Search

Efficient management of industrial assets and equipment depends heavily on the selection of appropriate maintenance strategies. This research presents a dataset generated through Monte Carlo simulations to evaluate 12 key criteria relevant to maintenance strategy selection. The dataset covers a wide range of potential maintenance scenarios, providing comprehensive data for researchers to explore various strategies in industrial settings. The data were normalized and structured in a way that facilitates their use for further modeling or analysis. The dataset offers an opportunity for researchers to reproduce the data collection process, enabling comparisons with their own studies. By providing this dataset, we aim to support the development of new models for maintenance strategy selection and encourage further exploration of data-driven approaches in industrial maintenance. Additionally, the dataset can serve educational purposes, assisting in the teaching of decision-making in the context of maintenance operations.

El presente trabajo, como estudio de caso, expone problemáticas situadas de carácter hídrico en la localidad Kilómetro 30, ubicada en la zona rural del municipio de Acapulco, Guerrero, México. Más que pretender proponer soluciones a partir de agendas ambientales estandarizadas internacionales, este documento resalta las relaciones de poder y formas de gobierno que emergen ante escenarios críticos de abastecimiento de agua, así como la asimetría en la gobernanza de dicho recurso. Se tiene como objetivo analizar las prácticas de gestión de agua para uso doméstico bajo la óptica de un enfoque sociocultural de las relaciones sociedad-Estado Para ello, se emplea metodología cualitativa, que involucra al mismo tiempo observaciones de tipo etnográfico y entrevistas a profundidad que siguen el modelo de mapeo de actores involucrados en políticas ambientales: actores institucionalizados estatales, institucionalizados no estatales y no institucionalizados. Se concluye que las prácticas como acciones, discursos, reglas y recursos que se ponen en juego en el marco de relaciones históricas de violencia política y social se encuentran en el punto marginal entre lo legal y lo ilegal, moviéndose libremente entre ambas dimensiones mientras esto permita la sobrevivencia en condiciones socioambientales hostiles.

Abstract Progressive hepatic damage and fibrosis are major features of chronic liver diseases of different etiology, yet the underlying molecular mechanisms remain to be fully defined. N-RAS, a member of the RAS family of small guanine nucleotide-binding proteins also encompassing the highly homologous H-RAS and K-RAS isoforms, was previously reported to modulate cell death and renal fibrosis; however, its role in liver damage and fibrogenesis remains unknown. Here, we approached this question by using N-RAS deficient (N-RAS−/−) mice and two experimental models of liver injury and fibrosis, namely carbon tetrachloride (CCl4) intoxication and bile duct ligation (BDL). In wild-type (N-RAS+/+) mice both hepatotoxic procedures augmented N-RAS expression in the liver. Compared to N-RAS+/+ counterparts, N-RAS−/− mice subjected to either CCl4 or BDL showed exacerbated liver injury and fibrosis, which was associated with enhanced hepatic stellate cell (HSC) activation and leukocyte infiltration in the damaged liver. At the molecular level, after CCl4 or BDL, N-RAS−/− livers exhibited augmented expression of necroptotic death markers along with JNK1/2 hyperactivation. In line with this, N-RAS ablation in a human hepatocytic cell line resulted in enhanced activation of JNK and necroptosis mediators in response to cell death stimuli. Of note, loss of hepatic N-RAS expression was characteristic of chronic liver disease patients with fibrosis. Collectively, our study unveils a novel role for N-RAS as a negative controller of the progression of liver injury and fibrogenesis, by critically downregulating signaling pathways leading to hepatocyte necroptosis. Furthermore, it suggests that N-RAS may be of potential clinical value as prognostic biomarker of progressive fibrotic liver damage, or as a novel therapeutic target for the treatment of chronic liver disease.

Intramedullary nailing remains the most popular and preferred method of fixation for tibial shaft fractures. The infrapatellar approach through the patellar tendon has long been considered the gold standard. However, the suprapatellar approach has gained popularity because of the advantages of being easier to perform when treating proximal shaft and metaphyseal fractures and there being less postoperative anterior knee pain. Despite increased use of this approach, the removal of the implant from the same suprapatellar approach is tricky, and in most cases, the removal is performed through a new transpatellar tendon approach. This article describes arthroscopically assisted suprapatellar tibial nail removal using the same approach and instrumentation of the nail insertion. The technique has the advantage of preserving the patellar tendon without causing secondary damage to it. Through arthroscopy, direct visualization of the patellofemoral joint aids in preventing possible cartilage injury. Moreover, any associated intra-articular lesions can be diagnosed and addressed.

IntroductionThe Unfolded Protein Response, a mechanism triggered by the cell in response to Endoplasmic reticulum stress, is linked to inflammatory responses. Our aim was to identify novel Unfolded Protein Response-mechanisms that might be involved in triggering or perpetuating the inflammatory response carried out by the Intestinal Epithelial Cells in the context of Inflammatory Bowel Disease.MethodsWe analyzed the transcriptional profile of human Intestinal Epithelial Cell lines treated with an Endoplasmic Reticulum stress inducer (thapsigargin) and/or proinflammatory stimuli. Several genes were further analyzed in colonic biopsies from Ulcerative Colitis patients and healthy controls. Lastly, we generated Caco-2 cells lacking HMGCS2 by CRISPR Cas-9 and analyzed the functional implications of its absence in Intestinal Epithelial Cells.ResultsExposure to a TLR ligand after thapsigargin treatment resulted in a powerful synergistic modulation of gene expression, which led us to identify new genes and pathways that could be involved in inflammatory responses linked to the Unfolded Protein Response. Key differentially expressed genes in the array also exhibited transcriptional alterations in colonic biopsies from active Ulcerative Colitis patients, including NKG2D ligands and the enzyme HMGCS2. Moreover, functional studies showed altered metabolic responses and epithelial barrier integrity in HMGCS2 deficient cell lines.ConclusionWe have identified new genes and pathways that are regulated by the Unfolded Protein Response in the context of Inflammatory Bowel Disease including HMGCS2, a gene involved in the metabolism of Short Chain Fatty Acids that may have an important role in intestinal inflammation linked to Endoplasmic Reticulum stress and the resolution of the epithelial damage.

The aim of the current research is trying to fill in the gap that exists in regard with the lack of knowledge about the psychological status of social care professionals who worked in an emergency social service for homeless people during the COVID-19 pandemic. This study measured work sastisfaction, burnout, fatigue, depression, and anxiety symptoms in a sample of 44 Spanish social care professionals who worked in the IFEMA Pabellón 14 Social Emergency Centre for Homeless People in Madrid, Spain. The study was carried out in four measurement moments (between April and May), and results showed that, overall, workers displayed good levels of psychological adaptation to their workplace during the two months and a half that the emergency centre was running, in spite of all the uncertainty and risks existing throughout that time.

Abstract 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.

Introduction: Partial meniscectomy is one of the most common surgical strategy for a meniscal injury, but sometimes, patients complain of knee pain due to an overload in the ablated compartment. In these cases, implantation of tissue engineering scaffold could be indicated. Currently, two commercial scaffolds, based on collagen or polycaprolactone-polyurethane (PCL-PU), are available for meniscus scaffolding. In short term follow-up assessments, both showed clinical improvement and tissue formation. However, long-term studies carried out in PCL-PU showed that the new tissue decreased in volume and assumed an irregular shape. Moreover, in some cases, the scaffold was totally reabsorbed, without new tissue formation.Mesenchymal stem cells (MSCs) combined with scaffolds could represents a promising approach for treating meniscal defects because of their multipotency and self-renewal. In this work, we aimed to compare the behaviour of MSCs and chondrocytes on a PCL-PU scaffold in vitro. MSCs express integrins that binds to fibronectin (FN), so we also investigate the effect of a FN coating on the bioactivity of the scaffold. Methods: We isolated rabbit bone marrow MSCs (rBM-MSCs) from two skeletally mature New Zealand white rabbits and stablished the optimum culture condition to expand them. Then, they were seeded over non-coated and FN-coated scaffolds and cultured in chondrogenic conditions. To evaluate cell functionality, we performed an MTS assay to compare cell proliferation between both conditions. Finally, a histologic study was performed to assess extracellular matrix (ECM) production in both samples, and to compare them with the ones obtained with rabbit chondrocytes (rCHs) seeded in a non-coated scaffold. Results: A culture protocol based on low FBS concentration was set as the best for rBM-MSCs expansion. The MTS assay revealed that rBM-MSCs seeded on FN-coated scaffolds have more cells on proliferation (145%; 95% CI: 107%–182%) compared with rBM-MSCs seeded on non-coated scaffolds. Finally, the histologic study demonstrated that rCHs seeded on non-coated scaffolds displayed the highest production of ECM, followed by rBM-MSCs seeded on FN-coated scaffolds. Furthermore, both cell types produced a comparable ECM pattern. Conclusion: These results suggest that MSCs have low capacity attachment to PCL-PU scaffolds, but the presence of integrin alpha5beta1 (FN-receptor) in MSCs allows them to interact with the FN-coated scaffolds. These results could be applied in the design of scaffolds, and might have important clinical implications in orthopaedic surgery of meniscal injuries.

Hepatitis B virus (HBV) infection and DNA integration is a frequent cause of hepatocellular carcinoma (HCC), but the consequences of this process are not fully understood. Here the authors use whole-genome and long-read sequencing data from HCC patient samples to study the timing and alterations induced by HBV insertions.

Hyaline cartilage’s inability to self-repair can lead to osteoarthritis and joint replacement. Various treatments, including cell therapy, have been developed for cartilage damage. Autologous chondrocyte implantation (ACI) is considered the best option for focal chondral lesions. In this article, we aimed to create a narrative review that highlights the evolution and enhancement of our chondrocyte implantation technique: High-Density-ACI (HD-ACI) Membrane-assisted Autologous Chondrocyte Implantation (MACI) improved ACI using a collagen membrane as a carrier. However, low cell density in MACI resulted in softer regenerated tissue. HD-ACI was developed to improve MACI, implanting 5 million chondrocytes per cm2, providing higher cell density. In animal models, HD-ACI formed hyaline-like cartilage, while other treatments led to fibrocartilage. HD-ACI was further evaluated in patients with knee or ankle defects and expanded to treat hip lesions and bilateral defects. HD-ACI offers a potential solution for cartilage defects, improving outcomes in regenerative medicine and cell therapy. HD-ACI, with its higher cell density, shows promise for treating chondral defects and advancing cartilage repair in regenerative medicine and cell therapy.

Introduction: In this work we describe the use of high-density autologous chondrocyte implantation (HD-ACI) to treat 2 patients with chondral defects in the hip. Case Presentation: Two male, 35- and 37-year-old, with chondral lesions and femoroacetabular impingement (FAI) were included. Chondrocytes were isolated expanded in vitro and then implanted at a density of 5 million cells per cm2 onto a type I/III porcine collagen membrane. None of the patients had surgery-derived complications. Pain disappeared in both cases at 6 months after surgery and was maintained until follow-up end (36 months). International Hip Outcome Tool (iHOT) score increased at 6 and 12 months and then leveled off until month 36.Three-year arthro-MRI showed the cartilage defects had been filled with a material similar to the surrounding healthy cartilage. Conclusion: HD-ACI is a safe and effective technique for focal cartilage lesion treatment in patients affected by evolved FAI.

Abstract The most common oxidative DNA lesion is 8-oxoguanine which is mainly recognized and excised by the 8-oxoG DNA glycosylase 1 (OGG1), initiating the base excision repair (BER) pathway. Telomeres are particularly sensitive to oxidative stress (OS) which disrupts telomere homeostasis triggering genome instability. In the present study, we have investigated the effects of inactivating BER in OS conditions, by using a specific inhibitor of OGG1 (TH5487). We have found that in OS conditions, TH5487 blocks BER initiation at telomeres causing an accumulation of oxidized bases, that is correlated with telomere losses, micronuclei formation and mild proliferation defects. Moreover, the antimetabolite methotrexate synergizes with TH5487 through induction of intracellular reactive oxygen species (ROS) formation, which potentiates TH5487-mediated telomere and genome instability. Our findings demonstrate that OGG1 is required to protect telomeres from OS and present OGG1 inhibitors as a tool to induce oxidative DNA damage at telomeres, with the potential for developing new combination therapies for cancer treatment.

BackgroundPARP1 plays a critical role in the base excision repair (BER) pathway, and PARP1 inhibition leads to specific cell death, through a synthetic lethal interaction, in the context of BRCA1/2 deficiency. To date, up to five different PARP inhibitors (PARPi), have been approved, nevertheless, the acquisition of resistance to PARPi is common and there is increasing interest in enhancing responses and expand their use to other tumour types.MethodsWe hypothesized that other BER members could be additional synthetic lethal partners with mutated BRCA genes. To test this, we decided to evaluate the glycosylase OGG1 as a potential candidate, by treating BRCA1 proficient and deficient breast cancer cells with PARPi olaparib and the OGG1 inhibitor TH5478.ResultsKnocking out BRCA1 in triple-negative breast cancer cell lines causes hypersensitivity to the OGG1 inhibitor TH5487. Besides, TH5487 enhances the sensitivity to the PARP inhibitor olaparib, especially in the context of BRCA1 deficiency, reflecting an additive interaction.DiscussionThese results provide the first evidence that OGG1 inhibition is a promising new synthetic lethality strategy in BRCA1-deficient cells, and could lead to a new framework for the treatment of hereditary breast and ovarian cancer.

The development of advanced gene and cell therapies for the treatment of genetic diseases requires reliable animal and cellular models to test their efficacy. Moreover, the availability of the target human primary cells of these therapies is reduced in many diseases. The development of endonucleases that can cut into specific sites of the cell genome, as well as the repair of the generated break by non-homologous end-joining, results in a variety of outcomes, insertions, deletions, and inversions that can induce the disruption of any specific gene. Among the many methods that have been developed for gene editing, CRISPR-Cas9 technology has become one of the most widely used endonuclease tools due to its easy design and its low cost. It has also been reported that the use of two guides, instead of just the one required, reduces the outcomes of non-homologous end joining mainly to the precise genomic sequences between the cutting sites of the guides used. We have explored this strategy to generate useful cellular and animal models. Different distances between the two guides have been tested (from 8 to 500 bp apart), and using the optimal range of 30–60 bp we have obtained a human primary cellular model of a genetic disease, pyruvate kinase deficiency, where the availability of the target cells is limited. We have also generated an in vivo model of glycolate oxidase (GO) deficiency, which is an enzyme involved in the glyoxylate metabolism following the same strategy. We demonstrate that the use of two-guide CRISPR-Cas9-induced non-homologous end joining is a feasible and useful tool for disease modeling, and it is most relevant to those diseases in which it is difficult to get the cells that will be genetically manipulated.

Abstract Background Mutations in the coding region of FOXP2 are known to cause speech and language impairment. However, it is not clear how dysregulation of the gene contributes to language deficit. Interestingly, microdeletions of the region downstream the gene have been associated with cognitive deficits. Methods Here, we investigate changes in FOXP2 expression in the SK-N-MC neuroblastoma human cell line after deletion by CRISPR-Cas9 of two enhancers located downstream of the gene. Results Deletion of any of these two functional enhancers downregulates FOXP2, but also upregulates the closest 3′ gene MDFIC. Because this effect is not statistically significant in a HEK 293 cell line, derived from the human kidney, both enhancers might confer a tissue specific regulation to both genes. We have also found that the deletion of any of these enhancers downregulates six well-known FOXP2 target genes in the SK-N-MC cell line. Conclusions We expect these findings contribute to a deeper understanding of how FOXP2 and MDFIC are regulated to pace neuronal development supporting cognition, speech and language.

Este artículo evalúa por qué algunas pequeñas y medianas empresas, o pymes, exportan y otras no, incluso cuando enfrentan situaciones macroeconómicas y de política comercial similares. Con este fin, se analizan estadísticamente las diferencias entre las pymes que son exportadoras y las que no lo son durante el período 2000-2012. El análisis permite confirmar la modesta orientación de la estructura industrial colombiana hacia los mercados internacionales. Las pymes que exportaron crecieron más en su producción industrial que las no exportadoras; además, exhibieron los mayores tamaños en capital y número total de ocupados. Se verifica así mismo la hipótesis sobre preselección de las pymes para exportar según niveles de productividad laboral. De igual manera, las empresas que registraron los mayores niveles de productividad presentaron las más altas probabilidades de exportar, aunque dicha probabilidad registró una tendencia decreciente en el período analizado. La probabilidad de exportar también se vio afectada positivamente por aquellas empresas que lo hicieron en el pasado.

It has been proposed that the accumulation of farnesylated phosphatase of regenerating liver-1 (PRL-1) at the plasma membrane is mediated by static electrostatic interactions of a polybasic region with acidic membrane lipids and assisted by oligomerization. Nonetheless, localization at early and recycling endosomes suggests that the recycling compartment might also contribute to its plasma membrane accumulation. Here, we investigated in live cells the dynamics of PRL-1 fused to the green fluorescent protein (GFP-PRL-1). Blocking the secretory pathway and photobleaching techniques suggested that plasma membrane accumulation of PRL-1 was not sustained by recycling endosomes but by a dynamic exchange of diffusible protein pools. Consistent with this idea, fluorescence correlation spectroscopy in cells overexpressing wild type or monomeric mutants of GFP-PRL-1 measured cytosolic and membrane-diffusing pools of protein that were not dependent on oligomerization. Endogenous expression of GFP-PRL-1 by CRISPR/Cas9 genome edition confirmed the existence of fast diffusing cytosolic and membrane pools of protein. We propose that plasma membrane PRL-1 replenishment is independent of the recycling compartment and the oligomerization state and mainly driven by fast diffusion of the cytosolic pool.

The CD69 gene encodes a C-type lectin glycoprotein with immune regulatory properties which is expressed on the cell surfaces of all activated hematopoietic cells. CD69 activation kinetics differ by developmental stage, cell linage and activating conditions, and these differences have been attributed to the participation of complex gene regulatory networks. An evolutionarily conserved regulatory element, CNS2, located 4kb upstream of the CD69 gene transcriptional start site, has been proposed as the major candidate governing the gene transcriptional activation program. To investigate the function of human CNS2, we studied the effect of its endogenous elimination via CRISPR-Cas9 on CD69 protein and mRNA expression levels in various immune cell lines. Even when the entire promoter region was maintained, CNS2-/- cells did not express CD69, thus indicating that CNS2 has promoter-like characteristics. However, like enhancers, inverted CNS2 sustained transcription, although at a diminished levels, thereby suggesting that it has dual promoter and enhancer functions. Episomal luciferase assays further suggested that both functions are combined within the CNS2 regulatory element. In addition, CNS2 directs its own bidirectional transcription into two different enhancer-derived RNAs molecules (eRNAs) which are transcribed from two independent transcriptional start sites in opposite directions. This eRNA transcription is dependent on only the enhancer sequence itself, because in the absence of the CD69 promoter, sufficient RNA polymerase II levels are maintained at CNS2 to drive eRNA expression. Here, we describe a regulatory element with overlapping promoter and enhancer functions, which is essential for CD69 gene transcriptional regulation.

The durability of the concrete of the precast Great Soviet Panel system is valued through the resistance to compression, ultrasonic pulse velocity, surface methods, humidity and potential of corrosion. The evaluation is approached, essentially, through experimental and statistical methods, nevertheless, historical-logical and technical methods, such as surveys and interviews, are used in order to gather a bigger amount of information on the resistance to compression of the elements in the original project. While analyzing the results, we can conclude that, in elements in a good technical-constructive state that conform the constructions in exploitation, concrete has an average resistance. However, in elements with the presence of pathological damages, the resistance is low due to the fact that elements show chemical deterioration processes caused by water exposure, which generates the formation of soluble paste compounds, loss of mass, and decrease in mechanical resistance, among other alterations. At the same time, carbonation of concrete is triggered, which, in turn, causes the corrosion of the reinforcing steel. This corrosion leads to the cracking of concrete, delamination of steel, decrease of the concrete-steel adhesion, and other manifestations that affect the durability of concrete. Therefore, the incidence of the durability of concrete should be valued in the structural seismic behavior of constructions.

Summary: Tumor cell plasticity, including transdifferentiation, is thought to be a key driver of therapy failure, tumor dormancy, and metastatic dissemination. Although melanoma cells have been shown to adopt various phenotypic features in vitro, direct in vivo evidence of metastatic cell plasticity remains sparse. Here, we combine lineage tracing in a spontaneous metastatic mouse model of melanoma, advanced imaging, and single-cell RNA sequencing approaches to search for pathophysiologically relevant melanoma cellular states. We identify melanoma cells in intravascular niches of various metastatic organs. These cells are quiescent, are negative for characteristic melanoma markers, and acquire endothelial cell features. We replicate the endothelial transdifferentiation (EndT) finding in another mouse model and provide evidence of EndT in BRAFV600E-metastatic biopsies from human lung, brain, and small intestine, thus highlighting the clinical relevance of these findings. The tumor-vasculature pattern described herein may contribute to melanoma dormancy within metastatic organs and represent a putative target for therapies.

Autoimmune polyendocrine syndrome (APS) is assumed to involve an immune system malfunction and entails several autoimmune diseases co-occurring in different tissues of the same patient; however, they are orphans of its accurate diagnosis, as its genetic basis and pathogenic mechanism are not understood. Our previous studies uncovered alterations in the ATPase H+/K+ Transporting Subunit Alpha (ATP4A) proton pump that triggered an internal cell acid–base imbalance, offering an autoimmune scenario for atrophic gastritis and gastric neuroendocrine tumors with secondary autoimmune pathologies. Here, we propose the genetic exploration of APS involving gastric disease to understand the underlying pathogenic mechanism of the polyautoimmune scenario. The whole exome sequencing (WES) study of five autoimmune thyrogastric families uncovered different pathogenic variants in SLC4A2, SLC26A7 and SLC26A9, which cotransport together with ATP4A. Exploratory in vitro studies suggested that the uncovered genes were involved in a pathogenic mechanism based on the alteration of the acid–base balance. Thus, we built a custom gene panel with 12 genes based on the suggested mechanism to evaluate a new series of 69 APS patients. In total, 64 filtered putatively damaging variants in the 12 genes of the panel were found in 54.17% of the studied patients and none of the healthy controls. Our studies reveal a constellation of solute carriers that co-express in the tissues affected with different autoimmune diseases, proposing a unique genetic origin for co-occurring pathologies. These results settle a new-fangled genetics-based mechanism for polyautoimmunity that explains not only gastric disease, but also thyrogastric pathology and disease co-occurrence in APS that are different from clinical incidental findings. This opens a new window leading to the prediction and diagnosis of co-occurring autoimmune diseases and clinical management of patients.

We report the generation-characterization of a fetal liver (FL) B-cell progenitor (BCP)-derived human induced pluripotent stem cell (hiPSC) line CRISPR/Cas9-edited to carry/express a single copy of doxycycline-inducible Cas9 gene in the “safe locus” AAVS1 (iCas9-FL-BCP-hiPSC). Gene-edited iPSCs remained pluripotent after CRISPR/Cas9 genome-edition. Correct genomic integration of a unique copy of Cas9 was confirmed by PCR and Southern blot. Cas9 was robustly and specifically expressed on doxycycline exposure. T7-endonuclease assay demonstrated that iCas9 induces robust gene-edition when gRNAs against hematopoietic transcription factors were tested. This iCas9-FL-BCP-hiPSC will facilitate gene-editing approaches for studies on developmental biology, drug screening and disease modeling.

Medial patellofemoral ligament (MPFL) reconstruction for patellofemoral instability is a common procedure. Although MPFL reconstruction is a successful procedure in terms of return to normal life or sports, revision cases are challenging due to previous holes into the patella or implants placed in the anatomical femoral insertion site. In this technical note, the use of a partial quadriceps tendon transfer to the adductor magnus tendon is presented as a good solution for revision cases to avoid the use of implants, bone drilling, use of allografts, or two-stage surgical procedures. In addition, this procedure could be also used as a primary procedure in skeletally immature patients. Keywords: Medial patellofemoral ligament, Reconstruction, Revision surgery, Partial quadriceps tendon transfer

Este pequeño ensayo pretende revisar la vieja teoría del agón literario entre Heinrich von Kleist y Johann Wolfgang Goethe, aportando algo novedoso desde el punto de vista de la Grecística, y tomando, a modo de ilustración, elementos de la tragedia Pentesilea del escritor prusiano. La Antigüedad, la androginia y el agón mismo son puntos de partida desde los que podemos sacar provecho al aproximarnos al llamado Goethezeit.

Background and study aims Zenker's diverticulum may cause disabling symptoms, especially in the elderly. Treatment has changed in recent decades from open surgery to management with flexible endoscopy, resulting in lower morbidity and mortality. The goal of this study was to present the largest series, with the longest follow-up, of patients with Zenker's diverticulum receiving outpatient treatment with flexible endoscopy using a diverticuloscope and Ligasure (Covidien, Minneapolis, Minnesota, United States), a device that allows tissue sealing and coagulation of vessels before cutting the septum between the diverticulum and esophagus. Patients and methods We performed 79 diverticulotomies in 69 patients (65.2 % male, mean age 73.4 years). The mean diverticulum size was 2.8 cm. In three cases with a diverticulum ≤ 1.5 cm, the diverticuloscope could not be placed. Results The technical success was 95.83 % and the clinical success 96.7 %: 84 % of the 56 patients followed for a mean of 34.6 months (24 – 64 months) had no dysphagia. The recurrence rate was 10.4 %, with a good response to a second diverticulotomy at 12 months (IQR: 11.5 – 17) in most cases. The most severe complications were two microperforations, resolved with conservative treatment, and one case of delayed bleeding endoscopically-controlled with a clip. Conclusions Diverticulotomy of the esophageal-diverticular septum with Ligasure is an outpatient endoscopic technique that is simple, effective in the long term and very safe for the treatment of patients with Zenker's diverticulum. In symptomatic recurrences, a second procedure was equally safe and effective in most patients.

Este trabajo tiene como objeto de estudio el análisis del discurso de los candidatos a la presidencia de Colombia para el período 2018-2022 y cómo este cambió en el tiempo bajo la influencia de la intención de voto, reflejada en las encuestas. Esto se llevó a cabo mediante el seguimiento de debates y entrevistas. Con la información recolectada se identificó el cambio en el contenido del discurso a lo largo del tiempo y se contrastó con la evolución de los resultados de intención de voto de las encuestadoras escogidas.

The chromosome 1q21.1 duplication syndrome (OMIM# 612475) is characterized by head anomalies, mild facial dysmorphisms, and cognitive problems, including autistic features, mental retardation, developmental delay, and learning disabilities. Speech and language development are sometimes impaired, but no detailed characterization of language problems in this condition has been provided to date. We report in detail on the cognitive and language phenotype of a child who presents with a duplication in 1q21.1 (arr[hg19] 1q21.1q21.2(145,764,455-147,824,207) × 3), and who exhibits cognitive delay and behavioral disturbances. Language is significantly perturbed, being the expressive domain the most impaired area (with significant dysphemic features in absence of pure motor speech deficits), although language comprehension and use (pragmatics) are also affected. Among the genes found duplicated in the child, CDH1L is upregulated in the blood of the proband. ROBO1, a candidate for dyslexia, is also highly upregulated, whereas, TLE3, a target of FOXP2, is significantly downregulated. These changes might explain language, and particularly speech dysfunction in the proband.

The emerging chikungunya virus (CHIKV), is an arbovirus causing intense outbreaks in North America. The situation in Mexico is alarming, and CHIKV threatens to spread further throughout North America. Clinical and biological features of CHIKF outbreaks in Mexico have not been well described; thus, we conducted a cross sectional study of a CHIKV outbreak in Chiapas, Southern Mexico to further characterize these features.We collected blood samples from patients suspected of having chikungunya fever (CHIKF) who presented to Clinical Hospital ISSSTE Dr. Roberto Nettel in Tapachula, Chiapas, Mexico. In addition to the clinical examination, real-time polymerase chain reaction (PCR) standardized for the Asian Chikungunya lineage and/or enzyme-linked immunosorbent assay for immunoglobulin M (IgM) were used to confirm CHIKV diagnosis. Of a total of 850 patients who presented with probably CHIKV at Hospital "Dr. Roberto Nettel", 112 probable CHIKF cases were enrolled in this study from November 2014- June 2015, of which 95 patients (84.8%) were CHIKV positive and 17 were negative (15.2%). Of these 95 CHIKV positive patients, 62 were positive by real-time reverse transcriptase PCR (+qRT-PCR); and 33 were seropositive to +IgM with a negative qRT-PCR. The most frequent symptoms reported were fever (100%), headache (82.3%), polyarthralgia (72.1%), and exanthem (82.3%). Biological abnormalities observed during CHIKV infection were lymphopenia (41.1%), leukopenia (51.6%), elevated transaminases (30.5%-46.3%) and high LDH (46.3%) and CRP (60.0%).Clinical and biological data obtained from this study is providing more useful information for benchmarking purposes with outbreaks from different parts of the world and would be helpful for better patient care and treatment.

At a first glance, the German poet Johann Wolfgang Goethe had little to do with philosophy: moreover, he thought of it with contempt. Plato however was —nevertheless Goethe's first distrustful approachment to Greek philosophy— one of the most significative influences of his development as a universal thinker. A proof of which statement could be the Idee of his novel DieWahlvenvandtschaften.

Introducción: el embarazo constituye un proceso natural que provoca una serie de cambios fisiológicos, patológicos y psicológicos que las convierten en pacientes especiales que demandan cuidados exclusivos. Objetivo: determinar las principales enfermedades bucodentales que afectan a las embarazadas del Policlínico Pedro Díaz Coello. Métodos: Se realizó un estudio transversal de enero de 2014 a enero de 2015 en el Policlínico Pedro Díaz Coello de Holguín a un total de 395 embarazadas que acudieron a la consulta en el período de estudio. Las variables estudiadas fueron: edad, nivel educacional, área de residencia, clasificación epidemiológica, factores de riesgo y principales enfermedades bucales. Resultados: predominó como área de residencia la zona rural, el grupo de edad de 25 a 29 años, el nivel educacional preuniversitario con 53,9%, 35,2% y 53,7% respectivamente. El mayor número de las pacientes se encontraban enfermas (grupo III) con el 52,9%. El factor de riesgo que más incidió fue la higiene bucal deficiente representado por el 94,2%. La caries dental se identificó como la enfermedad que más afectó a las gestantes con el 47,8%. Conclusiones: la realización de trabajos educativos dirigidos a mejorar el estado de salud bucal en este grupo priorizado constituye una necesidad del momento actual. La caries dental es la afección más frecuente en las gestantes y el factor de riesgo la higiene bucal deficiente. Palabras clave: embarazadas, enfermedades bucodentales, caries dental, higiene bucal.

La tecnología constituye uno de los puntos fuertes para garantizar el desarrollo exitoso de de un país. Cuba, país bloqueado, con limitaciones de financiamiento ve limitada la adquisición de tecnologías que permitan hacer competitivos sus productos en el mercado nacional e internacional. La producción de básculas para la medición del ganado constituye una necesidad de la economía toda vez que el parque actual de las mismas en el país ha sufrido un deterioro notable. Cuba importa los componentes en el exterior a precios muy elevados y realiza su ensamblaje. Por encargo del Área de Ganadería del Ministerio de la Agricultura desde el año 1998 fue asignada la tarea al CEMA de la construcción de básculas electrónicas para el pesaje del ganado mayor. A partir de cálculos conservadores se estima una demanda nacional de no menos mil unidades necesarias para satisfacer la demanda de las empresas genéticas del país. El CEMA trabajó en la producción de varios modelos, los cuales satisfacen en gran medida y ahorrando recursos la demanda nacional. El presente trabajo tiene como objetivo general realizar el estudio de mercado para la comercialización del modelo CEMA TED-1000 V de básculas electrónicas para el pesaje de ganado mayor. Permite constatar que su producción es viable para el país por lo que se recomienda autorizar su comercialización a gran escala a partir de la aprobación del financiamiento necesario para su extensión, acorde a la demanda nacional.

Se diseñó, construyó y calibró un transductor de fuerza tipo S en el Centro de Mecanización Agropecuaria (CEMA) de la Universidad Agraria de La Habana (UNAH), sobre la base del análisis de tensiones y deformaciones, concentración y uniformidad de las deformaciones unitarias en la zona de colocación de los extensómetros, empleando el análisis numérico por el método de los elementos finitos. El valor máximo del esfuerzo normal equivalente brindado por el programa profesional Solid Works versión 2010, según el criterio de resistencia Von Misses, está dentro del límite de proporcionalidad del material seleccionado con un factor de seguridad de 7,05 garantizando la linealidad durante los regímenes de carga y descarga a los cuales será sometido, un nivel de sensibilidad de salida igual a 0,456 mV/V encontrándose dentro del rango recomendado para este tipo de transductor así como un bajo efecto de histéresis. El valor de la pendiente de la calibración con tres repeticiones de carga y descarga es de 0,0386 N/mV y un error de ± 0,024 N. Del análisis del procesamiento estadístico se determinó que para valores de la fuerza de tracción superiores a 5,8 N los errores cometidos se encuentra en el orden del 2,8% y a partir de valores superiores a 29,5 N los errores se encuentran por debajo del 1%.

Con el objetivo de conocer el valor del coeficiente fricción dinámico suelo-metal como dato de entrada para la evaluación de los modelos físicos matemáticos desarrollados con vista al diseño de parámetros geométricos de sondas utilizadas en la agricultura de precisión, se determinó experimentalmente sus valores para un suelo Ferralítico rojo en función de tres variables controladas: humedad volumétrica entre 20,5 y 26,1%; la velocidad de deslizamiento de la plancha metálica sobre el suelo, entre 0,673 y 1,234 m/s y para presiones específicas de 2,068 y 3,951 kPa. El intervalo de los valores del coeficiente de fricción dinámico obtenido, como primera aproximación, es de 0,57 a 0,82, en función de las variables independientes estudiadas. Éste manifiesta una tendencia de aumentar a medida que: disminuye la presión específica sobre el suelo; aumenta la velocidad inicialmente desde 0,59 hasta 0,9 m/s y, posteriormente, tiende a mantenerse constante hasta valores de 1,73 m/s, para un nivel de presión bajo (2,068 kPa) y a disminuir para un nivel de presión mayor (3,951 kPa). Las variables que más influyen en la variación del valor del coeficiente de fricción dinámico suelo-metal son, en orden descendiente: la presión, la velocidad y, por último, la humedad.

The theoretical calculation of pKa values for Brønsted acids is a challenging task that involves sophisticated and time-consuming methods. Therefore, heuristic approaches are efficient and appealing methodologies to approximate these values. Herein, we used the maximum surface electrostatic potential (VS,max) on the acidic hydrogen atoms of carboxylic acids to describe the H-bond interaction with water (the same descriptor that is used to characterize σ-bonded complexes) and correlate the results with experimental pKa values to obtain a predictive model for other carboxylic acids. We benchmarked six different methods, all including an implicit solvation model (water): Five density functionals and the Møller–Plesset second order perturbation theory in combination with six different basis sets for a total of thirty-six levels of theory. The ωB97X-D/cc-pVDZ level of theory stood out as the best one for consistently reproducing the reported pKa values, with a predictive power of 98% correlation in a test set of ten other carboxylic acids.