Microfluidic device-fabricated spiky nano-burflower shape gold nanomaterials facilitate large biomolecule delivery into cells using infrared light pulses.

Photothermal nanoparticle-sensitised photoporation is an emerging approach, which is considered an efficient tool for the intracellular delivery of biomolecules. Nevertheless, using this method to achieve high transfection efficiency generally compromises cell viability and uneven distribution of nanoparticles results in non-uniform delivery. Here, we show that high aspect ratio gold nano-burflowers, synthesised in a microfluidic device, facilitate highly efficient small to very-large cargo delivery uniformly using infrared light pulses without sacrificing cell viability. By precisely controlling the flow rates of shaping reagent and reducing agent, high-density (24 numbers) sharply branched spikes (∼80 nm tip-to-tip length) of higher aspect ratios (∼6.5) with a small core diameter (∼45 nm) were synthesised. As produced gold burflower-shape nanoparticles are biocompatible, colloidally stable (large surface zeta potential value), and uniform in morphology with a higher plasmonic peak (max. 890 nm). Theoretical analysis revealed that spikes on the nanoparticles generate a higher electromagnetic field enhancement upon interaction with light pulses. It induces plasmonic nanobubbles in the vicinity of the cells, followed by pore formation on the membrane leading to diverse biomolecular delivery into cells. Our platform has been successfully implemented for uniform delivery of small to very large biomolecules, including siRNA (20-24 bp), plasmid DNA expressing green fluorescent protein (6.2 kbp), Cas-9 plasmid (9.3 kbp), and ß-galactosidase enzyme (465 kDa) into diverse mammalian cells with high transfection efficiency and cell viability. For very large biomolecules such as enzymes, the best results were achieved as ∼100% transfection efficiency and ∼100% cell viability in SiHa cells. Together, our findings demonstrate that the spiky gold nano-burflower shape nanoparticles manufactured in a microfluidic system exhibited excellent plasmonic behaviour and could serve as an effective tool in manipulating cell physiology.

Neuromodulation of spinal reflex pathway for the treatment of detrusor overactivity by medial plantar nerve stimulation at surface of sole of foot in patients with spinal cord injury.

Objectives: Suprasacral spinal cord lesions are prone to have neurogenic detrusor overactivity leading to urinary incontinence. Current medical management has known side-effects and often surgical managements are irreversible. Electrical stimulation to modulate spinal reflex pathway having same nerve root as urinary bladder is reported in the literature. This study aimed to reduce detrusor overactivity in patients with spinal cord injury (SCI) using surface electrical stimulation of medial plantar nerve at the sole of foot. Materials and Methods: Twenty adults with SCI having episode of at least 1 leak/day due to detrusor overactivity as diagnosed by cystometrogram (CMG), were on clean intermittent catheterization and ankle jerk was present consented for the study. Participants were asked to maintain bladder diary a week before and during 2 weeks of treatment. CMG was done on day-0 and day-14. cmcUroModul@tor®, an inhouse developed electrical stimulator was used for ½ h daily for period of 2 weeks. Patient satisfaction feedback questionnaire was taken on completion of treatment. CMG data were analyzed using Wilcoxon signed-ranked test while bladder diary was analyzed using binomial distribution. P < 0.05 was considered as statistically significant. Institutional Review Board (IRB) and ethics committee of Christian Medical College, Vellore, approved the study (CMC/IRB/11061). Results: Statistical significant improvement in maximum detrusor pressure (P = 0.03) and cystometric capacity (P = 0.04) was observed. Of 20 subjects, 18 showed improvement in bladder diary. Conclusion: Neuromodulation of medial plantar nerve at sole of foot by surface electrical stimulation is non-invasive, cost-effective, and alternative simple treatment modality for urinary incontinence due to detrusor overactivity.

Ankle dorsiflexion assist using a single sensor-based FES: Results from clinical study on patients with stroke.

Objective: Ankle foot orthosis (AFO) commonly prescribed to manage foot-drop following stroke restricts ankle mobility. Commercially available functional electrical stimulation (FES) is an expensive alternative to achieve desired dorsiflexion during swing phase of the gait cycle. An in-house cost-effective innovative solution was designed and developed to address this problem.The aim of the study was to compare spatiotemporal gait characteristics of patients with foot-drop following stroke using commercially available FES against in-house developed versatile single sensor-based FES. Material and Methods: Ten patients with cerebrovascular accident of at least 3 months duration and ambulant with/without AFO were recruited prospectively. They were trained with Device-1 (Commercial Device) and Device-2 (In-house developed, Re-Lift) for 7 h over 3 consecutive days with each device. Outcome measures included timed-up-and-go-test (TUG), six-minute-walk-test (6MWT), ten-meter-walk-test (10MWT), physiological cost index (PCI), instrumented gait analysis derived spatiotemporal parameters, and patient satisfaction feedback questionnaire. We calculated intraclass correlation between devices and median interquartile range. Statistical analysis included Wilcoxon-signed-rank-test and F-test (P < 0.05 was considered statistically significant). Bland Altman and scatter plots were plotted for both devices. Results: Intraclass correlation coefficient for 6MWT (0.96), 10MWT (0.97), TUG test (0.99), and PCI (0.88) reflected high agreement between the two devices. Scatter plot and Bland Altman plots for the outcome parameters showed good correlation between two FES devices. Patient satisfaction scores were equal for both Device-1 and Device-2. There was statistically significant change in swing phase ankle dorsiflexion. Conclusions: The study demonstrated good correlation between commercial FES and Re-Lift suggestive of the utility of low-cost FES device in clinical setting.

Gait Characteristics Following Stroke: A Prospective Crossover Study to Compare Ankle-Foot Orthosis with Functional Electrical Stimulation.

Background: Management of foot-drop following stroke can be addressed with ankle-foot orthosis (AFO) or functional electrical stimulation (FES) of the peroneal nerve. There is limited evidence regarding the efficacy of FES as a substitute for a conventional ankle-foot orthosis. Objective: The aim of this study was to compare efficacy of FES against AFO in management of foot-drop in patients following stroke. Materials and Methods: Twenty patients (ten per group) were enrolled in this prospective crossover trial. Group A patients received gait training with AFO during first week followed by training with FES during second week and vice-versa for group B. Outcome parameters following AFO/FES training included Ten-meter, Six-minute walk test and spatiotemporal gait parameters. Patient satisfaction level was assessed using feedback questionnaire. Friedman test and Wilcoxon signed-rank test were performed to compare outcomes between barefoot, AFO and FES. The P value < 0.05 was considered statistically significant. Results: Nineteen males and one female aged 45.5 ± 9.45 years were recruited. Statistically significant improvement was observed in Ten-meter and Six-minute walk tests, gait speed, Timed up and go test (TUG), stance-swing ratio and single-limb support among users of FES as compared to AFO and barefoot. There was no statistical difference observed in other gait parameters. Physiological cost index (PCI) showed trend in improvement among FES users. Patient satisfaction scores were higher for FES users. Conclusions: Quantitative and qualitative results were in favour of FES as compared to AFO and barefoot suggesting that FES can be a potential orthotic intervention in hemiplegic patients.

Validation of wearable inertial sensor-based gait analysis system for measurement of spatiotemporal parameters and lower extremity joint kinematics in sagittal plane.

Wearable inertial sensor-based motion analysis systems are promising alternatives to standard camera-based motion capture systems for the measurement of gait parameters and joint kinematics. These wearable sensors, unlike camera-based gold standard systems, find usefulness in outdoor natural environment along with confined indoor laboratory-based environment due to miniature size and wireless data transmission. This study reports validation of our developed (i-Sens) wearable motion analysis system against standard motion capture system. Gait analysis was performed at self-selected speed on non-disabled volunteers in indoor (n = 15) and outdoor (n = 8) environments. Two i-Sens units were placed at the level of knee and hip along with passive markers (for indoor study only) for simultaneous 3D motion capture using a motion capture system. Mean absolute percentage error (MAPE) was computed for spatiotemporal parameters from the i-Sens system versus the motion capture system as a true reference. Mean and standard deviation of kinematic data for a gait cycle were plotted for both systems against normative data. Joint kinematics data were analyzed to compute the root mean squared error (RMSE) and Pearson's correlation coefficient. Kinematic plots indicate a high degree of accuracy of the i-Sens system with the reference system. Excellent positive correlation was observed between the two systems in terms of hip and knee joint angles (Indoor: hip 3.98° ± 1.03°, knee 6.48° ± 1.91°, Outdoor: hip 3.94° ± 0.78°, knee 5.82° ± 0.99°) with low RMSE. Reliability characteristics (defined using standard statistical thresholds of MAPE) of stride length, cadence, walking speed in both outdoor and indoor environment were well within the "Good" category. The i-Sens system has emerged as a potentially cost-effective, valid, accurate, and reliable alternative to expensive, standard motion capture systems for gait analysis. Further clinical trials using the i-Sens system are warranted on participants across different age groups.

Neuromodulation by surface electrical stimulation of peripheral nerves for reduction of detrusor overactivity in patients with spinal cord injury: A pilot study.

OBJECTIVES: To demonstrate reduction in detrusor overactivity using surface electrical stimulation of posterior tibial nerve (PTN) or dorsal penile nerve (DPN) in patients with spinal cord injury (SCI). DESIGN: Patients with SCI with symptoms of urinary urgency/leaks, with cystometrogram (CMG) proven detrusor overactivity were recruited in this study. Ten persons with observable F-wave from tibial nerve were included in the PTN group. Five persons who had F-wave absent but preserved bulbocavernosus reflex were included in the DPN group. Stimulation was given at 20 Hz, 10-40 mA for 20 minutes/session/day for 14 consecutive days. Detrusor overactivity was recorded using CMG on days 1 and 15. SETTINGS: Rehabilitation Institute, Department of Physical Medicine and Rehabilitation, Christian Medical College and Hospital, Vellore, TN, India. PARTICIPANTS: Patients with SCI. INTERVENTIONS: Surface stimulation of peripheral nerves for reduction of detrusor overactivity. OUTCOME MEASURES: Qualitative analysis using voiding diary data and quantitative analysis using CMG data comparing pre- and post-intervention. RESULTS: P value obtained from voiding chart was 0.021 for PTN and 0.062 for DPN. P value obtained from CMG data was not significant in both groups. In one subject, treatment was extended to 4 weeks and further improvement in voiding diary was seen. CONCLUSIONS: In this pilot study of 15 patients, voiding chart data showed statistically significant improvement following PTN stimulation and trend of improvement following DPN stimulation. However, the CMG data were not statistically significant in this sample population. Further studies with larger, appropriately powered sample size would be helpful to demonstrate the associations of symptoms with CMG data. Trial registration CTRI no.; CTRI/2012/12/003234; CMCH Approval no.: CMC/IRB/6735/2008/12/18.

A palmar pressure sensor for measurement of upper limb weight bearing by the hands during transfers by paraplegics.

Paraplegic patients have to effect transfer from one seat to another by using their upper limbs. In this process the hands bear almost the entire weight of the body in at least some phases of the transfer. It is desirable to train patients, especially those who are elderly and otherwise weak, to distribute their weight so as to avoid large forces being sustained on any one hand for an extended period. It is also desirable to evaluate the effectiveness of assistive devices like lower limb FES in sharing the load on the hand. This study presents a simple and versatile method of measuring palmar hand force during transfers by paraplegic patients. It is important that this force sensor should not interfere with the grasping and stabilizing properties of the hands and should permit normal transferring. The force sensor comprises an air-filled pouch or pillow that can be placed on any surface. This pneumatic sensor feels like upholstery padding on the surface on which it is placed. The sensor integrates the total pressure applied to the surface of the pouch, thereby obtaining the total force exerted by the palm/hand. The fabrication of the sensor is described, as well as the associated measurement circuit. The static calibration shows that the sensor is linear up to 350 N and the dynamic calibration shows that it has a bandwidth of 13 Hz. The sensor was fabricated using an inflated inelastic airbag attached to a pressure transducer. An automatic offset correction circuit in the preamplifier module ensures that any offset due to initial pressure or sensor drift is removed and the output is zero under no load condition. The key to this sensor arrangement is the ease of fitting it into the intended location without disturbing the existing arrangement for the subject's activities of daily living (ADL).