Hyperelastic Membrane Actuators: Analysis of Toroidal and Helical Multifunctional Configurations.

Technologies that provide mechanical assistance are required in the medical field, such as implants that regenerate tissue through elongation and stimulation. One of the challenges is to develop actuators that combine the benefits of high axial extension at low pressures, modularity, multifunction, and load-bearing capabilities into one design while maintaining their shape and softness. Overcoming such a challenge will provide implants with enhanced capacity for mechanical assistance to induce tissue regeneration. We introduce two novel actuators (M2H) built of stacked Hyperelastic Ballooning Membrane Actuators (HBMAs) that can be realized using helical and toroidal configurations. By restraining the HBMA expansion deterministically using a semisoft exoskeleton, the actuators are endowed with axial extension and radial expansion capabilities. These actuators are thus built of modules that can be configured to different therapeutical needs and multifunctionality, to provide anatomically congruent stimulation. We present the design, fabrication, testing, and numerical and experimental validation of the M2H-HBMAs. They can axially extend up to 41% and 32% in their helical and toroidal configurations at input pressures as low as 26 and 24 kPa, respectively. If the axial extension module is used separately, its extension capacity reaches >170%. The M2H-HBMAs can perform independent and simultaneous expansion and extension motions with negligible intraluminal deformation as well as stand at least 1 kg of axial force without collapsing. The M2H-HBMAs overcome the limitations of hyperexpanding machines that show low resistance to load. We envisage M2H-HBMAs as promising tools to perform tissue regeneration procedures.

Deflected Versus Preshaped Soft Pneumatic Actuators: A Design and Performance Analysis Toward Reliable Soft Robots.

Soft pneumatic actuators (SPAs) are customizable and conformable devices that enable desired motions in soft robots. Interactions with the environment or handling during their fabrication could introduce defects into SPAs that affect their performance. These defects could lead to high-stress concentrations in the SPA body and heterogeneous, unrepeatable, or inconsistent expansion affecting their reliability. In this work, we aim to improve the reliability of soft robots by modeling and characterizing the performance of SPAs with widely used chamber shapes and cross-sectional geometries under variable loading conditions. We also compare their capacity to provide homogeneous, repeatable, and time-wise consistent expansion with low-stress concentrations and provide a set of principles for the design of reliable SPAs. Expansion of SPAs with Straight chambers demonstrated to be more repeatable, with an average deviation of 0.06 mm and showed more than a thousand times less stress than any other chamber types. The expansion of preshaped SPAs with helical chambers showed to be up to 500% more homogeneous and 300% more efficient than their deflected counterparts. SPAs with squared cross-sectional geometries displayed more than 1000 times more time-wise consistent expansion over their circular counterparts. We conclude that SPAs that retain less potential energy or are less affected by its effects are more reliable. We derive these results into a set of principles for the design of reliable SPAs. These principles offer solutions to make informed decisions before fabrication to mitigate the most common reliability problems for SPAs and soft robots.

Flexible and Expandable Robot for Tissue Therapies - Modeling and Design.

OBJECTIVE: Implantable technologies should be mechanically compliant with the tissue in order to maximize tissue quality and reduce inflammation during tissue reconstruction. We introduce the development of a flexible and expandable implantable robotic (FEIR) device for the regenerative elongation of tubular tissue by applying controlled and precise tension to the target tissue while minimizing the forces produced on the surrounding tissue. METHODS: We introduce a theoretical framework based on iterative beam theory static analysis for the design of an expandable robot with a flexible rack. The model takes into account the geometry and mechanics of the rack to determine a trade-off between its stiffness and capability to deliver the required tissue tension force. We empirically validate this theory on the benchtop and with biological tissue. RESULTS: We show that FEIR can apply the required therapeutical forces on the tissue while reducing the amount of force it applies to the surrounding tissues as well as reducing self-damage. CONCLUSION: The study demonstrates a method to develop robots that can change size and shape to fit their dynamic environment while maintaining the precision and delicacy necessary to manipulate tissue by traction. SIGNIFICANCE: The method is relevant to designers of implantable technologies. The robot is a precursor medical device for the treatment of Long-Gap Esophageal Atresia and Short Bowel Syndrome.

Regenerative robotics.

Congenital diseases requiring reconstruction of parts of the gastrointestinal tract, skin, or bone are a challenge to alleviate especially in rapidly growing children. Novel technologies may be the answer. This article presents the state-of-art in regenerative robotic technologies, which are technologies that assist tissues and organs to regenerate using sensing and mechanotherapeutical capabilities. It addresses the challenges in the development of such technologies, among which are autonomy and fault-tolerance for long-term therapy as well as morphological conformations and compliance of such devices to adapt to gradual changes of the tissues in vivo. The potential as medical devices for delivering therapies for tissue growth and as tools for scientific exploration of regenerative mechanisms is also discussed.

In vivo tissue regeneration with robotic implants.

Robots that reside inside the body to restore or enhance biological function have long been a staple of science fiction. Creating such robotic implants poses challenges both in signaling between the implant and the biological host, as well as in implant design. To investigate these challenges, we created a robotic implant to perform in vivo tissue regeneration via mechanostimulation. The robot is designed to induce lengthening of tubular organs, such as the esophagus and intestines, by computer-controlled application of traction forces. Esophageal testing in swine demonstrates that the applied forces can induce cell proliferation and lengthening of the organ without a reduction in diameter, while the animal is awake, mobile, and able to eat normally. Such robots can serve as research tools for studying mechanotransduction-based signaling and can also be used clinically for conditions such as long-gap esophageal atresia and short bowel syndrome.

Haptic wearables as sensory replacement, sensory augmentation and trainer - a review.

Sensory impairments decrease quality of life and can slow or hinder rehabilitation. Small, computationally powerful electronics have enabled the recent development of wearable systems aimed to improve function for individuals with sensory impairments. The purpose of this review is to synthesize current haptic wearable research for clinical applications involving sensory impairments. We define haptic wearables as untethered, ungrounded body worn devices that interact with skin directly or through clothing and can be used in natural environments outside a laboratory. Results of this review are categorized by degree of sensory impairment. Total impairment, such as in an amputee, blind, or deaf individual, involves haptics acting as sensory replacement; partial impairment, as is common in rehabilitation, involves haptics as sensory augmentation; and no impairment involves haptics as trainer. This review found that wearable haptic devices improved function for a variety of clinical applications including: rehabilitation, prosthetics, vestibular loss, osteoarthritis, vision loss and hearing loss. Future haptic wearables development should focus on clinical needs, intuitive and multimodal haptic displays, low energy demands, and biomechanical compliance for long-term usage.

Ultrasound aspect of mesenteric panniculitis. Case report.

Mesenteric panniculitis represents a cronic inflammation of the adipose tissue of the mesentery which can present sometimes with the imagistic aspect of one or multiples pseudotumors. We present the case of female patient in which mesenteric panniculitis was found accidentally during a routine abdominal ultrasound examination leading to differential diagnostics problems. Color Doppler and contrast enhancement ultrasonography were helpful for diagnosis evidencing a benign circulatory signal.

Unknown complicated celiac disease as an unexpected finding in patients investigated with capsule endoscopy for Crohn's disease. A case series.

Atypical symptoms of celiac disease may cause a late diagnosis, revealed by the onset of complications, which may inaccurately be attributed to Crohn's disease, as manifestations frequently overlap. Assessing the entire small bowel mucosa, capsule endoscopy may be an accurate procedure in these challenging situations. We present four Crohn's disease patients diagnosed with ulcerative jejunoilieitis complicating celiac disease after capsule endoscopy procedure. In three of these patients, the ulcerative jejunoileitis led in time to stricture formation, suggesting Crohn's disease. Administration of non-steroidal anti-inflammatory drugs made the diagnosis even more difficult in one case. In patients with Crohn's disease not responding to immunosuppressive or biological treatment, complicated celiac disease should be considered and capsule endoscopy should be performed for reassessing the diagnosis.

Design and evaluation of a multi-modal haptic skin stimulation apparatus.

Human grasping and manipulation are facilitated by cutaneous mechanoreceptors that provide information about contact location, pressure, and events such as making and breaking contact. A challenge in designing haptic feedback devices for the wearer of a prosthetic hand is simultaneous display of multiple types of haptic information. We present the preliminary design and evaluation of an apparatus for relaying multi-modal haptic information. The apparatus moves a set of contact points tangentially over the skin at a controlled speed, with controlled normal force. We apply this stimulus to an artificial skin instrumented with an embedded accelerometer, and characterize the resulting signals. Vibration frequency increases with applied normal force and tangential speed, whereas vibration amplitude increases with normal force and depends on skin properties. The results indicate that different forces and speeds can, under some conditions, be discriminated using vibration signals alone. Accurate identification of speeds is provided by series of vibration events that depend on the spatial distribution of contact points. This study motivates future work to perform human perception studies and create a wearable haptic display for prosthetics based on this concept.

High sustained virological response rate to combination therapy in genotype 1 patients with histologically mild hepatitis C.

BACKGROUND: Patients with mild hepatitis C have a significant risk of disease progression at medium- and long-term follow-up and should be considered for antiviral therapy. AIM: To evaluate the rate of sustained viral response (SVR) and predictive factors of SVR in HCV genotype 1 patients with mild hepatitis C (fibrosis stage F0/F1) treated with combination antiviral therapy. METHODS: 260 naïve patients were followed-up during 72 weeks in three referral hepatology centers between 2004 and 2006. Univariate and multivariate logistic regression analysis was conducted. RESULTS: Early virological response was 88.1% and SVR was 74.2%. In the univariate analysis, SVR was associated with young age (p=0.001), very low (< or = 400,000 IU/mL) baseline viremia (p=0.03) and high aminotransferase levels (p=0.04) and was not associated with gender, body mass index, inflammatory activity, steatosis, ribavirin and peginterferon dose changes, premature cessation of therapy. Multivariate analysis identified the following independent predictors of SVR: age <50 years (p=0.0009), viral load < or = 400,000 IU/mL (p=0.03) and aminotransferase level >2 times normal value (p=0.02). CONCLUSIONS: Genotype 1 HCV patients with mild hepatitis have a high rate of SVR, similar to genotype non-1. Young age, very low viremia and significant hepatocytolisis are independent predictors of SVR in patients with mild hepatitis.

Efficacy, tolerability and predictive factors for early and sustained virologic response in patients treated with weight-based dosing regimen of PegIFN alpha-2b ribavirin in real-life healthcare setting.

BACKGROUND AND AIM: Increasing evidence to date highlights that individualized treatment regimens with pegylated interferon (PegIFN) and ribavirin represent a better approach for patients nowadays showing negative predictive factors for sustained virological response. The aims of this study were to assess the rate of early (EVR) and sustained virological response (SVR), tolerability and baseline predictive factors associated with EVR and SVR in patients with chronic hepatitis C treated with individualized weight-based dosing regimen for both PegIFN alpha-2b and ribavirin. METHODS: The observational analysis included 234 consecutive patients with chronic hepatitis C genotype 1 treated with PegIFN alpha-2b and ribavirin on an out-patient basis between January 2003-March 2006. RESULTS: The mean age of the study group was 49.5 years, and 35% were male patients; the group was slightly overweight (mean BMI=26.5 kg/sq.m). EVR was achieved in 84.6% (198/234 patients). The end-of-treatment and sustained biochemical responses were 76.3% and 66.1%, respectively. At the end of follow-up, an overall intent-to-treat SVR was achieved by 71 of 127 patients (in 55.9%). Lower baseline (< 1,000 000 IU/mL) HCV viral load was the only predictive factor associated with EVR (p=0.04); absent or mild fibrosis (F0-1) and a low histological activity (HAI < 8) were independently associated with SVR. Side effects resulted in PegIFN and ribavirin dose reductions in 9.4% and, respectively, 18.1%, but definitive discontinuation of therapy was necessary only in 8.7% of patients. CONCLUSION: PegIFN alpha-2b and ribavirin can be safe and successful when using a weight-based dosing regimen, leading to high response rates even in overweight patients.

Effectiveness and tolerability of pegylated Interferon alpha-2a and ribavirin combination therapy in Romanian patients with chronic hepatitis C: from clinical trials to clinical practice.

BACKGROUND AND AIM: Pegylated interferon alpha in combination with ribavirin represents nowadays the gold standard therapy in patients with chronic hepatitis C. The aim of this study was to assess early (EVR) and sustained virological response (SVR), tolerability and baseline predictive factors for SVR in patients with chronic hepatitis C treated with peginterferon alpha-2a and ribavirin combination therapy in day-to-day clinical practice. METHODS: The analysis included 174 consecutive patients with chronic hepatitis C (naive, relapsers and non-responders after standard therapy) managed in two expertise gastroenterology centers in Romania, mainly on an outpatient basis. The combination therapy was initiated between 1st of June 2002 - 30th of June 2003. RESULTS: The mean age of the study population was 47 years; 41% were men, mean BMI was 26.5 kg/sq.m. Only 7.5% of them had bridging fibrosis/cirrhosis on liver biopsy. EVR and SVR were noted in 78.7% and 51.1%, respectively. Multivariate analysis showed two independent variables associated with SVR: absence of bridging fibrosis/cirrhosis and absence of hepatic steatosis. The rate and profile of side effects associated with pegylated interferon alpha-2a and ribavirin in our clinical setting were all predictable, based on previous experience in the literature. Side effects resulted in interferon and ribavirin dose reductions in 9.2% and, respectively, 25.3%, but permanent discontinuation of the combination therapy was required in only 5.74% of patients. CONCLUSION: Combination antiviral therapy can be safely and successfully used outside clinical trials. To achieve high response rates and tolerability, similar or better than those reported in clinical trials, hepatitis C patients have to be managed in expertise centers, by experienced physicians, aiming at minimizing side effects, optimizing dosing, and enhancing compliance.

Impaired health-related quality of life in Romanian patients with chronic viral hepatitis before antiviral therapy.

BACKGROUND AND AIM: Chronic hepatitis is a disabling condition leading to impairment of a patient's quality of life. We investigated the impact of chronic viral hepatitis on health-related quality of life. The relationship between transaminase level and score in the quality-of-life questionnaire was also investigated. METHODS: We studied 66 patients with chronic viral hepatitis (27 with hepatitis B, 38 with hepatitis C, 1 with hepatitis B+C; 32 men, 34 women) naive to any previous antiviral therapy. All had high levels of transaminases. Patients with chronic disease or those using drugs to modify their quality of life were discarded. The control group consisted of 36 healthy volunteers (17 men, 19 women). Both groups completed the Short Form 36 health survey, with the exception of the items concerning bodily pain. RESULTS: Significant differences between the two groups for every domain of quality of life (physical functioning, role physical, mental health, role emotional, social functioning, vitality and general health) were recorded. We found no significant correlation between the level of transaminases and any item of the health-related quality-of-life questionnaire. In hepatitis B patients, several quality-of-life scores (general health, social functioning, mental health) were better than in hepatitis C patients. CONCLUSIONS: Patients with chronic viral hepatitis not receiving antiviral therapy have an impaired quality of life as estimated by the Short Form 36 health survey.