Sin nombre virus glycoprotein trafficking

AbstractSin Nombre virus (SNV) is a major representative of the New World hantaviruses and the most common cause of hantavirus pulmonary syndrome (HPS) with high mortality in North America. Unlike other members of the family Bunyaviridae which mature in the Golgi complex, New World hantaviruses have been previously reported to mature at the cell surface. For family Bunyaviridae viruses, retention of the viral glycoproteins at the Golgi complex is thought to be responsible for their Golgi maturation. In our studies, the majority of SNV glycoproteins, G1 and G2, was localized in the Golgi complex when expressed from a full-length GPC clone or in SNV-infected cells, in agreement with data for other members of the family Bunyaviridae, including the Old World hantaviruses. However, the SNV glycoproteins could also be detected at the cell surface at advanced posttransfection or postinfection time points. G1 expressed in the absence of G2 did not accumulate in the Golgi, but remained predominantly associated with the endoplasmic reticulum (ER). Overexpressed amounts of apparently misfolded G1 were aggregated in a subcellular compartment likely to represent the aggresome. Unexpectedly, an additional major pool of G1 was detected intracellularly in SNV-infected and GPC-expressing transfected cells, by using a SNV G1-specific Fab antibody. This pool of G1 is predominantly localized in late endosomes–lysosomes

Towards a First-Person Perspective Mixed Reality Guidance System for Needle Interventions

While ultrasound (US) guidance has been used during central venous catheterization to reduce complications, including the puncturing of arteries, the rate of such problems remains non-negligible. To further reduce complication rates, mixed-reality systems have been proposed as part of the user interface for such procedures. We demonstrate the use of a surgical navigation system that renders a calibrated US image, and the needle and its trajectory, in a common frame of reference. We compare the effectiveness of this system, whereby images are rendered on a planar monitor and within a head-mounted display (HMD), to the standard-of-care US-only approach, via a phantom-based user study that recruited 31 expert clinicians and 20 medical students. These users performed needle-insertions into a phantom under the three modes of visualization. The success rates were significantly improved under HMD-guidance as compared to US-guidance, for both expert clinicians (94% vs. 70%) and medical students (70% vs. 25%). Users more consistently positioned their needle closer to the center of the vessel’s lumen under HMD-guidance compared to US-guidance. The performance of the clinicians when interacting with this monitor system was comparable to using US-only guidance, with no significant difference being observed across any metrics. The results suggest that the use of an HMD to align the clinician’s visual and motor fields promotes successful needle guidance, highlighting the importance of continued HMD-guidance research

Multi-View 3D Transesophageal Echocardiography Registration and Volume Compounding for Mitral Valve Procedure Planning

Three-dimensional ultrasound mosaicing can increase image quality and expand the field of view. However, limited work has been done applying these compounded approaches for cardiac procedures focused on the mitral valve. For procedures targeting the mitral valve, transesophageal echocardiography (TEE) is the primary imaging modality used as it provides clear 3D images of the valve and surrounding tissues. However, TEE suffers from image artefacts and signal dropout, particularly for structures lying below the valve, including chordae tendineae, making it necessary to acquire alternative echo views to visualize these structures. Due to the limited field of view obtainable, the entire ventricle cannot be directly visualized in sufficient detail from a single image acquisition in 3D. We propose applying an image compounding technique to TEE volumes acquired from a mid-esophageal position and several transgastric positions in order to reconstruct a high-detail volume of the mitral valve and sub-valvular structures. This compounding technique utilizes both fully and semi-simultaneous group-wise registration to align the multiple 3D volumes, followed by a weighted intensity compounding step based on the monogenic signal. This compounding technique is validated using images acquired from two excised porcine mitral valve units and three patient data sets. We demonstrate that this compounding technique accurately captures the physical structures present, including the mitral valve, chordae tendineae and papillary muscles. The chordae length measurement error between the compounded ultrasound and ground-truth CT for two porcine valves is reported as 0.7 ± 0.6 mm and 0.6 ± 0.6 mm

3D Localization of Vena Contracta using Doppler ICE Imaging in Tricuspid Valve Interventions

PURPOSE: Tricuspid valve (TV) interventions face the challenge of imaging the anatomy and tools because of the ‘TEE-unfriendly’ nature of the TV. In edge-to-edge TV repair, a core step is to position the clip perpendicular to the coaptation gap. In this study, we provide a semi-automated method to localize the VC from Doppler intracardiac echo (ICE) imaging in a tracked 3D space, thus providing a pre-mapped location of the coaptation gap to assist device positioning. METHODS: A magnetically tracked ICE probe with Doppler imaging capabilities is employed in this study for imaging three patient-specific TVs placed in a pulsatile heart phantom. For each of the valves, the ICE probe is positioned to image the maximum regurgitant flow for five cardiac cycles. An algorithm then extracts the regurgitation imaging and computes the exact location of the vena contracta on the image. RESULTS: Across the three pathological, patient-specific valves, the average distance error between the detected VC and the ground truth model is [Formula: see text] mm. For each of the valves, one case represented the outlier where the algorithm misidentified the vena contracta to be near the annulus. In such cases, it is recommended to retake the five-second imaging data. CONCLUSION: This study presented a method for ultrasound-based localization of vena contracta in 3D space. Mapping such anatomical landmarks has the potential to assist with device positioning and to simplify tricuspid valve interventions by providing more contextual information to the interventionalists, thus enhancing their spatial awareness. Additionally, ICE can be used to provide live US and Doppler imaging of the complex TV anatomy throughout the procedure

Towards fluoro-free interventions: Using radial intracardiac ultrasound for vascular navigation

Transcatheter cardio-vascular interventions have the advantage of patient safety,reduced surgery time, and minimal trauma to the patient\u27s body. Transcathetherinterventions, which are performed percutaneously, suffer from the lack of direct line-of-sight with the surgical tools and the patient anatomy. Therefore, such interventionalprocedures rely heavily on image guidance for navigating towards and deliveringtherapy at the target site. Vascular navigation via the inferior vena cava (IVC), from thegroin to the heart, is an imperative part of most transcatheter cardiovascularinterventions such as valve repair surgeries and ablation therapy. Traditionally, the IVCis navigated using fluoroscopic techniques such as angiography or CT venography.These X-ray based techniques can have detrimental effects on the patient as well asthe surgical team, causing increased radiation exposure, increased risk of cancer, fetaldefects, eye cataracts. The use of heavy lead apron has also been reported to causeback pain and spine issues thus leading to interventionalist’s disc disease. We proposethe use of a catheter-based ultrasound augmented with electromagnetic (EM) trackingtechnology to generate a vascular roadmap in real-time and perform navigation withoutharmful radiation. In this pilot study, we use intracardiac echocardiography (ICE) and tracking technology to reconstruct a vessel from a phantom in a 3D virtual space. Thispaper presents a pilot phantom study on ICE-based vessel reconstruction anddemonstrates how the proposed ultrasound-based navigation will appear in a virtualspace, by navigating a tracked guidewire within the vessels in the phantom without anyradiation-based imaging. The geometric accuracy is assessed using a CT scan of thephantom, with a Dice coefficient of 0.79. The average distance between the surface ofthe two models comes out to be 1.7 ± 1.12mm

Gravitational radiation reaction in compact binary systems: Contribution of the magnetic dipole-magnetic dipole interaction

We study the gravitational radiation reaction in compact binary systems composed of neutron stars with spin and huge magnetic dipole moments (magnetars). The magnetic dipole moments undergo a precessional motion about the respective spins. At sufficiently high values of the magnetic dipole moments, their interaction generates second post-Newtonian order contributions both to the equations of motion and to the gravitational radiation escaping the system. We parametrize the radial motion and average over a radial period in order to find the secular contributions to the energy and magnitude of the orbital angular momentum losses, in the generic case of \textit{eccentric} orbits. Similarly as for the spin-orbit, spin-spin, quadrupole-monopole interactions, here too we deduce the secular evolution of the relative orientations of the orbital angular momentum and spins. These equations, supplemented by the evolution equations for the angles characterizing the orientation of the dipole moments form a first order differential system, which is closed. The circular orbit limit of the energy loss agrees with Ioka and Taniguchi's earlier result

Systematic review of coexistent epileptic seizures and Alzheimer's disease : incidence and prevalence

Background/Objectives Coexistent seizures add complexity to the burden of Alzheimer's disease (AD). We aim to estimate the incidence and prevalence of coexistent seizures and AD and summarize characteristics. Design A systematic review and meta‐analysis (PROSPERO protocol registration CRD42020150479). Setting Population‐, community‐, hospital‐, or nursing home‐based. Participants and measurements Thirty‐nine studies reporting on seizure incidence and prevalence in 21,198 and 380,777 participants with AD, respectively, and AD prevalence in 727,446 participants with seizures. When statistical heterogeneity and inconsistency (assessed by Q statistic and I2) were not shown, rates were synthesized using random effect. Results Studies were conducted in Australia, Brazil, Finland, France, Ireland, Italy, Japan, Netherlands, Portugal, Sweden, Taiwan, United Kingdom, and United States. The incidence of seizures among people with clinically diagnosed AD ranged from 4.2 to 31.5 per 1000 person‐years. Prevalence of seizures among people with clinically diagnosed AD ranged from 1.5% to 12.7% generally, but it rose to the highest (49.5% of those with early‐onset AD) in one study. Meta‐analysis reported a combined seizure prevalence rate among people with pathologically verified AD at 16% (95% confidence interval [CI] 14–19). Prevalence of seizure in autosomal dominant AD (ADAD) ranged from 2.8% to 41.7%. Being younger was associated with higher risk of seizure occurrence. Eleven percent of people with adult‐onset seizures had AD (95%CI, 7‐14). Conclusion Seizures are common in those with AD, and seizure monitoring may be particularly important for younger adults and those with ADAD

α-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson’s disease

A diagnosis of motor Parkinson’s disease (PD) is preceded by a prolonged premotor phase with accumulating neuronal damage. Here we examined the temporal relation between α-synuclein (α-syn) T cell reactivity and PD. A longitudinal case study revealed that elevated α-syn-specific T cell responses were detected prior to the diagnosis of motor PD, and declined after. The relationship between T cell reactivity and early PD in two independent cohorts showed that α-syn-specific T cell responses were highest shortly after diagnosis of motor PD and then decreased. Additional analysis revealed significant association of α-syn-specific T cell responses with age and lower levodopa equivalent dose. These results confirm the presence of α-syn-reactive T cells in PD and show that they are most abundant immediately after diagnosis of motor PD. These cells may be present years before the diagnosis of motor PD, suggesting avenues of investigation into PD pathogenesis and potential early diagnosis