum women (with infants up to 6 months of age). The assessment includes measures on COVID-19 epidemiology and public health measures (Oxford COVID-19 Government Response Tracker dataset), Coronavirus Perinatal Experiences (COPE questionnaires), psychological distress (BSI-18), depression (EPDS), anxiety (GAD-7) and post-traumatic stress symptoms (PTSD checklist for DSM-V). Discussion: This study will provide important information for understanding the impact of the COVID-19 pandemic on perinatal mental health and well-being, including the identification of potential risk and protective factors by implementing predictive models using machine learning techniques. The findings will help policymakers develop suitable guidelines and prevention strategies for perinatal mental health and contribute to designing tailored mental health interventions. Trial registration: ClinicalTrials.gov Identifier: NCT04595123.The project is part of the COST Action Riseup-PPD CA 18138 and was supported by COST under COST Action Riseup-PPD CA18138; also, by the Spanish Ministry of Health, the Institute of Health Carlos III, and the European Regional Development Fund «Una manera de hacer Europa» by the Prevention and Health Promotion Research Network ‘redIAPP’ (RD16/0007). Raquel Costa is supported by the FSE and FCT under an individual Post-Doctoral Grant SFRH/BPD/117597/2016. Rena Bina and Drorit Levy received funding from the Bar-Ilan Dangoor Centre for Personalized Medicine, Israel. Ana Mesquita is supported from the Portuguese Foundation for Science and Technology (FCT) and from EU through the European Social Fund and from the Human Potential Operational Program - IF/00750/2015. Ana Osório received financial support from CAPES/Proex no. 0653/2018 and CAPES/PrInt grant no. 88887.310343/2018-00.The funders of the study had no role in the study design or the writing the protocol. The corresponding author had final responsibility for the decision to submit for publication

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets