First-line maintenance treatment in metastatic colorectal cancer (mCRC) : Quality and clinical benefit overview

Different strategies of maintenance therapy (sequential CT, intermittent CT, intermittent CT and MAbs, or de-escalation MAbs monotherapy) after first-line treatment are undertaken. Many randomized clinical trials (RCT), which evaluated these approaches, suffer from incorrect design, heterogenous primary endpoints, inadequate size, and other methodology flaws. Drawing any conclusions becomes challenging and recommendations are mainly vague. We evaluated those studies from another perspective, focusing on the design quality and the clinical benefit measure with a more objective and accurate methodology. These data allowed a clearer and more exact overview of the statement in maintenance treatment

Spatiotemporal Control of Vascular Endothelial Growth Factor Expression Using a Heat-Shock-Activated, Rapamycin-Dependent Gene Switch

A major challenge in regenerative medicine is to develop methods for delivering growth and differentiation factors in specific spatial and temporal patterns, thereby mimicking the natural processes of development and tissue repair. Heat shock (HS)-inducible gene expression systems can respond to spatial information provided by localized heating, but are by themselves incapable of sustained expression. Conversely, gene switches activated by small molecules provide tight temporal control and sustained expression, but lack mechanisms for spatial targeting. Here we combine the advantages of HS and ligand-activated systems by developing a novel rapamycin-regulated, HS-inducible gene switch that provides spatial and temporal control and sustained expression of transgenes such as firefly luciferase and vascular endothelial growth factor (VEGF). This gene circuit exhibits very low background in the uninduced state and can be repeatedly activated up to 1 month. Furthermore, dual regulation of VEGF induction in vivo is shown to stimulate localized vascularization, thereby providing a route for temporal and spatial control of angiogenesis.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140102/1/hgtb.2013.026.pd

Mental health, suicide attempt, and family function for adolescents' primary health care during the COVID-19 pandemic

Background: The study's purpose was to identify associations between mental health risk, suicide attempts, and family function. Methods: A correlational, descriptive, and cross-sectional study was carried out in a group of adolescents in the last grade of secondary school to establish the association between mental health risk, suicide attempt, and family functionality. The instruments used were the self-report questionnaire, the suicide risk assessment scale, and the family APGAR. Data analysis was performed using the artificial intelligence algorithm (gower clustering). Results: 246 adolescents responded to the three instruments, which made it possible to select those with correlations of sensitive interest and, based on these, an intervention plan. Psychological distress was found in 28%, psychotic symptoms in 85%, and problematic alcohol use in 9%. Good family functioning was identified in 34% and some type of family dysfunction in 66%. In terms of suicide risk, there was a low suicide risk of 74%, 24% medium risk, and 2% high risk. It could be shown that there is a correlation in a group of 15% of the respondents. Conclusions: The risk of suffering mental health deterioration and the suicide risk, during this pandemic period, seems to be related to family functionality

Electrical characterization of single molecule and Langmuir-Blodgett monomolecular films of a pyridine-terminated oligo(phenylene-ethynylene) derivative

Monolayer Langmuir–Blodgett (LB) films of 1,4-bis(pyridin-4-ylethynyl)benzene (1) together with the “STM touch-to-contact” method have been used to study the nature of metal–monolayer–metal junctions in which the pyridyl group provides the contact at both molecule–surface interfaces. Surface pressure vs area per molecule isotherms and Brewster angle microscopy images indicate that 1 forms true monolayers at the air–water interface. LB films of 1 were fabricated by deposition of the Langmuir films onto solid supports resulting in monolayers with surface coverage of 0.98 × 10−9 mol·cm−2. The morphology of the LB films that incorporate compound 1 was studied using atomic force microscopy (AFM). AFM images indicate the formation of homogeneous, monomolecular films at a surface pressure of transference of 16 mN·m−1. The UV–vis spectra of the Langmuir and LB films reveal that 1 forms two dimensional J-aggregates. Scanning tunneling microscopy (STM), in particular the “STM touch-to-contact” method, was used to determine the electrical properties of LB films of 1. From these STM studies symmetrical I–V curves were obtained. A junction conductance of 5.17 × 10−5 G 0 results from the analysis of the pseudolinear (ohmic) region of the I–V curves. This value is higher than that of the conductance values of LB films of phenylene-ethynylene derivatives contacted by amines, thiols, carboxylate, trimethylsilylethynyl or acetylide groups. In addition, the single molecule I–V curve of 1 determined using the I(s) method is in good agreement with the I–V curve obtained for the LB film, and both curves fit well with the Simmons model. Together, these results not only indicate that the mechanism of transport through these metal–molecule–metal junctions is non-resonant tunneling, but that lateral interactions between molecules within the LB film do not strongly influence the molecule conductance. The results presented here complement earlier studies of single molecule conductance of 1 using STM-BJ methods, and support the growing evidence that the pyridyl group is an efficient and effective anchoring group in sandwiched metal–monolayer–metal junctions prepared under a number of different conditions.S. M., M. C. L, and P. C. are grateful for financial assistance from Ministerio de Economía y Competitividad from Spain in the framework of project CTQ2012-33198 and support from DGA and Fondos Feder for funding the Platon research group. S. M. also thanks his JIUZ-2013-CIE-05 grant. S. M and P. C. are grateful for the award of the CTQ2013-50187-EXP grant. P. J. L. thanks EPSRC for funding and also gratefully acknowledges support from the Australian Research Council (DP 140100855) and the award of the Future Fellowship (FT120100073). R. J. N. and S. J. H. thank EPSRC for funding (grant EP/H035184/1 and EP/K007785/1).Peer Reviewe

Phase-Locking of Vortex Lattices Interacting with Periodic Pinning

We examine Shapiro steps for vortex lattices interacting with periodic pinning arrays driven by AC and DC currents. The vortex flow occurs by the motion of the interstitial vortices through the periodic potential generated by the vortices that remain pinned at the pinning sites. Shapiro steps are observed for fields B_{\phi} < B < 2.25B_{\phi} with the most pronouced steps occuring for fields where the interstitial vortex lattice has a high degree of symmetry. The widths of the phase-locked current steps as a function of the magnitude of the AC driving are found to follow a Bessel function in agreement with theory.Comment: 5 pages 5 postscript figure

Electronic cigarette use among adult population: a cross-sectional study in Barcelona, Spain (2013–2014)

Objective: This study seeks to analyse the prevalence and correlates of electronic cigarette (e-cigarette) use, purchase location and satisfaction with its use in a sample of the general population of the city of Barcelona, Spain. Design, setting and participants We used participants from a longitudinal study of a representative sample of the adult (≥16 years old) population of Barcelona (336 men and 400 women). The field work was conducted between May 2013 and February 2014. We computed the prevalence, adjusted odds ratios (ORs) and their corresponding 95% confidence interval (CI). Results: The prevalence of ever e-cigarette use was 6.5% (95% CI 4.7% to 8.3%): 1.6% current use, 2.2% past use and 2.7% only e-cigarette experimentation. 75% (95% CI 62.8% to 87.3%) of ever e-cigarette users were current cigarette smokers at the moment of the interview. E-cigarette use was more likely among current smokers (OR=54.57; 95% CI 7.33 to 406.38) and highly dependent cigarette smokers (OR=3.96; 95% CI 1.60 to 9.82). 62.5% of the ever users charged their e-cigarettes with nicotine with 70% of them obtaining the liquids with nicotine in a specialised shop. 39.6% of ever e-cigarette users were not satisfied with their use, a similar percentage of not satisfied expressing the smokers (38.9%) and there were no statistically significant differences in the satisfaction between the users of e-cigarettes with and without nicotine. Conclusions: E-cigarette use is strongly associated with current smoking (dual use) and most users continue to be addicted to nicotine. Six out of 10 e-cigarette users preferred devices that deliver nicotine. The satisfaction with e-cigarette use is very low

Attitudes towards Electronic Cigarettes Regulation in Indoor Workplaces and Selected Public and Private Places: A Population-Based Cross-Sectional Study

Background: Currently, there is an intensive debate about the regulation of the use of electronic cigarettes (e-cigarettes) in indoor places. The aim of this study was to assess the attitudes toward e-cigarette use in indoor workplaces and selected public and private venues among the general population in Barcelona (Spain) in 2013–2014. Methods: This is a cross-sectional study of a representative sample of the population of Barcelona (n = 736). The field work was conducted between May 2013 and February 2014. We computed the prevalence and the adjusted odds ratios (OR) derived from multivariable logistic regression models. Results: The awareness of e-cigarettes was 82.3%. Forty five percent of respondents did not agree with the use of e-cigarettes in public places and 52.3% in workplaces. The proportion of disapproval of the use of e-cigarettes in indoor places was higher at 71.5% for schools and 65.8% for hospitals and health care centers; while the prevalence of disapproval of e-cigarette use in homes and cars was lower (18.0% and 32.5%, respectively). Respondents who disagreed on the use of e-cigarettes in indoor workplaces were more likely to be older (OR = 1.64 and 1.97 for groups 45–64 and ≧65 years old, respectively), those with a high educational level (OR = 1.60), and never and former smokers (OR = 2.34 and 2.16, respectively). Increased scores in the Fagerström test for cigarette dependence were also related to increased support for their use. Conclusions: Based on this population based study, half of the general population of Barcelona does not support the use of e-cigarettes in indoor workplaces and public places, with the percentage reaching 65% for use in schools, hospitals and health care centers. Consequently, there is good societal support in Spain for the politicians and legislators to promote policies restricting e-cigarettes use in workplaces and public places, including hospitality venues

SEOM clinical guideline for the diagnosis and treatment of gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJA) (2019)

Gastric cancer (GC) is the fifth most common cancer worldwide with a varied geographic distribution and an aggressive behavior. In Spain, it represents the sixth cause of cancer death. In Western countries, the incidence is decreasing slightly, with an increase in gastroesophageal junction adenocarcinoma (GEJA), a different entity that we separate specifically in the guideline. Molecular biology advances have been done recently, but do not yet lead to the choice in treatment approach except in advanced disease with overexpression of HER2. Endoscopic resection in very early stage, perioperative chemotherapy in locally advanced tumors and preliminary immune therapy resulting in advanced disease are the main treatment innovations in the GC/GEJA treatment. We describe the different evidences and recommendations following the statements of the American College of Physicians

Low variability of single-molecule conductance assisted by bulky metal-molecule contacts

A detailed study of the trimethylsilylethynyl moiety, –C[triple bond]CSiMe3 (TMSE) , as an anchoring group in metalmoleculemetal junctions, using a combination of experiment and density functional theory is presented. It is shown that the TMSE anchoring group provides improved control over the molecule-substrate arrangement within metalmoleculemetal junctions, with the steric bulk of the methyl groups limiting the number of highly transmissive binding sites at the electrode surface, resulting in a single sharp peak in the conductance histograms recorded by both the in situ break junction and I(s) STM techniques. As a consequence of the low accessibility of the TMSE group to surface binding configurations of measurable conductance, only about 10% of gold break junction formation cycles result in the clear formation of molecular junctions in the experimental histograms. The DFT-computed transmission characteristics of junctions formed from the TMSE-contacted oligo(phenylene)ethynylene (OPE)-based molecules described here are dominated by tunneling effects through the highest-occupied molecular orbitals (HOMOs). This gives rise to similar conductance characteristics in these TMSE-contacted systems as found in low conductance-type junctions based on comparably structured OPE-derivatives with amine-contacts that also conduct through HOMO-based channels.R. R. F. thanks the Consejería de Educación del Principado de Asturias for a Severo Ochoa grant (BP11-069). V. M. G.-S. thanks the Spanish Ministerio de Economía y Competitividad for a Ramón y Cajal fellowship (RYC-2010-06053). R. R. F., J. F. and V. M. G.-S. wish to acknowledge financial support from the Spanish grant FIS2012-34858 and the Marie Curie Network MOLESCO. P. C. and S. M. are grateful for financial assistance from the Ministerio de Economía y Competitividad of Spain in the framework of the project CTQ2012-33198 as well as the award of the CTQ2013-50187-EXP grant. H. M. O., P. C., and S. M. thank the support from DGA and Fondos FEDER for funding through the Platon research group. H. M. O. is also grateful for financial assistance from the Secretaría Nacional de Educación Superior, Ciencia, Tecnología e Innovaciín from Ministerio de Educación (Ecuador). S. M. thanks the Ministerio de Educación from Spain for financial support through the framework of the Campus de Excelencia Internacional, CEI Iberus. S. J. H., R. J. N., P. J. L. and S. M.-G. thank the EPSRC for funding (EPSRC grants EP/K007785/1, EP/H035184/1, EP/K007548/1, EP/H005595/1). P. J. L. holds an Australian Research Council Future Fellowship (FT120100073) and gratefully acknowledges funding for this work from the ARC (DP140100855).Peer Reviewe