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The current standard of care for peripheral chronic total occlusions involves the manual routing of a guidewire under fluoroscopy. Despite significant improvements in recent decades, navigation remains clinically challenging with high rates of procedural failure and iatrogenic injury. To address this challenge, we present a proof-of-concept robotic guidewire system with forward-viewing ultrasound imaging to allow visualization and maneuverability through complex vasculature.
A 0.035" guidewire-specific ultrasound transducer with matching layer and acoustic backing was designed, fabricated, and characterized. The effect of guidewire motion on signal decorrelation was assessed with simulations and experimentally, driving the development of a synthetic aperture beamforming approach to form images as the transducer is steered on the robotic guidewire. System performance was evaluated by imaging wire targets in water. Finally, proof-of-concept was demonstrated by imaging an ex vivo artery.
The designed custom transducer was fabricated with a center frequency of 15.7 MHz, 45.4% fractional bandwidth, and 31 dB SNR. In imaging 20 μm wire targets at a depth of 6 mm, the lateral -6 dB target width was 0.25 ± 0.03 mm. The 3D artery reconstruction allowed visualization of vessel wall structure and lumen.
Initial proof-of-concept for an ultrasound transducer-tipped steerable guidewire including 3D image formation without an additional sensor to determine guidewire position was demonstrated for a sub-mm system with an integrated ultrasound transducer and a robotically-steered guidewire.
The developed forward-viewing, robotically-steered guidewire may enable navigation through occluded vascular regions that cannot be crossed with current methods.
The developed forward-viewing, robotically-steered guidewire may enable navigation through occluded vascular regions that cannot be crossed with current methods.The dendritic cell receptor Clec9A facilitates processing of dead cell-derived antigens for cross-presentation and the induction of effective CD8+ T cell immune responses. Here, we show that this process is regulated by E3 ubiquitin ligase RNF41 and define a new ubiquitin-mediated mechanism for regulation of Clec9A, reflecting the unique properties of Clec9A as a receptor specialized for delivery of antigens for cross-presentation. RMC6236 We reveal RNF41 is a negative regulator of Clec9A and the cross-presentation of dead cell-derived antigens by mouse dendritic cells. Intriguingly, RNF41 regulates the downstream fate of Clec9A by directly binding and ubiquitinating the extracellular domains of Clec9A. At steady-state, RNF41 ubiquitination of Clec9A facilitates interactions with ER-associated proteins and degradation machinery to control Clec9A levels. However, Clec9A interactions are altered following dead cell uptake to favor antigen presentation. These findings provide important insights into antigen cross-presentation and have implications for development of approaches to modulate immune responses.Using multiple human annotators and ensembles of trained networks can improve the performance of deep-learning methods in research.The symptoms of foodborne histamine poisoning are similar to those of IgE-mediated food allergies. In this study, we investigated the histamine-binding capacity of lactic acid bacteria (LAB) strains as potential preventive agents against histamine poisoning. Histamine biosorption capacity was determined for 16 LAB strains. Leuconostoc mesenteroides TOKAI 51 m, Lactobacillus paracasei TOKAI 65 m, Lactobacillus plantarum TOKAI 111 m and Pediococcus pentosaceus TOKAI 759 m showed especially high biosorption rates and reached saturation within 30 min. Adsorption isotherms showed better conformance to the Freundlich model than to the Langmuir model. Analyses after heat, periodic acid and guanidine hydrochloride treatments suggested that histamine was bound to the bacterial cell surface. HPLC analysis revealed that exopolysaccharides produced by Lact. paracasei TOKAI 65 m strongly bound to histamine. In the detachment test with 1 mol l-1 HCl solution, the dissociation rate of histamine for Lact. paracasei TOKAI 65 m was less then 10 %. This strain is presumably a suitable candidate for use against histamine poisoning.
Few primary care patients are screened for substance use. As part of a phased feasibility study examining the implementation of electronic health record-integrated screening with the Tobacco, Alcohol, and Prescription Medication Screening (TAPS) Tool and clinical decision support (CDS) in rural primary care clinics, focus groups were conducted to identify early indicators of success and challenges to screening implementation.
Focus groups (
= 6) were conducted with medical assistants (MAs
= 3 19 participants) and primary care providers (PCPs
= 3 13 participants) approximately one month following screening implementation in three Federally Qualified Health Centers in Maine. Rapid analysis and matrix analysis using Proctor's Taxonomy of Implementation Outcomes were used to explore implementation outcomes.
There was consensus that screening is being used, but use of the CDS was lower, in part due to limited positive screens. Fidelity was high among MAs, though discomfort with the CDS surfaced amoin three Federally Qualified Health Centers in Maine. Rapid analysis and matrix analysis using Proctor's Taxonomy of Implementation Outcomes were used to explore implementation outcomes. Results There was consensus that screening is being used, but use of the CDS was lower, in part due to limited positive screens. Fidelity was high among MAs, though discomfort with the CDS surfaced among PCPs, impacting adoption and fidelity. The TAPS Tool's content, credibility and ease of workflow integration were favorably assessed. Challenges include screening solely at annual visits and self-administered screening for certain patients. Conclusions Results reveal indicators of implementation success and strategies to address challenges to screening for substance use in primary care.
Among cancer prevention studies, little is known about knowledge, attitudes, and beliefs toward triage adherence in the context of the human papillomavirus self-collection test. This formative research aims to identify knowledge, attitudes, and beliefs related to human papillomavirus and cervical cancer prevention specifically about adherence to Pap triage among women residing in a low-income province in Argentina.
We conducted six focus groups, stratified by residence and age. All participants were aged 30 or older and had performed human papillomavirus self-collection. Data collection and thematic analysis were carried out using constructs from the Health Belief Model.
Misinformation regarding human papillomavirus and cervical cancer was common and was a source of distress. Women could not distinguish Pap screening from triage; human papillomavirus risk perception was limited but cervical cancer was perceived as a threatening disease. Women were willing to follow-up after receiving an abnormal screeniults and follow-up are needed. Also, health services should be organized to respond to women's needs and reduce access barriers to follow-up.
To use egocentric network analysis to understand how composition and structure of egonetworks relate to violence victimization among college students.
697 students from a large southeastern university completed online surveys.
Hierarchical logistic regression analyses assessed the relationship between egocentric network variables and a history of violence victimization.
Being connected to others with a history of violence victimization increased a student's odds of indicating their own history of physical, emotional, and sexual violence victimization. Having less dense egonetworks was related to sexual violence victimization, while being connected to less people of the same gender was related to emotional violence victimization.
The way college students' networks are composed and structured could help in understanding violence victimization in this population, and should be considered in prevention and reactionary efforts on campuses. These findings add to the current literature largely focused forts on campuses. These findings add to the current literature largely focused on individual-level risk factors related to violence.Pulmonary angiogenesis is a key driver of alveolarization. Our prior studies showed that NF-κB promotes pulmonary angiogenesis during early alveolarization. However, the mechanisms regulating temporal-specific NF-κB activation in the pulmonary vasculature are unknown. To identify mechanisms that activate proangiogenic NF-κB signaling in the developing pulmonary vasculature, proteomic analysis of the lung secretome was performed using two-dimensional difference gel electrophoresis. NF-κB activation and angiogenic function was assessed in primary pulmonary endothelial cells (PECs) and TGFBI (transforming growth factor-β-induced protein)-regulated genes identified using RNA sequencing. Alveolarization and pulmonary angiogenesis was assessed in wild-type and Tgfbi null mice exposed to normoxia or hyperoxia. Lung TGFBI expression was determined in premature lambs supported by invasive and noninvasive respiratory support. Secreted factors from the early alveolar, but not the late alveolar or adult lung, promoted proliferation and migration in quiescent, adult PECs. Proteomic analysis identified TGFBI as one protein highly expressed by the early alveolar lung that promoted PEC migration by activating NF-κB via αvβ3 integrins. RNA sequencing identified Csf3 as a TGFBI-regulated gene that enhances nitric oxide production in PECs. Loss of TGFBI in mice exaggerated the impaired pulmonary angiogenesis induced by chronic hyperoxia, and TGFBI expression was disrupted in premature lambs with impaired alveolarization. Our studies identify TGFBI as a developmentally regulated protein that promotes NF-κB-mediated angiogenesis during early alveolarization by enhancing nitric oxide production. We speculate that dysregulation of TGFBI expression may contribute to diseases marked by impaired alveolar and vascular growth.Neuropathic pain is a type of spontaneous pain that causes damage to the central nervous system. Long noncoding RNAs (lncRNAs) participate in the progression of various nervous system diseases, including neuropathic pain. However, the biological function of GAS5 in neuropathic pain remains unclear. Our findings revealed that GAS5 was downregulated in chronic constriction injury (CCI) rats. Besides, ELISA showed that the concentration of IL-6, TNF-α, and IL-1β were reduced by overexpressed GAS5 in spinal cord homogenates of CCI rats. Moreover, mechanical allodynia and thermal hyperalgesia in CCI rats were inhibited by GAS5 overexpression, suggesting that GAS5 overexpression attenuated neuropathic pain. Subsequently, we found that GAS5 served as a sponge for miR-452-5p in CCI rats and CELF2 was the downstream target of miR-452-5p. Finally, through a rescue assay, we found that GAS5 ameliorated neuropathic pain in CCI rats by sponging miR-452-5p to regulate CELF2 expression. Our study confirmed that GAS5 ameliorated neuropathic pain in rats by modulation of the miR-452-5p/CELF2 axis, which may provide some clues for neuropathic pain treatment.
Website: https://www.selleckchem.com/products/rmc-6236.html
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