Phase I Study of Safety and Immunogenicity of an Escherichia coli-Derived Recombinant Protective Antigen (rPA) Vaccine to Prevent Anthrax in Adults

The fatal disease caused by Bacillus anthracis is preventable with a prophylactic vaccine. The currently available anthrax vaccine requires a lengthy immunization schedule, and simpler and more immunogenic options for protection against anthrax are a priority for development. In this report we describe a phase I clinical trial testing the safety and immunogenicity of an anthrax vaccine using recombinant Escherichia coli-derived, B. anthracis protective antigen (rPA).A total of 73 healthy adults ages 18-40 were enrolled and 67 received 2 injections separated by 4 weeks of either buffered saline placebo, or rPA formulated with or without 704 µg/ml Alhydrogel® adjuvant in increasing doses (5, 25, 50, 100 µg) of rPA. Participants were followed for one year and safety and immunologic data were assessed. Tenderness and warmth were the most common post-injection site reactions. No serious adverse events related to the vaccine were observed. The most robust humoral immune responses were observed in subjects receiving 50 µg of rPA formulated with Alhydrogel® with a geometric mean concentration of anti-rPA IgG antibodies of 283 µg/ml and a toxin neutralizing geometric 50% reciprocal geometric mean titer of 1061. The highest lymphoproliferative peak cellular response (median Lymphocyte Stimulation Index of 29) was observed in the group receiving 25 µg Alhydrogel®-formulated rPA.The vaccine was safe, well tolerated and stimulated a robust humoral and cellular response after two doses.ClinicalTrials.gov NCT00057525

Modes of Aβ toxicity in Alzheimer’s disease

Alzheimer’s disease (AD) is reaching epidemic proportions, yet a cure is not yet available. While the genetic causes of the rare familial inherited forms of AD are understood, the causes of the sporadic forms of the disease are not. Histopathologically, these two forms of AD are indistinguishable: they are characterized by amyloid-β (Aβ) peptide-containing amyloid plaques and tau-containing neurofibrillary tangles. In this review we compare AD to frontotemporal dementia (FTD), a subset of which is characterized by tau deposition in the absence of overt plaques. A host of transgenic animal AD models have been established through the expression of human proteins with pathogenic mutations previously identified in familial AD and FTD. Determining how these mutant proteins cause disease in vivo should contribute to an understanding of the causes of the more frequent sporadic forms. We discuss the insight transgenic animal models have provided into Aβ and tau toxicity, also with regards to mitochondrial function and the crucial role tau plays in mediating Aβ toxicity. We also discuss the role of miRNAs in mediating the toxic effects of the Aβ peptide

Higher frequency of hamstring injuries in elite track and field athletes who had a previous injury to the ankle - a 17 years observational cohort study

Abstract Background Inversion injury to the ankle and hamstring injuries are common problems in most sports. It is not known whether these injuries constitute a predisposing factor or a precursor of injury or re-injury of these anatomical locations. Therefore, we wished to test the hypothesis that a previous inversion ankle injury exerted a significant effect on the chance of an athlete suffering from a subsequent ipsilateral hamstring injury and vice versa. Methods In an observational cohort study over 17 years (1998–2015), 367 elite track and field athletes, were grouped according to their first traumatic isolated ankle or hamstring injury. Fifty athletes experienced both injuries. The Mann-Whitney U and Chi-square tests (p < 0.05) were performed to test possible associations of ankle and hamstring injury with age, gender, athletics discipline, grade, and type of antecedent injury. Results Athletes with a preceding ankle injury had a statistically significantly higher chance of experiencing a subsequent hamstring injury compared with athletes who had experienced a hamstring injury as their first traumatic event (x2 = 4.245, p = 0.039). The proportion of both ankle and hamstring injury events was not statistically different between female (18%) and male (11%) athletes. Age and grade of injury did not influence the proportion of ankle and/or hamstring injury events. Conclusion There is a statistically significantly higher frequency of hamstring injuries in elite track and field athletes having experienced a previous ankle ligament injury

Scenarios of countercultural representation: an analysis of inventory books’ visualities

This article explores the social implications of the page layouts of ‘inventory books’, a series of non-fiction mass-market paperbacks published during the 1960s and 70s that employed eccentric printing strategies characterized primarily by a proliferation of imagery and nonlinear text layout and argumentation. Inventory books all use text and imagery in unique ways, appearing to include visual cultural references with connotative value that would have appealed to readers’ understandings of self and society. Drawing from scholarship from medieval, visual and literary studies, this article argues that inventory books’ visualities represented and affirmed the countercultural movements of 1960s/70s America. They did so by accentuating each individual reader’s power for meaning-making and by (figuratively and literally) turning conventional reader expectations upside-down. Not only do inventory books reflect their contexts of production, but they also serve to establish and perpetuate contemporary readers’ senses of connection with countercultural identities