Immunopathology of Kidney Transplantation

Renal transplantation is currently the best alternative for patients with end-stage renal disease. Immune responses activated against the allograft are a decisive factor in transplantation outcomes and patient survival. Although short-term graft and patient survival have improved significantly as a result of better donor matching systems, novel immunosuppressive agents and enhanced care, long-term outcomes remain unfavorable and reflect sub-clinical injury caused by chronic rejection. The immune system lies at the intersection of immunogenic tolerance and graft failure; thus, it is a major determinant of pathology in the context of renal transplantation. During the early stages of transplantation increased expression of cytokines has been observed in addition to increased expression of adhesion proteins and immune cells. This early inflammatory response does not necessarily end in graft rejection, although this will depend on the severity of the inflammation. Activation of Toll-like Receptors (TLRs), damaging molecular patterns (DAMPs), and other components of innate immunity is key to the formation of atherosclerotic plaques and the development of autoimmune diseases. Initially the donor antigens are presented to the T lymphocytes of the recipient. This activation induces their proliferation, differentiation and cytokine production. Successful kidney transplant recipients need to develop immunologic tolerance against donor antigens. In this chapter, we address some of the innate and adaptive immune mechanisms associated with kidney transplantation; emphasizing their role in allograft rejection

Advanced hydrogels for treatment of diabetes

Diabetes mellitus is a chronic disease characterized by high levels of glucose in the blood, which leads to metabolic disorders with severe consequences. Today, there is no cure for diabetes. The current management for diabetes and derived medical conditions, such as hyperglycemia, cardiovascular diseases or diabetic foot ulcer, includes life style changes and hypoglycemia based therapy, which do not fully restore euglycemia or the functionality of damaged tissues in patients. This encourages scientists to work outside their boundaries to develop routes that can potentially tackle such metabolic disorders. In this regard, acellular and cellular approaches have represented an alternative for diabetics, although such treatments still face shortcomings related to limited effectiveness and immunogenicity. The advent of biomaterials has brought significant improvements for such approaches, and three-dimensional extracellular matrix analogous, such as hydrogels, have played a key role in this regard. Advanced hydrogels are being developed to monitor high blood glucose levels and release insulin, as well as serve as a therapeutic technology. Herein, the state of the art in advanced hydrogels for improving treatment of diabetes, from laboratory technology to commercial products approved by drug safety regulatory authorities, will be concisely summarized and discussed. [Abstract copyright: This article is protected by copyright. All rights reserved.

A Mathematical Model to Optimize the Neoadjuvant Chemotherapy Treatment Sequence for Triple-Negative Locally Advanced Breast Cancer

Background: Triple-negative locally advanced breast cancer is an aggressive tumor type. Currently, the standard sequence treatment is applied, administering anthracyclines first and then a taxane plus platinum. Clinical studies for all possible treatment combinations are not practical or affordable, but mathematical modeling of the active mitotic cell population is possible. Our study aims to show the regions with the tumor’s most substantial cellular population variation by utilizing all possible values of the parameters () that define the annihilatory drug capacity according to the proposed treatment. Method: A piecewise linear mathematical model was used to analyze the cell population growth by applying four treatments: standard sequences of 21 days (SS21) and 14 days (SS14), administering anthracyclines first, followed by a taxane plus platinum, and inverted sequences of 21 days (IS21) and 14 days (IS14), administering a taxane plus platinum first then anthracyclines. Results: The simulation showed a higher effect of IS14 over SS14 when the rate of drug resistance was larger in the cell population during DNA synthesis (G1 and S) compared to cells in mitosis (G2 and M). However, if the proportion of resistant cells in both populations was equivalent, then treatments did not differ. Conclusions: When resistance is considerable, IS14 is more efficient than SS14, reducing the tumor population to a minimum

Regulation of cell death receptor S-nitrosylation and apoptotic signaling by Sorafenib in hepatoblastoma cells

Nitric oxide (NO) plays a relevant role during cell death regulation in tumor cells. The overexpression of nitric oxide synthase type III (NOS-3) induces oxidative and nitrosative stress, p53 and cell death receptor expression and apoptosis in hepatoblastoma cells. S-nitrosylation of cell death receptor modulates apoptosis. Sorafenib is the unique recommended molecular-targeted drug for the treatment of patients with advanced hepatocellular carcinoma. The present study was addressed to elucidate the potential role of NO during Sorafenib-induced cell death in HepG2 cells. We determined the intra- and extracellular NO concentration, cell death receptor expression and their S-nitrosylation modifications, and apoptotic signaling in Sorafenib-treated HepG2 cells. The effect of NO donors on above parameters has also been determined. Sorafenib induced apoptosis in HepG2 cells. However, low concentration of the drug (10nM) increased cell death receptor expression, as well as caspase-8 and -9 activation, but without activation of downstream apoptotic markers. In contrast, Sorafenib (10 µM) reduced upstream apoptotic parameters but increased caspase-3 activation and DNA fragmentation in HepG2 cells. The shift of cell death signaling pathway was associated with a reduction of S-nitrosylation of cell death receptors in Sorafenib-treated cells. The administration of NO donors increased S-nitrosylation of cell death receptors and overall induction of cell death markers in control and Sorafenib-treated cells. In conclusion, Sorafenib induced alteration of cell death receptor S-nitrosylation status which may have a relevant repercussion on cell death signaling in hepatoblastoma cells.Instituto de Salud Carlos III PI13/00021Ministerio de Economía y Competitividad BFU2012-32056Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía BIO-0216Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía CTS-6264Consejería de Salud, Junta de Andalucía PI13/ 0002

A Lower Baseline CD4/CD8 T-Cell Ratio Is Independently Associated with Immunodiscordant Response to Antiretroviral Therapy in HIV-Infected Subjects

We explored if baseline CD4/CD8 T-cell ratio is associated with immunodiscordant response to antiretroviral therapy in HIV-infected subjects. Comparing immunodiscordant and immunoconcordant subjects matched by pretreatment CD4 counts, we observed a lower pretreatment CD4/CD8 T-cell ratio in immunodiscordant subjects. Furthermore, pretreatment CD4/CD8 T-cell ratio, but not CD4 counts, correlated with the main immunological alterations observed in immunodiscordants, including increased regulatory T-cell (Treg) frequency and T-cell turnover-related markers. Then, in a larger cohort, only baseline CD4/CD8 T-cell ratio was independently associated with immunodiscordance, after adjusting by the viral CXCR4-tropic HIV variants. Our results suggest that the CD4/CD8 T-cell ratio could be an accurate biomarker of the subjacent immunological damage triggering immunodiscordance.The HIV BioBank, integrated in the Spanish AIDS Research Network, is supported by Instituto de Salud Carlos III, Spanish Health Ministry (grants RD06/0006/0035 and RD12/0017/0037), as part of the Plan Nacional R + D + I and cofinanced by ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) and Fundación para la investigación y prevención del SIDA en España (FIPSE). The RIS Cohort (CoRIS) is funded by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en SIDA by the RD12/0017/0018 project, as part of the Plan Nacional R + D + I, and cofinanced by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER). The project number is RIS_EPICLIN 20/2015. This work was supported by grants from the Fondo de Investigación Sanitaria, ISCIII (FIS; PI14/01693), and the Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (Proyecto de Investigación de Excelencia; CTS2593), and cofunded by Fondos Europeos para el Desarrollo Regional (FEDER). I. Rosado-Sánchez was supported by the Spanish AIDS Research Network of Excellence (RIS; RD12/0017/0029). Y. M. Pacheco was supported by the Fondo de Investigación Sanitaria through the Miguel Servet program (CPII13/00037) and by the Servicio Andaluz de Salud through the Nicolás Monardes program (C-0010/13).Peer reviewe

International conference on the healthy effect of virgin olive oil

Ageing represents a great concern in developed countries because the number of people involved and the pathologies related with it, like atherosclerosis, morbus Parkinson, Alzheime's disease, vascular dementia, cognitive decline, diabetes and cancer. Epidemiological studies suggest that a Mediterranean diet (which is rich in virgin olive oil) decreases the risk of cardiovascular disease. The Mediterranean diet, rich in virgin olive oil, improves the major risk factors for cardiovascular disease, such as the lipoprotein profile, blood pressure, glucose metabolism and antithrombotic profile. Endothelial function, inflammation and oxidative stress are also positively modulated. Some of these effects are attributed to minor components of virgin olive oil. Therefore, the definition of the Mediterranean diet should include virgin olive oil. Different observational studies conducted in humans have shown that the intake of monounsaturated fat may be protective against age-related cognitive decline and Alzheimer's disease. Microconstituents from virgin olive oil are bioavailable in humans and have shown antioxidant properties and capacity to improve endothelial function. Furthermore they are also able to modify the haemostasis, showing antithrombotic properties. In countries where the populations fulfilled a typical Mediterranean diet, such as Spain, Greece and Italy, where virgin olive oil is the principal source of fat, cancer incidence rates are lower than in northern European countries. The protective effect of virgin olive oil can be most important in the first decades of life, which suggests that the dietetic benefit of virgin olive oil intake should be initiated before puberty, and maintained through life. The more recent studies consistently support that the Mediterranean diet, based in virgin olive oil, is compatible with a healthier ageing and increased longevity. However, despite the significant advances of the recent years, the final proof about the specific mechanisms and contributing role of the different components of virgin olive oil to its beneficial effects requires further investigations. © 2005 Blackwell Publishing Ltd

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Experiencias de aprendizaje

Libro de experiencias de aprendizaje del grupo de investigación Giteca y de los semilleros de investigación en la que se visualizan las diferentes experiencias lideradas por instructores y aprendices en las diferentes áreas y líneas de formación.Book of learning experiences of the Giteca research group and the research hotbeds in which the different experiences led by instructors and apprentices in the different areas and lines of training are visualized.Propagación in vitro como un camino de aprendizaje para la formación profesional integral -- Experiencias significativas de aprendizaje, laboratorio de hematología y parasitología animal del Complejo Tecnológico para la Gestión Agroempresarial CTPGA-SENA -- Experiencias significativas adquiridas por aprendices en el área de SENNOVA, Complejo Tecnológico para la Gestión Agroempresarial. Regional – Antioquia -- El papel de la prensa escrita en el desarrollo de la competencia textual -- Aprendiendo a Emprender con un emprendedor -- Ven y te cuento sobre ADSI -- Observaciones fenológicas del cultivo de cacao (Theobroma cacao) en los municipios de Tarazá, El Bagre y Caucasia dentro de la formación del programa SENA emprende rural -- Tejiendo sueños desde la formación -- Forraje verde hidropónico como alternativa para disminuir la expansión de la frontera agrícola en el Putumayo -- La importancia del saber hacer para ser competente en el sector agrícola -- Experiencia significativa de aprendizaje semilleros de investigación -- La investigación como ente transformador de pensamientos -- Piscícola Paraguay; Mi Sueño, Mi Proyecto de Vida! -- Estrategia de aprendizaje a través de la investigación y la empresa aplicando un programa de Responsabilidad Social Empresarial –RSE -- Matemática aplicada para procesos agroindustriales de panificaciónna85 página

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research