Multisession, noninvasive closed-loop neuroprosthetic control of grasping by upper limb amputees.

Upper limb amputation results in a severe reduction in the quality of life of affected individuals due to their inability to easily perform activities of daily living. Brain-machine interfaces (BMIs) that translate grasping intent from the brain's neural activity into prosthetic control may increase the level of natural control currently available in myoelectric prostheses. Current BMI techniques demonstrate accurate arm position and single degree-of-freedom grasp control but are invasive and require daily recalibration. In this study we tested if transradial amputees (A1 and A2) could control grasp preshaping in a prosthetic device using a noninvasive electroencephalography (EEG)-based closed-loop BMI system. Participants attempted to grasp presented objects by controlling two grasping synergies, in 12 sessions performed over 5 weeks. Prior to closed-loop control, the first six sessions included a decoder calibration phase using action observation by the participants; thereafter, the decoder was fixed to examine neuroprosthetic performance in the absence of decoder recalibration. Ability of participants to control the prosthetic was measured by the success rate of grasping; ie, the percentage of trials within a session in which presented objects were successfully grasped. Participant A1 maintained a steady success rate (63±3%) across sessions (significantly above chance [41±5%] for 11 sessions). Participant A2, who was under the influence of pharmacological treatment for depression, hormone imbalance, pain management (for phantom pain as well as shoulder joint inflammation), and drug dependence, achieved a success rate of 32±2% across sessions (significantly above chance [27±5%] in only two sessions). EEG signal quality was stable across sessions, but the decoders created during the first six sessions showed variation, indicating EEG features relevant to decoding at a smaller timescale (100ms) may not be stable. Overall, our results show that (a) an EEG-based BMI for grasping is a feasible strategy for further investigation of prosthetic control by amputees, and (b) factors that may affect brain activity such as medication need further examination to improve accuracy and stability of BMI performance.

Liposome-encapsulated EF24-HPßCD inclusion complex: a preformulation study and biodistribution in a rat model.

3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a "drug-in-CD-in liposome" approach. An aqueous solution of EF24 and hydroxypropyl-ß-cyclodextrin (HPßCD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze-thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HPßCD mixture provided k(1:1) value of 9.9 M(-1). The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HPßCD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 ± 2.6 nm) by dehydration-rehydration technique. With extrusion technique, the size of 177 ± 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 µM dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an α-t(1/2) of 21.4 min and ß-t(1/2) of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using "drug-in-CD-in liposome" approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

Magnetic resonance spectroscopy for evaluation of liposome-encapsulated hemoglobin as a resuscitation fluid.

Liposome-encapsulated hemoglobin (LEH) based on a novel, synthetic, non-phospholipid was developed, and evaluated for cerebral energy metabolism in a 40% hemorrhage rat model. The markers of tissue energetics were monitored by (1)H- and (31)P-magnetic resonance spectroscopy (MRS). After hemorrhage, (1)H-MRS showed an increase in the levels of lactate and pyruvate. These markers returned to baseline values following LEH resuscitation. Both LEH and saline were able to exert a neuron-protective effect as indicated by the recovery of N-acetylaspartate. (31)P MRS showed a fall in phosphocreatine after hemorrhage, which upon LEH or saline resuscitation returned to the baseline values. Similarly, inorganic phosphate increased after bleeding, but returned to normal after resuscitation. LEH resuscitation also recovered beta-ATP levels, but saline resuscitation provided only a modest recovery. The results indicate the utility of MRS to monitor cerebral metabolism in hemorrhage/resuscitation. The data is also supportive of the new LEH formulation as an oxygen carrier.