Design, Fabrication, and Testing of a Capsule With Hybrid Locomotion for Gastrointestinal Tract Exploration

Abstract—This paper describes a novel solution for the active lo-comotion of a miniaturized endoscopic capsule in the gastrointesti-nal (GI) tract. The authors present the design, development, and testing of a wireless endocapsule with hybrid locomotion, where hybrid locomotion is defined as the combination between internal actuation mechanisms and external magnetic dragging. The cap-sule incorporates an internal actuating legged mechanism, which modifies the capsule profile, and small permanent magnets, which interact with an external magnetic field, thus imparting a dragging motion to the device. The legged mechanism is actuated whenever the capsule gets lodged in collapsed areas of the GI tract. This allows modification of the capsule profile and enables magnetic dragging to become feasible and effective once again. A key com-ponent of the endoscopic pill is the internal mechanism, endowed with a miniaturized brushless motor and featuring compact design, and adequate mechanical performance. The internal mechanism is able to generate a substantial force, which allows the legs to open against the intestinal tissue that has collapsed around the capsule body. An accurate simulation of the performance of the minia-turized motor under magnetic fields was carried out in order to define the best configuration of the internal permanent magnets (which are located very close to the motor) and the best tradeoff operating distance for the external magnet, which is responsible for magnetically dragging the capsule. Finally, a hybrid capsule was developed generating 3.8 N at the tip of the legged mechanism and a magnetic link force up to 135 mN. The hybrid capsule and its wireless control were extensively tested in vitro, ex vivo, and in vivo, thus confirming fulfilment of the design specifications and demon-strating a good ability to manage collapsed areas of the intestinal tract. Index Terms—Capsule endoscopy, endoscopic capsule, magnetic locomotion, robotic surgery. I

Magnetically Activated Stereoscopic Vision System for Laparoendoscopic Single-Site Surgery

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Discovery of novel mutations in the dihydropyrimidine dehydrogenase gene associated with toxicity of fluoropyrimidines and viewpoint on preemptive pharmacogenetic screening in patients

Background: Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme of the metabolic pathway of 5-fluorouracil (5-FU) and other fluoropyrimidines to inactive compounds. For this reason, severe, life-threatening toxicities may occur in patients with deficient DPD activity when administered standard doses of 5-FU and its prodrugs. Materials and methods: We selected three patients with colorectal adenocarcinoma who displayed unexpected severe adverse reactions after treatment with 5-FU and capecitabine. To investigate the possible involvement of deficient variants of the DPD gene (DPYD), a denaturing HPLC (dHPLC) approach followed by target exon sequencing of DPYD was performed on DNA extracted from peripheral blood. Results: Three novel non-synonymous mutations of DPYD, c.2509-2510insC, c.1801G>C, and c.680G>A, were detected in these subjects. Due to the absence of other deficient variants of DPYD and the compatibility of adverse reactions with fluoropyrimidine treatment, the novel variants were associated with a poor-metabolizer phenotype. Conclusions: Stratification of patients on the basis of their genotype may help prevent toxicity, and the large body of evidence about the pathogenesis of fluoropyrimidine-induced adverse reactions strongly encourages the adoption of best practice recommendations to appropriately address this important clinical issue. This approach is of utmost importance within a preventive, prognostic, and personalized approach to patient care in the oncology setting

Efficacy and safety of venous angioplasty of the extracranial veins for multiple sclerosis. Brave Dreams Study (Brain Venous Drainage Exploited Against Multiple Sclerosis): study protocol for a randomized controlled trial.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with a disabling progressive course. Chronic cerebrospinal venous insufficiency (CCSVI) has recently been described as a vascular condition characterized by restricted venous outflow from the brain, mainly due to blockages of the internal jugular and azygos veins. Despite a wide variability among studies, it has been found to be associated with MS. Data from a few small case series suggest possible improvement of the clinical course and quality of life by performing percutaneous balloon angioplasty (PTA) of the stenotic veins.Study design and methodsThis is a multicenter, randomized, parallel group, blinded, sham-controlled trial to assess the efficacy and safety of PTA. Participants with relapsing remitting MS or secondary progressive MS and a sonographic diagnosis of CCSVI will be enrolled after providing their informed consent. Each participant will be centrally randomized to receive catheter venography and PTA or catheter venography and sham PTA. Two primary end points with respect to efficacy at 12 months are (1) a combined end point obtained through the integration of five functional indicators, walking, balance, manual dexterity, bladder control, and visual acuity, objectively measured by instruments; and (2) number of new brain lesions measured by T2-weighted MRI sequences. Secondary end points include annual relapse rate, change in Expanded Disability Status Scale score, proportion of patients with zero, one or two, or more than two relapses; fatigue; anxiety and depression; general cognitive state; memory/attention/calculus; impact of bladder incontinence; and adverse events. Six hundred seventy-nine patients will be recruited. The follow-up is scheduled at 12 months. Patients, treating neurologists, trained outcome assessors, and the statistician in charge of data analysis will be masked to the assigned treatment. DISCUSSION: The study will provide an answer regarding the efficacy of PTA on patients' functional disability in balance, motor, sensory, visual and bladder function, cognitive status, and emotional status, which are meaningful clinical outcomes, beyond investigating the effects on inflammation. In fact, an important part of patients' expectations, sustained and amplified by anecdotal data, has to do precisely with these functional aspects.Trial registrationClinicaltrials.gov NCT01371760

High-resolution melting analysis : a new molecular approach for the early detection of Diplodia pinea in Austrian pine

The differentiation of Diplodia pinea from closely related species, such as Diplodia scrobiculata and Diplodia seriata, and its detection in plant tissue, represented a critical issue for a long time. Molecular screening tools have recently been developed to address this topic. In this study we applied one of the most sensitive and rapid diagnostic screening method so far developed, called High-Resolution Melting Analysis (HRMA), to detect D. pinea in Austrian pine (Pinus nigra). HRMA exploits differences in the melting behaviour of PCR products to rapidly identify DNA sequence variants without the need for cumbersome post-PCR methods. We developed a HRMA method to detect specific fungal sequences in the mitochondrial small subunit ribosome gene (mt SSU rDNA). The reliability of this technique was firstly assessed on DNA extracted from pure cultures of D. pinea and closely related species. Amplicon differences were screened by HRMA and the results confirmed by direct DNA sequencing. Subsequently, HRMA was tested on DNA from symptomatic and symptomless pine shoots, and the presence of the fungus was also confirmed by both conventional and molecular quantitative approaches. The HRMA allowed the distinction of D. pinea from closely related species, showing specific melting profiles for the each pathogen. This new molecular technique, here tested in a plantefungus pathosystem for the first time, was very reliable in both symptomatic and symptomless shoots. HRMA is therefore a highly effective and accurate technique that permits the rapid screening of pathogens in the host.This work was supported by grant to Nicola Luchi from the Consorzio Interuniversitario Biotecnologie (CIB, Italy).http://www.elsevier.com/locate/funbionf201