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Radionuclides are of paramount importance in nuclear medicine both for clinical uses and radiopharmaceutical production. Among the others, nuclides suitable for theranostics like Copper-64 are particularly attractive since they can play both a diagnostic and therapeutic role. In the last years, the growing demand for these nuclides stimulated the research of new solutions, along with cyclotrons already in use, for their production. In this respect, a promising alternative is laser-driven proton accelerators based on the interaction of superintense laser pulses with target materials. Because of their potential compactness and flexibility, they are under investigation for several applications ranging from materials science to nuclear medicine. Moreover, the use of advanced Double-Layer targets (DLTs) was identified as a viable route to increase the number and energy of the accelerated protons to satisfy the requirements of demanding applications. In this contribution, we numerically investigate the use of DLT-based laser-driven sources for Copper-64 production. We show that activities relevant to pre-clinical studies can be achieved with an existing 150 TW laser and DLTs. Moreover, we extend the discussion by considering a broad range of laser systems by exploiting a theoretical model. Our results can guide the choice of laser and target parameters for future experimental investigations.

Abstract Introduction Entrustable professional activities (EPAs) are one way to assess competencies, and are designed to bridge the gap between theoretical competencies and real world clinical practice. Aims This was a systematic review which aims to answer the question: “Which EPAs related to Emergency Medicine are described for medical schools?”. Methods We included original qualitative, interventional and observational studies (cross-sectional, case-control, and cohort studies) that described EPAs relevant to Emergency Medicine for Medical School. The search strategy was created using a combination of keywords and standardized index terms related to EPAs and Emergency Medicine. Results The search strategy identified 991 citations. After screening the titles and abstracts, we identified 85 potentially relevant studies. After the full-text review, a total of 11 reports met the criteria for inclusion. Conclusion Recognizing a patient requiring urgent or emergent care and initiating evaluation and management is the most common EPA related to Emergency Medicine described at Medical Schools. Use of EPAs is associated with increased student satisfaction and improved competences. However, there is a lack of undergraduate EM specific EPAs being systematically developed and published, and this should be an area to be explored in future studies.

Introdução: durante a pandemia, as fragilidades do sistema refletiram negativamente na saúde mental da equipe de saúde que atuou na linha de frente. Objetivo: identificar os fatores associados ao estresse, ansiedade e depressão entre profissionais de enfermagem, um ano após o início do enfrentamento à pandemia causada pela COVID-19. Métodos: estudo exploratório e transversal, realizado com profissionais de enfermagem de uma unidade específica para cuidados aos acometidos pela COVID-19. Foi utilizado questionário sociodemográfico e laboral, além de uma escala para avaliação da ansiedade, depressão e estresse já validada no Brasil. Resultados: dos 106 participantes, houve predomínio de mulheres (87,7%), técnicos de enfermagem (77,4%), com idade média de 36,7 anos. Entre os profissionais avaliados, 49,5% apresentaram ansiedade, 49,5% depressão e 35,84% estresse. Esses transtornos mentais comuns estiveram associados à categoria profissional, vínculo empregatício, sobrecarga de trabalho, satisfação e motivação no trabalho. Conclusão: Os fatores associados à ansiedade, estresse e depressão, entre profissionais de enfermagem que atuam no enfrentamento da COVID-19, um ano após o início da pandemia foram identificados por meio do presente estudo.

Abstract Objective To determine the relationship between early age at menarche, late age at menopause with specific subtypes of breast cancer (BC). Methods A literature search was conducted in Embase, Lilacs, PubMed, Scopus, and Scielo databases, following the Joanna Briggs Institute scoping review protocol and answering the question “How early age at menarche or late age at menopause are related to different breast cancer subtypes?”. Results A number of 4,003 studies were identified, of which 17 were selected. Most of the included articles found a clear relationship between early menarche, late menopause and some subtypes of BC, mainly, PR+, ER+, luminal, and HER-2 tumors. However, some studies have found a contradictory relationship and one study didn’t find any relationship between them. Conclusion A relationship between early age at menarche and advanced age at menopause was observed with some subtypes of breast cancer, since other factors must be considered in its understanding.

Brain is most cholesterol-rich organ in the body. Since cholesterol does not cross the blood brain barrier, its metabolism is provided in situ by astrocytes and neurons, and it is crucial for maintaining sterol levels and neuronal integrity and function. Recent studies have shown that the levels of cholesterol precursors and metabolites are lower in the brains of animal models of Huntington's disease (HD) while reduced levels of its catabolite are detected in the plasma of patients. In this study, we introduce a novel analytical method designed to fulfill the complex analytical requirements associated with cholesterol metabolites detection in neurodegenerative disorders. The method allows for the simultaneous quantification of a specific set of oxysterols along with cholesterol precursors in biological samples.The proposed method uses an Ultra-High-Performance Liquid Chromatography-Mass Spectrometry (UHPLC-MS) system operating in multiple reaction monitoring (MRM). Since sterols can be found in biological matrices in either free form or esterified to various fatty acids, a three-step extraction procedure was devised, consisting of alkaline hydrolysis, liquid-liquid extraction and final concentration omitting the need for a solid-phase extraction (SPE) step.The validated method achieved a detection limit of 10 ng/mL in plasma and 1 ng/mg in brain tissue, reaching a comparable sensitivity to previously published LC-MS and GC–MS methods. All target analytes were separated on a reverse-phase column employing a segmented gradient and a temperature ramp. This strategy enabled the elution and separation of all selected metabolites within a 30-minutes timeframe. This innovative approach was employed to quantify cholesterol metabolites in both plasma and brain samples from wild-type (WT) and R6/2 mice, a mouse model of HD. The results obtained from the sample analysis highlighted a significant reduction in desmosterol levels in the R6/2 brain at 12 weeks.In conclusion, the proposed method paves the way for further development of high-sensitive and reproducible protocols to comprehensively investigate simultaneous alterations in both cholesterol biosynthesis and catabolism in HD samples.

RESUMO Nessa resenha apresentamos e discutimos a obra Supporting Multilingual Learners’ Academic Language Development: A Language-Based Approach to Content Instruction, de Luciana C. de Oliveira, publicada em 2023 pela Routledge. O livro apresenta uma abordagem inovadora direcionada a profissionais que atuam na Educação Básica lecionando a estudantes multilíngues (EMs), o Language-Based Approach to Content Instruction (LACI) ou o Ensino de Conteúdo por Meio da Língua (ECML), o qual caracteriza-se tanto como um referencial para subsidiar o planejamento de aulas, quanto um modelo para formação de professores que integra língua e conteúdo. A proposta da autora visa a contemplar a crescente presença de EMs em todo o mundo, com especial ênfase na realidade dos EUA e sua imigração. Apesar de ser originária de um contexto que pode ser considerado bastante distinto do brasileiro, o LACI/ECML apresenta subsídios relacionados às metodologias e às especificidades da linguagem disciplinar de cada área, que podem ser adaptadas às escolas e à formação de professores no Brasil para a educação bi/multilíngue, área em recente ascensão no país que carece de orientações teórico-práticas.

ABSTRACT Objective To evaluate, characterize and search for trends in the underreporting of diabetes mellitus (DM) as the cause of death in Bauru, São Paulo, Brazil, over 40 years. Subjects and methods This was a documental study. Clinical and mortality data were collected from individuals known to have type 1 (DM1) and type 2 diabetes mellitus (DM2), residing in Bauru, State of São Paulo, followed at a local endocrinology clinic from 1982 to 2021, who deceased during this period. Results A significant underreporting of DM as the cause of death (64.41%) was found, mostly associated with male gender (OR = 1.59 [95% CI: 1.18; 2.15]; p < 0.01), DM2 (OR = 2.64 [95% CI: 1.32; 5.26]; p < 0.01), dying in the first decade of the study (OR = 4.07 [95% CI: 1.54; 10.71]; p < 0.001) and shorter DM duration (OR = 1.02 [95% CI: 1.01; 1.04]; p < 0.01). Age, type of treatment, body mass index, marital status and ethnicity, did not show a significant association with DM underreporting. There was a decreasing trend in DM1 underreporting (Decade Percentual Change = -7.10 [95% CI: -11.35; -3.40]), but a stationary trend for DM and DM2. The main primary cause of death was cardiovascular-related complications. Conclusion The underreporting of DM as the cause of death was very frequently found, and was associated with male gender, decade of death, shorter DM duration and DM2. If our data could be applied to the whole country, DM would possibly emerge as a more prominent cause of death in Brazil. Future studies in other cities and geographic regions are warranted to confirm our findings.

Background and purpose: To assess feasibility, toxicity and outcome of moderately hypofractionated radiotherapy concomitant to capecitabine after induction chemotherapy for advanced pancreatic cancer. Materials and methods: Patients with advanced pancreatic cancer without distant progression after induction chemotherapy (CHT) were considered. Radiochemotherapy (RCT) consisted of 44.25 Gy in 15 fractions to the tumor and involved lymph-nodes concomitant to capecitabine 1250 mg/m2/day. Feasibility and toxicity were evaluated in all pts. Overall survival (OS), progression free survival (PFS), distant PFS (DPFS) and local PFS (LPFS) were assessed only in stage III patients. Results: 254 patients, 220 stage III, 34 stage IV, were treated. Median follow up was 19 months. Induction CHT consisted of Gemcitabine (35 patients), or drug combination (219 patients); median duration was 6 months.Four patients (1.6 %) did not complete RT (1 early progression, 3 toxicity), median duration of RT was 20 days, 209 patients (82 %) received ≥ 75 % of capecitabine dose.During RCT G3 gastrointestinal toxicity occurred in 3.2% of patients, G3-G4 hematologic toxicity in 5.4% of patients. Subsequently, G3, G4, G5 gastric or duodenal lesions occurred in 10 (4%), 2 (0.8%) and 1 patients (0.4%), respectively.Median PFS, LPFS, and DPFS were 11.9 months (95 % CI:11.4–13), 16 months (95 % CI:14.2–17.3) and 14.0 months (95 % CI:12.6–146.5), respectively.Median OS was 19.5 months (95 % CL:18.1–21.3). One- and two-year survival were 85.2 % and 36 %, respectively. Conclusions: The present schedule of hypofractionated RT after induction CHT is feasible with acceptable toxicity rate and provides an outcome comparable with that achievable with standard doses and fractionation.

IntroductionAmong girls assessed for pubertal precocity, pelvic ultrasound (pUS) may represent a pivotal tool to predict the time expected to elapse between sonographic assessment and the onset of menarche (TUS-M). Accordingly, the present analysis is meant to define the statistical relationship between sonographic parameters and TUS-M, in order to identify the most reliable predictor of the timing of menarche.MethodsRetrospective, multicenter analysis. Girls assessed for sexual precocity and showing sonographic and clinical findings consistent with pubertal onset upon referral were considered eligible. Patients treated with GnRH analogues were excluded and only those who had subsequently achieved complete and spontaneous pubertal attainment and for whom the exact date of menarche was available were included. Overall, we enrolled 184 girls from five tertiary care Italian Centers.ResultsThe time elapsed (months) between baseline endocrine assessment and spontaneous achievement of menarche showed a negative statistically significant correlation (p

Nanofoam materials are gaining increasing interest in the scientific community, thanks to their unique properties such as ultralow density, complex nano‐ and microstructure, and high surface area. Nanofoams are attractive for multiple applications, ranging from advanced catalysis and energy storage to nuclear fusion and particle acceleration. The main issues hindering the widespread use of nanofoams are related to the choice of synthesis technique, highly dependent on the desired elemental composition and leading to a limited control over the main material properties. Herein, femtosecond pulsed laser deposition is proposed as a universal tool for the synthesis of nanofoams with tailored characteristics. Nanofoams made by elements with significantly different properties—namely, boron, silicon, copper, tungsten, and gold—can be produced by suitably tuning the deposition parameters. The effect of the background pressure is studied in detail, in relation to the morphological features and density of the resulting nanofoams and nanostructured films. This, together with the analysis of the specific features shown by nanofoams made of different elements, offers fresh insights into the aggregation process and its relation to the corresponding nanofoam properties down to the nanoscale, opening new perspectives toward the application of nanofoam‐based materials.

Esta investigación se centra en proporcionar una nueva perspectiva desde la cual examinar la respuesta dogmático-penal en casos de ciberincidentes, en los que la información afectada sea recuperable mediante copias de seguridad. Con este propósito se analizará el delito de sabotaje contra datos informáticos, conforme al artículo 264.1 del Código Penal español reformado por la Ley Orgánica 1/2015, en atención a las reformas legislativas comunitarias en materia penal y de ciberseguridad. Además, se explorarán diversas perspectivas doctrinarias y jurisprudenciales. Como se demostrará en este trabajo, la recuperabilidad del objeto material del delito convierte el supuesto fáctico descrito en un caso de atipicidad. Asimismo, en situaciones de pérdida total o parcial de la información, la reacción penal solo estará justificada si se cumple con el elemento típico de la doble gravedad, como consecuencia del sentido interpretativo restrictivo plasmado en el texto legal y a la política criminal de la Unión Europea en materia de ciberdelincuencia.

Pulsed laser deposition and subsequent thermal treatment were used to create compact tungsten layers with various grain sizes (1μm, 100 nm, and 10 nm). The layers were self-damaged at room temperature up to 0.23 dpa using 20.3 MeV W ions and annealed in vacuum at 473 K or 673 K prior to exposure to deuterium plasma to populate the surviving displacement defects. Thermal desorption spectroscopy was used to measure deuterium retention and study the desorption profile. Rate-equation modeling of the desorption spectra was performed to study the behavior of individual traps at both annealing temperatures. After annealing the 1μm and 100 nm samples at 473 K, the deuterium retention was found to decrease by 24% and 9%, respectively, whereas the total deuterium retention in the 10 nm sample did not change. Annealing at 673 K reduced total deuterium retention by additional 27%, 14%, and 34% in the case of the samples with a grain size of 1μm, 100 nm, and 10 nm, respectively.

Abstract Prune belly syndrome (PBS), also known as Eagle-Barret syndrome, is a rare, multi-system congenital myopathy primarily affecting males. Phenotypically, PBS cases manifest three cardinal pathological features: urinary tract dilation with poorly contractile smooth muscle, wrinkled flaccid ventral abdominal wall with skeletal muscle deficiency, and intra-abdominal undescended testes. Genetically, PBS is poorly understood. After performing whole exome sequencing in PBS patients, we identify one compound heterozygous variant in the PIEZO1 gene. PIEZO1 is a cation-selective channel activated by various mechanical forces and widely expressed throughout the lower urinary tract. Here we conduct an extensive functional analysis of the PIEZO1 PBS variants that reveal loss-of-function characteristics in the pressure-induced normalized open probability (NPo) of the channel, while no change is observed in single-channel currents. Furthermore, Yoda1, a PIEZO1 activator, can rescue the NPo defect of the PBS mutant channels. Thus, PIEZO1 mutations may be causal for PBS and the in vitro cellular pathophysiological phenotype could be rescued by the small molecule, Yoda1. Activation of PIEZO1 might provide a promising means of treating PBS and other related bladder dysfunctional states.

The influence of grain boundaries on deuterium (D) retention and transport was investigated in nanocrystalline tungsten (W) by exposing the samples to sub eV D atoms. Thin tungsten films with nanometer-sized grains were produced by pulsed laser deposition on tungsten substrates. Their grain size was increased up to one micrometer by thermal annealing in vacuum up to 1223 K. Irradiation damage was created by 20 MeV W ions at 290 K. The transmission electron microscopy analysis showed one order of magnitude larger dislocation density in nanometer-grained samples compared with the larger-grained samples. The samples were after W irradiation exposed to 0.3 eV D atoms at 600 K. D retention and D depth profiles were measured by nuclear reaction analysis. In the as-deposited nanometer-grained samples, D populated the damaged region more than three times faster than in the samples with larger grains, indicating that grain-boundaries increase D transport through the material. The concentration of defects was assessed by the final D concentration in the samples. The sample with the smallest grain size showed slightly larger D concentration in the irradiated area, but the difference in the D concentration was not substantial between different-grained samples. A large D concentration in the non-irradiated nanometer-grained sample was measured which is an indication for a high defect density in the initial material. From our observations, it can be postulated that the nanocrystalline microstructure did not substantially influence the generation of irradiation-induced defects by defect annihilation at grain boundaries.

This work presents a comprehensive study of the burst of an LPG tank in Gravedona, Italy. The possible causes of the burst were investigated through analytical methods and numerical simulations. That is, an analytical lumped system analysis was conducted to accurately predict the thermodynamic properties of the LPG–air mixture within the tank during filling operations. Additionally, computational fluid dynamics (CFD) simulations were carried out to (i) better capture local effects and (ii) determine if the mixture reached explosive conditions during these operations. The likelihood that possible mechanical defects led to the burst of the tank during filling operations was also evaluated through numerical simulations. The proposed methods were validated against experimental observations, confirming their accuracy and reliability. Furthermore, a specifically developed analytical model was used to describe the tank’s dynamic response after the burst. The results provided a comprehensive understanding of the cause of the burst thanks to the combination of analytical models and numerical simulations. The derived insights not only pinpointed the factors leading to the incident, but also provided valuable perspectives for predicting and preventing similar occurrences.

In this paper, we present a bolt preload monitoring system, including the system architecture and algorithms. We show how Finite Element Method (FEM) simulations aided the design and how we processed signals to achieve experimental validation. The preload is measured using a Piezoelectric Micromachined Ultrasonic Transducer (PMUT) in pulse-echo mode, by detecting the Change in Time-of-Flight (CTOF) of the acoustic wave generated by the PMUT, between no-load and load conditions. We performed FEM simulations to analyze the wave propagation inside the bolt and understand the effect of different configurations and parameters, such as transducer bandwidth, transducer position (head/tip), presence or absence of threads, as well as the frequency of the acoustic waves. In order to couple the PMUT to the bolt, a novel assembly process involving the deposition of an elastomeric acoustic impedance matching layer was developed. We achieved, for the first time with PMUTs, an experimental measure of bolt preload from the CTOF, with a good signal-to-noise ratio. Due to its low cost and small size, this system has great potential for use in the field for continuous monitoring throughout the operative life of the bolt.

Abstract Background One in five adults in the US experience mental illness and over half of these adults do not receive treatment. In addition to the access gap, few innovations have been reported for ensuring the right level of mental healthcare service is available at the right time for individual patients. Methods Historical observational clinical data was leveraged from a virtual healthcare system. We conceptualize mental healthcare services themselves as therapeutic interventions and develop a prototype computational framework to estimate their potential longitudinal impacts on depressive symptom severity, which is then used to assess new treatment schedules and delivered to clinicians via a dashboard. We operationally define this process as “session dosing”: 497 patients who started treatment with severe symptoms of depression between November 2020 and October 2021 were used for modeling. Subsequently, 22 mental health providers participated in a 5-week clinical quality improvement (QI) pilot, where they utilized the prototype dashboard in treatment planning with 126 patients. Results The developed framework was able to resolve patient symptom fluctuations from their treatment schedules: 77% of the modeling dataset fit criteria for using the individual fits for subsequent clinical planning where five anecdotal profile types were identified that presented different clinical opportunities. Based on initial quality thresholds for model fits, 88% of those individuals were identified as adequate for session optimization planning using the developed dashboard, while 12% supported more thorough treatment planning (e.g. different treatment modalities). In the clinical pilot, 90% of clinicians reported using the dashboard a few times or more per member. Although most clinicians (67.5%) either rarely or never used the dashboard to change session types, numerous other discussions were enabled, and opportunities for automating session recommendations were identified. Conclusions It is possible to model and identify the extent to which mental healthcare services can resolve depressive symptom severity fluctuations. Implementation of one such prototype framework in a real-world clinic represents an advancement in mental healthcare treatment planning; however, investigations to assess which clinical endpoints are impacted by this technology, and the best way to incorporate such frameworks into clinical workflows, are needed and are actively being pursued.

Abstract The interest in compact, cost-effective, and versatile accelerators is increasing for many applications of great societal relevance, ranging from nuclear medicine to agriculture, pollution control, and cultural heritage conservation. For instance, Particle Induced X-ray Emission (PIXE) is a non-destructive material characterization technique applied to environmental analysis that requires MeV-energy ions. In this context, superintense laser-driven ion sources represent a promising alternative to conventional accelerators. In particular, the optimization of the laser-target coupling by acting on target properties results in an enhancement of ion current and energy with reduced requirements on the laser system. Among the advanced target concepts that have been explored, one appealing option is given by double-layer targets (DLTs), where a very low-density layer, which acts as an enhanced laser absorber, is grown to a thin solid foil. Here we present some of the most recent results concerning the production with deposition techniques of advanced DLTs for laser-driven particle acceleration. We assess the potential of these targets for laser-driven ion acceleration with particle-in-cell simulations, as well as their application to PIXE analysis of aerosol samples with Monte Carlo simulations. Our investigation reports that MeV protons, accelerated with a ∼20 TW compact laser and optimized DLTs, can allow performing PIXE with comparable performances to conventional sources. We conclude that compact DLT-based laser-driven accelerators can be relevant for environmental monitoring.

Objectives: To compare the utilization of prenatal services between immigrant and Italian women during the COVID-19 pandemic.Methods: A cross-sectional survey was conducted at 3 maternity care centers in Italy.Results: We included 1,312 women, 1,198 (91.3%) were Italian and 114 (8.7%) were immigrants. A significantly higher proportion of Italians underwent 8 or more prenatal care visits (64.4% vs. 54.4%, p = 0.03) and more immigrants than Italians attended their appointments at hospital settings (45% vs. 18%, p < 0.001). Regarding prenatal course, Italians were more likely than immigrants to attend a non-hospital setting or an online class (49.6% and 30.2% vs. 34.9% and 11.6%, p = 0.008). A higher influenza vaccine uptake among immigrants compared with Italians was observed (39.5% vs. 19.8%, p < 0.001). Among women not receiving certain prenatal services, immigrants were more likely to state COVID-19 pandemic was the main reason for non-compliance.Conclusion: Immigrant pregnant women were more likely to receive prenatal services at a hospital setting than their Italian counterparts. Among women who did not comply with prenatal services, immigrants were more likely to cite the pandemic as their main reason.

The influence of grain boundaries (GBs) on the deuterium (D) transport and the creation of defects in nanocrystalline tungsten (W) films deposited on a W substrate was studied. Samples with three different grain sizes were produced for this purpose: a sample with a film having nanometer-size grains, a sample with hundred nanometer-grained film and a sample with micrometer-grained film. Samples were irradiated by 20 MeV W ions at 300 K to create displacement damage and exposed to 300 eV D ions at 450 K to populate the created and any pre-existing defects. The D transport and retention was assessed by measuring D depth profiles after certain exposure times by nuclear reaction analysis (NRA) using a 3He ion beam. From the final D concentration in the damaged area we could determine the concentration of defects that trap hydrogen, showing that the sample with the smallest grain size had the highest D concentration and it decreases with the increase of the grain size. Therefore, in nanocrystalline tungsten irradiated at 300 K, GBs do not improve radiation resistance, which would lead to fewer defects. For the first time, we show experimentally, that D transport is faster inside the nanometer-grained sample as compared to the micrometer-grained sample, meaning that D atoms have enhanced bulk diffusion along GBs. Accidentally, the film thickness was so thin that the W irradiation reached the interface between the W film and substrate, where NRA showed enhanced retention of oxygen. At that depth, two times higher D concentration was observed compared to D concentration in the damaged area in the middle of the film indicating on defect stabilization due to the presence of oxygen.

We describe the development and validation of a HPLC-MS/MS method to assess the pharmacokinetics and tumor distribution of fenretinide, a synthetic retinoid chemically related to all-trans-retinoic acid, after administration of a novel oral nanoformulation of fenretinide, called bionanofenretinide (BNF). BNF was developed to overcome the major limitation of fenretinide: its poor aqueous solubility and bioavailability due to its hydrophobic nature. The method proved to be reproducible, precise and highly accurate for the measurement of the drug and the main metabolites. The lower limit of quantification resulted in 1 ng/mL. The curve range of 1–500 ng/mL and 50–2000 ng/mL, for plasma and tumor homogenate, respectively, was appropriate for the analysis, as demonstrated by the accuracy of between 96.8% and 102.4% for plasma and 96.6 to 102.3% for the tumor. The interdays precision and accuracy determined on quality controls at three different levels were in the ranges of 6.9 to 7.5% and 99.3 to 101.0%, and 0.96 to 1.91% and 102.3 to 105.8% for plasma and tumor, respectively. With the application of the novel assay in explorative pharmacokinetic studies, following acute and chronic oral administration of the nanoformulation, fenretinide was detected in plasma and tumor tissue at a concentration higher than the IC50 value necessary for in vitro inhibitory activity (i.e., 1–5 µM) in different cancer cells lines. We were also able to detect the presence in plasma and tumor of active and inactive metabolites of fenretinide.

RESUMO Objetivo: Identificar se a capacitação dos enfermeiros pode interferir nas taxas de prevalência de lesão por pressão em pacientes internados em uma Unidade de Terapia Intensiva. Métodos: Trata-se de um estudo quase experimental, de caráter quantitativo, com delineamento antes e depois da aplicação da intervenção educativa, a qual avaliou a influência da capacitação para enfermeiros atuantes em uma unidade de terapia intensiva sobre os índices de LPP. Resultados: A amostra total do estudo foi composta por 39 pacientes, dos quais 16 foram avaliados na primeira coleta de dados, com prevalência de 56,3% de LPP e 23 foram avaliados na segunda coleta, dos quais 60,9% apresentaram lesões. A maioria dessas LPP foram avaliadas como estágio 2, sendo o calcâneo, o segmento mais acometido. Conclusão: Os resultados demonstraram que a capacitação realizada somente com os enfermeiros de tais unidades não influenciou significativamente na redução da prevalência de LPP, podendo estar relacionada ao intervalo temporal entre a capacitação e a avaliação. Porém, os resultados demonstraram um aumento significativo na utilização de medidas preventivas, fato que, que possivelmente poderá resultar em uma redução destes indicadores em um segundo momento. Palavras-chave: Lesão por pressão; Capacitação profissional; Unidades de terapia intensiva; Cuidados de enfermagem.

Different kinds of W layers resembling the ones found after campaigns in tokamak were produced by Pulsed Laser Deposition: namely nanocrystalline, amorphous and porous W layers. Films were exposed to divertor relevant D plasma, in PSI-2; D retention as well as nanostructure formation were investigated. For nanocrystalline W films we found lamellar structures that coalesce with increasing D fluence. Instead, on amorphous W no lamellas were formed but a new random string-like shape. A higher oxygen content in the W layer results in an evolution of the shape of the nanostructures in straight parallel lines with acute angles. The presence of a porous structure morphology hinders the formation of surface nanostructures. Reviewing results from different linear devices including also bulk W, we observe that, when formed, nanostructures appear in general with a fluence threshold of 3–5 × 1025 D/m2 regardless the impinging D flux. D retention shows an unusual trend increasing fluence and is enhanced by the presence of amorphous structure and open morphology. Amorphous W films exhibit higher D retention (3 orders of magnitude) compared to crystalline W. When the amorphous W is annealed, retention returns to the standard values of bulk W regardless the presence of a layered structure parallel to the substrate. Porous W, thanks to the high surface to volume ratio and the presence of void distribution along the growth direction, favors higher recycling and thus limits the D uptake during exposure. The presence of O, in the investigated coatings, seems to have little effect on D retention.

Evidence that Huntington's disease (HD) is characterized by impaired cholesterol biosynthesis in the brain has led to strategies to increase its level in the brain of the rapidly progressing R6/2 mouse model, with a positive therapeutic outcome. Here we tested the long-term efficacy of chronic administration of cholesterol to the brain of the slowly progressing zQ175DN knock-in HD mice in preventing (“early treatment”) or reversing (“late treatment”) HD symptoms. To do this we used the most advanced formulation of cholesterol loaded brain-permeable nanoparticles (NPs), termed hybrid-g7-NPs-chol, which were injected intraperitoneally. We show that one cycle of treatment with hybrid-g7-NPs-chol, administered in the presymptomatic (“early treatment”) or symptomatic (“late treatment”) stages is sufficient to normalize cognitive defects up to 5 months, as well as to improve other behavioral and neuropathological parameters. A multiple cycle treatment combining both early and late treatments (“2 cycle treatment”) lasting 6 months generates therapeutic effects for more than 11 months, without severe adverse reactions. Sustained cholesterol delivery to the brain of zQ175DN mice also reduces mutant Huntingtin aggregates in both the striatum and cortex and completely normalizes synaptic communication in the striatal medium spiny neurons compared to saline-treated HD mice. Furthermore, through a meta-analysis of published and current data, we demonstrated the power of hybrid-g7-NPs-chol and other strategies able to increase brain cholesterol biosynthesis, to reverse cognitive decline and counteract the formation of mutant Huntingtin aggregates. These results demonstrate that cholesterol delivery via brain-permeable NPs is a therapeutic option to sustainably reverse HD-related behavioral decline and neuropathological signs over time, highlighting the therapeutic potential of cholesterol-based strategies in HD patients. Data availability: This study does not include data deposited in public repositories. Data are available on request to the corresponding authors.

Radionuclides are of paramount importance in nuclear medicine both for clinical uses and radiopharmaceutical production. Among the others, nuclides suitable for theranostics like Copper-64 are particularly attractive since they can play both a diagnostic and therapeutic role. In the last years, the growing demand for these nuclides stimulated the research of new solutions, along with cyclotrons already in use, for their production. In this respect, a promising alternative is laser-driven proton accelerators based on the interaction of superintense laser pulses with target materials. Because of their potential compactness and flexibility, they are under investigation for several applications ranging from materials science to nuclear medicine. Moreover, the use of advanced Double-Layer targets (DLTs) was identified as a viable route to increase the number and energy of the accelerated protons to satisfy the requirements of demanding applications. In this contribution, we numerically investigate the use of DLT-based laser-driven sources for Copper-64 production. We show that activities relevant to pre-clinical studies can be achieved with an existing 150 TW laser and DLTs. Moreover, we extend the discussion by considering a broad range of laser systems by exploiting a theoretical model. Our results can guide the choice of laser and target parameters for future experimental investigations.

Tokamak à configuration variable (TCV), recently celebrating 30 years of near-continual operation, continues in its missions to advance outstanding key physics and operational scenario issues for ITER and the design of future power plants such as DEMO. The main machine heating systems and operational changes are first described. Then follow five sections: plasma scenarios. ITER Base-Line (IBL) discharges, triangularity studies together with X3 heating and N2 seeding. Edge localised mode suppression, with a high radiation region near the X-point is reported with N _2 injection with and without divertor baffles in a snowflake configuration. Negative triangularity (NT) discharges attained record, albeit transient, β _N ∼ 3 with lower turbulence, higher low-Z impurity transport, vertical stability and density limits and core transport better than the IBL. Positive triangularity L-Mode linear and saturated ohmic confinement confinement saturation, often-correlated with intrinsic toroidal rotation reversals, was probed for D, H and He working gases. H-mode confinement and pedestal studies were extended to low collisionality with electron cyclotron heating obtaining steady state electron iternal transport barrier with neutral beam heating (NBH), and NBH driven H-mode configurations with off-axis co-electron cyclotron current drive. Fast particle physics. The physics of disruptions, runaway electrons and fast ions (FIs) was developed using near-full current conversion at disruption with recombination thresholds characterised for impurity species (Ne, Ar, Kr). Different flushing gases (D2, H2) and pathways to trigger a benign disruption were explored. The 55 kV NBH II generated a rich Alfvénic spectrum modulating the FI fas ion loss detector signal. NT configurations showed less toroidal Alfvén excitation activity preferentially affecting higher FI pitch angles. Scrape-off layer and edge physics. gas puff imaging systems characterised turbulent plasma ejection for several advanced divertor configurations, including NT. Combined diagnostic array divertor state analysis in detachment conditions was compared to modelling revealing an importance for molecular processes. Divertor physics. Internal gas baffles diversified to include shorter/longer structures on the high and/or low field side to probe compressive efficiency. Divertor studies concentrated upon mitigating target power, facilitating detachment and increasing the radiated power fraction employing alternative divertor geometries, optimised X-point radiator regimes and long-legged configurations. Smaller-than-expected improvements with total flux expansion were better modelled when including parallel flows. Peak outer target heat flux reduction was achieved (>50%) for high flux-expansion geometries, maintaining core performance ( H _98 > 1). A reduction in target heat loads and facilitated detachment access at lower core densities is reported. Real-time control. TCV’s real-time control upgrades employed MIMO gas injector control of stable, robust, partial detachment and plasma β feedback control avoiding neoclassical tearing modes with plasma confinement changes. Machine-learning enhancements include trajectory tracking disruption proximity and avoidance as well as a first-of-its-kind reinforcement learning-based controller for the plasma equilibrium trained entirely on a free-boundary simulator. Finally, a short description of TCV’s immediate future plans will be given.

Within the 9th European Framework programme, since 2021 EUROfusion is operating five tokamaks under the auspices of a single Task Force called ‘Tokamak Exploitation’. The goal is to benefit from the complementary capabilities of each machine in a coordinated way and help in developing a scientific output scalable to future largre machines. The programme of this Task Force ensures that ASDEX Upgrade, MAST-U, TCV, WEST and JET (since 2022) work together to achieve the objectives of Missions 1 and 2 of the EUROfusion Roadmap: i) demonstrate plasma scenarios that increase the success margin of ITER and satisfy the requirements of DEMO and, ii) demonstrate an integrated approach that can handle the large power leaving ITER and DEMO plasmas. The Tokamak Exploitation task force has therefore organized experiments on these two missions with the goal to strengthen the physics and operational basis for the ITER baseline scenario and for exploiting the recent plasma exhaust enhancements in all four devices (PEX: Plasma EXhaust) for exploring the solution for handling heat and particle exhaust in ITER and develop the conceptual solutions for DEMO. The ITER Baseline scenario has been developed in a similar way in ASDEX Upgrade, TCV and JET. Key risks for ITER such as disruptions and run-aways have been also investigated in TCV, ASDEX Upgrade and JET. Experiments have explored successfully different divertor configurations (standard, super-X, snowflakes) in MAST-U and TCV and studied tungsten melting in WEST and ASDEX Upgrade. The input from the smaller devices to JET has also been proven successful to set-up novel control schemes on disruption avoidance and detachment.

An overview is presented of the progress since 2021 in the construction and scientific programme preparation of the Divertor Tokamak Test (DTT) facility. Licensing for building construction has been granted at the end of 2021. Licensing for Cat. A radiologic source has been also granted in 2022. The construction of the toroidal field magnet system is progressing. The prototype of the 170 GHz gyrotron has been produced and it is now under test on the FALCON facility. The design of the vacuum vessel, the poloidal field coils and the civil infrastructures has been completed. The shape of the first DTT divertor has been agreed with EUROfusion to test different plasma and exhaust scenarios: single null, double null, X-divertor and negative triangularity plasmas. A detailed research plan is being elaborated with the involvement of the EUROfusion laboratories.

Psoriasis is a chronic immune-mediated disease that is linked to an increased risk of cancer. Although numerous studies have explored whether neoplasms are concurrent conditions or are induced by psoriasis, a definitive definition remains elusive. In this study, we conducted a comprehensive narrative literature review to offer practical guidance to oncologists and dermatologists regarding the initiation and discontinuation of biologics for psoriasis. The findings indicate that a customized approach is recommended for each patient, and that a history of malignancies does not constitute an absolute contraindication for biologics. Growing evidence supports the treatment of selected patients, emphasizing a nuanced assessment of benefits and risks. There is a lack of data specifying a safe timeframe to initiate biologics following a neoplasm diagnosis due to influences from cancer-related and patient-specific characteristics impacting prognosis. Some patients may continue anti-psoriasis therapy during cancer treatments. Enhanced comprehension of the biological mechanisms in cancer progression and the immune microenvironment of psoriasis holds promise for refining therapeutic strategies. In conclusion, a personalized treatment approach necessitates collaboration between oncologists and dermatologists, considering factors such as cancer prognosis, psoriasis clinical manifestations, patient characteristics, and preferences when making treatment decisions.

BackgroundGermline variants in the melanocortin 1 receptor gene (MC1R) might increase the risk of childhood and adolescent melanoma, but a clear conclusion is challenging because of the low number of studies and cases. We assessed the association of MC1R variants with childhood and adolescent melanoma in a large study comparing the prevalence of MC1R variants in child or adolescent patients with melanoma to that in adult patients with melanoma and in healthy adult controls.MethodsIn this retrospective pooled analysis, we used the M-SKIP Project, the Italian Melanoma Intergroup, and other European groups (with participants from Australia, Canada, France, Greece, Italy, the Netherlands, Serbia, Spain, Sweden, Turkey, and the USA) to assemble an international multicentre cohort. We gathered phenotypic and genetic data from children or adolescents diagnosed with sporadic single-primary cutaneous melanoma at age 20 years or younger, adult patients with sporadic single-primary cutaneous melanoma diagnosed at age 35 years or older, and healthy adult individuals as controls. We calculated odds ratios (ORs) for childhood and adolescent melanoma associated with MC1R variants by multivariable logistic regression. Subgroup analysis was done for children aged 18 or younger and 14 years or younger.FindingsWe analysed data from 233 young patients, 932 adult patients, and 932 healthy adult controls. Children and adolescents had higher odds of carrying MC1R r variants than did adult patients (OR 1·54, 95% CI 1·02-2·33), including when analysis was restricted to patients aged 18 years or younger (1·80, 1·06-3·07). All investigated variants, except Arg160Trp, tended, to varying degrees, to have higher frequencies in young patients than in adult patients, with significantly higher frequencies found for Val60Leu (OR 1·60, 95% CI 1·05-2·44; p=0·04) and Asp294His (2·15, 1·05-4·40; p=0·04). Compared with those of healthy controls, young patients with melanoma had significantly higher frequencies of any MC1R variants.InterpretationOur pooled analysis of MC1R genetic data of young patients with melanoma showed that MC1R r variants were more prevalent in childhood and adolescent melanoma than in adult melanoma, especially in patients aged 18 years or younger. Our findings support the role of MC1R in childhood and adolescent melanoma susceptibility, with a potential clinical relevance for developing early melanoma detection and preventive strategies.FundingSPD-Pilot/Project-Award-2015; AIRC-MFAG-11831.

Background and aim: The knowledge about the acute kidney injury (AKI) incidence in patients with coronavirus disease 2019 (COVID-19) can help health teams to carry out a targeted care plan. This study aimed to determine the AKI incidence in patients hospitalized with COVID-19. Methods: The electronic search covered research published until June 20, 2020, and included five databases, PubMed, Embase, Web of Science, Scopus, and Lilacs (Latin American and Caribbean Health Sciences Library). Eligible studies were those including data from AKI occurrence in adult patients hospitalized with COVID-19. The primary outcome was AKI incidence, and the secondary outcome assessed was the AKI mortality. Additionally, the estimated incidence of renal replacement therapy (RRT) need also was verified. Using a standardized form prepared in Microsoft Excel, data were extracted by two independents authors, regarding the description of studies, characteristics of patients and clinical data on the AKI occurrence. Results: We included 30 studies in this systematic review, of which 28 were included in the meta-analysis. Data were assessed from 18.043 adult patients with COVID-19. The AKI estimate incidence overall and at the ICU was 9.2% (4.6–13.9) and 32.6% (8.5–56.6), respectively. AKI estimate incidence in the elderly patients and those with acute respiratory disease syndrome was 22.9% (−4.0–49.7) and 4.3% (1.8–6.8), respectively. Patients with secondary infection, AKI estimate incidence was 31.6% (12.3–51.0). The estimate incidence of patients that required RRT was 3.2% (1.1–5.4) and estimate AKI mortality was 50.4% (17.0–83.9). Conclusion: The occurrence of AKI is frequent among adult patients hospitalized with COVID-19, and affects on average, up to 13.9% of these patients. It is believed that AKI occurs early and in parallel with lung injury. Resumen: Antecedentes y objetivo: El conocimiento de la incidencia de lesión renal aguda (LRA) en pacientes con enfermedad por coronavirus 2019 (COVID-19) puede ayudar a los equipos de atención médica a llevar a cabo un plan de atención específico. Este estudio tuvo como objetivo determinar la incidencia de LRA en pacientes hospitalizados con COVID-19. Métodos: La búsqueda electrónica cubrió la investigación publicada hasta el 20 de junio del 2020 e incluyó 5 bases de datos: PubMed, Embase, Web of Science, Scopus y Lilacs (Biblioteca de Ciencias de la Salud de América Latina y el Caribe). Los estudios elegibles fueron aquellos que incluyeron datos sobre la aparición de LRA en pacientes adultos hospitalizados con COVID-19. El resultado primario fue la incidencia de LRA y el resultado secundario evaluado fue la mortalidad por LRA. Además, también se verificó la incidencia estimada de necesidad de terapia de reemplazo renal (TRR). Mediante un formulario estandarizado elaborado en Microsoft Excel, los datos fueron extraídos por 2 autores independientes, haciendo referencia a la descripción de los estudios, las características de los pacientes y los datos clínicos sobre la ocurrencia de LRA. Resultados: En esta revisión sistemática se incluyeron 30 estudios, de los cuales 28 se incluyeron en el metaanálisis. Se evaluaron los datos de 18.043 pacientes adultos con COVID-19. La incidencia estimada de LRA en general y en la UCI fue del 9,2% (4,6-13,9) y del 32,6% (8,5-56,6), respectivamente. La incidencia estimada de LRA en pacientes ancianos y pacientes con síndrome de enfermedad respiratoria aguda fue del 22,9% (–4,0-49,7) y del 4,3% (1,8-6,8), respectivamente. En pacientes con infección secundaria, la incidencia estimada de LRA fue del 31,6% (12,3-51,0). La incidencia estimada de pacientes que requirieron TRR fue del 3,2% (1,1-5,4) y la mortalidad estimada por LRA fue del 50,4% (17,0-83,9). Conclusión: La ocurrencia de LRA es frecuente en pacientes adultos hospitalizados con COVID-19 y afecta, en promedio, hasta al 13,9% de estos pacientes. Se cree que la LRA ocurre temprano y en paralelo con la lesión pulmonar.