Promoting Circular Economy around Plastic Waste: A New Design of Recycled Plastic Shredder

The development and construction of the plastic shredder presented here is part of the MAREA Plastic project, which aims to be a meeting point between the university community and society, through science and technology. The project’s main goal consists in developing a circular economy environment that reduces both, the input of raw materials and the output of waste, closing the ecological and economic flows of resources. Thereby, this machine becomes essential for the continuation and proper development of such a research and social awareness project. The new version of the plastic shredder entails a solid design that meets the needs and requirements of the task assigned in its working environment, focusing on its design and manufacture from a sustainable point of view, reusing parts of the prototype itself, as well as other disused resources, mostly provided by the University of Malaga. This concept of sustainability even extends to its operation, controlling the consumption of the engine and paying special attention to durability, reliability and, above all, the safety of both, users and the shredder itself. Among other design priorities, the possibility to visualise and perfectly understand how and why the reused plastic passes through the shredder is one of the most important due to the educational purpose of the project towards a younger audience about circular economy. To achieve this, the machine should not only be able to show the process in an illustrative way, but also the interaction with the machine should be simple and fluid, without the need for previous knowledge or experience operating industrial machinery.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Prenatal Betamethasone Exposure and its Impact on Pediatric Type 1 Diabetes Mellitus : A Preliminary Study in a Spanish Cohort

Betamethasone, a glucocorticoid used to induce lung maturation when there is a risk of preterm delivery, can affect the immune system maturation and type 1 diabetes (T1D) incidence in the progeny. It has been described that prenatal betamethasone protects offspring from experimental T1D development. The main aim of this study was to evaluate the possible association between betamethasone prenatal exposure and T1D in humans. Research Design and Methods. A retrospective case-control study with a total of 945 children, including 471 patients with T1D and 474 healthy siblings, was performed. Participants were volunteers from the Germans Trias i Pujol Hospital and DiabetesCero Foundation. Parents of children enrolled in the study completed a questionnaire that included questions about weeks of gestation, preterm delivery risk, weight at birth, and prenatal betamethasone exposure of their children. Multiple logistic regression was used to detect the association between betamethasone exposure and T1D. We compared T1D prevalence between subjects prenatally exposed or unexposed to betamethasone. The percent of children with T1D in the exposed group was 37.5% (21 of 56), and in the unexposed group was 49.52% (410 of 828) (p = 0.139). The percentage of betamethasone-treated subjects with T1D in the preterm group (18.05%, 13 of 72) was significantly higher than that found in the control group (12.5%, 9 of 72) (p = 0.003). The odds ratio for T1D associated with betamethasone in the univariate logistic regression was 0.59 (95% confidence interval, 0.33; 1.03 [ p = 0.062]) and in the multivariate logistic regression was 0.83 (95% confidence interval, 0.45; 1.52 [ p = 0.389]). The results demonstrate that the prenatal exposure to betamethasone does not increase T1D susceptibility, and may even be associated with a trend towards decreased risk of developing the disease. These preliminary findings require further prospective studies with clinical data to confirm betamethasone exposure effect on T1D risk

Impaired Phagocytosis in Dendritic Cells From Pediatric Patients With Type 1 Diabetes Does Not Hamper Their Tolerogenic Potential

Type 1 diabetes (T1D) is prompted by defective immunological tolerance, an event in which dendritic cells (DCs) are crucial as immune response orchestrators. In fact, they contribute to maintaining tolerance to self-antigens, but they can also prompt an immunogenic response against them, leading to autoimmunity. Countless factors can potentially impact on the proper functionality of the DCs, which range from altered subset distribution, impaired phagocytic function to abnormal gene expression. Moreover, in T1D, metabolic dysregulation could impair DC functions as well. Indeed, since T1D clinical course is likely to be more aggressive in children and adolescents and entails severe dysglycemia, the aim of this study was to analyze circulating DCs subpopulations in pediatric T1D at different stages, as well as to characterize their phagocytosis ability and tolerance induction potential. Thus, pediatric patients newly diagnosed with T1D, with established disease and control subjects were recruited. Firstly, DCs subsets from peripheral blood were found quantitatively altered during the first year of disease, but recovered in the second year of progression. Secondly, to study the tolerogenic functionality of DCs, liposomes with phosphatidylserine (PS) were designed to mimic apoptotic beta cells, which are able to induce tolerance, as previously demonstrated by our group in DCs from adult patients with T1D. In this study, monocyte-derived DCs from pediatric patients with T1D and control subjects were assessed in terms of PS-liposomes capture kinetics, and transcriptional and phenotypic changes. DCs from pediatric patients with T1D were found to phagocyte PS-liposomes more slowly and less efficiently than DCs from control subjects, inversely correlating with disease evolution. Nonetheless, the transcription of PS receptors and immunoregulatory genes, cytokine profile, and membrane expression of immunological markers in DCs was consistent with tolerogenic potential after PS-liposomes phagocytosis. In conclusion, T1D progression in childhood entails altered peripheral blood DCs subsets, as well as impaired DCs phagocytosis, although tolerance induction could still function optimally. Therefore, this study provides useful data for patient follow-up and stratification in immunotherapy clinical trials

Impact of Betamethasone Pretreatment on Engrafment of Cord Blood-Derived Hematopoietic Stem Cells

Hematopoietic stem cell (HSC) transplantation is crucial to cure hematologic malignancies. Umbilical cord blood (UCB) is a source of stem cells, but 90% of UCB units are discarded due to low cellularity. Improving the engraftment capacities of CD34 + stem cells would allow the use of UCB that were so far rejected. Betamethasone induces long-term transcriptomic and epigenomic changes in immune cells through glucocorticoid receptor. We hypothesize that discarded UCB could be used owing to improvements induced by betamethasone. Isolated CD34 + HSC from UCB were exposed to the synthetic glucocorticoids betamethasone and fluticasone for 20 h, and cell phenotype was determined before transplantation. NSG mice were sub-lethally irradiated (1 Gy or 2 Gy) 6 h before intravenously transferring 2-5 × 10 5 CD34 + HSC. The peripheral blood engraftment levels and the leukocyte subsets were followed up for 20 weeks using flow cytometry. At end point, the engraftment and leukocyte subsets were determined in the spleen and bone marrow. We demonstrated that betamethasone has surprising effects in recovering immune system homeostasis. Betamethasone and fluticasone increase CXCR4 and decrease HLA class II and CD54 expression in CD34 + HSCs. Both glucocorticoids-exposed cells showed a similar engraftment in 2 Gy-irradiated NSG mice. Interestingly, betamethasone-exposed cells showed enhanced engraftment in 1 Gy-irradiated NSG mice, with a trend to increase regulatory T cell percentage when compared to control. Betamethasone induces alterations in CD34 + HSCs and improve the engraftment, leading to a faster immune system recovery, which will contribute to engrafted cells survival

Increased plasma neurofilament light chain levels in patients with type-1 diabetes with impaired awareness of hypoglycemia

Altres ajuts: This work was financially supported by a grant from the SPANISH DIABETES SOCIETY.Impaired awareness of hypoglycemia (IAH) is a common complication in patients with type-1 diabetes (T1D). IAH is a major risk factor for severe hypoglycemic events, leading to adverse clinical consequences and cerebral damage. Non-invasive, cost-effective, and logistically efficient biomarkers for this condition have not been validated. Here, we propose plasma neurofilament light chain (NfL) levels as a biomarker of neuroaxonal damage in patients with T1D-IAH. 54 patients were included into the study (18 T1D-IAH, 18 T1D with normal awareness of hypoglycemia (NAH) and 18 healthy controls). We measured plasma NfL levels and studied cerebral gray matter alterations on MRI. We found that NfL levels were increased in patients with T1D-IAH compared with patients with T1D-NAH and healthy controls. Importantly, increased NfL levels correlated with reduced cerebral gray matter volume and increased IAH severity in patients with T1D-IAH. Overall, our findings identify plasma NfL levels as a potential biomarker of cerebral damage in this population, motivating further confirmatory studies with potential implications in clinical trials

NK Cell Subsets Changes in Partial Remission and Early Stages of Pediatric Type 1 Diabetes

Type 1 diabetes (T1D) is a chronic metabolic disease characterized by the autoimmune destruction of β-cells in the pancreatic islets. T1D is preceded by islet-specific inflammation led by several immune cells. Among them, natural killer (NK) cells are emerging as important players in T1D development. Human NK cells are characterized by CD56 and CD16 expression, which allows classifying NK cells into four subsets: 1) CD56 dim CD16 + or effector NK cells (NK); 2) CD56 bright CD16 − or regulatory NK cells (NK); 3) intermediate CD56 bright CD16 + NK cells; and 4) CD56 dim CD16 − NK cells, whose function is not well determined. Since many studies have shown that T1D progression is associated with changes in various immune cell types, we hypothesize that the kinetics of NK cell subsets in the blood could correlate with different stages of T1D. To that aim, pediatric patients newly diagnosed with T1D were recruited, and peripheral NK cell subsets were analyzed by flow cytometry at several disease checkpoints: disease onset, partial remission (PR), 8 months (for non-remitters), and 12 months of progression. Our results showed that total NK cells and their four subsets are altered at the early stages of T1D. A decrease in the counts and percentage of total NK cells and NK cells at the different disease stages was found when compared to controls. These results suggest the extravasation of these cells into the islets at disease onset, which is maintained throughout the follow-up. By contrast, NK cells increased during the early stages after T1D onset, and both intermediate NK cells and CD56 dim CD16 - NK cells diminished at the PR stage, which might reflect the immunoregulatory attempts and could be candidate biomarkers for this stage. Also, CD56 dim CD16 - NK cells increased during T1D progression. Finally, changes in CD16 expression were identified in the different T1D stages, highlighting a CD16 expression reduction in total NK cells and NK cells 1 year after diagnosis. That may reflect a state of exhaustion after multiple cell-to-cell interactions. Altogether, our preliminary data provide a longitudinal picture of peripheral NK cell subpopulations during the different T1D stages, which could be potential candidate biomarkers indicators of disease progression

Prediction and Monitoring of Partial Remission in Pediatric Type 1 Diabetes

[EN] The partial remission (PR) phase, a period experienced by most patients with type 1 diabetes (T1D) soon after diagnosis, is characterized by low insulin requirements and improved glycemic control. Given the great potential of this phase as a therapeutic window for immunotherapies because of its association with immunoregulatory mechanisms and beta-cell protection, our objective was to find peripheral immunological biomarkers for its better characterization, monitoring, and prediction. The longitudinal follow-up of 17 pediatric patients with new-onset T1D over one year revealed that, during the PR phase, remitter patients show increased percentages of effector memory (EM) T lymphocytes, terminally differentiated EM T lymphocytes, and neutrophils in comparison to non-remitter patients. On the contrary, remitter patients showed lower percentages of naive T lymphocytes, regulatory T cells (T-REG), and dendritic cells (DCs). After a year of follow-up, these patients also presented increased levels of regulatory B cells and transitional T1 B lymphocytes. On the other hand, although none of the analyzed cytokines (IL-2, IL-6, TGF-beta 1, IL-17A, and IL-10) could distinguish or predict remission, IL-17A was increased at T1D diagnosis in comparison to control subjects, and remitter patients tended to maintain lower levels of this cytokine than non-remitters. Therefore, these potential monitoring immunological biomarkers of PR support that this stage is governed by both metabolic and immunological factors and suggest immunoregulatory attempts during this phase. Furthermore, since the percentage of T-REG, monocytes, and DCs, and the total daily insulin dose at diagnosis were found to be predictors of the PR phase, we next created an index-based predictive model comprising those immune cell percentages that could potentially predict remission at T1D onset. Although our preliminary study needs further validation, these candidate biomarkers could be useful for the immunological characterization of the PR phase, the stratification of patients with better disease prognosis, and a more personalized therapeutic management.Funding for this study was provided by the Spanish Government (FIS PI18/00436) co-financed with the European Regional Development funds (FEDER), and by DiabetesCero Foundation. LGM is supported by the Generalitat de Catalunya (PERIS PIF-Salut Grant No. SLT017/20/000049). This work has been supported by positive discussion through Consolidated Research Group #2017 SGR 103, AGAUR, Generalitat de Catalunya

Carcinoma de paladar blando. Descripción de una serie de casos

Introduction and objective: To describe clinical and anatomical features, and surgical treatment including several techniques of reconstructive surgery of soft palate carci-nomas. Description: We conducted a retrospective study with 5 patients. All of them were diagnosed and treated in our department during 2018 and 2019. Discussion: We present our results and make a review on soft palate tumors pointing out anatomical details and most employed reconstructive surgical techniques for soft palate carci-noma´s removal. Conclusions: The incidence of oropharyngeal carcinoma is increas-ing world-wide essentially due to increasing prevalence of human papillomavirus. Soft palate carcinomas are typically HPV negative. Initially, soft palate tumors are silent, and we should suspect them to avoid late diagnosis. Transoral surgery devel-opment has promoted surgical treatment in these tumors and allows better manage-ment and need for adjuvant therapy. Reconstruction is mandatory when resection is over 50% of the soft palate.Introducción y objetivo: Describir las características clínicas, anatómicas y el trata-miento quirúrgico, incluyendo las distintas opciones de reconstrucción de los tumo-res de paladar blando. Descripción: Estudio retrospectivo de 6 pacientes diagnosti-cados y tratados en el servicio de Otorrinolaringología del hospital San Pedro de Logroño entre los años 2018 y 2019. Discusión: Exponemos los resultados de nues-tros pacientes y realizamos una revisión de los tumores de orofaringe localizados en el paladar blando, los detalles anatómicos y técnicas quirúrgicas reconstructivas más utilizadas en el tratamiento quirúrgico de los tumores de paladar blando. Conclusio-nes: La prevalencia de los tumores de orofaringe ha aumentado en los últimos años a expensas de la infección por el virus del papiloma humano (VPH). Sin embargo, los carcinomas de paladar blando son mayoritariamente P16 negativos. Estos tumores son poco sintomáticos en fases iniciales y es necesario un alto índice de sospecha para evitar diagnósticos tardíos. El desarrollo de la cirugía transoral ha impulsado el tratamiento quirúrgico de los tumores de paladar blando y puede reducir la necesidad de tratamientos complementarios hasta en un 40% de los casos. La reconstrucción se hace necesaria en resecciones mayores del 50%

Immunoregulatory Biomarkers of the Remission Phase in Type 1 Diabetes : miR-30d-5p Modulates PD-1 Expression and Regulatory T Cell Expansion

The partial remission (PR) phase of type 1 diabetes (T1D) is an underexplored period characterized by endogenous insulin production and downmodulated autoimmunity. To comprehend the mechanisms behind this transitory phase and develop precision medicine strategies, biomarker discovery and patient stratification are unmet needs. MicroRNAs (miRNAs) are small RNA molecules that negatively regulate gene expression and modulate several biological processes, functioning as biomarkers for many diseases. Here, we identify and validate a unique miRNA signature during PR in pediatric patients with T1D by employing small RNA sequencing and RT-qPCR. These miRNAs were mainly related to the immune system, metabolism, stress, and apoptosis pathways. The implication in autoimmunity of the most dysregulated miRNA, miR-30d-5p, was evaluated in vivo in the non-obese diabetic mouse. MiR-30d-5p inhibition resulted in increased regulatory T cell percentages in the pancreatic lymph nodes together with a higher expression of CD200. In the spleen, a decrease in PD-1 + T lymphocytes and reduced PDCD1 expression were observed. Moreover, miR-30d-5p inhibition led to an increased islet leukocytic infiltrate and changes in both effector and memory T lymphocytes. In conclusion, the miRNA signature found during PR shows new putative biomarkers and highlights the immunomodulatory role of miR-30d-5p, elucidating the processes driving this phase

Resistance to taxanes in triple negative breast cancer associates with the dynamics of a CD49f+ tumor initiating population

Taxanes are a mainstay of treatment for breast cancer, but resistance often develops followed by metastatic disease and mortality. Aiming to reveal the mechanisms underlying taxane resistance, we used breast cancer patient-derived orthoxenografts (PDX). Mimicking clinical behavior, triple-negative breast tumors (TNBCs) from PDX models were more sensitive to docetaxel than luminal tumors, but they progressively acquired resistance upon continuous drug administration. Mechanistically, we found that a CD49f+ chemoresistant population with tumor-initiating ability is present in sensitive tumors and expands during the acquisition of drug resistance. In the absence of the drug, the resistant CD49f+ population shrinks and taxane sensitivity is restored. We describe a transcriptional signature of resistance, predictive of recurrent disease after chemotherapy in TNBC. Together, these findings identify a CD49f+ population enriched in tumor-initiating ability and chemoresistance properties and evidence a drug holiday effect on the acquired resistance to docetaxel in triple-negative breast cancer