Pulmonary vasospasm in systemic sclerosis: noninvasive techniques for detection

In a subgroup of patients with systemic sclerosis (SSc), vasospasm affecting the pulmonary circulation may contribute to worsening respiratory symptoms, including dyspnea. Noninvasive assessment of pulmonary blood flow (PBF), utilizing inert-gas rebreathing (IGR) and dual-energy computed-tomography pulmonary angiography (DE-CTPA), may be useful for identifying pulmonary vasospasm. Thirty-one participants (22 SSc patients and 9 healthy volunteers) underwent PBF assessment with IGR and DE-CTPA at baseline and after provocation with a cold-air inhalation challenge (CACh). Before the study investigations, participants were assigned to subgroups: group A included SSc patients who reported increased breathlessness after exposure to cold air (n = 11), group B included SSc patients without cold-air sensitivity (n = 11), and group C patients included the healthy volunteers. Median change in PBF from baseline was compared between groups A, B, and C after CACh. Compared with groups B and C, in group A there was a significant decline in median PBF from baseline at 10 minutes (−10%; range: −52.2% to 4.0%; P < 0.01), 20 minutes (−17.4%; −27.9% to 0.0%; P < 0.01), and 30 minutes (−8.5%; −34.4% to 2.0%; P < 0.01) after CACh. There was no significant difference in median PBF change between groups B or C at any time point and no change in pulmonary perfusion on DE-CTPA. Reduction in pulmonary blood flow following CACh suggests that pulmonary vasospasm may be present in a subgroup of patients with SSc and may contribute to worsening dyspnea on exposure to cold

Localisation of [131I]MIBG in nude mice bearing SK-N-SH human neuroblastoma xenografts: effect of specific activity.

The biodistribution of no-carrier-added (n.c.a.) meta-[131I]iodobenzylguanidine ([131I]MIBG) and that prepared by the standard isotopic exchange method were compared in athymic mice bearing SK-N-SH human neuroblastoma xenografts. No advantage in tumour uptake was observed for the n.c.a. preparation. BALB/c nu/nu mice exhibited lower uptake in highly innervated normal tissues (heart and adrenals) than normal BALB/c mice. In another experiment, the distribution of n.c.a. [131I]MIBG in the absence or presence (3-9 micrograms) of MIBG carrier was determined. At both 4 h and 24 h, the heart uptake was reduced by a factor of 1.5 even at a dose of 3 micrograms MIBG. Tumour uptake was not significantly altered by various amounts of unlabelled MIBG at either time point

Controlled Inhibition of the Mesenchymal Stromal Cell Pro-inflammatory Secretome via Microparticle Engineering

Mesenchymal stromal cells (MSCs) are promising therapeutic candidates given their potent immunomodulatory and anti-inflammatory secretome. However, controlling the MSC secretome post-transplantation is considered a major challenge that hinders their clinical efficacy. To address this, we used a microparticle-based engineering approach to non-genetically modulate pro-inflammatory pathways in human MSCs (hMSCs) under simulated inflammatory conditions. Here we show that microparticles loaded with TPCA-1, a small-molecule NF-κB inhibitor, when delivered to hMSCs can attenuate secretion of pro-inflammatory factors for at least 6 days in vitro. Conditioned medium (CM) derived from TPCA-1-loaded hMSCs also showed reduced ability to attract human monocytes and prevented differentiation of human cardiac fibroblasts to myofibroblasts, compared with CM from untreated or TPCA-1-preconditioned hMSCs. Thus, we provide a broadly applicable bioengineering solution to facilitate intracellular sustained release of agents that modulate signaling. We propose that this approach could be harnessed to improve control over MSC secretome post-transplantation, especially to prevent adverse remodeling post-myocardial infarction.United States. National Institutes of Health (HL097172)United States. National Institutes of Health (HL095722

Seismicity and crustal structure of the southern main Ethiopian rift: new evidence from Lake Abaya

The Main Ethiopian Rift (MER) has developed during the 18 Ma-Recent separation of the Nubian and Somalian plates. Extension in its central and northern sectors is associated with seismic activity and active magma intrusion, primarily within the rift, where shallow (urn:x-wiley:15252027:media:ggge22586:ggge22586-math-00015 km) seismicity along magmatic centers is commonly caused by fluid flow through open fractures in hydrothermal systems. However, the extent to which similar magmatic rifting persists into the southern MER is unknown. Using data from a temporary network of five seismograph stations, we analyze patterns of seismicity and crustal structure in the Abaya region of the southern MER. Magnitudes range from 0.9 to 4.0; earthquake depths are 0–30 km. urn:x-wiley:15252027:media:ggge22586:ggge22586-math-0002 ratios of urn:x-wiley:15252027:media:ggge22586:ggge22586-math-00031.69, estimated from Wadati diagram analysis, corroborate bulk-crustal urn:x-wiley:15252027:media:ggge22586:ggge22586-math-0004 ratios determined via teleseismic P-to-S receiver function H-urn:x-wiley:15252027:media:ggge22586:ggge22586-math-0005 stacking and reveal a relative lack of mafic intrusion compared to the MER rift sectors to the north. There is a clear association of seismicity with the western border fault system of the MER everywhere in our study area, but earthquake depths are shallow near Duguna volcano, implying a shallowed geothermal gradient associated with rift valley silicic magmatism. This part of the MER is thus interpreted best as a young magmatic system that locally impacts the geothermal gradient but that has not yet significantly modified continental crustal composition via rift-axial magmatic rifting

Lower Crustal Earthquakes in the March 2018 Sequence Along the Western Margin of Afar

During the evolution of continental rift systems, extension is thought to progressively focus in-rift to the future breakup boundary while faults along the rift margins progressively deactivate. However, observational constraints on how strain is partitioned between rift axis and rift margins are still lacking. The Afar rift records the latest stages of rifting and incipient continental breakup. Here, we analyzed the recent MW 5.2 earthquake on the Western Afar Margin on March 24, 2018 and the associated seismic sequence of &gt;500 earthquakes using 24 temporary seismic stations deployed during 2017–2018. We show seismicity occurring at lower crustal depths, from ∼15 to ∼30&nbsp;km, with focal mechanisms and relocated earthquakes highlighting both west-dipping and east-dipping normal faults. We tested earthquake depth using InSAR by processing six independent interferograms using Sentinel-1 data acquired from both ascending and descending tracks. None of them shows evidence of surface deformation. We tested possible ranges of depth by producing forward models for a fault located at progressively increasing depths. Models show that surface deformation is not significant for fault slip at depths greater than 15&nbsp;km, in agreement with the hypocentral depth of 19&nbsp;km derived from seismic data for the largest earthquake. Due to the localized nature of deep earthquakes near hot springs coupled with subsurface evidence for magmatism, we favor an interpretation of seismicity induced by migrating fluids such as magma or CO2. We suggest that deep fluid migration can occur at the rifted-margin influencing seismicity during incipient continental rupture

Lower Crustal Earthquakes in the March 2018 Sequence Along the Western Margin of Afar

During the evolution of continental rift systems, extension is thought to progressively focus in-rift to the future breakup boundary while faults along the rift margins progressively deactivate. However, observational constraints on how strain is partitioned between rift axis and rift margins are still lacking. The Afar rift records the latest stages of rifting and incipient continental breakup. Here, we analyzed the recent M W 5.2 earthquake on the Western Afar Margin on March 24, 2018 and the associated seismic sequence of &gt;500 earthquakes using 24 temporary seismic stations deployed during 2017–2018. We show seismicity occurring at lower crustal depths, from ∼15 to ∼30 km, with focal mechanisms and relocated earthquakes highlighting both west-dipping and east-dipping normal faults. We tested earthquake depth using InSAR by processing six independent interferograms using Sentinel-1 data acquired from both ascending and descending tracks. None of them shows evidence of surface deformation. We tested possible ranges of depth by producing forward models for a fault located at progressively increasing depths. Models show that surface deformation is not significant for fault slip at depths greater than 15 km, in agreement with the hypocentral depth of 19 km derived from seismic data for the largest earthquake. Due to the localized nature of deep earthquakes near hot springs coupled with subsurface evidence for magmatism, we favor an interpretation of seismicity induced by migrating fluids such as magma or CO 2. We suggest that deep fluid migration can occur at the rifted-margin influencing seismicity during incipient continental rupture. </p

Mechanism for deep crustal seismicity: Insight from modeling of deformation process at the Main Ethiopian Rift

We combine numerical modeling of lithospheric extension with analysis of seismic moment release and earthquake b-value in order to elucidate the mechanism for deep crustal seismicity and seismic swarms in the Main Ethiopian Rift (MER). We run 2-D numerical simulations of lithospheric deformation calibrated by appropriate rheology and extensional history of the MER to simulate migration of deformation from mid-Miocene border faults to ∼30 km wide zone of Pliocene to recent rift floor faults. While currently the highest strain rate is localized in a narrow zone within the rift axis, brittle strain has been accumulated in a wide region of the rift. The magnitude of deviatoric stress shows strong variation with depth. The uppermost crust deforms with maximum stress of 80 MPa, at 8–14 km depth stress sharply decreases to 10 MPa and then increases to a maximum of 160 MPa at ∼18 km depth. These two peaks at which the crust deforms with maximum stress of 80 MPa or above correspond to peaks in the seismic moment release. Correspondingly, the drop in stress at 8–14 km correlates to a low in seismic moment release. At this depth range, the crust is weaker and deformation is mainly accommodated in a ductile manner. We therefore see a good correlation between depths at which the crust is strong and elevated seismic deformation, while regions where the crust is weaker deform more aseismically. Overall, the bimodal depth distribution of seismic moment release is best explained by the rheology of the deforming crust