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Conjugation of therapeutic payloads to biologics including antibodies and albumin can enhance the selectively of drug delivery to solid tumors. However, achieving activity in tumors while avoiding healthy tissues remains a challenge, and payload activity in off-target tissues can cause toxicity for many such drug-conjugates. Here, we address this issue by presenting a drug-conjugate linker strategy that releases an active therapeutic payload upon exposure to ionizing radiation. Localized X-ray irradiation at clinically relevant doses (8 Gy) yields 50% drug (doxorubicin or monomethyl auristatin E, MMAE) release under hypoxic conditions that are traditionally associated with radiotherapy resistance. As proof-of-principle, we apply the approach to antibody- and albumin-drug conjugates and achieve2000-fold enhanced MMAE cytotoxicity upon irradiation. Overall, this work establishes ionizing radiation as a strategy for spatially localized cancer drug delivery.

Bacterial nanocellulose (BNC) surface has a negative charge that allows the adsorption of calcium ions to initiate the nucleation of different calcium phosphate phases. The aim of this study was to investigate different methods of mineralization on three-dimensional microporous bacterial nanocellulose, to mimetize the composition, structure, and biomechanical properties of natural bone. To generate 3D microporous biomaterial, the porogen particles were incorporated during the BNC fermentation with the strain Komagataeibacter medellinensis. Calcium phosphates (CPs) were deposited on BNC scaffolds by five alternating immersing cycles with calcium and phosphate solutions. Scanning electron microscopy micrograph showed that the scaffolds have different pore sizes, between 70 and 350 µm, but the porous interconnectivity was affected by the biomineralization method and time. The crystals on the BNC surface are shown to be rod-shaped with a calcium phosphate ratio similar to that of immature bone, increasing from 1.13 to 1.6 with cycle numbers. The main mineral phases obtained by X-ray diffraction were Octacalcium Dihydrogen Hexakis (phosphate (V)) Pentahydrate (OCP). In vitro cell studies showed good cellular adhesion and higher cell viability to 95% in all the scaffolds. Osteogenic differentiation of human bone marrow mesenchymal stem cells on the scaffolds was evaluated by bone expression markers like alkaline phosphatase, osteocalcin, and osteopontin. In conclusion, it is possible to prepare 3D BNC scaffolds with controlled microporosity, which could allow osteoblast adhesion, proliferation, and differentiation.

Bacterial nanocellulose (BNC) has a negative surface charge in physiological environments, which allows the adsorption of calcium ions to initiate the nucleation of different calcium phosphate phases. The aim of this study was to investigate different methods of mineralization in three-dimensional microporous bacterial nanocellulose with the intention of mimicking the composition, structure, and biomechanical properties of natural bone. To generate the 3D microporous biomaterial, porogen particles were incorporated during BNC fermentation with the Komagataeibacter medellinensis strain. Calcium phosphates (CPs) were deposited onto the BNC scaffolds in five immersion cycles, alternating between calcium and phosphate salts in their insoluble forms. Scanning electron microscopy (SEM) showed that the scaffolds had different pore sizes (between 70 and 350 µm), and their porous interconnectivity was affected by the biomineralization method and time. The crystals on the BNC surface were shown to be rod-shaped, with a calcium phosphate ratio similar to that of immature bone, increasing from 1.13 to 1.6 with increasing cycle numbers. These crystals also increased in size with an increasing number of cycles, going from 25.12 to 35.9 nm. The main mineral phase observed with X-ray diffraction was octacalcium dihydrogen hexakis phosphate (V) pentahydrate (OCP). In vitro studies showed good cellular adhesion and high cell viability (up to 95%) with all the scaffolds. The osteogenic differentiation of human bone marrow mesenchymal stem cells on the scaffolds was evaluated using bone expression markers, including alkaline phosphatase, osteocalcin, and osteopontin. In conclusion, it is possible to prepare 3D BNC scaffolds with controlled microporosity that allow osteoblast adhesion, proliferation, and differentiation.

El tiroteo ocurrido en la secundaria Stoneman Douglas el 14 de febrero de 2018, en el estado de la Florida, derivó en un intenso debate público en torno a la tenencia, comercialización y uso de armas en los Estados Unidos. Con proyección global más allá del territorio norteamericano, esta tragedia en particular se convirtió en el punto de partida para encontrar una solución a este problema. Por tanto, el presente artículo de análisis, a través de la aplicación de los postulados del análisis crítico del discurso de Teun A. van Dijk, combinado con las categorías del orden del discurso propuestas por Michel Foucault, refleja la convergencia de la materialidad política de los principales discursos emitidos tras el tiroteo. El análisis propuesto contrasta cuatro discursos que conforman un dispositivo que junta lo gubernamental (presidente de los Estados Unidos Donald Trump), la seguridad local (Sheriff del Condado de Broward Scott Israel) y la posición ciudadana (Activista Cameron Kasky), frente a lo institucional (Segunda Enmienda de la Constitución de los estados Unidos). El principal resultado muestra que, aún cuando los cuatro discursos son enunciados por diversos sujetos discursivos, se articulan convergentemente en torno a un proceso ideológico con fines políticos claramente definidos. En el caso de los sujetos analizados, se evidencia una interdiscursividad no intencionada, su relación, especialmente con las materialidades del poder y la ideología muestran tres diferentes posturas con un mismo fin, el imponer sus propósitos y objetivos a través del discurso hacia receptores que puedan subordinarse a los mecanismos de poder y saber. Ningún discurso está aislado y en este caso en particular la incidencia significativa del proceso discursivo está equiparada con el principio del comentario. Los tres sujetos convergen discursivamente en una imposición ideológica que no contempla sus orígenes tampoco la investidura social que representan. La realidad constitucional de una Enmienda, la cual defiende la naturaleza de un derecho no forma parte de la estructura discursiva de los sujetos analizados.

[Resumen] Se describe el estilo de vida y las lógicas discursivas de personas que hacen parte de comunidades virtuales Pro Ana en las redes sociales de Facebook y WhatsApp. A través de una indagación basada en la etnografía virtual –Netnografía– se recolectaron datos provenientes de la interacción digital de mujeres con rasgos anoréxicos que se congregaban en grupos Pro Ana. Posteriormente, mediante el método cualitativo de teoría fundamentada, se integraron diversas categorías de análisis que permitieron describir el fenómeno de estudio a partir de una perspectiva que expone las evidencias halladas y las contrasta con la producción académica examinada al respecto. Los resultados alcanzados indican la incidencia de aspectos como la cultura, la identidad o las emociones en las representaciones y concepciones fundamentales que convocan a las mujeres a hacer parte de estas comunidades virtuales y que refuerzan prácticas a favor de un estilo de vida pro anorexia. [Abstract] This article examines the lifestyle and discursive logic of members of virtual pro-ana communities on Facebook and WhatsApp. A virtual ethnography (netnography) methodology was used to collect data from the online interactions of women with anorexic tendencies and/or behaviours who meet in pro-ana groups. A qualitative grounded theory method was used to combine the different categories of analysis in order to obtain a description of the phenomenon based on the data from the study and the findings of previous research on the topic. The results show the influence of factors such as culture, identity and emotions on the representations and conceptualisations that prompt women to participate in these virtual communities and reinforce pro-anorexic lifestyle practices.

BACKGROUND Liquid-based cytology (LBC) has improved exfoliative cytology by facilitating the extraction of more precise information from epithelial cells. The aim of this study was to optimize a protocol using a conventional cytobrush to perform LBC, obtaining oral keratinocytes for their further cellular and molecular analysis. METHODS LBC was performed in 30 healthy donors from buccal mucosa. We evaluated the use of diethyl pyrocarbonate (DEPC)-treated Dulbecco's Modified Eagle Medium (DMEM) medium right after the collection of the cells. Cell morphology and viability were determined by Orcein staining and flow cytometry, respectively. RNA was extracted by the trizol method, and evaluated with spectrometry and electrophoresis. Finally, RNA was copied into cDNA and GAPDH and TLR2 genes were amplified by reverse transcription polymerase chain reaction (RT-PCR) and quantitative reverse transcription polymerase chain reaction (RT-qPCR) using specific primers. RESULTS Only DEPC-treated DMEM preserved the viability of intact intraepithelial keratinocytes. RNA quantity and quality improves in samples treated with DEPC. RNA integrity is comparable with a cell line control. GAPDH gene was successfully amplified by RT-PCR and RT-qPCR. CONCLUSIONS Therefore, LBC performed under these conditions becomes a reproducible technique for the retrieval of intraepithelial oral keratinocytes with good cell viability for cytomorphometric analysis, and extraction of good RNA quality suitable for molecular analyses such as PCR. We propose this LBC protocol as a complementary method to the cellular and molecular study of oral mucosa pathologies; however, it requires further study.

Background Oral lichen planus (OLP) is a chronic inflammatory disease with a strong immune mechanism involved. Although no causal factor is identified in OLP, a cellular hypersensitivity has been associated with its pathophysiology. Furthermore, the chronicity of the disease could cause its malignant transformation. Highlight Herein, we present a literature review focusing on the interrelationship of Toll-like receptors (TLRs) and OLP, mainly on the molecular behavior of oral keratinocytes once TLR signals are activated. A family of transcription factors, the Interferon Regulatory Factor (IRF) family, could be having a novel role in the prognosis of OLP. Specifically, Interferon Regulatory Factor 6 (IRF6) as a key component of the TLR signaling could impart specificity to downstream responses in oral keratinocytes. Conclusion We propose a hypothetical model after TLR2 activation in which a plausible TLR2-IRF6 regulatory mechanism could be a key factor to be evaluated in OLP as a convenient chronic inflammatory model. Further molecular studies are required to fully understand the role of oral keratinocytes in the initiation of OLP.

Several studies have shown the potential use of bone marrow mesenchymal stem cells (BM-MSCs) as a therapeutic approach to infectious diseases. Since BM-MSCs can exert antimicrobial properties and influence the immune response against pathogens, our aim was to study the antimicrobial therapeutic potential of BM-MSCs in an experimental model of paracoccidioidomycosis (PCM). BM-MSCs were isolated from BALB/c donor mice. Paracoccidioides brasiliensis–infected male BALB/c mice were injected with purified BM-MSCs at 8th week post-infection. Mice were sacrificed at 12th week postinfection. Homing of BM-MSCs was confirmed by cellular labeling with fluorescent lipophilic dye and detected by flow cytometry. We found that, in comparison with nontransplanted infected animals, BM-MSCs-treated and P. brasiliensis-infected mice showed a significant increase in (i) fungal burdens, (ii) neutrophils, eosinophils and M2 macrophages counts, and (iii) interleukin (IL)-6, IL-9, GM-CSF, CXCL1, CXCL9, and CCL5 levels, while presenting a decrease in M1 macrophages and Treg cells in lungs. In addition, the histopathological analysis of the lungs showed an increased inflammatory process. This is the first study to our knowledge that evaluates the effects of BM-MSCs treatment in PCM. Our results indicate that the immunoregulatory function of BM-MSCs may be triggered by the interaction with P. brasiliensis, which exacerbates chronic pulmonary inflammatory response. COL0126131 COL0013709

This paper analyses the effect of Covid-19 on health and economic indicators of Bogota, the capital of Colombia, and the responses of the local government to ease the economic shock. We highlight the importance of designing policies that adapt to the local context and complement the existing strategies at the national level, and the implementation of ambitious local programs that would be too difficult to execute nationwide. We also emphasize on the benefits on having an ample fiscal space due to the good behavior of previous administrations, allowing the funding of these programs with sustainable debt.

Se describe la incidencia de las falencias en la comprension de lectura sobre el rendimiento academico de estudiantes de la Corporacion Universitaria Autonoma Del Cauca (Uniautonoma) y la Universidad Cooperativa De Colombia, Sede Popayan (UCC). A traves del metodo cualitativo de teorA­a fundamentada, se expone una revision teorica y conceptual sobre las variables implA­citas en las problematicas de comprension lectora en universitarios y se ofrece un analisis de las diversas dificultades psicoeducativas, que, reflejadas en los diagnosticos institucionales y representadas en las logicas discursivas de estudiantes, docentes y directivos, configuran una percepcion intersubjetiva al respecto de los factores que intervienen en la comprension de textos y su repercusion sobre el desempeA±o que exhiben los estudiantes dentro del aula de clase. Tras conceptualizar las categorA­as cualitativas descriptoras del fenomeno, el trabajo concluye con la formulacion de algunas estrategias psicopedagogicas que contribuyan a disminuir las dificultades academicas vinculadas a los bajos niveles de comprension lectora evidenciados en estudiantes de las dos universidades objeto del estudio.

Advanced therapies in medicine use stem cells, gene editing, and tissues to treat a wide range of conditions. One of their goals is to stimulate endogenous repair of tissues and organs by manipulating stem cells and their niche, as well as to optimize the intrinsic characteristics and plasticity of differentiated cells in adult tissues. In this context, fibroblasts emerge as an alternative source to stem cells because they share phenotypic and regenerative characteristics. Specifically, fibroblasts of the oral mucosae have been shown to have improved regenerative capacity compared to other fibroblast populations. Additionally, their easy access by means of minimally invasive procedures without generating aesthetic problems, with easy and rapid in vitro expansion and with great capacity to respond to extrinsic factors, make oral fibroblasts an attractive and interesting resource for regenerative medicine. This review summarizes current concepts regarding the phenotypic and functional aspects of human Gingival Fibroblasts and their niche, differentiating them from other fibroblast populations of oral-lining mucosa and skin fibroblasts. Furthermore, some applications are presented in regenerative medicine, emphasizing on the biological potential of human Gingival Fibroblasts.

Objective To determine the genetic diversity of Streptococcus mutans (S. mutans) serotype c isolated from white spot and cavitated caries lesions of schoolchildren. Methods S. mutans isolates were obtained and identify by Polymerase Chain Reaction (PCR) from 28 schoolchildren. A total of 92 S. mutans isolates, identified as serotype c by PCR, were analyzed by pulsed field gel electrophoresis after digestion of genomic DNA with SmaI enzyme. 62 isolates were obtained from white spot and cavitated caries lesions of schoolchildren that presented both lesions simultaneously and 30 isolates were from saliva and biofilm samples of schoolchildren without dental caries. Cluster analyses were performed using the Dice coefficient of the BioNumerics software version 6.0. Results It was possible to determine the serotype in 190 isolates out of 255 isolates identified as S. mutans. Serotype c was the most frequent (n = 139), followed by serotype f (n = 31) and serotype e (n = 20). After analyzing the dendograms of the 92 serotype c isolates, this study identified three strains present in both types of lesions, two strains specific to the type of lesion: one strain from the white spot lesion and one strain from the cavitated caries lesion, and five strains specific to children with caries versus four strains for children without caries. Conclusion S. mutans serotype c genetic variability is similar in terms of the number of strains present according to the caries status and type of lesion.

Background aims. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the loss of brain and spinal cord motor neurons (MN). The intraspinal and systemic grafting of mesenchymal stromal cells (MSC) was used to treat symptomatic transgenic rats overexpressing human superoxide dismutase 1 (SOD1) in order to alleviate the disease course and prolong the animals ' lifespan. Methods. At the age of 16 weeks (disease onset) the rats received two grafts of MSC expressing green fl uorescent protein (GFPMSC) on the same day, intraspinally (10 5 cells) and intrave- nously (2 � 10 6 cells). Sham-treated animals were injected with phosphate-buffered saline (PBS). Motor activity, grip strength and body weight were tested, followed by immunohistochemical analysis. Results. The combined grafting of MSC into symptomatic rats had a signifi cant effect on motor activity and grip strength starting 4 weeks after transplantation. The lifespan of animals in the treated group was 190 � 3.33 days compared with 179 � 3.6 days in the control group of animals. Treated rats had a larger number of MN at the thoracic and lumbar levels; these MN were of larger size, and the intensity of terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining in the somas of apoptotic MN at the thoracic level was much lower than in sham-treated animals. Transplanted GFPMSC survived in the spinal cord until the end stage of the disease and migrated both rostrally and caudally from the injection site. Conclusions . Intraspinal and intravenous transplantation of MSC has a benefi cial and possibly synergistic effect on the lifespan of ALS animals.

Olfactory ensheathing glia (OEG) and mesenchymal stromal cells (MSC) are suitable candidates for transplantation therapy of spinal cord injury (SCI). Both facilitate functional improvement after SCI by producing trophic factors and cytokines. In this study, the co-transplantation of both types of cells was studied to clarify their additive and/ or synergistic effects on SCI.A balloon-induced compression lesion was used to produce SCI in rats. OEG, MSC or both OEG and MSC (3 x 10(5) cells of each cell type) were implanted by intraspinal injection 1 week after SCI. The effect of transplantation was assessed using behavioral, electrophysiologic and histologic methods.Hindlimb function was examined with Basso, Beattie and Bresnahan (BBB) and Plantar tests. Improvement was found in all three groups of transplanted rats with different time-courses, but there was no significant difference among the groups at the end of the experiment. Motor-evoked potentials after SCI decreased in amplitude from 7 mV to 10 microV. Linear regression analysis showed a modest recovery in amplitude following transplantation, but no change in the control rats. Histologic findings showed that the white and gray matter were significantly spared by transplantation after SCI.Functional improvement was achieved with transplantation of OEG and/or MSC, but the co-transplantation of OEG and MSC did not show synergistic effects. The poor migration of OEG and MSC might prevent their concerted action. Pre-treatment with a Rho antagonist and a combination of intraspinal and intravenous injection of the cells might be beneficial for SCI therapy.

Este artículo parte de la vigencia de los planteamientos del profesor Gabriel Ignacio Gómez Sánchez en su artículo “La investigación, la producción y las prácticas del saber jurídico en la Facultad de Derecho de la Universidad de Antioquia”. Eltrabajo realizado por el profesor Gómez causó cierta curiosidad por ahondar en el tema de la función social del derecho y su relación con los centros de enseñanza, y analizar el deber ser del derecho como área del conocimiento con el fin de establecer cómo los programas de derecho pueden contribuir por medio de la investigación a la materialización de su función social mediante el diseño de políticas públicas encaminadas a resolver las problemáticas sociales.Palabras clave: investigación, formación, función social del derecho, políticas públicas, Estado social de derecho.

Adipose-derived stromal cells (ASCs) are an alternative source of stem cells for cell-based therapies of neurological disorders such as spinal cord injury (SCI). In the present study, we predifferentiated ASCs (pASCs) and compared their behavior with naïve ASCs in vitro and after transplantation into rats with a balloon-induced compression lesion. ASCs were predifferentiated into spheres before transplantation, then pASCs or ASCs were injected intraspinally 1 week after SCI. The cells' fate and the rats' functional outcome were assessed using behavioral, histological, and electrophysiological methods. Immunohistological analysis of pASCs in vitro revealed the expression of NCAM, NG2, S100, and p75. Quantitative RT-PCR at different intervals after neural induction showed the up-regulated expression of the glial markers NG2 and p75 and the neural precursor markers NCAM and Nestin. Patch clamp analysis of pASCs revealed three different types of membrane currents; however, none were fast activating Na(+) currents indicating a mature neuronal phenotype. Significant improvement in both the pASC and ASC transplanted groups was observed in the BBB motor test. In vivo, pASCs survived better than ASCs did and interacted closely with the host tissue, wrapping host axons and oligodendrocytes. Some transplanted cells were NG2- or CD31-positive, but no neuronal markers were detected. The predifferentiation of ASCs plays a beneficial role in SCI repair by promoting the protection of denuded axons; however, functional improvements were comparable in both the groups, indicating that repair was induced mainly through paracrine mechanisms.

Chronic spinal cord injury (SCI) is characterized by tissue loss and a stable functional deficit. While several experimental therapies have proven to be partly successful for the treatment of acute SCI, treatment of chronic SCI is still challenging. We studied whether we can bridge a chronic spinal cord lesion by implantation of our newly developed hydrogel based on 2-hydroxypropyl methacrylamide, either alone or seeded with mesenchymal stem cells (MSCs), and whether this treatment leads to functional improvement. A balloon-induced compression lesion was performed in adult 2-month-old male Wistar rats. Five weeks after injury, HPMA-RGD hydrogels [N-(2-hydroxypropyl)-methacrylamide with attached amino acid sequences--Arg-Gly-Asp] were implanted into the lesion, either with or without seeded MSCs. Animals with chronic SCI served as controls. The animals were behaviorally tested using the Basso–Beattie-Breshnahan (BBB) (motor) and plantar (sensory) tests once a week for 6 months. Behavioral analysis showed a statistically significant improvement in rats with combined treatment, hydrogel and MSCs, compared with the control group (P < 0.05). Although a tendency toward improvement was found in rats treated with hydrogel only, this was not significant. Subsequently, the animals were sacrificed 6 months after SCI, and the spinal cord lesions evaluated histologically. The combined therapy (hydrogel with MSCs) prevented tissue atrophy (P < 0.05), and the hydrogels were infiltrated with axons myelinated with Schwann cells. Blood vessels and astrocytes also grew inside the implant. MSCs were present in the hydrogels even 5 months after implantation. We conclude that 5 weeks after injury, HPMA-RGD hydrogels seeded with MSCs can successfully bridge a spinal cord cavity and provide a scaffold for tissue regeneration. This treatment leads to functional improvement even in chronic SCI.

Shear-induced platelet responses are triggered by VWF binding to the platelet GpIb-IX complex, and there is evidence that this ligand-receptor coupling stimulates transmembranous signaling through the cytoplasmic tail of glycoprotein (Gp) Ib alpha. To investigate the mechanism by which signaling is effected, new molecular interactions involving GpIb-IX that develop in response to pathological shearing stress were examined in intact human platelets. Exposure to shear, but not alpha-thrombin, results in the co-immunoprecipitation of the actin cross-linking protein alpha-actinin with the GpIb-IX complex. Blockers of VWF binding to GpIb alpha or actin polymerization inhibit the association of alpha-actinin with the GpIb-IX complex, but the association of alpha-actinin with the GpIb-IX complex is not affected by inhibiting VWF binding to platelet integrin alpha IIb beta 3 (GpIIb-IIIa). alpha-Actinin becomes tyrosine phosphorylated in response to pathological shear stress, and phosphorylated alpha-actinin associates with GpIb-IX. In resting platelets, class IA heterodimeric phosphatidylinositol 3-kinase (PI 3-K) and protein kinase N (PKN) associate with nonphosphorylated alpha-actinin. Shear stress causes PI 3-K to disassociate from alpha-actinin, while it stimulates PKN binding to alpha-actinin. These results demonstrate that shear-induced VWF binding to GpIb alpha causes enhanced binding of cytoskeletal alpha-actinin to GpIb-IX and suggest that alpha-actinin, perhaps through tyrosine phosphorylation, serves as an adapter for a signaling complex that could regulate VWF-induced platelet aggregation.