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Cannabinoids, derived from the Cannabis sativa plant, have garnered increasing attention for their potential therapeutic applications in various diseases. The pharmacologically active compounds in Cannabis, such as delta-9-tetrahydrocannabinol and cannabidiol, exhibit diverse immunomodulatory properties. Although studies have explored the effects of cannabinoids on immune function, their specific interactions with the thymus, a primary immune organ critical for T-cell development and maturation, remain an intriguing area of investigation. As the thymus plays a fundamental role in shaping the immune repertoire, understanding the interplay between cannabinoids and thymic function may shed light on potential benefits or concerns associated with Cannabis-based therapies. This article aims to provide an overview of the current scientific knowledge regarding the impact of medicinal Cannabis on the thymus and its implications for disease treatment and immune health., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Construction projects significantly affect a country's development, consume many resources, and impact many stakeholders. Project sustainability requirements are essential to overcome the current social and environmental challenges, yet entrepreneurs, decision-makers, and technical professionals still ignore them. This research aims to reveal the leading players that can influence implementing sustainability requirements in construction project development, the barriers, and possible solutions. The results show that organizational strategies, maturity level in sustainability, and the ability to change corporate values and beliefs play a significant role in this pivotal movement. At the same time, a set of external stakeholders, such as investors, banks, communities, suppliers, regulatory agencies, and insurance companies, may push a specific behavior to the market and influence change. On top of this, organizations shall build their strategy toward sustainability and implement sustainable project management. This study employs the Complex Holographic Assessment of Paradoxical Problems (CHAP2) to investigate the current situation in Brazil related to the integration of construction project development and sustainability requirements., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Growth hormone (GH) is a classic pituitary-derived hormone crucial to body growth and metabolism. In the pituitary gland, GH production is stimulated by GH-releasing hormone and inhibited by somatostatin. GH secretion can also be induced by other peptides, such as ghrelin, which interacts with receptors present in somatotropic cells. It is well established that GH acts directly on target cells or indirectly by stimulating the production of insulin-like growth factors (IGFs), particularly IGF-1. Notably, such somatotropic circuitry is also involved in the development and function of immune cells and organs, including the thymus. Interestingly, GH, IGF-1, ghrelin, and somatostatin are expressed in the thymus in the lymphoid and microenvironmental compartments, where they stimulate the secretion of soluble factors and extracellular matrix molecules involved in the general process of intrathymic T-cell development. Clinical trials in which GH was used to treat immunocompromised patients successfully recovered thymic function. Additionally, there is evidence that the reduction in the function of the somatotropic axis is associated with age-related thymus atrophy. Treatment with GH, IGF-1 or ghrelin can restore thymopoiesis of old animals, thus in keeping with a clinical study showing that treatment with GH, associated with metformin and dehydroepiandrosterone, could induce thymus regeneration in healthy aged individuals. In conclusion, the molecules of the somatotrophic axis can be envisioned as potential therapeutic targets for thymus regeneration in age-related or pathological thymus involution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Reis, Veneziani, Porto, Lins, Mendes-da-Cruz and Savino.)

The COVID-19 pandemic required managerial and structural changes inside hospitals to address new admission demands, frequently reducing their care capacity for other diseases. In this regard, this study aims to support the recovery of hospital productivity in the post-pandemic context. The major challenge will be to make use of all the resources the institution has obtained (equipment, beds, temporarily hired human resources) and to increase production to meet the existing repressed demand. To support evidence-based decision-making at a major university hospital in Rio de Janeiro, hospital managers and operations research analysts designed an approach based on multiple methodologies. Besides multimethodology, one important novelty of this study is the application of a productivity frontier function to future scenario planning through the quantitative DEA methodology. Concept maps were used to structure the problem and emphasize stakeholders' perspectives. In sequence, data envelopment analysis (DEA) was applied, as it combines benchmarking best practices and assigns weights to inputs and outputs. To guarantee that the efficiency measurement considers all inputs and outputs before any inclusion of expert judgment, the scope was redirected to full dimensional efficient facet, if any, or to maximum efficient faces. The results indicate that production scenarios proposed by stakeholders based on the Ministry of Health parameters overestimate the viable production framework and that the scenario that maintains temporary human resource contracts is more compatible with quality in health provision, teaching, and research. These findings will serve as a basis for decision-making by the governmental agency that provided temporary contracts. The present methodology can be applied in different settings and scales., Competing Interests: None., (© 2022 Elsevier Ltd. All rights reserved.)

Insulin-like growth factor-1 (IGF-1), in addition to its classic effects on cell proliferation and organism growth, has pleiotropic actions on the immune system, particularly on the thymus. Thus, the objective of this study was to evaluate the influence of IGF-1 on molecules involved in the survival of thymocytes in vitro using a co-culture system with thymic stromal cells obtained from C57BL/6 mice. The obtained thymic stroma has contained thymic epithelial cells, macrophages, dendritic cells, fibroblasts, and preserved the expression of the major histocompatibility complex (MHC) molecules. Fresh thymocytes were added to these cultures and the co-culture were treated daily with IGF-1 (100 ng/mL) for 3 days. In this scheme, the viability of the thymocytes was about 70%, either in the control (non-treated cells) or in the IGF-1-treated cultures. It was found that IGF-1 was able to increase the percentage of thymocytes from the CD4 + single-positive (SP) subset. This result was accompanied by an increase in the MHC II expression on thymic stromal cells and an augment on the interleukin-7 receptor (CD127) on the surface of the CD4 SP thymocytes after treatment with IGF-1. Finally, IGF-1 treatment increased the expression of the ThPOK encoding gene Zbtb7b, which is involved in the differentiation of CD4+ SP thymocytes. Our study demonstrates the participation of IGF-1 in the thymocyte/thymic stroma interactions, especially in the extended survival of the CD4 + lineage in the thymus., (© 2022. The Society for In Vitro Biology.)

The generation of T lymphocytes (thymopoiesis) is one of the major functions of the thymus that occurs throughout life. Thymic epithelial cells actively participate in this process. However, less attention has been paid to extracellular matrix (ECM) elements of thymus and their role in thymocyte differentiation. To clarify this topic, we selected some studies that deal with thymic ECM, its modulation, and its effects on thymopoiesis in different models. We emphasize that further studies are needed in order to deepen this knowledge and to propose new alternatives for thymic ECM functions during thymopoiesis.

Background: The thymus is responsible for thymocyte differentiation into immunocompetent T lymphocytes. Different cell types in the thymic microenvironment actively cooperate in this process, interacting with the developing thymocytes through soluble factors, extracellular matrix (ECM) molecules, and receptors. In addition, this microenvironment can be influenced by several factors, such as semaphorin-3A (Sema3A), which is a multifunctional protein involved in cell migration. We evaluated the Sema3A effects on the cellular parameters and functional features of thymic stromal cells., Methods: Thymic stromal cells were obtained by enzymatic digestion of the murine thymus. These cells were treated with Sema3A and evaluated as follows: cell morphology by scanning electron microscope, F-actin cytoskeleton and deposition of ECM molecules by fluorescence microscopy, and adhesion assays with freshly obtained thymocytes., Results: The obtained thymic stroma was composed of 67% of thymic epithelial cells (TECs), and 90% of the TECs were positive for the Sema3A receptor neuropilin-1. These cells secreted CXCL12, IL-7 and extended thymocyte survival. Sema3A changed the morphology of thymic stromal cells and promoted F-actin reorganization. In addition, the fibronectin fibers were reoriented, and the laminin production was increased in Sema3A-treated thymic stromal cells. In the adhesion assays, there was an increase in the number of adhered thymocytes when thymic stromal cells were pretreated with Sema3A., Conclusion: Our data strongly suggest the active participation of Sema3A in thymic physiology, highlighting its role as an immunomodulatory molecule. This may provide important knowledge for understanding the interactions of thymic cells.

Understanding the pathogenesis of certain viral agents is essential for developing new treatments and obtaining a clinical cure. With the onset of the new coronavirus (SARS-CoV-2) pandemic in the beginning of 2020, a rush to conduct studies and develop drugs has led to the publication of articles that seek to address knowledge gaps and contribute to the global scientific research community. There are still no reports on the infectivity or repercussions of SARS-CoV-2 infection on the central lymphoid organ, the thymus, nor on thymocytes or thymic epithelial cells. In this brief review, we present a hypothesis about lymphopenia observed in SARS patients and the probable pathological changes that the thymus may undergo due to this new virus.

The prolactin hormone (PRL), in addition to its known effects on breast development and lactation, exerts effects on the immune system, including pleiotropic effects on the thymus. The aim of this study was to evaluate the influence of PRL on the epithelial compartment of the thymus. Thymic epithelial cells (TECs) (2BH4 cells) and fresh thymocytes were used. Immunofluorescence assay revealed that PRL treatment (10 ng/ mL) increases the deposition of laminin and expression of the chemokine CXCL12 in 2BH4 cells. However, no change was observed in the deposition of fibronectin. Moreover, PRL altered F-actin polymerisation, allowing the formation of focal adhesion complexes in treated cells. When 2BH4 cells were pre-treated with PRL, thymocyte adhesion was not altered. However, in the cell migration assay, pre-treatment with PRL potentiated the chemotactic effect of CXCL12 on the migration of total, double-positive, CD4-positive, and CD8-positive thymocytes. Together, the results of this study demonstrate the effect of PRL on thymic epithelial cells, particularly on CXCL12-driven thymocyte migration, confirming that this hormone is a regulator of thymic physiology.

Growth hormone (GH), in addition to its classic actions on growth and metabolism in the body, exerts pleiotropic effects on the immune system, particularly on the thymus. The aim of this study was to evaluate the influence of GH on the interactions between mature thymocytes and the thymic endothelium involved in the migratory process. To this end, fresh thymocytes (C57BL/6 mice) and the thymic endothelial cell line (tEnd.1) were used. In the cell adhesion assay, the GH-treated thymocytes adhered more to tEnd.1 cells. Additionally, there was an improvement in the deposition of fibronectin by tEnd.1 cells when co-cultured with GH-pre-treated thymocytes. Furthermore, GH induced thymocyte F-actin polymerization. In the transendothelial migration assay, a large number of GH-treated thymocytes, mainly the CD4 - CD8 + subset, migrated towards the endothelium under the stimulus of insulin-like growth factor 1. In conclusion, we demonstrated the positive actions of GH in thymocyte/thymic endothelium interactions, including transendothelial migration.

The integration of quantitative indicators with qualitative descriptions of context is a noticeable demand from many different scientific disciplines, since it contributes to linking theoretical and practical approaches to problem solving. Amongst them are the problem structuring methods, systems thinking and multimethodology. This work presents a mixed quantitative and qualitative methodological approach to aid formulation and structuring of performance measurement of health care in 5565 Brazilian municipalities. Data mining and data envelopment analysis (DEA) are applied in the context of conceptual mapping, thus shedding light on both quantitative and qualitative factors that influence health performance. Our aim is to propose a methodology for performance indicators to support health care policy making in Brazil, using quantitative indicators. However, the approach does not lose track of the role of important qualitative factors in the attribution of meaning to performance assessments. The methodological and analytical results can strengthen mutual understanding by analysts and stakeholders of the problem at hand. Quantitative results allow inefficient municipalities to understand the causes of their overall efficiency in terms of particular low partial DEA efficiencies combined with high deathrates.

Background: Class 3 semaphorins are soluble proteins involved in cell adhesion and migration. Semaphorin-3A (Sema3A) was initially shown to be involved in neuronal guidance, and it has also been reported to be associated with immune disorders. Both Sema3A and its receptors are expressed by most immune cells, including monocytes, macrophages, and lymphocytes, and these proteins regulate cell function. Here, we studied the correlation between Sema3A-induced changes in biophysical parameters of thymocytes, and the subsequent repercussions on cell function., Methods: Thymocytes from mice were treated in vitro with Sema3A for 30min. Scanning electron microscopy was performed to assess cell morphology. Atomic force microscopy was performed to further evaluate cell morphology, membrane roughness, and elasticity. Flow cytometry and/or fluorescence microscopy were performed to assess the F-actin cytoskeleton and ROCK2. Cell adhesion to a bovine serum albumin substrate and transwell migration assays were used to assess cell migration., Results: Sema3A induced filopodia formation in thymocytes, increased membrane stiffness and roughness, and caused a cortical distribution of the cytoskeleton without changes in F-actin levels. Sema3A-treated thymocytes showed reduced substrate adhesion and migratory ability, without changes in cell viability. In addition, Sema3A was able to down-regulate ROCK2., Conclusions: Sema3A promotes cytoskeletal rearrangement, leading to membrane modifications, including increased stiffness and roughness. This effect in turn affects the adhesion and migration of thymocytes, possibly due to a reduction in ROCK2 expression., General Significance: Sema3A treatment impairs thymocyte migration due to biomechanical alterations in cell membranes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Nanoparticles have extremely wide applications in the medical and biological fields. They are being used in biosensors, local drug delivery, diagnostics, and medical therapy. However, the potential effects of nanoparticles on target cell and tissue function, apart from cytotoxicity, are not completely understood. Thus, the aim of this study was to investigate the in vitro effects of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) on human fibroblasts with respect to their interaction with the extracellular matrix and in cell migration. Immunofluorescence analysis revealed that treatment with AgNPs or AuNPs decreased collagen and laminin production at all the concentrations tested (0.1, 1, and 10 μg/mL). Furthermore, cytofluorometric analysis showed that treatment with AgNPs reduced the percentage of cells expressing the collagen receptor very late antigen 2, α 2 β 1 integrin (VLA-2) and the laminin receptor very late antigen 6, α 6 β 1 integrin (VLA-6). In contrast, AuNP treatment increased and decreased the percentages of VLA-2-positive and VLA-6-positive cells, respectively, as compared to the findings for the controls. Analysis of cytoskeletal reorganization showed that treatment with both types of nanoparticles increased the formation of stress fibres and number of cell protrusions and impaired cell polarity. Fibroblasts exposed to different concentrations of AuNPs and AgNPs showed reduced migration through transwell chambers in the functional chemotaxis assay. These results demonstrated that metal nanoparticles may influence fibroblast function by negatively modulating the deposition of extracellular matrix molecules (ECM) and altering the expression of ECM receptors, cytoskeletal reorganization, and cell migration.

Background: Several evidences indicate that hormones and neuropeptides function as immunomodulators. Among these, growth hormone (GH) is known to act on the thymic microenvironment, supporting its role in thymocyte differentiation. The aim of this study was to evaluate the effect of GH on human thymocytes and thymic epithelial cells (TEC) in the presence of laminin., Results: GH increased thymocyte adhesion on BSA-coated and further on laminin-coated surfaces. The number of migrating cells in laminin-coated membrane was higher in GH-treated thymocyte group. In both results, VLA-6 expression on thymocytes was constant. Also, treatment with GH enhanced laminin production by TEC after 24 h in culture. However, VLA-6 integrin expression on TEC remained unchanged. Finally, TEC/thymocyte co-culture model demonstrated that GH elevated absolute number of double-negative (CD4(-)CD8(-)) and single-positive CD4(+) and CD8(+) thymocytes. A decrease in cell number was noted in double-positive (CD4(+)CD8(+)) thymocytes., Conclusions: The results of this study demonstrate that GH is capable of enhancing the migratory capacity of human thymocytes in the presence of laminin and promotes modulation of thymocyte subsets after co-culture with TEC.

Uvaol, a triterpene present in olives and virgin olive oil, has been shown to possess anti-inflammatory properties and antioxidant effects. However, until now, no studies have demonstrated its potential effects on allergic inflammation. The aim of this study was to evaluate the anti-inflammatory effects of uvaol in a mouse model of allergy characterized by eosinophil-dominant inflammation in actively sensitized mice. The anti-inflammatory effect of uvaol was analyzed in two murine models of allergic inflammation (pleurisy and asthma). In these models, Swiss mice were sensitized and challenged with ovalbumin (OVA). In the pleurisy model, the pleural eosinophilic inflammation and IL-5 concentrations were examined 24h after the OVA challenge, while in the asthma model were examined the airway inflammation via bronchoalveolar lavage (BAL) fluid cytology and lung histopathology analyses. Our results showed that uvaol decreased the accumulation of eosinophils and the concentration of IL-5 in pleural effluent. Uvaol also demonstrated important anti-inflammatory activity by inhibiting production of IL-5 and influx of leukocytes, mainly of eosinophils, in BAL fluid, but without interfering with levels of reactive oxygen species in leukocytes. Moreover, the eosinophil infiltration, mucus production, number of alveoli that collapsed, and IL-5 levels in the lung were clearly decreased by uvaol treatment. These findings indicate that uvaol can be a good candidate for the treatment of allergic inflammation by inhibiting eosinophil influx and IL-5 production in ovalbumin-induced allergy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To develop an assessment tool to evaluate the efficiency of federal university general hospitals., Methods: Data envelopment analysis, a linear programming technique, creates a best practice frontier by comparing observed production given the amount of resources used. The model is output-oriented and considers variable returns to scale. Network data envelopment analysis considers link variables belonging to more than one dimension (in the model, medical residents, adjusted admissions, and research projects). Dynamic network data envelopment analysis uses carry-over variables (in the model, financing budget) to analyze frontier shift in subsequent years. Data were gathered from the information system of the Brazilian Ministry of Education (MEC), 2010-2013., Results: The mean scores for health care, teaching and research over the period were 58.0%, 86.0%, and 61.0%, respectively. In 2012, the best performance year, for all units to reach the frontier it would be necessary to have a mean increase of 65.0% in outpatient visits; 34.0% in admissions; 12.0% in undergraduate students; 13.0% in multi-professional residents; 48.0% in graduate students; 7.0% in research projects; besides a decrease of 9.0% in medical residents. In the same year, an increase of 0.9% in financing budget would be necessary to improve the care output frontier. In the dynamic evaluation, there was progress in teaching efficiency, oscillation in medical care and no variation in research., Conclusions: The proposed model generates public health planning and programming parameters by estimating efficiency scores and making projections to reach the best practice frontier.

Therapeutic angiogenesis may be applied in medical conditions to promote stimulation of angiogenesis. Angiogenesis is a multistep process, which includes endothelial cell proliferation, migration, and tube formation, which is mediated by various angiogenic polypeptides. Thus, studies that elucidate the cellular mechanisms involved in these processes are necessary to develop novel therapeutic strategies. This study investigated the in vitro effects of the pro-angiogenic factors, insulin-like growth factor-1 (IGF-1) and/or chemokine (CC motif) ligand 2 (CCL2), on endothelial cells. Flow cytometry analysis showed that IGF-1 and CCL2 treatment did not interfere with IGF-1 receptor (IGF-1R) expression, but CCL2 treatment increased CCL2 receptor (CCR2) expression. Immunofluorescence analysis revealed that the IGF-1/CCL2 combination induced a greater increase in fibronectin deposition, but the treatments did not alter the expression of the fibronectin receptors, CD49e and CD44. The interaction of fibronectin with cytokines demonstrated that IGF-1/CCL2 promoted changes in intermediate F-actin remodeling that may result in increased endothelial cell adhesion and cell migration mediated by fibronectin. Furthermore, IGF-1/CCL2 stimulated endothelial cells, grown on fibronectin, to form capillary-like structures and intercellular lumina with greater luminal area. These data suggest that IGF-1/CCL2 combination and a fibronectin matrix may contribute to the angiogenesis process to stimulate adhesion, migration, and tube formation by endothelial cells as a result of F-actin remodeling.

Objective: To assess the performance and integration between the health care and teaching dimensions in Brazilian university hospitals., Methods: A network data envelopment analysis (DEA) model was designed to measure the performance of federal university hospitals, which enables the relationship between the teaching and health care dimensions to be considered simultaneously. Data from the Ministry of Education Information System of University Hospitals, in the second semester of 2003, were used. Results of the network model were compared to those of classical DEA models to assess the advantages of the new methodological proposal., Results: The efficiency of the hospitals assessed varied between 0.19 and 1.00 (mean = 0.54). The dimensional score showed that hospitals prioritize the gain in health care efficiency. It was observed that there was a need to double the number of medical students and increase the number of residents by 14% to obtain efficiency in the teaching dimension., Conclusions: The model was useful for both unit managers, aiming to integrate teaching and health care, and regulatory organizations, when defining policies and incentives.

Objective: To assess the impact of funding reform on the productivity of teaching hospitals., Methods: Based on the Information System of Federal University Hospitals of Brazil, 2003 and 2006 efficiency and productivity were measured using frontier methods with a linear programming technique, data envelopment analysis, and input-oriented variable returns to scale model. The Malmquist index was calculated to detect changes during the study period: 'technical efficiency change,' or the relative variation of the efficiency of each unit; and 'technological change' after frontier shift., Results: There was 51% mean budget increase and improvement of technical efficiency of teaching hospitals (previously 11, 17 hospitals reached the empirical efficiency frontier) but the same was not seen for the technology frontier. Data envelopment analysis set benchmark scores for each inefficient unit (before and after reform) and there was a positive correlation between technical efficiency and teaching intensity and dedication., Conclusions: The reform promoted management improvements but there is a need of further follow-up to assess the effectiveness of funding changes.

Objective: To apply the Data Envelopment Analysis (DEA) methodology for evaluating the performance of public hospitals, in terms of clinical medical admissions., Methods: The efficiency of the hospitals was measured according to the performance of decision-making units in relation to the variables studied for each hospital, in the year 2000. Data relating to clinical medical admissions in hospitals within the public system in Brazilian state capitals and Federal District (mortality rate, mean length of stay, mean cost of stay and disease profile) were analyzed. The canonical correlation analysis technique was introduced to restrict the variation range of the variables used. The constant returns to scale model was used to generate scores that would enable assessment of the efficiency of the units. From the scores obtained, these cities were classified according to their relative performance in the variables analyzed. It was sought to correlate between the classification scores and the exogenous variables of the expenditure on primary care programs per inhabitant and the human development index for each state capital., Results: In the hospitals studied, circulatory diseases were the most prevalent (23.6% of admissions), and the mortality rate was 10.3% of admissions. Among the 27 state capitals, four reached 100% efficiency (Palmas, Macapá, Teresina and Goiânia), seven were between 85 and 100%, ten were between 70 and 85% and ten had efficiency of less than 70%., Conclusions: The tool utilized was shown to be applicable for evaluating the performance of public hospitals. It revealed large variations among the Brazilian state capitals in relation to clinical medical admissions.