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BACKGROUND: Dural arteriovenous fistulas (dAVF) are arteriovenous shunts in communication with the dural vasculature in the brain or spine. Apart from single-center series, risk factors and treatment outcomes for pediatric dAVFs are largely undescribed. METHODS: We performed a systematic literature review of pediatric (< 18 years at diagnosis) intracranial and spinal dAVF according to PRISMA guidelines. We queried PubMed, CINAHL, SCOPUS, and Embase databases without time/date restriction. Search strings included a variety of MeSH keywords relating to dural AV fistulas in combination with MeSH keywords related to pediatric cases (see Appendix). Manuscripts describing patients diagnosed with dural sinus malformations or pial AVF were excluded. RESULTS: We identified 61 studies describing 69 individual patients. Overall, dAVF were more common in males (55.1%) with a mean age of diagnosis (5.17 ± 4.42 years). Approximately 20.2% of patients presented with cardiovascular disease (CVD), and 31.9% were discovered incidentally on neuroimaging studies. Transverse-sigmoid junction was the most common location (17.3%). Ninety-three percent (64 patients) were treated, most commonly using endovascular embolization (68.1%) followed by surgery (8.7%) and radiosurgery (2.9%). Almost half (43.8%) of dAVFs were completely obliterated. Of the 64 procedures, there were 19 neurological complications (29.7%) of varying severity where 12.5% were considered transient (i.e., pseudomeningocele) and 17.2% permanent (i.e., mortality secondary to acute sinus thrombosis, etc.). CONCLUSION: There is a paucity of information on pediatric dAVFs. This systematic review summarizes the published cases of dAVFs in the pediatric population. While the rate of missing data is high, there is publication bias, and precise details regarding complications are difficult to ascertain, this review serves as a descriptive summary of pediatric dAVFs.
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Fístula Arteriovenosa , Malformações Vasculares do Sistema Nervoso Central , Embolização Terapêutica , Radiocirurgia , Masculino , Humanos , Criança , Lactente , Pré-Escolar , Resultado do Tratamento , Embolização Terapêutica/métodos , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/terapia , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/terapia , Fístula Arteriovenosa/etiologiaRESUMO
INTRODUCTION: Pediatric non-galenic pial arteriovenous fistulas (pAVFs) are rare vascular malformations that are characterized by a pial arterial-venous connection without an intervening capillary bed. Outcomes and treatment strategies for pAVFs are highly individualized, owing to the rarity of the disease and lack of large-scale data guiding optimal treatment approaches. METHODS: We performed a systematic review of pediatric patients (< 18 years at diagnosis) diagnosed with a pAVF by digital subtraction angiogram (DSA). The demographics, treatment modalities, and outcomes were documented for each patient and clinical outcome data was collected. Descriptive information stratified by outcome scores were classified as follows: 1 = excellent (no deficit and full premorbid activity), 2 = good (mild deficit and full premorbid activity), 3 = fair (moderate deficit and impaired activity), 4 = poor (severe deficit and dependent on others), 5 = death. RESULTS: A total of 87 studies involving 231 patients were identified. Median age at diagnosis was 3 years (neonates to 18 years). There was slight male preponderance (55.4%), and 150 subjects (81.1%*) experienced excellent outcomes after treatment. Of the 189 patients treated using endovascular approaches, 80.3% experienced excellent outcomes and of the 15 patients surgically treated subjects 75% had an excellent outcome. The highest rate of excellent outcomes was achieved in patients treated with Onyx (95.2%) and other forms of EvOH (100%). High output heart failure and comorbid vascular lesions tended to result in worse outcomes, with only 54.2% and 68% of subjects experiencing an excellent outcome, respectively. *Outcomes were reported in only 185 patients. CONCLUSION: pAVFs are rare lesions, necessitating aggregation of patient data to inform natural history and optimal treatment strategies. This review summarizes the current literature on pAVF in children, where children presenting with heart failure as a result of high flow through the lesion were less likely to experience an excellent outcome. Prospective, large-scale studies would further characterize pediatric pAVFs and enable quantitative analysis of outcomes to inform best treatment practices.
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Fístula Arteriovenosa , Pia-Máter , Humanos , Criança , Fístula Arteriovenosa/cirurgia , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/terapia , Pia-Máter/irrigação sanguínea , Pré-Escolar , Adolescente , Lactente , Feminino , Recém-Nascido , Resultado do Tratamento , Masculino , Malformações Arteriovenosas Intracranianas/terapia , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/cirurgiaRESUMO
BACKGROUND: The Woven EndoBridge (WEB) devices have been used for treating wide neck bifurcation aneurysms (WNBAs) with several generational enhancements to improve clinical outcomes. The original device dual-layer (WEB DL) was replaced by a single-layer (WEB SL) device in 2013. This study aimed to compare the effectiveness and safety of these devices in managing intracranial aneurysms. METHODS: A multicenter cohort study was conducted, and data from 1,289 patients with intracranial aneurysms treated with either the WEB SL or WEB DL devices were retrospectively analyzed. Propensity score matching was utilized to balance the baseline characteristics between the two groups. Outcomes assessed included immediate occlusion rate, complete occlusion at last follow-up, retreatment rate, device compaction, and aneurysmal rupture. RESULTS: Before propensity score matching, patients treated with the WEB SL had a significantly higher rate of complete occlusion at the last follow-up and a lower rate of retreatment. After matching, there was no significant difference in immediate occlusion rate, retreatment rate, or device compaction between the WEB SL and DL groups. However, the SL group maintained a higher rate of complete occlusion at the final follow-up. Regression analysis showed that SL was associated with higher rates of complete occlusion (OR: 0.19; CI: 0.04 to 0.8, p = 0.029) and lower rates of retreatment (OR: 0.12; CI: 0 to 4.12, p = 0.23). CONCLUSION: The WEB SL and DL devices demonstrated similar performances in immediate occlusion rates and retreatment requirements for intracranial aneurysms. The SL device showed a higher rate of complete occlusion at the final follow-up.
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Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Humanos , Resultado do Tratamento , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/etiologia , Embolização Terapêutica/efeitos adversos , Pontuação de Propensão , Estudos Retrospectivos , Estudos de Coortes , Procedimentos Endovasculares/efeitos adversosRESUMO
The Woven EndoBridge (WEB) device is primarily used for treating wide-neck intracranial bifurcation aneurysms under 10 mm. Limited data exists on its efficacy for large aneurysms. We aim to assess angiographic and clinical outcomes of the WEB device in treating large versus small aneurysms. We conducted a retrospective review of the WorldWide WEB Consortium database, from 2011 to 2022, across 30 academic institutions globally. Propensity score matching (PSM) was employed to compare small and large aneurysms on baseline characteristics. A total of 898 patients were included. There was no significant difference observed in clinical presentations, smoking status, pretreatment mRS, presence of multiple aneurysms, bifurcation location, or prior treatment between the two groups. After PSM, 302 matched pairs showed significantly lower last follow-up adequate occlusion rates (81% vs 90%, p = 0.006) and higher retreatment rates (12% vs 3.6%, p < 0.001) in the large aneurysm group. These findings may inform treatment decisions and patient counseling. Future studies are needed to further explore this area.
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Procedimentos Endovasculares , Aneurisma Intracraniano , Pontuação de Propensão , Humanos , Aneurisma Intracraniano/terapia , Aneurisma Intracraniano/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Procedimentos Endovasculares/métodos , Resultado do Tratamento , Adulto , Embolização Terapêutica/métodosRESUMO
INTRODUCTION: The Woven EndoBridge (WEB) device is emerging as a novel therapy for intracranial aneurysms, but its use for off-label indications requires further study. Using machine learning, we aimed to develop predictive models for complete occlusion after off-label WEB treatment and to identify factors associated with occlusion outcomes. METHODS: This multicenter, retrospective study included 162 patients who underwent off-label WEB treatment for intracranial aneurysms. Baseline, morphological, and procedural variables were utilized to develop machine-learning models predicting complete occlusion. Model interpretation was performed to determine significant predictors. Ordinal regression was also performed with occlusion status as an ordinal outcome from better (Raymond Roy Occlusion Classification [RROC] grade 1) to worse (RROC grade 3) status. Odds ratios (OR) with 95% confidence intervals (CI) were reported. RESULTS: The best performing model achieved an AUROC of 0.8 for predicting complete occlusion. Larger neck diameter and daughter sac were significant independent predictors of incomplete occlusion. On multivariable ordinal regression, higher RROC grades (OR 1.86, 95% CI 1.25-2.82), larger neck diameter (OR 1.69, 95% CI 1.09-2.65), and presence of daughter sacs (OR 2.26, 95% CI 0.99-5.15) were associated with worse aneurysm occlusion after WEB treatment, independent of other factors. CONCLUSION: This study found that larger neck diameter and daughter sacs were associated with worse occlusion after WEB therapy for aneurysms. The machine learning approach identified anatomical factors related to occlusion outcomes that may help guide patient selection and monitoring with this technology. Further validation is needed.
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Encapsulins are microbial protein nanocages capable of efficient self-assembly and cargo enzyme encapsulation. Due to their favorable properties, including high thermostability, protease resistance, and robust heterologous expression, encapsulins have become popular bioengineering tools for applications in medicine, catalysis, and nanotechnology. Resistance against physicochemical extremes like high temperature and low pH is a highly desirable feature for many biotechnological applications. However, no systematic search for acid-stable encapsulins has been carried out, while the influence of pH on encapsulin shells has so far not been thoroughly explored. Here, we report on a newly identified encapsulin nanocage from the acid-tolerant bacterium Acidipropionibacterium acidipropionici. Using transmission electron microscopy, dynamic light scattering, and proteolytic assays, we demonstrate its extreme acid tolerance and resilience against proteases. We structurally characterize the novel nanocage using cryo-electron microscopy, revealing a dynamic five-fold pore that displays distinct "closed" and "open" states at neutral pH but only a singular "closed" state under strongly acidic conditions. Further, the "open" state exhibits the largest pore in an encapsulin shell reported to date. Non-native protein encapsulation capabilities are demonstrated, and the influence of external pH on internalized cargo is explored. Our results expand the biotechnological application range of encapsulin nanocages toward potential uses under strongly acidic conditions and highlight pH-responsive encapsulin pore dynamics.
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Bactérias , Proteínas de Bactérias , Proteínas de Bactérias/química , Microscopia Crioeletrônica , Bactérias/metabolismo , Biotecnologia , NanotecnologiaRESUMO
Background The Woven EndoBridge (WEB) device was explicitly designed for wide-neck intracranial bifurcation aneurysms. Small-scale reports have evaluated the off-label use of WEB devices for the treatment of sidewall aneurysms, with promising outcomes. Purpose To compare the angiographic and clinical outcomes of the WEB device for the treatment of sidewall aneurysms compared with the treatment of bifurcation aneurysms. Materials and Methods A retrospective review of the WorldWideWEB Consortium, a synthesis of retrospective databases spanning from January 2011 to June 2021 at 22 academic institutions in North America, South America, and Europe, was performed to identify patients with intracranial aneurysms treated with the WEB device. Characteristics and outcomes were compared between bifurcation and sidewall aneurysms. Propensity score matching (PSM) was used to match by age, pretreatment ordinal modified Rankin Scale score, ruptured aneurysms, location of aneurysm, multiple aneurysms, prior treatment, neck, height, dome width, daughter sac, and incorporated branch. Results A total of 683 intracranial aneurysms were treated using the WEB device in 671 patients (median age, 61 years [IQR, 53-68 years]; male-to-female ratio, 1:2.5). Of those, 572 were bifurcation aneurysms and 111 were sidewall aneurysms. PSM was performed, resulting in 91 bifurcation and sidewall aneurysms pairs. No significant difference was observed in occlusion status at last follow-up, deployment success, or complication rates between the two groups. Conclusion No significantly different outcomes were observed following the off-label use of the Woven EndoBridge, or WEB, device for treatment of sidewall aneurysms compared with bifurcation aneurysms. The correct characterization of the sidewall aneurysm location, neck angle, and size is crucial for successful treatment and lower retreatment rate. © RSNA, 2022 See also the editorial by Hetts in this issue.
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Aneurisma Roto , Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Aneurisma Roto/terapia , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Compartmentalization is an essential feature of all cells. It allows cells to segregate and coordinate physiological functions in a controlled and ordered manner. Different mechanisms of compartmentalization exist, with the most relevant to prokaryotes being encapsulation via self-assembling protein-based compartments. One widespread example of such is that of encapsulins-cage-like protein nanocompartments able to compartmentalize specific reactions, pathways, and processes in bacteria and archaea. While still relatively nascent bioengineering tools, encapsulins exhibit many promising characteristics, including a number of defined compartment sizes ranging from 24 to 42 nm, straightforward expression, the ability to self-assemble via the Hong Kong 97-like fold, marked physical robustness, and internal and external handles primed for rational genetic and molecular manipulation. Moreover, encapsulins allow for facile and specific encapsulation of native or heterologous cargo proteins via naturally or rationally fused targeting peptide sequences. Taken together, the attributes of encapsulins promise substantial customizability and broad usability. This review discusses recent advances in employing engineered encapsulins across various fields, from their use as bionanoreactors to targeted delivery systems and beyond. A special focus will be provided on the rational engineering of encapsulin systems and their potential promise as biomolecular research tools.
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Archaea , Proteínas Arqueais , Bactérias , Proteínas de Bactérias , Nanoestruturas/química , Peptídeos , Engenharia de Proteínas , Proteínas Recombinantes de Fusão , Archaea/química , Archaea/genética , Archaea/metabolismo , Proteínas Arqueais/química , Proteínas Arqueais/genética , Proteínas Arqueais/metabolismo , Bactérias/química , Bactérias/genética , Bactérias/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Peptídeos/química , Peptídeos/genética , Peptídeos/metabolismo , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismoRESUMO
Protein nanocages play crucial roles in sub-cellular compartmentalization and spatial control in all domains of life and have been used as biomolecular tools for applications in biocatalysis, drug delivery, and bionanotechnology. The ability to control their assembly state under physiological conditions would further expand their practical utility. To gain such control, we introduced a peptide capable of triggering conformational change at a key structural position in the largest known encapsulin nanocompartment. We report the structure of the resulting engineered nanocage and demonstrate its ability to disassemble and reassemble on demand under physiological conditions. We demonstrate its capacity for in vivo encapsulation of proteins of choice while also demonstrating in vitro cargo loading capabilities. Our results represent a functionally robust addition to the nanocage toolbox and a novel approach for controlling protein nanocage disassembly and reassembly under mild conditions.
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Nanopartículas/química , Engenharia de Proteínas , Proteínas/química , Modelos MolecularesRESUMO
Access to safe and effective sexual healthcare services for transgender and male sex workers (TMSW) is a human right. Globally, TMSW experience a higher prevalence of human immunodeficiency virus (HIV) and sexually transmitted infections than the general population or other sex workers, suggesting the existence of unique challenges for this group when accessing healthcare. A systematic database search identified 22 qualitative papers addressing barriers to accessing sexual healthcare services for TMSW. These papers were critically evaluated for adherence to best practice standards for qualitative research and research with sex workers. A coding process identified five themes. Stigma was the predominant barrier, and was divided into stigma related to sexuality, gender identity, HIV status, sex worker status, and internalised stigma. Other barriers were confidentiality concerns, sexual health literacy, fatalism, and structural barriers. Each of these themes were informed by the wider context of stigma. The literature presents a complex syndemic of social disadvantage and exclusion acting to produce and reinforce health disparities related to sexual health and access to screening and treatment for TMSW.
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Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde , Profissionais do Sexo , Saúde Sexual , Estigma Social , Pessoas Transgênero , Confidencialidade , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Infecções por HIV/terapia , Letramento em Saúde , Humanos , Masculino , Programas de Rastreamento , Distância Psicológica , Pesquisa Qualitativa , Comportamento Sexual , Sexualidade , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/prevenção & controle , Infecções Sexualmente Transmissíveis/terapia , SindemiaRESUMO
Herein we report the first structure of topoisomerase I determined from the gram-positive bacterium, S. mutans. Bacterial topoisomerase I is an ATP-independent type 1A topoisomerase that uses the inherent torsional strain within hyper-negatively supercoiled DNA as an energy source for its critical function of DNA relaxation. Interest in the enzyme has gained momentum as it has proven to be essential in various bacterial organisms. In order to aid in further biochemical characterization, the apo 65-kDa amino-terminal fragment of DNA topoisomerase I from the gram-positive model organism Streptococcus mutans was crystalized and a three-dimensional structure was determined to 2.06â¯Å resolution via x-ray crystallography. The overall structure illustrates the four classic major domains that create the traditional topoisomerase I "lock" formation comprised of a sizable toroidal aperture atop what is considered to be a highly dynamic body. A catalytic tyrosine residue resides at the interface between two domains and is known to form a 5' phosphotyrosine DNA-enzyme intermediate during transient single-stranded cleavage required for enzymatic relaxation of hyper negative DNA supercoils. Surrounding the catalytic tyrosine residue is the remainder of the highly conserved active site. Within 5â¯Å from the catalytic center, only one dissimilar residue is observed between topoisomerase I from S. mutans and the gram-negative model organism E. coli. Immediately adjacent to the conserved active site, however, S. mutans topoisomerase I displays a somewhat unique nine residue loop extension not present in any bacterial topoisomerase I structures previously determined other than that of an extremophile.
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DNA Topoisomerases Tipo I/química , Streptococcus mutans/enzimologia , Sequência de Aminoácidos , Cristalização , Cristalografia por Raios X , Modelos MolecularesRESUMO
Type IA topoisomerases represent promising antibacterial drug targets. Data exists suggesting that the two bacterial type IA topoisomerase enzymes-topoisomerase I and topoisomerase III-share an overlapping biological role. Furthermore, topoisomerase I has been shown to be essential for the survival of certain organisms lacking topoisomerase III. With this in mind, it is plausible that topoisomerase I may represent a potential target for selective antibacterial drug development. As many reported bacterial topoisomerase I purification protocols have either suffered from relatively low yield, numerous steps, or a simple failure to report target protein yield altogether, a high-yield and high-purity bacterial topoisomerase I expression and purification protocol is highly desirable. The goal of this study was therefore to optimize the expression and purification of topoisomerase I from Streptococcus mutans, a clinically relevant organism that plays a significant role in oral and extra-oral infection, in order to quickly and easily attain the requisite quantities of pure target enzyme suitable for use in assay development, compound library screening, and carrying out further structural and biochemical characterization analyses. Herein we report the systematic implementation and analysis of various expression and purification techniques leading to the development and optimization of a rapid and straightforward protocol for the auto-induced expression and two-step, affinity tag purification of Streptococcus mutans topoisomerase I yielding >20 mg/L of enzyme at over 95% purity.
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Proteínas de Bactérias , DNA Topoisomerases Tipo I , Expressão Gênica , Streptococcus mutans/enzimologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , DNA Topoisomerases Tipo I/biossíntese , DNA Topoisomerases Tipo I/química , DNA Topoisomerases Tipo I/isolamento & purificaçãoRESUMO
PURPOSE: Dynamic contrast-enhanced imaging provides unique physiological information, notably the endothelial permeability (K(trans)), and may improve the diagnosis and management of multiple pathologies. Current acquisition methods provide limited spatial-temporal resolution and field-of-view, often preventing characterization of the entire pathology and precluding measurement of the arterial input function. We present a method for highly accelerated dynamic imaging and demonstrate its utility for dynamic contrast-enhanced modeling. METHODS: We propose a novel Poisson ellipsoid sampling scheme and enforce multiple spatial and temporal l1-norm constraints during image reconstruction. Retrospective and prospective analyses were performed to validate the approach. RESULTS: Retrospectively, no mean bias or diverging trend was observed as the acceleration rate was increased from 3× to 18×; less than 10% error was measured in K(trans) at any individual rates in this range. Prospectively accelerated images at a rate of 36× enabled full brain coverage with 0.94 × 0.94 × 1.9 mm(3) spatial and 4.1 s temporal resolutions. Images showed no visible degradation and provided accurate K(trans) values when compared to a clinical population. CONCLUSION: Highly accelerated dynamic MRI using compressed sensing and parallel imaging provides accurate permeability modeling and enables full brain, high resolution acquisitions.
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Imageamento por Ressonância Magnética/métodos , Encéfalo/anatomia & histologia , Neoplasias Encefálicas/diagnóstico , Meios de Contraste , Endotélio/fisiologia , Humanos , Esclerose Múltipla/diagnóstico , Permeabilidade , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Pediatric neurointervention differs from the adult in several important respects. Here we describe a modern approach to readily acquire diagnostic quality images of children. Preparation, access, angiogragraphy and closure have evolved along with new knowledge and technology. This timely "how I do it" series addresses each topic utilizing literature review and our own experience over 35 years.
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Encapsulins are self-assembling protein nanocompartments capable of selectively encapsulating dedicated cargo proteins, including enzymes involved in iron storage, sulfur metabolism, and stress resistance. They represent a unique compartmentalization strategy used by many pathogens to facilitate specialized metabolic capabilities. Encapsulation is mediated by specific cargo protein motifs known as targeting peptides (TPs), though the structural basis for encapsulation of the largest encapsulin cargo class, dye-decolorizing peroxidases (DyPs), is currently unknown. Here, we characterize a DyP-containing encapsulin from the enterobacterial pathogen Klebsiella pneumoniae. By combining cryo-electron microscopy with TP and TP-binding site mutagenesis, we elucidate the molecular basis for cargo encapsulation. TP binding is mediated by cooperative hydrophobic and ionic interactions as well as shape complementarity. Our results expand the molecular understanding of enzyme encapsulation inside protein nanocompartments and lay the foundation for rationally modulating encapsulin cargo loading for biomedical and biotechnological applications.
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Proteínas de Bactérias , Peroxidase , Proteínas de Bactérias/metabolismo , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Microscopia Crioeletrônica , Peroxidases/metabolismoRESUMO
The anticancer drug Gefitinib is a tyrosine kinase inhibitor with selectivity for the Epidermal Growth Factor Receptor (EGFR/ErbB1). As the C. elegans EGF receptor LET-23 shares notable structural homology over its kinase domain with human EGFR, we wished to examine whether Gefitinib treatment can interfere with LET-23-dependent processes. We show that Gefitinib disrupts C. elegans stress-induced sleep (SIS) but does not impact EGF overexpression-induced sleep nor vulva induction. These findings indicate that Gefitinib does not interfere with LET-23 signaling and impairs SIS through an off-target mechanism.
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Magnetic resonance imaging (MRI) of the brain has been implemented to evaluate multiple intracranial pathologies. Non-contrast T2-weighted images are a routinely acquired sequence in almost all neuroimaging protocols. It is not uncommon to encounter various cerebrovascular lesions incidentally on brain imaging. Neuroradiologists should evaluate the routine T2-weighted images for incidental cerebrovascular lesions, irrespective of the primary indication of the study. Vascular structures typically demonstrate a low signal flow-void on the T2-weighted images. In our experience, large cerebrovascular abnormalities are easily visible to a typical neuroradiologist. In this article, we present the spectrum of the characteristic imaging appearance of various intracranial cerebrovascular lesions on routine non-contrast T2-weighted MRI. These include aneurysm, arteriovenous malformation, arterial occlusion, capillary telangiectasia, cavernous malformation, dural arteriovenous fistula, moyamoya, proliferative angiopathy, and vein of Galen malformation.
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BACKGROUND AND OBJECTIVES: Vein of Galen malformation (VOGM), the result of arteriovenous shunting between choroidal and/or subependymal arteries and the embryologic prosencephalic vein, is among the most severe cerebrovascular disorders of childhood. We hypothesized that in situ analysis of the VOGM lesion using endoluminal tissue sampling (ETS) is feasible and may advance our understanding of VOGM genetics, pathogenesis, and maintenance. METHODS: We collected germline DNA (cheek swab) from patients and their families for genetic analysis. In situ VOGM "endothelial" cells (ECs), defined as CD31+ and CD45-, were obtained from coils through ETS during routine endovascular treatment. Autologous peripheral femoral ECs were also collected from the access sheath. Single-cell RNA sequencing of both VOGM and peripheral ECs was performed to demonstrate feasibility to define the transcriptional architecture. Comparison was also made with a published normative cerebrovascular transcriptome atlas. A subset of VOGM ECs was reserved for future DNA sequencing to assess for somatic and second-hit mutations. RESULTS: Our cohort contains 6 patients who underwent 10 ETS procedures from arterial and/or venous access during routine VOGM treatment (aged 12 days to â¼6 years). No periprocedural complications attributable to ETS occurred. Six unique coil types were used. ETS captured 98 ± 88 (mean ± SD; range 17-256) experimental ECs (CD31+ and CD45-). There was no discernible correlation between cell yield and coil type or route of access. Single-cell RNA sequencing demonstrated hierarchical clustering and unique cell populations within the VOGM EC compartment compared with peripheral EC controls when annotated using a publicly available cerebrovascular cell atlas. CONCLUSION: ETS may supplement investigations aimed at development of a molecular-genetic taxonomic classification scheme for VOGM. Moreover, results may eventually inform the selection of personalized pharmacologic or genetic therapies for VOGM and cerebrovascular disorders more broadly.
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OBJECTIVE: The Woven EndoBridge (WEB) device is an intrasaccular flow disruptor designed for wide-necked bifurcation aneurysms. These aneurysms may require the use of a concomitant stent. The objective of this study was to determine the clinical and radiological outcomes of patients undergoing stent-assisted WEB treatment. In addition, the authors also sought to determine the predictors of a concomitant stent in aneurysms treated with the WEB device. METHODS: The data for this study were taken from the WorldWideWEB Consortium, an international multicenter cohort including patients treated with the WEB device. Aneurysms were classified into two groups based on treatment: stent-assisted WEB and WEB device alone. The authors compared clinical and radiological outcomes of both groups. Univariable and multivariable binary logistic regression analyses were performed to determine factors that predispose to stent use. RESULTS: The study included 691 intracranial aneurysms (31 with stents and 660 without stents) treated with the WEB device. The adequate occlusion status did not differ between the two groups at the latest follow-up (83.3% vs 85.6%, p = 0.915). Patients who underwent stenting had more thromboembolic (32.3% vs 6.5%, p < 0.001) and procedural (16.1% vs 3.0%, p < 0.001) complications. Aneurysms treated with a concomitant stent had wider necks, greater heights, and lower dome-to-neck ratios. Increasing neck size was the only significant predictor for stent use. CONCLUSIONS: This study demonstrates that there is no difference in the degree of aneurysm occlusion between the two groups; however, complications were more frequent in the stent group. In addition, a wider aneurysm neck predisposes to stent assistance in WEB-treated aneurysms.
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Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , StentsRESUMO
OBJECTIVE: This study was conducted to investigate the impact of antiplatelet administration in the periprocedural period on the occurrence of thromboembolic complications (TECs) in patients undergoing treatment using the Woven EndoBridge (WEB) device for intracranial wide-necked bifurcation aneurysms. The primary objective was to assess whether the use of antiplatelets in the pre- and postprocedural phases reduces the likelihood of developing TECs, considering various covariates. METHODS: A retrospective multicenter observational study was conducted within the WorldWideWEB Consortium and comprised 38 academic centers with endovascular treatment capabilities. Univariable and multivariable logistic regression analyses were performed to determine the association between antiplatelet use and TECs, adjusting for covariates. Missing predictor data were addressed using multiple imputation. RESULTS: The study comprised two cohorts: one addressing general thromboembolic events and consisting of 1412 patients, among whom 103 experienced TECs, and another focusing on symptomatic thromboembolic events and comprising 1395 patients, of whom 50 experienced symptomatic TECs. Preprocedural antiplatelet use was associated with a reduced likelihood of overall TECs (OR 0.32, 95% CI 0.19-0.53, p < 0.001) and symptomatic TECs (OR 0.49, 95% CI 0.25-0.95, p = 0.036), whereas postprocedural antiplatelet use showed no significant association with TECs. The study also revealed additional predictors of TECs, including stent use (overall: OR 4.96, 95% CI 2.38-10.3, p < 0.001; symptomatic: OR 3.24, 95% CI 1.26-8.36, p = 0.015), WEB single-layer sphere (SLS) type (overall: OR 0.18, 95% CI 0.04-0.74, p = 0.017), and posterior circulation aneurysm location (symptomatic: OR 18.43, 95% CI 1.48-230, p = 0.024). CONCLUSIONS: The findings of this study suggest that the preprocedural administration of antiplatelets is associated with a reduced likelihood of TECs in patients undergoing treatment with the WEB device for wide-necked bifurcation aneurysms. However, postprocedural antiplatelet use did not show a significant impact on TEC occurrence.