Developing and Evaluating a Flexible Wireless Microcoil Array Based Integrated Interface for Epidural Cortical Stimulation.

Stroke leads to serious long-term disability. Electrical epidural cortical stimulation has made significant improvements in stroke rehabilitation therapy. We developed a preliminary wireless implantable passive interface, which consists of a stimulating surface electrode, receiving coil, and single flexible passive demodulated circuit printed by flexible printed circuit (FPC) technique and output pulse voltage stimulus by inductively coupling an external circuit. The wireless implantable board was implanted in cats\u27 unilateral epidural space for electrical stimulation of the primary visual cortex (V1) while the evoked responses were recorded on the contralateral V1 using a needle electrode. The wireless implantable board output stable monophasic voltage stimuli. The amplitude of the monophasic voltage output could be adjusted by controlling the voltage of the transmitter circuit within a range of 5-20 V. In acute experiment, cortico-cortical evoked potential (CCEP) response was recorded on the contralateral V1. The amplitude of N2 in CCEP was modulated by adjusting the stimulation intensity of the wireless interface. These results demonstrated that a wireless interface based on a microcoil array can offer a valuable tool for researchers to explore electrical stimulation in research and the dura mater-electrode interface can effectively transmit electrical stimulation

PAR1 Agonists Stimulate APC-Like Endothelial Cytoprotection and Confer Resistance to Thromboinflammatory Injury

Stimulation of protease-activated receptor 1 (PAR1) on endothelium by activated protein C (APC) is protective in several animal models of disease, and APC has been used clinically in severe sepsis and wound healing. Clinical use of APC, however, is limited by its immunogenicity and its anticoagulant activity. We show that a class of small molecules termed “parmodulins” that act at the cytosolic face of PAR1 stimulates APC-like cytoprotective signaling in endothelium. Parmodulins block thrombin generation in response to inflammatory mediators and inhibit platelet accumulation on endothelium cultured under flow. Evaluation of the antithrombotic mechanism showed that parmodulins induce cytoprotective signaling through Gβγ, activating a PI3K/Akt pathway and eliciting a genetic program that includes suppression of NF-κB–mediated transcriptional activation and up-regulation of select cytoprotective transcripts. STC1 is among the up-regulated transcripts, and knockdown of stanniocalin-1 blocks the protective effects of both parmodulins and APC. Induction of this signaling pathway in vivo protects against thromboinflammatory injury in blood vessels. Small-molecule activation of endothelial cytoprotection through PAR1 represents an approach for treatment of thromboinflammatory disease and provides proof-of-principle for the strategy of targeting the cytoplasmic surface of GPCRs to achieve pathway selective signaling

Developing and Evaluating a Flexible Wireless Microcoil Array Based Integrated Interface for Epidural Cortical Stimulation

Stroke leads to serious long-term disability. Electrical epidural cortical stimulation has made significant improvements in stroke rehabilitation therapy. We developed a preliminary wireless implantable passive interface, which consists of a stimulating surface electrode, receiving coil, and single flexible passive demodulated circuit printed by flexible printed circuit (FPC) technique and output pulse voltage stimulus by inductively coupling an external circuit. The wireless implantable board was implanted in cats’ unilateral epidural space for electrical stimulation of the primary visual cortex (V1) while the evoked responses were recorded on the contralateral V1 using a needle electrode. The wireless implantable board output stable monophasic voltage stimuli. The amplitude of the monophasic voltage output could be adjusted by controlling the voltage of the transmitter circuit within a range of 5–20 V. In acute experiment, cortico-cortical evoked potential (CCEP) response was recorded on the contralateral V1. The amplitude of N2 in CCEP was modulated by adjusting the stimulation intensity of the wireless interface. These results demonstrated that a wireless interface based on a microcoil array can offer a valuable tool for researchers to explore electrical stimulation in research and the dura mater-electrode interface can effectively transmit electrical stimulation

Dependent functional status rather than age is a better predictor of adverse outcomes after excision of an infected abdominal aortic graft

OBJECTIVE: The optimal management of infected abdominal aortic grafts is complete surgical excision plus in situ or extra-anatomic revascularization in patients who can tolerate this morbid operation. In addition to using age and the presence of comorbidities for risk assessment, physicians form a global clinical impression when deciding whether to offer excision or to manage conservatively. Functional status is a distinct objective measure that can inform this decision. This study examines the relative impact of age and functional status on outcomes of infected abdominal aortic graft excision to guide surgical decision-making. METHODS: Current Procedural Terminology code 35907 was used to identify patients undergoing excision of infected abdominal aortic graft in the 2005 to 2017 American College of Surgeons - National Surgical Quality Improvement Program (NSQIP) database. Patients were stratified by the upper age quartile (75 years old) as a cutoff, and then by functional status, independent vs dependent (as defined by NSIQIP). The patients were then stratified into four groups: Younger (\u3c75)/Independent, Younger (\u3c75)/Dependent, Older (≥75)/Independent, and Older (≥75)/Dependent. Outcomes measured included 30-day mortality and major organ-system dysfunction. RESULTS: There were 814 patients who underwent infected abdominal aortic graft excision: 508 patients (62%) were Younger/Independent, 89 patients (11%) were Younger/Dependent, 176 patients (22%) were Older/Independent, and 41 patients (5%) were Older/Dependent. There was no statistically significant difference in 30-day mortality for Younger/Dependent (odds ratio [OR], 1.66; 95% confidence interval [CI], 0.90-3.09; P = .536) or Older/Independent (OR, 1.31; 95% CI, 0.78-2.19; P = .311) patients when compared with Younger/Independent patients, which suggests that neither old age nor dependent functional status by itself adversely affects mortality. However, when both factors were present, Older/Dependent patients had three times higher mortality when compared with Younger/Independent patients (41.5% vs 13.4%, respectively; OR, 3.13; 95% CI, 1.46-6.71; P = .003). Furthermore, as long as patients presented with independent functional status, old age by itself did not adversely affect major organ-system dysfunction (ORs for Older/Independent vs Younger/Independent were 0.76 [P = .454], 1.04 [P = .874], and 0.90 [P = .692] for cardiac, pulmonary, and renal complications, respectively). On the contrary, even in younger patients, dependent functional status was significantly associated with higher pulmonary complications (Younger/Dependent vs Younger/Independent: OR, 2.22; 95% CI, 1.33-3.73; P = .002) and higher rates of unplanned reoperation (OR, 2.67; 95% CI, 1.62-4.41; P \u3c .0001). CONCLUSIONS: Dependent functional status has significant association with adverse outcomes after excision of infected abdominal aortic grafts, whereas old age alone does not. Therefore, this procedure could be considered in appropriately selected elderly patients with otherwise good functional status. However, caution should be applied in dependent patients regardless of age due to the risk of pulmonary complications