The natural killer (NK) type of aggressive large granular lymphocytic (LGL) leukemia is a fatal illness that pursues a rapid clinical course. There are no effective therapies for this illness, and pathogenetic mechanisms remain undefined. Here we report that the survivin was highly expressed in both aggressive and chronic leukemic NK cells but not in normal NK cells. In vitro treatment of human and rat NK-LGL leukemia cells with cell-permeable, short-chain C₆-ceramide (C₆) in nanoliposomal formulation led to caspase-dependent apoptosis and diminished survivin protein expression, in a time- and dose-dependent manner. Importantly, systemic intravenous delivery of nanoliposomal ceramide induced complete remission in the syngeneic Fischer F344 rat model of aggressive NK-LGL leukemia. Therapeutic efficacy was associated with decreased expression of survivin in vivo. These data suggest that in vivo targeting of survivin through delivery of nanoliposomal C₆-ceramide may be a promising therapeutic approach for a fatal leukemia.

Post-amputation phantom limb pain (PLP) is a widespread phenomenon that can have physical, psychological, and functional impacts on amputees who experience the condition. The varying presentations and mechanisms of PLP make it difficult to effectively provide long-term pain relief. Multiple neuromodulatory approaches to treating PLP have focused on electrical stimulation of the peripheral nervous system, with varying degrees of success. More recently, research has been done to study the effects of neuroprosthetic approaches on PLP. Neuroprosthetics combine the use of a functional prosthetic with stimulation to the peripheral nerves in the residual limb. Although many of the neuroprosthetic studies focus on improving function, several have shown preliminary evidence for the reduction of severity of PLP. In this review we provide an overview of the current understanding of the neurological mechanisms that initiate and sustain PLP, as well as the neuromodulatory and neuroprosthetic approaches under development for treatment of the condition.Muscle Nerve 59:154-167, 2019

In the United States, over 1.5 million people live with lower-limb amputation. Existing prosthetic limbs do not restore somatosensory feedback from the limb, resulting in functional impairments including balance deficits and an increased risk of falls. Further, these prostheses do not alleviate the severe phantom limb pain that often follows amputation. Leveraging clinically available spinal cord stimulation electrodes, we designed a system that restores somatosensation in the missing limb, thereby improving balance and gait and reducing phantom limb pain. We show that spinal cord stimulation can evoke sensations in the missing foot and that we can control the location and intensity of those sensations. Further, by modulating stimulation intensity in real time based on signals from a wireless pressure-sensitive shoe insole, subjects exhibit improvements in functional measures of balance and gait stability. Finally, over the duration of the implant period, subjects experienced a clinically meaningful decrease in phantom limb pain. These combined results demonstrate that, with an electrode technology that is currently in widespread clinical use, our approach has the potential to become an important intervention for lower-limb amputation.

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