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Abstract Background Male sex has been identified as a risk factor for worse COVID-19 outcomes. This sex difference has been mostly attributed to the complex role of sex hormones. Cell surface entry of SARS-CoV-2 is mediated by the transmembrane protease serine 2 (TMPRSS2) which is under transcriptional regulation by androgens. P450 aromatase enzyme converts androgens to estrogens. This study measured concentrations of aromatase enzyme, testosterone, estradiol, and TMPRSS-2 in plasma of hospitalized COVID-19 patients to elucidate the dynamics of sex-linked disparity in COVID-19 and correlate them with disease severity and mortality. Methods In this prospective cohort study, a total of 265 patients (41% women), age 18 years and older, who had a positive COVID-19 PCR test and were hospitalized for COVID-19 at Memorial Hermann Hospital in Houston, (between May 2020 and May 2021) were enrolled in the study if met inclusion criteria. Plasma concentrations of Testosterone, aromatase, TMPRSS-2, and estradiol were measured by ELISA. COVID-19 patients were dichotomized based on disease severity into moderate-severe (n = 146) or critical (n = 119). Mann Whitney U and logistic regression were used to correlate the analytes with disease severity and mortality. Results TMPRSS2 (2.5 ± 0.31 vs. 1.73 ± 0.21 ng/mL, p

During the COVID-19 pandemic, the challenges associated with the transition from face-to-face to emergency remote education increased concerns about student dropout. Aligned with this concern, this study investigates the impact of the pandemic on the dropout patterns of 3371 undergraduate students from a Brazilian institution. Using data mining and machine learning techniques, we developed predictive dropout models based on student data preceding and succeeding the onset of the pandemic. Through the interpretation and comparison of these models and with the support of statistical and graphical analyses, we identify that the patterns persistently indicate that young students in their initial semesters, characterized by lower income, academic performance, and interaction, remain most susceptible to dropping out. Despite the pandemic leading to an enhanced predictive capability of data regarding student interaction within the virtual learning environment, our analysis revealed a lack of significant variation in dropout patterns. Institutionally, this indicates that a considerable number of dropouts likely encountered challenges in adapting to higher education, both before and throughout the pandemic.

BACKGROUND: The need for arterial blood data in quantitative PET research limits the wider usability of this imaging method in clinical research settings. Image-derived input function (IDIF) approaches have been proposed as a cost-effective and non-invasive alternative to gold-standard arterial sampling. However, this approach comes with its own limitations-partial volume effects and radiometabolite correction among the most important-and varying rates of success, and the use of IDIF for brain PET has been particularly troublesome. MAIN BODY: This paper summarizes the limitations of IDIF methods for quantitative PET imaging and discusses some of the advances that may make IDIF extraction more reliable. The introduction of automated pipelines (both commercial and open-source) for clinical PET scanners is discussed as a way to improve the reliability of IDIF approaches and their utility for quantitative purposes. Survey data gathered from the PET community are then presented to understand whether the fields opinion of the usefulness and validity of IDIF is improving. Finally, as the introduction of next-generation PET scanners with long axial fields of view, ultra-high sensitivity, and improved spatial and temporal resolution, has also brought IDIF methods back into the spotlight, a discussion of the possibilities offered by these state-of-the-art scanners-inclusion of large vessels, less partial volume in small vessels, better description of the full IDIF kinetics, whole-body modeling of radiometabolite production-is included, providing a pathway for future use of IDIF. CONCLUSION: Improvements in PET scanner technology and software for automated IDIF extraction may allow to solve some of the major limitations associated with IDIF, such as partial volume effects and poor temporal sampling, with the exciting potential for accurate estimation of single kinetic rates. Nevertheless, until individualized radiometabolite correction can be performed effectively, IDIF approaches remain confined at best to a few tracers.

Abstract Background To evaluate transparency practices in randomized controlled trials (RCTs) in dentistry. Methods This meta-research study included RCTs in dentistry regardless of topic, methods, or level of detail reported. Only studies in English were considered. We searched PubMed for RCTs in dentistry published in English from December 31, 2016, to December 31, 2021. The screening was performed in duplicate, and data extracted included journal and author details, dental specialty, protocol registration, data and code sharing, conflict of interest declaration, and funding information. A descriptive analysis of the data was performed. We generated maps illustrating the reporting of transparency items by country of the corresponding author and a heat table reflecting reporting levels by dental specialty. Results A total of 844 RCTs were included. Only 12.86% of studies reported any information about data and code sharing. Protocol registration was reported for 50.36% of RCTs. Conflict of interest (83.41%) and funding (71.68%) declarations were present in most studies. Conflicts of interest and funding were consistently reported regardless of country or specialty, while data and code sharing had a low level of reporting across specialties, as well as low dissemination across the world. Protocol registration exhibited considerable variability. Conclusions Considering the importance of RCTs for evidence-based dentistry, it is crucial that everyone who participates in the scientific production and dissemination process actively and consistently promotes adherence to transparent scientific standards, particularly registration of protocols, and sharing of data and code.

Background The present in vitro study aimed to evaluate the fatigue behavior of teeth filled with a calcium silicate-based sealer (Bio-C Sealer, BC) or an epoxy resin-based sealer (AH Plus, AH), in bulk or associated with gutta-percha as main core material. Methods Seventy-two sound human maxillary anterior teeth were initially selected. Sixty of them, were randomly chosen, and had their root canals prepared using nickel-titanium reciprocating instruments, being again randomly assigned to five experimental groups (n = 12): C+ (control + prepared but not filled); BC-B (BC in bulk); BC-GP (BC+ gutta-percha); AP-B (AH in bulk); AP-GP (AH+ gutta-percha). An additional negative control group (C−) was considered (n = 12), consisting only on sound teeth, without preparation and filling. The specimens were submitted to a survival analysis after the cyclic fatigue test. Results Sound teeth (C−) presented the best fatigue performance (P < 0.05), being similar only to the AP-GP group (P > 0.05). Despite that, all experimental groups showed similar fatigue behavior (P > 0.05) to C+ (BC-B = BC-GP = AP-B = AP-GP = C+). Based on that, it can be seen that the use of gutta-percha, as a main core material, associated with the AH Plus sealer, reestablished the mechanical fatigue performance of endodontically treated teeth comparable to sound teeth, still consisting on the most promising approach to rehabilitate such scenario. Teeth filled in bulk, had discreetly higher risk of premature failures and inferior fatigue performance.

Objetivo: Analisar o perfil epidemiológico das hospitalizações por anemia ferropriva em mulheres no Brasil nos últimos cinco anos. Métodos: Realizou-se um estudo de base populacional, descritivo e transversal, com dados do DATASUS no Sistema de Informações Hospitalares do SUS (SIH-SUS), com ênfase na população feminina internada por anemia ferropriva no período de maio de 2019 a maio de 2024. Os dados foram filtrados a partir dos marcadores epidemiológicos: quantidade total de internações hospitalares por ano e região, caráter de atendimento, tempo médio de permanência na unidade hospitalar, valor médio da internação hospitalar por paciente, número total de óbitos, faixa etária, raça e taxa de mortalidade. Por tratar-se de fonte de dados de acesso público, a aprovação pelo comitê de ética e pesquisa em humanos foi irrisória. Resultados: Nesse quinquênio, foram registradas 38.924 internações por anemia ferropriva. Anualmente, obteve-se uma oscilação, sendo 2023 com o maior número, 9.205 (23,64%) casos, seguido por 2022 com 8.127 (20,87%) e o de 2021 com 7.560 (19,42%). Até maio de 2024, haviam sido registrados 3.437 casos. Regionalmente, notou-se maior incidência no Sudeste com 16.022 (41,16%) casos e a menor no Norte com 2.988 (7,68%). Além disso, a maioria das hospitalizações ocorreu em situações de urgência 36.546 (71,44%). A média de permanência da paciente na unidade hospitalar foi de 4,6 dias e o valor médio da internação foi de R$436,16. Foram registrados 1.470 óbitos, 28,02% em pacientes com 70 a 79 anos, 27,38% em 80 anos ou mais e 20,34% em 60 a 69 anos. A taxa total de mortalidade foi de 3,78%. Em relação à faixa etária, a maior parte das internações foi de mulheres com 40 a 49 anos, registrando 7.230 casos, seguida pela de 80 anos ou mais com 6.503 e pela de 70 a 79 anos com 6.046. A raça parda foi a mais prevalente com 16.969 (43,59%) registros, seguida pela preta com 13.194 (33,89%) e com 6.068 (15,58%) sem informação. Discussão: A anemia ferropriva é uma doença carencial capaz de influenciar o número de internações devido à alta prevalência e sintomas clínicos. Diante da análise, é possível notar a superioridade dos casos na população entre 40 a 49 anos quando comparado às outras faixas etárias. Ademais, há uma predominância de internação na população parda. Não obstante, a prevalência das internações em caráter de urgência evidencia a necessidade de medidas para diagnóstico precoce. Devem ser consideradas as variadas etiologias, como a menorragia, sobretudo em mulheres em idade reprodutiva. Episódios de perdas sanguíneas que requerem rápida intervenção terapêutica devem ser investigados por possível associação a condições como malignidades ou sangramentos do trato gastrointestinal. Além disso, a categoria “sem informação” para cor/raça foi a terceira em maior número de registros, o que prejudica uma análise mais precisa dos dados. A letalidade, apesar de baixa, foi maior em idades avançadas, possivelmente pelas comorbidades e maior fragilidade da paciente senil. Conclusão: A anemia ferropriva é um importante problema de saúde pública devido à sua elevada incidência e sequelas, sobretudo, entre camadas socialmente menos favorecidas. Sua prevalência segue a tendência mundial dos países em desenvolvimento, justificando a adoção de medidas eficazes de prevenção e intervenção precoce com o fito de reduzir o número das internações, priorizando-se a investigação da causa base e tratamento efetivo.

In Veneto Region, HPV vaccine has been actively offered to 12 year-old females since 2008, and to 12 year-old males since 2015. The study aims to analyze the safety profile of HPV4v and HPV9v vaccines and perform a case-by-case review of conditions of interest.Spontaneous reports related to HPV uploaded to the database of the Regional Pharmacovigilance Center between 2008–2022 were included. HPV vaccine doses administered until April 2022 in the Veneto Region were considered to calculate the reporting rate (RR).Potential “safety concerns” examined as conditions of interest were included through Standardized MedDRA or preferred terms searching queries. The level of diagnostic certainty was evaluated as per the Brighton Collaboration case definition criteria.A total of 637 reports and 1316 Adverse Events Following Immunizations (AEFI) were retrieved: 469 for HPV4v (73.6 %) and 168 for HPV9v (26.4 %). Serious reports were 71 (11.1 %): 49 (10.4 %) for HPV4v and 22 (13.1 %) for HPV9v. The RR for serious events between 2008–2022 was 6.9/100,000 administered doses, with no differences by vaccine type. Females and adults showed higher overall RR compared to males and to children and adolescents (p

Abstract Background Overexpressed in various solid tumors, gastrin-releasing peptide receptor (GRPR) is a promising cancer imaging marker and therapeutic target. Although antagonists are preferable for the development of GRPR-targeted radiopharmaceuticals due to potentially fewer side effects, internalization of agonists may lead to longer tumor retention and better treatment efficacy. In this study, we systematically investigated unnatural amino acid substitutions to improve in vivo stability and tumor uptake of a previously reported GRPR-targeted agonist tracer, [68Ga]Ga-TacBOMB2 (68Ga-DOTA-Pip-D-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Leu13-Thz14-NH2). Results Unnatural amino acid substitutions were conducted for Gln7, Trp8, Ala9, Val10, Gly11 and His12, either alone or in combination. Out of 25 unnatural amino acid substitutions, tert-Leu10 (Tle10) and NMe-His12 substitutions were identified to be preferable modifications especially in combination. Compared with the previously reported [68Ga]Ga-TacBOMB2, the Tle10 and NMe-His12 derived [68Ga]Ga-LW01110 showed retained agonist characteristics and improved GRPR binding affinity (Ki = 7.62 vs 1.39 nM), in vivo stability (12.7 vs 89.0% intact tracer in mouse plasma at 15 min post-injection) and tumor uptake (5.95 vs 16.6 %ID/g at 1 h post-injection). Conclusions Unnatural amino acid substitution is an effective strategy to improve in vivo stability and tumor uptake of peptide-based radiopharmaceuticals. With excellent tumor uptake and tumor-to-background contrast, [68Ga]Ga-LW01110 is promising for detecting GRPR-expressing cancer lesions with PET. Since agonists can lead to internalization upon binding to receptors and foreseeable long tumor retention, our optimized GRPR-targeted sequence, [Tle10,NMe-His12,Thz14]Bombesin(7–14), is a promising template for use for the design of GRPR-targeted radiotherapeutic agents.

Abstract Background The need for arterial blood data in quantitative PET research limits the wider usability of this imaging method in clinical research settings. Image-derived input function (IDIF) approaches have been proposed as a cost-effective and non-invasive alternative to gold-standard arterial sampling. However, this approach comes with its own limitations—partial volume effects and radiometabolite correction among the most important—and varying rates of success, and the use of IDIF for brain PET has been particularly troublesome. Main body This paper summarizes the limitations of IDIF methods for quantitative PET imaging and discusses some of the advances that may make IDIF extraction more reliable. The introduction of automated pipelines (both commercial and open-source) for clinical PET scanners is discussed as a way to improve the reliability of IDIF approaches and their utility for quantitative purposes. Survey data gathered from the PET community are then presented to understand whether the field’s opinion of the usefulness and validity of IDIF is improving. Finally, as the introduction of next-generation PET scanners with long axial fields of view, ultra-high sensitivity, and improved spatial and temporal resolution, has also brought IDIF methods back into the spotlight, a discussion of the possibilities offered by these state-of-the-art scanners—inclusion of large vessels, less partial volume in small vessels, better description of the full IDIF kinetics, whole-body modeling of radiometabolite production—is included, providing a pathway for future use of IDIF. Conclusion Improvements in PET scanner technology and software for automated IDIF extraction may allow to solve some of the major limitations associated with IDIF, such as partial volume effects and poor temporal sampling, with the exciting potential for accurate estimation of single kinetic rates. Nevertheless, until individualized radiometabolite correction can be performed effectively, IDIF approaches remain confined at best to a few tracers.

Abstract Stroke is the most common cause of long-term disability and places a high economic burden on the global healthcare system. Functional outcomes from stroke are largely determined by the extent of ischemic injury, however, there is growing recognition that systemic inflammatory responses also contribute to outcomes. Mast cells (MCs) rapidly respond to injury and release histamine (HA), a pro-inflammatory neurotransmitter that enhances inflammation. The gut serves as a major reservoir of HA. We hypothesized that cromolyn, a mast cell stabilizer that prevents the release of inflammatory mediators, would decrease peripheral and central inflammation, reduce MC trafficking to the brain, and improve stroke outcomes. We used the transient middle cerebral artery occlusion (MCAO) model of ischemic stroke in aged (18 mo) male mice to investigate the role of MC in neuroinflammation post-stroke. After MCAO we treated mice with 25 mg/kg body weight of cromolyn (MC stabilizer) by oral gavage. Cromolyn was administered at 3 h, 10 h, 24 h and every 24 h for 3 days post-stroke. Three control groups were used. One group underwent a sham surgery and was treated with cromolyn, one received sham surgery with PBS vehicle and the third underwent MCAO with PBS vehicle. Mice were euthanized at 24 h and 3 days post-stroke. Cromolyn administration significantly reduced MC numbers in the brain at both 24 h and 3 days post-stroke. Infarct volume was not significantly different between groups, however improved functional outcomes were seen at 3 days post-stroke in mice that received cromolyn. Treatment with cromolyn reduced plasma histamine and IL-6 levels in both the 24-h and 3-day cohorts. Gut MCs numbers were significantly reduced after cromolyn treatment at 24 h and 3 days after stroke. To determine if MC trafficking from the gut to the brain occurred after injury, GFP+MCs were adoptively transferred to c-kit−/− MC knock-out animals prior to MCAO. 24 h after stroke, elevated MC recruitment was seen in the ischemic brain. Preventing MC histamine release by cromolyn improved gut barrier integrity and an improvement in stroke-induced dysbiosis was seen with treatment. Our results show that preventing MC histamine release possesses prevents post-stroke neuroinflammation and improves neurological and functional outcomes. Graphical abstract

Gastrin-releasing peptide receptor (GRPR), overexpressed in many solid tumors, is a promising imaging marker and therapeutic target. Most reported GRPR-targeted radioligands contain a C-terminal amide. Based on the reported potent antagonist D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH, we synthesized C-terminal hydroxamate-derived [68Ga]Ga-LW02075 ([68Ga]Ga-DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH) and [68Ga]Ga-LW02050 ([68Ga]Ga-DOTA-Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH), and compared them with the closely related and clinically validated [68Ga]Ga-SB3 ([68Ga]Ga-DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt). Binding affinities (Ki) of Ga-SB3, Ga-LW02075, and Ga-LW02050 were 1.20 ± 0.31, 1.39 ± 0.54, and 8.53 ± 1.52 nM, respectively. Both Ga-LW02075 and Ga-LW02050 were confirmed to be GRPR antagonists by calcium release assay. Imaging studies showed that PC-3 prostate cancer tumor xenografts were clearly visualized at 1 h post injection by [68Ga]Ga-SB3 and [68Ga]Ga-LW02050 in PET images, but not by [68Ga]Ga-LW02075. Ex vivo biodistribution studies conducted at 1 h post injection showed that the tumor uptake of [68Ga]Ga-LW02050 was comparable to that of [68Ga]Ga-SB3 (5.38 ± 1.00 vs. 6.98 ± 1.36 %ID/g), followed by [68Ga]Ga-LW02075 (3.97 ± 1.71 %ID/g). [68Ga]Ga-SB3 had the highest pancreas uptake (37.3 ± 6.90 %ID/g) followed by [68Ga]Ga-LW02075 (17.8 ± 5.24 %ID/g), while the pancreas uptake of [68Ga]Ga-LW02050 was only 0.53 ± 0.11 %ID/g. Our data suggest that [68Ga]Ga-LW02050 is a promising PET tracer for detecting GRPR-expressing cancer lesions.

Domesticated apple is a drought-sensitive species that spread from continental to Mediterranean temperate regions, where it can particularly experience prolonged water stress. One strategy to improve drought resistance in apple is engrafting on selected rootstocks. This study explores the potential of fast chlorophyll a fluorescence for the comparison of rootstock sensitivity to drought, looking for significant correlations with fruit productivity. The experiment was conducted in a field located in the coastal Po River Plain, Northern Italy, characterized by a loamy sandy soil, particularly prone to drought (86% sand). Mature plants of apple cv. Superchief® Sandidge engrafted on three different rootstocks (CIVP21pbr, MM106, M26) were monitored throughout the summer of 2021 and compared between irrigated and non-irrigated parcels, and at the end of the season, fruit production was evaluated. Despite soil water tension only reaching −13 kPa, the non-irrigated plants experienced a small but consistent loss of Photosystem II (PSII) activity and a lesser capacity of light energy conservation in the photosynthetic electron transport chain. The fruit weight correlated with PSII photochemical indexes recorded during early drought, particularly FV/FM and PIABS; a correlation emerged between fruit number per plant and median values of electron transport parameters, including PITOT. Although all rootstocks underwent a 40% loss of productivity, the fluorescence parameters revealed a graded susceptibility to drought, M26 > CIVP21pbr > MM106, which matched well with the plant vigour. The least drought-sensitive MM106 produced less numerous but heavier fruits than the other two rootstocks.

African swine fever (ASF) is an acute, highly contagious and deadly infectious disease. It is a threat to animal health with major potential economic and societal impact. Despite decades of ASF vaccine research, still some gaps in knowledge are hindering the development of a functional vaccine. Worth mentioning are gaps in understanding the mechanism of ASF infection and immunity, as well as the fact that - in case of this disease - virus proteins, so-called protective antigens, responsible for inducing protective immune responses in pigs are not identified yet. In this paper we elaborate on a methodology to identify protective antigens based on epitope mapping by microarray technology. High density peptide microarrays, combined with fluorescence scanning, have been used to analyze the interaction of peptide sequences of African swine fever virus (ASFV) proteins with antibodies present in inactivated serum from infected and healthy animals. The study evidenced ASFV proteins already under the radar for vaccine development, such as p54, and identified specific sequences in those proteins that may become the focus for future vaccine candidates. Such methodology is amenable to automation and high-throughput and may help developing better targeting for next generation vaccines.

ABSTRACT Excessive phosphorus (P) applications can increase nutrient levels in the soil, facilitating its transference to aquatic environments and causing contamination. Thus, the environmental P threshold (P-threshold) is a tool to establish a sound level of P in the soil, in which P values below the threshold are harmless to the environment. This study aimed to establish a P-threshold equation for the soils of Mato Grosso State, Brazil. Twenty samples of representative soils from the main swine production regions of the State were collected. These samples were characterized chemically and in terms of P adsorption capacity, then incubated with P rates for 30 days. After incubation, the water-soluble P content (P-water) and the available P content were determined by Mehlich-1 method (P-Mehlich-1). The relationship between P-water and P-Mehlich-1 allowed the determination of the P-Mehlich-1 content from which the amount of nutrient in water increases abruptly, establishing this point as the limit P (P-limit). Subsequently, the P-limit values were plotted against the clay content of the soils, and the resulting equation was used to calculate the P-threshold by adding a safety margin of 20 % to the P-limit versus clay equation. The model was tested on 120 soil samples from Mato Grosso State, and it was able to separate them into two groups with low and high P-water, classified as below or above P-threshold, respectively. Based on that, the simplified equation “P-threshold (mg dm-3) = 13 + 0.5 * % clay” was proposed.

Abstract Background Glycogen Synthase Kinase-3 (GSK-3) α and β are two serine-threonine kinases controlling insulin, Wnt/β-catenin, NF-κB signaling and other cancer-associated transduction pathways. Recent evidence suggests that GSK-3 could function as growth-promoting kinases, especially in malignant cells. In this study, we have investigated GSK-3α and GSK-3β function in multiple myeloma (MM). Methods GSK-3 α and β expression and cellular localization were investigated by Western blot (WB) and immunofluorescence analysis in a panel of MM cell lines and in freshly isolated plasma cells from patients. MM cell growth, viability and sensitivity to bortezomib was assessed upon treatment with GSK-3 specific inhibitors or transfection with siRNAs against GSK-3 α and β isoforms. Survival signaling pathways were studied with WB analysis. Results GSK-3α and GSK-3β were differently expressed and phosphorylated in MM cells. Inhibition of GSK-3 with the ATP-competitive, small chemical compounds SB216763 and SB415286 caused MM cell growth arrest and apoptosis through the activation of the intrinsic pathway. Importantly, the two inhibitors augmented the bortezomib-induced MM cell cytotoxicity. RNA interference experiments showed that the two GSK-3 isoforms have distinct roles: GSK-3β knock down decreased MM cell viability, while GSK-3α knock down was associated with a higher rate of bortezomib-induced cytotoxicity. GSK-3 inhibition caused accumulation of β-catenin and nuclear phospho-ERK1, 2. Moreover, GSK-3 inhibition and GSK-3α knockdown enhanced bortezomib-induced AKT and MCL-1 protein degradation. Interestingly, bortezomib caused a reduction of GSK-3 serine phosphorylation and its nuclear accumulation with a mechanism that resulted partly dependent on GSK-3 itself. Conclusions These data suggest that in MM cells GSK-3α and β i) play distinct roles in cell survival and ii) modulate the sensitivity to proteasome inhibitors.

Este artigo discute a atuação da comunidade epistêmica ligada à formação de técnicos em saúde a partir da análise das ações desencadeadas pelo Centro Colaborador da Organização Pan-Americana da Saúde/Organização Mundial da Saúde (OPAS/OMS) para a educação desses técnicos durante a pandemia de covid-19, com o objetivo de cotejar essas ações com os principais elementos que definem a constituição e o funcionamento de comunidades epistêmicas conforme a literatura especializada. Argumenta-se que, a despeito das diferenças na configuração histórica dos sistemas nacionais de saúde e dos sistemas formadores, o surgimento de desafios comuns na formação de técnicos propiciou articulação de demandas, compartilhamento de avaliações diagnósticas e cooperação entre a Rede Internacional de Educação de Técnicos em Saúde, a Rede Ibero-Americana de Educação de Técnicos em Saúde e a Rede de Escolas Técnicas de Saúde da Comunidade dos Países de Língua Portuguesa, promovendo troca de experiências, busca de soluções estratégicas e disseminação de recomendações entre os países. Ao reafirmar o papel central dos técnicos nas ações de vigilância epidemiológica, diagnóstico e assistência, a emergência sanitária exigiu respostas imediatas e consistentes de governos e instituições formadoras, favorecendo o fortalecimento da comunidade epistêmica de formação de técnicos em saúde pela circulação de discursos e da hegemonização de sentidos para a educação de técnicos em saúde. Essa atuação, no entanto, não confere estabilidade ou homogeneidade à comunidade epistêmica de formação de técnicos em saúde, uma vez que suas articulações são provisórias e contingentes, nem assegura capacidade de influência direta sobre as políticas em cada país.

Gastrin-releasing peptide receptor (GRPR) is overexpressed in various cancers and is a promising target for cancer diagnosis and therapy. However, the high pancreas uptake and/or metabolic instability observed for most reported GRPR-targeted radioligands might limit their clinical applications. Our group recently reported a GRPR-targeted antagonist tracer, [68Ga]Ga-TacsBOMB2 ([68Ga]Ga-DOTA-Pip-D-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Leu13ψThz14-NH2), which showed a minimal pancreas uptake in a preclinical mouse model. In this study, we synthesized four derivatives with unnatural amino acid substitutions (Tle10-derived Ga-LW01158, NMe-His12-derived Ga-LW01160, α-Me-Trp8- and Tle10-derived Ga-LW01186, and Tle10- and N-Me-Gly11-derived Ga-LW02002) and evaluated their potential for detecting GRPR-expressing tumors with positron emission tomography (PET). The binding affinities (Ki(GRPR)) of Ga-LW01158, Ga-LW01160, Ga-LW01186, and Ga-LW02002 were 5.11 ± 0.47, 187 ± 17.8, 6.94 ± 0.95, and 11.0 ± 0.39 nM, respectively. [68Ga]Ga-LW01158, [68Ga]Ga-LW01186, and [68Ga]Ga-LW02002 enabled clear visualization of subcutaneously implanted human prostate cancer PC-3 tumor xenografts in mice in PET images. Ex vivo biodistribution studies showed that [68Ga]Ga-LW01158 had the highest tumor uptake (11.2 ± 0.65 %ID/g) and good tumor-to-background uptake ratios at 1 h post-injection. Comparable in vivo stabilities were observed for [68Ga]Ga-LW01158, [68Ga]Ga-LW01186, and [68Ga]Ga-LW02002 (76.5–80.7% remaining intact in mouse plasma at 15 min post-injection). In summary, the Tle10 substitution, either alone or combined with α-Me-Trp8 or NMe-Gly11 substitution, in Ga-TacsBOMB2 generates derivatives that retained good GRPR binding affinity and in vivo stability. With good tumor uptake and tumor-to-background imaging contrast, [68Ga]Ga-LW01158 is promising for detecting GRPR-expressing lesions with PET.

Among the physical and chemical properties of nanomaterials, hydrophobicity is considered to play a key role in their impact on the environment. Changes in hydrophobicity resulting from abiotic and biotic processes can be used to predict the behaviours of nanoparticles (NPs) in the environment (e.g., aggregation, toxicity, and bioaccumulation). Hydrophobicity changes induced by sulfidation and natural organic matter (NOM) corona formation were evaluated by monitoring the binding rate of silver (Ag) NPs on engineered surfaces using dark-field microscopy (DFM). It was found that this DFM-based method was more capable of distinguishing the hydrophobicity of environmentally relevant AgNPs than the dye adsorption method. Under the conditions tested in this study, sulfidation and adsorption of sulfidized NOM/“lipid-free” (LF-)NOM increased the hydrophobicity of AgNPs. Both methods demonstrate the tendency of AgNPs to become more hydrophobic after sulfidation. This study shows that DFM-based methods can effectively measure the hydrophobicity of environmentally relevant NPs and have the potential to be widely used as fate predictors in the future.

Dorelia Lipsa, Ana Ruiz Moreno, Cloé Desmet, Ivana Bianchi, Otmar Geiss, Pascal Colpo, Susanne Bremer-Hoffmann European Commission, Joint Research Centre (JRC), Ispra, ItalyCorrespondence: Susanne Bremer-Hoffmann, Email susanne.bremer-hoffmann@ec.europa.euIntroduction: The role of the human immune system in pathologic responses to chemicals including nanomaterials was identified as a gap in current hazard assessments. However, the complexity of the human immune system as well as interspecies variations make the development of predictive toxicity tests challenging. In the present study, we have analysed to what extent fluctuations of the complement system of different individuals will have an impact on the standardisation of immunological tests.Methods: We treated commercially available pooled sera (PS) from healthy males, individual sera from healthy donors and from patients suffering from cancer, immunodeficiency and allergies with small molecules and liposomes. Changes of iC3b protein levels measured in enzyme-linked immunosorbent assays served as biomarker for complement activation.Results: The level of complement activation in PS differed significantly from responses of individual donors (p < 0.01). Only seven out of 32 investigated sera from healthy donors responded similarly to the pooled serum. This variability was even more remarkable when investigating the effect of liposomes on the complement activation in sera from donors with pre-existing pathologies. Neither the 26 sera of donors with allergies nor sera of 16 donors with immunodeficiency responded similar to the PS of healthy donors. Allergy sufferers showed an increase in iC3b levels of 4.16-fold changes when compared to PS treated with liposomes.Discussion: Our studies demonstrate that the use of pooled serum can lead to an over- or under-estimation of immunological response in particular for individuals with pre-existing pathologies. This is of high relevance when developing medical products based on nanomaterials and asks for a review of the current practice to use PS from healthy donors for the prediction of immunological effects of drugs in patients. A better understanding of individual toxicological responses to xenobiotics should be an essential part in safety assessments.Graphical Abstract: Keywords: inter-individual variability, complement activation, liposomes, standardisation, patients with pre-existing pathologies, healthy donors

O Currículo Integrado pressupõe movimentos integradores entre os saberes, mesmo sabendo que a interdisciplinaridade é um grande desafio, um edifício a ser construído. No entanto, neste texto, pretendemos mostrar a importância de buscarmos esforços possíveis e aproveitar momentos integradores em nossas unidades de Ensino para fortalecer e consolidar o Ensino Médio Integrado, oportunizando o múltiplo diálogo entre os saberes e fazeres, para tornar a aprendizagem dos discentes saborosa, criativa e emancipatória. A experiência que sugerimos aqui como reflexão é como o envolvimento da comunidade escolar do Instituto Federal de Educação, Ciência e Tecnologia Farroupilha (IFFar) — campus Jaguari, na preparação, organização e realização de um evento em alusão à uva pode servir como projeto integrador e oportunidade de concretizarmos diálogos e conexões entre os múltiplos saberes e fazeres.