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Background In a recent high-profile case study, we used functional magnetic resonance imaging (fMRI) to monitor improvements in motor function related to neuroplasticity following rehabilitation for severe traumatic brain injury (TBI). The findings demonstrated that motor function improvements can occur years beyond current established limits. The current study extends the functional imaging investigation to characterize neuromodulation effects on neuroplasticity to further push the limits. Methods Canadian Soldier Captain (retired) Trevor Greene (TG) survived a severe open-TBI when attacked with an axe during a 2006 combat tour in Afghanistan. TG has since continued intensive daily rehabilitation to recover motor function, experiencing an extended plateau using conventional physical therapy. To overcome this plateau, we paired translingual neurostimulation (TLNS) with the continuing rehabilitation program. Results Combining TLNS with rehabilitation resulted in demonstrable clinical improvements along with corresponding changes in movement evoked electro-encephalography (EEG) activity. High-density magneto-encephalography (MEG) characterized cortical activation changes in corresponding beta frequency range (27 Hz). MEG activation changes corresponded with reduced interhemispheric inhibition in the post-central gyri regions together with increased right superior/middle frontal activation suggesting large scale network level changes. Conclusions The findings provide valuable insight into the potential importance of non-invasive neuromodulation to enhance neuroplasticity mechanisms for recovery beyond the perceived limits of rehabilitation.

Using a longitudinal case study design, we have tracked the recovery of motor function following severe traumatic brain injury (TBI) through a multimodal neuroimaging approach. In 2006, Canadian Soldier Captain (retired) Trevor Greene (TG) was attacked with an axe to the head while on tour in Afghanistan. TG continues intensive daily rehabilitation, which recently included the integration of physical therapy (PT) with neuromodulation using translingual neurostimulation (TLNS) to facilitate neuroplasticity. Recent findings with PT + TLNS demonstrated that recovery of motor function occurred beyond conventional time limits, currently extending past 14-years post-injury. To investigate whether PT + TLNS similarly resulted in associated cognitive function improvements, we examined event-related potentials (ERPs) with the brain vital signs framework. In parallel with motor function improvements, brain vital signs detected significant increases in basic attention (as measured by P300 response amplitude) and cognitive processing (as measured by contextual N400 response amplitude). These objective cognitive improvements corresponded with TG’s self-reported improvements, including a noteworthy and consistent reduction in ongoing symptoms of post-traumatic stress disorder (PTSD). The findings provide valuable insight into the potential importance of non-invasive neuromodulation in cognitive rehabilitation, in addition to initial indications for physical rehabilitation.

Background Despite growing evidence of a critical link between neuromodulation technologies and neuroplastic recovery, the underlying mechanisms of these technologies remain elusive. Objective To investigate physiological evidence of central nervous system (CNS) changes in humans during translingual neurostimulation (TLNS). Methods We used high-density electroencephalography (EEG) to measure changes in resting brain activity before, during, and after high frequency (HF) and low frequency (LF) TLNS. Results Wavelet power analysis around Cz and microstate analysis revealed significant changes after 20 min of stimulation compared to baseline. A secondary effect of exposure order was also identified, indicating a differential neuromodulatory influence of HF TLNS relative to LF TLNS on alpha and theta signal power. Conclusions These results further our understanding of the effects of TLNS on underlying resting brain activity, which in the long-term may contribute to the critical link between clinical effect and changes in brain activity.

Hepatocellular carcinoma (HCC) continues to be a major cause of cancer death globally, with aflatoxin B1 (AFB1) as a prevalent risk factor in low- and middle-income countries. MicroRNAs have been shown to be differentially expressed in HCC and may serve as predictive biomarkers. In this study, we analyzed tumor and non-tumor tissue from rats dosed with AFB1 (200 µg/kg BW) for 28 consecutive days that received vehicle only or AFB1 plus the chemopreventive agent CDDO-Im (30 µmol), and control animals (Johnson et al., CaPR, 2014). Total RNA was isolated from tumor or non-tumor tissue at the time of sacrifice and sequenced. MicroRNA transcriptomic analysis revealed 17 miRNAs significantly upregulated (> 5 fold) in tumors compared to non-tumor tissue. The top ten dysregulated miRNAs determined by fold change and biological significance were selected for further investigation: rno-miR- 205, 200b-3p, 182, 429, 31a-5p, 10b-5p, 141-3p, 132-3p, 802-5p. Validation of sequencing results by quantitative PCR (qPCR) confirmed the upregulation of the majority of candidate miRNAs in tumors and rno-miR-224-5p as the most dysregulated miRNA (over 400 fold). We also examined the levels of these candidates in terminal sera of the same animals by qPCR. Circulating miRs-224-5p, 182, and 122-5p were increased (> 1.5 fold) in animals diagnosed with HCC compared to untreated animals and those previously dosed with AFB1 plus CDDO-Im. Analysis of tracking of serum miR-182 by generalized estimating equations (GEE) revealed significantly increased levels (5 fold; CI: 2.17- 2.50) in animals that developed HCC. This sustained increase in serum miR-182 is seen months before any tumors or other symptoms are present, and highlights this miRNA as a potential predictive biomarker in AFB1-induced HCC. Supported by T32ES007141-31A1 and CA197222. Citation Format: Merricka C. Livingstone, Natalie M. Johnson, Bill D. Roebuck, Thomas W. Kensler, John D. Groopman. Dysregulated microRNAs in aflatoxin-induced hepatocellular carcinoma: Serum miR-182 as a potential predictive biomarker [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5401.

This paper describes medication management by elderly patients living in their own homes, and the effects of patient counselling during five domiciliary pharmacy visits on patient compliance and medication management. The 190 subjects who completed the 12-month study were randomly allocated to either an intervention group (receiving counselling on the correct use and storage of their drugs during five domiciliary visits), a control (V) group (receiving visits but no counselling), or a control (NV) group (having no contact between an initial visit and the end of the study). The patients' drug knowledge, dexterity and cognitive functioning were assessed, and patients in all three groups were well matched at baseline. At each follow-up visit, patient compliance was measured using pill counts and interviews. After the initial visit, patients in the intervention group demonstrated better compliance, better drug storage practices and a reduced tendency to hoard drugs, and required fewer GP consultations, than patients in either of the control groups. The provision of the domiciliary pharmacy service was effective in detecting drug-related problems in a potentially high risk patient group. The effectiveness of such a service may be improved by increased transfer of patient information between community pharmacists and general medical practitioners.

Surveys were undertaken to determine both the current extent of provision of non-dispensing services by community pharmacists, and pharmacists' attitudes, together with those of medical practitioners and district/practice nurses, towards the development of domiciliary and other community pharmacy services. Five out of a list of 10 professional services were available on the premises in the majority of pharmacies. Approximately 65 per cent of pharmacists undertook prescription collection and medicine delivery and 43 per cent provided domiciliary patient counselling at least once a week. Medical practitioners and nurses expressed high levels of support for the majority of the established services; the exceptions were blood pressure testing and cholesterol monitoring for both of which only 30 per cent of each group were in favour. Most pharmacists were willing, in principle, to train for and to provide a domiciliary service which would include counselling on the use and storage of medicines and the supply or fitting of appliances; support for these services was high among medical practitioners and nurses (85–88 per cent). The proportions of pharmacists who were willing, after training, to provide domiciliary management of total parenteral nutrition, pain control and chemotherapy were 68, 85 and 36 per cent, respectively, but medical practitioners and nurses generally were not in favour of these extended roles. The length of professional registration and frequency of contact with pharmacists were both factors which significantly influenced the level of support by medical practitioners but not by nurses.

The Moving-Object Detection Experiment (MODEX) of the Radarsat 2 platform will allow object motion extraction and measurement by partitioning the radar antenna into fore and aft apertures. Accurate extraction of object motion requires compensation to produce two equivalent radar channels. Calibration of MODEX signals is best accomplished by a transponder that receives and measures the signal transmitted by the satellite and uses the captured radar waveform to generate moving point-target signals with precisely known properties. We are proposing to use a computed approach to implement a synthetic target generator (STG) as a transponder for the motion calibration of Radarsat 2 MODEX. With this approach, the incoming pulses are digitized, manipulated using a fast digital signal processor (DSP) to synthesize signals simulating moving point-targets, and then converted back to analog for transmission. This paper reviews theoretical considerations for the synthesis of moving-object signals, demonstrates the concepts with simulations, and discusses implementation issues.