Sleep disturbance is common in critically ill patients up to 12 months after hospital discharge. Both subjective and objective studies, however, suggest that sleep disturbance improves over time. More research is needed to understand and optimize sleep in recovery from critical illness.
Neurons in primary visual cortex (V1) are more resilient than those in dorsolateral prefrontal cortex (dlPFC) in aging, schizophrenia and Alzheimer’s disease. The current study compared glutamate and neuromodulatory actions in macaque V1 to those in dlPFC, and found striking regional differences. V1 neuronal firing to visual stimuli depended on AMPA receptors, with subtle NMDA receptor contributions, while dlPFC depends primarily on NMDA receptors. Neuromodulatory actions also differed between regions. In V1, cAMP signaling increased neuronal firing, and the phosphodiesterase PDE4A was positioned to regulate cAMP effects on glutamate release from axons. HCN channels in V1 were classically located on distal dendrites, and enhanced cell firing. These data contrast with dlPFC, where PDE4A and HCN channels are concentrated in thin spines, and cAMP-HCN signaling gates inputs and weakens firing. These regional differences may explain why V1 neurons are more resilient than dlPFC neurons to the challenges of age and disease.
BackgroundIn medical intensive care unit (MICU) patients, the predictors of post-discharge sleep disturbance and functional disability are poorly understood. ICU delirium is a risk factor with a plausible link to sleep disturbance and disability. This study evaluated the prevalence of self-reported post-ICU sleep disturbance and increased functional disability, and their association with MICU delirium and other ICU factors.MethodsThis was an observational cohort study of MICU patients enrolled in a biorepository and assessed upon MICU admission by demographics, comorbidities, and baseline characteristics. Delirium was assessed daily using the Confusion Assessment Method for the ICU. Telephone follow-up interview instruments occurred after hospital discharge and included the Pittsburgh Sleep Quality Index (PSQI), and basic and instrumental activities of daily living (BADLs, IADLs) for disability. We define sleep disturbance as a PSQI score > 5 and increased disability as an increase in composite BADL/IADL score at follow-up relative to baseline. Multivariable regression modeled the associations of delirium and other MICU factors on follow-up PSQI scores and change in disability scores.ResultsPSQI and BADL/IADL instruments were completed by 112 and 122 participants, respectively, at mean 147 days after hospital discharge. Of those surveyed, 63% had sleep disturbance by PSQI criteria, and 37% had increased disability by BADL/IADL scores compared to their pre-MICU baseline. Total days of MICU delirium (p = 0.013), younger age (p = 0.013), and preexisting depression (p = 0.025) were significantly associated with higher PSQI scores at follow-up. Lower baseline disability (p < 0.001), older age (p = 0.048), and less time to follow-up (p = 0.024) were significantly associated with worsening post-ICU disability, while the occurrence of MICU delirium showed a trend toward association (p = 0.077).ConclusionsAfter adjusting for important covariates, total days of MICU delirium were significantly associated with increased post-discharge sleep disturbance. Delirium incidence showed a trend toward association with increased functional disability in the year following discharge.
Ductal carcinoma in situ (DCIS) is a premalignant condition, whose incidence is increasing in the current era of widespread screening mammography. While eminently treatable, there are innumerable controversies that surround this disease in terms of its diagnosis and treatment. We discuss these issues and review the data to date regarding this condition which affects roughly 20 per cent of all patients presenting with breast cancer.
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