A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report

Background: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in humans included in the group of Transmissible Spongiform Encephalopathies or prion diseases. The vast majority of sCJD cases are molecularly classified according to the abnormal prion protein (PrPSc) conformations along with polymorphism of codon 129 of the PRNP gene. Recently, a novel human disease, termed "protease-sensitive prionopathy", has been described. This disease shows a distinct clinical and neuropathological phenotype and it is associated to an abnormal prion protein more sensitive to protease digestion. Case presentation: We report the case of a 75-year-old-man who developed a clinical course and presented pathologic lesions compatible with sporadic Creutzfeldt-Jakob disease, and biochemical findings reminiscent of "protease-sensitive prionopathy". Neuropathological examinations revealed spongiform change mainly affecting the cerebral cortex, putamen/globus pallidus and thalamus, accompanied by mild astrocytosis and microgliosis, with slight involvement of the cerebellum. Confluent vacuoles were absent. Diffuse synaptic PrP deposits in these regions were largely removed following proteinase treatment. PrP deposition, as revealed with 3F4 and 1E4 antibodies, was markedly sensitive to pre-treatment with proteinase K. Molecular analysis of PrPSc showed an abnormal prion protein more sensitive to proteinase K digestion, with a five-band pattern of 28, 24, 21, 19, and 16 kDa, and three aglycosylated isoforms of 19, 16 and 6 kDa. This PrPSc was estimated to be 80% susceptible to digestion while the pathogenic prion protein associated with classical forms of sporadic Creutzfeldt-Jakob disease were only 2% (type VV2) and 23% (type MM1) susceptible. No mutations in the PRNP gene were found and genotype for codon 129 was heterozygous methionine/valine. Conclusions: A novel form of human disease with abnormal prion protein sensitive to protease and MV at codon 129 was described. Although clinical signs were compatible with sporadic Creutzfeldt-Jakob disease, the molecular subtype with the abnormal prion protein isoforms showing enhanced protease sensitivity was reminiscent of the "protease-sensitive prionopathy". It remains to be established whether the differences found between the latter and this case are due to the polymorphism at codon 129. Different degrees of proteinase K susceptibility were easily determined with the chemical polymer detection system which could help to detect proteinase-susceptible pathologic prion protein in diseases other than the classical ones.

Toward a measure of social-ecological resilience for human communities

The purpose of this essay is to clarify the theoretical understanding of the concept of resilience in order to explore problems surrounding the empirical measurement and application of the concept, as well as to examine strategic examples of empirical measures and policy applications in the literature of several disciplines, fields, and professions. The examination of resilience occurs in two streams: one conceptual and one methodological. At the conceptual level, the focus will be on definitions, distinctions between resilience and related concepts, and the theoretical frameworks that underlie usage of the concept. At the empirical level, the examination of resilience will be centered on the methodological challenges associated with research on resilience as well as previous attempts to operationalize and measure resilience. (PDF contains 4 pages)

The global human security index: Can disaggregations help us to forge progress?

A Human Security Index (HIS) enumerating 200 countries was introduced in 2008. A community-level HSI is under development in the USA. Coastal communities face large disparities in components of human security. How can a HSI support improved policies/services (such as environmental or public health forecasts or warnings) for improving lives? Several issues are discussed. (PDF contains 4 pages)

Oceans and human health: Sentinel habitats and sentinel species

The health of the oceans and people are inextricably linked. For many years we focused research and policy on anthropogenic impacts to oceans and coasts. Recently we have started to think about how the health of the oceans affects us. In response to the Oceans and Human Health Act of 2004, a NOAA initiative was created to explore the “One Health” of the oceans and coasts. The Center of Excellence in Oceans and Human Health at Hollings Marine Laboratory (HML) is one of three Centers dedicated to understanding the connections and forecasting changes in ocean and coastal health and human health. The Center at HML is developing new tools and approaches, including sentinel habitats and sentinel species, to evaluate linkages between ecological process and human health and wellbeing. The results provide environmental and public health managers, policy-makers and communities forecasts and assessments to improve ecosystem-based management that protects health and mitigates risks for the oceans, coasts and people.(PDF contains 4 pages)

Effects of international trade of food and feed and human diet shifts on food security and environmental safety: integrating scales

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