ABSTRACT
Background: Aortic mural thrombus is a rare acute aortic syndrome that can present with embolism to a distal organ. No guidelines or randomized evidence exist to guide therapy for patients with aortic mural thrombus. Cardiac and cerebral embolism is a particularly unusual presentation of aortic thrombus but has significant implications for patient management. Case summary: We present an unusual case of a young patient with simultaneous embolization of aortic thrombus to the coronary and cerebral vasculature, causing cerebral infarcts and a myocardial infarction. He presented with chest pain, slurred speech, right homonymous hemianopia, and inferior ST-elevation on electrocardiogram (ECG). Bedside echocardiography identified an inferoseptal regional wall motion abnormality. Emergent computerised tomography (CT) brain and aorta showed acute cerebral infarcts and aortic mural thrombus. He was managed medically with anticoagulation and discharged without disability after a period of rehabilitation. Discussion: This case demonstrates the value of careful clinical assessment in the setting of ST-elevation prior to transferring a patient for invasive angiography, as well as highlighting the role of echocardiography and CT imaging in the diagnosis of acute aortic syndromes. We describe the various management options for aortic mural thrombus, the role of multi-disciplinary decision-making, and our rationale for selecting a strategy of anticoagulation.
ABSTRACT
Sleep disconnects animals from the external world, at considerable risks and costs that must be offset by a vital benefit. Insight into this mysterious benefit will come from understanding sleep homeostasis: to monitor sleep need, an internal bookkeeper must track physiological changes that are linked to the core function of sleep. In Drosophila, a crucial component of the machinery for sleep homeostasis is a cluster of neurons innervating the dorsal fan-shaped body (dFB) of the central complex. Artificial activation of these cells induces sleep, whereas reductions in excitability cause insomnia. dFB neurons in sleep-deprived flies tend to be electrically active, with high input resistances and long membrane time constants, while neurons in rested flies tend to be electrically silent. Correlative evidence thus supports the simple view that homeostatic sleep control works by switching sleep-promoting neurons between active and quiescent states. Here we demonstrate state switching by dFB neurons, identify dopamine as a neuromodulator that operates the switch, and delineate the switching mechanism. Arousing dopamine caused transient hyperpolarization of dFB neurons within tens of milliseconds and lasting excitability suppression within minutes. Both effects were transduced by Dop1R2 receptors and mediated by potassium conductances. The switch to electrical silence involved the downregulation of voltage-gated A-type currents carried by Shaker and Shab, and the upregulation of voltage-independent leak currents through a two-pore-domain potassium channel that we term Sandman. Sandman is encoded by the CG8713 gene and translocates to the plasma membrane in response to dopamine. dFB-restricted interference with the expression of Shaker or Sandman decreased or increased sleep, respectively, by slowing the repetitive discharge of dFB neurons in the ON state or blocking their entry into the OFF state. Biophysical changes in a small population of neurons are thus linked to the control of sleep-wake state.
