The complex organic molecular content in the L1517B starless core

Recent observations of the pre-stellar core L1544 and the younger starless core L1498 have revealed that complex organic molecules (COMs) are enhanced in the gas phase toward their outer and intermediate-density shells. Our goal is to determine the level of chemical complexity toward the starless core L1517B, which seems younger than L1498, and compare it with the other two previously studied cores to see if there is a chemical evolution within the cores. We have carried out 3 mm high-sensitivity observations toward two positions in the L1517B starless core: the core's centre and the position where the methanol emission peaks (at a distance of $\sim$5000 au from the core's centre). Our observations reveal that a lower number of COMs and COM precursors are detected in L1517B with respect to L1498 and L1544, and also show lower abundances. Besides methanol, we only detected CH$_3$O, H$_2$CCO, CH$_3$CHO, CH$_3$CN, CH$_3$NC, HCCCN, and HCCNC. Their measured abundances are $\sim$3 times larger toward the methanol peak than toward the core's centre, mimicking the behaviour found toward the more evolved cores L1544 and L1498. We propose that the differences in the chemical complexity observed between the three studied starless cores are a consequence of their evolution, with L1517B being the less evolved one, followed by L1498 and L1544. Chemical complexity in these cores seems to increase over time, with N-bearing molecules forming first and O-bearing COMs forming at a later stage as a result of the catastrophic depletion of CO.Comment: 18 pages, 13 figure

Incorporación De La Sustentabilidad En El Modelo De Negocio De Las Empresas Más Grandes De La Industria Del Cemento En México A Través De La Gestión Estratégica

In order to operationalize the concept of sustainability in the business world, organizations have to transform their mission, align the design of the complete business system and innovate their business model (Markevich, 2009). In this sense, the purpose of the work is to study the way in which two companies in the cement industry in Mexico incorporate sustainability in the strategic management of their business model. The study was carried out through the content analysis of the sustainability reports of the companies between 2015 and 2017. The results show that sustainability is incorporated through the elements included in the four stages of the business model and in all the hierarchical levels of the companies. However, there is no balanced orientation towards the three dimensions of sustainability in both companies

Gas phase Elemental abundances in Molecular cloudS (GEMS). IX. Deuterated compounds of H2S in starless cores

H2S is thought to be the main sulphur reservoir in the ice, being therefore a key molecule to understand sulphur chemistry in the star formation process and to solve the missing sulphur problem. The H2S deuterium fraction can be used to constrain its formation pathways. We investigate for the first time the H2S deuteration in a large sample of starless cores (SC). We use observations of the GEMS IRAM 30m Large Program and complementary IRAM 30m observations. We consider a sample of 19 SC in Taurus, Perseus, and Orion, detecting HDS in 10 and D2S in five. The H2S single and double deuterium fractions are analysed with regard to their relation with the cloud physical parameters, their comparison with other interstellar sources, and their comparison with deuterium fractions in early stage star-forming sources of c-C3H2, H2CS, H2O, H2CO, and CH3OH. We obtain a range of X(HDS)/X(H2S)~0.025-0.2 and X(D2S)/X(HDS)~0.05-0.3. H2S single deuteration shows an inverse relation with the cloud kinetic temperature. H2S deuteration values in SC are similar to those observed in Class 0. Comparison with other molecules in other sources reveals a general trend of decreasing deuteration with increasing temperature. In SC and Class 0 objects H2CS and H2CO present higher deuteration fractions than c-C3H2, H2S, H2O, and CH3OH. H2O shows single and double deuteration values one order of magnitude lower than those of H2S and CH3OH. Differences between c-C3H2, H2CS and H2CO deuterium fractions and those of H2S, H2O, and CH3OH are related to deuteration processes produced in gas or solid phases, respectively. We interpret the differences between H2S and CH3OH deuterations and that of H2O as a consequence of differences on the formation routes in the solid phase, particularly in terms of the different occurrence of the D-H and H-D substitution reactions in the ice, together with the chemical desorption processes.Comment: Accepted for publication in A&

First-in-human phase I clinical trial of a TLR4-binding DNA aptamer, ApTOLL: Safety and pharmacokinetics in healthy volunteers.

ApTOLL is an aptamer that antagonizes Toll-like receptor 4 and improves functional outcomes in models of ischemic stroke and myocardial infarction. The aim of this study was to characterize the safety and pharmacokinetics of ApTOLL in healthy volunteers. A first-in-human dose-ascending, randomized, placebo-controlled phase I clinical trial to assess safety and pharmacokinetics of ApTOLL (30-min infusion intravenously) was performed in 46 healthy adult male volunteers. The study was divided into two parts: part A included seven single ascending dose levels, and part B had one multiple dose cohort. Safety and pharmacokinetic parameters were evaluated. No serious adverse events or biochemistry alterations were detected at any dose nor at any administration pattern studied. Maximum concentration was detected at the end of the infusion and mean half-life was 9.3 h. Interestingly, exposure increased in the first four levels receiving doses from 0.7 mg to 14 mg (AUC of 2,441.26 h∗ng/mL to 23,371.11 h∗ng/mL) but remained stable thereafter (mean of 23,184.61 h∗ng/mL after 70 mg). Consequently, the multiple dose study did not show any accumulation of ApTOLL. These results show an excellent safety and adequate pharmacokinetic profile that, together with the efficacy demonstrated in nonclinical studies, provide the basis to start clinical trials in patients.This study was sponsored by aptaTargets S.L. (Madrid, Spain) and was conducted at the Clinical Trials Unit (La Princesa Hospital, Madrid, Spain). The study was supported by a grant from the Spanish Ministry of Science, Innovation and Universities (RTC-2017-6651- 1). Authors acknowledge David Segarra and M. Eugenia Zarabozo (aptaTargets S.L.) for their contribution in the management and funding of the trial, and Alba Singla (Anagram; Barcelona, Spain) for her contribution in the monitoring of the trial.S

A Case of Bicuspid Aorta with Stanford Type a Aortic Dissection

Bicuspid aortic valve disease (BAV) is a congenital disease that frequently produces complications during adulthood, and is considered not only a problem of valvulogenesis, but also a more complex genetic alteration that involves the development of the heart and the aorta, which entails a high morbidity and mortality in these patients. In 50% of adults with this pathology, non-valvular anomalies are observed, with dilation of the ascending aorta being the most common. Genes such as NOTCH1, UFDL1, ACTA2, eNOS, among others, have been identified as responsible for the appearance of aneurysms, which increases the risk in these patients of complications such as aortic dissection and its subsequent rupture. Painless aortic dissection may be seen in less than 5% of patients and may have an atypical clinical presentation. A case and review of the literature is presented in which we can observe the great complexity of this pathology, in the case of a patient with BAV, annulo-ectatic dilation of the aortic root and ascending aorta who developed heart failure, syncope and presented as a complication Stanford type A aortic dissection, requiring highly specialized surgical treatment

Boletín NUESTRA AMÉRICA XXI - Desafíos y alternativas, num.53, Marzo 2021

Una excelente iniciativa del Grupo de Trabajo Crisis y economía mundial, coordinado por María Josefina Morales, Julio Gambina y Gabriela Roffinelli

Educació farmacèutica en la prevenció de l'ictus

Treballs d'Educació Farmacèutica als ciutadans. Unitat Docent d'Estades en Pràctiques Tutelades. Facultat de Farmàcia, Universitat de Barcelona. Curs: 2018-2019. Tutors: Montserrat Iracheta i Marian March Pujol.Des de la farmàcia comunitària podem fer activitats assistencials per la millora en la qualitat de vida de les persones, sent les de caire preventiu de gran relevància. L’Ictus és l’alteració sobtada de la circulació de la sang al cervell així com la causant d’una gran discapacitat en la majoria de les persones que el pateixen. En aquest treball hem volgut apropar-nos a sanitaris (metges, infermers, farmacèutics) i pacients que estan relacionats amb aquest problema de salut, per que ens expliquessin que en pensen, com ho treballen i com ho viuen i el més important, com els farmacèutics comunitaris hi podem intervenir

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index <= 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission

A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis

We report a medium‐throughput drug‐screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood–brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug‐screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere