CNS Infiltration of Peripheral Immune Cells: D-Day for Neurodegenerative Disease?

While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as “immune privilege,” it is now clear that immune responses do occur in the CNS—giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue

Cognitive Neuropsychology of HIV-Associated Neurocognitive Disorders

Advances in the treatment of the human immunodeficiency virus (HIV) have dramatically improved survival rates over the past 10 years, but HIV-associated neurocognitive disorders (HAND) remain highly prevalent and continue to represent a significant public health problem. This review provides an update on the nature, extent, and diagnosis of HAND. Particular emphasis is placed on critically evaluating research within the realm of cognitive neuropsychology that aims to elucidate the component processes of HAND across the domains of executive functions, motor skills, speeded information processing, episodic memory, attention/working memory, language, and visuoperception. In addition to clarifying the cognitive mechanisms of HAND (e.g., impaired cognitive control), the cognitive neuropsychology approach may enhance the ecological validity of neuroAIDS research and inform the development of much needed novel, targeted cognitive and behavioral therapies

Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes

Identity metamorphoses in digital disruption: a relational theory of identity

Digital technologies have disrupted a variety of organizations; however, Information Systems research has yet to explore in-depth why this may be occurring or the implications of this process for those involved. In this paper we present an exemplary case of digital technology disruption in a newspaper company - an organization in the midst of an identity crisis. On the basis of ethnographic data, we explore the changes that resulted from the introduction of the digital medium, and how this has led to the evolution of the newspaper, as well as the metamorphosis of identities of the company, the company's practitioners, and the consumers of the company's content. Our findings suggest that shifts in the evolutionary trajectory of an organization can be traced to the rate and nature of identity metamorphoses among its key actors. Hence, in order to navigate and adapt to digital disruptions, we argue that an ongoing strategic renegotiation of the identities of all the actors involved is not only possible, but is required for an organization's survival. In doing so, we provide a relational theory of identity

Predictors of change in suicidal ideation across treatment phases of major depressive disorder: analysis of the STAR*D data

The effects of common antidepressants on suicidal ideation (SI) is unclear. In the landmark STAR*D trial antidepressants were effective for Major Depressive Disorder (MDD) in early treatment phases, but less effective in later phases. The effects of antidepressants on SI across the entire sample of the STAR*D trial has never been investigated. We performed a secondary analysis of the STAR*D data with the primary outcome of change in score on the suicide item (item three) of the Hamilton Rating Scale for Depression (HRSD17) across all four study levels. We used descriptive statistics and logistic regression analyses. Pearson correlation was used for change in SI versus change in depression (HRSD16). Reduction in mean (SD) SI was greater in levels one: 0.29 (±0.78) (p < 0.001) and two: 0.26 (±0.88) (p < 0.001) than in levels three: 0.16 (±0.92) (p = 0.005) and four: 0.18 (±0.93) (p = 0.094). A history of past suicide attempts (OR 1.72, p = 0.007), comorbid medical illness (OR 2.23, p = 0.005), and a family history of drug abuse (OR 1.69, p = 0.008) were correlated with worsening of SI across level one. Treatment with bupropion (OR 0.24, p < 0.001) or buspirone (OR 0.24, p = 0.001) were correlated with lowering of SI across level two. Improvement in SI was correlated with improvement in overall depression (HRSD16) at level one: r(3756) = 0.48; level two: r(1027) = 0.38; level three: r(249) = 0.31; and level four: r(75) = 0.42 (p < 0.001 for all levels). Improvement in SI is limited with pharmacotherapy in patients with treatment-resistant depression. Treatments with known anti-suicidal effects in MDD, such as ECT, should be considered in these patients