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Medical imaging research is often limited by data scarcity and availability. Governance, privacy concerns and the cost of acquisition all restrict access to medical imaging data, which, compounded by the data-hungry nature of deep learning algorithms, limits progress in the field of healthcare AI. Generative models have recently been used to synthesize photorealistic natural images, presenting a potential solution to the data scarcity problem. But are current generative models synthesizing morphologically correct samples? In this work we present a three-dimensional generative model of the human brain that is trained at the necessary scale to generate diverse, realistic-looking, high-resolution and morphologically preserving samples and conditioned on patient characteristics (for example, age and pathology). We show that the synthetic samples generated by the model preserve biological and disease phenotypes and are realistic enough to permit use downstream in well-established image analysis tools. While the proposed model has broad future applicability, such as anomaly detection and learning under limited data, its generative capabilities can be used to directly mitigate data scarcity, limited data availability and algorithmic fairness.
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Background: Research into the identity development of trans people has been emerging, but there is still a need for further study. While significant processes for identity construction take place during late adolescence and early adulthood, it is important to understand which milestones are associated with the trajectories of gender identity (GI) development. Aims: The present study aimed at exploring the gender identity (GI) developmental trajectories of young Portuguese trans people and the processes associated with them. Methods: Interviews were conducted with sixteen young people aged between 16 and 26, recruited through LGBTI+ formal associations and informal online groups, as well as through psychology and sexology consultations. The interviews were conducted face-to-face and online and were analyzed through thematic analysis, which aims to identify, analyze and report patterns in a qualitative data series. Results: Six themes were identified and linked to developmental milestones. These were related to: (1) Discomfort in relation to the gender assigned at birth and its social roles; (2) Body discomfort; (3) Discovery of trans identities; (4) Disclosure of GI; (5) Perceived support; (6) Authentic living of GI. Linked to these themes, four sub-themes were identified as well. Discussion: Based on the life course theory, moments of transition and turning points were identified, as well as social influences such as historical time and place. Thereby, this study contributed to a better understanding of trans youth's GI developmental trajectories in the Portuguese context, where the study on this topic is still emergent, also contributing to inform the path to be taken at the international level regarding socio-legal policies concerning trans youth.
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The steep increase in carbon dioxide (CO2) emissions has created great concern due to its role in the greenhouse effect and global warming. One approach to mitigate CO2 levels involves its application in specific technologies. In this context, CO2 can be used for a more sustainable synthesis of polycarbonates (CO2-PCs). In this research, CO2-PC films and composites with multiwalled carbon nanotubes (MWCNTs, ranging from 0.2 to 7.0 wt.%) have been prepared to achieve more sustainable multifunctional sensing devices. The inclusion of the carbonaceous fillers allows for the electrical conductivity to be enhanced, reaching the percolation threshold (Pc) at 0.1 wt.% MWCNTs and a maximum electrical conductivity of 0.107 S·m-1 for the composite containing 1.5 wt.% MWCNTs. The composite containing 3.0 wt.% MWCNTs was also studied, showing a stable and linear response under temperature variations from 40 to 100 °C and from 30 to 45 °C, with a sensitivity of 1.3 × 10-4 °C-1. Thus, this investigation demonstrates the possibility of employing CO2-derived PC/MWCNT composites as thermoresistive sensing materials, allowing for the transition towards sustainable polymer-based electronics.
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Radioligand therapy is an emerging and effective treatment option for various types of malignancies, but may be intricately linked to hematological side effects such as anemia, lymphopenia or thrombocytopenia. The safety and efficacy of novel theranostic agents, targeting increasingly complex targets, can be well served by comprehensive dosimetry. However, optimization in patient management and patient selection based on risk-factors predicting adverse events and built upon reliable dose-response relations is still an open demand. In this context, artificial intelligence methods, especially machine learning and deep learning algorithms, may play a crucial role. This review provides an overview of upcoming opportunities for integrating artificial intelligence methods into the field of dosimetry in nuclear medicine by improving bone marrow and blood dosimetry accuracy, enabling early identification of potential hematological risk-factors, and allowing for adaptive treatment planning. It will further exemplify inspirational success stories from neighboring disciplines that may be translated to nuclear medicine practices, and will provide conceptual suggestions for future directions. In the future, we expect artificial intelligence-assisted (predictive) dosimetry combined with clinical parameters to pave the way towards truly personalized theranostics in radioligand therapy.
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Inteligencia Artificial , Médula Ósea , Medicina de Precisión , Radiometría , Humanos , Medicina de Precisión/métodos , Médula Ósea/efectos de la radiación , LigandosRESUMEN
SH-SY5Y is a human neuroblastoma cell line that can be differentiated into several neuronal phenotypes, depending on culture conditions. For this reason, this cell line has been widely used as an in vitro model of neurodegenerative conditions, such as Parkinson's disease (PD). However, most studies published to date used fetal bovine serum (FBS) as culture medium supplement for SH-SY5Y cell differentiation. We report on the testing of human platelet lysate (hPL) as a culture medium supplement to support SH-SY5Y cell culture. Both standard hPL and a fibrinogen-depleted hPL (FD-hPL) formulation, which does not require the addition of anticoagulants to culture media, promoted an increase in SH-SY5Y cell proliferation in comparison to FBS, without compromising metabolic activity. SH-SY5Y cells cultured in hPL or FD-hPL also displayed a higher number of neurite extensions and stained positive for MAP2 and synaptophysin, in the absence of differentiation stimuli; reducing hPL or FD-hPL concentration to 1% v/v did not affect cell proliferation or metabolic activity. Furthermore, following treatment with retinoic acid (RA) and further stimulation with brain-derived neurotrophic factor (BDNF) and nerve growth factor beta (NGF-ß), the percentage of SH-SY5Y cells stained positive for dopaminergic neuronal differentiation markers (tyrosine hydroxylase [TH] and Dopamine Transporter [DAT]) was higher in hPL or FD-hPL than in FBS, and gene expression of dopaminergic markers TH, DAT, and DR2 was also detected. Overall, the data herein presented supports the use of hPL to differentiate SH-SY5Y cells into a neuronal phenotype with dopaminergic features, and the adoption of FD-hPL as a fully xenogeneic free alternative to FBS to support the use of SH-SY5Y cells as a neurodegeneration model.
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Plaquetas , Técnicas de Cultivo de Célula , Diferenciación Celular , Proliferación Celular , Neuronas Dopaminérgicas , Neuroblastoma , Humanos , Proliferación Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Neuroblastoma/metabolismo , Neuroblastoma/patología , Línea Celular Tumoral , Plaquetas/metabolismo , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/citología , Técnicas de Cultivo de Célula/métodos , Medios de Cultivo/química , Medios de Cultivo/farmacología , Tretinoina/farmacología , FenotipoRESUMEN
The aim of this guideline is to provide recommendations for the implementation of an effective and efficient quality control (QC) programme for SPECT and PET systems in a preclinical imaging lab. These recommendations aim to strengthen the translational power of preclinical imaging results obtained using preclinical SPECT and PET. As for clinical imaging, reliability, reproducibility, and repeatability are essential when groups of animals are used in a longitudinal imaging experiment. The larger the variability of the imaging endpoint, the more animals are needed to be able to observe statistically significant differences between groups. Therefore, preclinical imaging requires quality control procedures to maintain reliability, reproducibility, and repeatability of imaging procedures, and to ensure the accuracy and precision of SPECT and PET quantification. While the Physics Committee of the European Association of Nuclear Medicine (EANM) has already published excellent procedure guidelines for Routine Quality Control Recommendations for Nuclear Medicine Instrumentation that also includes procedures for small animal PET systems, and important steps have already been made concerning preclinical quality control aspects, this new guideline provides a review and update of these previous guidelines such that guidelines are also adapted to new technological developments.
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Despite their unique histologic features, gliosarcomas belong to the group of glioblastomas and are treated according to the same standards. Fibroblast activation protein (FAP) is a component of a tumor-specific subpopulation of fibroblasts that plays a critical role in tumor growth and invasion. Some case studies suggest an elevated expression of FAP in glioblastoma and a particularly strong expression in gliosarcoma attributed to traits of predominant mesenchymal differentiation. However, the prognostic impact of FAP and its diagnostic and therapeutic potential remain unclear. Here, we investigate the clinical relevance of FAP expression in gliosarcoma and glioblastoma and how it correlates with 68Ga-FAP inhibitor (FAPI)-46 PET uptake. Methods: Patients diagnosed with gliosarcoma or glioblastoma without sarcomatous differentiation with an overall survival of less than 2.5 y were enrolled. Histologic examination included immunohistochemistry and semiquantitative scoring of FAP (0-3, with higher values indicating stronger expression). Additionally, 68Ga-FAPI-46 PET scans were performed in a subset of glioblastomas without sarcomatous differentiation patients. The clinical SUVs were correlated with FAP expression levels in surgically derived tumor tissue and relevant prognostic factors. Results: Of the 61 patients who were enrolled, 13 of them had gliosarcoma. Immunohistochemistry revealed significantly more FAP in gliosarcomas than in glioblastomas without sarcomatous differentiation of tumor tissue (P < 0.0001). In the latter, FAP expression was confined to the perivascular space, whereas neoplastic cells additionally expressed FAP in gliosarcoma. A significant correlation of immunohistochemical FAP with SUVmean and SUVpeak of 68Ga-FAPI-46 PET indicates that clinical tracer uptake represents FAP expression of the tumor. Although gliosarcomas express higher levels of FAP than do glioblastomas without sarcomatous differentiation, overall survival does not significantly differ between the groups. Conclusion: The analysis reveals a significant correlation between SUVmean and SUVpeak in 68Ga-FAPI-46 PET and immunohistochemical FAP expression. This study indicates that FAP expression is much more abundant in the gliosarcoma subgroup of glioblastomas. This could open not only a diagnostic but also a therapeutic gap, since FAP could be explored as a theranostic target to enhance survival in a distinct subgroup of high-risk brain tumor patients with poor survival prognosis.
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Glioblastoma , Gliosarcoma , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Endopeptidasas , Gelatinasas/metabolismo , Glioblastoma/diagnóstico por imagen , Glioblastoma/metabolismo , Glioblastoma/patología , Gliosarcoma/diagnóstico por imagen , Gliosarcoma/metabolismo , Gliosarcoma/patología , Proteínas de la Membrana/metabolismo , Tomografía de Emisión de Positrones , Pronóstico , Quinolinas , Serina Endopeptidasas/metabolismo , Análisis de SupervivenciaRESUMEN
Tumor cells may develop alterations in glycosylation patterns during the initial phase of carcinogenesis. These alterations may be important therapeutic targets for lectins with antitumor action. This work aimed to evaluate the in vitro cytotoxicity of VML on tumor and non-tumor cells (concentration of 25 µg/mL and then microdiluted) and evaluate its in vivo toxicity at different concentrations (1.8, 3.5 and 7.0 µg/mL), using Drosophila melanogaster. Toxicity in D. melanogaster evaluated mortality rate, as well as oxidative stress markers (TBARS, iron levels, nitric oxide levels, protein and non-protein thiols). The cytotoxicity assay showed that VML had cytotoxic effect on leukemic lines HL-60 (IC50 = 3.5 µg/mL), KG1 (IC50 = 18.6 µg/mL) and K562 (102.0 µg/mL). In the toxicity assay, VML showed no reduction in survival at concentrations of 3.5 and 7.0 µg/mL and did not alter oxidative stress markers at any concentrations tested. Cytotoxicity of VML from HL-60, KG1 and K562 cells could arise from the interaction between the lectin and specific carbohydrates of tumor cells. In contrast, effective concentrations of VML against no-tumor cells human keratinocyte - HaCat and in the D. melanogaster model did not show toxicity, suggesting that VML is a promising molecule in vivo studies involving leukemic cells.
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Drosophila melanogaster , Lectinas , Animales , Humanos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Drosophila melanogaster/efectos de los fármacos , Células HL-60 , Lectinas/farmacología , Lectinas/toxicidad , Estrés Oxidativo/efectos de los fármacosRESUMEN
Objective.The partial-volume effect (PVE) is an important factor impairing tumour quantification in molecular imaging. The commonly used contour-volume-of-interest (contour-VOI) approach to correct for this effect employs phantom-based recovery coefficients. Applying oversize-VOIs could offer superior quantification accuracy in small lesions. The oversize-VOI approach uses a large oversize volume to determine the total tumour activity after applying a background correction. Aims of this study were to provide a procedure for the application of the oversize-VOI approach and to compare its performance to the contour-VOI approach in PET imaging.Approach.A sphere tumour model was simulated to determine the oversize diameter that contained 90%, 95%, and 98% of the total activity as a function of the tumour size. Experimental investigations involving phantom and clinical data were conducted on a digital PET/CT scanner. In the phantom investigation, 12 spherical tumour inserts (diameters ranging from 3.7 to 37.4 mm) containing18F-solution were used. The accuracy of the contour- and oversize-VOI approach was evaluated for different signal-to-background ratios (20-3). Clinically, both approaches were applied on PET/CT images acquired with18F-labelled prostate-specific membrane antigen in prostate cancer patients.Main results.From the tumour model, we deduced that an oversize-VOI of two PET spatial resolutions larger than the physical lesion diameter contains at least 98% of the total activity for lesions with diameters down to one PET spatial resolution, while minimizing the background contribution. Both approaches were robust against varying phantom and clinical imaging conditions. Performance of the oversize-VOI approach was favorable for lesions below 10 mm in diameter, whereas the contour-VOI approach was slightly more accurate for sizes above 10 mm.Significance.The oversize-VOI approach facilitates image quantification of small tumours. It is simple and effective to correct for the PVE and may be used in pre-therapeutic (small) tumour dosimetry.
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Fantasmas de Imagen , Tomografía de Emisión de Positrones , Radiometría , Planificación de la Radioterapia Asistida por Computador , Planificación de la Radioterapia Asistida por Computador/métodos , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Procesamiento de Imagen Asistido por Computador/métodos , Carga Tumoral , Dosificación Radioterapéutica , Neoplasias/radioterapia , Neoplasias/diagnóstico por imagenRESUMEN
The advancement of nanobiocomposites reinforced with 2D nano-materials plays a pivotal role in enhancing bone tissue engineering. In this study, we introduce a nanobiocomposite that reinforces bovine collagen with 2D nano-talc, a recently exfoliated nano-mineral. These nanobiocomposites were prepared by blending collagen with varying concentrations of 2D nano-talc, encompassing mono- and few-layers talc from soapstone nanomaterial. Extensive characterization techniques including AFM, XPS, nano-FTIR, s-SNOM nanoimaging, Force Spectroscopy, and PeakForce QNM® were employed. The incorporation of 2D nano-talc significantly enhanced the mechanical properties of the nanobiocomposites, resulting in increased stiffness compared to pristine collagen. In vitro studies supported the growth and proliferation of osteoblasts onto 2D nano-talc-reinforced nanobiocomposites, as well as showed the highest mineralization potential. These findings highlight the substantial potential of the developed nanobiocomposite as a scaffold material for bone tissue engineering applications.
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Huesos , Colágeno , Nanocompuestos , Osteoblastos , Ingeniería de Tejidos , Ingeniería de Tejidos/métodos , Colágeno/química , Animales , Bovinos , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Nanocompuestos/química , Andamios del Tejido/química , Proliferación Celular/efectos de los fármacos , Humanos , Materiales Biocompatibles/químicaRESUMEN
2D materials, given their form-factor, high surface-to-volume ratio, and chemical functionality have immense use in sensor design. Engineering 2D heterostructures can result in robust combinations of desirable properties but sensor design methodologies require careful considerations about material properties and orientation to maximize sensor response. This study introduces a sensor approach that combines the excellent electrical transport and transduction properties of graphite film with chemical reactivity derived from the edge sites of semiconducting molybdenum disulfide (MoS2) through a two-step chemical vapour deposition method. The resulting vertical heterostructure shows potential for high-performance hybrid chemiresistors for gas sensing. This architecture offers active sensing edge sites across the MoS2 flakes. We detail the growth of vertically oriented MoS2 over a nanoscale graphite film (NGF) cross-section, enhancing the adsorption of analytes such as NO2, NH3, and water vapor. Raman spectroscopy, density functional theory calculations and scanning probe methods elucidate the influence of chemical doping by distinguishing the role of MoS2 edge sites relative to the basal plane. High-resolution imaging techniques confirm the controlled growth of highly crystalline hybrid structures. The MoS2/NGF hybrid structure exhibits exceptional chemiresistive responses at both room and elevated temperatures compared to bare graphitic layers. Quantitative analysis reveals that the sensitivity of this hybrid sensor surpasses other 2D material hybrids, particularly in parts per billion concentrations.
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Flexible esophagogastroduodenoscopy is the gold standard for removing FB of the upper gastrointestinal tract. However large sharped FB are usually challenging to remove and are the subtype that most often requires surgery. We describe a case of a patient with a dental prothesis impacted in the proximal oesophagus. After a failed conventional approach, we made a successful attempt with two regular scopes with two independent operators.
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AIMS: This study aimed to evaluate the efficiency of two phages [VB_VaC_TDDLMA (phage TDD) and VB_VaC_SRILMA (phage SRI)] alone and in a cocktail to control Vibrio alginolyticus in brine shrimp before their administration in larviculture. METHODS AND RESULTS: Phages were isolated from seawater samples and characterized by host spectrum, growth parameters, adsorption rate, genomic analysis, and inactivation efficiency. Both phages belong to the Caudoviricetes class and lack known virulence or antibiotic-resistance genes. They exhibit specificity, infecting only their host, V. alginolyticus CECT 521. Preliminary experiments in a culture medium showed that phage TDD (reduction of 5.8 log CFU ml-1 after 10 h) outperformed phage SRI (reduction of 4.6 log CFU ml-1 after 6 h) and the cocktail TDD/SRI (reduction of 5.2 log CFU ml-1 after 8 h). In artificial marine water experiments with Artemia franciscana, both single phage suspensions and the phage cocktail, effectively inactivated V. alginolyticus in culture water (reduction of 4.3, 2.1, and 1.9 log CFU ml-1 for phages TDD, SRI, and the phage cocktail, respectively, after 12 h) and in A. franciscana (reduction of 51.6%, 87.3%, and 85.3% for phages TDD, SRI, and the phage cocktail, respectively, after 24 h). The two phages and the phage cocktail did not affect A. franciscana natural microbiota or other Vibrio species in the brine shrimp. CONCLUSIONS: The results suggest that phages can safely and effectively control V. alginolyticus in A. franciscana prior to its administration in larviculture.
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Acuicultura , Artemia , Bacteriófagos , Vibrio alginolyticus , Vibrio alginolyticus/virología , Animales , Artemia/microbiología , Artemia/virología , Alimentación Animal , Agua de Mar/microbiología , Larva/microbiologíaRESUMEN
The speciation of arsenic in fish has been widely investigated, but bioaccumulation and biotransformation of inorganic As in different tissues of Nile tilapia (Oreochromis niloticus) are not fully understood. The present study aimed to investigate the bioaccumulation of As in Nile tilapia, as well as to evaluate the distribution of the main arsenic species (As(III), As(V), MMA, DMA, and AsB) in liver, stomach, gill, and muscle, after controlled exposures to As(III) and As(V) at concentrations of 5.0 and 10.0 mg L-1 during periods of 1 and 7 days. Total As was determined by inductively coupled plasma mass spectroscopy (ICP-MS). For both exposures (As(III) and As(V)), the total As levels after 7-day exposure were highest in the liver and lowest in the muscle. Overall, the Nile tilapia exposed to As(III) showed higher tissue levels of As after the treatments, compared to As(V) exposure. Speciation of arsenic present in the tissues employed liquid chromatography coupled to ICP-MS (LC-ICP-MS), revealing that the biotransformation of As included As(V) reduction to As(III), methylation to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and subsequent conversion to nontoxic arsenobetaine (AsB), which was the predominant arsenic form. Finally, the interactions and antagonistic effects of selenium in the bioaccumulation processes were tested by the combined exposure to As(III), the most toxic species of As, together with tetravalent selenium (Se(IV)). The results indicated a 4-6 times reduction of arsenic toxicity in the tilapia.
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Arsénico , Bioacumulación , Biotransformación , Cíclidos , Hígado , Selenio , Contaminantes Químicos del Agua , Animales , Arsénico/metabolismo , Cíclidos/metabolismo , Contaminantes Químicos del Agua/metabolismo , Selenio/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Branquias/metabolismo , Músculos/metabolismoRESUMEN
Understanding interactions between legacy and emerging environmental contaminants has important implications for risk assessment, especially when mutagens and carcinogens are involved, whose critical effects are chronic and therefore difficult to predict. The current work aimed to investigate potential interactions between benzo[a]pyrene (B[a]P), a carcinogenic polycyclic aromatic hydrocarbon and legacy pollutant, and diclofenac (DFC), a non-steroidal anti-inflammatory drug and pollutant of emerging concern, and how DFC affects B[a]P toxicity. Exposure to binary mixtures of these chemicals resulted in substantially reduced cytotoxicity in human HepG2 cells compared to single-chemical exposures. Significant antagonistic effects were observed in response to high concentrations of B[a]P in combination with DFC at IC50 and â IC50. While additive effects were found for levels of intracellular reactive oxygen species, antagonistic mixture effects were observed for genotoxicity. B[a]P induced DNA strand breaks, γH2AX activation, and micronuclei formation at ½ IC50 concentrations or lower, whereas DFC induced only low levels of DNA strand breaks. Their mixture caused significantly lower levels of genotoxicity by all three endpoints compared to those expected based on concentration additivity. In addition, antagonistic mixture effects on CYP1 enzyme activity suggested that the observed reduced genotoxicity of B[a]P was due to its reduced metabolic activation as a result of enzymatic inhibition by DFC. Overall, the findings further support the growing concern that co-exposure to environmental toxicants and their non-additive interactions may be a confounding factor that should not be neglected in environmental and human health risk assessment.
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Benzo(a)pireno , Carcinógenos Ambientales , Diclofenaco , Humanos , Diclofenaco/toxicidad , Benzo(a)pireno/toxicidad , Células Hep G2 , Carcinógenos Ambientales/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Ciclooxigenasa 1/metabolismo , Supervivencia Celular/efectos de los fármacos , Inhibidores de la Ciclooxigenasa/farmacología , Inhibidores de la Ciclooxigenasa/toxicidad , Ciclooxigenasa 2/metabolismo , Daño del ADN/efectos de los fármacos , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/toxicidad , HistonasRESUMEN
Microtextures imprinted on the surface of quartz grains provide in-depth information on the environmental conditions and sedimentary processes that affected the study sediments. Microtextural analyses are therefore widely used in the provenance studies of sediments. In order to minimize the subjectivity of microtextural recognition, we propose a new software, called DeepGrain (source codes are available at https://github.com/deepgrains/deepgrain), for the automatic identification of microtextures on the surface of quartz grains using the DeepLabV3 model with applied improving techniques. The approach provides an accuracy of 99â¯% of the area of the tested grains and 63â¯% of the mechanical features on the surfaces of the tested grains. The inference of a single SEM image of quartz grain took an average of 3.10â¯sec, leading to a significant reduction in the analysis time of a single grain.
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BACKGROUND: The extent of pelvic lymphadenectomy (PLND) as part of radical cystectomy (RC) for bladder cancer (BC) remains unclear. Sentinel-based and lymphangiographic approaches could lead to reduced morbidity without sacrificing oncologic safety. OBJECTIVE: To evaluate the feasibility and diagnostic value of fluorescence-guided template sentinel region dissection (FTD) using a handheld near-infrared fluorescence (NIRF) camera in open radical cystectomy. DESIGN, SETTING, AND PARTICIPANTS: After peritumoral cystoscopic injection of indocyanine green (ICG) 21 patients underwent open RC with FTD due to BC between June 2019 and June 2021. Intraoperatively, the FIS-00 Hamamatsu Photonics® NIRF camera was used to identify and resect fluorescent template sentinel regions (FTRs) followed by extended pelvic lymphadenectomy (ePLND) as oncological back-up. OUTCOME MEASUREMENT AND STATISTICAL ANALYSIS: Descriptive analysis of positive and negative results per template region. RESULTS AND LIMITATIONS: FTRs were identified in all 21 cases. Median time (range) from ICG injection to fluorescence detection was 75 (55-125) minutes. On average (SD), 33.4 (9.6) lymph nodes were dissected per patient. Considering template regions as the basis of analysis, 67 (38.3%) of 175 resected regions were NIRF-positive, with 13 (7.4%) regions harboring lymph node metastases. We found no metastatic lymph nodes in NIRF-negative template regions. Outside the standard template, two NIRF-positive benign nodes were identified. CONCLUSION: The concept of NIRF-guided FTD proved for this group all lymph node metastases to be found in NIRF-positive template regions. Pending validation in a larger collective, resection of approximately 40% of standard regions may be sufficient and may result in less morbidity.
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Cistectomía , Escisión del Ganglio Linfático , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Escisión del Ganglio Linfático/métodos , Escisión del Ganglio Linfático/instrumentación , Cistectomía/métodos , Cistectomía/instrumentación , Femenino , Masculino , Anciano , Persona de Mediana Edad , Verde de Indocianina , Estudios de Factibilidad , Fluorescencia , Pronóstico , Estudios de Seguimiento , Espectroscopía Infrarroja Corta/métodos , Espectroscopía Infrarroja Corta/instrumentación , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/diagnóstico por imagen , Anciano de 80 o más Años , ColorantesRESUMEN
Para-aminohippurate, also known as p-aminohippuric acid (PAH), is used clinically to measure effective renal plasma flow. Preclinically, it was shown to reduce 177Lu-DOTATOC uptake in the kidneys while improving bioavailability compared with amino acid (AA) coinfusion. We report the safety and efficacy of PAH coinfusion during peptide receptor radiotherapy in patients with neuroendocrine tumors. Methods: Twelve patients with metastatic or unresectable gastroenteropancreatic neuroendocrine tumors received 177Lu-DOTATOC in 33 treatment cycles. Either 8 g of PAH or a mixture of 25 g of arginine and 25 g of lysine were coinfused. Safety was assessed by monitoring laboratory data, including hematologic and renal data, as well as electrolytes obtained before and 24 h after treatment. For radiation dosimetry, whole-body scans were performed at 1, 24, and 48 h and a SPECT/CT scan was performed at 48 h, along with blood sampling at 5 min and 0.5, 2, 4, 24, and 48 h after administration. Absorbed dose estimations for the kidneys and bone marrow were performed according to the MIRD concept. Results: In 15 treatment cycles, PAH was coinfused. No changes in mean creatinine level, glomerular filtration rate, and serum electrolytes were observed before or 24 h after treatment when using PAH protection (P ≥ 0.20), whereas serum chloride and serum phosphate increased significantly under AA (both P < 0.01). Kidney-absorbed dose coefficients were 0.60 ± 0.14 Gy/GBq with PAH and 0.53 ± 0.16 Gy/GBq with AA. Based on extrapolated cumulative kidney-absorbed doses for 4 cycles, 1 patient with PAH protection and 1 patient with AA protection in our patient group would exceed the 23-Gy conservative threshold. The bone marrow-absorbed dose coefficient was 0.012 ± 0.004 Gy/GBq with PAH and 0.012 ± 0.003 Gy/GBq with AA. Conclusion: PAH is a promising alternative to AA for renal protection during peptide receptor radiotherapy. Further research is required to systematically investigate the safety profile and radiation dosimetry at varying PAH plasma concentrations.
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Riñón , Tumores Neuroendocrinos , Octreótido , Humanos , Tumores Neuroendocrinos/radioterapia , Tumores Neuroendocrinos/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Anciano , Octreótido/análogos & derivados , Octreótido/uso terapéutico , Octreótido/efectos adversos , Riñón/efectos de la radiación , Riñón/metabolismo , Receptores de Péptidos/metabolismo , Adulto , Protección Radiológica , Seguridad , Compuestos Organometálicos/uso terapéutico , Compuestos Organometálicos/efectos adversosRESUMEN
With the rapid increase of the number of patients with gastrointestinal diseases in modern society, the need for the development of physiologically relevant in vitro intestinal models is key to improve the understanding of intestinal dysfunctions. This involves the development of a scaffold material exhibiting physiological stiffness and anatomical mimicry of the intestinal architecture. The current work focuses on evaluating the scaffold micromorphology of gelatin-methacryloyl-aminoethyl-methacrylate-based nonporous and porous intestinal 3D, intestine-like constructs, fabricated via digital light processing, on the cellular response. To this end, Caco-2 intestinal cells were utilized in combination with the constructs. Both porous and nonporous constructs promoted cell growth and differentiation toward enterocyte-like cells (VIL1, ALPI, SI, and OCLD expression showed via qPCR, ZO-1 via immunostaining). The porous constructs outperformed the nonporous ones regarding cell seeding efficiency and growth rate, confirmed by MTS assay, live/dead staining, and TEER measurements, due to the presence of surface roughness.
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Hidrogeles , Andamios del Tejido , Humanos , Porosidad , Hidrogeles/química , Células CACO-2 , Andamios del Tejido/química , Proliferación Celular , Gelatina/química , Intestinos/citología , Metacrilatos/química , Ingeniería de Tejidos/métodos , Diferenciación CelularRESUMEN
Screen printing is one of the most used techniques for developing printed electronics. It stands out for its simplicity, scalability, and effectivity. Specifically, the manufacturing of hybrid integrated circuits has promoted the development of the technique, and the photovoltaic industry has enhanced the printing process by developing high-performance metallization pastes and high-end screens. In recent years, fine lines of 50 µm or smaller are about to be adopted in mass production, and screen printing has to compete with digital printing techniques such as inkjet printing, which can reach narrower lines. In this sense, this work is focused on testing the printing resolution of a high-performance stainless-steel screen with commercial conductive inks and functional lab-made inks based on reduced graphene oxide using an interdigitated structure. We achieved electrically conductive functional patterns with a minimum printing resolution of 40 µm for all inks.