SUMMARY
Generalization of fear responses to non-threatening stimuli is a feature of anxiety disorders. It has been challenging to target maladaptive generalized memories without affecting adaptive memories. Synapse-specific long-term plasticity underlying memory involves the targeting of plasticity-related proteins (PRPs) to activated synapses. If distinct tags and PRPs are used for different forms of plasticity, one could selectively remove distinct forms of memory. Using a stimulation paradigm in which associative long-term facilitation (LTF) occurs at one input and non-associative LTF at another input to the same postsynaptic neuron in an Aplysia sensorimotor preparation, we found that each form of LTF is reversed by inhibiting distinct isoforms of protein kinase M (PKM), putative PRPs, in the postsynaptic neuron. A dominant negative atypical PKM selectively reversed associative LTF, while a dominant negative classical PKM selectively reversed non-associative LTF. While both PKMs are formed from calpain-mediated cleavage of PKCs, each form of LTF is sensitive to a distinct dominant negative calpain expressed in the postsynaptic neuron. Associative LTF is blocked by dominant negative classical calpain, while non-associative LTF is blocked by dominant negative small optic lobe (SOL) calpain. Interfering with a putative synaptic tag, the adaptor protein KIBRA, which protects the atypical PKM from degradation, selectively erases associative LTF. Thus, the activity of distinct PRPs and tags in a postsynaptic neuron contribute to the maintenance of different forms of synaptic plasticity at separate inputs allowing for selective reversal of synaptic plasticity and providing a cellular basis for developing therapeutic strategies for selectively reversing maladaptive memories.
Introduction: Detecting cognitive impairment in diverse, health disparities communities is an urgent health care priority. Methods: The Brooklyn Cognitive Impairments in Health Disparities Pilot Study investigated quantitative aspects and liking of a computerized cognitive performance assessment, Cognigram, among individuals 40 years in traditional and nontraditional primary care settings. Results: Cognigram was piloted in the Emergency Department, Family Medicine, and Geriatric Psychiatry clinics: 58 adults (23 men, 35 women), 67.9 6 9.8 years (range 43-91), completed the Cognigram and 5-item liking survey. The observed liking range was 2 to maximum score 5 (67% scored 4-5; no sex or age differences).Discussion: The Cognigram was well liked in waiting rooms of primary care settings. Assistance from a trained adult and clinic endorsement were keys to success. How the Cognigram performs in a geographically compact, population-dense global setting, such as Brooklyn with high vascular disease risk and a plethora of health disparities, is being tested.
Penile calciphylaxis, a rare manifestation of calcific uremic arteriolopathy, is infrequently reported in the literature. Surgical management has demonstrated similar outcomes as conservative management in terms of mean survival time. Therefore, the benefits of surgical intervention for this disease remain controversial. In this report, we present a case of penile calciphylaxis in a hemodialysis-dependent patient with end stage renal disease (ESRD). The interest of this case lies in the severity of illness on initial presentation, which precluded the possibility of conservative management and necessitated penectomy as a means of halting disease progression and improving patient quality of life.
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