Potent Cardioprotective Effect of the 4-Anilinoquinazoline Derivative PD153035: Involvement of Mitochondrial KATP Channel Activation

Background: The aim of the present study was to evaluate the protective effects of the 4-anilinoquinazoline derivative PD153035 on cardiac ischemia/reperfusion and mitochondrial function. Methodology/Principal Findings: Perfused rat hearts and cardiac HL-1 cells were used to determine cardioprotective effects of PD153035. Isolated rat heart mitochondria were studied to uncover mechanisms of cardioprotection. Nanomolar doses of PD153035 strongly protect against heart and cardiomyocyte damage induced by ischemia/reperfusion and cyanide/aglycemia. PD153035 did not alter oxidative phosphorylation, nor directly prevent Ca(2+) induced mitochondrial membrane permeability transition. The protective effect of PD153035 on HL-1 cells was also independent of AKT phosphorylation state. Interestingly, PD153035 activated K(+) transport in isolated mitochondria, in a manner prevented by ATP and 5-hydroxydecanoate, inhibitors of mitochondrial ATP-sensitive K(+) channels (mitoK(ATP)). 5-Hydroxydecanoate also inhibited the cardioprotective effect of PD153035 in cardiac HL-1 cells, demonstrating that this protection is dependent on mitoK(ATP) activation. Conclusions/Significance: We conclude that PD153035 is a potent cardioprotective compound and acts in a mechanism involving mitoK(ATP) activation

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

Aguas del Iténez o Guaporé

Bolivia y Brasil comparten una de las cuencas más atractivas y preservadas de la te-giuri amazônica: la cuenca del rio llénez o Guaporé, que escurre tanto sobre el lecho rocoso del Escudo Precámbrico Brasilefto como sobre las Hanuras del Beni. Estas influencias hacen que la cuenca del iténez tenga una elevada heterogeneidad de habitats, una fauna acuálica peculiar y un alto valor de conservation. Este patrimo­nio binacional posée un potencial importante para la conservación de la diversidad regional y cl dcsar rollo sostcniblc participativo de las comunidades locales. El libro contiene un resumen del conotimìento de la cuenca y sus recursos, generado en los últimos 10 anos por un equipo de investigadores bolivianos, brasilefios y de otras nacionalidades. Se presenta una descripeión del medio fisico, así como resultados relevantes sobre la biodiversidad acuática, con énfasis en algas, peces, reptiles y mamíferos. El aporte más notable del libro, adernas de la descripeión ecológica del ecosistema, son las lecciones aprendidas que surgieron de experiências locales sobre la élaboration participativa de herramientas para la gestion de los recursos hidrobiológicos.A Bolívia e o Brasil compartilham uma das bacias hidrográficas mais atrativas e preservadas da região amazônica: a bacia do Rio Iténez ou Guaporé. A combinação das influências do escudo pré-cambriano brasileiro e da planícies do Beni é uma das razões pela qual existem na região elevada heterogeneidade de habitats, fauna aquática peculiar e alto grau valor dc conservação. Eslc patrimônio binacional possui potencial significativo para a conservação da diversidade regional e desenvolvimento sustentável participativo das comunidades locais. O livro contém um resumo do conhecimento da bacia e seus recursos, gerado nos últimos dez anos por uma equipe de pesquisadores bolivianos, brasileiros e de outras nacionalidades. Apresentamos uma descrição do meio físico, bem como resultados relevantes da biodiversidade aquática, com ênfase em algas, peixes, répteis e mamíferos. A contribuição mais notável do livro, além da descrição ecológica do ecossistema, é a descrição das lições aprendidas que surgiram a partir de experiências locais sobre elaboração participativa de ferramentas para a gestão dos recursos aquáticos presentes nesta bacia

Anales del III Congreso Internacional de Vivienda y Ciudad "Debate en torno a la nueva agenda urbana"

Acta de congresoEl III Congreso Internacional de Vivienda y Ciudad “Debates en torno a la NUEVa Agenda Urbana”, ha sido una apuesta de alto compromiso por acercar los debates centrales y urgentes que tensionan el pleno ejercicio del derecho a la ciudad. Para ello las instituciones organizadoras (INVIHAB –Instituto de Investigación de Vivienda y Hábitat y MGyDH-Maestría en Gestión y Desarrollo Habitacional-1), hemos convidado un espacio que se concretó con potencia en un debate transdisciplinario. Convocó a intelectuales de prestigio internacional, investigadores, académicos y gestores estatales, y en una metodología de innovación articuló las voces académicas con las de las organizaciones sociales y/o barriales en el Foro de las Organizaciones Sociales que tuvo su espacio propio para dar voz a quienes están trabajando en los desafíos para garantizar los derechos a la vivienda y los bienes urbanos en nuestras ciudades del Siglo XXI

Secondary Amines from Catalytic Amination of Bio-Derived Phenolics over Pd/C and Rh/C: Effect of Operation Parameters

The production of renewable chemicals using lignocellulosic biomass has gained significant attention in green chemistry. Among biomass-derived chemicals, secondary amines have emerged as promising intermediates for synthetic applications. Here, we report a systematic study on the reductive amination of phenolics with cyclohexylamine using Pd/C and Rh/C as catalysts. The catalytic tests were performed in batch reactors under different reaction conditions (various: amine concentration (0.1–0.4 mol/L), hydrogen pressure (0–2.5 bar), temperature (80–160 °C), and substituted phenols (phenol, o-cresol, p-cresol, and methoxyphenol)) and using tert-amyl alcohol as a solvent. The experimental observations were consistent with a multi-step mechanism, where hydrogenation of phenol to cyclohexanone is followed by condensation of the ketone with cyclohexylamine to form an imine, which is finally hydrogenated to produce secondary amines. In addition, there was evidence of parallel self-condensation of the cyclohexylamine. The study also supported a limited dehydrogenation capacity of Rh/C, unlike Pd/C, which increases this capacity at higher temperatures generating a higher yield of cyclohexylaniline (up to 15%). The study of the alkylated phenols demonstrated that the nature and propensity of hydrogenation of the phenolic controls their amination. Kinetic analysis revealed reaction orders between 0.4 and 0.7 for H, indicating its dissociative adsorption. Meanwhile, phenol’s order (between 1–1.8) suggests a single participation of this compound in the hydrogenation step. The order of 0.4 for cyclohexylamine suggests its participation as a surface-abundant species. The apparent activation energies derived from a power law approximation were of 37 kJ/mol and 10 kJ/mol on Pd/C and Rh/C, respectively.This research was funded by Agencia Nacional de Investigaciones (Chile), grant number FONDECYT 1190063 and the University of Bio-Bio through the internal project 2260311 AD/EQ

La accesibilidad universal al medio físico: Un reto para la arquitectura moderna

The purpose of this article is to understand the challenge that architecture has in this new era to create spaces that are fully accessible and suitable for everyone’s enjoyment. To talk of inclusive cities is to talk of autonomy, security and above all of appropriation of public space; much more, in a world where the incorporation of people with disabilities into the working environment and social life is gradually increasing, which means that adequate urban and architectural spaces are required to guarantee the satisfaction of the needs that come with the various disabilities, benefiting the entire conglomerate and allowing for greater social inclusion; so that people with disabilities can live independently and fully participate in all aspects of life.La siguiente investigación tiene como finalidad conocer el reto que tiene la arquitectura en esta nueva era para crear espacios que sean completamente accesibles y que estén aptos para el disfrute de todos. Hablar de ciudades inclusivas es hablar de autonomía, seguridad y sobre todo de apropiación del espacio público; mucho más, en un mundo en donde paulatinamente se va acrecentando la incorporación de personas con discapacidad al medio laboral y a la vida social, lo que hace que se requieran de espacios urbanos y arquitectónicos adecuados que garanticen la satisfacción de las necesidades que conllevan las diversas discapacidades

Data from: Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer

Using an ORF kinome screen in MCF-7 cells treated with the CDK4/6 inhibitor ribociclib plus fulvestrant, we identified FGFR1 as a mechanism of drug resistance. FGFR1-amplified/ER+ breast cancer cells and MCF-7 cells transduced with FGFR1 were resistant to fulvestrant ± ribociclib or palbociclib. This resistance was abrogated by treatment with the FGFR tyrosine kinase inhibitor (TKI) lucitanib. Addition of the FGFR TKI erdafitinib to palbociclib/fulvestrant induced complete responses of FGFR1-amplified/ER+ patient-derived-xenografts. Next generation sequencing of circulating tumor DNA (ctDNA) in 34 patients after progression on CDK4/6 inhibitors identified FGFR1/2 amplification or activating mutations in 14/34 (41%) post-progression specimens. Finally, ctDNA from patients enrolled in MONALEESA-2, the registration trial of ribociclib, showed that patients with FGFR1 amplification exhibited a shorter progression-free survival compared to patients with wild type FGFR1. Thus, we propose breast cancers with FGFR pathway alterations should be considered for trials using combinations of ER, CDK4/6 and FGFR antagonists

Global attitudes in the management of acute appendicitis during COVID-19 pandemic: ACIE Appy Study

Background: Surgical strategies are being adapted to face the COVID-19 pandemic. Recommendations on the management of acute appendicitis have been based on expert opinion, but very little evidence is available. This study addressed that dearth with a snapshot of worldwide approaches to appendicitis. Methods: The Association of Italian Surgeons in Europe designed an online survey to assess the current attitude of surgeons globally regarding the management of patients with acute appendicitis during the pandemic. Questions were divided into baseline information, hospital organization and screening, personal protective equipment, management and surgical approach, and patient presentation before versus during the pandemic. Results: Of 744 answers, 709 (from 66 countries) were complete and were included in the analysis. Most hospitals were treating both patients with and those without COVID. There was variation in screening indications and modality used, with chest X-ray plus molecular testing (PCR) being the commonest (19\ub78 per cent). Conservative management of complicated and uncomplicated appendicitis was used by 6\ub76 and 2\ub74 per cent respectively before, but 23\ub77 and 5\ub73 per cent, during the pandemic (both P < 0\ub7001). One-third changed their approach from laparoscopic to open surgery owing to the popular (but evidence-lacking) advice from expert groups during the initial phase of the pandemic. No agreement on how to filter surgical smoke plume during laparoscopy was identified. There was an overall reduction in the number of patients admitted with appendicitis and one-third felt that patients who did present had more severe appendicitis than they usually observe. Conclusion: Conservative management of mild appendicitis has been possible during the pandemic. The fact that some surgeons switched to open appendicectomy may reflect the poor guidelines that emanated in the early phase of SARS-CoV-2