Molecular examination of differentially expressed genes in the brains of experimental autoimmune encephalomyelitis mice post herceptin treatment

Objective: Herceptin (trastuzumab) is an approved drug for treating HER2+ breast cancer patients, but its use for other diseases is not established. We sought to investigate the effects of Herceptin on ameliorating experimental autoimmune encephalomyelitis (EAE) and to examine its effects on the expression of various genes. Methods: We used in-silico analysis of publicly available data, qRT-PCR, and immunohisto-chemistry (IHC) to determine the expression of HER2+ cells in the brains of EAE mice. IHC was also utilized to determine the anti-inflammatory effects of Herceptin. The ability of Herceptin to alleviate the EAE clinical score was measured in these mice. Bioinformatics analysis of publicly available data and qRT-PCR were performed to investigate the differentially expressed genes that were either up-regulated or down-regulated during the high clinical score (HCS) of the disease. Results: We observed that HER2/Erbb2, the receptor for Herceptin is upregulated in the brains of EAE mice when the brains were examined at the HCS stage. Further, we demonstrated that Herceptin ameliorates the EAE disease, increasing re-myelination, reducing brain inflammation, CD3+ T cell accumulation, and HER2+ cells in the brains of these mice. Molecular analysis demonstrated the expression of different genes that were either up-regulated or down-regulated during the HCS of the disease. Our combined bioinformatics and qRT-PCR analyses show increased mRNA expression of Atp6v0d2, C3, C3ar1, Ccl3, Ccl6, Cd74, Clec7a, Cybb, H2-Aa, Hspb1, Lilr4b, Lilrb4a, Mpeg1, Ms4a4a, Ms4a6c, Saa3, Serpina3n and Timp1, at HCS. Except for the mRNA levels of Cd74 and Clec7a which were increased at HCS when Herceptin was used in both prophylactic and therapeutic regimens, the levels of other described mRNAs were reduced. Conclusion: These novel findings show that Herceptin ameliorates the clinical score in EAE mice and are the first to investigate in detail the differential gene expression post-treatment with the drug.</p

Molecular examination of differentially expressed genes in the brains of experimental autoimmune encephalomyelitis mice post herceptin treatment

Objective: Herceptin (trastuzumab) is an approved drug for treating HER2+ breast cancer patients, but its use for other diseases is not established. We sought to investigate the effects of Herceptin on ameliorating experimental autoimmune encephalomyelitis (EAE) and to examine its effects on the expression of various genes. Methods: We used in-silico analysis of publicly available data, qRT-PCR, and immunohisto-chemistry (IHC) to determine the expression of HER2+ cells in the brains of EAE mice. IHC was also utilized to determine the anti-inflammatory effects of Herceptin. The ability of Herceptin to alleviate the EAE clinical score was measured in these mice. Bioinformatics analysis of publicly available data and qRT-PCR were performed to investigate the differentially expressed genes that were either up-regulated or down-regulated during the high clinical score (HCS) of the disease. Results: We observed that HER2/Erbb2, the receptor for Herceptin is upregulated in the brains of EAE mice when the brains were examined at the HCS stage. Further, we demonstrated that Herceptin ameliorates the EAE disease, increasing re-myelination, reducing brain inflammation, CD3+ T cell accumulation, and HER2+ cells in the brains of these mice. Molecular analysis demonstrated the expression of different genes that were either up-regulated or down-regulated during the HCS of the disease. Our combined bioinformatics and qRT-PCR analyses show increased mRNA expression of Atp6v0d2, C3, C3ar1, Ccl3, Ccl6, Cd74, Clec7a, Cybb, H2-Aa, Hspb1, Lilr4b, Lilrb4a, Mpeg1, Ms4a4a, Ms4a6c, Saa3, Serpina3n and Timp1, at HCS. Except for the mRNA levels of Cd74 and Clec7a which were increased at HCS when Herceptin was used in both prophylactic and therapeutic regimens, the levels of other described mRNAs were reduced. Conclusion: These novel findings show that Herceptin ameliorates the clinical score in EAE mice and are the first to investigate in detail the differential gene expression post-treatment with the drug.</p

Personal identity: an issue that demands revision in today’s philosophical and interdisciplinary dialogue

Today we are witnessing an unprecedented crisis caused by the Covid-19 pandemic. Its unparalleled and unpredictable character, added to its expansion and the way it has affected contemporary society, also emphasizes the underlying question, who are we? Why and in what sense? In the current context, where, on the one hand, there is a loss of confidence in the ways in which we govern ourselves, as well as an uncertainty regarding the direction that this crisis may take and the threshold to which it can lead us, the question certainly arises as to whether what we are has a background on which to support ourselves; if anything, that "who" that we claim to be and to whom we bear witness in our work can withstand the test of the unpredictable and unexpected, of what has plunged us into a situation as unusual as it is incomprehensible. As tragic as this situation affects us worldwide, it affects us both collectively and personally. With all the momentum with which this even strikes us, do we not live it precisely as a challenge to the security whereby we usually respond to the question of our personal identity? Is it not at such an exceptional moment as this, when the question of personal identity worries us greatly as soon as our temporal condition takes on real importance, which, irreversible as such, offers us in turn the opportunity to reverse the situation we are involved in? Is it not during this worldwide crisis, which we first experienced as a personal rupture, which in turn gives us the opportunity to appreciate the tension we live in, but which is present, however, most of the time, invisible to us, namely, that of being engaged in a habitual, inhabited space, consolidated by a sense that we inherit, at the same time that we believe we are called to innovate on that? Isn't this time the one that certainly makes history in our personal and social fabric? However, it seems that we also can, in an unprecedented way, experience this crisis as an identity crisis insofar as it enhances its problematic dimension. The articles we present here have the quality of confronting this question from multiple perspectives that, irreducible between them, still manage to give certain lucidity to that which we comprehend around the question of “who am I?, which is especially necessary at this moment. In this sense, the texts put us, in one hand, on the phenomenological-eventual scope just like it has been elaborated by the French thinker, Claude Romano, who interrogates the human being in his capacity to embrace the events that shock the subject’s existencial unfolding. On the other hand, we have collected articles that revolve around the hermeneutic phenomenology of Paul Ricœur, focusing their attention both on the ontological condition of human beings, as well as on the perspective of his hermeneutics of action and narrative. We finally conclude with a text by Shaumann which questions the relationship between identity and alienation, interrogating the philosophies of Paul Ricœur and Martin Heidegger

Effect of 24-h blood pressure dysregulations and reduced ocular perfusion pressure in open-angle glaucoma progression

Background: Low ocular perfusion pressure (OPP), which depends on the mean arterial pressure (MAP) and intraocular pressure (IOP), is associated with glaucoma. We studied 24-h MAP dysregulations and OPP in relation to the progression of glaucoma damage. Methods: We retrospectively analyzed 155 normal-tension glaucoma (NTG) and 110 primary open-angle glaucoma (POAG) patients aged 18 years old followed at the University Hospital Leuven with repeated visual field tests (n = 7000 measures, including both eyes) who underwent 24-h ambulatory blood pressure monitoring. Twenty-four-hour MAP dysregulations were variability independent of the mean (VIM), and the five lowest dips in MAP readings over 24 h. OPP was the difference between 2/3 of the MAP and IOP. Glaucoma progression was the deterioration of the visual field, expressed as decibel (dB) changes in mean deviation analyzed by applying multivariable linear mixed regression models. Results: The mean age was 68 years (53% were women). High 24-h VIMmap was associated with glaucoma progression in POAG (P \u3c 0.001) independently of the 24-h MAP level. The estimated changes in mean deviation in relation to dip MAP measures ranged from −2.84 dB [95% confidence interval (CI) −4.12 to −1.57] to −2.16 dB (95% CI −3.46 to −0.85) in POAG. Reduced OPP along with high variability and dips in MAP resulted in worse mean deviation deterioration. Conclusion: The progression of glaucoma damage associates with repetitive and extreme dips in MAP caused by high variability in MAP throughout 24 h. This progression exacerbates if 24-h MAP dysregulations occur along with reduced OPP

Normal-tension glaucomatous optic neuropathy is related to blood pressure variability in the Maracaibo Aging Study

Hypoperfusion of the optic nerve might be involved in the pathogenesis of normal-tension glaucomatous optic neuropathy (GON). Mean arterial pressure (MAP) drives ocular perfusion, but no previous studies have addressed the risk of GON in relation to blood pressure (BP) variability, independent of BP level. In a cross-sectional study, 93 residents of Maracaibo, Venezuela, underwent optical coherence tomography, visual field assessments and 24-h ambulatory BP monitoring between 2011 and 2016. We investigated the association of normal-tension GON with or without visual field defects with reading-to reading variability of 24-h MAP, as captured by variability independent of the MAP level (VIMmap). Odds ratios (ORs) were adjusted for 24-h MAP level and for a propensity score of up to five risk factors. Among the 93 participants (87.1% women; mean age, 61.9 years), 26 had open-angle normal-tension GON at both eyes; 14 had visual field defects; and 19 did not have visual field defects. The OR ratios for normal-tension GON, expressed per 1-SD increment in VIMmap (2 mm Hg), were 2.17 (95% confidence interval, 1.33–3.53) unadjusted; 2.20 (1.35–3.61) adjusted for 24-h MAP level only; 1.93 (1.10–3.41) with additional adjustment for age, educational attainment, high-density lipoprotein (HDL) cholesterol and office hypertension; and 1.95 (1.10–3.45) in models including intraocular pressure. We confirmed our a priori hypothesis that BP variability, most likely operating via hypoperfusion of the optic nerve, is associated with normal-tension GON. 24-H ambulatory BP monitoring might therefore help stratify the risk of normal-tension GON

Approximation to the spanish alternative media

En este trabajo se reflexiona sobre el concepto de medios alternativos y su vinculación con algunos medios digitales e impresos que nacen con posterioridad a la crisis económica en España (2008). Se detallan algunas de sus características en el modelo jurídico y de financiación para posteriormente conocer detalles de sus principios y lineamientos, a partir de una revisión de la información que publican en sus páginas web, en sus apartados de presentación. Se revisaron los siguientes medios finalistas en la categoría medios enfocados de los Premios Enfoque de Periodismo (2013, 2014, 2016 y 2017):elsaltodiario.com, lamarea.com, ctxt.es, revista5w.com, eldiario.es, infolibre.es, periodismohumano.com, revistapikaramagazine.com, elcritic.catyunitedexplanations.org. Entre los resultados obtenidos se observa que dos de los términos más frecuentes en sus definiciones son “independencia” y “calidad”. Del mismo modo, aparecen otros conceptos como “libertad”, “transformación”, “crisis”, “alternativo” y “comprometido” como valores que definen sus proyectos.This paper reflects on the concept of alternative media and its link with some digital and print media that are born after the economic crisis in Spain (2008). Their legal and financing model, their principles and guidelines are detailed, based on a review of the information published on its web pages. The following media finalists in the focused media category of the ‘Premios Enfoque’ (2013, 2014, 2016 y 2017) awards were reviewed: elsaltodiario.com, lamarea.com, ctxt.es, revista5w.com, eldiario.es, infolibre.es, periodismohumano.com, revistapikaramagazine.com, elcritic.cat, unitedexplanations.org. It is observed that two of the most frequent terms in their definitions are “independence” and “quality”. In addition, other concepts appear as “freedom”, “transformation”, “crisis”, “alternative” and “committed” as values that define their projects.Ministerio de Economía y Competitividad CSO2016-78386-

A regional scale modeling analysis of aerosol and trace gas distributions over the eastern Pacific during the INTEX-B field campaign

The Sulfur Transport and dEposition Model (STEM) is applied to the analysis of observations obtained during the Intercontinental Chemical Transport Experiment-Phase B (INTEX-B), conducted over the eastern Pacific Ocean during spring 2006. Predicted trace gas and aerosol distributions over the Pacific are presented and discussed in terms of transport and source region contributions. Trace species distributions show a strong west (high) to east (low) gradient, with the bulk of the pollutant transport over the central Pacific occurring between similar to 20 degrees N and 50 degrees N in the 2-6 km altitude range. These distributions are evaluated in the eastern Pacific by comparison with the NASA DC-8 and NSF/NCAR C-130 airborne measurements along with observations from the Mt. Bachelor (MBO) surface site. Thirty different meteorological, trace gas and aerosol parameters are compared. In general the meteorological fields are better predicted than gas phase species, which in turn are better predicted than aerosol quantities. PAN is found to be significantly overpredicted over the eastern Pacific, which is attributed to uncertainties in the chemical reaction mechanisms used in current atmospheric chemistry models in general and to the specifically high PAN production in the SAPRC-99 mechanism used in the regional model. A systematic underprediction of the elevated sulfate layer in the eastern Pacific observed by the C-130 is another issue that is identified and discussed. Results from source region tagged CO simulations are used to estimate how the different source regions around the Pacific contribute to the trace gas species distributions. During this period the largest contributions were from China and from fires in South/Southeast and North Asia. For the C-130 flights, which operated off the coast of the Northwest US, the regional CO contributions range as follows: China (35%), South/Southeast Asia fires (35%), North America anthropogenic (20%), and North Asia fires (10%). The transport of pollution into the western US is studied at MBO and a variety of events with elevated Asian dust, and periods with contributions from China and fires from both Asia and North America are discussed. The role of heterogeneous chemistry on the composition over the eastern Pacific is also studied. The impacts of heterogeneous reactions at specific times can be significant, increasing sulfate and nitrate aerosol production and reducing gas phase nitric acid levels appreciably (~50%)

Research on aging during the Venezuelan humanitarian crisis: the experience of the Maracaibo aging study

Background Venezuela is in the throes of a complex humanitarian crisis that is one of the worst in decades to impact any country outside of wartime. This case analysis describes the challenges faced by the ongoing Maracaibo Aging Study (MAS) during the deteriorating conditions in Venezuela. When the MAS began in 1997, it focused on memory-related disorders. Since then, strategic planning and proactive community participation allowed us to anticipate and address logistical, funding, and ethical challenges, and facilitated the enrollment and retention of more than 2500 subjects over 55 years of age. All participants, who are residents of the city of Maracaibo, Venezuela, underwent various assessments on several occasions. Here, we discuss how our approach to implementing a longitudinal, population-based study of age-related conditions has allowed our research program to continue throughout this period of political, economic, and social upheaval. Discussion As the social context in Venezuela became more complicated, new challenges emerged, and strategies to sustain the study and participation were refined. We identified five main mechanisms through which the evolving humanitarian crisis has affected implementation of the MAS: 1) community dynamics; 2) morale of researchers, staff, and participants; 3) financial feasibility; 4) components of the research process; and 5) impact on the health of staff, participants, and their families. Strategies to compensate for the impact on these components were implemented, based on inputs from community members and staff. Improved communication, greater involvement of stakeholders, broadening the scope of the project, and strengthening international collaboration have been the most useful strategies. Particular demands emerged, related to the increased mortality and comorbidities of participants and staff, and deterioration of basic services and safety. Conclusion Although the MAS has faced numerous obstacles, it has been possible to continue a longitudinal research project throughout the humanitarian crisis, because our research team has engaged the community deeply and developed a sense of mutual commitment, and also because our project has provided funding to help keep researchers employed, somewhat attenuating the brain drain

Fluorescent "turn-Off" detection of fluoride and cyanide ions using zwitterionic spirocyclic meisenheimer compounds

Stable zwitterionic spirocyclic Meisenheimer compounds were synthesized using a one-step reaction between picric acid and diisopropyl (ZW1) or dicyclohexyl (ZW3) carbodiimide. A solution of these compounds displays intense orange fluorescence upon UV or visible light excitation, which can be quenched or "turned-off" by adding a mole equivalent amount of F⁻ or CN⁻ ions in acetonitrile.Fluorescence is not quenched in the presence of other ions such as Cl⁻, Br⁻, I⁻, NO₂⁻ , NO₃⁻ , or H₂PO₄⁻ These compounds can therefore be utilized as practical colorimetric and fluorescent probes for monitoring the presence of F⁻ or CN⁻ anions