Intraneuronal β-Amyloid Accumulation: Aging HIV-1 Human and HIV-1 Transgenic Rat Brain

The prevalence of HIV-1 associated neurocognitive disorders (HAND) is significantly greater in older, relative to younger, HIV-1 seropositive individuals; the neural pathogenesis of HAND in older HIV-1 seropositive individuals, however, remains elusive. To address this knowledge gap, abnormal protein aggregates (i.e., β-amyloid) were investigated in the brains of aging (\u3e12 months of age) HIV-1 transgenic (Tg) rats. In aging HIV-1 Tg rats, double immunohistochemistry staining revealed abnormal intraneuronal β-amyloid accumulation in the prefrontal cortex (PFC) and hippocampus, relative to F344/N control rats. Notably, in HIV-1 Tg animals, increased β-amyloid accumulation occurred in the absence of any genotypic changes in amyloid precursor protein (APP). Furthermore, no clear amyloid plaque deposition was observed in HIV-1 Tg animals. Critically, β-amyloid was co-localized with neurons in the cortex and hippocampus, supporting a potential mechanism underlying synaptic dysfunction in the HIV-1 Tg rat. Consistent with these neuropathological findings, HIV-1 Tg rats exhibited prominent alterations in the progression of temporal processing relative to control animals; temporal processing relies, at least in part, on the integrity of the PFC and hippocampus. In addition, in post-mortem HIV-1 seropositive individuals with HAND, intraneuronal β-amyloid accumulation was observed in the dorsolateral PFC and hippocampal dentate gyrus. Consistent with observations in the HIV-1 Tg rat, no amyloid plaques were found in these post-mortem HIV-1 seropositive individuals with HAND. Collectively, intraneuronal β-amyloid aggregation observed in the PFC and hippocampus of HIV-1 Tg rats supports a potential factor underlying HIV-1 associated synaptodendritic damage. Further, the HIV-1 Tg rat provides a biological system to model HAND in older HIV-1 seropositive individuals

Intraneuronal β-amyloid Accumulation: Aging HIV-1 Human and HIV-1 Transgenic Rat Brain

The prevalence of HIV-1 associated neurocognitive disorders (HAND) is significantly greater in older, relative to younger, HIV-1 seropositive individuals; the neural pathogenesis of HAND in older HIV-1 seropositive individuals, however, remains elusive. To address this knowledge gap, abnormal protein aggregates (i.e., β-amyloid) were investigated in the brains of aging (\u3e12 months of age) HIV-1 transgenic (Tg) rats. In aging HIV-1 Tg rats, double immunohistochemistry staining revealed abnormal intraneuronal β-amyloid accumulation in the prefrontal cortex (PFC) and hippocampus, relative to F344/N control rats. Notably, in HIV-1 Tg animals, increased β-amyloid accumulation occurred in the absence of any genotypic changes in amyloid precursor protein (APP). Furthermore, no clear amyloid plaque deposition was observed in HIV-1 Tg animals. Critically, β-amyloid was co-localized with neurons in the cortex and hippocampus, supporting a potential mechanism underlying synaptic dysfunction in the HIV-1 Tg rat. Consistent with these neuropathological findings, HIV-1 Tg rats exhibited prominent alterations in the progression of temporal processing relative to control animals; temporal processing relies, at least in part, on the integrity of the PFC and hippocampus. In addition, in post-mortem HIV-1 seropositive individuals with HAND, intraneuronal β-amyloid accumulation was observed in the dorsolateral PFC and hippocampal dentate gyrus. Consistent with observations in the HIV-1 Tg rat, no amyloid plaques were found in these post-mortem HIV-1 seropositive individuals with HAND. Collectively, intraneuronal β-amyloid aggregation observed in the PFC and hippocampus of HIV-1 Tg rats supports a potential factor underlying HIV-1 associated synaptodendritic damage. Further, the HIV-1 Tg rat provides a biological system to model HAND in older HIV-1 seropositive individuals

Controversies in the antiphospholipid syndrome: can we ever stop warfarin?

Patients with antiphospholipid syndrome are at increased risk for recurrent arterial and venous thrombosis and therefore benefit from long term warfarin therapy. The optimal duration of warfarin therapy after a first venous thromboembolic event is however a matter of some controversy and many questions remain unanswered. After reviewing and analysing the available evidence, we discuss some common scenarios in everyday clinical practice where treatment decisions are difficult

Modeling the Role of Boundary Spanners-in-Practice in the Nondeterministic Model of Engineering Design Activity

Boundary spanners-in-practice are individuals who inhabit more than one social world and bring overlapping place perspectives to bear on the function(s) performed within and across each world. Different from nominated boundary spanners, they are practitioners responsible for the 'translation' of each small world's perspectives thereby increasing collaboration effectiveness to permit the small worlds to work synergistically. The literature on Knowledge Management (KM) has emphasized the organizational importance of individuals performing boundary spanning roles by resolving cross-cultural and cross-organizational knowledge system conflicts helping teams pursue common goals through creation of "joint fields" - a third dimension that is co-jointly developed between the two fields or dimensions that the boundary spanner works to bridge. The Copeland and O'Connor Nondeterministic Model of Engineering Design Activity was utilized as the foundation to develop models of communication mechanics and dynamics when multiple simultaneous interactions of the single nondeterministic user model, the BSIP and two Subject Matter Experts (SMEs), engage during design activity in the Problem-Solving Space. The Problem-Solving Space defines the path through the volumes of plausible answers or 'solution spaces' that will satisfice the problem presented to the BSIP and SMEs. Further model refinement was performed to represent expertise seeking behaviors and the physical and mental models constructed by boundary spanners-in-practice during knowledge domain mapping. This was performed by mapping the three levels of communication complexity (transfer, translation and transformation) to each knowledge boundary (syntactic, semantic and pragmatic) that must be bridged during knowledge domain mapping