El apoyo de la ciencia a los derechos de los niños: La identificación genética

La esclavitud infantil y la trata de seres humanos se van a convertir en breve plazo, según algunos expertos, en la actividad criminal más lucrativa del mundo, superando al tráfico de drogas o al de armas. Desde 1989, año en el que la Asamblea General de Naciones Unidas aprobó la “Convención de los Derechos del Niño”, encuadrada en la “Declaración Universal de los Derechos Humanos” de 1948, son muchas las instituciones que trabajan para evitar, o cuanto menos reducir, dicha situación, tan grave y extendida a nivel internacional. Dentro de los avances científicos, la identificación genética es una de las herramientas que más se han desarrollado en pos de tal objetivo. En este artículo se analizan desde un punto de vista científico y social los procedimientos metodológicos y herramientas que en la actualidad se utilizan en dichos procesos de identificación. También se describe a modo de ejemplo una de las iniciativas que se llevan a cabo en la práctica en España, la de DNA-PROKIDS para luchar contra el tráfico de seres humanos a través de las pruebas de ADN. A través de esta vía se dispone de un banco de muestras genéticas de niños y padres, mediante el cual se intenta dificultar las adopciones ilegales, la explotación laboral, sexual o el comercio de órgano

Efficacy and Security of Tetrodotoxin in the Treatment of Cancer-Related Pain: Systematic Review and Meta-Analysis

The pharmacological treatment of cancer-related pain is unsatisfactory. Tetrodotoxin (TTX) has shown analgesia in preclinical models and clinical trials, but its clinical efficacy and safety have not been quantified. For this reason, our aim was to perform a systematic review and meta-analysis of the clinical evidence that was available. A systematic literature search was conducted in four electronic databases (Medline, Web of Science, Scopus, and ClinicalTrials.gov) up to 1 March 2023 in order to identify published clinical studies evaluating the efficacy and security of TTX in patients with cancer-related pain, including chemotherapy-induced neuropathic pain. Five articles were selected, three of which were randomized controlled trials (RCTs). The number of responders to the primary outcome (≥30% improvement in the mean pain intensity) and those suffering adverse events in the intervention and placebo groups were used to calculate effect sizes using the log odds ratio. The meta-analysis showed that TTX significantly increased the number of responders (mean = 0.68; 95% CI: 0.19–1.16, p = 0.0065) and the number of patients suffering non-severe adverse events (mean = 1.13; 95% CI: 0.31–1.95, p = 0.0068). However, TTX did not increase the risk of suffering serious adverse events (mean = 0.75; 95% CI: −0.43–1.93, p = 0.2154). In conclusion, TTX showed robust analgesic efficacy but also increased the risk of suffering non-severe adverse events. These results should be confirmed in further clinical trials with higher numbers of patients.CTS-109 grant (Junta de Andalucía)FPU grant (FPU21/02736

Model-based active damping control for three-phase voltage source inverters with LCL filter

(c) 2016 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works.This paper presents a robust model-based active damping control in natural frame for a three-phase voltage source inverter with LCL filter. The presence of the LCL filter complicates the design of the control scheme, particularly when system parameters deviations are considered. The proposed control method is addressed to overcome such difficulties and uses a modified converter model in an state observer. In this proposal, the converter model is modified by introducing a virtual damping resistor. Then, a Kalman filter makes use of this model to estimate the system state-space variables. Although the state estimates do not obviously match the real world system variables, they permit designing three current sliding-mode controllers that provide the following features to the closed loop system: a) robust ande active damping capability like in the case of using a physical damping resistor, b) robustness because the control specifications are met independently of variation in the system parameters, c) noise immunity due to the application of the Kalman filter, and d) power loss minimization because the system losses caused by the physical damping resistor are avoided. An interesting side effect of the proposed control scheme is that the sliding surfaces for each controller are independent. This decoupling property for the three controllers allows using a fixed switching frequency algorithm that ensures perfect current control. To complete the control scheme, a theoretical stability analysis is developed. Finally, selected experimental results validate the proposed control strategy and permit illustrating all its appealing features.Peer ReviewedPostprint (author's final draft

Detección de Círculos Basada en la Orientación de Bordes y Triángulos Rectángulos

La Transformada de Hough para Círculos es el método estándar para la detección de círculos en imágenes. Debido a sus desventajas, varias modificaciones y nuevos algoritmos han sido sugeridos. En este trabajo se presenta un método eficaz de detección de círculos basado en la orientación de bordes y triángulos rectángulos dentro de un círculo. El método propuesto disminuye el requisito de almacenamiento y aumenta la velocidad para encontrar círculos en una imagen utilizando una técnica de segmentación y análisis entrelazado. Algunas imágenes sintéticas con diferentes niveles de ruido y algunas naturales se han utilizado para probar el rendimiento del método propuesto. Los resultados experimentales muestran que el método propuesto es más rápido y espacialmente más compacto que la Transformada de Hough para Círculos

177Lu-Dendrimer conjugated to folate and bombesin with gold nanoparticles in the dendritic cavity: A potential theranostic radiopharmaceutical

177Lu-labeled nanoparticles conjugated to biomolecules have been proposed as a new class of theranostic radiopharmaceuticals. The aim of this research was to synthesize 177Lu-dendrimer(PAMAM-G4)-folate-bombesin with gold nanoparticles (AuNPs) in the dendritic cavity and to evaluate the radiopharmaceutical potential for targeted radiotherapy and the simultaneous detection of folate receptors (FRs) and gastrin-releasing peptide receptors (GRPRs) overexpressed in breast cancer cells. p-SCN-Benzyl-DOTA was conjugated in aqueous-basic medium to the dendrimer.The carboxylate groups of Lys1Lys3(DOTA)-bombesin and folic acid were activatedwithHATUand also conjugated to the dendrimer.The conjugate was mixed with 1%HAuCl4 followed by the addition of NaBH4 and purified by ultrafiltration. Elemental analysis (EDS), particle size distribution (DLS), TEM analysis, UV-Vis, and infrared and fluorescence spectroscopies were performed. The conjugate was radiolabeled using 177LuCl3 or 68GaCl3 and analyzed by radio-HPLC. Studies confirmed the dendrimer functionalization with high radiochemical purity (>95%). Fluorescence results demonstrated that the presence ofAuNPs in the dendritic cavity confers useful photophysical properties to the radiopharmaceutical for optical imaging. Preliminary binding studies in T47D breast cancer cells showed a specific cell uptake (41.15 ± 2.72%). 177Ludendrimer( AuNP)-folate-bombesin may be useful as an optical and nuclear imaging agent for breast tumors overexpressing GRPR and FRs, as well as for targeted radiotherapy.CONACYT-SEP-CB-2014-01-242443 International Atomic Energy Agency (Grant 18358) LaboratorioNacional de Investigaci´on yDesarrollo de Radiof´armacos, CONACy

Trasplantes amigdalares embrionarios en ratas adultas con lesiones de la corteza motora: análisis molecular y electrofisiológico

Transplants of embryonic nervous tissue ameliorate motor deficits induced by motor cortex lesions in adult animals. Restoration of lost brain functions has been recently shown in grafts of homotopic cortical origin, to be associated with a functional integration of the transplant after development of reciprocal host-graft connections. Nevertheless little is known about physiological properties or gene expression profiles of cortical implants with functional restorative capacity but no cortical origin. In this study, we show molecular and electrophysiological evidence supporting the functional development and integration of heterotopic transplants of embryonic amygdalar tissue placed into pre-lesioned motor cortex of adult rats. Grafts were analyzed 3 months post-transplantation

Fluorescent, Plasmonic, and Radiotherapeutic Properties of the 177Lu–Dendrimer-AuNP–Folate–Bombesin Nanoprobe Located Inside Cancer Cells

The integration of fluorescence and plasmonic properties into one molecule is of importance in developing multifunctional imaging and therapy nanoprobes. The aim of this research was to evaluate the fluorescent properties and the plasmonic–photothermal, therapeutic, and radiotherapeutic potential of 177Lu–dendrimer conjugated to folate and bombesin with gold nanoparticles in the dendritic cavity (177Lu–DenAuNP–folate–bombesin) when it is internalized in T47D breast cancer cells. The intense near-Infrared (NIR) fluorescence emitted at 825 nm from the conjugate inside cells corroborated the usefulness of DenAuNP–folate–bombesin for optical imaging. After laser irradiation, the presence of the nanosystem in cells caused a significant increase in the temperature of the medium (46.8oC, compared to 39.1oC without DenAuNP–folate–bombesin, P < 0.05), resulting in a significant decrease in cell viability (down to 16.51% + 1.52%) due to the 177Lu–DenAuNP–folate–bombesin plasmonic properties. After treatment with 177Lu–DenAuNP–folate–bombesin, the T47D cell viability decreased 90% because of the radiation-absorbed dose (63.16 + 4.20 Gy) delivered inside the cells. The 177Lu–DenAuNP–folate–bombesin nanoprobe internalized in cancer cells exhibited properties suitable for optical imaging, plasmonic–photothermal therapy, and targeted radiotherapy.CONACYT-SEP-CB-2014-01-24244

Personalized Evaluation of Atrial Complexity of Patients Undergoing Atrial Fibrillation Ablation: A Clinical Computational Study

Current clinical guidelines establish Pulmonary Vein (PV) isolation as the indicated treatment for Atrial Fibrillation (AF). However, AF can also be triggered or sustained due to atrial drivers located elsewhere in the atria. We designed a new simulation workflow based on personalized computer simulations to characterize AF complexity of patients undergoing PV ablation, validated with non-invasive electrocardiographic imaging and evaluated at one year after ablation. We included 30 patients using atrial anatomies segmented from MRI and simulated an automata model for the electrical modelling, consisting of three states (resting, excited and refractory). In total, 100 different scenarios were simulated per anatomy varying rotor number and location. The 3 states were calibrated with Koivumaki action potential, entropy maps were obtained from the electrograms and compared with ECGi for each patient to analyze PV isolation outcome. The completion of the workflow indicated that successful AF ablation occurred in patients with rotors mainly located at the PV antrum, while unsuccessful procedures presented greater number of driving sites outside the PV area. The number of rotors attached to the PV was significantly higher in patients with favorable long-term ablation outcome (1-year freedom from AF: 1.61 ± 0.21 vs. AF recurrence: 1.40 ± 0.20; p-value = 0.018). The presented workflow could improve patient stratification for PV ablation by screening the complexity of the atria

Generation of NKX2.5(GFP) Reporter Human iPSCs and Differentiation Into Functional Cardiac Fibroblasts

Direct cardiac reprogramming has emerged as an interesting approach for the treatment and regeneration of damaged hearts through the direct conversion of fibroblasts into cardiomyocytes or cardiovascular progenitors. However, in studies with human cells, the lack of reporter fibroblasts has hindered the screening of factors and consequently, the development of robust direct cardiac reprogramming protocols.In this study, we have generated functional human NKX2.5(GFP) reporter cardiac fibroblasts. We first established a new NKX2.5(GFP) reporter human induced pluripotent stem cell (hiPSC) line using a CRISPR-Cas9-based knock-in approach in order to preserve function which could alter the biology of the cells. The reporter was found to faithfully track NKX2.5 expressing cells in differentiated NKX2.5(GFP) hiPSC and the potential of NKX2.5-GFP + cells to give rise to the expected cardiac lineages, including functional ventricular- and atrial-like cardiomyocytes, was demonstrated. Then NKX2.5(GFP) cardiac fibroblasts were obtained through directed differentiation, and these showed typical fibroblast-like morphology, a specific marker expression profile and, more importantly, functionality similar to patient-derived cardiac fibroblasts. The advantage of using this approach is that it offers an unlimited supply of cellular models for research in cardiac reprogramming, and since NKX2.5 is expressed not only in cardiomyocytes but also in cardiovascular precursors, the detection of both induced cell types would be possible. These reporter lines will be useful tools for human direct cardiac reprogramming research and progress in this field.This work was supported by PID 2019-107150RB-I00/AEI/ 10.13039/501100011033 to XC-V; by the “Ramón y Cajal” State Program, Ministry of Economy and Competitivenes

Principales medidas de profilaxis en endoscopia bariátrica. Guía Española de Recomendación de Expertos

Bariatric endoscopy (BE) encompasses a number of techniques -some consolidated, some under development- aiming to contribute to the management of obese patients and their associated metabolic diseases as a complement to dietary and lifestyle changes. To date different intragastric balloon models, suture systems, aspiration methods, substance injections and both gastric and duodenal malabsorptive devices have been developed, as well as endoscopic procedures for the revision of bariatric surgery. Their ongoing evolution conditions a gradual increase in the quantity and quality of scientific evidence about their effectiveness and safety. Despite this, scientific evidence remains inadequate to establish strong grades of recommendation allowing a unified perspective on prophylaxis in BE. This dearth of data conditions leads, in daily practice, to frequently extrapolate the measures that are used in bariatric surgery (BS) and/or in general therapeutic endoscopy. In this respect, this special article is intended to reach a consensus on the most common prophylactic measures we should apply in BE. The methodological design of this document was developed while attempting to comply with the following 5 phases: Phase 1: delimitation and scope of objectives, according to the GRADE Clinical Guidelines. Phase 2: setup of the Clinical Guide-developing Group: national experts, members of the Grupo Español de Endoscopia Bariátrica (GETTEMO, SEED), SEPD, and SECO, selecting 2 authors for each section. Phase 3: clinical question form (PICO): patients, intervention, comparison, outcomes. Phase 4: literature assessment and synthesis. Search for evidence and elaboration of recommendations. Based on the Oxford Centre for Evidence-Based Medicine classification, most evidence in this article will correspond to level 5 (expert opinions without explicit critical appraisal) and grade of recommendation C (favorable yet inconclusive recommendation) or D (inconclusive or inconsistent studies). Phase 5: External review by experts. We hope that these basic preventive measures will be of interest for daily practice, and may help prevent medical and/or legal conflicts for the benefit of patients, physicians, and BE in general