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BACKGROUND: Encephalitozoon cuniculi is an opportunistic intracellular pathogen that establishes a balanced relationship with immunocompetent individuals depending on the activity of their CD8+ T cells lymphocytes. However, lower resistance to experimental infection with E. cuniculi was found in B-1 deficient mice (Xid), besides increased the number of CD8 T lymphocytes. Here, we evaluated the profile of CD8+ T lymphocytes from Balb/c wild-type (WT) or Balb/c Xid mice (with B-1 cell deficiency) on the microbicidal activity of macrophages challenged with E. cuniculi. METHODS: Naïve CD8 T lymphocytes from WT or Xid mice uninfected and primed CD8 T lymphocytes from WT or Xid mice infected with E cuniculi were co-cultured with macrophages previously challenged with E. cuniculi. We evaluated macrophages viability and microbicidal activity, and CD8 T lymphocytes viability and presence of activating molecules (CD62L, CD69, and CD107a). RESULTS: Macrophages co-cultured with naïve CD8 T lymphocytes from WT demonstrated high microbicidal activity. Naïve CD8 T lymphocytes obtained from WT mice had a higher expression of CD69 and LAMP-1-activating molecules compared to Xid CD8+ T lymphocytes. Primed CD8 T lymphocytes from Xid mice proliferated more than those from WT mice, however, when the expression of the activating molecule CD69 associated with the expression of CD62L was kept low. In conclusion, naïve CD8+ T lymphocytes from Xid mice, deficient in B-1 cells, they had reduced expression of activation molecules and cytotoxic activity.

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INTRODUCTION: Aspirin is one of the most commonly used drugs worldwide. It is known to present antipyretic, anti-inflammatory and anti-thrombotic actions, making it extremely useful in a wide range of clinical contexts. Interestingly, homeopathically prepared Aspirin 15cH has been found to have a pro-thrombotic effect in rats, raising the hypothesis that Aspirin 15cH could also modulate the activity of inflammatory cells in different pathological processes. OBJECTIVE: Our objective was to assess what effect Aspirin 15cH has on RAW 264.7 macrophages in vitro. METHODS: The effects of Aspirin 15cH on biochemical and morphological activities of lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages were evaluated. These effects were compared with unchallenged macrophages (negative control), untreated LPS-stimulated macrophages, macrophages treated with succussed water (vehicle control), or aspirin 200 µg/mL (pharmacological inhibitor of LPS activity). Cell morphology (adhered cell area and cytoskeleton arrangements), cell viability, toll-like receptor-4 (TLR-4) expression, and the production of nitric oxide, cytokines and intracellular reactive oxygen species were assessed. RESULTS: Aspirin 15cH reduced the number of cells expressing TLR-4 on the surface (p = 0.03) and induced a "columnar" morphology of macrophage pseudopods, indicating changes in cytoskeleton arrangement. When cells were treated with both Aspirin 15cH and LPS, cell morphology became heterogeneous, suggesting that sub-populations of cells had differing sensitivities to LPS or Aspirin 15cH. Exposure of the cells to LPS alone, succussed water or aspirin 200 µg/mL produced effects consistent with the literature. CONCLUSION: Aspirin 15cH, aspirin 200 µg/mL, LPS and succussed water appear to act as independent stimuli able to induce different patterns of macrophage response. Aspirin 15cH induced changes suggestive of M2 polarization of the macrophages (i.e., toward a wound healing or tissue repair, rather than inflammatory, phenotype). These preliminary findings need to be confirmed in further specific studies.

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Encephalitozoon cuniculi is a unicellular, spore-forming, obligate intracellular eukaryote belonging to the phylum Microsporidia. It is known to infect mainly immunocompromised and immunocompetent mammals, including humans. The parasite-host relationship has been evaluated using both in vitro cell culturing and animal models. For example, Balb/c and C57BL/6 mouse strains have been used interchangeably, although the latter has been considered more susceptible due to the higher fungal load observed after infection. In the present study, we identified the characteristics of the immune response of C57BL/6 mice treated or not with the immunosuppressant cyclophosphamide (Cy) and challenged with E. cuniculi by intraperitoneal route. After 14 days of infection, serum was collected to analyze Th1, Th2, and Th17 cytokine levels. In addition, peritoneal washes were performed, and the spleen sample was collected for immune cell phenotyping, whereas liver, spleen, kidney, lung, intestine, and central nervous system (CNS) samples were collected for histopathological analysis. Although infected mice displayed a reduced absolute number of macrophages, they showed an M1 profile, an elevated number of CD4+T, CD8+T, B-1, and B-2 lymphocytes, with a predominance of Th1 inflammatory cytokines (interferon [IFN]-γ, tumor necrosis factor [TNF]-α, and interleukin [IL]-2) and Th17. Furthermore, Cy-Infected mice showed a reduced absolute number of macrophages with an M1 profile but a reduced number of CD4+T, CD8+T, B-1, and B-2 lymphocytes, with a predominance of Th1 inflammatory cytokines (IFN-γ, TNF-α, and IL-2) and Th2 (IL-4). This group displayed a higher fungal burden as well and developed more severe encephalitozoonosis, which was associated with a reduced number of T and B lymphocytes and a mixed profile of Th1 and Th2 cytokines.

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DisProt is the primary repository of Intrinsically Disordered Proteins (IDPs). This database is manually curated and the annotations there have strong experimental support. Currently, DisProt contains a relatively small number of proteins highlighting the importance of transferring annotations regarding verified disorder state and corresponding functions to homologous proteins in other species. In such a way, providing them with highly valuable information to better understand their biological roles. While the principles and practicalities of homology transfer are well-established for globular proteins, these are largely lacking for disordered proteins. We used DisProt to evaluate the transferability of the annotation terms to orthologous proteins. For each protein, we looked for their orthologs, with the assumption that they will have a similar function. Then, for each protein and their orthologs, we made multiple sequence alignments (MSAs). Disordered sequences are fast evolving and can be hard to align, therefore, we implemented alignment quality control steps ensuring robust alignments before mapping the annotations. We have designed a pipeline to obtain good-quality MSAs and to transfer annotations from any protein to their orthologs. Applying the pipeline to DisProt proteins, from the 1731 entries with 5623 annotations, we can reach 97,555 orthologs and transfer a total of 301,190 terms by homology. We also provide a web server for consulting the results of DisProt proteins and execute the pipeline for any other protein. The server Homology Transfer IDP (HoTIDP) is accessible at http://hotidp.leloir.org.ar.

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We possess rather little detailed information on the lives of the first inhabitants of Puerto Rico-the so-called "Archaic" or "Pre-Arawak" people-despite more than a century of archeological research. This is particularly true bioarchaeologically, as fewer than twenty burials of the several millennia of the Archaic Age have been recovered, let alone analyzed in any detail. Here, we present the results of archeological, osteological, radiometric, and isotopic analysis of five individuals from the Ortiz site in Cabo Rojo, southwestern Puerto Rico. Study of these previously unpublished remains, which represent a 20-25% increase in the sample size of remains attributed to the period, provides many critical insights into earliest Puerto Rican lifeways, including aspects of mortuary practice, paleodiet, and possibly even social organization. A review of their burial treatment finds a mostly standardized set of mortuary practices, a noteworthy finding given the site's potential millennium-long use as a mortuary space and the possibly distinct place(s) of origin of the individuals interred there. Although osteological analysis was limited by poor preservation, we were able to reconstruct aspects of the demography that indicate the presence of both male and female adults. Stable isotope analysis revealed dietary differences from later Ceramic Age individuals, while dental pathology indicated heavy masticatory wear attributable to diet and/or non-masticatory function. Perhaps most crucially, direct AMS dating of the remains confirms these as the oldest burials yet recovered from the island, providing us both with a glimpse into the lives of some of the island's first inhabitants, and with tantalizing clues to the existence of a different degree of cultural "complexity" than is often ascribed to these earliest peoples. The existence of what radiocarbon dates suggest may be a persistent formal cemetery space at the Ortiz site has potentially significant implications concerning the territoriality, mobility, and social organization of the earliest peoples of southwestern Puerto Rico.

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Periodontal disease (PD) and obesity are characterized by a dysregulated inflammatory state. Both conditions trigger inflammatory and immune responses with an increase in proinflammatory cytokines such as Interleukin 6 (IL-6) and the release of inflammatory mediators such as C-reactive protein (CRP). Individuals with a high body mass index (BMI) present a chronic inflammatory state. The aim of the present study was to perform a systematic review of inflammatory markers (IL-6 and CRP) in obese patients with PD and their possible relationship by analyzing the levels of these markers. A digital literature search was performed in three databases-PubMed, SciElo and Medigraphic-through an advanced search for original articles, employing IL-6 and CRP in obese patients with PD, within a publication period from 2010 to 2021. PRISMA guidelines, the JADAD scale and a qualitative analysis of scientific evidence were performed using the Cochrane collaboration method and the RoB 2 assessment tool. Ten articles were included in this analysis with the variables recorded and associated with subjects with obesity and PD. Of the ten articles included, three analyzed IL-6 and CRP, four analyzed IL-6 and three analyzed CRP. In conclusion, and based on the available evidence, the aforementioned markers of inflammation demonstrate that there is a relationship between PD and obesity.

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BACKGROUND: Currently, there is a need for models, methods, and tools that allow ergonomics/human factor (E/HF) practitioners to assess the level of E/HF integration into organizations from a macroergonomics perspective. OBJECTIVE: This paper aims to propose the Ergonomic Maturity Model (EMM) and the tools for its application as a framework for integrating E/HF in organizations. METHODS: The EMM is a macroergonomic tool that allows stakeholders to evaluate the degree of development and integration of E/HF in the organization based on a participatory and macroergonomic approach. The EMM classifies organizations into five gradual levels of maturity: Ignorance, Understanding, Experimentation, Regular use, and Innovation. RESULTS: In this paper, we provide a three-stage procedure for guiding the application of the EMM: preparation of the evaluation, evaluation, and improvement plan and implementation. We include four tools developed specifically for applying EMM in organizations: evaluation matrix, weighting questionnaire, quick questionnaire, and prioritization matrix. Also, we present a Colombian floriculture company's case study to exemplify the use of the EMM. CONCLUSIONS: The EMM provides a framework for integrating E/HF into organizations from the macroergonomics approach. E/HF practitioners can find in the EMM a tool to help them channel the actions taken by the different organizational actors to improve the safety, health, well-being, and performance of work systems. Finally, it should be noted that further studies on the reliability and validity of the EMM are needed, which would contribute to demonstrating that the EMM can effectively and successfully guide change in E/HF maturity levels in organizations.

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Los errores de medicación representan un problema de salud pública que afecta la seguridad del paciente y la calidad de los servicios de salud a escala global. En este artículo se presenta un procedimiento para el análisis y la prevención de los errores de medicación desde la perspectiva de la ergonomía, ejemplificándose su aplicación mediante un caso de estudio ilustrativo de administración de un medicamento inyectable. Como parte del procedimiento expuesto, se incluyeron los reconocidos métodos Hierarchical Task Analysis (HTA) para el análisis de la tarea y Systematic Human Error Reduction and Prediction Approach (SHERPA) para la identificación de los modos de error. Para la valoración de riegos se empleó la matriz de riesgos propuesta en la norma ISO 45001. El procedimiento propuesto quedó conformado por cuatro etapas: 1) selección de la tarea objeto de estudio, 2) análisis detallado de la tarea, 3) predicción de la posibilidad de error y 4) desarrollo de estrategias para la reducción del error. Se espera que la utilización sistemática de este procedimiento contribuya en la mejora de la calidad de los servicios de salud, disminuyendo los errores humanos y los posibles eventos adversos.

Medication errors represent a public health problem that affects patient safety and the quality of healthcare services globally. This article presents a procedure for the analysis and prevention of medication errors from the perspective of ergonomics, exemplifying its application through a case study. The well-known Hierarchical Task Analysis (HTA) and the Systematic Human Error Reduction and Prediction Approach (SHERPA) methods are included. The risk assessment was based on the risk matrix proposed in the ISO 45001 standard. The proposed procedure is structured in four stages: 1) selection of the task to be analysed, 2) detailed analysis of the task, 3) prediction of the possibility of error, 4) error reduction strategies. The use of the procedure is exemplified through a case study of the administration of an injectable drug. The systematic use of this procedure is expected to contribute to the improvement of the quality of health services by reducing human errors and possible adverse events.

Os erros de medicação representam um problema de saúde pública que afeta a segurança do paciente e a qualidade dos serviços de saúde em escala global. Este artigo apresenta um procedimento para a análise e prevenção de erros de medicação do ponto de vista ergonômico, exemplificado por um estudo de caso. Foram incluídos os métodos reconhecidos de Análise Hierárquica de Tarefas (HTA) para análise de tarefas e a Abordagem Sistemática de Redução e Previsão de Erros Humanos (SHERPA) para identificação de modos de erro. A avaliação do risco baseou-se na matriz de risco proposta na norma ISO 45001. O procedimento proposto é composto de quatro etapas: 1) seleção da tarefa em estudo, 2) análise detalhada da tarefa, 3) previsão da possibilidade de erro, 4) estratégias de redução de erros. A aplicação do procedimento é ilustrada por um estudo de caso de administração de um medicamento injetável. Espera-se que o uso sistemático deste procedimento contribua para a melhoria da qualidade dos serviços de saúde, reduzindo erros humanos e possíveis eventos adversos.

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Vasomotor symptoms (VMS) are the most common symptoms among menopausal women; these include hot flashes and night sweats, and palpitations often occur along with hot flashes. Some studies in Mexico reported that around 50% of women presented with VMS mainly in the menopausal transition. It has been proven that VMS are not only triggered by an estrogen deficiency, but also by nutritional risk factors. Evidence of an association between nutritional risk factors and VMS is limited in Mexican women. The aim of this study is to identify nutritional risk factors associated with VMS in women aged 40−65 years. This is a comparative cross-sectional study, undertaken in a retrospective way. A sample group (n = 406 women) was divided into four stages according to STRAW+10 (Stages of Reproductive Aging Workshop): late reproductive, menopausal transition, early postmenopause, and late postmenopause. Hot flashes were present mainly in the early postmenopause stage (38.1%, p ≤ 0.001). Two or more VMS were reported in 23.2% of women in the menopausal transition stage and 29.3% in the early postmenopause stage (p < 0.001). The presence of VMS was associated with different nutritional risk factors (weight, fasting glucose levels, cardiorespiratory fitness, and tobacco use) in women living in the northeast of Mexico.

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Motivation: Proteins involved in liquid-liquid phase separation (LLPS) and membraneless organelles (MLOs) are recognized to be decisive for many biological processes and also responsible for several diseases. The recent explosion of research in the area still lacks tools for the analysis and data integration among different repositories. Currently, there is not a comprehensive and dedicated database that collects all disease-related variations in combination with the protein location, biological role in the MLO, and all the metadata available for each protein and disease. Disease-related protein variants and additional features are dispersed and the user has to navigate many databases, with a different focus, formats, and often not user friendly. Results: We present DisPhaseDB, a database dedicated to disease-related variants of liquid-liquid phase separation proteins. It integrates 10 databases, contains 5,741 proteins, 1,660,059 variants, and 4,051 disease terms. It also offers intuitive navigation and an informative display. It constitutes a pivotal starting point for further analysis, encouraging the development of new computational tools.The database is freely available at http://disphasedb.leloir.org.ar.