Resistance of Bt and Non-Bt Soybean Cultivars Adapted to Novel Growing Regions of Brazil to Chrysodeixis includens and Spodoptera frugiperda.

Soybean is a highly valuable commodity crop for Brazil's economy. However, it faces significant threats from the attack of a complex of lepidopteran pests, particularly Chrysodeixis includens (Walker) and Spodoptera frugiperda (J. E. Smith). These pests have been managed primarily using transgenic Bt soybeans, but limited knowledge exists about the resistance levels of Bt and non-Bt cultivars adapted to novel soybean-growing areas in Brazil, such as the Minas Gerais state. This study evaluated the resistance levels of Bt and non-Bt soybean cultivars to C. includens and S. frugiperda, and whether the Bt cultivars can differentially affect these pests across larval stages. No-choice bioassays were conducted using Bt (NS6010 IPRO and P97R50 IPRO) and non-Bt soybeans (UFLA 6301 RR, P96R90 RR, and ANsc 80111 RR) at V4-stage in the laboratory with neonate (24 h) and third-instar larvae. Larvae were fed leaf discs in Petri dishes, recording the mortality, leaf consumption, and weight gain after 7 days. There was high mortality of C. includens neonates on the Bt cultivars, but this trend was not observed for older larvae. For S. frugiperda neonates, there was high mortality on the Bt cultivar NS 6010 IPRO and non-Bt cultivar UFLA 6301 RR, but only the former was effective for older larvae. Although the Bt cultivars did not kill the third instars, antinutritional effects were found, such that leaf tissue consumed was not converted to larval weight gain. These findings are important for defining regional strategies of integrated and resistance management of C. includens and S. frugiperda in expanding regions of soybean cultivation in Brazil.

Efficient α and ß- radionuclide therapy targeting fibroblast activation protein-α in an aggressive preclinical mouse tumour model.

PURPOSE: Targeted radionuclide therapy (TRT) is a cancer treatment with relative therapeutic efficacy across various cancer types. We studied the therapeutic potential of TRT using fibroblast activation protein-α (FAP) targeting sdAbs (4AH29) labelled with 225Ac or 131I in immunocompetent mice in a human FAP (hFAP) expressing lung cancer mouse model. We further explored the combination of TRT with programmed cell death ligand 1 (PD-L1) immune checkpoint blockade (ICB). METHODS: We studied the biodistribution and tumour uptake of [131I]I-GMIB-4AH29 and [225Ac]Ac-DOTA-4AH29 by ex vivo γ-counting. Therapeutic efficacy of [131I]I-GMIB-4AH29 and [225Ac]Ac-DOTA-4AH29 was evaluated in an immunocompetent mouse model. Flow cytometry analysis of tumours from [225Ac]Ac-DOTA-4AH29 treated mice was performed. Treatment with [225Ac]Ac-DOTA-4AH29 was repeated in combination with PD-L1 ICB. RESULTS: The biodistribution showed high tumour uptake of [131I]I-GMIB-4AH29 with 3.5 ± 0.5% IA/g 1 h post-injection (p.i.) decreasing to 0.9 ± 0.1% IA/g after 24 h. Tumour uptake of [225Ac]Ac-DOTA-4AH29 was also relevant with 2.1 ± 0.5% IA/g 1 h p.i. with a less steep decrease to 1.7 ± 0.2% IA/g after 24 h. Survival was significantly improved after treatment with low and high doses [131I]I-GMIB-4AH29 or [225Ac]Ac-DOTA-4AH29 compared to vehicle solution. Moreover, we observed significantly higher PD-L1 expression in tumours of mice treated with [225Ac]Ac-DOTA-4AH29 compared to vehicle solution. Therefore, we combined high dose [225Ac]Ac-DOTA-4AH29 with PD-L1 ICB showing therapeutic synergy. CONCLUSION: [225Ac]Ac-DOTA-4AH29 and [131I]I-GMIB-4AH29 exhibit high and persistent tumour targeting, translating into prolonged survival in mice bearing aggressive tumours. Moreover, we demonstrate that the combination of PD-L1 ICB with [225Ac]Ac-DOTA-4AH29 TRT enhances its therapeutic efficacy.

The Protective Effect of Juçara Fruit (Euterpe edulis Martius) Extracts on LPS-Activated J774 Macrophages.

This study investigated the anti-inflammatory effect of hydrophilic and lipophilic extracts from juçara fruits (Euterpe edulis Martius) through measurement of nitric oxide (NOx) and cytokines (IL-12p70, TNF-α, INF-γ, MCP-1, IL-6, and IL-10). J774 macrophages were stimulated with lipopolysaccharides (1 µg/mL) and treated with various concentrations (1-100 µg/mL) of juçara fruits extracts from crude extracts, and hexane, dichloromethane, ethyl acetate, and butanol fractions. Potential relationships between the phenolic composition of the extracts determined by LC-ESI-MS/MS and their anti-inflammatory capacity were also evaluated. Hexane and dichloromethane fractions inhibited NOx and IL-12p70 while increased IL-10. Hexane fractions also decreased IL-6 and IFN-γ production. Hexane and dichloromethane fractions showed a higher number of phenolic compounds (32 and 34, respectively) than the other extracts tested and were also the only ones that presented benzoic acid and pinocembrin. These results suggest juçara fruits compounds as potential anti-inflammatory agents, especially those of a more apolar nature.

Dimensions of Arachnoid Bulk Ratio: A Superior Optic Nerve Sheath Index for Intracranial Pressure.

Background Discrepancies in the literature regarding optimal optic nerve sheath diameter (ONSD) cutoffs for intracranial pressure (ICP) necessitate alternative neuroimaging parameters to improve clinical management. Purpose To evaluate the diagnostic accuracy of the dimensions of the perineural subarachnoid space to the optic nerve sheath ratio, measured using US, in predicting increased ICP. Materials and Methods In a prospective cohort study from April 2022 to December 2023, patients with suspected increased ICP underwent optic nerve US to determine the dimensions of arachnoid bulk (DAB) ratio and ONSD before invasive ICP measurement. Correlation between the parameters and ICP, as well as diagnostic accuracy, was assessed using area under the receiver operating characteristic curve (AUC) analysis. Results A total of 30 participants were included (mean age, 39 years ± 14 [SD]; 24 female). The DAB ratio and ONSD were significantly larger in participants with increased ICP (38% [0.16 of 0.42] and 14% [0.82 of 6.04 mm], respectively; P < .001). The DAB ratio showed a stronger correlation with ICP than ONSD (rs = 0.87 [P < .001] vs rs = 0.61 [P < .001]). The DAB ratio and ONSD optimal cutoffs for increased ICP were 0.5 and 6.5 mm, respectively, and the ratio had higher sensitivity (100% vs 92%) and specificity (94% vs 83%) compared with ONSD. Moreover, the DAB ratio better predicted increased ICP than ONSD, with a higher AUC (0.98 [95% CI: 0.95, 1.00] vs 0.86 [95% CI: 0.71, 0.95], P = .047). Conclusion An imaging ratio was proposed to predict ICP based on the relative anatomy of the cerebrospinal fluid space, demonstrating more accurate diagnosis of increased ICP and a strong correlation with ICP values, suggesting its potential utility as a neuroimaging marker in clinical settings. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Shepherd in this issue.

Generic semi-automated radiofluorination strategy for single domain antibodies: [18F]FB-labelled single domain antibodies for PET imaging of fibroblast activation protein-α or folate receptor-α overexpression in cancer.

BACKGROUND: Radiofluorination of single domain antibodies (sdAbs) via N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB) has shown to be a promising strategy in the development of sdAb-based PET tracers. While automation of the prosthetic group (PG) [18F]SFB production, has been successfully reported, no practical method for large scale sdAb labelling has been reported. Therefore, we optimized and automated the PG production, enabling a subsequently efficient manual conjugation reaction to an anti-fibroblast activation protein (FAP)-α sdAb (4AH29) and an anti-folate receptor (FR)-α sdAb (2BD42). Both the alpha isoform of FAP and the FR are established tumour markers. FAP-α is known to be overexpressed mainly by cancer-associated fibroblasts in breast, ovarian, and other cancers, while its expression in normal tissues is low or undetectable. FR-α has an elevated expression in epithelial cancers, such as ovarian, brain and lung cancers. Non-invasive imaging techniques, such as PET-imaging, using tracers targeting specific tumour markers can provide molecular information over both the tumour and its environment, which aides in the diagnosis, therapy selection and assessment of the cancer treatment. RESULTS: [18F]SFB was synthesized using a fully automated three-step, one-pot reaction. The total procedure time was 54 min and results in [18F]SFB with a RCP > 90% and a RCY d.c. of 44 ± 4% (n = 13). The manual conjugation reaction after purification produced [18F]FB-sdAbs with a RCP > 95%, an end of synthesis activity > 600 MBq and an apparent molar activity > 10 GBq/µmol. Overall RCY d.c., corrected to the trapping of [18F]F- on the QMA, were 9% (n = 1) and 5 ± 2% (n = 3) for [18F]FB-2BD42 and [18F]FB-4AH29, respectively. CONCLUSION: [18F]SFB synthesis was successfully automated and upscaled on a Trasis AllInOne module. The anti-hFAP-α and anti-hFR-α sdAbs were radiofluorinated, yielding similar RCYs d.c. and RCPs, showing the potential of this method as a generic radiofluorination strategy for sdAbs. The radiofluorinated sdAbs showed a favourable biodistribution pattern and are attractive for further characterization as new PET tracers for FAP-α and FR-α imaging.

Pearls & Oy-sters: A Challenging Optic Neuropathy-What Not to Miss in Optic Nerve Sheath Enhancement.

Optic neuropathies include a wide range of disorders from ischemic, toxic, demyelinating, or inflammatory processes with acute/subacute onset to more gradual compressive or genetic etiologies. Accurate clinical history and multimodality optic nerve imaging including MRI and optical coherence tomography have greatly improved the diagnosis of patients with optic neuropathies. We report a case of a woman with severe monocular visual acuity deficit. Optic nerve sheath enhancement seen on MRI led to a broad differential diagnosis including demyelinating causes, optic nerve sheath meningioma (ONSM), tuberculosis, and sarcoid optic neuropathy. Lack of response to treatment with steroids or plasmapheresis led to biopsy, which confirmed the diagnosis of ONSM.

The role of fidgety movements and early motor repertoire in predicting mobility outcomes in infants with myelomeningocele.

OBJECTIVE: To describe fidgety movements and co-occurring movements and postures in infants with myelomeningocele (MMC) and their association with mobility at preschool ages. METHODS: A retrospective cohort with early assessment via general movement assessment, followed by mobility assessment between 36 and 70 months of age. RESULTS: Twelve infants were included; 12 of 12 had fidgety movements in the upper limbs, with seven exhibiting them also in the hips and three in both the hips and ankles. The presence of fidgety movements in the lower limbs, kicking, a non-flat posture, a non-monotonous movement character, and a non-absent age-adequate movement repertoire were independently associated with mobility using the Hoffer modified classification and functional mobility scale (FMS) at 5 and 50 m. An optimality score was calculated based on leg movements and postures, ranging from 0 to 10 points. Infants who scored at least 4 points achieved household ambulation and FMS (5 m) of at least level 4. Community ambulation and an FMS (50 m) of level 5 were achieved with a score of at least 7.5. CONCLUSIONS: Assessing fidgety movements with other leg movements and postures in infants with MMC provided relevant information that could potentially predict mobility at preschool age and thus could be used for early intervention planning.

Estimating excess mortality and economic burden of Clostridioides difficile infections and recurrences during 2015-2019: the RECUR Germany study.

BACKGROUND: Clostridioides difficile infections (CDIs) and recurrences (rCDIs) remain a major public health challenge due to substantial mortality and associated costs. This study aims to generate real-world evidence on the mortality and economic burden of CDI in Germany using claims data between 2015 and 2019. METHODS: A longitudinal and matched cohort study using retrospective data from Statutory Health Insurance (SHI) was conducted in Germany with the BKK database. Adults diagnosed with CDI in hospital and community settings between 2015 and 2018 were included in the study. Patients had a minimum follow-up of 12-months. All-cause mortality was described at 6-, 12-, and 24-months. Healthcare resource usage (HCRU) and associated costs were assessed at 12-months of follow-up. A cohort of non-CDI patients matched by demographic and clinical characteristics was used to assess excess mortality and incremental costs of HCRU. Up to three non-CDI patients were matched to each CDI patient. RESULTS: A total of 9,977 CDI patients were included in the longitudinal cohort. All-cause mortality was 32%, 39% and 48% at 6-, 12-, and 24-months, respectively, with minor variations by number of rCDIs. When comparing matched CDI (n = 5,618) and non-CDI patients (n = 16,845), CDI patients had an excess mortality of 2.17, 1.35, and 0.94 deaths per 100 patient-months, respectively. HCRU and associated costs were consistently higher in CDI patients compared to non-CDI patients and increased with recurrences. Total mean and median HCRU cost per patient during follow-up was €12,893.56 and €6,050 in CDI patients, respectively, with hospitalisations representing the highest proportion of costs. A total mean incremental cost per patient of €4,101 was estimated in CDI patients compared to non-CDI patients, increasing to €13,291 in patients with ≥ 3 rCDIs. CONCLUSIONS: In this real-world study conducted in Germany, CDI was associated with increased risk of death and substantial costs to health systems due to higher HCRU, especially hospitalisations. HCRU and associated costs were exacerbated by rCDIs.

Epidemiological and clinical burden of Clostridioides difficile infections and recurrences between 2015 - 2019: the RECUR Germany study.

BACKGROUND: This real-world study assessed the epidemiology and clinical complications of Clostridioides difficile infections (CDIs) and recurrences (rCDIs) in hospital and community settings in Germany from 2015 - 2019. METHODS: An observational retrospective cohort study was conducted among adult patients diagnosed with CDI in hospital and community settings using statutory health insurance claims data from the BKK database. A cross-sectional approach was used to estimate the annual incidence rate of CDI and rCDI episodes per 100,000 insurants. Patients' demographic and clinical characteristics were described at the time of first CDI episode. Kaplan-Meier method was used to estimate the time to rCDIs and time to complications (colonic perforation, colectomy, loop ileostomy, toxic megacolon, ulcerative colitis, peritonitis, and sepsis). A Cox model was used to assess the risk of developing complications, with the number of rCDIs as a time-dependent covariate. RESULTS: A total of 15,402 CDI episodes were recorded among 11,884 patients. The overall incidence of CDI episodes declined by 38% from 2015 to 2019. Most patients (77%) were aged ≥ 65 years. Around 19% of CDI patients experienced at least one rCDI. The median time between index CDI episode to a rCDI was 20 days. The most frequent complication within 12-months of follow-up after the index CDI episode was sepsis (7.57%), followed by colectomy (3.20%). The rate of complications increased with the number of rCDIs. The risk of any complication increased by 31% with each subsequent rCDI (adjusted hazard ratio [HR]: 1.31, 95% confidence interval: 1.17;1.46). CONCLUSIONS: CDI remains a public health concern in Germany despite a decline in the incidence over recent years. A substantial proportion of CDI patients experience rCDIs, which increase the risk of severe clinical complications. The results highlight an increasing need of improved therapeutic management of CDI, particularly efforts to prevent rCDI.

Linking biodiversity, ecosystem function, and Nature's contributions to people: a macroecological energy flux perspective.

At macroecological scales, the provision of Nature's contributions to people (NCP) is mostly estimated with biophysical information, ignoring the ecological processes underlying them. This hinders our ability to properly quantify the impact of declining biodiversity and the provision of NCP. Here, we propose a framework that combines local-scale food web energy flux approaches and large-scale biodiversity models to evaluate ecosystem functions and flux-related NCP at extensive spatiotemporal scales. Importantly, this approach has the potential to upscale ecosystem functions, assess the vulnerability of flux-related NCP to the climate crisis, and support the development of multiscale mitigation policies.

Coping strategies and social support in nursing students during clinical practice: A scoping review.

AIM: To identify the coping strategies and social support received by nursing students during clinical practice. DESIGN: Scoping review. METHODS: Primary studies on coping strategies and social support, in full text, in English, French, Spanish or Portuguese and published in 2018 or later were included. Search was carried out in January 2023 on EBSCOhost, PubMed, SciELO, ScienceDirect, OpenAIRE, MedNar Search, WorldWideScience and the references of previously selected articles. RESULTS: A total of 24 studies were identified. Seven studies mentioned social support as a useful strategy and several instruments were identified that allow measurement. CONCLUSIONS: Few studies establish a direct relationship between the effectiveness of coping strategies with stressful situations. Positive coping strategies are associated with effective stress management. The relationship between social support and stress reduction is scarcely addressed. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Stressful situations can have an impact on students' health and on the quality of care. Nursing schools and healthcare institutions must work together in programmes to improve students coping abilities. IMPACT: This review addressed coping strategies used by nursing students during clinical practice. A set of relevant coping strategies were identified that can be used by teachers to improve students' outcomes. REPORTING METHOD: The review was performed according to Preferred Reporting Items for Scoping Reviews (PRISMA-ScR). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Quantitative description of six fish species' gut contents and prey abundances in the Baltic Sea (1968-1978).

The dataset presents a compilation of stomach contents from six demersal fish species from two functional groups inhabiting the Baltic Sea. It includes detailed information on prey identities, body masses, and biomasses recovered from both the fish's digestive systems and their surrounding environment. Environmental parameters, such as salinity and temperature levels, have been integrated to enrich this dataset. The juxtaposition of information on prey found in stomachs and in the environment provides an opportunity to quantify trophic interactions across different environmental contexts and investigate how fish foraging behaviour adapts to changes in their environment, such as an increase in temperature. The compilation of body mass and taxonomic information for all species allows approaching these new questions using either a taxonomic (based on species identity) or functional trait (based on body mass) approach.

Estimating excess mortality and economic burden of Clostridioides difficile infections and recurrences during 2015-2019: The RECUR England study.

OBJECTIVES: To generate real-world evidence on all-cause mortality and economic burden of Clostridioides difficile infections (CDIs) and recurrences (rCDIs) in England. METHODS: We conducted a cohort study using retrospective data from Clinical Practice Research Datalink linked to Hospital Episode Statistics. Patients diagnosed with CDI in hospital and community settings during 2015-2018 were included and followed for ≥1 year. All-cause mortality was described at 6, 12, and 24 months. Healthcare resource usage (HCRU) and associated costs were assessed at 12 months of follow-up. A cohort of non-CDI patients, matched by demographic and clinical characteristics including Charlson Comorbidity Index score, was used to assess excess mortality and incremental costs of HCRU. RESULTS: All-cause mortality among CDI patients at 6, 12, and 24 months was 15.87%, 20.37%, and 27.03%, respectively. A higher proportion of rCDI patients died at any point during follow-up. Compared with matched non-CDI patients, excess mortality was highest at 6 months with 1.81 and 2.53 deaths per 100 patient-months among CDI and ≥1 rCDI patients. Hospitalizations were the main drivers of costs, with an incremental cost of £1209.21 per CDI patient. HCRU and costs increased with rCDIs. CONCLUSION: CDI poses a substantial mortality and economic burden, further amplified by rCDIs.

Clostridioides difficile infections, recurrences, and clinical outcomes in real-world settings from 2015 to 2019: The RECUR England study.

OBJECTIVE: To estimate the epidemiological and clinical burden of Clostridioides difficile infections (CDIs) and recurrences (rCDIs) in England. METHODS: This retrospective study included adult patients diagnosed with CDI (community or hospital settings) over 2015-2019 from Clinical Practice Research Datalink and Hospital Episode Statistics databases. Incidences of CDI and rCDI were determined annually. Time to subsequent rCDI was estimated by Kaplan-Meier method. Rates of complications were assessed within 12 months from index episode. Association of risk factors with complications was evaluated using a Cox regression model. RESULTS: A total of 52,443 CDI episodes were recorded among 36,913 patients. Of these, 75% were aged ≥65 years, 59% were women; 73% were treated in community settings. CDI incidence remained stable (111 episodes per 100,000 patients in 2019). Around 21% of patients had ≥1 rCDI. Sepsis (12%) was the most common complication, followed by colectomy and ulcerative colitis. Age, gender, comorbidities, rCDI, preindex medical procedures, hospitalizations and consultations, and CDI treatment in hospital, were found to increase the risk of complication. CONCLUSIONS: CDI remains a concern in England. The study highlights the importance of managing primary and rCDI episodes via effective and improved therapies to prevent fatal complications.

Iron overload induces dysplastic erythropoiesis and features of myelodysplasia in Nrf2-deficient mice.

Iron overload (IOL) is hypothesized to contribute to dysplastic erythropoiesis. Several conditions, including myelodysplastic syndrome, thalassemia and sickle cell anemia, are characterized by ineffective erythropoiesis and IOL. Iron is pro-oxidant and may participate in the pathophysiology of these conditions by increasing genomic instability and altering the microenvironment. There is, however, lack of in vivo evidence demonstrating a role of IOL and oxidative damage in dysplastic erythropoiesis. NRF2 transcription factor is the master regulator of antioxidant defenses, playing a crucial role in the cellular response to IOL in the liver. Here, we crossed Nrf2-/- with hemochromatosis (Hfe-/-) or hepcidin-null (Hamp1-/-) mice. Double-knockout mice developed features of ineffective erythropoiesis and myelodysplasia including macrocytic anemia, splenomegaly, and accumulation of immature dysplastic bone marrow (BM) cells. BM cells from Nrf2/Hamp1-/- mice showed increased in vitro clonogenic potential and, upon serial transplantation, recipients disclosed cytopenias, despite normal engraftment, suggesting defective differentiation. Unstimulated karyotype analysis showed increased chromosome instability and aneuploidy in Nrf2/Hamp1-/- BM cells. In HFE-related hemochromatosis patients, NRF2 promoter SNP rs35652124 genotype TT (predicted to decrease NRF2 expression) associated with increased MCV, consistent with erythroid dysplasia. Our results suggest that IOL induces ineffective erythropoiesis and dysplastic hematologic features through oxidative damage in Nrf2-deficient cells.

In vitro production of cat-restricted Toxoplasma pre-sexual stages.

Sexual reproduction of Toxoplasma gondii, confined to the felid gut, remains largely uncharted owing to ethical concerns regarding the use of cats as model organisms. Chromatin modifiers dictate the developmental fate of the parasite during its multistage life cycle, but their targeting to stage-specific cistromes is poorly described1,2. Here we found that the transcription factors AP2XII-1 and AP2XI-2 operate during the tachyzoite stage, a hallmark of acute toxoplasmosis, to silence genes necessary for merozoites, a developmental stage critical for subsequent sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a marked change in the transcriptional program, promoting a full transition from tachyzoites to merozoites. These in vitro-cultured pre-gametes have unique protein markers and undergo typical asexual endopolygenic division cycles. In tachyzoites, AP2XII-1 and AP2XI-2 bind DNA as heterodimers at merozoite promoters and recruit MORC and HDAC3 (ref. 1), thereby limiting chromatin accessibility and transcription. Consequently, the commitment to merogony stems from a profound epigenetic rewiring orchestrated by AP2XII-1 and AP2XI-2. Successful production of merozoites in vitro paves the way for future studies on Toxoplasma sexual development without the need for cat infections and holds promise for the development of therapies to prevent parasite transmission.

Preclinical Evaluation of a Radiotheranostic Single-Domain Antibody Against Fibroblast Activation Protein α.

Fibroblast activation protein α (FAP) is highly expressed on cancer-associated fibroblasts of epithelial-derived cancers. Breast, colon, and pancreatic tumors often show strong desmoplastic reactions, which result in a dominant presence of stromal cells. FAP has gained interest as a target for molecular imaging and targeted therapies. Single-domain antibodies (sdAbs) are the smallest antibody-derived fragments with beneficial pharmacokinetic properties for molecular imaging and targeted therapy. Methods: We describe the generation, selection, and characterization of a sdAb against FAP. In mice, we assessed its imaging and therapeutic potential after radiolabeling with tracer-dose 131I and 68Ga for SPECT and PET imaging, respectively, and with 131I and 225Ac for targeted radionuclide therapy. Results: The lead sdAb, 4AH29, exhibiting picomolar affinity for a distinct FAP epitope, recognized both purified and membrane-bound FAP protein. Radiolabeled versions, including [68Ga]Ga-DOTA-4AH29, [225Ac]Ac-DOTA-4AH29, and [131I]I-guanidinomethyl iodobenzoate (GMIB)-4AH29, displayed radiochemical purities exceeding 95% and effectively bound to recombinant human FAP protein and FAP-positive GM05389 human fibroblasts. These radiolabeled compounds exhibited rapid and specific accumulation in human FAP-positive U87-MG glioblastoma tumors, with low but specific uptake in lymph nodes, uterus, bone, and skin (∼2-3 percentage injected activity per gram of tissue [%IA/g]). Kidney clearance of unbound [131I]I-GMIB-4AH29 was fast (<1 %IA/g after 24 h), whereas [225Ac]Ac-DOTA-4AH29 exhibited slower clearance (8.07 ± 1.39 %IA/g after 24 h and 2.47 ± 0.18 %IA/g after 96 h). Mice treated with [225Ac]Ac-DOTA-4AH29 and [131I]I-GMIB-4AH29 demonstrated prolonged survival compared with those receiving vehicle solution. Conclusion: [68Ga]Ga-DOTA-4AH29 and [131I]I-GMIB-4AH29 enable precise FAP-positive tumor detection in mice. Therapeutic [225Ac]Ac-DOTA-4AH29 and [131I]I-GMIB-4AH29 exhibit strong and sustained tumor targeting, resulting in dose-dependent therapeutic effects in FAP-positive tumor-bearing mice, albeit with kidney toxicity observed later for [225Ac]Ac-DOTA-4AH29. This study confirms the potential of radiolabeled sdAb 4AH29 as a radiotheranostic agent for FAP-positive cancers, warranting clinical evaluation.

Validação da escala Nurse-Parent Support Tool para a cultura portuguesa: Confiabilidade e validade / Validation of the Nurse-Parent Support Tool scale for Portuguese culture: Reliability and validity / Validación de la escala Nurse-Parent Support Tool para la cultura portuguesa: Fiabilidad y validez

Resumo Enquadramento: A avaliação da perceção dos pais de crianças hospitalizadas sobre o apoio dos enfermeiros constitui um contributo para aferir a qualidade dos cuidados de enfermagem pediátricos. Objetivo: Concluir o processo de Adaptação Cultural e Validação da Nurse-Parent Support Tool (NPST) para a realidade portuguesa, avaliando a confiabilidade e validade. Metodologia: Estudo metodológico quantitativo, com uma amostra de 291 pais de crianças hospitalizadas. As propriedades psicométricas do instrumento foram aferidas, avaliando a confiabilidade, através do cálculo do coeficiente do alfa de Crohnbach, e a validade de construto, pela análise fatorial exploratória, com rotação Varimax. Resultados: A NPST apresenta características psicométricas apropriadas à população portuguesa, de pais de crianças hospitalizadas (alfa de Cronhbach 0,925), garantindo-lhe a confiabilidade e validade para medir o apoio dado pelos enfermeiros. Conclusão: Os resultados demonstraram que a Escala de Apoio dos Enfermeiros aos Pais (EAEP), versão portuguesa da NPST, é um instrumento fiável e válido para avaliar o apoio dos enfermeiros, aos pais da criança hospitalizada e apresenta muito boa consistência interna.

Abstract Background: Assessing the perceptions of parents of hospitalized children about the support provided by nurses can contribute to assessing the quality of pediatric nursing care. Objective: To complete the cultural adaptation and validation of the Nurse-Parent Support Tool (NPST) for the Portuguese population by assessing its reliability and validity. Methodology: Quantitative methodological study, with a sample of 291 parents of hospitalized children. The psychometric properties of the instrument were measured by assessing its reliability using Cronbach's alpha coefficient and its construct validity through exploratory factor analysis with Varimax rotation. Results: The psychometric characteristics of the NPST show that it is appropriate to the Portuguese population of parents of hospitalized children (Cronbach's alpha of 0.925), as well as a reliable and valid tool to measure the support provided by nurses to these parents. Conclusion: The European Portuguese version of the NPST - Escala de Apoio dos Enfermeiros aos Pais (EAEP) - is a reliable and valid instrument with very good internal consistency to assess the support provided by nurses to parents during a child's hospitalization.

Resumen Marco contextual: La evaluación de la percepción de los padres de niños hospitalizados sobre el apoyo de los enfermeros es una contribución para evaluar la calidad de la atención de enfermería pediátrica. Objetivo: Completar el proceso de Adaptación Cultural y Validación del Nurse-Parent Support Tool (NPST) para la realidad portuguesa, evaluando fiabilidad y validez. Metodología: Estudio metodológico cuantitativo, con una muestra de 291 padres de niños hospitalizados. Se midieron las propiedades psicométricas del instrumento, evaluando la fiabilidad mediante el cálculo del coeficiente alfa de Crohnbach y la validez de constructo mediante análisis factorial exploratorio, con rotación Varimax. Resultados: El NPST presenta características psicométricas apropiadas para la población portuguesa de padres de niños hospitalizados (alfa de Cronhbach 0,925), garantizando su fiabilidad y validez para medir el apoyo dado por los enfermeiros. Conclusión: Los resultados mostraron que la Escala de Apoio dos Enfermeiros aos Pais (EAEP), versión portuguesa de NPST, es un instrumento confiable y válido para evaluar el apoyo de las enfermeras, a los padres, durante la hospitalización del niño y tiene muy buena consistencia interna.

Factors Associated with Parenting Adaptability in Facing the First COVID-19 Lockdown: A Study on Portuguese Parents.

Parenting was drastically challenged during the COVID-19 pandemic as families complied with the consequent containment for sanitary and social reasons. The purpose of this study is to explore the relationships among self-report measures (co-parenting, emotional experience and parental support network) and the employment condition (teleworking parents and at-home parents with governmental leave aid) that might be associated with the everyday life change, and their contribution towards family's daily routines during the first COVID-19 lockdown. A sample of 878 parents (90.2% mothers), aged from 21 to 61 years (39.58 ± 6.08), and mainly of Portuguese nationality (97.2%), was gathered through an online survey. Participants completed sociodemographic data and answered questions related to four positive parenting dimensions (Daily routines, Co-parenting, Emotional experience, and Support network) rating on a five-point Likert scale how much their behavior changed during the lockdown. Descriptive statistics and multilinear regression models were tested as well as a mediation model. The results showed that Emotional experience, Co-parenting, and Support network played an important role in family Daily routines, reinforcing that the first COVID-19 lockdown was lived differently by parents according to their employment conditions. Furthermore, the pathways model of factors associated with parental adaptability is suggestive that the direct effect of Emotional experience on Daily routines is partially mediated by Co-parenting and Support network. In line with previous studies on the complexity and dynamic ecology of parenting, the reported indicators showcase the interrelated facets of parenting and its corresponding support needs. Further, clear indicators for the design of family support interventions and family resilience enhancement to stressor events are discussed.

Handicap as a Measure of Perceived-Health Status in Parkinson's Disease.

Background: Handicap is a patient-centered measure of health status that encompasses the impact of social and physical environment on daily living, having been assessed in advanced and late-stage Parkinson's Disease (PD). Objective: To characterize the handicap of a broader sample of patients. Methods: A cross-sectional study of 405 PD patients during the MDS-UPDRS Portuguese validation study, using the MDS-UPDRS, Unified Dyskinesias Rating Scale, Nonmotor symptoms questionnaire, PDQ-8 and EQ-5D-3L. Handicap was measured using the London Handicap Scale (LHS). Results: Mean age was 64.42 (±10.3) years, mean disease duration 11.30 (±6.5) years and median HY 2 (IQR, 2-3). Mean LHS was 0.652 (±0.204); "Mobility," "Occupation" and "Physical Independence" were the most affected domains. LHS was significantly worse in patients with longer disease duration, older age and increased disability. In contrast, PDQ-8 did not differentiate age groups. Handicap was significantly correlated with disease duration (r = -0.35), nonmotor experiences of daily living (EDL) (MDS-UPDRS-I) (r = -0.51), motor EDL (MDS-UPDRS-II) (r = -0.69), motor disability (MDS-UPDRS-III) (r = -0.49), axial signs of MDS-UPDRS-III (r = -0.55), HY (r = -0.44), presence of nonmotor symptoms (r = -0.51) and PDQ-8 index (r = -0.64) (all P < 0.05). Motor EDL, MDS-UPDRS-III and PDQ-8 independently predicted Handicap (adjusted R 2 = 0.582; P = 0.007). Conclusions: The LHS was easily completed by patients and caregivers. Patients were mild-moderately handicapped, which was strongly determined by motor disability and its impact on EDL, and poor QoL. Despite correlated, handicap and QoL seem to differ in what they measure, and handicap may have an added value to QoL. Handicap seems to be a good measure of perceived-health status in a broad sample of PD.