Varicella zoster virus vasculopathy

Varicella zoster virus (VZV) associated vasculopathy has long been identified as a major risk factor for arterial ischaemic stroke (AIS) in both adults and children. The exact mechanisms of VZV-induced pathological vascular remodelling leading to AIS have however not been fully elucidated, thus hampering current therapeutic approaches for AIS prevention. Previous immunohistochemical analysis of the morphology and composition of the arterial wall, and the location of viral antigen in the adventitia of patients with early VZV cerebral vasculopathy suggested that human brain vascular adventitial fibroblasts (HBVAF) may be the point of VZV entry into the cerebral arterial wall. In this thesis, I explored the hypothesis that VZV exerts direct pathogenic effects affecting different cells of the vasculature that could result in occlusive cerebral vasculopathy. I showed that following infection in vitro, VZV promotes HBVAF transdifferentiation to myofibroblasts, with subsequent proliferation and migration as identified by induction of α-SMA and EdU expression, and scratch assay repair. RNAseq profile analysis of VZV-infected HBVAF revealed significant upregulation of a number of genes in the infected cells, highlighting pathways possibly underlying the morphological changes described. I also examined the interaction of VZV-infected HBVAF with endothelial cells, and showed activation and dysfunction in cultured endothelial cells induced by conditioned media from VZV-infected HBVAF. Further experiments revealed that VZV-infected HBVAF release proinflammatory cytokines and chemokines that could contribute to the pathogenesis of cerebral arteriopathy. Lastly, I explored whether some of these effects on endothelial cells could be mediated by microparticle (MP) release. MP are membrane vesicles that are released from cells upon activation or during apoptosis, and are key inflammatory and endothelial dysfunction mediators in several vascular diseases. I showed that MP derived from VZV infected HBVAF contain VZV particles as detected by flow cytometry, electron microscopy and mass spectrometry. These MP-VZV complexes could infect healthy HBVAF, and might suggest a completely novel mechanism of VZV infectivity with potential relevance to viral induced changes locally in the cerebral vasculature. In conclusion, these novel findings suggest that in the context of VZV related cerebral arteriopathy, HBVAF are important players for initiation and propagation of vascular inflammation and remodelling, and that MP act as key facilitators of cross talk an viral propagation between endothelial cells and neighbouring HBVAFs. These observations suggest an entirely novel mechanism of VZV vasculopathy that furthers our understanding of the pathogenesis of AIS

Childhood infections and trauma as risk factors for stroke

Stroke is as common as brain tumor in children. The etiology of childhood arterial ischemic stroke (AIS) appears to be multifactorial, resulting from the interaction between genetic predisposition and environmental triggers. The risk factors for AIS in children are markedly different from the atherosclerotic risk factors in adults. Trauma and infections have been identified as associations in previous studies and are exposures of particular interest because of their increased prevalence in the children. The aim of this review article is to provide an overview of the research studies that have addressed the role of infections and trauma in pediatric AIS

Magnetic Helicity Estimations in Models and Observations of the Solar Magnetic Field. Part III: Twist Number Method

We study the writhe, twist and magnetic helicity of different magnetic flux ropes, based on models of the solar coronal magnetic field structure. These include an analytical force-free Titov--D\'emoulin equilibrium solution, non force-free magnetohydrodynamic simulations, and nonlinear force-free magnetic field models. The geometrical boundary of the magnetic flux rope is determined by the quasi-separatrix layer and the bottom surface, and the axis curve of the flux rope is determined by its overall orientation. The twist is computed by the Berger--Prior formula that is suitable for arbitrary geometry and both force-free and non-force-free models. The magnetic helicity is estimated by the twist multiplied by the square of the axial magnetic flux. We compare the obtained values with those derived by a finite volume helicity estimation method. We find that the magnetic helicity obtained with the twist method agrees with the helicity carried by the purely current-carrying part of the field within uncertainties for most test cases. It is also found that the current-carrying part of the model field is relatively significant at the very location of the magnetic flux rope. This qualitatively explains the agreement between the magnetic helicity computed by the twist method and the helicity contributed purely by the current-carrying magnetic field.Comment: To be published in Ap

Additivity of relative magnetic helicity in finite volumes

CONTEXT: Relative magnetic helicity is conserved by magneto-hydrodynamic evolution even in the presence of moderate resistivity. For that reason, it is often invoked as the most relevant constraint on the dynamical evolution of plasmas in complex systems, such as solar and stellar dynamos, photospheric flux emergence, solar eruptions, and relaxation processes in laboratory plasmas. However, such studies often indirectly imply that relative magnetic helicity in a given spatial domain can be algebraically split into the helicity contributions of the composing subvolumes, in other words that it is an additive quantity. A limited number of very specific applications have shown that this is not the case. AIMS: Progress in understanding the nonadditivity of relative magnetic helicity requires removal of restrictive assumptions in favor of a general formalism that can be used in both theoretical investigations and numerical applications. METHODS: We derive the analytical gauge-invariant expression for the partition of relative magnetic helicity between contiguous finite volumes, without any assumptions on either the shape of the volumes and interface, or the employed gauge. RESULTS: We prove the nonadditivity of relative magnetic helicity in finite volumes in the most general, gauge-invariant formalism, and verify this numerically. We adopt more restrictive assumptions to derive known specific approximations, which yields a unified view of the additivity issue. As an example, the case of a flux rope embedded in a potential field shows that the nonadditivity term in the partition equation is, in general, non-negligible. CONCLUSIONS: The nonadditivity of relative magnetic helicity can potentially be a serious impediment to the application of relative helicity conservation as a constraint on the complex dynamics of magnetized plasmas. The relative helicity partition formula can be applied to numerical simulations to precisely quantify the effect of nonadditivity on global helicity budgets of complex physical processes

Magnetic Helicity Evolution and Eruptive Activity in NOAA Active Region 11158

Coronal mass ejections are among the Sun’s most energetic activity events yet the physical mechanisms that lead to their occurrence are not yet fully understood. They can drive major space weather impacts at Earth, so knowing why and when these ejections will occur is required for accurate space weather forecasts. In this study we use a 4 day time series of a quantity known as the helicity ratio, ∣H J ∣/∣H V ∣ (helicity of the current-carrying part of the active region field to the total relative magnetic helicity within the volume), which has been computed from nonlinear force-free field extrapolations of NOAA active region 11158. We compare the evolution of ∣H J ∣/∣H V ∣ with the activity produced in the corona of the active region and show this ratio can be used to indicate when the active region is prone to eruption. This occurs when ∣H J ∣/∣H V ∣ exceeds a value of 0.1, as suggested by previous studies. We find the helicity ratio variations to be more pronounced during times of strong flux emergence, collision and reconnection between fields of different bipoles, shearing motions, and reconfiguration of the corona through failed and successful eruptions. When flux emergence, collision, and shearing motions have lessened, the changes in helicity ratio are somewhat subtle despite the occurrence of significant eruptive activity during this time

Relapsed clubfoot correction with soft-tissue release and selective application of Ilizarov technique

The Ilizarov technique is an alternative for the treatment of complex foot deformities in children. The authors retrospectively reviewed children with relapsed clubfoot deformity, treated with soft tissue procedures and additional correction with an Ilizarov frame. Twelve consecutive patients (13 feet) with relapsed clubfoot deformity after previous surgical correction were reviewed. Treatment included open releases. An Ilizarov frame was applied as an adjunct in seven patients (mean age of 7.8 years) with severe deformity where complete intraoperative correction was not achieved. Clinical and radiographic assessment was undertaken. The mean Laaveg–Ponseti score, for the 7 feet treated with the Ilizarov frame, was 85.1 after minimum 4 years follow-up. One recurrence of forefoot deformity required metatarsal osteotomies. Postoperative radiographic measurements revealed values that can be considered as normal. Complications included pin tract infections (12% of inserted wires). Flat-topped talus was observed in 3 feet. Deformity correction was possible when soft tissue procedures were combined with the use of Ilizarov technique, in order to support and gradually improve surgical correction

Multidisciplinary approach to the forensic identification of a late discovery victim of a motorcycle accident

This paper presents a case of a late discovery of a motorcycle accident victim. The fact that the remains were almost skeletonized required the input of several disciplines in order to identify the victim. Therefore, anthropology, odontology, facial reconstruction, and genetics were employed. It was found that the victim was male, between the ages of 35 to 55 with a number of healed fractures. In addition, perimortem trauma with a pattern that was consistent with a motorcycle accident was found in the head and upper body regions. Dental findings included a tooth out of alignment with the rest of the dental arcade, as well as a heavily decayed tooth that was replaced by a dental bridge. Both of these findings were supported by ante mortem photographs of the victim. A two-dimensional facial reconstruction was carried out and produced a very good likeness of the deceased. The above findings were confirmed by DNA analysis that matched a bone sample to those of the family of the deceased. This case illustrates the benefits of combining several different methods to make an initial assessment of a case and narrow the list of potential candidates. This can help speed up the process of identification and save resources for law enforcement agencies