Enhancing dendritic cell immunotherapy for melanoma using a simple mathematical model

ABSTRACT Background: The immunotherapy using dendritic cells (DCs) against different varieties of cancer is an approach that has been previously explored which induces a specific immune response. This work presents a mathematical model of DCs immunotherapy for melanoma in mice based on work by Experimental Immunotherapy Laboratory of the Medicine Faculty in the Universidad Autonoma de Mexico (UNAM). Method: The model is a five delay differential equation (DDEs) which represents a simplified view of the immunotherapy mechanisms. The mathematical model takes into account the interactions between tumor cells, dendritic cells, naive cytotoxic T lymphocytes cells (inactivated cytotoxic cells), effector cells (cytotoxic T activated cytotoxic cells) and transforming growth factor β cytokine (TGF − β). The model is validated comparing the computer simulation results with biological trial results of the immunotherapy developed by the research group of UNAM. Results: The results of the growth of tumor cells obtained by the control immunotherapy simulation show a similar amount of tumor cell population than the biological data of the control immunotherapy. Moreover, comparing the increase of tumor cells obtained from the immunotherapy simulation and the biological data of the immunotherapy applied by the UNAM researchers obtained errors of approximately 10 %. This allowed us to use the model as a framework to test hypothetical treatments. The numerical simulations suggest that by using more doses of DCs and changing the infusion time, the tumor growth decays compared with the current immunotherapy. In addition, a local sensitivity analysis is performed; the results show that the delay in time “τ ”, the maximal growth rate of tumor “r” and the maximal efficiency of tumor cytotoxic cells rate “aT” are the most sensitive model parameters. Conclusion: By using this mathematical model it is possible to simulate the growth of the tumor cells with or without immunotherapy using the infusion protocol of the UNAM researchers, to obtain a good approximation of the biological trials data. It is worth mentioning that by manipulating the different parameters of the model the effectiveness of the immunotherapy may increase. This last suggests that different protocols could be implemented by the Immunotherapy Laboratory of UNAM in order to improve their results

Retrospective cohort analysis of Spanish national trends of coronary artery bypass grafting and percutaneous coronary intervention from 1998 to 2017

Introduction Spain is one of the countries with the lowest rates of revascularisation and highest ratio of percutaneous coronary intervention (PCI) to coronary artery bypass grafting (CABG). Objectives To investigate the changes and trends in the two revascularisation procedures between 1998 and 2017 in Spain. Design Retrospective cohort study. Analysis of in-hospital outcomes. Setting Minimum basic data set from the Spanish National Department of Health: mandatory database collecting information of patients who are attended in the Spanish public National Health System. Participants 603 976 patients who underwent isolated CABG or PCI in the Spanish National Health System. The study period was divided in four 5-year intervals. Patients with acute myocardial infarction on admission were excluded. Primary and secondary outcomes We investigated the volume of procedures nationwide, the changes of the risk profile of patients and in-hospital mortality of both techniques. Results We observed a 2.2-fold increase in the rate of any type of myocardial revascularisation per million inhabitants-year: 357 (1998) to 776 (2017). 93 682 (15.5%) had a coronary surgery. PCI to CABG ratio rose from 2.2 (1998-2002) to 8.1 (2013-2017). Charlson's index increased by 0.8 for CABG and 1 for PCI. The median annual volume of PCI/hospital augmented from 136 to 232, while the volume of CABG was reduced from 137 to 74. In the two decades, we detected a significant reduction of CABG in-hospital mortality (6.5% vs 2.6%, p<0.001) and a small increase in PCI (1.2% vs 1.5%, p<0.001). Risk adjusted mortality rate was reduced for both CABG (1.51 vs 0.48, p<0.001), and PCI (1.42 vs 1.05, p<0.001). Conclusion We detected a significant increase in the volume of revascularisations (particularly PCI) in Spain. Risk-adjusted in-hospital mortality was significantly reduce

Influencia de la radiación láser de CO2 en las propiedades mecánicas de pastas de cemento portland

This article presents the results of the treatment of fresh cement pastes with CO2 laser radiation (10.6μm), in order to improve its mechanical properties in addition to obtaining lower setting times than those of a natural setting (without radiation .) It was observed that the CO2 laser radiation has a positive influence on the mechanical properties of cement paste, not due to the heat produced during irradiation, but due to the effect of electric field propagation on water molecules, whose are arranged around functional groups of the binder and by the effect of ration, causes a micro vibration effect, resulting in a more compact and less porous paste which has better mechanical properties compared to natural setting paste. The internal and surface temperature of the samples, the evolution of setting, Young's modulus (using ultrasonic pulse velocity) and compressive strength were registered.En este artículo se presentan los resultados correspondientes al tratamiento de pastas frescas de cemento con radiación láser de CO2 (10.6µm), con el propósito de mejorar sus propiedades mecánicas además de obtener tiempos de fraguado menores a los del fraguado en forma natural (sin radiación). Se demostró que la radiación con láser de CO2 influye positivamente en las propiedades mecánicas de la pasta de cemento, no por el calentamiento producido durante la irradiación, sino por el efecto de la propagación del campo eléctrico sobre las moléculas de agua que están dispuestas alrededor de los grupos funcionales del aglutinante y que al rotar producen un efecto equivalente a micro vibraciones, dando como resultado un material más compacto, con menos poros y mejores propiedades mecánicas respecto al fraguado natural. Se registró la temperatura interna y superficial de las muestras, la evolución del fraguado, el módulo de Young y la resistencia a compresión

Synaptic Origins of the Complex Receptive Field Structure in Primate Smooth Monostratified Retinal Ganglion Cells

Considerable progress has been made in studying the receptive fields of the most common primate retinal ganglion cell (RGC) types, such as parasol RGCs. Much less is known about the rarer primate RGC types and the circuitry that gives rise to noncanonical receptive field structures. The goal of this study was to analyze synaptic inputs to smooth monostratified RGCs to determine the origins of their complex spatial receptive fields, which contain isolated regions of high sensitivity called hotspots. Interestingly, smooth monostratified RGCs co-stratify with the well-studied parasol RGCs and are thus constrained to receiving input from bipolar and amacrine cells with processes sharing the same layer, raising the question of how their functional differences originate. Through 3D reconstructions of circuitry and synapses onto ON smooth monostratified and ON parasol RGCs from central macaque retina, we identified four distinct sampling strategies employed by smooth and parasol RGCs to extract diverse response properties from co-stratifying bipolar and amacrine cells. The two RGC types differed in the proportion of amacrine cell input, relative contributions of co-stratifying bipolar cell types, amount of synaptic input per bipolar cell, and spatial distribution of bipolar cell synapses. Our results indicate that the smooth RGC\u27s complex receptive field structure arises through spatial asymmetries in excitatory bipolar cell input which formed several discrete clusters comparable with physiologically measured hotspots. Taken together, our results demonstrate how the striking differences between ON parasol and ON smooth monostratified RGCs arise from distinct strategies for sampling a common set of synaptic inputs

Age-associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade

Age-associated B cells (ABC) accumulate with age and in individuals with different immunological disorders, including cancer patients treated with immune checkpoint blockade and those with inborn errors of immunity. Here, we investigate whether ABCs from different conditions are similar and how they impact the longitudinal level of the COVID-19 vaccine response. Single-cell RNA sequencing indicates that ABCs with distinct aetiologies have common transcriptional profiles and can be categorised according to their expression of immune genes, such as the autoimmune regulator (AIRE). Furthermore, higher baseline ABC frequency correlates with decreased levels of antigen-specific memory B cells and reduced neutralising capacity against SARS-CoV-2. ABCs express high levels of the inhibitory FcγRIIB receptor and are distinctive in their ability to bind immune complexes, which could contribute to diminish vaccine responses either directly, or indirectly via enhanced clearance of immune complexed-antigen. Expansion of ABCs may, therefore, serve as a biomarker identifying individuals at risk of suboptimal responses to vaccination

Cells from discarded dressings differentiate chronic from acute wounds in patients with Epidermolysis Bullosa

Impaired wound healing complicates a wide range of diseases and represents a major cost to healthcare systems. Here we describe the use of discarded wound dressings as a novel, cost effective, accessible, and non-invasive method of isolating viable human cells present at the site of skin wounds. By analyzing 133 discarded wound dressings from 51 patients with the inherited skin-blistering disease epidermolysis bullosa (EB), we show that large numbers of cells, often in excess of 100 million per day, continually infiltrate wound dressings. We show, that the method is able to differentiate chronic from acute wounds, identifying significant increases in granulocytes in chronic wounds, and we show that patients with the junctional form of EB have significantly more cells infiltrating their wounds compared with patients with recessive dystrophic EB. Finally, we identify subsets of granulocytes and T lymphocytes present in all wounds paving the way for single cell profiling of innate and adaptive immune cells with relevance to wound pathologies. In summary, our study delineates findings in EB that have potential relevance for all chronic wounds, and presents a method of cellular isolation that has wide reaching clinical application

A Prospective, Multicenter, Real-World Registry of Coronary Lithotripsy in Calcified Coronary Arteries

BACKGROUND Intravascular lithotripsy (IVL) has demonstrated effectiveness in the treatment of calcified lesions in selected patients with stable coronary disease. OBJECTIVES The authors sought to assess the performance of coronary IVL in calcified coronary lesions in a real-life, all comers, setting. METHODS The REPLICA-EPIC18 study prospectively enrolled consecutive patients treated with IVL in 26 centers in Spain. An independent core laboratory performed the angiographic analysis and event adjudication. The primary effectiveness endpoint assessed procedural success (successful IVL delivery, final diameter stenosis <20%, and absence of in- hospital major adverse cardiovascular events [MACE]). The primary safety endpoint measured freedom from MACE at 30 days. A predefined substudy compared outcomes between acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) patients. RESULTS A total of 426 patients (456 lesions) were included, 63% of the patients presenting with ACS. IVL delivery was successful in 99% of cases. Before IVL, 49% of lesions were considered undilatable. The primary effectiveness endpoint was achieved in 66% of patients, with similar rates among CCS patients (68%) and ACS patients (65%). Likewise, there were no significant differences in angiographic success after IVL between CCS and ACS patients. The rate of MACE at 30 days (primary safety endpoint) was 3% (1% in CCS and 5% in ACS patients [P = 0.073]). CONCLUSIONS Coronary IVL proved to be a feasible and safe procedure in a real-life setting, effectively facilitating stent implantation in severely calcified lesions. Patients with ACS on admission showed similar angiographic success rates but showed a trend toward higher 30-day MACE compared with patients with CCS. (REPLICA-EPIC18 study [Registry of Coronary Lithotripsy in Spain]; NCT04298307) (c) 2024 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)