Genetische Atherosklerosedisposition an der Arteria brachiocephalica der Maus

Atherosklerotische Gefäßerkrankungen zählen heute weltweit zu den führenden Todesursachen. Aus Heretabilitätsuntersuchungen ist bekannt, dass die individuelle Atherosklerosedisposition zu einem erheblichen Teil (etwa 50 %) genetisch bedingt ist. Neben genomweiten Assoziationsstudien beim Menschen können auch Tiermodelle dazu beitragen, neue Modifikatoren der Atherosklerose zu identifizieren und die zugrundeliegenden molekularen Mechanismen aufzudecken. In Vorarbeiten wurde mit Hilfe einer Kopplungsanalyse bei atheroskleroseempfindlichen C57BL/6J-Mäusen und atheroskleroseresistenten FVB/N- sowie BALB/cByJ-Mäusen (alle jeweils auf dem Low-Density Lipoprotein-Rezeptor-defizienten Hintergrund) ein neuer Genort der Atherosklerosedisposition an der Arteria brachiocephalica auf dem distalen Chromosom 6 nachgewiesen. In der vorliegenden Arbeit wurde dieser Genort durch Chromosom 6-kongene Mäuse bestätigt. Durch genomweite Expressionsanalysen in Aorten- und Lebergewebe dieser Mäuse wurde Eno2 (Enolase 2) als Kandidatengen des Chromosom 6-Genortes eingegrenzt. Die Rolle von Eno2 in maßgeblichen Funktionen der Atherogenese und die molekularen Mechanismen der differentiellen Expression wurden mit Hilfe zellbiologischer und molekulargenetischer Methoden weiter charakterisiert. Zusammenfassend tragen diese Untersuchungen zu einem besseren Verständnis der Atherogenese bei

Genetische Atherosklerosedisposition an der Arteria brachiocephalica der Maus

Atherosklerotische Gefäßerkrankungen zählen heute weltweit zu den führenden Todesursachen. Aus Heretabilitätsuntersuchungen ist bekannt, dass die individuelle Atherosklerosedisposition zu einem erheblichen Teil (etwa 50 %) genetisch bedingt ist. Neben genomweiten Assoziationsstudien beim Menschen können auch Tiermodelle dazu beitragen, neue Modifikatoren der Atherosklerose zu identifizieren und die zugrundeliegenden molekularen Mechanismen aufzudecken. In Vorarbeiten wurde mit Hilfe einer Kopplungsanalyse bei atheroskleroseempfindlichen C57BL/6J-Mäusen und atheroskleroseresistenten FVB/N- sowie BALB/cByJ-Mäusen (alle jeweils auf dem Low-Density Lipoprotein-Rezeptor-defizienten Hintergrund) ein neuer Genort der Atherosklerosedisposition an der Arteria brachiocephalica auf dem distalen Chromosom 6 nachgewiesen. In der vorliegenden Arbeit wurde dieser Genort durch Chromosom 6-kongene Mäuse bestätigt. Durch genomweite Expressionsanalysen in Aorten- und Lebergewebe dieser Mäuse wurde Eno2 (Enolase 2) als Kandidatengen des Chromosom 6-Genortes eingegrenzt. Die Rolle von Eno2 in maßgeblichen Funktionen der Atherogenese und die molekularen Mechanismen der differentiellen Expression wurden mit Hilfe zellbiologischer und molekulargenetischer Methoden weiter charakterisiert. Zusammenfassend tragen diese Untersuchungen zu einem besseren Verständnis der Atherogenese bei

The social networks of manureshed management

Manureshed management—the strategic use of manure nutrients that prioritizes recycling between livestock systems and cropping systems—provides a comprehensive framework for sustainable nutrient management that necessitates the collaboration of many actors. Understanding the social dimensions of collaboration is critical to implement the strategic and technological requirements of functional manuresheds. To improve this understanding, we identified aspirational networks of actors involved in manureshed management across local, regional, and national scales, principally in the United States, elucidating key relationships and highlighting the breadth of interactions essential to successful manureshed management. We concluded that, although the social networks vary with scale, the involvement of a common core set of actors and relationships appears to be universal to the successful integration of modern livestock and crop production systems necessary for functional manuresheds. Our analysis also reveals that, in addition to agricultural producers, local actors in extension and advisory services and private and public sectors ensure optimal outcomes at all scales. For manureshed management to successfully integrate crop and livestock production and sustainably manage manure nutrient resources at each scale, the full complement of actors identified in these social networks is critical to generate innovation and ensure collaboration continuity

Interferon-beta-related tumefactive brain lesion in a Caucasian patient with neuromyelitis optica and clinical stabilization with tocilizumab

Background: Neuromyelitis optica (NMO) is a severely disabling inflammatory disorder of the central nervous system and is often misdiagnosed as multiple sclerosis (MS). There is increasing evidence that treatment options shown to be beneficial in MS, including interferon-β (IFN-β), are detrimental in NMO. Case presentation: We here report the first Caucasian patient with aquaporin 4 (AQP4) antibody (NMO-IgG)-seropositive NMO presenting with a tumefactive brain lesion on treatment with IFN-β. Disease started with relapsing optic neuritis and an episode of longitudinally extensive transverse myelitis (LETM) in the absence of any brain MRI lesions or cerebrospinal fluid-restricted oligoclonal bands. After initial misdiagnosis of multiple sclerosis (MS) the patient received subcutaneous IFN-β1b and, subsequently, subcutaneous IFN-β1a therapy for several years. Under this treatment, the patient showed persisting relapse activity and finally presented with a severe episode of subacute aphasia and right-sided hemiparesis due to a large T2 hyperintensive tumefactive lesion of the left brain hemisphere and a smaller T2 lesion on the right side. Despite rituximab therapy two further LETM episodes occurred, resulting in severe neurological deficits. Therapeutic blockade of the interleukin (IL)-6 signalling pathway by tocilizumab was initiated, followed by clinical and radiological stabilization. Conclusion: Our case (i) illustrates the relevance of correctly distinguishing NMO and MS since these disorders differ markedly in their responsiveness to immunomodulatory and -suppressive therapies; (ii) confirms and extends a previous report describing the development of tumefactive brain lesions under IFN-β therapy in two Asian NMO patients; and (iii) suggests tocilizumab as a promising therapeutic alternative in highly active NMO disease courses

Volumetric accuracy of different imaging modalities in acute intracerebral hemorrhage

Background: Follow-up imaging in intracerebral hemorrhage is not standardized and radiologists rely on different imaging modalities to determine hematoma growth. This study assesses the volumetric accuracy of different imaging modalities (MRI, CT angiography, postcontrast CT) to measure hematoma size. Methods: 28 patients with acute spontaneous intracerebral hemorrhage referred to a tertiary stroke center were retrospectively included between 2018 and 2019. Inclusion criteria were (1) spontaneous intracerebral hemorrhage (supra- or infratentorial), (2) noncontrast CT imaging performed on admission, (3) follow-up imaging (CT angiography, postcontrast CT, MRI), and (4) absence of hematoma expansion confirmed by a third cranial image within 6 days. Two independent raters manually measured hematoma volume by drawing a region of interest on axial slices of admission noncontrast CT scans as well as on follow-up imaging (CT angiography, postcontrast CT, MRI) using a semi-automated segmentation tool (Visage image viewer; version 7.1.10). Results were compared using Bland-Altman plots. Results: Mean admission hematoma volume was 18.79 +/- 19.86 cc. All interrater and intrarater intraclass correlation coefficients were excellent (1; IQR 0.98-1.00). In comparison to hematoma volume on admission noncontrast CT volumetric measurements were most accurate in patients who received postcontrast CT (bias of - 2.47%, SD 4.67: n = 10), while CT angiography often underestimated hemorrhage volumes (bias of 31.91%, SD 45.54; n = 20). In MRI sequences intracerebral hemorrhage volumes were overestimated in T2* (bias of - 64.37%, SD 21.65; n = 10). FLAIR (bias of 6.05%, SD 35.45; n = 13) and DWI (bias of-14.6%, SD 31.93; n = 12) over- and underestimated hemorrhagic volumes. Conclusions: Volumetric measurements were most accurate in postcontrast CT while CT angiography and MRI sequences often substantially over- or underestimated hemorrhage volumes

MSJ741191_supplementary_appendix_a – Supplemental material for Fulminant rebound of relapsing–remitting multiple sclerosis after discontinuation of dimethyl fumarate: A case report

<p>Supplemental material, MSJ741191_supplementary_appendix_a for Fulminant rebound of relapsing–remitting multiple sclerosis after discontinuation of dimethyl fumarate: A case report by Peter Harmel, Frieder Schlunk and Lutz Harms in Multiple Sclerosis Journal</p

MSJ741191_supplementary_appendix_b – Supplemental material for Fulminant rebound of relapsing–remitting multiple sclerosis after discontinuation of dimethyl fumarate: A case report

<p>Supplemental material, MSJ741191_supplementary_appendix_b for Fulminant rebound of relapsing–remitting multiple sclerosis after discontinuation of dimethyl fumarate: A case report by Peter Harmel, Frieder Schlunk and Lutz Harms in Multiple Sclerosis Journal</p

The effect of nanoscaffold porosity and surface chemistry on the Li-ion conductivity of LiBH4-LiNH2/metal oxide nanocomposites

Solid-state electrolytes are crucial for the realization of safer batteries with improved capacity. Lithium-based complex hydrides, for instance LiBH4, display promising characteristics as solid-state electrolytes. However, increasing their low room temperature conductivity (10-8 S cm-1 for LiBH4) is a prerequisite for application. Partial ionic substitution of BH4- with NH2- followed by nanoconfinement in mesoporous oxide scaffolds increases the conductivity to 5 × 10-4 S cm-1. Here, we show that the conductivity of LiBH4-LiNH2/metal oxide nanocomposites is strongly influenced by the chemical and physical nature of the scaffold material. By tuning both the surface chemistry and the pore structure, the conductivity can be varied by three orders of magnitude at room temperature. Unexpectedly, even though a significant influence of the scaffold surface chemistry is observed, the nanocomposite conductivity is largely dictated by the scaffold pore volume. This is in contrast to nanoconfined pure LiBH4, where the conductivity is governed by the chemical nature of the mesoporous scaffold. For nanoconfined LiBH4-LiNH2, the conductivity improvement is attributed to stabilization of a highly conductive phase inside the scaffold pores, rather than the formation of a conductive interfacial layer at the oxide/hydride interface as observed for nanoconfined LiBH4. These findings could be applicable to other cation- and anion-substituted nanocomposites and provide a useful tool to develop novel solid-state electrolytes with excellent ionic conductivities