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Background and aim: Cytokeratin 19 (CK19)-positive HCC is a subtype of hepatocellular carcinoma (HCC) with poor biological behavior and resistance to different treatments including transarterial chemoembolization (TACE). The current study aimed to investigate the predictive value of serum CK 19 fragment 21-1 (CYFRA 21-1) and serum CK 19 fragment 2G2 (CK 19-2G2) for TACE response in patients with hepatitis C virus (HCV)-related HCC. Methods: This prospective study assessed the pretreatment serum CYFRA 21-1 and CK 19-2G2 levels in 64 patients with HCV-related naïve HCC who underwent TACE to predict 1-year overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Additionally, 40 healthy individuals were included as controls. Pretreatment alpha-fetoprotein (AFP) was also measured for comparison. Results: After exclusions, 60 patients completed TACE sessions, and the 1-year OS was 52%, and ORR post TACE was 71.8%. HCC patients with elevated levels of CYFRA 21-1, CK 19-2G2, or baseline AFP measuring ≥400 ng/ml have decreased 1-year OS and PFS after TACE. Serum CK19-2G2 was an independent predictor of 1-year OS using multivariate hazard regression analysis. Pretreatment normal serum CYFRA 21-1 levels (P = 0.047), serum AFP measuring <400 ng/ml (P = 0.016), and lower AST (P = 0.002) were independent predictors of ORR to TACE using multivariate logistic regression analysis. The predictive ability of pretreatment elevated serum CYFRA 21-1, AFP measuring ≥400 ng/ml, AFP + CYFRA 21-1, AFP + CK 19-2G2, or AFP + CYFRA 21-1+ CK19-2G2 to predict nonresponse (progressive disease) to TACE (area under the curve = 0.795, 0.690, 0.830, 0.725, and 0.850, respectively). Conclusions: This study demonstrated that incorporating the measurement of serum CYFRA 21-1 or CK19-2G2 levels, along with AFP, during the initial diagnosis can aid in predicting poor 1-year OS, PFS, and ORR to TACE in patients with HCV-related HCC.
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The development of artificial Antigen Presenting Cells (aAPCs) has led to improvements in adoptive T cell therapy (ACT), an immunotherapy, for cancer treatment. aAPCs help to streamline the consistent production and expansion of T cells, thus reducing the time and costs associated with ACT. However, several issues still exist with ACT, such as insufficient T cell potency, which diminishes the translational potential for ACT. While aAPCs have been used primarily to increase production efficiency of T cells for ACT, the intrinsic properties of a biomaterial-based aAPC may affect T cell phenotype and function. In CD8+ T cells, reactive oxygen species (ROS) and oxidative stress accumulation can activate Forkhead box protein O1 (FOXO1) to transcribe antioxidants which reduce ROS and improve memory formation. Alginate, a biocompatible and antioxidant rich biomaterial, is promising for incorporation into an aAPC formulation to modulate T cell phenotype. To investigate its utility, a novel alginate-based aAPC platform was developed that preferentially expanded CD8+ T cells with memory related features. Alginate-based aAPCs allowed for greater control of CD8+ T cell qualities, including, significantly improved in vivo persistence and augmented in vivo anti-tumor T cell responses.
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Alginatos , Células Apresentadoras de Antígenos , Linfócitos T CD8-Positivos , Memória Imunológica , Imunoterapia Adotiva , Alginatos/química , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Animais , Imunoterapia Adotiva/métodos , Células Apresentadoras de Antígenos/imunologia , Memória Imunológica/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Humanos , Proliferação de Células/efeitos dos fármacosRESUMO
Purpose: To apply methods for quantifying uncertainty of deep learning segmentation of geographic atrophy (GA). Design: Retrospective analysis of OCT images and model comparison. Participants: One hundred twenty-six eyes from 87 participants with GA in the SWAGGER cohort of the Nonexudative Age-Related Macular Degeneration Imaged with Swept-Source OCT (SS-OCT) study. Methods: The manual segmentations of GA lesions were conducted on structural subretinal pigment epithelium en face images from the SS-OCT images. Models were developed for 2 approximate Bayesian deep learning techniques, Monte Carlo dropout and ensemble, to assess the uncertainty of GA semantic segmentation and compared to a traditional deep learning model. Main Outcome Measures: Model performance (Dice score) was compared. Uncertainty was calculated using the formula for Shannon Entropy. Results: The output of both Bayesian technique models showed a greater number of pixels with high entropy than the standard model. Dice scores for the Monte Carlo dropout method (0.90, 95% confidence interval 0.87-0.93) and the ensemble method (0.88, 95% confidence interval 0.85-0.91) were significantly higher (P < 0.001) than for the traditional model (0.82, 95% confidence interval 0.78-0.86). Conclusions: Quantifying the uncertainty in a prediction of GA may improve trustworthiness of the models and aid clinicians in decision-making. The Bayesian deep learning techniques generated pixel-wise estimates of model uncertainty for segmentation, while also improving model performance compared with traditionally trained deep learning models. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Objective: Despite advances in artificial intelligence (AI) in glaucoma prediction, most works lack multicenter focus and do not consider fairness concerning sex, race, or ethnicity. This study aims to examine the impact of these sensitive attributes on developing fair AI models that predict glaucoma progression to necessitating incisional glaucoma surgery. Design: Database study. Participants: Thirty-nine thousand ninety patients with glaucoma, as identified by International Classification of Disease codes from 7 academic eye centers participating in the Sight OUtcomes Research Collaborative. Methods: We developed XGBoost models using 3 approaches: (1) excluding sensitive attributes as input features, (2) including them explicitly as input features, and (3) training separate models for each group. Model input features included demographic details, diagnosis codes, medications, and clinical information (intraocular pressure, visual acuity, etc.), from electronic health records. The models were trained on patients from 5 sites (N = 27 999) and evaluated on a held-out internal test set (N = 3499) and 2 external test sets consisting of N = 1550 and N = 2542 patients. Main Outcomes and Measures: Area under the receiver operating characteristic curve (AUROC) and equalized odds on the test set and external sites. Results: Six thousand six hundred eighty-two (17.1%) of 39 090 patients underwent glaucoma surgery with a mean age of 70.1 (standard deviation 14.6) years, 54.5% female, 62.3% White, 22.1% Black, and 4.7% Latinx/Hispanic. We found that not including the sensitive attributes led to better classification performance (AUROC: 0.77-0.82) but worsened fairness when evaluated on the internal test set. However, on external test sites, the opposite was true: including sensitive attributes resulted in better classification performance (AUROC: external #1 - [0.73-0.81], external #2 - [0.67-0.70]), but varying degrees of fairness for sex and race as measured by equalized odds. Conclusions: Artificial intelligence models predicting whether patients with glaucoma progress to surgery demonstrated bias with respect to sex, race, and ethnicity. The effect of sensitive attribute inclusion and exclusion on fairness and performance varied based on internal versus external test sets. Prior to deployment, AI models should be evaluated for fairness on the target population. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Backgrounds and aim: Viscoelastic tests (VET) like rotational thromboelastometry (ROTEM) assess global hemostasis in cirrhosis. We aimed to assess whether ROTEM-guided blood product transfusion results in lower blood product requirements in patients with cirrhosis undergoing elective invasive procedures as compared to standard of care (SOC) based on conventional coagulation test (CCT). Methods: In this open label randomized controlled trial, patients with cirrhosis and abnormal CCT who were undergoing an invasive procedure were randomized to receive blood products either by ROTEM-guidance or SOC. The primary outcome was the difference in blood products (fresh frozen plasma (FFP) or platelets) transfused between the groups. The secondary outcome was procedure-related bleeding or complications within 7 days of the procedure. The trial protocol is registered at clinicaltrails.gov; NCT05698134. Results: From August 2021 to January 2023, a total of 40 patients were recruited (ROTEM (n = 20) and SOC (n = 20)). The trial was terminated earlier during interim analyses due to compelling benefit in the ROTEM group after a scheduled interim analysis. The ROTEM group required substantially less blood transfusion than the SOC group (40% [8/20] vs 100% [20/20], P < 0.001). The benefit was consistent across all types of blood product, including fresh frozen plasma (<0.001) and pooled platelets (P = 0.046). No patients experienced clinically significant bleeding events. Transfusion-associated adverse events occurred in one patient (5%) in the SOC group (allergic reaction) and none in the ROTEM group (P = NS). The mortality in both groups at 30 and 90 days was similar. Conclusions: Viscoelastic tests like ROTEM provide global assessment of hemostasis in patients with cirrhosis. Institution of ROTEM based transfusion strategy significantly reduces the need for blood product transfusion in patients with cirrhosis undergoing elective procedure without any increased risk of bleeding events. Clinical trial number: NCT05698134.
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Purpose: To evaluate the capabilities of Chat Generative Pre-Trained Transformer (ChatGPT), as a large language model (LLM), for diagnosing glaucoma using the Ocular Hypertension Treatment Study (OHTS) dataset, and comparing the diagnostic capability of ChatGPT 3.5 and ChatGPT 4.0. Design: Prospective data collection study. Participants: A total of 3170 eyes of 1585 subjects from the OHTS were included in this study. Methods: We selected demographic, clinical, ocular, visual field, optic nerve head photo, and history of disease parameters of each participant and developed case reports by converting tabular data into textual format based on information from both eyes of all subjects. We then developed a procedure using the application programming interface of ChatGPT, a LLM-based chatbot, to automatically input prompts into a chat box. This was followed by querying 2 different generations of ChatGPT (versions 3.5 and 4.0) regarding the underlying diagnosis of each subject. We then evaluated the output responses based on several objective metrics. Main Outcome Measures: Area under the receiver operating characteristic curve (AUC), accuracy, specificity, sensitivity, and F1 score. Results: Chat Generative Pre-Trained Transformer 3.5 achieved AUC of 0.74, accuracy of 66%, specificity of 64%, sensitivity of 85%, and F1 score of 0.72. Chat Generative Pre-Trained Transformer 4.0 obtained AUC of 0.76, accuracy of 87%, specificity of 90%, sensitivity of 61%, and F1 score of 0.92. Conclusions: The accuracy of ChatGPT 4.0 in diagnosing glaucoma based on input data from OHTS was promising. The overall accuracy of ChatGPT 4.0 was higher than ChatGPT 3.5. However, ChatGPT 3.5 was found to be more sensitive than ChatGPT 4.0. In its current forms, ChatGPT may serve as a useful tool in exploring disease status of ocular hypertensive eyes when specific data are available for analysis. In the future, leveraging LLMs with multimodal capabilities, allowing for integration of imaging and diagnostic testing as part of the analyses, could further enhance diagnostic capabilities and enhance diagnostic accuracy. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Microbial sample analysis has received growing attention within the last decade, driven by important findings in microbiome research and promising applications in the biotechnological field. Modern mass spectrometry-based methodology has been established in this context, providing sufficient sensitivity, resolution, dynamic range, and throughput to analyze the so-called metaproteome of complex microbial mixtures from clinical or environmental samples. While proteomic analyses were previously restricted to common model organisms, next-generation sequencing technologies nowadays allow for the rapid and cost-efficient characterization of whole metagenomes of microbial consortia and specific genomes from non-model organisms to which microbes contribute by significant amounts. This proteogenomic approach, meaning the combined application of genomic and proteomic methods, enables researchers to create a protein database that presents a tailored blueprint of the microbial sample under investigation. This contribution provides an overview of the computational challenges and opportunities in proteogenomics and metaproteomics as of January 2018. For practical application, we first showcase an integrative proteogenomic method that circumvents existing reference databases by creating sample-specific transcripts. The underlying algorithm uses a graph network approach that combines RNA-Seq and peptide information. As a second example, we provide a tutorial for a simulation tool that estimates the computational limits of detecting microbial non-model organisms. This method evaluates the potential influence of error-tolerant searches and proteogenomic approaches on databases of interest. Finally, we discuss recommendations for developing future strategies that may help overcome present limitations by combining the strengths of genome- and proteome-based methods and moving toward an integrated metaproteogenomics approach.
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Microbiota , Proteogenômica , Proteogenômica/métodos , Microbiota/genética , Biologia Computacional/métodos , Proteômica/métodos , Software , Bases de Dados de Proteínas , Metagenômica/métodos , Algoritmos , Metagenoma , Humanos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Espectrometria de Massas/métodos , Proteoma/genéticaRESUMO
The use of quantum dot nanoparticles (QDs) in bio-applications has gained quite some interest and requires a deep understanding of their interactions with model cell membranes. This involves assessing the extent of nanoparticle disruption of the membrane and how it depends on both nanoparticle and membrane physicochemical properties. Surface charge plays an important role in nanoparticle adsorption, which is primarily driven by electrostatic interactions; yet, once adsorbed, most reported works overlook the subsequent spatial nanoparticle insertion and location within the membrane. There is therefore a need for studies to assess the mutual role of membrane and nanoparticle charge into membrane structure and stability at the nanoscale, with a view to better design and control the functionality of these nanomaterials. In this work, we have resolved the extent of the interactions between hydrophilic, negatively charged CdTe QDs and positively charged lipid bilayers. A multiscale combination of surface-sensitive techniques enabled probing how surface charge mediates QD adsorption and membrane reorganization. Increasing membrane surface charge results into a larger adsorption of oppositely charged QDs, concomitantly inducing structural changes. Hydration of the membrane hydrophobic parts by QDs goes deeper into the inner leaflet with increasing membrane charge, resulting in supported lipid bilayers with decreased nanomechanical stability.
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Non-viral nanoparticles (NPs) have seen heightened interest as a delivery method for a variety of clinically relevant nucleic acid cargoes in recent years. While much of the focus has been on lipid NPs, non-lipid NPs, including polymeric NPs, have the possibility of improved efficacy, safety, and targeting, especially to non-liver organs following systemic administration. A safe and effective systemic approach for intracellular delivery to the lungs could overcome limitations to intratracheal/intranasal delivery of NPs and improve clinical benefit for a range of diseases including cystic fibrosis. Here, engineered biodegradable poly (beta-amino ester) (PBAE) NPs are shown to facilitate efficient delivery of mRNA to primary human airway epithelial cells from both healthy donors and individuals with cystic fibrosis. Optimized NP formulations made with differentially endcapped PBAEs and systemically administered in vivo lead to high expression of mRNA within the lungs in BALB/c and C57 B/L mice without requiring a complex targeting ligand. High levels of mRNA-based gene editing were achieved in an Ai9 mouse model across bronchial, epithelial, and endothelial cell populations. No toxicity was observed either acutely or over time, including after multiple systemic administrations of the NPs. The non-lipid biodegradable PBAE NPs demonstrate high levels of transfection in both primary human airway epithelial cells and in vivo editing of lung cell types that are targets for numerous life-limiting diseases particularly single gene disorders such as cystic fibrosis and surfactant deficiencies.
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Pulmão , Camundongos Endogâmicos C57BL , Nanopartículas , Polímeros , RNA Mensageiro , Animais , Pulmão/metabolismo , Humanos , Nanopartículas/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Polímeros/química , Camundongos Endogâmicos BALB C , Camundongos , Fibrose Cística , Feminino , Ligantes , Células Epiteliais/metabolismoRESUMO
Pro-fibrotic M2-like macrophages are widely implicated in the pathogenesis and progression of lung fibrosis due to their production of pro-fibrotic growth factors and cytokines. Yeast beta-glucan (YBG) microparticles have shown potential as immunomodulators that can convert macrophage polarization from a pro-fibrotic phenotype to an anti-fibrotic phenotype through the engagement of the Dectin-1 receptor. However, the processing conditions used to fabricate YBG microparticles can lead to unpredictable immunomodulatory effects. Herein, we report the use of Pressurized Gas eXpanded liquids (PGX) Technology® to fabricate YBG (PGX-YBG) microparticles with higher surface areas, lower densities, and smaller and more uniform size distributions compared to commercially available spray-dried YBGs. PGX-YBG is shown to activate Dectin-1 more efficiently in vitro while avoiding significant TLR 2/4 activation. Furthermore, PGX-YBG microparticles effectively modulate M2-like fibrosis-inducing murine and human macrophages into fibrosis-suppressing macrophages both in vitro as well as in ex vivo precision-cut murine lung slices, suggesting their potential utility as a therapeutic for addressing a broad spectrum of fibrotic end-point lung diseases.
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Macrófagos , beta-Glucanas , Animais , beta-Glucanas/química , beta-Glucanas/farmacologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Humanos , Camundongos Endogâmicos C57BL , Lectinas Tipo C/metabolismo , Células RAW 264.7 , Fibrose Pulmonar/patologia , Fibrose Pulmonar/tratamento farmacológico , Saccharomyces cerevisiae , Tamanho da PartículaRESUMO
Significance: ALA-PpIX and second-window indocyanine green (ICG) have been studied widely for guiding the resection of high-grade gliomas. These agents have different mechanisms of action and uptake characteristics, which can affect their performance as surgical guidance agents. Elucidating these differences in animal models that approach the size and anatomy of the human brain would help guide the use of these agents. Herein, we report on the use of a new pig glioma model and fluorescence cryotomography to evaluate the 3D distributions of both agents throughout the whole brain. Aim: We aim to assess and compare the 3D spatial distributions of ALA-PpIX and second-window ICG in a glioma-bearing pig brain using fluorescence cryotomography. Approach: A glioma was induced in the brain of a transgenic Oncopig via adeno-associated virus delivery of Cre-recombinase plasmids. After tumor induction, the pro-drug 5-ALA and ICG were administered to the animal 3 and 24 h prior to brain harvest, respectively. The harvested brain was imaged using fluorescence cryotomography. The fluorescence distributions of both agents were evaluated in 3D in the whole brain using various spatial distribution and contrast performance metrics. Results: Significant differences in the spatial distributions of both agents were observed. Indocyanine green accumulated within the tumor core, whereas ALA-PpIX appeared more toward the tumor periphery. Both ALA-PpIX and second-window ICG provided elevated tumor-to-background contrast (13 and 23, respectively). Conclusions: This study is the first to demonstrate the use of a new glioma model and large-specimen fluorescence cryotomography to evaluate and compare imaging agent distribution at high resolution in 3D.
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Neoplasias Encefálicas , Glioma , Imageamento Tridimensional , Verde de Indocianina , Animais , Verde de Indocianina/farmacocinética , Verde de Indocianina/química , Suínos , Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Glioma/patologia , Imageamento Tridimensional/métodos , Ácido Aminolevulínico/farmacocinética , Encéfalo/diagnóstico por imagem , Imagem Óptica/métodos , Modelos Animais de DoençasRESUMO
PURPOSE: Although Ω-plot-driven quantification of in vivo amide exchange properties has been demonstrated, differences in scan parameters may complicate the fidelity of determination. This work systematically evaluated the use of quasi-steady-state (QUASS) Z-spectra reconstruction to standardize in vivo amide exchange quantification across acquisition conditions and further determined it in vivo. METHODS: Simulation and in vivo rodent brain chemical exchange saturation transfer (CEST) data at 4.7 T were fit with and without QUASS reconstruction using both multi-Lorentzian and model-based fitting approaches. pH modulation was accomplished both in simulation and in vivo by inducing global ischemia via cardiac arrest. Amide parameters were determined via Ω-plots and compared across methods. RESULTS: Simulation showed that Ω-plots using multi-Lorentzian fitting could underestimate the exchange rate, with error increasing as conditions diverged from the steady state. In comparison, model-based fitting using QUASS estimated the same exchange rate within 2%. These results aligned with in vivo findings where multi-Lorentzian fitting of native Z-spectra resulted in an exchange rate of 64 ± 13 s-1 (38 ± 16 s-1 after cardiac arrest), whereas model-based fitting of QUASS Z-spectra yielded an exchange rate of 126 ± 25 s-1 (49 ± 13 s-1). CONCLUSION: The model-based fitting of QUASS CEST Z-spectra enables consistent and accurate quantification of exchange parameters through Ω-plot construction by reducing error due to signal overlap and nonequilibrium CEST effects.
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Algoritmos , Encéfalo , Imageamento por Ressonância Magnética , Animais , Ratos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Simulação por Computador , Reprodutibilidade dos Testes , Processamento de Imagem Assistida por Computador/métodos , Ratos Sprague-Dawley , MasculinoRESUMO
Aging often leads to a decline in various cognitive domains, potentially contributing to spatial navigation challenges among older individuals. While the Morris water maze is a common tool in rodents research for evaluating allocentric spatial memory function, its translation to studying aging in humans, particularly its association with hippocampal dysfunction, has predominantly focused on spatial reference memory assessments. This study expanded the adaptation of the Morris water maze for older adults to assess flexible, rapid, one-trial working memory. This adaptation involved a spatial search task guided by allocentric cues within a 3-D virtual reality (VR) environment. The sensitivity of this approach to aging was examined in 146 community-living adults from three Chinese cities, categorized into three age groups. Significant performance deficits were observed in participants over 60 years old compared to younger adults aged between 18 and 43. However, interpreting these findings was complicated by factors such as psychomotor slowness and potential variations in task engagement, except during the probe tests. Notably, the transition from the 60â¯s to the 70â¯s was not associated with a substantial deterioration of performance. A distinction only emerged when the pattern of spatial search over the entire maze was examined in the probe tests when the target location was never revealed. The VR task's sensitivity to overall cognitive function in older adults was reinforced by the correlation between Montreal Cognitive Assessment (MoCA) scores and probe test performance, demonstrating up to 17â¯% shared variance beyond that predicted by chronological age alone. In conclusion, while implementing a VR-based adaptation of rodent water maze paradigms in older adults was feasible, our experience highlighted specific interpretative challenges that must be addressed before such a test can effectively supplement traditional cognitive assessment tools in evaluating age-related cognitive decline.
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Envelhecimento , Aprendizagem em Labirinto , Memória de Curto Prazo , Memória Espacial , Realidade Virtual , Humanos , Memória de Curto Prazo/fisiologia , Masculino , Idoso , Pessoa de Meia-Idade , Feminino , Memória Espacial/fisiologia , Envelhecimento/fisiologia , Adulto , Aprendizagem em Labirinto/fisiologia , Adulto Jovem , Adolescente , Navegação Espacial/fisiologia , Teste do Labirinto Aquático de Morris , Idoso de 80 Anos ou mais , Vida IndependenteRESUMO
This study investigated the antibacterial effect of ultrasound (US) combined with Litsea cubeba essential oil nanoemulsion (LEON) on Salmonella Typhimurium in kiwifruit juice and effect on the quality and sensory properties of kiwifruit juice. In this study, LEON prepared by ultrasonic emulsification method had a good particle size distribution and high stability. The US+LEON treatment significantly (P < 0.05) improved antibacterial efficacy, compared to the control, and would not destroy the nutritional components containing ascorbic acid, flavonoids, total phenol and total soluble solids. Meanwhile, US+LEON treatment enhanced 2, 2-diphenyl-1-picrylhydrazyl (DPPH), 2, 2'-azino-bis-(3-ethylbenzothiazoline-6 sulfonic acid) (ABTS) radical scavenging capacity and ferric ion reducing antioxidant power (FRAP). In terms of sensory properties, US and LEON had a significant (P < 0.05) effect on the odor and overall morphology of kiwifruit juice. The enhance of antibacterial efficacy and the retention of nutrients by combined treatments shows that US+LEON is a promising antibacterial method that will provide new ideas for the processing and safety of fruit juices, and the US parameters and LEON concentration should be adjusted to reduce the effect on food sensory properties in future studies.
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Actinidia , Antibacterianos , Emulsões , Sucos de Frutas e Vegetais , Litsea , Óleos Voláteis , Salmonella typhimurium , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/crescimento & desenvolvimento , Sucos de Frutas e Vegetais/microbiologia , Antibacterianos/farmacologia , Actinidia/química , Actinidia/microbiologia , Emulsões/farmacologia , Litsea/química , Óleos Voláteis/farmacologia , Humanos , Paladar , Microbiologia de Alimentos , Antioxidantes/farmacologiaRESUMO
Preclinical studies of optic nerve injury models have led to significant insight into the mechanism underlying retinal ganglion cell neurodegeneration. During the process of ganglion cell injury, morphological changes can occur prior to gross structural changes and cell death. Similarly, following injury, functional changes can occur in the absence of substantive structural changes. These more subtle effects can often be detected using functional tools such as the electroretinogram. Moreover, the electroretinogram is a sensitive and complementary means to quantify treatment efficacy. Here, we describe in vivo electroretinography for assessing ganglion cell injury in rodent models.
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Modelos Animais de Doenças , Eletrorretinografia , Traumatismos do Nervo Óptico , Células Ganglionares da Retina , Animais , Eletrorretinografia/métodos , Células Ganglionares da Retina/patologia , Traumatismos do Nervo Óptico/fisiopatologia , Traumatismos do Nervo Óptico/patologia , Ratos , Camundongos , RoedoresRESUMO
JOURNAL/nrgr/04.03/01300535-202505000-00027/figure1/v/2024-07-28T173839Z/r/image-tiff Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy. Physical exercise enhances neurogenesis and synaptogenesis, and has been widely used for functional rehabilitation after stroke. In this study, we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia. We also examined the role of exercise-induced circulating factors in these effects. Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion. We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area, inhibited gliogenesis, protected synaptic proteins, and improved novel object and spatial memory function. Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise. Agonist activation of adiponectin receptors by AdipoRon mimicked the effects of exercise, while inhibiting receptor activation abolished the exercise effects. In summary, our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.
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Objetivo: investigar a percepção do peso corporal e as dificuldades encontradas pelas pessoas com deficiência visual na aquisição, na preparação e no consumo dos alimentos. Metodologia: estudo observacional transversal, com adultos e idosos com deficiência visual em Pelotas/RS, realizado no período de abril a maio de 2023. Foi utilizado um questionário composto de 42 itens. Os dados coletados foram analisados por análise descritiva e analítica, e apresentados como média ± desvio padrão ou percentual. Resultados: a amostra contou com 20 pessoas, predominantemente do sexo feminino e idosas. Em relação ao consumo alimentar, 50% dos participantes consomem feijão, 75% frutas e hortaliças, 50% bebidas adoçadas, biscoitos recheados e doces. Referente à percepção do peso corporal, percebeu-se que a maior parte do grupo sente que está acima do peso adequado e se sentem "insatisfeitos(as)". Sobre as dificuldades encontradas, 85% dos participantes relataram dificuldade extrema para identificar a validade dos alimentos, 70% para comprar alimentos frescos e perecíveis e 40% para usar a faca para cortar e descascar os alimentos. Conclusão: verificou-se que a maior parte do grupo sente que está acima do peso adequado e estão "insatisfeitos(as)" em relação ao peso corporal. Além disso, dependem de outra pessoa para escolher os alimentos a serem comprados, saber o prazo de validade, preparar alimentos que precisam ser porcionados, servir refeições no prato, cortar carnes, descascar vegetais e frutas, utilizar faca, entre outros. Esta dependência pode influenciar diretamente no seu consumo alimentar quando essas pessoas se encontram sozinhas, optando por consumir alimentos industrializados de fácil preparo ou prontos.
Objective: to investigate the perception of body weight and the difficulties encountered by people with visual impairments in acquiring, preparing and consuming food. Methodology: cross-sectional observational study, with adults and elderly people with visual impairment in Pelotas/RS, carried out from April to May 2023. A questionnaire composed of 42 items was used. The collected data were analyzed using descriptive and analytical analysis, and presented as mean ± standard deviation or percentage. Results: the sample included 20 people, predominantly female and elderly. Regarding food consumption, 50% of participants consume beans, 75% fruits and vegetables, 50% sweetened drinks, stuffed cookies and sweets. Regarding the perception of body weight, it was noticed that the majority of the group feels that they are overweight and feel "dissatisfied". Regarding the difficulties encountered, 85% of participants reported extreme difficulty in identifying the expiration date of food, 70% in purchasing fresh and perishable foods and 40% in using a knife to cut and peel food. Conclusion: it was found that the majority of the group feels that they are overweight and are "dissatisfied" with their body weight. Furthermore, they depend on someone else to choose the food to be purchased, know the expiration date, prepare food that needs to be portioned, serve meals on the plate, cut meat, peel vegetables and fruits, use a knife, among others. This dependence can directly influence their food consumption when these people are alone, choosing to consume easily prepared or ready-made processed foods.
Assuntos
Humanos , Masculino , FemininoRESUMO
Objetivo: verificar a influência da pandemia de Covid-19 no risco de desenvolvimento de transtornos alimentares em mulheres. Metodologia: pesquisa quantitativa, com mulheres com acesso ao computador, a celular e à internet. A coleta de dados foi realizada a partir de um questionário on-line contendo 60 perguntas, com respostas fechadas, que visavam conhecer a sua relação com a alimentação. Foram verificados o consumo alimentar e o risco de desenvolvimento de anorexia nervosa (Eating Attitudes Test - EAT-26) e bulimia nervosa (Bulimic Investigatory Test, Edinburgh- BITE). Resultados: participaram da pesquisa 92 mulheres, sendo que 81,50% (n=75) referiram que ficaram em casa durante a pandemia. Sobre a ingestão de alimentos, 45,70% (n=42) relataram que consumiram diariamente frutas e hortaliças, 55,40% (n=51) ingeriram de 1 a 2 vezes/semana bolachas, salgadinhos, doces e guloseimas e 62,00% (n=57) consumiam embutidos pelo menos 1 vez/semana. Ainda, 18,50% (n=17) apresentaram risco para o desenvolvimento de anorexia nervosa e 83,60% (n=73) risco de bulimia nervosa. Entretanto, analisando se esse risco estava associado à pandemia, verificou-se que não houve diferença significativa entre o grupo que permaneceu em casa e o grupo que saiu para trabalhar (p > 0,05). Conclusão: portanto, grande parte das voluntárias apresentaram um risco de desenvolver algum transtorno alimentar, entretanto, não houve uma relação entre o possível risco de desenvolver transtornos alimentares influenciado pela pandemia.
Objective: to verify the influence of the Covid-19 pandemic on the risk of developing eating disorders in women. Methodology: quantitative research, with women with access to a computer, cell phone and internet. Data collection was carried out using an online questionnaire containing 60 questions, with closed answers, which aimed to understand their relationship with food. Food consumption Abstract and the risk of developing nervous anorexia (Eating Attitudes Test - EAT-26) and nervous bulimia (Bulimic Investigatory Test, Edinburgh - BITE) were verified. Results: 92 women participated in the research, with 81.50% (n=75) reporting that they stayed at home during the pandemic. Regarding food intake, 45.70% (n=42) reported that they consumed fruits and vegetables daily, 55.40% (n=51) ate cookies, snacks, sweets and sweets 1 to 2 times/week and 62, 00% (n=57) consumed sausages at least once/week. Furthermore, 18.50% (n=17) were at risk for developing nervous anorexia and 83.60% (n=73) were at risk for nervous bulimia. However, analyzing whether this risk was associated with the pandemic, it was found that there was no significant difference between the group that remained at home and the group that went out to work (p > 0.05). Conclusion: therefore, most of the volunteers presented a risk of developing an eating disorder, however, there was no relationship between the possible risk of developing eating disorders influenced by the pandemic.
Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-IdadeRESUMO
Leadless cardiac pacemakers (LCPs) mitigate the risks of traditional transvenous devices such as lead fracture and infection. Two LCPs are clinically available, using either a helix or tined active fixation approach. There are rare reports of LCP infection-all involving the tined device. We report the first pathologically confirmed fungal endocarditis involving a helix-based LCP. This was successfully managed by catheter-based mechanical vacuum evacuation of the vegetation, followed by device extraction and replacement.