Challenges of neural interfaces for stroke motor rehabilitation.

More than 85% of stroke survivors suffer from different degrees of disability for the rest of their lives. They will require support that can vary from occasional to full time assistance. These conditions are also associated to an enormous economic impact for their families and health care systems. Current rehabilitation treatments have limited efficacy and their long-term effect is controversial. Here we review different challenges related to the design and development of neural interfaces for rehabilitative purposes. We analyze current bibliographic evidence of the effect of neuro-feedback in functional motor rehabilitation of stroke patients. We highlight the potential of these systems to reconnect brain and muscles. We also describe all aspects that should be taken into account to restore motor control. Our aim with this work is to help researchers designing interfaces that demonstrate and validate neuromodulation strategies to enforce a contingent and functional neural linkage between the central and the peripheral nervous system. We thus give clues to design systems that can improve or/and re-activate neuroplastic mechanisms and open a new recovery window for stroke patients.

High-sensitivity C-reactive protein in type 2 diabetic patients with and without the metabolic syndrome.

OBJECTIVE: To describe the distribution of serum high-sensitivity C-reactive protein (hsCRP) in type 2 diabetes mellitus outpatients, and relate it to cardiovascular disease risk. DESIGN: Cross-sectional descriptive study. SETTING: Kenyatta National Hospital, a tertiary referral hospital. SUBJECTS: One hundred and ninety seven type 2 diabetic outpatients and fifty age- and sex-matched non-diabetic hypertensive outpatients. RESULTS: The distribution of hsCRP in the diabetic population was skewed, with a mean of 4.33 mg/L and a median of 2.53 mg/L. The majority (42%) of diabetics had hsCRP levels in the high-risk category (hsCRP > 3 mg/L). The median hsCRP was non-significantly higher in the diabetic patients with metabolic syndrome compared to those without (2.68 vs 2.30 mg/L, p = 0.433). The median hsCRP was non-significantly higher in the hypertensive group compared to that in matched diabetic non-metabolic syndrome group (2.30 vs 2.23 mg/L, p = 0.297). HsCRP increased with number of metabolic syndrome components, patients with four components having higher hsCRP levels than those with one, though the difference was not statistically significant (3.59 vs 1.57 mg/L, p = 0.095). CONCLUSION: Our study, though cross-sectional in nature, supports the existence of a correlation between hsCRP levels and cardiovascular disease risk. The small difference in CRP levels between diabetic metabolic and non-metabolic groups underpowered the study. Cohort studies are needed to determine the predictive power of hsCRP for cardiovascular disease in our setup.

Oncogenic RIT1 mutations in lung adenocarcinoma.

Lung adenocarcinoma is comprised of distinct mutational subtypes characterized by mutually exclusive oncogenic mutations in RTK/RAS pathway members KRAS, EGFR, BRAF and ERBB2, and translocations involving ALK, RET and ROS1. Identification of these oncogenic events has transformed the treatment of lung adenocarcinoma via application of therapies targeted toward specific genetic lesions in stratified patient populations. However, such mutations have been reported in only ∼55% of lung adenocarcinoma cases in the United States, suggesting other mechanisms of malignancy are involved in the remaining cases. Here we report somatic mutations in the small GTPase gene RIT1 in ∼2% of lung adenocarcinoma cases that cluster in a hotspot near the switch II domain of the protein. RIT1 switch II domain mutations are mutually exclusive with all other known lung adenocarcinoma driver mutations. Ectopic expression of mutated RIT1 induces cellular transformation in vitro and in vivo, which can be reversed by combined PI3K and MEK inhibition. These data identify RIT1 as a driver oncogene in a specific subset of lung adenocarcinomas and suggest PI3K and MEK inhibition as a potential therapeutic strategy in RIT1-mutated tumors.

SU-E-T-627: Optimal Partial Arcs in VMAT Planning.

PURPOSE: To describe a method for producing minimal delivery time partial arc VMAT plans. METHODS: We begin with the assumption that dose quality is the primary treatment planning goal. Therefore the first step in the partial arc computation is a 180 beam equi-spaced IMRT multi-criteria optimized treatment plan, which serves as an ideal plan, along with a set of user- specified allowable deviations from this plan. This defines a set of target coverage and healthy organ sparing constraints. We then seek a partial arc plan which recovers this ideal plan but is minimal in delivery time. The search for the optimal partial arc which fulfills the hard constraints is done by wrapping a VMAT fluence map optimization/merging/simplification algorithm called VMERGE. The search is performed over all possible partial arcs, with start and end locations discretized to 20 degree increments, and respecting that the gantry cannot pass underneath the couch. This results in 169 partial arcs. For the ones that yield feasible plans, the complete VMERGE algorithm is run, which minimizes the delivery time for that arc. The minimal delivery time plan that fulfills the dosimetric requirements is returned. RESULTS: We apply the method to a lung and liver case. The time savings are as follows: (full arc time, optimal partial arc time): lung (185 s, 94 s), liver (263 s, 165 s). The optimal arc for the lung lesion, a left anterior target, is 140 degrees centered at 50 degrees. The optimal arc for the liver lesion is 160 degrees centered at -90 degrees. CONCLUSIONS: By wrapping a fast VMAT optimization/sequencing routine by an exhaustive search over 169 possible partial arcs, we are able to determine the fastest delivery partial arc. The use of partial arcs can significantly shorten delivery time in VMAT delivery. The project described was supported by Award Number R01CA103904 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the ocial views of the National Cancer Institute or the National Institutes of Health.