Individual-specific tonometry on porcine eyes

Intraocular pressure (IOP) monitoring is important in the diagnosis and management of glaucoma. The measurement of IOP is affected by corneal properties, but the effect of corneal stiffness on IOP measurement is unaccounted for in pressure measurement instruments such as the Goldmann Applanation Tonometer (GAT). A new instrumented non-invasive indentation tonometry that can measure IOPIST, a corneal stiffness-corrected intraocular pressure is developed. The inter-individual corneal variations of 12 porcine eyes ex vivo were independently characterized; and their true intraocular pressure, IOPT's, were set using a manometer before indentation using the new indentation tonometry. Analyses of the load–displacement data showed that porcine corneal stiffness varied more than five times from 0.045 to 0.253 N/mm. Analysis showed that, without individual stiffness correction, inter-individual variation of IOPGAT can vary up to 8 mm Hg from IOPT at 15 mm Hg; the error becomes larger at high IOPT. In comparison when corneal stiffness is accounted for, IOPIST has a significantly smaller error of 1.82 ± 1.70 mm Hg for IOPT between 12 and 40 mm Hg than IOPGAT. The results showed that the new tonometry successfully accounted for inter-individual variations in IOP measurement.     

The inflation response of the posterior bovine sclera

An in vitro inflation test method was developed to characterize the mechanical behavior of the bovine posterior sclera. The method used digital image correlation to provide a spatially resolved, full-field deformation map of the surface of the posterior sclera in response to controlled pressurization. A series of experiments were performed in the range of 2–6 kPa (15–45 mmHg) to characterize the load–unload displacement response at various pressure rates and the time-dependent displacement response at different applied pressures. The magnitude of the displacement was largest in the peripapillary region, mainly between the apex and the optic nerve head. Further, the results showed that bovine scleral tissue exhibited nonlinear and viscoelastic behavior characterized by a rate-dependent displacement response, hysteresis during unloading and creep. The creep rate was insensitive to the applied pressure, suggesting that the tissue can be modeled as a quasilinear viscoelastic material in the physiological pressure range of 2–6 kPa.     

Comparative study of corneal tangent elastic modulus measurement using corneal indentation device

The aim of this study is to examine the corneal tangent modulus measurement repeatability and performance of the corneal indentation device (CID). Twenty enucleated porcine eyes were measured and the eyes were pressurized using saline solution-filled manometer to 15 and 30 mmHg. Corneal tangent moduli measured using the CID were compared with those measured using high precision universal testing machine (UTM). The within-subject standard deviation (Sw), repeatability (2.77 × Sw), coefficient of variation (CV) (Sw/overall mean), and intraclass correlation coefficient (ICC) were determined. The mean corneal tangent moduli measured using UTM and CID were 0.094 ± 0.030 and 0.094 ± 0.028 MPa at 15 mmHg, and 0.207 ± 0.056 and 0.207 ± 0.055 MPa at 30 mmHg, respectively, with a difference less than 0.13%. The 95% limit of agreement was between −0.009 and 0.009 MPa. The Sw, repeatability, CV and ICC of corneal tangent moduli measured by the CID were 0.006 MPa, 0.015 MPa, 4.3% and 0.993, respectively. The results showed that the corneal tangent moduli measured by the CID are repeatable and are in good agreement with the results measured by the high precision UTM.     

Modification,crosslinking and reactive electrospinning of a thermoplastic medical polyurethane for vascular graft applications

Thermoplastic polyurethanes are used in a variety of medical devices and experimental tissue engineering scaffolds. Despite advances in polymer composition to improve their stability, the correct balance between chemical and mechanical properties is not always achieved. A model compound (MC) simulating the structure of a widely used medical polyurethane (Pellethane®) was synthesized and reacted with aliphatic and olefinic acyl chlorides to study the reaction site and conditions. After adopting the conditions to the olefinic modification of Pellethane®, processing into flat sheets, and crosslinking by thermal initiation or ultraviolet radiation, mechanical properties were determined. The modified polyurethane was additionally electrospun under ultraviolet light to produce a crosslinked tubular vascular graft prototype. Model compound studies showed reaction at the carbamide nitrogen, and the modification of Pellethane with pentenoyl chloride could be accurately controlled to up to 20% (correlation: ρ = 0.99). Successful crosslinking was confirmed by insolubility of the materials. Initiator concentrations were optimized and the crosslink densities shown to increase with increasing modification. Crosslinking of Pellethane containing an increasing number of pentenoyl groups resulted in decreases (up to 42%, p < 0.01) in the hysteresis and 44% in creep (p < 0.05), and in a significant improvement in degradation resistance in vitro. Modified Pellethane was successfully electrospun into tubular grafts and crosslinked using UV irradiation during and after spinning to render them insoluble. Prototype grafts had sufficient burst pressure (>550 mmHg), and compliances of 12.1 ± 0.8 and 6.2 ± 0.3%/100 mmHg for uncrosslinked and crosslinked samples, respectively. It is concluded that the viscoelastic properties of a standard thermoplastic polyurethane can be improved by modification and subsequent crosslinking, and that the modified material may be electrospun and initiated to yield crosslinked scaffolds. Such materials hold promise for the production of vascular and other porous scaffolds, where decreased hysteresis and creep may be required to prevent aneurismal dilation.     

Estimation of grip force using the Grip-ball dynamometer

The Grip-ball is an innovative device that has been designed to measure grip strength. The Grip-ball consists of an airtight ball that contains a pressure sensor and Bluetooth communication system. The Grip-ball can be inflated to different initial pressures, with data available continuously in real time. The aim of this study was to build a model to predict the force applied to the Grip-ball dynamometer based only on the pressure measured by the Grip-ball and its initial pressure. Forces ranging from 2 to 70 kg were applied to a hybrid version of the device for 10 different initial pressures, ranging from atmospheric pressure of 100 kPa through to 190 kPa. A model was constructed to predict applied force, with force as a function of the initial pressure and the pressure measured. The error of the model was calculated as 1.29 kg across all initial pressures and forces applied. The results of the study are comparable with the errors observed for the gold standard in grip force measurement, the Jamar dynamometer. The best results for force prediction were obtained over the range in which frailty is typically detected. The Grip-ball will now be tested using a large population in order to establish clinical norms.     

Mechanical properties of completely autologous human tissue engineered blood vessels compared to human saphenous vein and mammary artery

We have previously reported the initial clinical feasibility with our small diameter tissue engineered blood vessel (TEBV). Here we present in vitro results of the mechanical properties of the TEBVs of the first 25 patients enrolled in an arterio-venous (A-V) shunt safety trial, and compare these properties with those of risk-matched human vein and artery. TEBV average burst pressures (3490 ± 892 mmHg, n = 230) were higher than native saphenous vein (SV) (1599 ± 877 mmHg, n = 7), and not significantly different from native internal mammary artery (IMA) (3196 ± 1264 mmHg, n = 16). Suture retention strength for the TEBVs (152 ± 50 gmf) was also not significantly different than IMA (138 ± 50 gmf). Compliance for the TEBVs prior to implantation (3.4 ± 1.6%/100 mmHg) was lower than IMA (11.5 ± 3.9%/100 mmHg). By 6 months post-implant, the TEBV compliance (8.8 ± 4.2%/100 mmHg, n = 5) had increased to values comparable to IMA, and showed no evidence of dilation or aneurysm formation. With clinical time points beyond 21 months as an A–V shunt without intervention, the mechanical tests and subsequent lot release criteria reported here would seem appropriate minimum standards for clinical use of tissue engineered vessels.     

Discrete sensors distribution for accurate plantar pressure analyses

The aim of this study was to determine the distribution of discrete sensors under the footprint for accurate plantar pressure analyses. For this purpose, two different sensor layouts have been tested and compared, to determine which was the most accurate to monitor plantar pressure with wireless devices in research and/or clinical practice. Ten healthy volunteers participated in the study (age range: 23–58 years). The barycenter of pressures (BoP) determined from the plantar pressure system (W-inshoe®) was compared to the center of pressures (CoP) determined from a force platform (AMTI) in the medial-lateral (ML) and anterior-posterior (AP) directions. Then, the vertical ground reaction force (vGRF) obtained from both W-inshoe® and force platform was compared for both layouts for each subject. The BoP and vGRF determined from the plantar pressure system data showed good correlation (SCC) with those determined from the force platform data, notably for the second sensor organization (ML SCC= 0.95; AP SCC = 0.99; vGRF SCC = 0.91). The study demonstrates that an adjusted placement of removable sensors is key to accurate plantar pressure analyses. These results are promising for a plantar pressure recording outside clinical or laboratory settings, for long time monitoring, real time feedback or for whatever activity requiring a low-cost system.     

Finger beat-to-beat blood pressure responses to successive hand elevations

We investigated finger beat-to-beat blood pressure responses to a series of successive hand elevations in 14 normal volunteers. By passive elevation of the hand by 40 cm and lowering it again after a minute, calibrated hydrostatic pressure changes were induced in the finger arteries of the subjects. Three successive procedures with a 2-min interval between them were performed. Transitions between positions were completed smoothly over a 10-s period. Non-invasive beat-to-beat mean arterial pressure (MAP) in the finger arteries was measured by applying the servo-oscillometric physiograph (University of Tartu, Estonia). A good agreement between the evoked MAP changes during all the three hand elevations (?31.2, ?30.4 and ?30.0 mmHg, respectively) and the calculated hydrostatic pressure change (?31.0 mmHg) was obtained. The height difference of approximately 40 cm and rate of 4–5 cm/s can be recommended for the hand elevation test, greater postural changes and higher rates may diminish agreement between the measured blood pressure response and the corresponding hydrostatic pressure change. The applied hydrostatic test may be helpful for assessing the accuracy of beat-to-beat finger blood pressure measurement.     

Real-time pinch force estimation by surface electromyography using an artificial neural network

The palmar pinch force estimation is highly relevant not only in biomechanical studies, the analysis of sports activities, and ergonomic design analyses but also in clinical applications such as rehabilitation, in which information about muscle forces influences the physician's decisions on diagnosis and treatment. Force transducers have been used for such purposes, but they are restricted to grasping points and inevitably interfere with the human haptic sense because fingers cannot directly touch the environmental surface. We propose an estimation method of the palmar pinch force using surface electromyography (SEMG). Three myoelectric sites on the skin were selected on the basis of anatomical considerations and a Fisher discriminant analysis (FDA), and SEMG at these sites yields suitable information for pinch force estimation. An artificial neural network (ANN) was implemented to map the SEMG to the force, and its structure was optimized to avoid both under- and over-fitting problems. The resulting network was tested using SEMG signals recorded from the selected myoelectric sites of ten subjects in real time. The training time for each subject was short (approximately 96 s), and the estimation results were promising, with a normalized root mean squared error (NRMSE) of 0.081 ± 0.023 and a correlation (CORR) of 0.968 ± 0.017.     

A novel MRI compatible soft tissue indentor and fibre Bragg grating force sensor

MRI is an ideal method for non-invasive soft tissue mechanical properties investigation. This requires mechanical excitation of the body's tissues and measurement of the corresponding boundary conditions such as soft tissue deformation inside the MRI environment. However, this is technically difficult since load application and measurement of boundary conditions requires MRI compatible actuators and sensors. This paper describes a novel MRI compatible computer controlled soft tissue indentor and optical Fibre Bragg Grating (FBG) force sensor. The high acquisition rate (100 Hz) force sensor was calibrated for forces up to 15 N and demonstrated a maximum error of 0.043 N. Performance and MRI compatibility of the devices was verified using indentation tests on a silicone gel phantom and the upper arm of a volunteer. The computer controlled indentor provided a highly repeatable tissue deformation. Since the indentor and force sensor are composed of non-ferromagnetic materials, they are MRI compatible and no artefacts or temporal SNR reductions were observed. In a phantom study the mean and standard deviation of the temporal SNR levels without the indentor present were 500.18 and 207.08, respectively. With the indentor present the mean and standard deviation were 501.95 and 200.45, respectively. This computer controlled MRI compatible soft tissue indentation system with an integrated force sensor has a broad range of applications and will be used in the future for the non-invasive analysis of the mechanical properties of skeletal muscle tissue.     

Advances in hormone replacement therapy with drospirenone,a unique progestogen with aldosterone receptor antagonism

Unlike other currently available progestogens, drospirenone (DRSP) has a pharmacological profile, which closely mimics that of endogenous progesterone, most notably potent anti-aldosterone and anti-androgenic effects. Consequently, DRSP, when combined with 17β-estradiol (E2) as hormone replacement therapy (HRT), offsets E2-related water and sodium retention by blocking the mineralocorticoid receptor. This review evaluates the potential benefits offered by DRSP as the progestin component of HRT with respect to its anti-aldosterone activity, which translates into positive effects on body weight and blood pressure in clinical trials of continuous, combined E2/DRSP in post-menopausal women. In a 1-year, large-scale, randomised, controlled trial, E2 1 mg/DRSP 2 mg significantly decreased mean body weight by 1.2 kg versus baseline (P < 0.001), whereas patients receiving E2 1 mg gained weight. E2 1 mg/DRSP 2 mg also significantly lowered mean systolic blood pressure (SBP) by 9.0 mmHg from baseline (P < 0.05) versus 3.7 mmHg in the E2 1 mg group (P = 0.220) in a sub-group of hypertensive women. In addition, E2/DRSP was not associated with hyperkalaemia (potassium ≥5.5 meq/L) irrespective of concomitant use of ACE inhibitors, angiotensin II receptor antagonists or non-steroidal anti-inflammatory drugs, and co-morbid diabetes mellitus. In summary, as well as effectively treating climacteric symptoms, DRSP 2 mg combined with E2 1 mg has shown positive effects on body weight and blood pressure in clinical trials, most likely due to DRSP's anti-aldosterone properties. This combination may therefore offer an alternative therapeutic option with additional benefits beyond current HRT agents for symptomatic post-menopausal women.     

Are we estimating the adverse effects of shock-wave lithotripsy on a faulty scale?

The adverse effect of shock-wave lithotripsy (SWL) for renal stones on blood pressure is currently defined as its post-treatment increase. On the contrary, we hypothesize that even mild, unilateral renal obstruction initiates an increase in blood pressure. Then, in absence of treatment-induced injury, the stone removal should decrease the blood pressure. We derived the formula to assess the expected change in the mean arterial pressure following relief of renal obstruction without affecting the kidney functions. The predictions were well replicated in the cohort of patients with renal stone treated with parenchyma-saving open surgery, with 6.4 mmHg decrease at 3 months. On the contrary, in SWL cohort, instead of the expected 4.7 mmHg decrease, the blood pressure was unchanged. In conclusion, the absence of decrease in blood pressure is a very common adverse effect of SWL, leading to an epidemiologically significant increase in the risk of arterial vascular events.     

Microstructural characterization of vocal folds toward a strain-energy model of collagen remodeling

Collagen fibrils are believed to control the immediate deformation of soft tissues under mechanical load. Most extracellular matrix proteins remain intact during frozen sectioning, which allows them to be scanned using atomic force microscopy (AFM). Collagen fibrils are distinguishable because of their periodic roughness wavelength. In the present study, the shape and organization of collagen fibrils in dissected porcine vocal folds were quantified using nonlinear laser scanning microscopy data at the micrometer scale and AFM data at the nanometer scale. Rope-shaped collagen fibrils were observed. The geometric characteristics for the fibrils were fed into a hyperelastic model to predict the biomechanical response of the tissue. The model simulates the micrometer-scale unlocking behavior of collagen bundles when extended from their unloaded configuration. Force spectroscopy using AFM was used to estimate the stiffness of collagen fibrils (1 ± 0.5 MPa). The presence of rope-shaped fibrils is postulated to change the slope of the force–deflection response near the onset of nonlinearity. The proposed model could ultimately be used to evaluate changes in elasticity of soft tissues that result from the collagen remodeling.     

Design and validation of the Grip-ball for measurement of hand grip strength

The Grip-ball is a new dynamometer used to evaluate grip strength, as well as for use in home-based rehabilitation of the hand and forearm. The Grip-ball consists of pressure and temperature sensors and an electronic wireless communication system contained in an airtight ball. That can be inflated to different pressures. The device has advantages over standard dynamometers in that it looks like a simple ball, and can wirelessly communicate via Bluetooth to any compatible receiver, thus have potential to be used for clinical assessment and rehabilitation in a remote setting. The reliability and reproducibility of the device were assessed for the pressure sensor itself, as well as the relationship between the force applied and the pressure measured by the Grip-ball. The initial validation was performed using the pressure sensor without the ball in order to confirm the accuracy of the sensor used. A second validation study was conducted using the Grip-ball rather than just its sensor to examine the relationship between the pressure measured inside the ball and force applied. The results showed that there is a very good correlation (r = 0.997, p < 0.05) between the pressure measured by the Grip-ball sensor and that measured by a Vigorimeter, thus confirming the reliability of the sensor used in the Grip-ball. A quadratic regression equation was calculated in order to predict the force applied based on the pressure measured inside the ball, and the initial pressure to which the ball was inflated (R² = 0.97, standard error 10.9 N). Such a finding compares favourably with the variability inherent in Jamar recordings, thus indicating that the Grip-ball could be used to assess grip force. An industrial version of the Grip-ball, which is currently under development, will be able to be used for the entire range of grip force in the population.     

Microwave-processed nanocrystalline hydroxyapatite: Simultaneous enhancement of mechanical and biological properties

Despite the excellent bioactivity of hydroxyapatite (HA) ceramics, poor mechanical strength has limited the applications of these materials primarily to coatings and other non-load-bearing areas as bone grafts. Using synthesized HA nanopowder, dense compacts with grain sizes in the nanometer to micrometer range were processed via microwave sintering between 1000 and 1150 °C for 20 min. Here we demonstrate that the mechanical properties, such as compressive strength, hardness and indentation fracture toughness, of HA compacts increased with a decrease in grain size. HA with 168 ± 86 nm grain size showed the highest compressive strength of 395 ± 42 MPa, hardness of 8.4 ± 0.4 GPa and indentation fracture toughness of 1.9 ± 0.2 MPa m^1/2. To study the in vitro biological properties, HA compacts with grain size between 168 nm and 1.16 μm were assessed for in vitro bone cell–material interactions with human osteoblast cell line. Vinculin protein expression for cell attachment and bone cell proliferation using MTT assay showed that surfaces with finer grains provided better bone cell–material interactions than coarse-grained samples. Our results indicate simultaneous improvements in mechanical and biological properties in microwave sintered HA compacts with nanoscale grain size.     

Monitoring contractile dermal lymphatic activity following uniaxial mechanical loading

It is proposed that direct mechanical loading can impair dermal lymphatic function, contributing to the causal pathway of pressure ulcers. The present study aims to investigate the effects of loading on human dermal lymphatic vessels.Ten participants were recruited with ages ranging from 24 to 61 years. Participants had intradermal Indocyanine Green injections administrated between left finger digits. Fluorescence was imaged for 5 min sequences with an infra-red camera prior to lymph vessel loading, immediately after axial loading (60 mmHg) and following a recovery period. Image processing was employed to defined transient lymph packets and compare lymph function between each test phase.The results revealed that between 1-8 transient events (median = 4) occurred at baseline, with a median velocity of 8.1 mm/sec (range 4.1–20.1 mm/sec). Immediately post-loading, there was a significant (p < 0.05) reduction in velocity (median = 6.4, range 2.2–13.5 mm/sec), although the number of transient lymph packages varied between participants. During the recovery period the number (range 1–7) and velocity (recovery median = 9.6 mm/sec) of transient packets were largely restored to basal values.The present study revealed that some individuals present with impaired dermal lymphatic function immediately after uniaxial mechanical loading. More research is needed to investigate the effects of pressure and shear on lymphatic vessel patency.     

Development of a shear measurement sensor for measuring forces at human–machine interfaces

Measuring shear force is crucial for investigating the pathology and treatment of pressure ulcers. In this study, we introduced a bi-axial shear transducer based on strain gauges as a new shear sensor. The sensor consisted of aluminum and polyvinyl chloride plates placed between quadrangular aluminum plates. On the middle plate, two strain gauges were placed orthogonal to one another. The shear sensor (54 mm × 54 mm × 4.1 mm), which was validated by using standard weights, displayed high accuracy and precision (measurement range, −50 to 50 N; sensitivity, 0.3 N; linear relationship, R² = 0.9625; crosstalk error, 0.635% ± 0.031%; equipment variation, 4.183). The shear force on the interface between the human body and a stand-up wheelchair was measured during sitting or standing movements, using two mats (44.8 cm × 44.8 cm per mat) that consisted of 24 shear sensors. Shear forces on the sacrum and ischium were almost five times higher (15.5 N at last posture) than those on other sites (3.5 N on average) during experiments periods. In conclusion, the proposed shear sensor may be reliable and useful for measuring the shear force on human–machine interfaces.     

The association of health literacy and blood pressure reduction in a cohort of patients with hypertension: The heart healthy lenoir trial

ObjectiveLower health literacy is associated with poorer health outcomes. Few interventions poised to mitigate the impact of health literacy in hypertensive patients have been published. We tested if a multi-level quality improvement intervention could differentially improve Systolic Blood Pressure (SBP) more so in patients with low vs. higher health literacy.MethodsWe conducted a non-randomized prospective cohort trial of 525 patients referred with uncontrolled hypertension. Stakeholder informed and health literacy sensitive strategies were implemented at the practice and patient level. Outcomes were assessed at 0, 6, 12, 18 and 24 months.ResultsAt 12 months, the low and higher health literacy groups had statistically significant decreases in mean SBP (6.6 and 5.3 mmHg, respectively), but the between group difference was not significant (Δ 1.3 mmHg, P = 0.067). At 24 months, the low and higher health literacy groups reductions were 8.1 and 4.6 mmHg, respectively, again the between group difference was not significant (Δ 3.5 mmHg, p = 0.25).Conclusions/practice implicationsA health literacy sensitive multi-level intervention may equally lower SBP in patients with low and higher health literacy. Practical health literacy appropriate tools and methods can be implemented in primary care settings using a quality improvement approach.     

Biodegradable hybrid polymeric membranes for ocular drug delivery

Ophthalmic delivery systems such as ocular inserts are useful strategies to improve the ocular bioavailability of topically administered drugs. In the present study polyvinyl alcohol and sodium carboxymethylcellulose based ocular inserts were prepared by solution casting for sustained drug delivery of ciprofloxacin for treatment of topical infections. The polymers were esterified and the formation of ester bonds was confirmed by Fourier transform infrared spectroscopy. The inserts had a smooth structure with a surface roughness of 7.3 nm. Inserts were found to be wettable by simulated tear fluid with contact angle <45°. Mechanical testing results indicated that the tensile strength of polyvinyl alcohol–sodium carboxymethylcellulose (10:2 wt.%) inserts was up to 8.9 ± 1.9 MPa, which is adequate to resist the pressure likely to be exerted during application. In vitro drug release kinetics showed sustained release of ciprofloxacin for up to 48 h from the inserts. Sodium fluorescein-loaded inserts showed higher penetration of the dye in the posterior segment tissues of explanted goat eye balls as compared with an eye drop solution of sodium fluorescein. The inserts were non-toxic to corneal epithelial cells and showed no signs of acute ocular toxicity in in vivo studies in albino rabbits.