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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
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
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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Protección Radiológica , Encuestas y Cuestionarios , Humanos , Internet , Participación de los Interesados , Masculino , FemeninoRESUMEN
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
Fragile X syndrome (FXS) is the most frequent inherited form of intellectual disability and autism spectrum disorder. Loss of the fragile X mental retardation protein, FMRP, engenders molecular, behavioral, and cognitive deficits in FXS patients. Experiments using different animal models advanced our knowledge of the pathophysiology of FXS and led to the discovery of many targets for drug treatments. In this review, we discuss the potential of metformin, an antidiabetic drug approved by the US Food and Drug Administration, to correct core symptoms of FXS and other neurological disorders in humans. We summarize its mechanisms of action in different animal and cellular models and human diseases.
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Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Metformina/uso terapéutico , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Animales , Trastorno Autístico/diagnóstico , Trastorno Autístico/tratamiento farmacológico , Modelos Animales de Enfermedad , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/genética , Humanos , Ratones , Enfermedad de Parkinson/tratamiento farmacológico , Pronóstico , Serina-Treonina Quinasas TOR/genética , Resultado del TratamientoRESUMEN
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.
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Equinococosis Hepática/patología , Equinococosis/patología , Echinococcus/aislamiento & purificación , Trasplante de Hígado , Hígado/parasitología , Animales , Femenino , Supervivencia de Injerto , Hepatitis Autoinmune/cirugía , Humanos , Persona de Mediana Edad , Donantes de Tejidos/estadística & datos numéricos , Adulto JovenRESUMEN
Legacy sites are a global issue. Experience has shown that every legacy site is different and case-specific management and remediation options have to be considered. Each site presents a unique mix of physical, chemical and radiological hazards and the significance of those hazards is likely to change over time. A life-cycle approach to remediation is therefore appropriate, with priority consideration allocated according to the major hazards, as technically determined by reference to policy on protection objectives and the corresponding regulatory requirements. Additionally, consideration will typically need to be given to wider issues as may be raised by stakeholders. The remediation approach also needs to take account of the waste management options on-site or involving off-site management and disposal. Radiological and wider environmental impact assessments are a crucial part of the holistic evaluation of hazards and risks (along with economic and societal impacts), which in turn underpin project planning, regulatory and wider decision making. This paper examines the role of radioecology in the assessment process, its contribution to reduction of scientific uncertainties in modelling ecosystem processes of release, transport and fate of radionuclides and evaluation of potential ensuing impacts on humans and the environment. Relevant examples are presented to illustrate the complexities of the processes in regulatory decision making, the various conditions that significantly affect the final solutions and how radioecology can be used in these situations. Whilst a case-specific approach will usually need to be taken to legacy sites, future remediation and clean-up work can be helpfully informed through sharing of experience from other sites. Continued international collaboration between all parties involved in legacy site management is therefore needed to inform on the development of practical regulatory guidance and to ensure that radioecological research is focussed on addressing the key issues that give rise to uncertainties that challenge regulatory and wider decision making.
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Restauración y Remediación Ambiental , Contaminantes Radiactivos , Administración de Residuos/métodos , Ecosistema , Exposición a Riesgos Ambientales , Humanos , Internacionalidad , Monitoreo de Radiación , Medición de RiesgoRESUMEN
The risk from naturally occurring radioactive materials (NORM) has been extensively assessed, and this has led to the integration of specific NORM radiation protection requirements within the latest EU Directive 2013/59. Nevertheless, it has been internationally recognised that remaining NORM knowledge gaps and uncertainties now present similarly significant issues in addressing recent regulatory requirements. The multi-tiered nature of environmental impact assessment (EIA) implies per se possibility for uncertainties, but when EIA at radiation exposure sites includes consideration of sites with multiple radiation and contamination sources, different ecosystem transport pathways, effects and risks by applying different parameters and models, level of overall uncertainty increases. The results of EIA study in the Fen area in Norway, comprised of undisturbed and legacy NORM sites, have been evaluated in this analysis, in order to identify all existing input uncertainties and how they may impact the final conclusions, and thus, influence any subsequent decision-making. The main uncertainties have been identified in the measurement and exposure analysis tier, and were related to the heterogeneous distribution of radionuclides, radionuclide speciation, as well as to generic variability issues in the concepts used for mobility and biota uptake analysis (such as distribution coefficient, transfer factors and concentration ratios) as well as radioecological modelling. The uncertainties in the input values to the calculation of the dose arising from radon exposure in the Fen area led to an overall elevated uncertainty of the magnitude of the radiation exposure dose of humans. It has been concluded that an integrated, ecosystem-based approach with consideration of complexity of prevailing environmental conditions and interconnections must be applied to fully understand possible radiation effects and risks.
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Ecosistema , Exposición a la Radiación , Exposición a Riesgos Ambientales , Monitoreo del Ambiente , Humanos , Noruega , IncertidumbreRESUMEN
OBJECTIVE: To investigate the relationship of the effective dose and dose area product (DAP) in dental cone beam computed tomography (CBCT) examinations and to propose conversion factors for estimation of effective doses of the patients using DAP. Dependence of organ doses on DAP was also investigated. MATERIALS AND METHODS: Different exposure geometries in Cranex3Dx CBCT device were simulated using Monte Carlo simulation and computational anthropomorphic phantom. Then organ doses and effective dose for every exposure geometry was compared to DAP and analysed. RESULTS: The effective dose in all simulated CBCT protocols and positions with 180° tube rotation ranged from 5 µSv for 50 × 50 mm2 field of view (FOV) localised on one tooth using lowest resolution to 265 µSv for the largest FOV and highest resolution. In case of 360° tube rotation the effective dose ranges from 6 to 332 µSv for the same FOV sizes and positions as well as resolutions as in 180° tube rotation. CONCLUSIONS: Though the DAP introduces a large uncertainty in the risk measure in dental CBCT, it represents the dose and FOV size which are the most important scanning parameters affecting the dose. To decrease uncertainty in the risk measure, the effective dose has to be estimated for usual clinical positions of the FOV.
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Tomografía Computarizada de Haz Cónico , Dosis de Radiación , Radiografía Dental/métodos , Humanos , Fantasmas de Imagen , RadiometríaRESUMEN
Previously we observed that prolonged exposure to propofol anesthesia causes caspase-3- and calpain-mediated neuronal death in the developing brain. The present study examines the effects of propofol anesthesia on the expression of tumor necrosis factor-α (TNFα), pro-nerve growth factor (NGF), and their receptors in the cortex and the thalamus. We also investigated how propofol influences the expression of Akt and X-linked inhibitor of apoptosis (XIAP) expression, proteins that promote prosurvival pathways. Seven-day-old rats (P7) were exposed to propofol anesthesia lasting 2, 4, or 6 hr and killed 0, 4, 16, or 24 hr after anesthesia termination. The relative levels of mRNA and protein expression were estimated by RT-PCR and Western blot analysis, respectively. The treatments caused marked activation of TNFα and its receptor TNFR-1 and pro-NGF and p75(NTR) receptor expression. In parallel with the induction of these prodeath signals, we established that propofol anesthesia promotes increased expression of the prosurvival molecules pAkt and XIAP during the 24-hr postanesthesia period. These results show that different brain structures respond to propofol anesthesia with a time- and duration of exposure-dependent increase in proapoptotic signaling and with concomitant increases in activities of prosurvival proteins. We hypothesized that the fine balance between these opposing processes sustains homeostasis in the immature rat brain and prevents unnecessary damage after exposure to an injurious stimulus. The existence of this highly regulated process provides a time frame for potential therapeutic intervention directed toward suppressing the deleterious component of propofol anesthesia.
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Anestésicos Intravenosos/farmacología , Encéfalo/efectos de los fármacos , Factor de Crecimiento Nervioso/metabolismo , Proteína Oncogénica v-akt/metabolismo , Propofol/farmacología , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Proteína Inhibidora de la Apoptosis Ligada a X/metabolismo , Análisis de Varianza , Animales , Animales Recién Nacidos , Encéfalo/crecimiento & desarrollo , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Proteínas del Tejido Nervioso , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Receptores de Factores de Crecimiento , Receptores de Factor de Crecimiento Nervioso/genética , Receptores de Factor de Crecimiento Nervioso/metabolismoRESUMEN
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
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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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
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) 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
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) 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
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 present study was done in the Fen Complex, a Norwegian area rich in naturally occurring radionuclides, especially in thorium ((232)Th). Measurement of radioactivity levels was conducted at the decommissioned iron (Fe) and niobium (Nb) mining sites (TENORM) as well as at the undisturbed wooded sites (NORM), all open for free public access. The soil activity concentrations of (232)Th (3280-8395 Bq kg(-1)) were significantly higher than the world and the Norwegian average values and exceeded the Norwegian screening level (1000 Bq kg(-1)) for radioactive waste, while radium ((226)Ra) was present at slightly elevated levels (89-171 Bq kg(-1)). Terrestrial gamma dose rates were also elevated, ranging 2.6-4.4 µGy h(-1). Based on long-term surveys, the air concentrations of thoron ((220)Rn) and radon ((222)Rn) reached 1786 and 82 Bq m(-3), respectively. Seasonal variation in the outdoor gamma dose rates and Rn concentrations was confirmed. Correlation analyses showed a linear relationship between air radiation levels and the abundance of (232)Th in soil. The annual outdoor effective radiation doses for humans (occupancy 5 h day(-1)) were estimated to be in the range of 3.0-7.7 mSv, comparable or higher than the total average (summarized indoor and outdoor) exposure dose for the Norwegian population (2.9 mSv year(-1)). On the basis of all obtained results, this Norwegian area should be considered as enhanced natural radiation area (ENRA).
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Rayos gamma , Monitoreo de Radiación , Radón/análisis , Contaminantes Radiactivos del Suelo/análisis , Contaminantes Radiactivos del Aire/análisis , Humanos , Minería , Noruega , Dosis de Radiación , Estaciones del Año , Suelo/química , Torio/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.