The neuropathology of kuru and variant Creutzfeldt–Jakob disease

A comparison of the pathological profiles of two spongiform encephalopathies with a similar presumptive route of infection was performed. Archival kuru and recent variant Creutzfeldt–Jakob disease (vCJD) cases reveal distinct lesional differences, particularly with respect to prion protein, suggesting that the strain of agent is important in determining the phenotype. Genotype analysis of the polymorphism on codon 129 reveals (in conjunction with updated information from more kuru cases) that all three genotypes (VV, MV and MM (where M is methionine and V is valine)) are detected in kuru with some preference for MM homozygosity. The presence of valine does not therefore appear to determine peripheral selection of PrPCJD. vCJD remains restricted to date to MM homozygosity on codon 129. It remains to be determined whether this genotype is dictating a shorter incubation period

Grassroots Social Resistance Movements: The Influence of Conflict Narratives in Relation to Mining Policy Development in Australia and the United Kingdom

The development of unconventional gas is widely disputed and has generated a global anti-fracking movement protest. Using a qualitative approach, this study seeks to explore if and how the anti-fracking movements in Australia and the UK influence the mining policies and politics around fracking. Using thematic and narrative analysis, I argue that the anti-fracking movement is a social movement that has three characteristics: (i) key pro- and anti- narratives, (ii) use of the discretionary principle and (iii) deployment of a range of protest mechanisms to drive and shape conflict about unconventional gas, which in turn affects policy. Pro- and anti-fracking narratives across Australia and the UK have impelled a range of circumstances. The anti-fracking narratives have spurred social conflict and organised protest. Pro-fracking narratives have motivated governments to exercise their discretionary power to favour industry by establishing governance regimes that facilitate industry projects, inhibit community engagement, and criminalise protest. A social movement has grown in response to these inherent tensions. The anti-fracking movement is galvanised by community identity, values, and perception, thus building opposition to fracking through numerous forms of protest. The resolutions for this conflict lie in their reconciliation between community and government. The analysis concludes that governance regimes that afford greater public participation, consideration of community concerns in decision-making and knowledge production will work towards resolving the social problems of the industry and thus the tensions at the heart of the anti-fracking movement.Thesis (Ph.D.) -- University of Adelaide, School of Social Sciencs, 202

Brain cell reservoirs of latent virus in presymptomatic HIV-infected individuals

We detected HIV-1 DNA in pure populations of perivascular macrophages, parenchymal microglia, and astrocytes, isolated using laser microdissection from brain tissue of five untreated individuals who died in the presymptomatic stage of infection from non-HIV causes. HIV-1 DNA was detected in the three cell populations, most consistently in perivascular macrophages, without evidence of productive infection. The percentage of PCR reactions detecting HIV-1 DNA in perivascular macrophages correlated inversely with peripheral blood CD4 counts. These findings demonstrate that brain cell reservoirs of latent HIV-1 exist before pathological HIV encephalitis and suggest that perivascular macrophage trafficking of latent virus into the brain increases with immunosuppression

A histopathologic study of fatal paediatric cerebral malaria caused by mixed Plasmodium falciparum/Plasmodium vivax infections

Microvascular sequestration of Plasmodium falciparum underlies cerebral malaria. Despite suggestive ex vivo evidence, this phenomenon has not been convincingly demonstrated in coma complicating Plasmodium vivax malaria. Severely-ill Papua New Guinean children with mixed P. falciparum/P. vivax infections are more likely to develop cerebral malaria and die than those with P. falciparum alone, possibly reflecting P. vivax sequestration. Nested PCR was performed on post mortem brain tissue from three such children dying from cerebral malaria due to mixed-species infections. No P. vivax DNA was detected. These findings do not support the hypothesis that P. vivax sequestration occurs in human brain

Development and management of systemic lupus erythematosus in an HIV-infected man with hepatitis C and B co-infection following interferon therapy: a case report

<p>Abstract</p> <p>Introduction</p> <p>The association of human immunodeficiency virus and immune dysfunction leading to development of autoimmune markers is well described, but human immunodeficiency virus infection is relatively protective for the development of systemic lupus erythematosus. In contrast, development of systemic lupus erythematosus with hepatitis C and with interferon therapy is well described in a number of case reports. We here describe the first case of systemic lupus erythematosus developing in a man infected with human immunodeficiency virus, hepatitis C and hepatitis B co-infection where the onset seems to have been temporally related to interferon therapy.</p> <p>Case presentation</p> <p>We report the occurrence of systemic lupus erythematosus complicating interferon-α therapy for hepatitis C in a 47-year-old asplenic male with haemophilia co-infected with human immunodeficiency virus and hepatitis B. He presented with a truncal rash, abdominal pains and headache and later developed grade IV lupus nephritis requiring haemodialysis, mycophenolate mofetil and steroid therapy. We were able to successfully withdraw dialysis and mycophenolate while maintaining stable renal function.</p> <p>Conclusion</p> <p>Interferon-α is critical in antiviral immunity against hepatitis C but also acts as a pathogenic mediator for systemic lupus erythematosus, a condition associated with activation of plasmacytoid dendritic cells that are depleted in human immunodeficiency virus infection. The occurrence of auto-antibodies and lupus-like features in the coinfections with hepatitis C require careful assessment. Immunosuppressant therapy for lupus risks exacerbating underlying infections in patients with concurrent human immunodeficiency virus, hepatitis B and C.</p

Family Clustering of Viliuisk Encephalomyelitis in Traditional and New Geographic Regions

Transmission occurs through patient contact; human migration from disease-endemic villages leads to disease emergence in new communities

Neuropathology of childhood‐onset basal ganglia degeneration caused by mutation of VAC14

ObjectiveTo characterize the clinical features and neuropathology associated with recessive VAC14 mutations.MethodsWhole‐exome sequencing was used to identify the genetic etiology of a rapidly progressive neurological disease presenting in early childhood in two deceased siblings with distinct neuropathological features on post mortem examination.ResultsWe identified compound heterozygous variants in VAC14 in two deceased siblings with early childhood onset of severe, progressive dystonia, and neurodegeneration. Their clinical phenotype is consistent with the VAC14–related childhood‐onset, striatonigral degeneration recently described in two unrelated children. Post mortem examination demonstrated prominent vacuolation associated with degenerating neurons in the caudate nucleus, putamen, and globus pallidus, similar to previously reported ex vivo vacuoles seen in the late‐endosome/lysosome of VAC14‐deficient neurons. We identified upregulation of ubiquitinated granules within the cell cytoplasm and lysosomal‐associated membrane protein (LAMP2) around the vacuole edge to suggest a process of vacuolation of lysosomal structures associated with active autophagocytic‐associated neuronal degeneration.InterpretationOur findings reveal a distinct clinicopathological phenotype associated with recessive VAC14 mutations.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142276/1/acn3487_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142276/2/acn3487.pd