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Gene editing technologies have the potential to correct genetic disorders by modifying, inserting, or deleting specific DNA sequences or genes, paving the way for a new class of ...genetic therapies. While gene editing tools continue to be improved to increase their precision and efficiency, the limited efficacy of in vivo delivery remains a major hurdle for clinical use. An ideal delivery vehicle should be able to target a sufficient number of diseased cells in a transient time window to maximize on-target editing and mitigate off-target events and immunogenicity.
Here, we review major advances in novel delivery platforms based on cell-derived vesicles − extracellular vesicles and virus-like particles − for transient delivery of gene editing payloads. We discuss major findings regarding packaging, in vivo biodistribution, therapeutic efficacy, and safety concerns of cell-derived vesicles delivery of gene editing cargos and their potential for clinical translation.
Oral cancer incidence and mortality are increasing over time. The most common therapies for oral cancers are surgery and radiotherapy, either used alone or combined, and immunotherapy can be also an ...option. Although there are several therapeutic options, none of them are completely effective, and in addition, there are numerous associated side effects. To overcome these limitations, researchers have been trying to reduce these drawbacks by using drug delivery systems that carry drugs for specific delivery to cancer cells. For that purpose, RNA-coated liposomes to selectively deliver the ligands C8 (acridine orange derivative) and dexamethasone to oral cancer cells were produced, characterized, and biologically evaluated.
Firstly, the RNA structure and binding interaction with ligands (C8 and dexamethasone) were evaluated by circular dichroism (CD), thermal difference spectroscopy (TDS), nuclear magnetic resonance (NMR) and fluorescence titrations. The biophysical assays evidenced the formation of an RNA hairpin and duplex structure. Moreover, steady-state and time-resolved fluorescence intensity and anisotropy experiments show that C8 forms a complex with RNA and adopts an open conformation upon RNA binding.
Then, RNA-coated liposomes were characterized by dynamic light scattering, and diameters near 160 nm were observed. Time-resolved anisotropy measurements of C8 loaded in RNA-functionalized liposomes indicate the co-existence of free C8 in solution (inside the liposome) and C8 bound to RNA at the external liposome surface. The RNA-functionalized liposomes loaded with C8 or dexamethasone mediated a significant reduction in the cell viability of malignant UPCI-SCC-154 cells while maintaining viable non-malignant NHDF cells. Additionally, the liposomes were able to internalize the cells, with higher uptake by the malignant cell line.
Overall, the results obtained in this work can contribute to the development of new drug delivery systems based on RNA-coated liposomes.
Background and Aims
The Point of Care Ultrasound and Point‐of‐Care Ultrasound in Resource‐Limited Settings are differentiated diagnostic methods using ultrasound, essential in urgent patients ...screening, allowing better guidance in the diagnostic process and therapeutic approach. This study intends to observe the impact of these techniques in two Basic Emergency Services (SUB) in Portugal.
Methods
A longitudinal study was carried out in two remote locations in Portugal (SUB N and SUB S). Data were collected by trained radiographers in each location, and a total of 972 exams were considered. Imaging findings were documented by exam type, the exam normality and the resolution after exam. χ2 and Cramer's V tests were performed to check significant correlations between the variables.
Results
Regarding the type of echographic findings, 289 (29.7%) were considered normal, 628 (64.6%) were classified as abnormal and 55 (5.7%) were considered inconclusive. As for the type of resolution, 58% had local resolution, 24% were referred to a hospital emergency service and 18% referred to ambulatory care. Regarding the Location versus Resolution after exam versus Findings variables, it was verified a stronger statistically significant association for the exams considered “Abnormal” (Cramer's V = 0.414; p < 0.001). In the variables Location versus Findings versus Resolution after exam, it was verified a stronger statistical significance for “Referral to Ambulatory” (Cramer V = 0.443; p < 0.001) although Referral for Hospital (Cramer V = 0.252; p = 0.003) or Local Resolution (Cramer V = 0.252; p < 0.001) also had a moderate association strength.
Conclusion
Ultrasonography is a useful diagnostic tool for patients screening, having an influence on patient management in remote settings. Given the limited literature in Portugal about this matter, further research and literature will be needed to support and complement the results of this study.
The main goal of this literature review is to discuss the emerging trends, challenges and opportunities in the field of medical imaging education in Europe due to the Covid-19 pandemic scenario that ...forced the remodeling of the teaching and learning process. A bibliographic search was carried out in the main databases and from resources available in scientific and professional associations in Europe. Exclusion criteria included articles without contributions on distance learning or active learning. Education and training in medical imaging field had to readapt and the usual opportunities for medical imaging and radiotherapy (MIR) students to learn in person in the classroom, lab and clinical settings, had to be quickly transformed into distance learning opportunities. Thus, online education became a pedagogical shift from traditional method to the modern approach of teaching and learning from classroom to Zoom, from personal to virtual and from seminars to webinars, leading to the emergence of innovative teaching models. Moreover, student-centered strategies such as flipped classroom and game-based learning have been recently applied in health professions education with positive and very promising results. In conclusion, due to the pandemic crisis, MIR educators and students find themselves in the situation where they felt compelled to embrace the digital academic experience, allowing the progressive innovation of e-learning. In this context, game-based learning appears to be effective for improving knowledge, skills, attitudes and satisfaction and should be considered as a potential systematic tool in the field of medical imaging education. Therefore, preparedness of radiographers depends on the application of effective training and education methodologies that allows excellent clinical performance and maintaining high quality and safety standards, both through undergraduate course and continuous professional development.
A exposição a fontes de radiação para fins médicos é uma componente essencial e estabelecida na prática médica que apresenta benefícios inquestionáveis, mas também riscos associados. Como tal, é ...necessária a sensibilização da população para a perceção dos riscos de forma a melhorar os seus níveis de literacia. Através de um estudo descritivo-correlacional pretendeu-se avaliar o conhecimento dos utentes sobre a radiação ionizante e os seus potenciais efeitos. Foi adotado um método de amostragem não probabilístico acidental, e a amostra foi constituída por 181 utentes. Face aos resultados atingidos, foi possível concluir que, apesar de a maioria dos utentes apresentar conhecimentos básicos acerca das radiações ionizantes e das técnicas imagiológicas que as utilizam, existe carência e necessidade de prestação de esclarecimentos acerca dos procedimentos imagiológicos bem como dos riscos e benefícios inerentes à sua realização. Constatou-se também que o grau de conhecimento acerca da temática em questão depende da faixa etária, verificando-se uma maior literacia radiológica em indivíduos mais jovens. Apesar dos resultados relativamente favoráveis do estudo, considera-se necessária a adoção de estratégias de comunicação da informação adequadas que contribuam para o incremento da literacia radiológica da população.
To measure the scattered radiation dose at different positions simulating hip surgery.
We simulated fluoroscopy-assisted hip surgery in order to study the distribution of scattered radiation in the ...operating room. To simulate the patient, we used a anthropomorphic whole-body phantom, and we used an X-ray-specific detector to quantify the radiation. Radiographs were obtained with a mobile C-arm X-ray system in continuous scan mode, with the tube at 0º (configuration 1) or 90º (configuration 2). The operating parameters employed (voltage, current, and exposure time) were determined by a statistical analysis based on the observation of orthopedic surgical procedures involving the hip.
For all measurements, higher exposures were observed in configuration 2. In the measurements obtained as a function of height, the maximum dose rates observed were 1.167 (± 0.023) µSv/s and 2.278 (± 0.023) µSv/s in configurations 1 and 2, respectively, corresponding to the chest level of health care professionals within the operating room. Proximal to the patient, the maximum values were recorded in the position occupied by the surgeon.
We can conclude that, in the scenario under study, health care professionals workers are exposed to low levels of radiation, and that those levels can be reduced through the use of personal protective equipment.
The main goals of this study were to describe, in an integrated and multidimensional way, the conditions related to the quality of care in radiology departments from Algarve (Portugal), to assess the ...perspective of radiographers on the use of scientific evidence in clinical practice and to validate a model that characterizes the conditions for continuous improvement.
A cross sectional study was performed in four radiology departments from public and private healthcare facilities from Algarve region (Portugal). A paper-based survey was sent to all radiographers to assess the quality systems implemented in their radiology departments and their perspective on the use of scientific evidence in clinical practice.
In total, 62 radiographers (61.4%) completed the survey. The quality dimensions that obtained the highest degree of compliance were the existence of quality assurance and improvement activities (43.0%), existence of standards in clinical practice of radiographers (42.7%) and the existence of special provisions (37.6%). The quality dimension related to patient's involvement was the one with the lowest level of compliance. Moreover, from the radiographers perspective, positive responses were obtained related to evidence-based actions (83.0%), sources of evidence (76.0%) and the significance of research activities (74.0%).
These findings suggest that a new framework based on four factors (Support for Information; Organizational Capability to Technical Quality of Care; Patient Involvement and Evidence-Based Radiology), should be considered in the establishment of strategic policies that better define the provision of diagnostic procedures and professional practices in radiology departments from Algarve region, based on quality improvement systems and better patient safety.
There is a need to include patients in the decision-making process, to involve radiographers in quality assurance and improvement activities and to implement quality monitoring mechanisms within radiology departments under study.
Les principaux objectifs de cette étude étaient de décrire, de manière intégrée et multidimensionnelle, les conditions liées à la qualité des soins dans les départements de radiologie de l'Algarve (Portugal), d'évaluer la perspective des radiographes sur l'utilisation des preuves scientifiques dans la pratique clinique et de valider un modèle qui caractérise les conditions d'amélioration continue.
Une étude transversale a été réalisée dans quatre services de radiologie d'établissements de santé publics et privés de la région d'Algarve (Portugal). Une enquête sur papier a été envoyée à tous les radiographes pour évaluer les systèmes de qualité mis en œuvre dans leurs services de radiologie et leur point de vue sur l'utilisation des preuves scientifiques dans la pratique clinique.
Au total, 62 radiographes (61,4%) ont répondu à l'enquête. Les dimensions de la qualité qui ont obtenu le plus haut degré de conformité sont l'existence d'activités d'assurance et d'amélioration de la qualité (43,0%), l'existence de normes dans la pratique clinique des radiographes (42,7%) et l'existence de dispositions spéciales (37,6%). La dimension de la qualité liée à l'implication du patient est celle dont le niveau de conformité est le plus faible. De plus, du point de vue des radiographes, des réponses positives ont été obtenues concernant les actions fondées sur des preuves (83,0%), la source des preuves (76,0%) et l'importance des activités de recherche (74,0%).
Ces résultats suggèrent qu'un nouveau cadre basé sur 4 facteurs (soutien à l'information, capacité organisationnelle à la qualité technique des soins, participation du patient et radiologie fondée sur des preuves), devrait être pris en compte dans l'établissement de politiques stratégiques qui définissent mieux la fourniture de procédures de diagnostic et de pratiques professionnelles dans les départements de radiologie de la région d'Algarve, sur la base de systèmes d'amélioration de la qualité et d'une meilleure sécurité du patient.
•Ulva spp., Gracilaria spp. and Fucus spp. were tested as dietary supplementation.•Seaweeds were tested at 2.5 and 7.5% supplementation levels in seabass diets.•Ulva spp. supplementation altered ...digestive capacity in seabass.•Gracilaria spp. affected fish redox status, regardless of supplementation level.•Dietary level of seaweed incorporation affected seabass immune responses.
This work aimed to appraise growth performance, digestive capacity and immune and stress responsiveness in European seabass (Dicentrarchus labrax) when fed diets supplemented with seaweeds. A control diet (without supplementation) was tested against 6 practical diets supplemented either with Gracilaria spp., Ulva spp., or Fucus spp., at 2.5 or 7.5% levels, plus an additional diet with a blend of the three seaweeds, each supplemented at 2.5% (Mix). Seabass juveniles (24.0±6.3g) were fed the experimental diets for 84days. Dietary seaweed supplementation had no effect on growth rate (DGI: 1.0–1.1), voluntary feed intake (11.3–12.6gkg −1ABW−1day−1), feed conversion ratio (FCR: 1.2–1.4) and protein efficiency ratio (PER: 1.5–1.8). Lipase activity was significantly higher in fish fed Mix diet when compared to control (P<0.05). Glutathione peroxidase (GPx) was significantly affected by seaweeds presence regardless its level of supplementation (P<0.05). The innate immune system was significantly altered by dietary seaweed supplementation (P<0.05). Fish fed the 7.5% seaweed supplemented diets had a significant decrease in the ACH50 level, when compared to fish fed 2.5% seaweed supplemented diets (P<0.05). Moreover, a combined effect of seaweed and supplementation level significantly affected lysozyme (LYS) activity (P<0.05). Fish fed diet with Ulva at 2.5% had an increase in LYS when compared to fish fed control and Ulva at 7.5% diets. Overall, our results indicate that the use of dietary seaweed supplementation improves immune and antioxidant responses in European seabass without compromising growth performance.
Pharmacoinvasive strategy is an effective myocardial reperfusion therapy when primary percutaneous coronary intervention (p-PCI) cannot be performed in a timely manner.
Authors sought to evaluate ...metrics of care and cardiovascular outcomes in a decade-long registry of a pharmacoinvasive strategy network for the treatment of ST-elevation myocardial infarction (STEMI). Data from a local network including patients undergoing fibrinolysis in county hospitals and systematically transferred to the tertiary center were accessed from March 2010 to September 2020. Numerical variables were described as median and interquartile range. Area under the curve (AUC-ROC) was used to analyze the predictive value of TIMI and GRACE scores for in-hospital mortality.
A total of 2,710 consecutive STEMI patients aged 59 51-66 years, 815 women (30.1%) and 837 individuals with diabetes (30.9%) were analyzed. The time from symptom onset to first-medical-contact was 120 60-210 minutes and the door-to-needle time was 70 43-115 minutes. Rescue-PCI was required in 929 patients (34.3%), in whom the fibrinolytic-catheterization time was 7.2 4.9-11.8 hours, compared to 15.7 6.8-22,7 hours in those who had successful lytic reperfusion. All cause in-hospital mortality occurred in 151 (5.6%) patients, reinfarction in 47 (1.7%) and ischemic stroke in 33 (1.2%). Major bleeding occurred in 73 (2.7%) patients, including 19 (0.7%) cases of intracranial bleeding. C-statistic confirmed that both scores had high predictive values for in-hospital mortality, demonstrated by TIMI AUC-ROC of 0.80 0,77-0.84 and GRACE AUC-ROC of 0.86 0.83-0.89.
In a real world registry of a decade-long network for the treatment of ST-elevation myocardial infarction based on the pharmacoinvasive strategy, low rates of in-hospital mortality and cardiovascular outcomes were observed, despite prolonged time metrics for both fibrinolytic therapy and rescue-PCI. Register Clinicaltrials.gov NCT02090712 date of first registration 18/03/2014.
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