Search results for: carrier waveform

Authors: Anita Conti, Riccardo Ossanna, Lindsey A. Quintero, Giamaica Conti, Andrea Sbarbati

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Ischemia/reperfusion (IR) injury induces muscle fiber atrophy and skeletal muscle fiber death with subsequently functionality loss. The heterogeneous pool of cells, especially mesenchymal stem cells, contained in the stromal vascular fraction (SVF) of adipose tissue could promote muscle fiber regeneration. To prevent SVF dispersion, it has been proposed the use of injectable biopolymers that work as cells carrier. A significant element of the extracellular matrix is hyaluronic acid (HA), which has been widely used in regenerative medicine as a cell scaffold given its biocompatibility, degradability, and the possibility of chemical functionalization. Connective tissue micro-fragments enriched with SVF obtained from mechanical disaggregation of adipose tissue were evaluated for IR muscle injury regeneration using low molecular weight HA as a scaffold. IR induction. Hindlimb ischemia was induced in 9 athymic nude mice through the clamping of the right quadriceps using a plastic band. Reperfusion was induced by cutting the plastic band after 3 hours of ischemic period. Contralateral (left) muscular tissue was used as healthy control. Treatment. Twenty-four hours after the IR induction, animals (n=3) were intramuscularly injected with 100 µl of SVF mixed with HA (SVF-HA). Animals treated with 100 µl of HA (n=3) and 100 µl saline solution (n=3) were used as control. Treatment monitoring. All animals were in vivo monitored by magnetic resonance imaging (MRI) at 5, 7, 14 and 18 days post-injury (dpi). High-resolution morphological T2 weighed, quantitative T2 map and Dynamic Contrast-Enhanced (DCE) images were acquired in order to assess the regenerative potential of SVF-HA treatment. Ex vivo evaluation. After 18 days from IR induction, animals were sacrificed, and the muscles were harvested for histological examination. At 5 dpi T2 high-resolution MR images clearly reveal the presence of an extensive edematous area due to IR damage for all groups identifiable as an increase of signal intensity (SI) of muscular and surrounding tissue. At 7 dpi, animals of the SVF-HA group showed a reduction of SI, and the T2relaxation time of muscle tissue of the HA-SVF group was 29±0.5ms, comparable with the T2relaxation time of contralateral muscular tissue (30±0.7ms). These suggest a reduction of edematous overflow and swelling. The T2relaxation time at 7dpi of HA and saline groups were 84±2ms and 90±5ms, respectively, which remained elevated during the rest of the study. The evaluation of vascular regeneration showed similar results. Indeed, DCE-MRI analysis revealed a complete recovery of muscular tissue perfusion after 14 dpi for the SVF-HA group, while for the saline and HA group, controls remained in a damaged state. Finally, the histological examination of SVF-HA treated animals exhibited well-defined and organized fibers morphology with a lateralized nucleus, similar to contralateral healthy muscular tissue. On the contrary, HA and saline-treated animals presented inflammatory infiltrates, with HA slightly improving the diameter of the fibers and less degenerated tissue. Our findings show that connective tissue micro-fragments enriched with SVF induce higher muscle homeostasis and perfusion restoration in contrast to control groups.

Keywords: ischemia/reperfusion injury, regenerative medicine, resonance imaging, stromal vascular fraction

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Authors: Vijay Samuel, Tina Thekkekkara, Shoma Ganguly

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There is no reported Hanta Seoul virus infection in children in the UK so far, making it quite challenging for clinicians in diagnosing, predicting and prognosticating the outcome of the infection to patients and parents. We report a case of a ten-year-old girl who presented with pyrexia associated with headache, photophobia and abdominal pain. The family had recently acquired two pet rats six weeks ago. She appeared flushed with peri-oral pallor, coated the strawberry tongue, inflamed tonsils and bilateral cervical lymphadenopathy. Her liver and splenic edges were palpable. Investigations showed that she was thrombocytopenic with deranged renal and liver functions. An ultrasound abdomen demonstrated a mildly enlarged spleen, peripancreatic lymph node and an acalculous cholecystitis. In view of her clinical presentation, a diagnosis of leptospirosis was considered and she was commenced on intravenous benzylpenicillin. The following day she became oliguric, developed significant proteinuria and her renal function deteriorated. Following conservative management, her urine output gradually improved along with her renal function, proteinuria and thrombocytopaenia. Serology for leptospirosis and various other viruses were negative. Following discussion with the Rare and Imported Pathogens Laboratory at Porton hanta virus serology was requested and found to be strongly positive for Seoul hanta virus. Following discharge she developed palpitations, fatigue, severe headache and cognitive difficulties including memory loss and difficulties in spelling, reading and mathematics. Extensive investigations including ECG, MRI brain and CSF studies were performed and revealed no significant abnormalities. Since 2012, there have been six cases of acute kidney injury due to Hantavirus infection in the UK. Two cases were from the Humber region and were exposure to wild rats and the other four were exposed to specially bred pet fancy rats. Hanta virus infections can cause mild flu like symptoms but two clinical syndromes are associated with severe disease including haemorrhagic fever with renal syndrome, which may be associated with thrombocytopenia and Hantavirus cardiopulmonary syndrome. Neuropsychological impairments reported following hantavirus pulmonary syndrome and following Puumala virus infection have been reported. Minor white matter lesions were found in about half of the patients investigated with MRI brain. Seoul virus has a global distribution owing to the dispersal of its carrier host rats, through global trade. Several ports in the region could explain the possible establishment of Seoul virus in local populations of rats in the Yorkshire and Humber region. The risk of infection for occupationally exposed groups is 1-3% compared to 32.9% for specialist pet rat owners. The report highlight’s the importance of routinely asking about pets in the family. We hope to raise awareness of the emergence of hantavirus infection in the UK, particularly in the Yorkshire and Humber region. Clinicians should consider hantavirus infection as a potential cause of febrile illness causing renal impairment in children. Awareness of the possible neuro-cognitive sequele would help the clinicians offer appropriate information and support to children and their families. Contacting Rare and Imported Pathogens Laboratory at Porton is a useful resource for clinicians in UK when they consider unusual infections.

Keywords: Seoul hantavirus in child Porton, UK Acute kidney injury

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Authors: E. Locatelli, I. Monaco, R. C. Martin, Y. Li, R. Pini, M. Chiariello, M. Comes Franchini

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Despite the many advantages of application of nanomaterials in the field of nanomedicine, increasing concerns have been expressed on their potential adverse effects on human health. There is urgency for novel green strategies toward novel materials with enhanced biocompatibility using safe reagents. Photothermal ablation therapy, which exploits localized heat increase of a few degrees to kill cancer cells, has appeared recently as a non-invasive and highly efficient therapy against various cancer types; anyway new agents able to generate hyperthermia when irradiated are needed and must have precise biocompatibility in order to avoid damage to healthy tissues and prevent toxicity. Recently, there has been increasing interest in magnesium as a biomaterial: it is the fourth most abundant cation in the human body, and it is essential for human metabolism. However magnesium nanoparticles (Mg NPs) have had limited diffusion due to the high reduction potential of magnesium cations, which makes NPs synthesis challenging. Herein, we report the synthesis of Mg NPs and their surface functionalization for the obtainment of a stable and biocompatible nanomaterial suitable for photothermal ablation therapy against cancer. We synthesized the Mg crystals by reducing MgCl2 with metallic lithium and exploiting naphthalene as an electron carrier: the lithium–naphthalene complex acts as the real reducing agent. Firstly, the nanocrystal particles were coated with the ligand 12-ethoxy ester dodecanehydroxamic acid, and then entrapped into water-dispersible polymeric micelles (PMs) made of the FDA-approved PLGA-b-PEG-COOH copolymer using the oil-in-water emulsion technique. Lately, we developed a more straightforward methodology by introducing chitosan, a highly biocompatible natural product, at the beginning of the process, simultaneously using lithium–naphthalene complex, thus having a one-pot procedure for the formation and surface modification of MgNPs. The obtained MgNPs were purified and fully characterized, showing diameters in the range of 50-300 nm. Notably, when coated with chitosan the particles remained stable as dry powder for more than 10 months. We proved the possibility of generating a temperature rise of a few to several degrees once MgNPs were illuminated using a 810 nm diode laser operating in continuous wave mode: the temperature rise resulted significant (0-15 °C) and concentration dependent. We then investigated potential cytotoxicity of the MgNPs: we used HN13 epithelial cells, derived from a head and neck squamous cell carcinoma and the hepa1-6 cell line, derived from hepatocellular carcinoma and very low toxicity was observed for both nanosystems. Finally, in vivo photothermal therapy was performed on xenograft hepa1-6 tumor bearing mice: the animals were treated with MgNPs coated with chitosan and showed no sign of suffering after the injection. After 12 hours the tumor was exposed to near-infrared laser light. The results clearly showed an extensive damage to tumor tissue after only 2 minutes of laser irradiation at 3Wcm-1, while no damage was reported when the tumor was treated with the laser and saline alone in control group. Despite the lower photothermal efficiency of Mg with respect to Au NPs, we consider MgNPs a promising, safe and green candidate for future clinical translations.

Keywords: chitosan, magnesium nanoparticles, nanomedicine, photothermal therapy

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Authors: Michael Sonne Kristensen, Frank Loesche, James Foster, Elif Ozcan, Judy Edworthy

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Auditory alarms play an integral role in intensive care nurses’ daily work. Most medical devices in the intensive care unit (ICU) are designed to produce alarm sounds in order to make nurses aware of immediate or prospective safety risks. The utilisation of sound as a carrier of crucial patient information is highly dependent on nurses’ presence - both physically and mentally. For ICU nurses, especially the ones who work with stationary alarm devices at the patient bed space, it is a challenge to display ‘appropriate’ alarm responses at all times as they have to navigate with great flexibility in a complex work environment. While being primarily responsible for a small number of allocated patients they are often required to engage with other nurses’ patients, relatives, and colleagues at different locations inside and outside the unit. This work explores the social strategies used by a team of nurses to comprehend and react to the information conveyed by the alarms in the ICU. Two main research questions guide the study: To what extent do alarms from a patient bed space reach the relevant responsible nurse by direct auditory exposure? By which means do responsible nurses get informed about their patients’ alarms when not directly exposed to the alarms? A comprehensive video-ethnographic field study was carried out to capture and evaluate alarm-related events in an ICU. The study involved close collaboration with four nurses who wore eye-level cameras and ear-level binaural audio recorders during several work shifts. At all time the entire unit was monitored by multiple video and audio recorders. From a data set of hundreds of hours of recorded material information about the nurses’ location, social interaction, and alarm exposure at any point in time was coded in a multi-channel replay-interface. The data shows that responsible nurses’ direct exposure and awareness of the alarms of their allocated patients vary significantly depending on work load, social relationships, and the location of the patient’s bed space. Distributed listening is deliberately employed by the nursing team as a social strategy to respond adequately to alarms, but the patterns of information flow prompted by alarm-related events are not uniform. Auditory Spatiotemporal Trajectory (AST) is proposed as a methodological label to designate the integration of temporal, spatial and auditory load information. As a mixed-method metrics it provides tangible evidence of how nurses’ individual alarm-related experiences differ from one another and from stationary points in the ICU. Furthermore, it is used to demonstrate how alarm-related information reaches the individual nurse through principles of social and distributed cognition, and how that information relates to the actual alarm event. Thereby it bridges a long-standing gap in the literature on medical alarm utilisation between, on the one hand, initiatives to measure objective data of the medical sound environment without consideration for any human experience, and, on the other hand, initiatives to study subjective experiences of the medical sound environment without detailed evidence of the objective characteristics of the environment.

Keywords: auditory spatiotemporal trajectory, medical alarms, social cognition, video-ethography

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Authors: Meena Agrawal, Chaitanya P. Agrawal

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The power systems are transforming and becoming smarter with innovations in technologies to enable embark simultaneously upon the sustainable energy needs, rising environmental concerns, economic benefits and quality requirements. The advantages provided by inter-connection of renewable energy resources are becoming more viable and dependable with the smart controlling technologies. The limitation of most renewable resources have their diversity and intermittency causing problems in power quality, grid stability, reliability, security etc. is being cured by these efforts. A necessitate of optimal energy management by intelligent Micro-Grids at the distribution end of the power system has been accredited to accommodate sustainable renewable Distributed Energy Resources on large scale across the power grid. All over the world Smart Grids are emerging now as foremost concern infrastructure upgrade programs. The hardware setup includes NI cRIO 9022, Compact Reconfigurable Input Output microcontroller board connected to the PC on a LAN router with three hardware modules. The Real-Time Embedded Controller is reconfigurable controller device consisting of an embedded real-time processor controller for communication and processing, a reconfigurable chassis housing the user-programmable FPGA, Eight hot-swappable I/O modules, and graphical LabVIEW system design software. It has been employed for signal analysis, controls and acquisition and logging of the renewable sources with the LabVIEW Real-Time applications. The employed cRIO chassis controls the timing for the module and handles communication with the PC over the USB, Ethernet, or 802.11 Wi-Fi buses. It combines modular I/O, real-time processing, and NI LabVIEW programmable. In the presented setup, the Analog Input Module NI 9205 five channels have been used for input analog voltage signals from renewable energy sources and NI 9227 four channels have been used for input analog current signals of the renewable sources. For switching actions based on the programming logic developed in software, a module having Electromechanical Relays (single-pole single throw) with 4-Channels, electrically isolated and LED indicating the state of that channel have been used for isolating the renewable Sources on fault occurrence, which is decided by the logic in the program. The module for Ethernet based Data Acquisition Interface ENET 9163 Ethernet Carrier, which is connected on the LAN Router for data acquisition from a remote source over Ethernet also has the module NI 9229 installed. The LabVIEW platform has been employed for efficient data acquisition, monitoring and control. Control logic utilized in program for operation of the hardware switching Related to Fault Relays has been portrayed as a flowchart. A communication system has been successfully developed amongst the sources and loads connected on different computers using Hypertext transfer protocol, HTTP or Ethernet Local Stacked area Network TCP/IP protocol. There are two main I/O interfacing clients controlling the operation of the switching control of the renewable energy sources over internet or intranet. The paper presents experimental results of the briefed setup for intelligent control of the micro-grid for renewable energy sources, besides the control of Micro-Grid with data acquisition and control hardware based on a microcontroller with visual program developed in LabVIEW.

Keywords: data acquisition and control, LabVIEW, microcontroller cRIO, Smart Micro-Grid

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Authors: Areti Okalidou, Paul D. Hatzigiannakoglou, Aikaterini Vatou, George Kyriafinis

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Young children are nowadays adept at using technology. Hence, computer-based auditory training programs (CBATPs) have become increasingly popular in aural rehabilitation for children with hearing loss and/or with cochlear implants (CI). Yet, their clinical utility for prognostic, diagnostic, and monitoring purposes has not been explored. The purposes of the study were: a) to develop an updated version of the auditory rehabilitation tool for Greek-speaking children with cochlear implants, b) to develop a database for behavioral responses, and c) to compare accuracy rates and reaction times in children differing in hearing status and other medical and demographic characteristics, in order to assess the tool’s clinical utility in prognosis, diagnosis, and progress monitoring. The updated version of the auditory rehabilitation tool was developed on a tablet, retaining the User-Centered Design approach and the elements of the Virtual Reality (VR) serious game. The visual stimuli were farm animals acting in simple game scenarios designed to trigger children’s responses to animal sounds, names, and relevant sentences. Based on an extended version of Erber’s auditory development model, the VR game consisted of six stages, i.e., sound detection, sound discrimination, word discrimination, identification, comprehension of words in a carrier phrase, and comprehension of sentences. A familiarization stage (learning) was set prior to the game. Children’s tactile responses were recorded as correct, false, or impulsive, following a child-dependent set up of a valid delay time after stimulus offset for valid responses. Reaction times were also recorded, and the database was in Εxcel format. The tablet version of the auditory rehabilitation tool was piloted in 22 preschool children with Νormal Ηearing (ΝΗ), which led to improvements. The study took place in clinical settings or at children’s homes. Fifteen children with CI, aged 5;7-12;3 years with post-implantation 0;11-5;1 years used the auditory rehabilitation tool. Eight children with CI were monolingual, two were bilingual and five had additional disabilities. The control groups consisted of 13 children with ΝΗ, aged 2;6-9;11 years. A comparison of both accuracy rates, as percent correct, and reaction times (in sec) was made at each stage, across hearing status, age, and also, within the CI group, based on presence of additional disability and bilingualism. Both monolingual Greek-speaking children with CI with no additional disabilities and hearing peers showed high accuracy rates at all stages, with performances falling above the 3rd quartile. However, children with normal hearing scored higher than the children with CI, especially in the detection and word discrimination tasks. The reaction time differences between the two groups decreased in language-based tasks. Results for children with CI with additional disability or bilingualism varied. Finally, older children scored higher than younger ones in both groups (CI, NH), but larger differences occurred in children with CI. The interactions between familiarization of the software, age, hearing status and demographic characteristics are discussed. Overall, the VR game is a promising tool for tracking the development of auditory skills, as it provides multi-level longitudinal empirical data. Acknowledgment: This work is part of a project that has received funding from the Research Committee of the University of Macedonia under the Basic Research 2020-21 funding programme.

Keywords: VR serious games, auditory rehabilitation, auditory training, children with cochlear implants

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Authors: Sophio Kobauri, Temur Kantaria, Nina Kulikova, David Tugushi, Ramaz Katsarava

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Polymeric nanoparticles-based drug delivery systems and therapeutics have a great potential in the treatment of a numerous diseases, due to they are characterizing the flexible properties which is giving possibility to modify their structures with a complex definition over their structures, compositions and properties. Important characteristics of the polymeric nanoparticles (PNPs) used as drug carriers are high particle’s stability, high carrier capacity, feasibility of encapsulation of both hydrophilic and hydrophobic drugs, and feasibility of variable routes of administration, including oral application and inhalation; NPs are especially effective for intracellular drug delivery since they penetrate into the cells’ interior though endocytosis. A variety of PNPs based drug delivery systems including charged and neutral, degradable and non-degradable polymers of both natural and synthetic origin have been developed. Among these huge varieties the biodegradable PNPs which can be cleared from the body after the fulfillment of their function could be considered as one of the most promising. For intracellular uptake it is highly desirable to have positively charged PNPs since they can penetrate deep into cell membranes. For long-lasting circulation of PNPs in the body it is important they have so called “stealth coatings” to protect them from the attack of immune system of the organism. One of the effective ways to render the PNPs “invisible” for immune system is their PEGylation which represent the process of pretreatment of polyethylene glycol (PEG) on the surface of PNPs. The present work deals with constructing PNPs from amino acid based biodegradable polymers – regular poly(ester amide) (PEA) composed of sebacic acid, leucine and 1,6-hexandiol (labeled as 8L6), cationic PEA composed of sebacic acid, arginine and 1,6-hexandiol (labeled as 8R6), and comb-like co-PEA composed of sebacic acid, malic acid, leucine and 1,6-hexandiol (labeled as PEG-PEA). The PNPs were fabricated using the polymer deposition/solvent displacement (nanoprecipitation) method. The regular PEA 8L6 form stable negatively charged (zeta-potential within 2-12 mV) PNPs of desired size (within 150-200 nm) in the presence of various surfactants (Tween 20, Tween 80, Brij 010, etc.). Blending the PEAs 8L6 and 8R6 gave the 130-140 nm sized positively charged PNPs having zeta-potential within +20 ÷ +28 mV depending 8L6/8R6 ratio. The PEGylating PEA PEG-PEA was synthesized by interaction of epoxy-co-PEA [8L6]0,5-[tES-L6]0,5 with mPEG-amine-2000 The stable and positively charged PNPs were fabricated using pure PEG-PEA as a surfactant. A firm anchoring of the PEG-PEA with 8L6/8R6 based PNPs (owing to a high afinity of the backbones of all three PEAs) provided good stabilization of the NPs. In vitro biocompatibility study of the new PNPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed they are biocompatible. Considering high stability and cell compatibility of the elaborated PNPs one can conclude that they are promising for subsequent therapeutic applications. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 “New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications”.

Keywords: biodegradable poly(ester amide)s, cationic poly(ester amide), pegylating poly(ester amide), nanoparticles

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