Anthracycline-Related Cardiotoxicity in Patients with Acute Myeloid Leukemia and Down Syndrome: A Literature Review

Pediatric patients with Down syndrome (DS) are at an increased risk of developing certain cancers. Specifically, patients with DS have a reported 10–20-fold increased risk of developing acute myeloid leukemia (AML). Anthracycline-based treatment regimens achieve good results in patients with DS and AML. It has been proposed that DS status constitutes a risk factor for the cardiotoxicity associated with the use of anthracyclines in the pediatric setting. However, published evidence pointing toward an increased risk of cardiotoxicity in patients with DS is relatively scarce and conflictive. This concise review compiles literature relating to the incidence of anthracycline-related cardiotoxicity in pediatric patients with DS. In general, reports from trials using anthracyclines at the maximum recommended dose showed increases in the incidence of anthracycline-related cardiotoxicity in patients with DS in comparison with trials that used anthracyclines at reduced doses. Evidence from the literature suggests that patients with DS can achieve favorable therapeutic outcomes after receiving treatment with reduced doses of anthracyclines to minimize the potential for cardiotoxicity. Further prospective trials, along with the available evidence, would assist the design of treatment protocols for patients with pediatric leukemias and DS

Analysis of Heteroplasmic Variants in the Cardiac Mitochondrial Genome of Individuals with Down Syndrome

Individuals with Down syndrome (DS, trisomy 21) exhibit a pro-oxidative cellular environment as well as mitochondrial dysfunction. Increased oxidative stress may damage the mitochondrial DNA (mtDNA). The coexistence of mtDNA variants in a cell or tissue (i.e., heteroplasmy) may contribute to mitochondrial dysfunction. Given the evidence on mitochondrial dysfunction and the relatively high incidence of multiorganic disorders associated with DS, we hypothesized that cardiac tissue from subjects with DS may exhibit higher frequencies of mtDNA variants in comparison to cardiac tissue from donors without DS. This study documents the analysis of mtDNA variants in heart tissue samples from donors with (n = 12) and without DS (n = 33) using massively parallel sequencing. Contrary to the original hypothesis, the study’s findings suggest that the cardiac mitochondrial genomes from individuals with and without DS exhibit many similarities in terms of (1) total number of mtDNA variants per sample, (2) the frequency of mtDNA variants, (3) the type of mtDNA variants, and (4) the patterns of distribution of mtDNA variants. In both groups of samples, the mtDNA control region showed significantly more heteroplasmic variants in comparison to the number of variants in protein- and RNA-coding genes (P \u3c 1.00×10−4, ANOVA)

Characterization of coelacanth scales from the early cretaceous freshwater locality of las hoyas, upper Barremian (Cuenca, Spain)

Coelacanths are rare, mostly marine fishes, but the species from the Lower Cretaceous Spanish locality of Las Hoyas (Barremian) is a freshwater form and we know almost nothing about it. The Las Hoyas specimens are very rare and relatively incomplete, but there are still many things we can learn from the isolated skeletons and scales. First, the coelacanth scales were distinguished from other superficially similar scales (i.e., other “amioid” scales). Coelacanth scales are distinguished by the presence of a smooth central surface, a particular pattern of arrangement of concentric growth cessation marks, and mainly a relatively short posterior field with thick elongated ridges. Only a few articulated coelacanth specimens have been recovered from Las Hoyas to date, and only 7.3% (n = 11) of the total isolated scales are coelacanth. The Las Hoyas coelacanth scales represent relatively large individuals. This suggests that a natural population of the coelacanth may have not inhabited permanently the freshwater pool represented by the excavated area of Las Hoyas because small juveniles should be the most common sizesFunding for this project comes from a grant “Ayudas a la Investigación de la Sociedad Española de Paleontología, 2015-2016” provided to H.M.-A. This paper is a contribution to project CGL-2013-42643 P (MINECO, Spain

Geomorphological evolution of the calcareous coastal cliffs in North Iberia (Asturias and Cantabria regions)

This paper presents an analysis of the main morphologies observed in the coastal cliffs of northern Spain (Asturias and Cantabria regions). The objective of this contribution is to establish a hypothesis on the origin and evolution of this rocky coast, as well as to present a detailed inventory, to characterise quantitatively and qualitatively singular morphologies and to highlight the geological heritage of this protected coast. The evolution process starts with the formation of an ancient coastal planation surface characterised by a flat morphology caused by regional mainly uplift and to relative sea level falls. Afterwards, wave erosion processes would have started eroding the cliff foot and simultaneously, karst activity produced some exokarst morphologies (sinkholes, karren, etc.) through stratification and fracturing network, while the underground drainage systems produced some caves and chasms. In the following step, corresponding to the last glaciation from the paleoclimatic point of view, sea level fall together with a deepening of the fluvial network caused the preservation of the existing caves and chasms and the generation of new ones at a lower level. On the other hand, dissolution processes on limestones created sinkholes in those areas characterised by alternating layers of limestones and marls, generating collapses. When the sea level reached the maximum height during the Holocene a new erosion cycle of the coastal cliffs began. As a consequence, new landforms and processes were produced, like bays, caves fillings, and intrusion of new sediments in small confined estuaries. In these areas, other types of morphologies associated with the last sea level rise can be observed, such as closed beaches, uncommon closed estuaries developed inside a sinkhole, blowholes produced by mixed wave action and widening of prevailing vertical pipes inside the limestones (including the second largest in the world), total or partial sedimentary filling of small confined estuaries, as well as a tombolo deposit. It is important to point out, that some sites described are included in the Spanish Inventory of Sites of Geological Interest (IELIG). Due to the evolution model here proposed, a portion of the coastal sector described are included in the Global Geosites Project

Deep history of cultural and linguistic evolution among Central African hunter-gatherers

Human evolutionary history in Central Africa reflects a deep history of population connectivity. However, Central African hunter-gatherers (CAHGs) currently speak languages acquired from their neighbouring farmers. Hence it remains unclear which aspects of CAHG cultural diversity results from long-term evolution preceding agriculture and which reflect borrowing from farmers. On the basis of musical instruments, foraging tools, specialized vocabulary and genome-wide data from ten CAHG populations, we reveal evidence of large-scale cultural interconnectivity among CAHGs before and after the Bantu expansion. We also show that the distribution of hunter-gatherer musical instruments correlates with the oldest genomic segments in our sample predating farming. Music-related words are widely shared between western and eastern groups and likely precede the borrowing of Bantu languages. In contrast, subsistence tools are less frequently exchanged and may result from adaptation to local ecologies. We conclude that CAHG material culture and specialized lexicon reflect a long evolutionary history in Central Africa

The Multi-Chamber Electronic Nose—An Improved Olfaction Sensor for Mobile Robotics

One of the major disadvantages of the use of Metal Oxide Semiconductor (MOS) technology as a transducer for electronic gas sensing devices (e-noses) is the long recovery period needed after each gas exposure. This severely restricts its usage in applications where the gas concentrations may change rapidly, as in mobile robotic olfaction, where allowing for sensor recovery forces the robot to move at a very low speed, almost incompatible with any practical robot operation. This paper describes the design of a new e-nose which overcomes, to a great extent, such a limitation. The proposed e-nose, called Multi-Chamber Electronic Nose (MCE-nose), comprises several identical sets of MOS sensors accommodated in separate chambers (four in our current prototype), which alternate between sensing and recovery states, providing, as a whole, a device capable of sensing changes in chemical concentrations faster. The utility and performance of the MCE-nose in mobile robotic olfaction is shown through several experiments involving rapid sensing of gas concentration and mobile robot gas mapping

Peutz-Jeghers syndrome and duodeno-jejunal adenocarcinoma-therapeutic implications

The Peutz-Jeghers syndrome (PJS) is an autosomal dominant hamartomatous poliposis describred in 1921. Hemminki in 1997 described the presence of LKB-1 mutation tumor-suppressor gen.The patients with PJS develop a higher cumulative incidence of gastrointestinal, pancreas and extraintestinal tumors, being occasion of a renew interest on hamartomatous polyposis syndromes regarding the clinical care, cancer surveillance treatment and long term follow-up.We report the case of a 38 years old male, diagnosed of PJS who developed a multiple adenocarcinoma in duodenum and yeyunum. Surgically treated and with a long-term free disease survival of 11 years represents the sixth case reported in the spanish literature of PJS associated with a gastrointestinal tumor.A critical review, molecular alterations and the established criteria of tumor screening and surveillance are reviewed

Risk versus Benefit of Tyrosine Kinase Inhibitors for Hepatocellular Carcinoma: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

[EN]Although the treatment landscape has rapidly evolved over the last years, hepatocellular carcinoma (HCC) is one of the most lethal cancers. With recent advances, both immunotherapy and tyrosine kinase inhibitors (TKIs)-based chemotherapy constitute the standard treatment for advanced HCC. A systematic search of randomized clinical trials employing TKIs was performed in 17 databases, obtaining 25 studies evaluating the prognosis, tumor response, and presence of adverse events (AEs) related to TKIs in HCC. Overall effect sizes were estimated for the hazard ratios (HR) and odds ratios (OR) with 95% confidence interval (CI), either extracted or calculated with the Parmar method, employing STATA 16. Heterogeneity was assessed by Chi-square-based Q-test and inconsistency (I2) statistic; source of heterogeneity by meta-regression and subgroup analysis; and publication bias by funnel plot asymmetry and Egger's test. The research protocol was registered in PROSPERO (CRD42023397263). Meta-analysis revealed a correlation between survival and tumor response parameters and TKI treatment vs. placebo, despite detecting high heterogeneity. Combined TKI treatment showed a significantly better objective response rate (ORR) with no heterogeneity, whereas publication bias was only detected with time to progression (TTP). Few gastrointestinal and neurological disorders were associated with TKI treatment vs. placebo or with combined treatment. However, a higher number of serious AEs were related to TKI treatment vs. sorafenib alone. Results show positive clinical benefits from TKI treatment, supporting the approval and maintenance of TKI-based therapy for advanced HCC, while establishing appropriate strategies to maximize efficacy and minimize toxicity.SIPublicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCL

Intrapericardial Administration of Secretomes from Menstrual Blood-Derived Mesenchymal Stromal Cells: Effects on Immune-Related Genes in a Porcine Model of Myocardial Infarction.

Acute myocardial infarction (AMI) is a manifestation of ischemic heart disease where the immune system plays an important role in the re-establishment of homeostasis. We hypothesize that the anti-inflammatory activity of secretomes from menstrual blood-derived mesenchymal stromal cells (S-MenSCs) and IFNγ/TNFα-primed MenSCs (S-MenSCs*) may be considered a therapeutic option for the treatment of AMI. To assess this hypothesis, we have evaluated the effect of S-MenSCs and S-MenSCs* on cardiac function parameters and the involvement of immune-related genes using a porcine model of AMI. Twelve pigs were randomly divided into three biogroups: AMI/Placebo, AMI/S-MenSCs, and AMI/S-MenSCs*. AMI models were generated using a closed chest coronary occlusion-reperfusion procedure and, after 72 h, the different treatments were intrapericardially administered. Cardiac function parameters were monitored by magnetic resonance imaging before and 7 days post-therapy. Transcriptomic analyses in the infarcted tissue identified 571 transcripts associated with the Gene Ontology term Immune response, of which 57 were differentially expressed when different biogroups were compared. Moreover, a prediction of the interactions between differentially expressed genes (DEGs) and miRNAs from secretomes revealed that some DEGs in the infarction area, such as STAT3, IGFR1, or BCL6 could be targeted by previously identified miRNAs in secretomes from MenSCs. In conclusion, the intrapericardial administration of secretome early after infarction has a significant impact on the expression of immune-related genes in the infarcted myocardium. This confirms the immunomodulatory potential of intrapericardially delivered secretomes and opens new therapeutic perspectives in myocardial infarction treatment.This study was supported by competitive grants, such as: “PFIS” contract (FI19/00041) from the National Institute of Health Carlos III (ISCIII, 2019 Call Strategic Action in Health 2019) to M.Á.d.P.; Santander Bank “Convenio de colaboración empresarial en actividades de interés general” to F.M.; “Sara Borrell” grant (CD19/00048) from ISCIII to E.L.; grant “TE-0001-19” from Consejería de Educación y Empleo (co-funded by European Social Fund -ESF- “Investing in your future”), ayuda para el fomento de la contratación de personal de apoyo a la investigación en la Comunidad Autónoma de Extremadura to M.P. Costs for experimental development were funded by grant “CB16/11/00494” from CIBER-CV ISCIII, RD21/0017/0014 from ISCIII (co-funded by NextGenerationEU. Plan de Recuperación Transformación y Resiliencia) and Ayuda Grupos catalogados de la Junta de Extremadura (GR21201) from Junta de Extremadura, Consejería de Economía, Ciencia y Agenda Digital (co-funded by European Regional Development Fund—ERDF) to F.M.S.-M.; J.G.C. received fundings from the ISCIII through a “Miguel Servet I” grant (MS17/00021) co-funded by ERDF/ESF “A way to make Europe” “Investing in your future”, funding from the projects “CP17/00021” and “PI18/0911” (co-funded by ERDF/ESF), and by Junta de Extremadura. V.C. received fundings from ISCIII (grant number “PI16/01172” and “PI20/00247”). E.L. received fundings from Junta de Extremadura through a “IB20184” grant (co-funded by ERDF/ESF). The funders had no role in study designs, data collection and analysis, decision to publish, or preparation of the manuscript.S