Blood oxygenation-level dependent cerebrovascular reactivity imaging as strategy to monitor CSF-hemoglobin toxicity

Objectives: Cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) may be one of the main drivers of secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Haptoglobin scavenging of CSF-Hb has been shown to mitigate cerebrovascular disruption. Using digital subtraction angiography (DSA) and blood oxygenation-level dependent cerebrovascular reactivity imaging (BOLD-CVR) the aim was to assess the acute toxic effect of CSF-Hb on cerebral blood flow and autoregulation, as well as to test the protective effects of haptoglobin. Methods: DSA imaging was performed in eight anesthetized and ventilated sheep (mean weight: 80.4 kg) at baseline, 15, 30, 45 and 60 minutes after infusion of hemoglobin (Hb) or co-infusion with haptoglobin (Hb:Haptoglobin) into the left lateral ventricle. Additionally, 10 ventilated sheep (mean weight: 79.8 kg) underwent BOLD-CVR imaging to assess the cerebrovascular reserve capacity. Results: DSA imaging did not show a difference in mean transit time or cerebral blood flow. Whole-brain BOLD-CVR compared to baseline decreased more in the Hb group after 15 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs -0.01 ± 0.02) and remained diminished compared to Hb:Haptoglobin group after 30 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.0 ± 0.01), 45 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.01 ± 0.02) and 60 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.02 vs 0.01 ± 0.01). Conclusion: It is demonstrated that CSF-Hb toxicity leads to rapid cerebrovascular reactivity impairment, which is blunted by haptoglobin co-infusion. BOLD-CVR may therefore be further evaluated as a monitoring strategy for CSF-Hb toxicity after aSAH

Physical activity and brain health in patients with atrial fibrillation

Background and purpose: Vascular brain lesions, such as ischemic infarcts, are common among patients with atrial fibrillation (AF) and are associated with impaired cognitive function. The role of physical activity (PA) in the prevalence of brain lesions and cognition in AF has not been investigated. Methods: Patients from the multicenter Swiss‐AF cohort study were included in this cross‐sectional analysis. We assessed regular exercise (RE; at least once weekly) and minutes of weekly PA using a validated questionnaire. We studied associations with ischemic infarcts, white matter hyperintensities, cerebral microbleeds, and brain volume on brain magnetic resonance imaging and with global cognition measured with a cognitive construct (CoCo) score.ResultsAmong 1490 participants (mean age = 72 ± 9 years), 730 (49%) engaged in RE. In adjusted regression analyses, RE was associated with a lower prevalence of ischemic infarcts (odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.63–0.98, p = 0.03) and of moderate to severe white matter hyperintensities (OR = 0.78, 95% CI = 0.62–0.99, p = 0.04), higher brain volume (β‐coefficient = 10.73, 95% CI = 2.37–19.09, p = 0.01), and higher CoCo score (β‐coefficient = 0.08, 95% CI = 0.03–0.12, p < 0.001). Increasing weekly PA was associated with higher brain volume (β‐coefficient = 1.40, 95% CI = 0.65–2.15, p < 0.001). Conclusions: In AF patients, RE was associated with a lower prevalence of ischemic infarcts and of moderate to severe white matter disease, with larger brain volume, and with better cognitive performance. Prospective studies are needed to investigate whether these associations are causal. Until then, our findings suggest that patients with AF should be encouraged to remain physically active

Mites Parasitic on Australasian and African Spiders Found in the Pet Trade; a Redescription of Ljunghia pulleinei Womersley

Parasitic mites associated with spiders are spreading world-wide through the trade in tarantulas and other pet species. Ljunghia pulleinei Womersley, a mesostigmatic laelapid mite originally found in association with the mygalomorph spider Selenocosmia stirlingi Hogg (Theraphosidae) in Australia, is redescribed and illustrated on the basis of specimens from the African theraphosid spider Pterinochilus chordatus (Gersta¨cker) kept in captivity in the British Isles (Wales). The mite is known from older original descriptions of Womersley in 1956; the subsequent redescription of Domrow in 1975 seems to be questionable in conspecificity of treated specimens with the type material. Some inconsistencies in both descriptions are recognised here as intraspecific variability of the studied specimens. The genus Arachnyssus Ma, with species A. guangxiensis (type) and A. huwenae, is not considered to be a valid genus, and is included in synonymy with Ljunghia Oudemans. A new key to world species of the genus Ljunghia is provided

Corporate environmental responsibility and criminology

This article addresses corporate environmental responsibility (CER) and aims to present a criminological analysis of it. We studied the opinion of a number of principle actors involved in CER in Europe in order to determine how they perceive it in terms of its definition, aetiology and approaches. For each of these dimensions we relate back to a criminological framework to ascertain how it is positioned in the green criminological debate. We start out by providing information on what corporate environmental responsibility is and how it relates to corporate social responsibility and sustainable development. Then we outline the theoretical framework in accordance with the three central themes for the criminological analysis of CER: definition, aetiology and approaches. We also explain the method that was used (semi-structured interviews). Next, we present the results according to the same threefold structure. Finally we discuss these results in a last part, which is divided in two. First, we look at the challenges that the criminological perspective poses for CER in terms of definition, aetiology and approaches. The second part of the discussion turns the question around and wonders how CER could contribute to greening criminology

Criminology or Zemiology? Yes, please! on the refusal of choice between false alternatives

Buried deep within the zemiological movement and its supportive literature is the implicit assumption that the word zemia, the organising concept around which zemiology is built, simply represents ‘the Greek word for harm’. This interpretation has supported numerous drives to ‘move beyond criminology’ and erect strict borders between the study of crime and harm. However, a deeper, albeit still rather brief, exploration of zemia reveals that it possesses a broader range of meaning than that commonly afforded to it. By beginning to unpick zemia’s semantic genealogy, it appears that the conventional use of the word to support the imposition of false alternatives between criminology and zemiology is untenable. Accordingly, this chapter attempts to foreground a more integrated approach to the study of crime and harm

A Pandemic Influenza H1N1 Live Vaccine Based on Modified Vaccinia Ankara Is Highly Immunogenic and Protects Mice in Active and Passive Immunizations

The development of novel influenza vaccines inducing a broad immune response is an important objective. The aim of this study was to evaluate live vaccines which induce both strong humoral and cell-mediated immune responses against the novel human pandemic H1N1 influenza virus, and to show protection in a lethal animal challenge model.For this purpose, the hemagglutinin (HA) and neuraminidase (NA) genes of the influenza A/California/07/2009 (H1N1) strain (CA/07) were inserted into the replication-deficient modified vaccinia Ankara (MVA) virus - a safe poxviral live vector – resulting in MVA-H1-Ca and MVA-N1-Ca vectors. These live vaccines, together with an inactivated whole virus vaccine, were assessed in a lung infection model using immune competent Balb/c mice, and in a lethal challenge model using severe combined immunodeficient (SCID) mice after passive serum transfer from immunized mice. Balb/c mice vaccinated with the MVA-H1-Ca virus or the inactivated vaccine were fully protected from lung infection after challenge with the influenza H1N1 wild-type strain, while the neuraminidase virus MVA-N1-Ca induced only partial protection. The live vaccines were already protective after a single dose and induced substantial amounts of neutralizing antibodies and of interferon-γ-secreting (IFN-γ) CD4- and CD8 T-cells in lungs and spleens. In the lungs, a rapid increase of HA-specific CD4- and CD8 T cells was observed in vaccinated mice shortly after challenge with influenza swine flu virus, which probably contributes to the strong inhibition of pulmonary viral replication observed. In addition, passive transfer of antisera raised in MVA-H1-Ca vaccinated immune-competent mice protected SCID mice from lethal challenge with the CA/07 wild-type virus.The non-replicating MVA-based H1N1 live vaccines induce a broad protective immune response and are promising vaccine candidates for pandemic influenza

Loss of host-derived osteopontin creates a glioblastoma-promoting microenvironment

Background: Microglia and periphery-derived monocytes infiltrate human and mouse glioblastoma and their density is positively correlated with malignancy. Using microarray and RNA sequencing we have previously shown that glioblastoma-associated microglia/monocytes (GAMs) express osteopontin/SPP1. Methods: We used qRT-PCR, immunofluorescence stainings, western-blot, and flow-cytometry to identify the various sources of osteopontin (OPN) expression in human and mouse glioblastoma. We implanted wild type GL261 glioblastoma cells, which do not express significant levels of OPN, into wild-type and OPN(-/-) mice to investigate the role of microenvironment-derived OPN on glioblastoma progression. Results: Our data indicates that GAMs are the predominant source of OPN in both human and mouse glioblastoma and only express the secreted form of OPN. Loss of microenvironment-derived OPN enhanced tumor progression. Ki67 and TUNEL staining showed no difference in overall cell proliferation but a decreased apoptosis rate in tumors in OPN(-/-) mice. CD31 staining showed a significantly decreased number of microvessels in tumors in OPN(-/-) mice, accompanied by reduced coverage of vessels with PDGFRβ-positive pericytes. Flow cytometry analysis revealed a significant increase of CD11b(+)/CD45(low) microglia but not of CD11b(+)/CD45(high) macrophages/monocytes in tumors in OPN(-/-) mice. Sorted CD11b(+) cells from wild type and OPN(-/-) naïve brains and tumors did not show a significant difference in the expression pattern of activation marker genes. Conclusion: Our results show that in tested human and mouse glioblastoma OPN is predominantly expressed and secreted by GAMs and that, in contrast to OPN expression in the tumor cells per se, loss of stroma-derived OPN creates a glioblastoma-promoting microenvironment