Optimization of Radiation Protection in Pediatric Interventional Radiology in Latin America and the Caribbean: Development, Advancements, Challenges and Achievements of the OPRIPALC Program.

This article presents the development, advancements, challenges and achievements of the "Optimization of Protection in Pediatric Interventional Radiology in Latin America and the Caribbean" (OPRIPALC) program. This international initiative is led by the World Health Organization, the Pan American Health Organization and the International Atomic Energy Agency. The main objectives of OPRIPALC are to foster a culture of radiological protection in pediatric interventions, enhance these procedures' quality, and define optimization strategies such as the use of diagnostic reference levels (DRLs). Currently, 33 centers from 12 countries participate actively in the program. Significant progress has been made towards the proposed objectives, overcoming the challenges posed by the COVID-19 pandemic. Through many virtual meetings for coordination, planning, training and follow-up, a comprehensive set of DRLs for both diagnostic and therapeutic procedures, categorized by weight and age, have been established and are in use. A consensus document on good practices is in the final stage of development. The program's continuation into at least a second phase is essential to address pending issues, including the integration of automatic dose management systems, the levels of occupational radiation doses, their correlation with pediatric patient doses, and strategies to reduce them.

Local Diagnostic Reference Levels for Pediatric Interventional Cardiology Procedures in Argentina.

The aim of this work was to propose a preliminary local diagnostic reference levels (DRL) for pediatric interventional cardiology (PIC) procedures in Argentina, for different ranges of age and weight. This work has been conducted in the framework of the "Optimization of Protection in Pediatric Interventional Radiology in Latin America and the Caribbean" (OPRIPALC) program coordinated by the World Health Organization and the Pan American Health Organization in cooperation with the International Atomic Energy Agency to ensuring that radiation exposures of pediatric patients are the minimum necessary during fluoroscopy-guided interventional procedures. The local DRL values presented in this paper by weight group and age group were 7.1 Gy·cm2 (<5 kg), 10.7 Gy·cm2 (5-15 kg), 18.0 Gy·cm2 (15-30 kg), 15.9 Gy·cm2 (30-50 kg), and 28.2 Gy·cm2 (50-80 kg) and 5.3 Gy·cm2 (<1), 11.2 Gy·cm2 (1 to 5<), 19.6 Gy·cm2 (5 to 10<), and 21.4 Gy·cm2 (10 to 16<), respectively. Our dose results are among the values found in other international studies; however, there is great potential for dose optimization.

Diagnostic Reference Levels in Interventional Pediatric Cardiology: Two-Year Experience in a Tertiary Referral Hospital in Latin America.

The goal of the present study was to propose the first local diagnostic reference levels (DRLs) for interventional pediatric cardiology procedures in a large hospital in Colombia. The data collection period was from April 2020 to July 2022. The local DRLs were calculated as the 3rd quartile of patient-dose distributions for the kerma-area product (Pka) values. The sample of collected clinical procedures (255) was divided into diagnostic and therapeutic procedures and grouped into five weight and five age bands. The Pka differences found between diagnostic and therapeutic procedures were statistically significant in all weight and age bands, except for the 1-5-year age group. The local DRLs for weight bands were 3.82 Gy·cm2 (<5 kg), 7.39 Gy·cm2 (5-<15 kg), 19.72 Gy·cm2 (15-<30 kg), 28.99 Gy·cm2 (30-<50 kg), and 81.71 Gy·cm2 (50-<80 kg), respectively. For age bands, the DRLs were 3.97 Gy·cm2 (<1 y), 9.94 Gy·cm2 (1-<5 y), 20.82 Gy·cm2 (5-<10 y), 58.00 Gy·cm2 (10-<16 y), and 31.56 Gy·cm2 (<16 y), respectively. In conclusion, when comparing our results with other existing DRL values, we found that they are similar to other centers and thus there is scope to continue optimizing the radiation dose values. This will contribute to establishing national DRLs for Colombia in the near future.

Exacerbated response to oxidative stress in the Retinitis Pigmentosa CerklKD/KO mouse model triggers retinal degeneration pathways upon acute light stress.

The retina is particularly vulnerable to genetic and environmental alterations that generate oxidative stress and cause cellular damage in photoreceptors and other retinal neurons, eventually leading to cell death. CERKL (CERamide Kinase-Like) mutations cause Retinitis Pigmentosa and Cone-Rod Dystrophy in humans, two disorders characterized by photoreceptor degeneration and progressive vision loss. CERKL is a resilience gene against oxidative stress, and its overexpression protects cells from oxidative stress-induced apoptosis. Besides, CERKL contributes to stress granule-formation and regulates mitochondrial dynamics in the retina. Using the CerklKD/KO albino mouse model, which recapitulates the human disease, we aimed to study the impact of Cerkl knockdown on stress response and activation of photoreceptor death mechanisms upon light/oxidative stress. After acute light injury, we assessed immediate or late retinal stress response, by combining both omic and non-omic approaches. Our results show that Cerkl knockdown increases ROS levels and causes a basal exacerbated stress state in the retina, through alterations in glutathione metabolism and stress granule production, overall compromising an adequate response to additional oxidative damage. As a consequence, several cell death mechanisms are triggered in CerklKD/KO retinas after acute light stress. Our studies indicate that Cerkl gene is a pivotal player in regulating light-challenged retinal homeostasis and shed light on how mutations in CERKL lead to blindness by dysregulation of the basal oxidative stress response in the retina.

New Optimization Strategies on Radiation Protection in Fluoroscopy-Guided Interventional Procedures in Pediatrics.

The term fluoroscopically guided interventional procedure describes a clinical practice in medicine, where fluoroscopic systems are used to conduct diagnostic procedures or provide image guidance for therapeutic interventional procedures performed via percutaneous or other access routes [...].

Deficiency of the ywhaz gene, involved in neurodevelopmental disorders, alters brain activity and behaviour in zebrafish.

Genetic variants in YWHAZ contribute to psychiatric disorders such as autism spectrum disorder and schizophrenia, and have been related to an impaired neurodevelopment in humans and mice. Here, we have used zebrafish to investigate the mechanisms by which YWHAZ contributes to neurodevelopmental disorders. We observed that ywhaz expression was pan-neuronal during developmental stages and restricted to Purkinje cells in the adult cerebellum, cells that are described to be reduced in number and size in autistic patients. We then performed whole-brain imaging in wild-type and ywhaz CRISPR/Cas9 knockout (KO) larvae and found altered neuronal activity and connectivity in the hindbrain. Adult ywhaz KO fish display decreased levels of monoamines in the hindbrain and freeze when exposed to novel stimuli, a phenotype that can be reversed with drugs that target monoamine neurotransmission. These findings suggest an important role for ywhaz in establishing neuronal connectivity during development and modulating both neurotransmission and behaviour in adults.

Avances y desafíos de la protección radiológica en cardiología intervencionista pediátrica para Chile entre los años 2013-2021 / Updating radiological protection for interventional procedures in pediatric cardiology in Chile

RESUMEN: En el año 2013, se publicó un artículo acerca de lo realizado en Chile en temas de protección radiológica en cardiología intervencionista (CI) pediátrica. A continuación se muestra el trabajo de continuidad realizado en los últimos 8 años, destacando los principales resultados alcanzados y proponiendo mejoras en la seguridad y protección radiológica en esta práctica clínica. Desde el año 2013 se han seguido evaluando en términos de dosis de radiación y calidad de imagen, los sistemas de rayos X utilizados en Chile para procedimientos de CI pediátricos y, en particular, los equipos de los servicios de los Hospitales Luis Calvo Mackenna y Roberto del Rio. Se han medido las tasas de dosis de radiación dispersa a la posición habitual de los ojos y tobillos de los cardiólogos que operan los equipos de rayos X. También contamos con un conjunto de "Niveles de Referencia para Diagnóstico" clasificados por rangos de edad y peso, junto con la estimación de valores de dosis por órgano y dosis efectiva para los pacientes. Podemos afirmar que, actualmente, contamos con una metodología consolidada para caracterizar, en términos de dosis y calidad de imagen, los sistemas de rayos X. Sin embargo, sigue pendiente actualizar la normativa nacional que regula el uso seguro de las radiaciones ionizantes en medicina, como también aspectos de formación en protección radiológica para el personal médico implicado.

ABSRSCT: An article on the status of radiological protection during procedures of interventional cardiology in pediatric patients in Chile was published in 2013. The present article relates the continuing efforts to improve radiological protection highlighting their results and proposing additional measures to improve radiological protection during the procedure. Since 2013 we have continued the evaluation of radiation doses, image quality, and X Ray systems used in Chile. We have measured diffused radiation dose at operator´s eye and ankle levels to elaborate a "Reference guide" according to patient´s age and weight. However, we still lack a national regulatory norm for the X Ray systems to be used and for the appropriate training of those involved in procedures of interventional cardiology in pediatric patients.

Optimización de la protección en radiología y cardiología intervencionista pediatrica en América Latina y el Caribe (OPRIPALC) / Optimization of protection in pediatric interventional cardiology and radiology in Latin America and the Caribbean (OPRIPALC)

El objetivo del presente artículo ha sido describir el programa "Optimización de la Protección en Radiología Intervencionista Pediátrica en América Latina y el Caribe" (OPRIPALC) que nace el año 2018 como respuesta conjunta de la Organización Panamericana de la Salud y la Organización Mundial de la Salud, en cooperación con el Organismo Internacional de Energía Atómica, para colaborar con sus Estados miembros en asegurar que las exposiciones a la radiación de los pacientes pediátricos sean las mínimas necesarias durante los procedimientos intervencionistas. Actualmente, hay 18 centros de los siguientes 10 países que participan: Argentina, Brasil, Chile, Colombia, Costa Rica, Cuba, Ecuador, México, Perú y Uruguay. Para el desarrollo del programa se plantean una serie de objetivos, productos, actividades y resultados esperados. La puesta en marcha de la WEB de OPRIPALC ha significado un instrumento muy válido para seguir la información actualizada del programa. Un programa actualizado de formación en radioprotección para los profesionales implicados en el programa, se está realizando por medio de "webinars". Se deberá seguir actuando en la aplicación del programa de control de calidad básico para los equipos de rayos X participantes y validar los valores de los Niveles de Referencia para Diagnóstico (NRDs). Se propone formar un equipo de trabajo entre los Físicos Médicos y Tecnólogos Médicos participantes de OPRIPALC para implicarse en las pruebas de control básicas que todos los centros debieran realizar. Se han presentado algunos resultados iniciales de OPRIPALC en eventos científicos internacionales. Se está avanzando en proponer unos primeros valores sobre NRDs en procedimientos de intervencionismo cardiológico pediátrico por bandas de edad y peso. OPRIPALC es una de las pocas iniciativas de carácter regional para obtener valores de NRDs en procedimientos intervencionistas pediátricos. Se espera que tanto los valores de referencia como la metodología empleada en OPRIPALC, puedan ser utilizados en otras regiones del mundo.

The objective of this article has been to describe the program "Optimization of Protection in Pediatric Interventional Radiology in Latin America and the Caribbean" (OPRIPALC) that was born in 2018 as a joint response of the Pan American Health Organization and the World Organization of the Health, in cooperation with the International Atomic Energy Agency, to collaborate with its member states in ensuring that radiation exposures of pediatric patients are the minimum necessary during interventional procedures. Currently, there are 18 centers from the following 10 countries participating: Argentina, Brazil, Chile, Colombia, Costa Rica, Cuba, Ecuador, Mexico, Peru and Uruguay. For the development of the program, a series of objectives, products, activities and expected results are proposed. The launch of the OPRIPALC WEBSITE has been a very valid instrument for following up-to-date information on the program. An updated training program in radiation protection for the professionals involved in the program is being carried out through webinars. It should continue acting in the application of the basic quality control program for the participating X-ray equipment and validate the values of the Diagnostic Reference Levels (DRLs). It is proposed to form a work team among the OPRIPALC participating medical physicists to get involved in the basic control tests that all centers should carry out. Some initial results of OPRIPALC have been presented at international scientific events. Progress is being made in proposing first values on DRLs in pediatric cardiac intervention procedures by age and weight bands. OPRIPALC is one of the few regional initiatives to obtain DRLs values in pediatric interventional procedures. It is expected that both the reference values and the methodology used in OPRIPALC can be used in other regions of the world.

Aspectos Éticos de la Protección Radiológica en Procedimientos de Radiología Dental

RESUMEN: Se sabe de los beneficios que la radiología dental ha significado para mejorar la calidad de vida de las personas en todo el mundo, sin embargo, también conocemos los riesgos asociados a su uso. Para disminuir estos riegos, diferentes organizaciones a nivel internacional han desarrollado un SISTEMA DE PROTECCIÓN RADIOLÓGICA (SRP) basado en los principios de: Justificación, optimización y limitación de dosis, los cuales a su vez han evolucionado en base al desarrollo de la ciencia, los valores éticos, y la experiencia acumulada en la práctica cotidiana de los profesionales de la protección radiológica. Al revisar la normativa que regula el uso de las radiaciones ionizantes en Chile, analizamos que no se tienen en cuenta los aspectos o valores éticos al momento de hablar y aplicar el SPR en procedimientos de radiología dental. Por todo lo anterior, el objetivo del presente trabajo de revisión narrativa fue elaborar un nuevo documento de consulta para los odontólogos, que contenga de manera resumida y con definiciones precisas, los principales aspectos a tener en cuenta a la hora de comprender como funciona el SPR y los valores éticos que lo fundamentan, ayudando de esta manera a resolver objetivamente los juicios de valor que se pueden presentar durante la solicitud, ejecución e interpretación de los procedimientos de radiología dental.

ABSTRACT: The benefits of dental radiology that improve the quality of life of populations worldwide have been well established. However, the risks associated with its use are also known. With these risks in mind, various international organizations have developed a Radiological Protection System (RPS) based on the principles of: Justification, optimization and dose limitation, which in turn have evolved based on science, values ethics, and the experience accumulated during the daily practice by radiation protection professionals. While reviewing the standards that regulate the use of ionizing radiation in Chile, we observed that ethical aspects or values are not taken into account when applying the RPS in dental radiology procedures. In light of these findings, the objective of this narrative review was to develop a new consultation procedure for dentists, which contains the main aspects to consider when understanding how SPR works, in a summarized precise form, as well as the supporting ethical values. Thereby helping to resolve the value judgments that may arise during the performance and interpretation of dental radiology procedures.

New Genes Born-In or Invading Vertebrate Genomes.

Which is the origin of genes is a fundamental question in Biology, indeed a question older than the discovery of genes itself. For more than a century, it was uneven to think in origins other than duplication and divergence from a previous gene. In recent years, however, the intersection of genetics, embryonic development, and bioinformatics, has brought to light that de novo generation from non-genic DNA, horizontal gene transfer and, noticeably, virus and transposon invasions, have shaped current genomes, by integrating those newcomers into old gene networks, helping to shape morphological and physiological innovations. We here summarized some of the recent research in the field, mostly in the vertebrate lineage with a focus on protein-coding novelties, showing that the placenta, the adaptative immune system, or the highly developed neocortex, among other innovations, are linked to de novo gene creation or domestication of virus and transposons. We provocatively suggest that the high tolerance to virus infections by bats may also be related to previous virus and transposon invasions in the bat lineage.

CERKL, a retinal dystrophy gene, regulates mitochondrial function and dynamics in the mammalian retina.

The retina is a highly active metabolic organ that displays a particular vulnerability to genetic and environmental factors causing stress and homeostatic imbalance. Mitochondria constitute a bioenergetic hub that coordinates stress response and cellular homeostasis, therefore structural and functional regulation of the mitochondrial dynamic network is essential for the mammalian retina. CERKL (ceramide kinase like) is a retinal degeneration gene whose mutations cause Retinitis Pigmentosa in humans, a visual disorder characterized by photoreceptors neurodegeneration and progressive vision loss. CERKL produces multiple isoforms with a dynamic subcellular localization. Here we show that a pool of CERKL isoforms localizes at mitochondria in mouse retinal ganglion cells. The depletion of CERKL levels in CerklKD/KO(knockdown/knockout) mouse retinas cause increase of autophagy, mitochondrial fragmentation, alteration of mitochondrial distribution, and dysfunction of mitochondrial-dependent bioenergetics and metabolism. Our results support CERKL as a regulator of autophagy and mitochondrial biology in the mammalian retina.

Niveles de Referencia para Diagnóstico Locales en Procedimientos Radiográficos Dentales Periapicales. Primeros valores para Chile

RESUMEN: La información que aportan los procedimientos de radiología dental, tanto en la evaluación, como en el diagnóstico y tratamiento de patologías y/o alteraciones dento maxilofaciales, hace que correspondan al tipo más frecuente de estudio radiológico. Sin embargo, existe un escaso conocimiento en nuestro país respecto de los niveles de dosis que se imparten en dichos procedimientos, haciendo necesaria su determinación para maximizar el beneficio derivado de los mismos y minimizar el riesgo radiológico para los pacientes. El presente estudio determinó el nivel de referencia para diagnóstico (NRD) local en la radiografía periapical de Molar maxilar e Incisivo, para ello se realizaron simulaciones de los procedimientos radiográficos en un maniquí antropomorfo seccional y se determinó el valor de Kerma aire en la superficie de entrada con retrodispersión mediante dosimetría termoluminiscente. Los NRD locales determinados en la radiografía periapical de Molar maxilar fueron 5,6 mGy para adultos y 4,0 mGy para niños; mientras que en la radiografía periapical de Incisivo fue de 9,2 mGy para pacientes adultos y 1,8 mGy para niños. Los resultados obtenidos buscan orientar la ejecución de futuras investigaciones en el área y aportar información del nivel de radiación en estos procedimientos, con lo que se espera promover una cultura de radioprotección y motivar la optimización de las dosis registradas.

ABSTRACT: The information provided by dental radiology procedures, both in evaluation, as well as in the diagnosis and treatment of pathologies and / or dentomaxilofacial alterations, makes them the most frequent type of radiological study. However, there is a meager knowledge in our country regarding dose levels applied in such procedures, making their determination necessary to maximize the benefits and to minimize the radiological risk to patients. The present study determined the local diagnostic reference level (LDRL) for the periapical radiography of the Maxillary molar and Incisive. Simulations of radiographic procedures were performed and the value of air Kerma at the entrance surface with backscattering, was estimated using thermo luminescent dosimetry. The LDRL determined in the maxillary molar periapical radiography was 5.6 mGy for adults and 4.0 mGy for children; while on the incisive periapical radiography it was 9.2 mGy for adult patients and 1.8 mGy for children. The results obtained seek to guide the execution of future research in the area and provide information on the radiation doses delivered in these procedures, which is expected to promote a radiation protection culture and motivate the optimization of the registered doses.

Analysis of Fox genes in Schmidtea mediterranea reveals new families and a conserved role of Smed-foxO in controlling cell death.

The forkhead box (Fox) genes encode transcription factors that control several key aspects of development. Present in the ancestor of all eukaryotes, Fox genes underwent several duplications followed by loss and diversification events that gave rise to the current 25 families. However, few Fox members have been identified from the Lophotrochozoa clade, and specifically from planarians, which are a unique model for understanding development, due to the striking plasticity of the adult. The aim of this study was to identify and perform evolutionary and functional studies of the Fox genes of lophotrochozoan species and, specifically, of the planarian Schmidtea mediterranea. Generating a pipeline for identifying Forkhead domains and using phylogenetics allowed us the phylogenetic reconstruction of Fox genes. We corrected the annotation for misannotated genes and uncovered a new family, the QD, present in all metazoans. According to the new phylogeny, the 27 Fox genes found in Schmidtea mediterranea were classified into 12 families. In Platyhelminthes, family losses were accompanied by extensive gene diversification and the appearance of specific families, the A(P) and N(P). Among the newly identified planarian Fox genes, we found a single copy of foxO, which shows an evolutionary conserved role in controlling cell death.

RADIATION DOSE FOR PATIENTS WITH KAWASAKI DISEASE UNDERGOING FLUOROSCOPICALLY GUIDED CARDIAC CATHETERIZATION.

The goal of the present study was to estimate the radiation dose for a group of 45 Kawasaki disease (KD) patients undergoing fluoroscopically guided cardiac catheterization. The sample of procedures corresponds to a single hospital and was collected in 10 years. Anthropometric characteristics and the quantities of air kerma-area product (PKA) among others were recorded for each procedure. Monte Carlo PCXMC 2.0 software was used to estimate organ and effective doses. The PKA value of 7.2 Gy cm2 was proposed as the local Diagnostic Reference Level for KD. For organ absorbed doses, median values for thyroid, heart, lungs, esophagus, skin, active bone and breast were 1.2; 2.2; 4.6; 2.7; 1.1; 1.2 and 2.7 mGy, respectively. For effective dose, the mean value was 2.7 ± 2.5 mSv. This paper presents the first patient dose values for the KD using catheterization techniques, in Latin America and the Caribbean Region.

Kinetics of Torque Teno virus DNA in stools may predict occurrence of acute intestinal graft versus host disease early after allogeneic hematopoietic stem cell transplantation.

Torque Teno virus (TTV) DNA load in blood may act as a marker of immune competence after allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). Conflicting data have been reported as to the value of this biomarker for anticipating acute Graft versus host disease (aGvHD) occurrence. Here, we hypothesized that quantitation of TTV DNA load in stool specimens early after allo-HSCT could be used to identify patients at high risk of acute intestinal graft versus host disease (aIGvHD). In this prospective two-center study, we recruited a total of 83 nonconsecutive adult patients undergoing allo-HSCT. The study period comprised the first 120 days after allo-HSCT. TTV DNA was quantitated in paired stool samples collected at a median of 2 days prior to cell infusion and at a median of 14 days after allo-HSCT by real-time PCR. Thirty-seven patients developed aGVHD, of whom 25 had aIGVHD (diagnosed at a median of 42 days after allo-HSCT). Median TTV DNA load values in posttransplant stools specimens were comparable (P = .34) in patients with or without subsequent aIGvHD; nevertheless, a falling trajectory (decrease in TTV DNA load >0.5 log10 copies/0.1 g) in paired pretransplant and posttransplant specimens was independently associated with the occurrence of aIGvHD (OR, 5.2; 95% CI, 1.3-21.3; P = .02). Notably, displaying a rising trajectory had a negative predictive value of 87.5% for aIGvHD. In summary, in this hypothesis-generating study, we suggest that the decrease in TTV DNA load from baseline in stool specimens may identify patients at risk of aIGVHD.

The ADAR Family in Amphioxus: RNA Editing and Conserved Orthologous Site Predictions.

RNA editing is a relatively unexplored process in which transcribed RNA is modified at specific nucleotides before translation, adding another level of regulation of gene expression. Cephalopods use it extensively to increase the regulatory complexity of their nervous systems, and mammals use it too, but less prominently. Nevertheless, little is known about the specifics of RNA editing in most of the other clades and the relevance of RNA editing from an evolutionary perspective remains unknown. Here we analyze a key element of the editing machinery, the ADAR (adenosine deaminase acting on RNA) gene family, in an animal with a key phylogenetic position at the root of chordates: the cephalochordate amphioxus. We show, that as in cephalopods, ADAR genes in amphioxus are predominantly expressed in the nervous system; we identify a number of RNA editing events in amphioxus; and we provide a newly developed method to identify RNA editing events in highly polymorphic genomes using orthology as a guide. Overall, our work lays the foundations for future comparative analysis of RNA-editing events across the metazoan tree.