This brief review will focus on a new hypothesis for the role of epigenetic mechanisms in aging-related disruptions of synaptic plasticity and memory. Epigenetics refers to a set of potentially self-perpetuating, covalent modifications of DNA and post-translational modifications of nuclear proteins that produce lasting alterations in chromatin structure. These mechanisms, in turn, result in alterations in specific patterns of gene expression. Aging-related memory decline is manifest prominently in declarative/episodic memory and working memory, memory modalities anatomically based largely in the hippocampus and prefrontal cortex, respectively. The neurobiological underpinnings of age-related memory deficits include aberrant changes in gene transcription that ultimately affect the ability of the aged brain to be “plastic”. The molecular mechanisms underlying these changes in gene transcription are not currently known, but recent work points toward a potential novel mechanism, dysregulation of epigenetic mechanisms. This has led us to hypothesize that dysregulation of epigenetic control mechanisms and aberrant epigenetic “marks” drive aging-related cognitive dysfunction. Here we focus on this theme, reviewing current knowledge concerning epigenetic molecular mechanisms, as well as recent results suggesting disruption of plasticity and memory formation during aging. Finally, several open questions will be discussed that we believe will fuel experimental discovery.

Numerous therapeutic strategies have been applied to the management of patients with inhibitors to factors VIII or IX. Different treatment approaches are analysed including prothrombin complex concentrates (PCCs), activated prothrombin complex concentrates (aPCCs), porcine factor VIII concentrate, inhibitor neutralization, immune tolerance therapy, immunosuppressive regimens and recombinant factor VIIa. Clinical data are reported in the analysis of several treatments. PCCs and aPCCs have gained widespread acceptance as the standard first-line approach for patients with inhibitors. The aPCC AUTOPLEX T has achieved a high response rate with a low level of thrombotic events. Four case studies are presented in which AUTOPLEX T has been used successfully. Administration of platelet concentrate or, in elective surgery, waiting for inhibitor levels to decline are useful adjuncts to some treatments. The optimal treatment depends on the patient's inhibitor status--low responder (minimal or no increase in inhibitor levels upon administration of replacement clotting factor) or high responder (replacement clotting factor generates inhibitor production). A suggested algorithm for treating high-responder inhibitor patients is presented.

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In this paper, I recount my experiences teaching an undergraduate seminar on non-linear modernist narratives and discuss the ways in which such a framework makes it possible both to introduce students to trademark characteristics of modernism and to subject those elements to critique. Putting form at the center of a modernism course also provides an opening into larger issues of literary interpretation; students have an opportunity to consider critically the novelistic conventions that are defamiliarized, criticized, and skirted by modernists. Emphasis on form leads to important conversations regarding modernists' relations with other media as well, particularly visual art and popular magazines. I draw on recent studies in psychology and pedagogy to consider the ways in which modernist difficulty offers initial roadblocks for new readers, but then improves readers' engagement and memory over the long term.