A Non-Viral Plasmid DNA Delivery System Consisting on a Lysine-Derived Cationic Lipid Mixed with a Fusogenic Lipid

The insertion of biocompatible amino acid moieties in non-viral gene nanocarriers is an attractive approach that has been recently gaining interest. In this work, a cationic lipid, consisting of a lysine-derived moiety linked to a C12 chain (LYCl) was combined with a common fusogenic helper lipid (DOPE) and evaluated as a potential vehicle to transfect two plasmid DNAs (encoding green fluorescent protein GFP and luciferase) into COS-7 cells. A multidisciplinary approach has been followed: (i) biophysical characterization based on zeta potential, gel electrophoresis, small-angle X-ray scattering (SAXS), and cryo-transmission electronic microscopy (cryo-TEM); (ii) biological studies by fluorescence assisted cell sorting (FACS), luminometry, and cytotoxicity experiments; and (iii) a computational study of the formation of lipid bilayers and their subsequent stabilization with DNA. The results indicate that LYCl/DOPE nanocarriers are capable of compacting the pDNAs and protecting them efficiently against DNase I degradation, by forming Lα lyotropic liquid crystal phases, with an average size of ~200 nm and low polydispersity that facilitate the cellular uptake process. The computational results confirmed that the LYCl/DOPE lipid bilayers are stable and also capable of stabilizing DNA fragments via lipoplex formation, with dimensions consistent with experimental values. The optimum formulations (found at 20% of LYCl content) were able to complete the transfection process efficiently and with high cell viabilities, even improving the outcomes of the positive control Lipo2000*

AKT activation seems to be associated with apoptotic signals and not with pro-survival signals in a pristane-induced lupus model.

Several studies have shown that in addition to its role as a survival factor and tumor promoting agent, AKT is also able to exhibit pro-apoptotic effects under diverse conditions, including oxidative stress, cytokine stimulation and exposure to cytotoxic chemicals like staurosporine, methotrexate, docetaxel and etoposide. Moreover, phosphorylation of second mitochondria-derived activator of caspases (SMAC) by AKT promotes caspase-3 activation during etoposide-induced apoptosis in HeLa cells. Our data show that injection of pristane into the peritoneum induces apoptosis-mediated cell death of peritoneal exudate cells (PECs), as evidenced by the increased number of annexin V+ peritoneal cells and their increased levels of cleaved/active caspase-3. Indeed, the higher levels of activated caspase-3 protein in WT PECs, particularly at 2-weeks post pristane treatment, are indicative of a higher rate of apoptosis compared to Cd38¿/¿ cells. In contrast, no differences were observed in the levels of MCL-1, an anti-apoptotic protein and member of the BCL2 family. Furthermore, kinases ERK1/2 and AKT showed distinct activation kinetics in pristane-elicited PECs. Interestingly, caspase-3 activation followed similar kinetics to AKT activation in both WT and Cd38¿/¿ PECs, while ERK activation correlated with increased levels of MCL-1. In summary our data strongly suggest that in the pristane-induced lupus model AKT activation is associated with apoptotic signals and not with survival signals. Further studies, however, are required to identify specific pro- and anti-apoptotic target proteins that are phosphorylated by ERK or AKT following pristane treatment, and that regulate the apoptotic process

LALINET: The First Latin American–Born Regional Atmospheric Observational Network

Sustained and coordinated efforts of lidar teams in Latin America at the beginning of the 21st century have built LALINET (Latin American Lidar NETwork), the only observational network in Latin America created by the agreement and commitment of Latin American scientists. They worked with limited funding but an abundance of enthusiasm and commitment toward their joint goal. Before LALINET, there were a few pioneering lidar stations operating in Latin America, described briefly here. Bi-annual Latin American Lidar Workshops, held from 2001 to the present, supported both the development of the regional lidar community and LALINET. At those meetings, lidar researchers from Latin America meet to conduct regular scientific and technical exchanges among themselves and with experts from the rest of the world. Regional and international scientific cooperation has played an important role for the development of both the individual teams and the network. The current LALINET status and activities are described, emphasizing the processes of standardization of the measurements, methodologies, calibration protocols, and retrieval algorithms. Failures and successes achieved in the buildup of LALINET are presented. In addition, the first LALINET joint measurement campaign and a set of aerosol extinction profile measurements obtained from the aerosol plume produced by the Calbuco volcano eruption on April 22, 2015, are described and discussed.Fil: Antuña Marrero, Juan Carlos. Centro Meteorológico de Camagüey; CubaFil: Landulfo, Eduardo. Instituto de Pesquisas Energéticas e Nucleares; BrasilFil: Estevan, René. Centro Meteorológico de Camagüey; CubaFil: Barja, Boris. Centro Meteorológico de Camagüey; Cuba. Universidade de Sao Paulo; BrasilFil: Robock, Alan. State University of New Jersey; Estados UnidosFil: Wolfram, Elian Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Científicas y Técnicas para la Defensa. Centro de Investigación en Láseres y Aplicaciones; ArgentinaFil: Ristori, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Científicas y Técnicas para la Defensa. Centro de Investigación en Láseres y Aplicaciones; ArgentinaFil: Clemesha, Barclay. Upper Atmosphere Research Group; BrasilFil: Zaratti, Francesco. Universidad Mayor de San Andrés; BoliviaFil: Forno, Ricardo. Universidad Mayor de San Andrés; BoliviaFil: Armandillo, Errico. ESTEC; Países BajosFil: Bastidas, Álvaro E.. Universidad Nacional de Colombia. Sede Medellin; ColombiaFil: de Frutos Baraja, Ángel Máximo. Universidad de Valladolid; EspañaFil: Whiteman, David N.. National Aeronautics and Space Administration; Estados UnidosFil: Quel, Eduardo Jaime. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Científicas y Técnicas para la Defensa. Centro de Investigación en Láseres y Aplicaciones; ArgentinaFil: Barbosa, Henrique M. J.. Universidade de Sao Paulo; BrasilFil: Lopes, Fabio. Comissao Nacional de Energia Nuclear. Centro de Lasers e Aplicacoes. Instituto de Pesquisas Energeticas e Nucleares.; BrasilFil: Montilla-Rosero, Elena. Universidad de Concepción; Chile. Universidad Escuela de Administración, Finanzas e Instituto Tecnológico; ColombiaFil: Guerrero Rascado, Juan L.. Comissao Nacional de Energia Nuclear. Centro de Lasers e Aplicacoes. Instituto de Pesquisas Energeticas e Nucleares.; Brasil. Universidad de Granada; Españ

GEICAM Guidelines for the Management of Patients with Breast Cancer During the COVID-19 Pandemic in Spain

Breast cancer (BC) is the most common cancer in women in Spain. During the COVID-19 pandemic caused by the SARSCoV-2 virus, patients with BC still require timely treatment and follow-up; however, hospitals are overwhelmed with infected patients and, if exposed, patients with BC are at higher risk for infection and serious complications if infected. Thus, health care providers need to evaluate each BC treatment and in-hospital visit to minimize pandemic-associated risks while maintaining adequate treatment efficacy. Here we present a set of guidelines regarding available options for BC patient management and treatment by BC subtype in the context of the COVID-19 pandemic. Owing to the lack of evidence about COVID-19 infection, these recommendations are mainly based on expert opinion, medical organizations’ and societies’ recommendations, and some published evidence. We consider this a useful tool to facilitate medical decision making in this health crisis situation we are facing

Transiciones, conflictos y democracia : estudios de coyuntura

México ha vivido un largo proceso de transición que ha desencadenado dinamismos económicos, culturales y políticos. En la actual coyuntura, estos dinamismos muestran toda su complejidad, su inevitable articulación y la tensión entre las fuerzas que intentan sostener un viejo modelo de gobernar y decidir el rumbo del país, y aquellas que buscan abrirse a un espectro mucho más amplio y diversificado de actores. En ellos se conjuntan las aspiraciones más legítimas de los mexicanos por avanzar en el reconocimiento y respeto de la pluralidad étnica, de género y entre generaciones, y por impulsar una dinámica en la que —en medio de los procesos de mundialización— los distintos grupos e intereses de los mexicanos puedan ser incluidos. La transición mexicana tiende a centrarse en la dimensión política. La intensidad que cobran los procesos políticos y el énfasis que importantes analistas ponen en dichos procesos, contribuyen a que esta asociación vaya cobrandoíuerza. En este sentido, es necesario advertir que en las transiciones la tendencia privatizadora, la reducción del gasto social, así como la necesidad de pactos sociales que sean respetados, la participación creciente de la sociedad civil, etc. son factores importantes que, en medio de contradicciones, van generando nuevos esquemas de relación entre gobierno y sociedad.ITESO, A.C

A Precision Treatment Model for Internet-Delivered Cognitive Behavioral Therapy for Anxiety and Depression among University Students:A Secondary Analysis of a Randomized Clinical Trial

Importance: Guided internet-delivered cognitive behavioral therapy (i-CBT) is a low-cost way to address high unmet need for anxiety and depression treatment. Scalability could be increased if some patients were helped as much by self-guided i-CBT as guided i-CBT. Objective: To develop an individualized treatment rule using machine learning methods for guided i-CBT vs self-guided i-CBT based on a rich set of baseline predictors. Design, Setting, and Participants: This prespecified secondary analysis of an assessor-blinded, multisite randomized clinical trial of guided i-CBT, self-guided i-CBT, and treatment as usual included students in Colombia and Mexico who were seeking treatment for anxiety (defined as a 7-item Generalized Anxiety Disorder [GAD-7] score of ≥10) and/or depression (defined as a 9-item Patient Health Questionnaire [PHQ-9] score of ≥10). Study recruitment was from March 1 to October 26, 2021. Initial data analysis was conducted from May 23 to October 26, 2022. Interventions: Participants were randomized to a culturally adapted transdiagnostic i-CBT that was guided (n = 445), self-guided (n = 439), or treatment as usual (n = 435). Main Outcomes and Measures: Remission of anxiety (GAD-7 scores of ≤4) and depression (PHQ-9 scores of ≤4) 3 months after baseline. Results: The study included 1319 participants (mean [SD] age, 21.4 [3.2] years; 1038 women [78.7%]; 725 participants [55.0%] came from Mexico). A total of 1210 participants (91.7%) had significantly higher mean (SE) probabilities of joint remission of anxiety and depression with guided i-CBT (51.8% [3.0%]) than with self-guided i-CBT (37.8% [3.0%]; P =.003) or treatment as usual (40.0% [2.7%]; P =.001). The remaining 109 participants (8.3%) had low mean (SE) probabilities of joint remission of anxiety and depression across all groups (guided i-CBT: 24.5% [9.1%]; P =.007; self-guided i-CBT: 25.4% [8.8%]; P =.004; treatment as usual: 31.0% [9.4%]; P =.001). All participants with baseline anxiety had nonsignificantly higher mean (SE) probabilities of anxiety remission with guided i-CBT (62.7% [5.9%]) than the other 2 groups (self-guided i-CBT: 50.2% [6.2%]; P =.14; treatment as usual: 53.0% [6.0%]; P =.25). A total of 841 of 1177 participants (71.5%) with baseline depression had significantly higher mean (SE) probabilities of depression remission with guided i-CBT (61.5% [3.6%]) than the other 2 groups (self-guided i-CBT: 44.3% [3.7%]; P =.001; treatment as usual: 41.8% [3.2%]; P &lt;.001). The other 336 participants (28.5%) with baseline depression had nonsignificantly higher mean (SE) probabilities of depression remission with self-guided i-CBT (54.4% [6.0%]) than guided i-CBT (39.8% [5.4%]; P =.07). Conclusions and Relevance: Guided i-CBT yielded the highest probabilities of remission of anxiety and depression for most participants; however, these differences were nonsignificant for anxiety. Some participants had the highest probabilities of remission of depression with self-guided i-CBT. Information about this variation could be used to optimize allocation of guided and self-guided i-CBT in resource-constrained settings. Trial Registration: ClinicalTrials.gov Identifier: NCT04780542.</p