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To enhance stakeholder engagement and foster the inclusion of interests of citizens in radiation protection research, a comprehensive online survey was developed within the framework of the European Partnership PIANOFORTE. This survey was performed in 2022 and presented an opportunity for a wide range of stakeholders to voice their opinions on research priorities in radiation protection for the foreseeable future. Simultaneously, it delved into pertinent issues surrounding general radiation protection. The PIANOFORTE e-survey was conducted in the English language, accommodating a diverse range of participants. Overall, 440 respondents provided their insights and feedback, representing a broad geographical reach encompassing 29 European countries, as well as Canada, China, Colombia, India, and the United States. To assess the outcomes, the Positive Matrix Factorization numerical model was applied, in addition to qualitative and quantitative assessment of individual responses, enabling the discernment of four distinct stakeholder groups with varying attitudes. While the questionnaire may not fully represent all stakeholders due to the limited respondent pool, it is noteworthy that approximately 70% of the participants were newcomers to comparable surveys, demonstrating a proactive attitude, a strong willingness to collaborate and the necessity to continuously engage with stakeholder groups. Among the individual respondents, distinct opinions emerged particularly regarding health effects of radiation exposure, medical use of radiation, radiation protection of workers and the public, as well as emergency and recovery preparedness and response. In cluster analysis, none of the identified groups had clear preferences concerning the prioritization of future radiation protection research topics.
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To determine patients' knowledge about ionising radiation used in diagnostic imaging and whether they were adequately informed about the procedure they were referred to. A cross-sectional study was conducted at the University Hospital Merkur, Zagreb, Croatia during 2019-20. A questionnaire with 14 questions was given to patients in waiting rooms for imaging examinations. Statistical analysis was conducted using the standard software package. Chi-square with Yates correction was used to determine differences in patients' answers between those who received the explanation about the procedure and those who did not. The differences depending on the educational level were also evaluated. The survey was completed by 374 participants (200 women, 174 men) with a mean age of 55.45 ± 15.92 y. Of all patients, 8.63% had no formal education or only finished elementary school, 52.83% had finished high school and 38.55% had a college or a higher degree. The referring physicians informed 63.66% of participants about the radiological exam they were being referred to, and 226 thought that the given explanation was sufficient. Most patients knew that some radiological procedures use ionising radiation. Only 47.37% of respondents correctly identified MRI as a non-ionising method, whereas 37.40% of participants recognised chest X-ray as the modality with the lowest radiation dose. Higher-educated patients had better knowledge of radiological procedures and the potential risks. The study demonstrated suboptimal patients' knowledge about ionising radiation, and additional efforts in their education are needed.
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Conocimientos, Actitudes y Práctica en Salud , Exposición a la Radiación , Masculino , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Proyectos Piloto , Estudios Transversales , Dosis de Radiación , Encuestas y CuestionariosRESUMEN
Despite the EU states being under the umbrella of the European Directive 2013/59/Euratom, a certain degree of heterogeneity may be noticed in the implementation of EU recommendations concerning regulation and handling of NORM into national legislation and practice. This is mainly a result of the still existing incomplete international knowledge about different phenomena related to NORM. Therefore, the attempt to advance the understanding of the behaviour and exposure of NORM is at the core of the European RadoNorm project. Within this context, an international survey on NORM has been prepared. The goals of the survey were to gather information and data from European countries that will contribute making an updated and/or new (a) systematic overview of NORM exposure situations and their analysis with respect to different radiation protection aspects, (b) knowledge about applied radioecological models in a variety of NORM exposure situations to improve evaluation of possible exposure doses and risk for population and workers, as well as of environmental risk, and (c) overview of overall mitigation measures applied in NORM involving industries, and possible remediation activities applied at NORM affected legacy sites. The survey is built upon an extended list of NORM-involving industries and processes, covers general aspects of NORM, presence of multi-stressors, as well as practical procedures applied in management and regulation, also in the context of a circular economy. The survey responses were obtained from 19 countries. An analysis of survey responses proved that NORM control is still a complex issue for many countries, and the recently-introduced regulatory solutions require further interpretation for developing procedures and good practices. The present work provides a detailed analysis of the survey responses with respect to regulation, management and investigation of NORM.
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Protección Radiológica , Radiactividad , Humanos , Unión Europea , Europa (Continente) , IndustriasRESUMEN
Dysregulation of protein synthesis is one of the key mechanisms underlying autism spectrum disorder (ASD). However, the role of a major pathway controlling protein synthesis, the integrated stress response (ISR), in ASD remains poorly understood. Here, we demonstrate that the main arm of the ISR, eIF2α phosphorylation (p-eIF2α), is suppressed in excitatory, but not inhibitory, neurons in a mouse model of fragile X syndrome (FXS; Fmr1-/y). We further show that the decrease in p-eIF2α is mediated via activation of mTORC1. Genetic reduction of p-eIF2α only in excitatory neurons is sufficient to increase general protein synthesis and cause autism-like behavior. In Fmr1-/y mice, restoration of p-eIF2α solely in excitatory neurons reverses elevated protein synthesis and rescues autism-related phenotypes. Thus, we reveal a previously unknown causal relationship between excitatory neuron-specific translational control via the ISR pathway, general protein synthesis, and core phenotypes reminiscent of autism in a mouse model of FXS.
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Trastorno del Espectro Autista , Trastorno Autístico , Síndrome del Cromosoma X Frágil , Animales , Ratones , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/metabolismo , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Neuronas/metabolismo , Fenotipo , Ratones Noqueados , Modelos Animales de EnfermedadRESUMEN
The inferior vena cava agenesis (IVCA) is a rare and often asymptomatic malformation due to the abundant development of the collateral circulation. However, it is frequently found in young people and carries a significant risk of deep venous thrombosis (DVT). It is estimated that about 5% of patients under 30 years of age presenting with DVT have this condition. We report a case of a previously healthy 23-year-old patient presenting with signs of acute abdomen and hydronephrosis due to the thrombophlebitis of an unusual iliocaval venous collateral, which developed secondary to IVCA. After treatment, the iliocaval collateral and hydronephrosis completely regressed on a 1-year follow-up. To our knowledge, this is the first such case reported in the literature.
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Even before behavioral disturbances, neuroleptics, amphetamine, and domperidone application rapidly emerged severe occlusion/occlusion-like syndrome, shared innate vascular and multiorgan failure in rats, comparable to occlusion/occlusion-like syndrome described with vessel(s) occlusion or similar noxious procedures application. As therapy, i.e., activation of the collateral pathways, "bypassing key" (activated azygos vein pathway, direct blood flow delivery), the stable gastric pentadecapeptide BPC 157 is a novel solution. Recently, BPC 157 therapy particularly counteracted neuroleptic- or L-NAME-induced catalepsy, lithium intoxication, and schizophrenia positive and negative symptoms (amphetamine/methamphetamine/apomorphine/ketamine). In rats with complete calvariectomy, medication (BPC 157 10 µg/kg, 10 ng/kg ip or ig) was given 5 min after distinctive dopamine agents (mg/kg ip) (haloperidol (5), fluphenazine (5), clozapine (10), risperidone (5), olanzapine (10), quetiapine (10), or aripiprazole (10), domperidone (25), amphetamine (10), and combined amphetamine and haloperidol) and assessed at 15 min thereafter. All neuroleptic-, domperidone-, and amphetamine-induced comparable vascular and multiorgan failure severe syndrome was alleviated with BPC 157 therapy as before major vessel(s) occlusion or other similar noxious procedures. Specifically, all severe lesions in the brain (i.e., immediate swelling, hemorrhage), heart (i.e., congestion, arrhythmias), and lung (i.e., congestion, hemorrhage), as well as congestion in the liver, kidney, and gastrointestinal (stomach) tract, were resolved. Intracranial (superior sagittal sinus), portal, and caval hypertension and aortal hypotension were attenuated or eliminated. BPC 157 therapy almost annihilated arterial and venous thrombosis, peripherally and centrally. Thus, rapidly acting Virchow triad circumstances that occur as dopamine central/peripheral antagonists and agonist essential class-points, fully reversed by BPC 157 therapy, might be overwhelming for both neuroleptics and amphetamine.
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Naturally occurring radioactive materials (NORM) contribute to the dose arising from radiation exposure for workers, public and non-human biota in different working and environmental conditions. Within the EURATOM Horizon 2020 RadoNorm project, work is ongoing to identify NORM exposure situations and scenarios in European countries and to collect qualitative and quantitative data of relevance for radiation protection. The data obtained will contribute to improved understanding of the extent of activities involving NORM, radionuclide behaviours and the associated radiation exposure, and will provide an insight into related scientific, practical and regulatory challenges. The development of a tiered methodology for identification of NORM exposure situations and complementary tools to support uniform data collection were the first activities in the mentioned project NORM work. While NORM identification methodology is given in Michalik et al., 2023, in this paper, the main details of tools for NORM data collection are presented and they are made publicly available. The tools are a series of NORM registers in Microsoft Excel form, that have been comprehensively designed to help (a) identify the main NORM issues of radiation protection concern at given exposure situations, (b) gain an overview of materials involved (i.e., raw materials, products, by-products, residues, effluents), c) collect qualitative and quantitative data on NORM, and (d) characterise multiple hazards exposure scenarios and make further steps towards development of an integrated risk and exposure dose assessment for workers, public and non-human biota. Furthermore, the NORM registers ensure standardised and unified characterisation of NORM situations in a manner that supports and complements the effective management and regulatory control of NORM processes, products and wastes, and related exposures to natural radiation worldwide.
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Exposición a la Radiación , Monitoreo de Radiación , Protección Radiológica , Radiactividad , Radioisótopos/análisis , Europa (Continente)RESUMEN
In large parts of Europe, the Chernobyl accident of 1986 caused fallout of Cs-137. This led to the uptake of Cs-137 in trees or other materials used for bioenergy production or as firewood for domestic purposes. This Cs-137 may concentrate in the ashes of the combustion process in such a way that the clearance level of 100 Bq per kg, defined in Directive 2013/59/Euratom (EU BSS), may consequently be exceeded. There is currently no clear consensus in Europe regarding the regulatory approach to this issue: should the import and use of Cs-137 contaminated biomass and its ashes be considered as a planned exposure situation or rather as an existing exposure situation? If considered as an existing exposure situation, which reference level should be applied? We compare the approaches in various European countries, such as Finland, Norway, Sweden, Belgium and the Netherlands. Results of a recent measurement campaign performed in Belgium on firewood imported from Belarus, Ukraine and other countries show a quite large range of Cs-137 activity concentration in firewood. Analysis of samples from biomass combustion confirms that the clearance level of 100 Bq per kg Cs-137 may be exceeded even when the activity concentration in the initial pellet is trivial. A review of dose-assessment studies performed by STUK and from the literature is presented. The general context of biomass energy production is sketched: for instance, in the Netherlands, 40 large biomass firing plants (capacity > 10 MW) are operational and some 20 more are already planned. The fly ashes from the biomass combustion may be a valuable resource for the construction industry, and the issue of Cs-137 contamination is connected with the requirements of the EU BSS regarding the natural radioactivity of building materials. Assessing the impact of Cs-137 contamination and clarifying regulations in the frame of a graded approach are important elements in this context.
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Radioisótopos de Cesio , Biomasa , Europa (Continente) , BélgicaRESUMEN
Naturally occurring radioactive materials (NORM) are present worldwide and under certain circumstances (e.g., human activities) may give radiation exposure to workers, local public or occasional visitors and non-human biota (NHB) of the surrounding ecosystems. This may occur during planned or existing exposure situations which, under current radiation protection standards, require identification, management, and regulatory control as for other practices associated with man-made radionuclides that may result in the exposure of people and NHB. However, knowledge gaps exist with respect to the extent of global and European NORM exposure situations and their exposure scenario characteristics, including information on the presence of other physical hazards, such as chemical and biological ones. One of the main reasons for this is the wide variety of industries, practices and situations that may utilise NORM. Additionally, the lack of a comprehensive methodology for identification of NORM exposure situations and the absence of tools to support a systematic characterisation and data collection at identified sites may also lead to a gap in knowledge. Within the EURATOM Horizon 2020 RadoNorm project, a methodology for systematic NORM exposure identification has been developed. The methodology, containing consecutive tiers, comprehensively covers situations where NORM may occur (i.e., minerals and raw materials deposits, industrial activities, industrial products and residues and their applications, waste, legacies), and thus, allows detailed investigation and complete identification of situations where NORM may present a radiation protection concern in a country. Details of the tiered methodology, with practical examples on harmonised data collection using a variety of existing sources of information to establish NORM inventories, are presented in this paper. This methodology is flexible and thus applicable to a diversity of situations. It is intended to be used to make NORM inventory starting from the scratch, however it can be used also to systematise and complete existing data.
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Exposición a la Radiación , Monitoreo de Radiación , Protección Radiológica , Residuos Radiactivos , Humanos , Ecosistema , Radioisótopos/análisis , Unión Europea , Residuos Radiactivos/análisisRESUMEN
MAPK interacting protein kinases 1 and 2 (Mnk1/2) regulate a plethora of functions, presumably via phosphorylation of their best characterized substrate, eukaryotic translation initiation factor 4E (eIF4E) on Ser209. Here, we show that, whereas deletion of Mnk1/2 (Mnk double knockout) impairs synaptic plasticity and memory in mice, ablation of phospho-eIF4E (Ser209) does not affect these processes, suggesting that Mnk1/2 possess additional downstream effectors in the brain. Translational profiling revealed only a small overlap between the Mnk1/2- and phospho-eIF4E(Ser209)-regulated translatome. We identified the synaptic Ras GTPase activating protein 1 (Syngap1), encoded by a syndromic autism gene, as a downstream target of Mnk1 because Syngap1 immunoprecipitated with Mnk1 and showed reduced phosphorylation (S788) in Mnk double knockout mice. Knockdown of Syngap1 reversed memory deficits in Mnk double knockout mice and pharmacological inhibition of Mnks rescued autism-related phenotypes in Syngap1+/- mice. Thus, Syngap1 is a downstream effector of Mnk1, and the Mnks-Syngap1 axis regulates memory formation and autism-related behaviours.
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Trastorno Autístico , Factor 4E Eucariótico de Iniciación , Animales , Ratones , Factor 4E Eucariótico de Iniciación/genética , Ratones Noqueados , Fosforilación , Proteínas Activadoras de ras GTPasa/metabolismoRESUMEN
Protection of the population and of workers from exposure to radon is a unique challenge in radiation protection. Many coordinated actions and a variety of expertise are needed. Initially, a National Radon Action Plan (NRAP) has been developed and implemented by some countries, while it is currently recommended by international organizations (e.g., World Health Organization) and required by international regulations, such as the European Council Directive 2013/59/Euratom and the International Basic Safety Standards on Radiation Protection and Safety of Radiation Sources, cosponsored by eight international organizations. Within this framework, the Heads of the European Radiological Protection Competent Authorities (HERCA) have organized activities aimed at sharing experiences to contribute toward the development and implementation of effective NRAPs. Two workshops were held in 2014 and 2015, the latter on radon in workplaces. As a follow-up to these, an online event took place in March 2021, and a second specific workshop on NRAP is planned for June 2022. These workshops were attended by experts from the competent authorities of European countries, relevant national and international organizations. The experience of several countries and the outcomes from these workshops have highlighted the need for adequate indicators of the effectiveness and progress of the actions of NRAPs, which could also be useful to implement the principle of optimization and the graded approach in NRAPs. In this paper, the activities of HERCA to support the development and implementation of effective NRAPs are described and some examples of effectiveness indicators are reported, including those already included in the NRAP of some European countries.
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Monitoreo de Radiación , Protección Radiológica , Radón , Exposición a Riesgos Ambientales/análisis , Europa (Continente) , Humanos , Radón/análisisRESUMEN
While technical aspects of exposures to the naturally occurring radioactive material (NORM) are well explored, social science research on NORM is scarce, poorly indexed and dispersed across peer-reviewed literature, as well as various academic disciplines. Through an exploratory review of grey literature and a systematic review of scientific peer-reviewed articles published until December 2020, this paper addresses the following questions: (a) What are the societal challenges related to NORM? (b) What type of scientific research is being conducted on the societal aspects of NORM and (c) To what extent do the findings answer the identified challenges? Unfortunately, results of this study demonstrate a research gap related to the social, economic and cultural aspects of NORM management. Although the few existing studies offer some insights, for instance in relation to risk perception and risk communication, most of the societal challenges identified have not been addressed yet. This demonstrates the strong need for evidence based social science studies in order to improve the management of NORM.
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Monitoreo de RadiaciónRESUMEN
The dose absorbed by sensitive breast glandular tissue in abdominal computed tomography examinations, even when the breasts are outside the primary imaging beam, is still significant. Several studies have explored using breast shielding with a protective lead sheet or a bra. Since the source of radiation in computed tomography rotates by 360° around the patient, we made a custom-tailored shielding device that wraps around the entire thorax. The hypothesis is that such a custom-tailored breast shielding device provides significantly better dose reduction. Study participants were female patients with no anatomic anomalies. Entrance surface doses were measured using thermoluminescence dosimeters placed on the skin of the breast in the control group without shielding and on the surface and below the shielding device in the group with anterior shielding and the group with the new device. As expected, according to literature data, doses measured at breast level were above the threshold that epidemiological studies determine as an increased risk of breast cancer development although they were not in the primary imaging plane. Preliminary results of our study showed that average dose reduction was 42% with conventional anterior shielding and 57% with wrapped shielding compared to the doses measured with no shielding.
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Protección Radiológica , Femenino , Humanos , Masculino , Dosis de Radiación , Protección Radiológica/métodos , Fantasmas de Imagen , Tomografía Computarizada por Rayos X/métodos , AbdomenRESUMEN
Hereditary hemorrhagic telangiectasia (HHT) (Osler-Weber-Rendu Syndrome) is a rare autosomal dominant vascular disorder characterized by the presence of multiple arteriovenous malformations (AVMs) and recurrent bleeding episodes. The diagnosis is based on the Curacao criteria: (i) spontaneous recurrent epistaxis, (ii) mucocutaneous telangiectasia, (iii) AVMs of visceral organs, and (iv) first degree relatives with a similar condition (1). Due to a common genetic pathway and SMAD4 gene mutation, juvenile polyposis syndrome (JPS) may coexist with HHT (2). The disease burden is high in overlapping HHT/JPS, but digital clubbing may be the only physical finding. Continuous meticulous management may improve the quality of life and reduce the risk of complications. In 2000, a 15-year-old female patient was diagnosed with HHT based on epistaxis, multiple pulmonary AVMs, and a father who had similar symptoms. Other visceral AVMs were excluded. No telangiectasia was noted. On several occasions, pulmonary AVMs were managed with coil embolization (Figure 1), which successfully led to the resolution of dyspnea and cyanosis. Recurrent gastrointestinal bleedings led to severe transfusion-dependent anemia. Multiple polyps in the stomach, small intestine, and colon were repeatedly endoscopically removed, confirming the coexisting JPS. Genetic testing was not performed. Proctocolectomy was performed to prevent malignant transformation in the digestive tract. Telangiectasias are the dermatological hallmark of the HHT and occur in up to 90% of patients with the typical onset in childhood, becoming more apparent with increasing age. They are most frequently found on the face, with highest incidence on the nose, lips, tongue, and ears, followed by the fingertips, trunk, and feet; telangiectasia is recognized as the most common of the three criteria required for the diagnosis of HHT (1). Interestingly, no cutaneous telangiectasia developed in our patient during years of follow-up. However, pulmonary AVMs led to digital clubbing of her both fingers and toes (Figure 2). Digital clubbing is the focal enlargement of the connective tissue in the terminal phalanges, consequently changing the shape of nails, which become abnormally curved and shiny. It is associated with various infectious, neoplastic, inflammatory, and vascular conditions (3). Despite its well-known prevalence in certain conditions, the pathogenesis of this phenomenon remains elusive. Vascular, neural, and hormonal mechanisms have been considered, implicating the role of a wide range of substances, such as prostaglandins, bradykinin, estrogen, platelet-derived growth factor, hepatocyte growth factor, and growth hormone, however, none of these mechanisms provide a unifying explanation (4,5). In digital clubbing, the increased vascularity in the nail-bed leads to hyperplasia of fibrous tissue and edema, resulting in a loss of the hyponychial angle, fluctuance of the nail-bed, and an abnormal phalangeal depth ratio (5). The clinical assessment of the clubbing is based on the measurement of the distal phalangeal depth (DPD) of the finger (at the nail base) and the interphalangeal depth (IPD). A DPD/IPD ratio >1 is defined as clubbing, while a DPD/IPD ratio <1 is defined as normal (3). Clubbing is a potentially reversible phenomenon provided that the underlying condition is cured (4,5). In the context of pulmonary AVMs, abnormal communication between the pulmonary artery and pulmonary vein outside the capillary bed leads to right-to-left shunt physiology that clinically presents as dyspnea, cyanosis, and clubbing. Embolization of AVMs as the first-line therapy resolved systemic symptoms in our patient, and therefore no other treatment options were pulmonary considered further. However, 20 years later, despite the treatment, the severe clubbing of her both fingers and toes remained (Figure 2). Based on our findings, HHT should be considered in differential diagnosis of patients with digital clubbing resulting from AVMs, in particular when no skin telangiectasia is present.
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Poliposis Intestinal , Síndromes Neoplásicos Hereditarios , Telangiectasia Hemorrágica Hereditaria , Adolescente , Femenino , Humanos , Poliposis Intestinal/congénito , Síndromes Neoplásicos Hereditarios/complicaciones , Síndromes Neoplásicos Hereditarios/genética , Calidad de Vida , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/diagnósticoRESUMEN
The ALLIANCE Strategic Research Agenda (SRA) for radioecology is a living document that defines a long-term vision (20 years) of the needs for, and implementation of, research in radioecology in Europe. The initial SRA, published in 2012, included consultation with a wide range of stakeholders (Hinton et al., 2013). This revised version is an update of the research strategy for identified research challenges, and includes a strategy to maintain and develop the associated required capacities for workforce (education and training) and research infrastructures and capabilities. Beyond radioecology, this SRA update constitutes a contribution to the implementation of a Joint Roadmap for radiation protection research in Europe (CONCERT, 2019a). This roadmap, established under the H2020 European Joint Programme CONCERT, provides a common and shared vision for radiation protection research, priority areas and strategic objectives for collaboration within a European radiation protection research programme to 2030 and beyond. Considering the advances made since the first SRA, this updated version presents research challenges and priorities including identified scientific issues that, when successfully resolved, have the potential to impact substantially and strengthen the system and/or practice of the overall radiation protection (game changers) in radioecology with regard to their integration into the global vision of European research in radiation protection. An additional aim of this paper is to encourage contribution from research communities, end users, decision makers and other stakeholders in the evaluation, further advancement and accomplishment of the identified priorities.
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Monitoreo de Radiación , Protección Radiológica , Europa (Continente)RESUMEN
Mutations in HPRT1, a gene encoding a rate-limiting enzyme for purine salvage, cause Lesch-Nyhan disease which is characterized by self-injury and motor impairments. We leveraged stem cell and genetic engineering technologies to model the disease in isogenic and patient-derived forebrain and midbrain cell types. Dopaminergic progenitor cells deficient in HPRT showed decreased intensity of all developmental cell-fate markers measured. Metabolic analyses revealed significant loss of all purine derivatives, except hypoxanthine, and impaired glycolysis and oxidative phosphorylation. real-time glucose tracing demonstrated increased shunting to the pentose phosphate pathway for de novo purine synthesis at the expense of ATP production. Purine depletion in dopaminergic progenitor cells resulted in loss of RHEB, impairing mTORC1 activation. These data demonstrate dopaminergic-specific effects of purine salvage deficiency and unexpectedly reveal that dopaminergic progenitor cells are programmed to a high-energy state prior to higher energy demands of terminally differentiated cells.
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Neuronas Dopaminérgicas/metabolismo , Metabolismo Energético , Síndrome de Lesch-Nyhan/metabolismo , Síndrome de Lesch-Nyhan/patología , Mesencéfalo/patología , Biomarcadores/metabolismo , Linaje de la Célula , Corteza Cerebral/patología , Glucosa/metabolismo , Glucólisis , Humanos , Hipoxantina Fosforribosiltransferasa/deficiencia , Síndrome de Lesch-Nyhan/enzimología , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Células-Madre Neurales/metabolismo , Fosforilación Oxidativa , Vía de Pentosa Fosfato , Purinas/metabolismoRESUMEN
Computed tomography colonography (CTC) has become a key examination in detecting colonic polyps and colorectal carcinoma (CRC). It is particularly useful after incomplete optical colonoscopy (OC) for patients with sedation risks and patients anxious about the risks or potential discomfort associated with OC. CTC's main advantages compared with OC are its non-invasive nature, better patient compliance, and the ability to assess the extracolonic disease. Despite these advantages, ionizing radiation remains the most significant burden of CTC. This opinion review comprehensively addresses the radiation risk of CTC, incorporating imaging technology refinements such as automatic tube current modulation, filtered back projections, lowering the tube voltage, and iterative reconstructions as tools for optimizing low and ultra-low dose protocols of CTC. Future perspectives arise from integrating artificial intelligence in computed tomography machines for the screening of CRC.
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Clinical studies have reported that the psychedelic lysergic acid diethylamide (LSD) enhances empathy and social behavior (SB) in humans, but its mechanism of action remains elusive. Using a multidisciplinary approach including in vivo electrophysiology, optogenetics, behavioral paradigms, and molecular biology, the effects of LSD on SB and glutamatergic neurotransmission in the medial prefrontal cortex (mPFC) were studied in male mice. Acute LSD (30 µg/kg) injection failed to increase SB. However, repeated LSD (30 µg/kg, once a day, for 7 days) administration promotes SB, without eliciting antidepressant/anxiolytic-like effects. Optogenetic inhibition of mPFC excitatory neurons dramatically inhibits social interaction and nullifies the prosocial effect of LSD. LSD potentiates the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and 5-HT2A, but not N-methyl-D-aspartate (NMDA) and 5-HT1A, synaptic responses in the mPFC and increases the phosphorylation of the serine-threonine protein kinases Akt and mTOR. In conditional knockout mice lacking Raptor (one of the structural components of the mTORC1 complex) in excitatory glutamatergic neurons (Raptorf/f:Camk2alpha-Cre), the prosocial effects of LSD and the potentiation of 5-HT2A/AMPA synaptic responses were nullified, demonstrating that LSD requires the integrity of mTORC1 in excitatory neurons to promote SB. Conversely, in knockout mice lacking Raptor in GABAergic neurons of the mPFC (Raptorf/f:Gad2-Cre), LSD promotes SB. These results indicate that LSD selectively enhances SB by potentiating mPFC excitatory transmission through 5-HT2A/AMPA receptors and mTOR signaling. The activation of 5-HT2A/AMPA/mTORC1 in the mPFC by psychedelic drugs should be explored for the treatment of mental diseases with SB impairments such as autism spectrum disorder and social anxiety disorder.
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Conducta Animal/efectos de los fármacos , Dietilamida del Ácido Lisérgico/farmacología , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Conducta Social , Transmisión Sináptica/efectos de los fármacos , Animales , Reacción de Prevención/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Optogenética , Fosforilación/efectos de los fármacos , Corteza Prefrontal/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células Piramidales/efectos de los fármacos , Células Piramidales/metabolismo , Receptores AMPA/agonistas , Receptores AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/agonistas , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de Serotonina/metabolismo , Sinapsis/efectos de los fármacos , Sinapsis/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
As the current demand for liver transplantation exceeds our donor pool, the donor search is shifted towards the extended donor criteria. The livers harbouring hydatid disease are a controversial source of grafts. We report the use of a liver graft harbouring hydatid disease in urgent liver transplantation in a patient with autoimmune hepatitis. Corroborated with previous experiences, we show that the liver grafts harbouring hydatid cysts provide a rare but valuable source of organs.