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1.
Siglo cero (Madr.) ; 54(4): 65-83, oct.-dic. 2024.
Artigo em Espanhol | IBECS | ID: ibc-229229

RESUMO

La falta de información sobre el uso de la tecnología en niños con trastorno del espectro autista (TEA) de diferentes perfiles puede dificultar que docentes y alumnos se estén beneficiando del apoyo tecnológico más eficaz y ajustado a sus necesidades. El objetivo de esta revisión fue analizar y sintetizar la evidencia científica sobre la eficacia de los recursos tecnológicos en la mejora de la comprensión emocional de estudiantes con TEA con perfiles de alto y bajo funcionamiento. Para ello se realizó una revisión sistemática de las publicaciones científicas indexadas en algunas de las bases de datos de mayor relevancia siguiendo los criterios establecidos en la declaración PRISMA. En total se analizaron 38 artículos que cumplieron con los criterios de inclusión preestablecidos. Los resultados muestran la importancia de diseñar sistemas versátiles que puedan personalizarse y adaptarse en tiempo real y en contextos naturales con un enfoque claramente inclusivo. Pero también sugieren que la tecnología puede no ser una herramienta de intervención complementaria adecuada para todos los niños con TEA. Lo que subraya la necesidad de ensayos adicionales bien controlados sobre las características que permitan identificar qué estudiantes podrían o no beneficiarse de diferentes modalidades de tecnología. (AU)


The lack of information on the use of technology in children with autism spectrum disorder (ASD) of different profiles can make it difficult for teachers and students to benefit from the most effective technology support tailored to their needs. The aim of this review was to analyze and synthesize scientific evidence on the effectiveness of technological resources in improving the emotional understanding of students with high and low functioning ASD profiles. A systematic review of the scientific publications indexed in some of the most relevant databases was carried out following the criteria established in the PRISMA declaration. A total of 38 articles that met the pre-established inclusion criteria were analyzed. The results show the importance of designing versatile systems that can be customized and adapted in real time and in natural contexts with a clearly inclusive approach. But they also suggest that technology may not be an appropriate complementary intervention tool for all children with ASD. This underlines the need for additional well-controlled tests on the characteristics that would allow identifying which students might or might not benefit from different technology modalities. (AU)


Assuntos
Humanos , Pré-Escolar , Criança , Adolescente , Tecnologia Educacional , Transtorno do Espectro Autista , Transtorno Autístico
2.
Siglo cero (Madr.) ; 54(4): 65-83, oct.-dic. 2024.
Artigo em Espanhol | IBECS | ID: ibc-EMG-559

RESUMO

La falta de información sobre el uso de la tecnología en niños con trastorno del espectro autista (TEA) de diferentes perfiles puede dificultar que docentes y alumnos se estén beneficiando del apoyo tecnológico más eficaz y ajustado a sus necesidades. El objetivo de esta revisión fue analizar y sintetizar la evidencia científica sobre la eficacia de los recursos tecnológicos en la mejora de la comprensión emocional de estudiantes con TEA con perfiles de alto y bajo funcionamiento. Para ello se realizó una revisión sistemática de las publicaciones científicas indexadas en algunas de las bases de datos de mayor relevancia siguiendo los criterios establecidos en la declaración PRISMA. En total se analizaron 38 artículos que cumplieron con los criterios de inclusión preestablecidos. Los resultados muestran la importancia de diseñar sistemas versátiles que puedan personalizarse y adaptarse en tiempo real y en contextos naturales con un enfoque claramente inclusivo. Pero también sugieren que la tecnología puede no ser una herramienta de intervención complementaria adecuada para todos los niños con TEA. Lo que subraya la necesidad de ensayos adicionales bien controlados sobre las características que permitan identificar qué estudiantes podrían o no beneficiarse de diferentes modalidades de tecnología. (AU)


The lack of information on the use of technology in children with autism spectrum disorder (ASD) of different profiles can make it difficult for teachers and students to benefit from the most effective technology support tailored to their needs. The aim of this review was to analyze and synthesize scientific evidence on the effectiveness of technological resources in improving the emotional understanding of students with high and low functioning ASD profiles. A systematic review of the scientific publications indexed in some of the most relevant databases was carried out following the criteria established in the PRISMA declaration. A total of 38 articles that met the pre-established inclusion criteria were analyzed. The results show the importance of designing versatile systems that can be customized and adapted in real time and in natural contexts with a clearly inclusive approach. But they also suggest that technology may not be an appropriate complementary intervention tool for all children with ASD. This underlines the need for additional well-controlled tests on the characteristics that would allow identifying which students might or might not benefit from different technology modalities. (AU)


Assuntos
Humanos , Pré-Escolar , Criança , Adolescente , Tecnologia Educacional , Transtorno do Espectro Autista , Transtorno Autístico
3.
Eur J Cancer ; 205: 114104, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38733716

RESUMO

BACKGROUND: The epidemiology of colorectal cancer (CRC) has changed rapidly over the years. The aim of this study was to assess the trends in incidence, treatment, and relative survival (RS) of patients diagnosed with CRC in the Netherlands between 2000 and 2021. PATIENTS AND METHODS: 2 75667 patients diagnosed with CRC between 2000 and 2021 were included from the Netherlands Cancer Registry. Analyses were stratified for disease extent (localised: T1-3N0M0; regional: T4N0M0/T1-4N1-2M0; distant: T1-4N0-2M1) and localisation (colon; rectum). Trends were assessed with joinpoint regression. RESULTS: CRC incidence increased until the mid-2010s but decreased strongly thereafter to rates comparable with the early 2000s. Amongst other trend changes, local excision rates increased for patients with localised colon (2021: 13.6 %) and rectal cancer (2021: 34.9 %). Moreover, primary tumour resection became less common in patients with distant colon (2000-2021: 60.9-12.5 %) or rectal cancer (2000-2021: 47.8-6.9 %), while local treatment of metastases rates increased. Five-year RS improved continuously for localised and regional colon (97.7 % and 72.0 % in 2017, respectively) and rectal cancer (95.2 % and 76.3 % in 2017, respectively). The rate of anti-cancer treatments decreased in distant colon (2010-2021: 80.3 % to 67.2 %; p < 0.001) and rectal cancer (2011-2021: 86.0 % to 77.0 %; p < 0.001). The improvement of five-year RS stagnated for distant colon (2010-2017: 11.2 % to 11.9 %; average percentage of change [APC]: 2.1, 95 % confidence interval [CI]: -7.6, 4.7) and rectal cancer (2009-2017: 12.7 % to 15.6 %; APC: 1.4, 95 % CI: -19.1, 5.5). CONCLUSIONS: Major changes in the incidence and treatment of CRC between 2000 and 2021 were identified and quantified. Five-year RS increased continuously for patients with localised and regional CRC, but stagnated for patients with distant CRC, likely caused by decreased rates of anti-cancer treatment in this group.

4.
Front Endocrinol (Lausanne) ; 15: 1374825, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38742194

RESUMO

Increasing evidence suggests that female individuals have a higher Alzheimer's disease (AD) risk associated with post-menopausal loss of circulating estradiol (E2). However, clinical data are conflicting on whether E2 lowers AD risk. One potential contributing factor is APOE. The greatest genetic risk factor for AD is APOE4, a factor that is pronounced in female individuals post-menopause. Clinical data suggests that APOE impacts the response of AD patients to E2 replacement therapy. However, whether APOE4 prevents, is neutral, or promotes any positive effects of E2 is unclear. Therefore, our goal was to determine whether APOE modulates the impact of E2 on behavior and AD pathology in vivo. To that end, mice that express human APOE3 (E3FAD) or APOE4 (E4FAD) and overproduce Aß42 were ovariectomized at either 4 months (early) or 8 months (late) and treated with vehicle or E2 for 4 months. In E3FAD mice, we found that E2 mitigated the detrimental effect of ovariectomy on memory, with no effect on Aß in the early paradigm and only improved learning in the late paradigm. Although E2 lowered Aß in E4FAD mice in the early paradigm, there was no impact on learning or memory, possibly due to higher Aß pathology compared to E3FAD mice. In the late paradigm, there was no effect on learning/memory and Aß pathology in E4FAD mice. Collectively, these data support the idea that, in the presence of Aß pathology, APOE impacts the response to E2 supplementation post-menopause.


Assuntos
Doença de Alzheimer , Apolipoproteína E3 , Apolipoproteína E4 , Estradiol , Camundongos Transgênicos , Ovariectomia , Animais , Estradiol/farmacologia , Feminino , Apolipoproteína E3/genética , Apolipoproteína E3/metabolismo , Camundongos , Apolipoproteína E4/genética , Apolipoproteína E4/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , Humanos , Comportamento Animal/efeitos dos fármacos , Peptídeos beta-Amiloides/metabolismo , Modelos Animais de Doenças
6.
Opt Express ; 32(6): 9518-9552, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571185

RESUMO

X-ray waveguides are routinely used at synchrotron light sources in imaging setups and as a platform for experiments with quantum emitters, providing nanometer-sized confinement - even x-ray optics on a chip has been showcased. X-ray waveguides are weakly guiding and experience significant material absorption, such that the established waveguide theory is not immediately applicable. Here, a general self-contained nano-optical theory of planar waveguides is derived, which is appropriate for hard x-ray energies. Solutions of the electromagnetic fields and its Green's functions are derived in detail. Asymptotic expansions into resonant and non-resonant modes are derived, which are particularly useful in the presence of strong material absorption. A method to reliably find the resonant modes of x-ray waveguide structures is presented. Based on the general theory, certain common experimental geometries, namely evanescent coupling in grazing-incidence, front-coupling in forward-incidence and radiation from buried emitters, are discussed in more detail. Complementing the analytic discussion, numerical tools are provided and applied to quantitatively extract the main figures of merit. The theory provides an analytic foundation for the interpretation of past and future experiments and, combined with the numerical tools, will facilitate the computer-aided design of x-ray waveguides.

7.
MethodsX ; 12: 102686, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38585179

RESUMO

One of the initial steps in the preprocessing of digital fundoscopy images is the identification of pixels containing relevant information. This can be achieved through different approaches, one of them is implementing background extraction, reducing the set of pixels to be analyzed later in the process. In this work, we present a background extraction method for digital fundoscopy images based on computational topology. By interpreting binarized images as cubical complexes and extracting their homological groups in 1 and 2 dimensions we identify a subset of luminescence values that can be used to binarize the original grayscale image, obtaining a mask to achieve background extraction. This method is robust to noise and suboptimal image quality, facilitating the analytical pipeline in the context of computer aided diagnosis approaches. This method facilitates the segmentation of the background of a digital fundoscopy image, which allows further methods to focus on pixels with relevant information (eye fundus). This tool is best suited to be implemented in the preprocessing stages of the analytical pipeline by computational ophthalmology specialists.•It is robust to noise and low-quality images.•Output provides an ideal scenario for down-the-line analysis by facilitating only relevant pixels in a digital fundoscopy.

8.
Int J Mol Sci ; 25(8)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38674014

RESUMO

With genetic information gained from next-generation sequencing (NGS) and genome-wide association studies (GWAS), it is now possible to select for genes that encode reporter molecules that may be used to detect abnormalities such as alcohol-related liver disease (ARLD), cancer, cognitive impairment, multiple sclerosis (MS), diabesity, and ischemic stroke (IS). This, however, requires a thorough understanding of the gut-brain axis (GBA), the effect diets have on the selection of gut microbiota, conditions that influence the expression of microbial genes, and human physiology. Bacterial metabolites such as short-chain fatty acids (SCFAs) play a major role in gut homeostasis, maintain intestinal epithelial cells (IECs), and regulate the immune system, neurological, and endocrine functions. Changes in butyrate levels may serve as an early warning of colon cancer. Other cancer-reporting molecules are colibactin, a genotoxin produced by polyketide synthetase-positive Escherichia coli strains, and spermine oxidase (SMO). Increased butyrate levels are also associated with inflammation and impaired cognition. Dysbiosis may lead to increased production of oxidized low-density lipoproteins (OX-LDLs), known to restrict blood vessels and cause hypertension. Sudden changes in SCFA levels may also serve as a warning of IS. Early signs of ARLD may be detected by an increase in regenerating islet-derived 3 gamma (REG3G), which is associated with changes in the secretion of mucin-2 (Muc2). Pro-inflammatory molecules such as cytokines, interferons, and TNF may serve as early reporters of MS. Other examples of microbial enzymes and metabolites that may be used as reporters in the early detection of life-threatening diseases are reviewed.


Assuntos
Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/genética , Eixo Encéfalo-Intestino , Animais , Estudo de Associação Genômica Ampla , Bactérias/genética , Bactérias/metabolismo
9.
Endoscopy ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38670139

RESUMO

1: ESGE recommends cold snare polypectomy (CSP), to include a clear margin of normal tissue (1-2 mm) surrounding the polyp, for the removal of diminutive polyps (≤ 5 mm).Strong recommendation, high quality of evidence. 2: ESGE recommends against the use of cold biopsy forceps excision because of its high rate of incomplete resection.Strong recommendation, moderate quality of evidence. 3: ESGE recommends CSP, to include a clear margin of normal tissue (1-2 mm) surrounding the polyp, for the removal of small polyps (6-9 mm).Strong recommendation, high quality of evidence. 4: ESGE recommends hot snare polypectomy for the removal of nonpedunculated adenomatous polyps of 10-19 mm in size.Strong recommendation, high quality of evidence. 5: ESGE recommends conventional (diathermy-based) endoscopic mucosal resection (EMR) for large (≥ 20 mm) nonpedunculated adenomatous polyps (LNPCPs).Strong recommendation, high quality of evidence. 6: ESGE suggests that underwater EMR can be considered an alternative to conventional hot EMR for the treatment of adenomatous LNPCPs.Weak recommendation, moderate quality of evidence. 7: Endoscopic submucosal dissection (ESD) may also be suggested as an alternative for removal of LNPCPs of ≥ 20 mm in selected cases and in high-volume centers.Weak recommendation, low quality evidence. 8: ESGE recommends that, after piecemeal EMR of LNPCPs by hot snare, the resection margins should be treated by thermal ablation using snare-tip soft coagulation to prevent adenoma recurrence.Strong recommendation, high quality of evidence. 9: ESGE recommends (piecemeal) cold snare polypectomy or cold EMR for SSLs of all sizes without suspected dysplasia.Strong recommendation, moderate quality of evidence. 10: ESGE recommends prophylactic endoscopic clip closure of the mucosal defect after EMR of LNPCPs in the right colon to reduce to reduce the risk of delayed bleeding.Strong recommendation, high quality of evidence. 11: ESGE recommends that en bloc resection techniques, such as en bloc EMR, ESD, endoscopic intermuscular dissection, endoscopic full-thickness resection, or surgery should be the techniques of choice in cases with suspected superficial invasive carcinoma, which otherwise cannot be removed en bloc by standard polypectomy or EMR.Strong recommendation, moderate quality of evidence.

11.
Magn Reson Imaging ; 109: 264-270, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38522624

RESUMO

Proton exchange underpins essential mechanisms in diverse MR imaging contrasts. Omega plots have proven effective in mapping proton exchange rates (kex) in live human brains, enabling the differentiation of MS lesion activities and characterization of ischemic stroke. However, Omega plots require extended saturation durations (typically 5 to 10 s), resulting in high specific absorption rates (SAR) that can hinder clinical feasibility. In this study, we introduce a novel kex mapping approach, named induced Saturation Transfer Recovery Steady-States (iSTRESS). iSTRESS integrates an excitation flip angle pulse prior to chemical exchange saturation transfer (CEST) saturation, effectively aligning the magnetization with its steady-state value. This innovation reduces saturation times and mitigates SAR concerns. The formula for iSTRESS-based kex quantification was derived theoretically, involving two measurements with distinct excitation flip angles and saturation B1 values. Bloch-McConnell simulations confirmed that iSTRESS-based kex values closely matched input values (R2 > 0.99). An iSTRESS MRI sequence was implemented on a 9.4 T preclinical MRI, imaging protein phantoms with pH values ranging from 6.2 to 7.4 (n = 4). Z-spectra were acquired using excitation flip angles of 30° and 60°, followed by CEST saturation at powers of 30 and 120 Hz respectively, with a total saturation time of <1 s, resulting in two iSTRESS states for kex mapping. kex maps derived from the phantom study exhibited a linear correlation (R2 > 0.99) with Omega plot results. The developed iSTRESS method allows for kex quantification with significantly reduced saturation times, effectively minimizing SAR concerns.


Assuntos
Imageamento por Ressonância Magnética , Prótons , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Concentração de Íons de Hidrogênio , Meios de Contraste , Imagens de Fantasmas
12.
J Cardiovasc Magn Reson ; 26(1): 101035, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38460841

RESUMO

BACKGROUND: Patients are increasingly using Generative Pre-trained Transformer 4 (GPT-4) to better understand their own radiology findings. PURPOSE: To evaluate the performance of GPT-4 in transforming cardiovascular magnetic resonance (CMR) reports into text that is comprehensible to medical laypersons. METHODS: ChatGPT with GPT-4 architecture was used to generate three different explained versions of 20 various CMR reports (n = 60) using the same prompt: "Explain the radiology report in a language understandable to a medical layperson". Two cardiovascular radiologists evaluated understandability, factual correctness, completeness of relevant findings, and lack of potential harm, while 13 medical laypersons evaluated the understandability of the original and the GPT-4 reports on a Likert scale (1 "strongly disagree", 5 "strongly agree"). Readability was measured using the Automated Readability Index (ARI). Linear mixed-effects models (values given as median [interquartile range]) and intraclass correlation coefficient (ICC) were used for statistical analysis. RESULTS: GPT-4 reports were generated on average in 52 s ± 13. GPT-4 reports achieved a lower ARI score (10 [9-12] vs 5 [4-6]; p < 0.001) and were subjectively easier to understand for laypersons than original reports (1 [1] vs 4 [4,5]; p < 0.001). Eighteen out of 20 (90%) standard CMR reports and 2/60 (3%) GPT-generated reports had an ARI score corresponding to the 8th grade level or higher. Radiologists' ratings of the GPT-4 reports reached high levels for correctness (5 [4, 5]), completeness (5 [5]), and lack of potential harm (5 [5]); with "strong agreement" for factual correctness in 94% (113/120) and completeness of relevant findings in 81% (97/120) of reports. Test-retest agreement for layperson understandability ratings between the three simplified reports generated from the same original report was substantial (ICC: 0.62; p < 0.001). Interrater agreement between radiologists was almost perfect for lack of potential harm (ICC: 0.93, p < 0.001) and moderate to substantial for completeness (ICC: 0.76, p < 0.001) and factual correctness (ICC: 0.55, p < 0.001). CONCLUSION: GPT-4 can reliably transform complex CMR reports into more understandable, layperson-friendly language while largely maintaining factual correctness and completeness, and can thus help convey patient-relevant radiology information in an easy-to-understand manner.

14.
Radiologie (Heidelb) ; 2024 Mar 21.
Artigo em Alemão | MEDLINE | ID: mdl-38514506

RESUMO

BACKGROUND: Early treatment of cardiovascular risk factors and characterization of coronary plaques is essential to collect prognostic information about coronary artery disease (CAD) and prevent cardiovascular events. OBJECTIVES: Discussion of the most important risk factors of CAD, basic diagnostic of CAD, prevention, and prognostic factors of CAD with focus on cardiac computed tomography (CT). MATERIALS AND METHODS: Prevalence and prognostic impact of CAD risk factors; description of specific assessment of risk profiles; estimation of pretest probability; conventional prevention of CAD; prognostic assessment of CAD using the Calcium Scoring and coronary CT angiography. RESULTS: Assessment of risk profiles and estimation of pretest probability for obstructive coronary stenosis necessitates a thorough evaluation of medical history and laboratory values. The composition and extent of calcified and noncalcified plaques in CT exams based on the criteria of the Coronary Artery Disease-Reporting and Data System give important prognostic information about the risk of cardiovascular events, which increases with high plaque burden and vice versa. Initial imaging with CT for evaluation of CAD leads to a reduction of invasive coronary angiographies and catheter-associated complications. CONCLUSIONS: Besides early detection of cardiovascular risk factors, the additional assessment of plaque burden and significant stenosis in CT gives further prognostic information to facilitate effective therapies to prevent cardiovascular events and in the case of low plaque burden avoid invasive coronary angiography. However, systmatic screening using Calcium Scoring is not established yet due to insufficient data, although it could potentially be used for an early risk stratification in patients with multiple risk factors.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38521344

RESUMO

Persistent fetal vasculature is a spectrum of ocular abnormalities linked to an incomplete regression of the fetal ocular vasculature. A 21-years old male patient came to the outpatient clinic reporting low vision and strabismus in his left eye since 3 years of age. Ophtalmological examination revealed a normal right eye, while the left eye had a best corrected visual acuity of hand-motion perception, a 30 prism diopters esotropia, a "coralliform" cataract and a vitreous stalk joining the posterior face of the lens and the optic nerve. The coralliform cataract possessed spindle-shaped processes radiating out of its center in an axial direction and was located in the posterior subcapsular area. The patient elected to not undergo vitreoretinal surgery due to the poor visual prognosis. The unusual cataract present in the described patient could be related to his untreated status, as previous authors have reported that untreated cataracts in persistent fetal vasculature may undergo diverse degenerations.

16.
Viruses ; 16(3)2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-38543843

RESUMO

Healthcare faces a major problem with the increased emergence of antimicrobial resistance due to over-prescribing antibiotics. Bacteriophages may provide a solution to the treatment of bacterial infections given their specificity. Enzymes such as endolysins, exolysins, endopeptidases, endosialidases, and depolymerases produced by phages interact with bacterial surfaces, cell wall components, and exopolysaccharides, and may even destroy biofilms. Enzymatic cleavage of the host cell envelope components exposes specific receptors required for phage adhesion. Gram-positive bacteria are susceptible to phage infiltration through their peptidoglycan, cell wall teichoic acid (WTA), lipoteichoic acids (LTAs), and flagella. In Gram-negative bacteria, lipopolysaccharides (LPSs), pili, and capsules serve as targets. Defense mechanisms used by bacteria differ and include physical barriers (e.g., capsules) or endogenous mechanisms such as clustered regularly interspaced palindromic repeat (CRISPR)-associated protein (Cas) systems. Phage proteins stimulate immune responses against specific pathogens and improve antibiotic susceptibility. This review discusses the attachment of phages to bacterial cells, the penetration of bacterial cells, the use of phages in the treatment of bacterial infections, and the limitations of phage therapy. The therapeutic potential of phage-derived proteins and the impact that genomically engineered phages may have in the treatment of infections are summarized.


Assuntos
Infecções Bacterianas , Bacteriófagos , Humanos , Bacteriófagos/fisiologia , Bactérias , Infecções Bacterianas/terapia , Bactérias Gram-Negativas , Bactérias Gram-Positivas
17.
J Alzheimers Dis ; 97(4): 1629-1639, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38306049

RESUMO

APOE2 lowers Alzheimer's disease (AD) risk; unfortunately, the mechanism remains poorly understood and the use of mice models is problematic as APOE2 homozygosity is associated with hyperlipidemia. In this study, we developed mice that are heterozygous for APOE2 and APOE3 or APOE4 and overexpress amyloid-ß peptide (Aß) (EFAD) to evaluate the effect of APOE2 dosage on Aß pathology. We found that heterozygous mice do not exhibit hyperlipidemia. Hippocampal but not cortical levels of soluble Aß42 followed the order E2/2FAD > E2/3FAD≤E3/3FAD and E2/2FAD > E2/4FAD < E4/4FAD without an effect on insoluble Aß42. These findings offer initial insights on the impact of APOE2 on Aß pathology.


Assuntos
Doença de Alzheimer , Hiperlipidemias , Camundongos , Animais , Apolipoproteína E2/genética , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Camundongos Transgênicos , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Peptídeos beta-Amiloides/metabolismo , Apolipoproteína E4/metabolismo , Apolipoproteína E3 , Camundongos Endogâmicos , Hipocampo/patologia , Hiperlipidemias/genética
18.
J Neuroimmunol ; 388: 578309, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38335781

RESUMO

Blood-brain barrier (BBB) permeability can cause neuroinflammation and cognitive impairment. Caveolin-1 (Cav-1) critically regulates BBB permeability, but its influence on the BBB and consequent neurological outcomes in respiratory viral infections is unknown. We used Cav-1-deficient mice with genetically encoded fluorescent endothelial tight junctions to determine how Cav-1 influences BBB permeability, neuroinflammation, and cognitive impairment following respiratory infection with mouse adapted (MA10) SARS-CoV-2 as a model for COVID-19. We found that SARS-CoV-2 infection increased brain endothelial Cav-1 and increased transcellular BBB permeability to albumin, decreased paracellular BBB Claudin-5 tight junctions, and caused T lymphocyte infiltration in the hippocampus, a region important for learning and memory. Concordantly, we observed learning and memory deficits in SARS-CoV-2 infected mice. Importantly, genetic deficiency in Cav-1 attenuated transcellular BBB permeability and paracellular BBB tight junction losses, T lymphocyte infiltration, and gliosis induced by SARS-CoV-2 infection. Moreover, Cav-1 KO mice were protected from the learning and memory deficits caused by SARS-CoV-2 infection. These results establish the contribution of Cav-1 to BBB permeability and behavioral dysfunction induced by SARS-CoV-2 neuroinflammation.


Assuntos
COVID-19 , Disfunção Cognitiva , Animais , Camundongos , Barreira Hematoencefálica/metabolismo , Caveolina 1/genética , Caveolina 1/metabolismo , Disfunção Cognitiva/etiologia , COVID-19/complicações , Transtornos da Memória/etiologia , Doenças Neuroinflamatórias , Permeabilidade , SARS-CoV-2/metabolismo
19.
Brain ; 147(5): 1636-1643, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38306655

RESUMO

Respiratory infection with SARS-CoV-2 causes systemic vascular inflammation and cognitive impairment. We sought to identify the underlying mechanisms mediating cerebrovascular dysfunction and inflammation following mild respiratory SARS-CoV-2 infection. To this end, we performed unbiased transcriptional analysis to identify brain endothelial cell signalling pathways dysregulated by mouse adapted SARS-CoV-2 MA10 in aged immunocompetent C57Bl/6 mice in vivo. This analysis revealed significant suppression of Wnt/ß-catenin signalling, a critical regulator of blood-brain barrier (BBB) integrity. We therefore hypothesized that enhancing cerebrovascular Wnt/ß-catenin activity would offer protection against BBB permeability, neuroinflammation, and neurological signs in acute infection. Indeed, we found that delivery of cerebrovascular-targeted, engineered Wnt7a ligands protected BBB integrity, reduced T-cell infiltration of the brain, and reduced microglial activation in SARS-CoV-2 infection. Importantly, this strategy also mitigated SARS-CoV-2 induced deficits in the novel object recognition assay for learning and memory and the pole descent task for bradykinesia. These observations suggest that enhancement of Wnt/ß-catenin signalling or its downstream effectors could be potential interventional strategies for restoring cognitive health following viral infections.


Assuntos
Barreira Hematoencefálica , COVID-19 , Disfunção Cognitiva , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Proteínas Wnt , Animais , Barreira Hematoencefálica/metabolismo , COVID-19/complicações , Camundongos , Proteínas Wnt/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/etiologia , Via de Sinalização Wnt/fisiologia , Ligantes , SARS-CoV-2 , Masculino , Encéfalo/metabolismo
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