Search results for: minimally invasive lumbar discectomy

Authors: Siddhant Sethi, Yasuharu Takashima, Shigetaka Nakamura, Kenzo Fujimoto

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Site-directed mutagenesis is a renowned technique to introduce specific mutations in the genome. To achieve site-directed mutagenesis, many chemical and enzymatic approaches have been reported in the past like disulphite induced genome editing, CRISPR-Cas9, TALEN etc. The chemical methods are invasive whereas the enzymatic approaches are time-consuming and expensive. Most of these techniques are unusable in the cellular application due to their toxicity and other limitations. Photo-chemical cytosine deamination, introduced in 2010, is one of the major technique for enzyme-free single-point mutation of cytosine to uracil in DNA and RNA, wherein, 3-cyanovinylcarbazole nucleoside (CNVK) containing oligodeoxyribonucleotide (ODN) having CNVK at -1 position to that of target cytosine is reversibly crosslinked to target DNA strand using 366 nm and then incubated at 90ºC to accommodate deamination. This technique is superior to enzymatic methods of site-directed mutagenesis but has a disadvantage that it requires the use of high temperature for the deamination step which restricts its applicability in the in vivo applications. This study has been focused on improving the technique by reducing the temperature required for deamination. Firstly, the photo-cross-linker, CNVK has been modified by replacing cyano group attached to vinyl group with methyl ester (OMeVK), amide (NH2VK), and carboxylic acid (OHVK) to observe the acceleration in the deamination of target cytosine cross-linked to vinylcarbazole derivative. Among the derivatives, OHVK has shown 2 times acceleration in deamination reaction as compared to CNVK, while the other two derivatives have shown deceleration towards deamination reaction. The trend of rate of deamination reaction follows the same order as that of hydrophilicity of the vinylcarbazole derivatives. OHVK being most hydrophilic has shown highest acceleration while OMeVK is least hydrophilic has proven to be least active for deamination. Secondly, in the related study, the counter-base of the target cytosine, guanine has been replaced by inosine, 2-aminopurine, nebularine, and 5-nitroindole having distinct hydrogen bonding patterns with target cytosine. Among the ODNs with these counter bases, ODN with inosine has shown 12 fold acceleration towards deamination of cytosine cross-linked to CNVK at physiological conditions as compared to guanosine. Whereas, when 2-aminopurine, nebularine, and 5-nitroindole were used, no deamination reaction took place. It can be concluded that inosine has potential to be used as the counter base of target cytosine for the CNVK mediated photo-cross-linking induced deamination of cytosine. The increase in rate of deamination reaction has been attributed to pattern and number of hydrogen bonding between the cytosine and counter base. One of the important factor is presence of hydrogen bond between exo-cyclic amino group of cytosine and the counter base. These results will be useful for development of more efficient technique for site-directed mutagenesis for C → U transformations in the DNA/RNA which might be used in the living system for treatment of various genetic disorders and genome engineering for making designer and non-native proteins.

Keywords: C to U transformation, DNA editing, genome engineering, ultra-fast photo-cross-linking

Procedia PDF Downloads 210

Authors: Jing Zhang, Yvonne Reinwald, Nick Poulson, Alicia El Haj, Chung See, Mike Somekh, Melissa Mather

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Biomedical imaging of native tissue using light offers the potential to obtain excellent structural and functional information in a non-invasive manner with good temporal resolution. Image contrast can be derived from intrinsic absorption, fluorescence, or scatter, or through the use of extrinsic contrast. A major challenge in applying optical microscopy to in vivo tissue imaging is the effects of light attenuation which limits light penetration depth and achievable imaging resolution. Recently Selective Plane Illumination Microscopy (SPIM) has been used to map the 3D distribution of fluorophores dispersed in biological structures. In this approach, a focused sheet of light is used to illuminate the sample from the side to excite fluorophores within the sample of interest. Images are formed based on detection of fluorescence emission orthogonal to the illumination axis. By scanning the sample along the detection axis and acquiring a stack of images, 3D volumes can be obtained. The combination of rapid image acquisition speeds with the low photon dose to samples optical sectioning provides SPIM is an attractive approach for imaging biological samples in 3D. To date all implementations of SPIM rely on the use of fluorescence reporters be that endogenous or exogenous. This approach has the disadvantage that in the case of exogenous probes the specimens are altered from their native stage rendering them unsuitable for in vivo studies and in general fluorescence emission is weak and transient. Here we present for the first time to our knowledge a label-free implementation of SPIM that has downstream applications in the clinical setting. The experimental set up used in this work incorporates both label-free and fluorescent illumination arms in addition to a high specification camera that can be partitioned for simultaneous imaging of both fluorescent emission and scattered light from intrinsic sources of optical contrast in the sample being studied. This work first involved calibration of the imaging system and validation of the label-free method with well characterised fluorescent microbeads embedded in agarose gel. 3D constructs of mammalian cells cultured in agarose gel with varying cell concentrations were then imaged. A time course study to track cell proliferation in the 3D construct was also carried out and finally a native tissue sample was imaged. For each sample multiple images were obtained by scanning the sample along the axis of detection and 3D maps reconstructed. The results obtained validated label-free SPIM as a viable approach for imaging cells in a 3D gel construct and native tissue. This technique has the potential use in a near-patient environment that can provide results quickly and be implemented in an easy to use manner to provide more information with improved spatial resolution and depth penetration than current approaches.

Keywords: bioimaging, optics, selective plane illumination microscopy, tissue imaging

Procedia PDF Downloads 222

Authors: V. Giacometti, R. Mirabelli, V. Patera, D. Pinci, A. Sarti, A. Sciubba, G. Traini, M. Marafini

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The particle therapy (PT) is a very modern technique of non invasive radiotherapy mainly devoted to the treatment of tumours untreatable with surgery or conventional radiotherapy, because localised closely to organ at risk (OaR). Nowadays, PT is available in about 55 centres in the word and only the 20\% of them are able to treat with carbon ion beam. However, the efficiency of the ion-beam treatments is so impressive that many new centres are in construction. The interest in this powerful technology lies to the main characteristic of PT: the high irradiation precision and conformity of the dose released to the tumour with the simultaneous preservation of the adjacent healthy tissue. However, the beam interactions with the patient produce a large component of secondary particles whose additional dose has to be taken into account during the definition of the treatment planning. Despite, the largest fraction of the dose is released to the tumour volume, a non-negligible amount is deposed in other body regions, mainly due to the scattering and nuclear interactions of the neutrons within the patient body. One of the main concerns in PT treatments is the possible occurrence of secondary malignant neoplasm (SMN). While SMNs can be developed up to decades after the treatments, their incidence impacts directly life quality of the cancer survivors, in particular in pediatric patients. Dedicated Treatment Planning Systems (TPS) are used to predict the normal tissue toxicity including the risk of late complications induced by the additional dose released by secondary neutrons. However, no precise measurement of secondary neutrons flux is available, as well as their energy and angular distributions: an accurate characterization is needed in order to improve TPS and reduce safety margins. The project MONDO (MOnitor for Neutron Dose in hadrOntherapy) is devoted to the construction of a secondary neutron tracker tailored to the characterization of that secondary neutron component. The detector, based on the tracking of the recoil protons produced in double-elastic scattering interactions, is a matrix of thin scintillating fibres, arranged in layer x-y oriented. The final size of the object is 10 x 10 x 20 cm3 (squared 250µm scint. fibres, double cladding). The readout of the fibres is carried out with a dedicated SPAD Array Sensor (SBAM) realised in CMOS technology by FBK (Fondazione Bruno Kessler). The detector is under development as well as the SBAM sensor and it is expected to be fully constructed for the end of the year. MONDO will make data tacking campaigns at the TIFPA Proton Therapy Center of Trento, at the CNAO (Pavia) and at HIT (Heidelberg) with carbon ion in order to characterize the neutron component and predict the additional dose delivered on the patients with much more precision and to drastically reduce the actual safety margins. Preliminary measurements with charged particles beams and MonteCarlo FLUKA simulation will be presented.

Keywords: secondary neutrons, particle therapy, tracking detector, elastic scattering

Procedia PDF Downloads 203

Authors: S. B. R. Slagmulder

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Monitoring inspiratory effort and dynamic lung stress in patients on pressure support ventilation in the ICU is important for protecting against self inflicted lung injury (P-SILI) and diaphragm dysfunction. Strategies to address the detrimental effects of respiratory drive and effort can lead to improved patient outcomes. Two non-invasive estimation methods, occlusion pressure (Pocc) and P0.1, have been proposed for achieving lung and diaphragm protective ventilation. However, their relationship and interpretation in neuro ICU patients is not well understood. P0.1 is the airway pressure measured during a 100-millisecond occlusion of the inspiratory port. It reflects the neural drive from the respiratory centers to the diaphragm and respiratory muscles, indicating the patient's respiratory drive during the initiation of each breath. Occlusion pressure, measured during a brief inspiratory pause against a closed airway, provides information about the inspiratory muscles' strength and the system's total resistance and compliance. Research Objective: Understanding the relationship between Pocc and P0.1 in brain-injured patients can provide insights into the interpretation of these values in pressure support ventilation. This knowledge can contribute to determining extubation readiness and optimizing ventilation strategies to improve patient outcomes. The central goal is to asses a study protocol for determining the relationship between Pocc and P0.1 in brain-injured patients on pressure support ventilation and their ability to predict successful extubation. Additionally, comparing these values between brain-damaged and non-brain-damaged patients may provide valuable insights. Key Areas of Inquiry: 1. How do Pocc and P0.1 values correlate within brain injury patients undergoing pressure support ventilation? 2. To what extent can Pocc and P0.1 values serve as predictive indicators for successful extubation in patients with brain injuries? 3. What differentiates the Pocc and P0.1 values between patients with brain injuries and those without? Methodology: P0.1 and occlusion pressures are standard measurements for pressure support ventilation patients, taken by attending doctors as per protocol. We utilize electronic patient records for existing data. Unpaired T-test will be conducted to compare P0.1 and Pocc values between both study groups. Associations between P0.1 and Pocc and other study variables, such as extubation, will be explored with simple regression and correlation analysis. Depending on how the data evolve, subgroup analysis will be performed for patients with and without extubation failure. Results: While it is anticipated that neuro patients may exhibit high respiratory drive, the linkage between such elevation, quantified by P0.1, and successful extubation remains unknown The analysis will focus on determining the ability of these values to predict successful extubation and their potential impact on ventilation strategies. Conclusion: Further research is pending to fully understand the potential of these indices and their impact on mechanical ventilation in different patient populations and clinical scenarios. Understanding these relationships can aid in determining extubation readiness and tailoring ventilation strategies to improve patient outcomes in this specific patient population. Additionally, it is vital to account for the influence of sedatives, neurological scores, and BMI on respiratory drive and occlusion pressures to ensure a comprehensive analysis.

Keywords: brain damage, diaphragm dysfunction, occlusion pressure, p0.1, respiratory drive

Procedia PDF Downloads 41

Authors: Sajmina Khatun, Monika Pebam, Aravind Kumar Rengan

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Photothermal therapy, a subset of nanomedicine, takes advantage of light-absorbing agents to generate localized heat, selectively eradicating cancer cells. This innovative approach minimizes damage to healthy tissues and offers a promising avenue for targeted cancer treatment. Unlike conventional therapies, photothermal therapy harnesses the power of light to combat malignancies precisely and effectively, showcasing its potential to revolutionize cancer treatment paradigms. The combined strengths of nanomedicine and photothermal therapy signify a transformative shift toward more effective, targeted, and tolerable cancer treatments in the medical landscape. Utilizing natural products becomes instrumental in formulating diverse bioactive medications owing to their various pharmacological properties attributed to the existence of phenolic structures, triterpenoids, and similar compounds. Hyptis suaveolens, commonly known as pignut, stands as an aromatic herb within the Lamiaceae family and represents a valuable therapeutic plant. Flourishing in swamps and alongside tropical and subtropical roadsides, these noxious weeds impede the development of adjacent plants. Hyptis suaveolens ranks among the most globally distributed alien invasive species. The present investigation revealed that a versatile, biodegradable liposome nanosystem (HIL NPs), incorporating bioactive molecules from Hyptis suaveolens, exhibits effective bioavailability to cancer cells, enabling tumor ablation upon near-infrared (NIR) laser exposure. The components within the nanosystem, specifically the bioactive molecules from Hyptis, function as anticancer agents, aiding in the photothermal ablation of highly metastatic lung cancer cells. Despite being a prolific weed impeding neighboring plant growth, Hyptis suaveolens showcases therapeutic benefits through its bioactive compounds. The obtained HIL NPs, characterized as a photothermally active liposome nanosystem, demonstrate a pronounced fluorescence absorption peak in the NIR range and achieve a high photothermal conversion efficiency under NIR laser irradiation. Transmission electron microscopy (TEM) and particle size analysis reveal that HIL NPs possess a spherical shape with a size of 141 ± 30 nm. Moreover, in vitro assessments of HIL NPs against lung cancer cell lines (A549) indicate effective anticancer activity through a combined cytotoxic effect and hyperthermia. Tumor ablation is facilitated by apoptosis induced by the overexpression of ɣ-H2AX, arresting cancer cell proliferation. Consequently, the multifunctional and biodegradable nanosystem (HIL NPs), incorporating bioactive compounds from Hyptis, provides valuable perspectives for developing an innovative therapeutic strategy originating from a challenging weed. This approach holds promise for potential applications in both bioimaging and the combined use of phyto-photothermal therapy for cancer treatment.

Keywords: bioactive liposome, hyptis suaveolens, photothermal therapy, lung cancer

Procedia PDF Downloads 56

Authors: Pamela Chia, Tay Yoong Chuan

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Introduction: Severe pulmonary hypertension (PH) patients requiring non-cardiac surgery risk have increased mortality rates ranging. These patients are plagued with cardiorespiratory failure, dysrhythmias and anticoagulation potentially with concurrent sepsis and renal insufficiency, perioperative morbidity. We present a deaf-mute patient with severe idiopathic PH emergently prepared for ruptured ectopic laparotomy. Case Report: A 20 year-old female, 62kg (BMI 25 kg/m2) with severe idiopathic PH (2DE Ejection Fraction was 41%, Pulmonary Artery Systolic Pressure (PASP) 105 mmHg, Right ventricle strain and hypertrophy) and selective mutism was rushed in for emergency laparotomy after presenting to the emergency department for abdominal pain. The patient had an NYHA Class II with room air SpO2 93-95%. While awaiting lung transplant, the patient takes warfarin, Sildanefil, Macitentan and even Selexipag for rising PASP. At presentation, vital signs: BP 95/63, HR 119 SpO2 88% (room air). Despite decreasing haemoglobin 14 to 10g/dL, INR 2.59 was reversed with prothrombin concentrate, and Vitamin K. ECG revealed Right Bundle Branch Block with right ventricular strain and x-ray showed cardiomegaly, dilated Right Ventricle, Pulmonary Arteries, basal atelectasis. Arterial blood gas showed compensated metabolic acidosis pH 7.4 pCO2 32 pO2 53 HCO3 20 BE -4 SaO2 88%. The cardiothoracic surgeon concluded no role for Extracorporeal Membrane Oxygenation (ECMO). We inserted invasive arterial and central venous lines with blood transfusion via an 18G cannula before the patient underwent a midline laparotomy, haemostasis of ruptured ovarian cyst with 2.4L of clots under general anesthesia and FloTrac cardiac output monitoring. Rapid sequence induction was done with Midazolam/Propofol, remifentanil infusion, and rocuronium. The patient was maintained on Desflurane. Blood products and colloids were transfused for further 1.5L blood loss. Postoperatively, the patient was transferred to the intensive care unit and was extubated uneventfully 7hours later. The patient went home a week later. Discussion: Emergency hemostasis laparotomy in anticoagulated WHO Class I PH patient awaiting lung transplant with no ECMO backup poses tremendous stress on the deaf-mute patient and the anesthesiologist. Balancing hemodynamics avoiding hypotension while awaiting hemostasis in the presence of pulmonary arterial dilators and anticoagulation requires close titration of volatiles, which decreases RV contractility. We review the contraindicated anesthetic agents (ketamine, N2O), choice of vasopressors in hypotension to maintain Aortic-right ventricular pressure gradients and nitric oxide use perioperatively. Conclusion: Interdisciplinary communication with a deaf-mute moribund patient and anesthesia considerations pose many rare challenges worth sharing.

Keywords: pulmonary hypertension, case report, warfarin reversal, emergency surgery

Procedia PDF Downloads 183

Authors: Lazzat M. Zhamaliyeva, Nurgul A. Abenova, Gauhar S. Dilmagambetova, Ziyash Zh. Tanbetova, Moldir B. Ahmetzhanova, Tatyana P. Ostretcova, Aliya A. Yegemberdiyeva

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Introduction: There are many reasons for the weak training of family doctors in Kazakhstan: the unified national educational program is not focused on competencies, the role of a general practitioner (GP) is not clear, poor funding for the health care and education system, outdated teaching and assessment methods, inefficient management. We highlight two issues in particular. Firstly, academic teachers of family medicine (FM) in Kazakhstan do not practice as family doctors; most of them are narrow specialists (pediatricians, therapists, surgeons, etc.); they usually hold one-time consultations; clinical mentors from practical healthcare (non-academic teachers) do not have the teaching competences, and the vast majority of them are also narrow specialists. Secondly, clinical sites (polyclinics) are unprepared for general practice and do not follow the principles of family medicine; residents do not like to be in primary health care (PHC) settings due to the chaos that is happening there, as well as due to the lack of the necessary equipment for mastering and consolidating practical skills. Aim: We present the concept of the family physicians’ training office (FPTO), which is being created as a friendly learning environment for young general practitioners and for the involvement of academic teachers of family medicine in the practical work and innovative development of PHC. Methodology: In developing the conceptual framework and identifying practical activities, we drew on literature and expert input, and interviews. Results: The goal of the FPTO is to create a favorable educational and clinical environment for the development of the FM residents’ competencies, in which the residents with academic teachers and clinical mentors could understand and accept the principles of family medicine, improve clinical knowledge and skills, and gain experience in improving the quality of their practice in scientific basis. Three main areas of office activity are providing primary care to the patients, improving educational services for FM residents and other medical workers, and promoting research in PHC and innovations. The office arranges for residents to see outpatients at least 50% of the time, and teachers of FM departments at least 1/4 of their working time conduct general medical appointments next to residents. Taking into account the educational and scientific workload, the number of attached population for one GP does not exceed 500 persons. The equipment of the office allows FPTO workers to perform invasive and other manipulations without being sent to other clinics. In the office, training for residents is focused on their needs and aimed at achieving the required level of competence. International methodologies and assessment tools are adapted to local conditions and evaluated for their effectiveness and acceptability. Residents and their faculty actively conduct research in the field of family medicine. Conclusions: We propose to change the learning environment in order to create teams of like-minded people, to unite residents and teachers even more for the development of family medicine. The offices will also invest resources in developing and maintaining young doctors' interest in family medicine.

Keywords: educational environment, family medicine residents, family physicians’ training office, primary care research

Procedia PDF Downloads 103

Authors: Bissonnette Jean-François, Dossa Fabrice

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The project focuses on analyzing the spatial and temporal evolution of mangrove forest ecosystems near the city of Douala, Cameroon, in response to increasing human and environmental pressures. The selected study area, located in the Wouri River estuary, has a unique combination of economic importance, and ecological prominence. The study included valuable insights by conducting semi-structured interviews with resource operators and local officials. The thorough analysis of socio-economic data, farmer surveys, and satellite-derived information was carried out utilizing quantitative approaches in Excel and SPSS. Simultaneously, qualitative data was subjected to rigorous classification and correlation with other sources. The use of ArcGIS and CorelDraw facilitated the visual representation of the gradual changes seen in various land cover classifications. The research reveals complex processes that characterize mangrove ecosystems on Manoka and Cape Cameroon Islands. The lack of regulations in urbanization and the continuous growth of infrastructure have led to a significant increase in land conversion, causing negative impacts on natural landscapes and forests. The repeated instances of flooding and coastal erosion have further shaped landscape alterations, fostering the proliferation of water and mudflat areas. The unregulated use of mangrove resources is a significant factor in the degradation of these ecosystems. Activities including the use of wood for smoking and fishing, together with the coastal pollution resulting from the absence of waste collection, have had a significant influence. In addition, forest operators contribute to the degradation of vegetation, hence exacerbating the harmful impact of invasive species on the ecosystem. Strategic interventions are necessary to guarantee the sustainable management of these ecosystems. The proposals include advocating for sustainable wood exploitation techniques, using appropriate techniques, along with regeneration, and enforcing rules to prevent wood overexploitation. By implementing these measures, the ecological balance can be preserved, safeguarding the long-term viability of these precious ecosystems. On a conceptual level, this paper uses the framework developed by Elinor Ostrom and her colleagues to investigate the consequences of open access resources, where local actors have not been able to enforce measures to prevent overexploitation of mangrove wood resources. Governmental authorities have demonstrated limited capacity to enforce sustainable management of wood resources and have not been able to establish effective relationships with local fishing communities and with communities involved in the purchase of wood. As a result, wood resources in the mangrove areas remain largely accessible, while authorities do not monitor wood volumes extracted nor methods of exploitation. There have only been limited and punctual attempts at forest restoration with no significant consequence on mangrove forests dynamics.

Keywords: Mangroves, forest management, governance, open access resources, Cameroon

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Authors: Neerja Gupta

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Objective-Reconstruction of large cavities of the breast without contralateral symmetrisation Background- Reconstruction of breast includes a wide spectrum of procedures from displacement to regional and distant flaps. The pedicled Perforator flaps cover a wide spectrum of reconstruction surgery for all quadrants of the breast, especially in patients with comorbidities. These axial flaps singly or adjunct are based on a near constant perforator vessel, a ratio of 2:1 at its entry in a flap is good to maintain vascularity. The perforators of lateral chest wall viz LICAP, LTAP have overlapping perfurosomes without clear demarcation. LTAP is localized in the narrow zone between the lateral breast fold and anterior axillary line,2.5-3.8cm from the fold. MICAP are localized at 1-2 cm from sternum. Being 1-2mm in diameter, a Single perforator is good to maintain the flap. LICAP has a dominant perforator in 6th-11th spaces, while LTAP has higher placed dominant perforators in 4th and 5th spaces. Methodology-Six consecutive patients who underwent reconstruction of the breast with pedicled perforator flaps were retrospectively analysed. Selections of the flap was done based on the size and locations of the tumour, anticipated volume loss, willingness to undergo contralateral symmetrisation, cosmetic expectations, and finances available.3 patients underwent vertical LTAP, the distal limit of the flap being the inframammary crease. 3 patients underwent MICAP, oriented along the axis of rib, the distal limit being the anterior axillary line. Preoperative identification was done using a unidirectional hand held doppler. The flap was raised caudal to cranial, the pivot point of rotation being the vessel entry into the skin. The donor area is determined by the skin pinch. Flap harvest time was 20-25 minutes. Intra operative vascularity was assessed with dermal bleed. The patient immediate pre, post-operative and follow up pics were compared independently by two breast surgeons. Patients were given a breast Q questionnaire (licensed) for scoring. Results-The median age of six patients was 46. Each patient had a hospital stay of 24 hours. None of the patients was willing for contralateral symmetrisation. The specimen dimensions were from 8x6.8x4 cm to 19x16x9 cm. The breast volume reconstructed range was 30 percent to 45 percent. All wide excision had free margins on frozen. The mean flap dimensions were 12x5x4.5 cm. One LTAP underwent marginal necrosis and delayed wound healing due to seroma. Three patients were phyllodes, of which one was borderline, and 2 were benign on final histopathology. All other 3 patients were invasive ductal cancer and have completed their radiation. The median follow up is 7 months the satisfaction scores at median follow of 7 months are 90 for physical wellbeing and 85 for surgical results. Surgeons scored fair to good in Harvard score. Conclusion- Pedicled perforator flaps are a valuable option for 3/8th volume of breast defects. LTAP is preferred for tumours at the Central, upper, and outer quadrants of the breast and MICAP for the inner and lower quadrant. The vascularity of the flap is dependent on the angiosomalterritories; adequate venous and cavity drainage.

Keywords: breast, oncoplasty, pedicled, perforator

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Authors: Aurora Sheehy, Caitlin Prince

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Within current orthodox medical protocols, trauma and mental health issues are deemed to reside within the realm of cognitive or psychological therapists and are marginalised in these areas, in part due to limited drugs option available, mostly manipulating neurotransmitters or sedating patients to reduce symptoms. By contrast, this research presents examples from the clinical practice of how trauma can be assessed and treated physiologically. Adverse Childhood Experiences (ACEs) are a tally of different types of abuse and neglect. It has been used as a measurable and reliable predictor of the likelihood of the development of autoimmune disease. It is a direct way to demonstrate reliably the health impact of traumatic life experiences. A second assessment tool is Allostatic Load, which refers to the cumulative effects that chronic stress has on mental and physical health. It records the decline of an individual’s physiological capacity to cope with their experience. It uses a specific grouping of serum testing and physical measures. It includes an assessment of neuroendocrine, cardiovascular, immune and metabolic systems. Allostatic load demonstrates the health impact that trauma has throughout the body. It forms part of an initial intake assessment in clinical practice and could also be used in research to evaluate treatment. Examining medicinal plants for their physiological, neurological and somatic effects through the lens of Polyvagal theory offers new opportunities for trauma treatments. In situations where Polyvagal theory recommends activities and exercises to enable parasympathetic activation, many herbs that affect Effector Memory T (TEM) cells also enact these responses. Traditional or Indigenous European herbs show the potential to support the polyvagal tone, through multiple mechanisms. As the ventral vagal nerve reaches almost every major organ, plants that have actions on these tissues can be understood via their polyvagal actions, such as monoterpenes as agents to improve respiratory vagal tone, cyanogenic glycosides to reset polyvagal tone, volatile oils rich in phenyl methyl esters improve both sympathetic and parasympathetic tone, bitters activate gut function and can strongly promote parasympathetic regulation. Auricular Acupuncture uses a system of somatotopic mapping of the auricular surface overlaid with an image of an inverted foetus with each body organ and system featured. Given that the concha of the auricle is the only place on the body where the Vagus Nerve neurons reach the surface of the skin, several investigators have evaluated non-invasive, transcutaneous electrical nerve stimulation (TENS) at auricular points. Drawn from an interdisciplinary evidence base and developed through clinical practice, these assessment and treatment tools are examples of practitioners in the field innovating out of necessity for the best outcomes for patients. This paper draws on case studies to direct future research.

Keywords: polyvagal, auricular acupuncture, trauma, herbs

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Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal

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Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.

Keywords: CRISPR, nanoparticles, brain diseases, administration routes

Procedia PDF Downloads 64

Authors: Vitaliy Petrov, Natalia Shusharina, Vitaliy Kasymov, Maksim Patrushev, Evgeny Bogdanov

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The leading worldwide death reasons are ischemic heart disease and other cardiovascular illnesses. Generally, the common symptom is high blood pressure. Long-time blood pressure control is very important for the prophylaxis, correct diagnosis and timely therapy. Non-invasive methods which are based on Korotkoff sounds are impossible to apply often and for a long time. Implantable devices can combine longtime monitoring with high accuracy of measurements. The main purpose of this work is to create a real-time monitoring system for decreasing the death rate from cardiovascular diseases. These days implantable electronic devices began to play an important role in medicine. Usually implantable devices consist of a transmitter, powering which could be wireless with a special made battery and measurement circuit. Common problems in making implantable devices are short lifetime of the battery, big size and biocompatibility. In these work, blood pressure measure will be the focus because it’s one of the main symptoms of cardiovascular diseases. Our device will consist of three parts: the implantable pressure sensor, external transmitter and automated workstation in a hospital. The Implantable part of pressure sensors could be based on piezoresistive or capacitive technologies. Both sensors have some advantages and some limitations. The Developed circuit is based on a small capacitive sensor which is made of the technology of microelectromechanical systems (MEMS). The Capacitive sensor can provide high sensitivity, low power consumption and minimum hysteresis compared to the piezoresistive sensor. For this device, it was selected the oscillator-based circuit where frequency depends from the capacitance of sensor hence from capacitance one can calculate pressure. The external device (transmitter) used for wireless charging and signal transmission. Some implant devices for these applications are passive, the external device sends radio wave signal on internal LC circuit device. The external device gets reflected the signal from the implant and from a change of frequency is possible to calculate changing of capacitance and then blood pressure. However, this method has some disadvantages, such as the patient position dependence and static using. Developed implantable device doesn’t have these disadvantages and sends blood pressure data to the external part in real-time. The external device continuously sends information about blood pressure to hospital cloud service for analysis by a physician. Doctor’s automated workstation at the hospital also acts as a dashboard, which displays actual medical data of patients (which require attention) and stores it in cloud service. Usually, critical heart conditions occur few hours before heart attack but the device is able to send an alarm signal to the hospital for an early action of medical service. The system was tested with wireless charging and data transmission. These results can be used for ASIC design for MEMS pressure sensor.

Keywords: MEMS sensor, RF power, wireless data, oscillator-based circuit

Procedia PDF Downloads 558

Authors: Huan Peng, Chenye Zeng, Zhao Wang

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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Authors: Maria Amelia V. C. Araujo, Billy J. Araujo, Brian Greenwood

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The flow over a backward-facing step is characterized by the presence of flow separation, recirculation and reattachment, for a simple geometry. This type of fluid behaviour takes place in many practical engineering applications, hence the reason for being investigated. Historically, fluid flows over a backward-facing step have been examined in many experiments using a variety of measuring techniques such as laser Doppler velocimetry (LDV), hot-wire anemometry, particle image velocimetry or hot-film sensors. However, some of these techniques cannot conveniently be used in separated flows or are too complicated and expensive. In this work, the applicability of the acoustic Doppler velocimetry (ADV) technique is investigated to such type of flows, at various Reynolds numbers corresponding to different flow regimes. The use of this measuring technique in separated flows is very difficult to find in literature. Besides, most of the situations where the Reynolds number effect is evaluated in separated flows are in numerical modelling. The ADV technique has the advantage in providing nearly non-invasive measurements, which is important in resolving turbulence. The ADV Nortek Vectrino+ was used to characterize the flow, in a recirculating laboratory flume, at various Reynolds Numbers (Reh = 3738, 5452, 7908 and 17388) based on the step height (h), in order to capture different flow regimes, and the results compared to those obtained using other measuring techniques. To compare results with other researchers, the step height, expansion ratio and the positions upstream and downstream the step were reproduced. The post-processing of the AVD records was performed using a customized numerical code, which implements several filtering techniques. Subsequently, the Vectrino noise level was evaluated by computing the power spectral density for the stream-wise horizontal velocity component. The normalized mean stream-wise velocity profiles, skin-friction coefficients and reattachment lengths were obtained for each Reh. Turbulent kinetic energy, Reynolds shear stresses and normal Reynolds stresses were determined for Reh = 7908. An uncertainty analysis was carried out, for the measured variables, using the moving block bootstrap technique. Low noise levels were obtained after implementing the post-processing techniques, showing their effectiveness. Besides, the errors obtained in the uncertainty analysis were relatively low, in general. For Reh = 7908, the normalized mean stream-wise velocity and turbulence profiles were compared directly with those acquired by other researchers using the LDV technique and a good agreement was found. The ADV technique proved to be able to characterize the flow properly over a backward-facing step, although additional caution should be taken for measurements very close to the bottom. The ADV measurements showed reliable results regarding: a) the stream-wise velocity profiles; b) the turbulent shear stress; c) the reattachment length; d) the identification of the transition from transitional to turbulent flows. Despite being a relatively inexpensive technique, acoustic Doppler velocimetry can be used with confidence in separated flows and thus very useful for numerical model validation. However, it is very important to perform adequate post-processing of the acquired data, to obtain low noise levels, thus decreasing the uncertainty.

Keywords: ADV, experimental data, multiple Reynolds number, post-processing

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Authors: Dong Yue, Hua Chen

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The study region Xihu Harbor in Xiangshan County, Ningbo City is located in the central coast of Zhejiang Province. Concerning the wave dispating issue, Ningbo government firstly introduced Spartina alterniflora in 1980s. In the 1990s, S. alterniflora spread so rapidly thus a ‘grassland’ in the sea has been created nowadays. It has become the most important invasive plant of China’s coastal tidal flats. Although S. alterniflora had some ecological and economic functions, it has also brought series of hazards. It has ecological hazards on many aspects, including biomass and biodiversity, hydrodynamic force and sedimentation process, nutrient cycling of tidal flat, succession sequence of soil and plants and so on. On engineering, it courses problems of poor drainage and channel blocking. On economy, the hazard mainly reflected in the threat on aquaculture industry. The purpose of this study is to explore an ecological, feasible and economical way to manage Spartina alterniflora and use the land formed by it, taking Xihu Harbor in Xiangshan County as a case. Comparison method, mathematical modeling, qualitative and quantitative analysis are utilized to proceed the study. Main outcomes are as follows. By comparing a series of S. alterniflora managing methods which include the combination of mechanical cutting and hydraulic reclamation, waterlogging, herbicide and biological substitution from three standpoints – ecology, engineering and economy. It is inferred that the combination of mechanical cutting and hydraulic reclamation is among the top rank of S. alternifora managing methods. The combination of mechanical cutting and hydraulic reclamation means using large-scale mechanical equipment like large screw seagoing dredger to excavate the S. alterniflora with root and mud together. Then the mix of mud and grass was blown off nearby coastal tidal zone transported by pipelines, which can cushion the silt of tidal zone to form a land. However, as man-made land by coast, the reclamation area’s ecological sensitivity is quite high and will face high possibility of flood threat. Therefore, the reclamation area has many reasonability requirements, including ones on location, specific scope, water surface rate, direction of main watercourse, site of water-gate, the ratio of ecological land to urban construction land. These requirements all became important basis when the planning was being made. The water system planning, green space system planning, road structure and land use all need to accommodate the ecological requests. Besides, the profits from the formed land is the managing project’s source of funding, so how to utilize land efficiently is another considered point in the planning. It is concluded that by aiming at managing a large area of S. alterniflora, the combination of mechanical cutting and hydraulic reclamation is an ecological, feasible and economical method. The planning of reclamation area should fully respect the natural environment and possible disasters. Then the planning which makes land use efficient, reasonable, ecological will promote the development of the area’s city construction.

Keywords: ecological management, ecological planning method, reclamation area, Spartina alternifora, Xihu harbor

Procedia PDF Downloads 287

Authors: Pedro Felgueiras, Ana Miguel, Nélson Almeida, Raquel Silva

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Objective: Through the study of a clinical case of delusional somatic disorder secondary to phantogeusia, we aim to highlight the importance of considering psychosomatic conditions in differential diagnosis, as well as to emphasize the complexity of its comprehension, treatment, and respective impact on patients’ functioning. Methods: Bearing this in mind, we conducted a critical analysis of a case series based on patient observations, clinical data, and complementary diagnostic methods, as well as a non-systematic review of the literature on the subject. Results: A 61-year-old female patient with no history of psychiatric conditions. Family psychiatric history of mood disorder (depression), with psychotic features found in her mother. Medical history of many comorbidities affecting different organ systems (endocrine, gastrointestinal, genitourinary, ophthalmological). Documented neuroticism traits of personality. The patient’s family described a persistent concern about several physical symptoms across her life, with a continuous effort to obtain explanations about any sensation out of her normal perception. Since being subjected to endoscopy in 2018, she started complaints of persistent phantogeusia (acid taste) and developed excessive thoughts, feelings, and behaviors associated with this somatic symptom. The patient was evaluated by several medical specialties, and an extensive panel of medical exams was carried out, excluding any disease. Besides all the investigation and with no evidence of disease signs, acute anxiety, time, and energy dispended to this symptom culminated in severe psychosocial impairment. The patient was admitted to a psychiatric ward for investigation and treatment of this clinical picture, leading to the diagnosis of the delusional somatic disorder. In order to exclude the acute organic etiology of this psychotic disorder, an analytic panel was carried out with no abnormal results. In the context of a psychotic clinical picture, a CT scan was performed, which revealed a right cortical vascular lesion. Neuropsychological evaluation was made, with the description of cognitive functioning being globally normative. During treatment with an antipsychotic (pimozide), a complete remission of the somatic delusion was associated with the disappearance of gustative perception disturbance. In follow-up, a relapse of gustative sensation was documented, and her thoughts and speech were dominated by concerns about multiple somatic symptoms. Conclusion: In terms of abnormal bodily sensations, the oral cavity is one of the frequent sites of delusional disorder. Patients with these gustatory perception distortions complain about unusual sensations without corresponding abnormal findings in the oral area. Its pathophysiology has not been fully elucidated yet. In terms of its comprehensive psychopathology, this case was hypothesized as a paranoid development of a delusional somatic disorder triggered by a post-invasive procedure phantogeusia (which is described as a possible side effect of an endoscopy) in a patient with an anankastic personality. This case presents interesting psychopathology, reinforcing the complexity of psychosomatic disorders in terms of their etiopathogenesis, clinical treatment, and long-term prognosis.

Keywords: psychosomatics, delusional somatic disorder, phantogeusia, paranoid development

Procedia PDF Downloads 97

Authors: Michelle E. Taylor, Clare E. Morrall

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Microplastics are small particles produced for industrial purposes or formed by breakdown of anthropogenic debris. Caribbean nations import large quantities of plastic products. The Caribbean region is vulnerable to natural disasters and Climate Change is predicted to bring multiple additional challenges to island nations. Microplastics have been found in an array of marine environments and in a diversity of marine species. Occurrence of microplastic in the intestinal tracts of marine fish is a concern to human and ecosystem health as pollutants and pathogens can associate with plastics. Studies have shown that the incidence of microplastics in marine fish varies with species and location. Prevalence of microplastics (≤ 5 mm) in fish species from Grenadian waters (representing pelagic, semi-pelagic and demersal lifestyles) harvested for human consumption have been investigated via gut analysis. Harvested tissue was digested in 10% KOH and particles retained on a 0.177 mm sieve were examined. Microplastics identified have been classified according to type, colour and size. Over 97% of fish examined thus far (n=34) contained microplastics. Current and future work includes examining the invasive Lionfish (Pterois spp.) for microplastics, investigating marine invertebrate species as well as examining environmental sources of microplastics (i.e. rivers, coastal waters and sand). Owing to concerns of pollutant accumulation on microplastics and potential migration into organismal tissues, we plan to analyse fish tissue for mercury and other persistent pollutants. Despite having ~110,000 inhabitants, the island nation of Grenada imported approximately 33 million plastic bottles in 2013, of which it is estimated less than 5% were recycled. Over 30% of the imported bottles were ‘unmanaged’, and as such are potential litter/marine debris. A revised Litter Abatement Act passed into law in Grenada in 2015, but little enforcement of the law is evident to date. A local Non-governmental organization (NGO) ‘The Grenada Green Group’ (G3) is focused on reducing litter in Grenada through lobbying government to implement the revised act and running sessions in schools, community groups and on local media and social media to raise awareness of the problems associated with plastics. A local private company has indicated willingness to support an Anti-Litter Campaign in 2018 and local awareness of the need for a reduction of single use plastic use and litter seems to be high. The Government of Grenada have called for a Sustainable Waste Management Strategy and a ban on both Styrofoam and plastic grocery bags are among recommendations recently submitted. A Styrofoam ban will be in place at the St. George’s University campus from January 1st, 2018 and many local businesses have already voluntarily moved away from Styrofoam. Our findings underscore the importance of continuing investigations into microplastics in marine life; this will contribute to understanding the associated health risks. Furthermore, our findings support action to mitigate the volume of plastics entering the world’s oceans. We hope that Grenada’s future will involve a lot less plastic. This research was supported by the Caribbean Node of the Global Partnership on Marine Litter.

Keywords: Caribbean, microplastics, pollution, small island developing nation

Procedia PDF Downloads 183

Authors: Cai J. T. Ladd, Mollie F. Duggan-Edwards, Tjeerd J. Bouma, Jordi F. Pages, Martin W. Skov

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Salt marshes are valued for their role in coastal flood protection, carbon storage, and for supporting biodiverse ecosystems. As a biogeomorphic landscape, marshes evolve through the complex interactions between sea level rise, sediment supply and wave/current forcing, as well as and socio-economic factors. Climate change and direct human modification could lead to a global decline marsh extent if left unchecked. Whilst the processes of saltmarsh erosion and expansion are well understood, empirical evidence on the key drivers of long-term lateral marsh dynamics is lacking. In a GIS, saltmarsh areal extent in 25 estuaries across Great Britain was calculated from historical maps and aerial photographs, at intervals of approximately 30 years between 1846 and 2016. Data on the key perceived drivers of lateral marsh change (namely sea level rise rates, suspended sediment concentration, bedload sediment flux rates, and frequency of both river flood and storm events) were collated from national monitoring centres. Continuous datasets did not extend beyond 1970, therefore predictor variables that best explained rate change of marsh extent between 1970 and 2016 was calculated using a Partial Least Squares Regression model. Information about the spread of Spartina anglica (an invasive marsh plant responsible for marsh expansion around the globe) and coastal engineering works that may have impacted on marsh extent, were also recorded from historical documents and their impacts assessed on long-term, large-scale marsh extent change. Results showed that salt marshes in the northern regions of Great Britain expanded an average of 2.0 ha/yr, whilst marshes in the south eroded an average of -5.3 ha/yr. Spartina invasion and coastal engineering works could not explain these trends since a trend of either expansion or erosion preceded these events. Results from the Partial Least Squares Regression model indicated that the rate of relative sea level rise (RSLR) and availability of suspended sediment concentration (SSC) best explained the patterns of marsh change. RSLR increased from 1.6 to 2.8 mm/yr, as SSC decreased from 404.2 to 78.56 mg/l along the north-to-south gradient of Great Britain, resulting in the shift from marsh expansion to erosion. Regional differences in RSLR and SSC are due to isostatic rebound since deglaciation, and tidal amplitudes respectively. Marshes exposed to low RSLR and high SSC likely leads to sediment accumulation at the coast suitable for colonisation by marsh plants and thus lateral expansion. In contrast, high RSLR with are likely not offset deposition under low SSC, thus average water depth at the marsh edge increases, allowing larger wind-waves to trigger marsh erosion. Current global declines in sediment flux to the coast are likely to diminish the resilience of salt marshes to RSLR. Monitoring and managing suspended sediment supply is not common-place, but may be critical to mitigating coastal impacts from climate change.

Keywords: lateral saltmarsh dynamics, sea level rise, sediment supply, wave forcing

Procedia PDF Downloads 109

Authors: A. C. Facin, M. C. Maronezi , M. P. Menezes, G. L. Montanhim, L. Pavan, M. A. R. Feliciano, R. P. Nociti, R. A. R. Uscategui, P. C. Moraes

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The incidence of brachycephalic syndrome (BS) in the clinical routine of small animals has increased significantly giving the higher proportion of brachycephalic pets in the last years and has been considered as an animal welfare problem. The treatment of BS is surgical and the clinical signs related can be considerably attenuated. Nevertheless, the systemic effects of the BS are still poorly reported and little is known about these when the surgical correction is not performed early. Affected dogs are more likely to develop cardiopulmonary, gastrointestinal and sleep disorders in which the chronic hypoxemia plays a major role. This syndrome is compared with the obstructive sleep apnea (OSA) in humans, both considered as causes of systemic and metabolic dysfunction. Among the several consequences of the BS little is known if the syndrome also affects the hepatic tissue of brachycephalic patients. Elastography is a promising ultrasound technique that evaluates tissue elasticity and has been recently used with the purpose of diagnosis of liver fibrosis. In medicine, it is a growing concern regarding the hepatic injury of patients affected by OSA. This prospective study hypothesizes if there is any consequence of BS in the hepatic parenchyma of brachycephalic dogs that don’t receive any surgical treatment. This study was conducted following the approval of the Animal Ethics and Welfare Committee of the Faculdade de Ciências Agrárias e Veterinárias, UNESP, Campus Jaboticabal, Brazil (protocol no 17944/2017) and funded by Sao Paulo Research Foundation (FAPESP, process no 2017/24809-4). The methodology was based in ARFI elastography using the ACUSON S2000/SIEMENS device, with convex multifrequential transducer and specific software as well as clinical evaluation of the syndrome, in order to determine if they can be used as a prognostic non-invasive tool. On quantitative elastography, it was collected three measures of shear wave velocity (meters per second) and depth in centimeters in the left lateral, left medial, right lateral, right medial and caudate lobe of the liver. The brachycephalic patients, 16 pugs and 30 french bulldogs, were classified using a previously established 4-point functional grading system based on clinical evaluation before and after a 3-minute exercise tolerance test already established and validated. The control group was based on the same features collected in 22 beagles. The software R version 3.3.0 was used for the analysis and the significance level was set at 0.05. The data were analysed for normality of residuals and homogeneity of variances by Shapiro-Wilks test. Comparisons of parametric continuous variables between breeds were performed by using ANOVA with a post hoc test for pair wise comparison. The preliminary results show significant statistic differences between the brachycephalic groups and the control group in all lobes analysed (p ≤ 0,05), with higher values of shear wave velocities in the hepatic tissue of brachycephalic dogs. In this context, the results obtained in this study contributes to the understanding of BS as well as its consequences in our patients, reflecting in evidence that one more systemic consequence of the syndrome may occur in brachycephalic patients, which was not related in the veterinary literature yet.

Keywords: airway obstruction, brachycephalic airway obstructive syndrome, hepatic injury, obstructive sleep apnea

Procedia PDF Downloads 87

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

Procedia PDF Downloads 243

Authors: Shereen Ismail Fawaz, Shin-Ichi Izumi, Nouran Mohamed Salah, Heba G. Saber, Ibrahim Mohamed Roushdi

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Background: Multiple sclerosis (MS) is a chronic, inflammatory, mainly demyelinating disease of the central nervous system, more common in young adults. Cerebellar involvement is one of the most disabling lesions in MS and is usually a sign of disease progression. It plays a major role in the planning, initiation, and organization of movement via its influence on the motor cortex and corticospinal outputs. Therefore, it contributes to controlling movement, motor adaptation, and motor learning, in addition to its vast connections with other major pathways controlling balance, such as the cerebellopropriospinal pathways and cerebellovestibular pathways. Hence, trying to stimulate the cerebellum by facilitatory protocols will add to our motor control and balance function. Non-invasive brain stimulation, both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), has recently emerged as effective neuromodulators to influence motor and nonmotor functions of the brain. Anodal tDCS has been shown to improve motor skill learning and motor performance beyond the training period. Similarly, rTMS, when used at high frequency (>5 Hz), has a facilitatory effect on the motor cortex. Objective: Our aim was to determine the effect of high-frequency rTMS over the cerebellum in improving balance and functional ambulation of multiple sclerosis patients with Ataxia. Patients and methods: This was a randomized single-blinded placebo-controlled prospective trial on 40 patients. The active group (N=20) received real rTMS sessions, and the control group (N=20) received Sham rTMS using a placebo program designed for this treatment. Both groups received 12 sessions of high-frequency rTMS over the cerebellum, followed by an intensive exercise training program. Sessions were given three times per week for four weeks. The active group protocol had a frequency of 10 Hz rTMS over the cerebellar vermis, work period 5S, number of trains 25, and intertrain interval 25s. The total number of pulses was 1250 pulses per session. The control group received Sham rTMS using a placebo program designed for this treatment. Both groups of patients received an intensive exercise program, which included generalized strengthening exercises, endurance and aerobic training, trunk abdominal exercises, generalized balance training exercises, and task-oriented training such as Boxing. As a primary outcome measure the Modified ICARS was used. Static Posturography was done with: Patients were tested both with open and closed eyes. Secondary outcome measures included the expanded Disability Status Scale (EDSS) and 8 Meter walk test (8MWT). Results: The active group showed significant improvements in all the functional scales, modified ICARS, EDSS, and 8-meter walk test, in addition to significant differences in static Posturography with open eyes, while the control group did not show such differences. Conclusion: Cerebellar high-frequency rTMS could be effective in the functional improvement of balance in MS patients with ataxia.

Keywords: brain neuromodulation, high frequency rTMS, cerebellar stimulation, multiple sclerosis, balance rehabilitation

Procedia PDF Downloads 53

Authors: Rob Schindler

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Industry-standard methods of mitigating erosion of seabed sediments rely on ‘hard engineering’ approaches which have numerous environmental shortcomings: (1) direct loss of habitat by smothering of benthic species, (2) disruption of sediment transport processes, damaging geomorphic and ecosystem functionality (3) generation of secondary erosion problems, (4) introduction of material that may propagate non-local species, and (5) provision of pathways for the spread of invasive species. Recent studies have also revealed the importance of biological cohesion, the result of naturally occurring extra-cellular polymeric substances (EPS), in stabilizing natural sediments. Mimicking the strong bonding kinetics through the deliberate addition of EPS to sediments – henceforth termed ‘biostabilisation’ - offers a means in which to mitigate against erosion induced by structures or episodic increases in hydrodynamic forcing (e.g. storms and floods) whilst avoiding, or reducing, hard engineering. Here we present unique experiments that systematically examine how biostabilisation reduces scour around a monopile in a current, a first step to realizing the potential of this new method of scouring reduction for a wide range of engineering purposes in aquatic substrates. Experiments were performed in Plymouth University’s recirculating sediment flume which includes a recessed scour pit. The model monopile was 0.048 m in diameter, D. Assuming a prototype monopile diameter of 2.0 m yields a geometric ratio of 41.67. When applied to a 10 m prototype water depth this yields a model depth, d, of 0.24 m. The sediment pit containing the monopile was filled with different biostabilised substrata prepared using a mixture of fine sand (D50 = 230 μm) and EPS (Xanthan gum). Nine sand-EPS mixtures were examined spanning EPS contents of 0.0% < b0 < 0.50%. Scour development was measured using a laser point gauge along a 530 mm centreline at 10 mm increments at regular periods over 5 h. Maximum scour depth and excavated area were determined at different time steps and plotted against time to yield equilibrium values. After 5 hours the current was stopped and a detailed scan of the final scour morphology was taken. Results show that increasing EPS content causes a progressive reduction in the equilibrium depth and lateral extent of scour, and hence excavated material. Very small amounts equating to natural communities (< 0.1% by mass) reduce scour rate, depth and extent of scour around monopiles. Furthermore, the strong linear relationships between EPS content, equilibrium scour depth, excavation area and timescales of scouring offer a simple index on which to modify existing scour prediction methods. We conclude that the biostabilisation of sediments with EPS may offer a simple, cost-effective and ecologically sensitive means of reducing scour in a range of contexts including OWFs, bridge piers, pipeline installation, and void filling in rock armour. Biostabilisation may also reduce economic costs through (1) Use of existing site sediments, or waste dredged sediments (2) Reduced fabrication of materials, (3) Lower transport costs, (4) Less dependence on specialist vessels and precise sub-sea assembly. Further, its potential environmental credentials may allow sensitive use of the seabed in marine protection zones across the globe.

Keywords: biostabilisation, EPS, marine, scour

Procedia PDF Downloads 144

Authors: Rajeswari Raguraman, Sowmya Parameswaran, Krishnakumar Subramanian, Jagat Kanwar, Rupinder Kanwar

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Background: Tumor microenvironment has been implicated in several cancers to regulate cell growth, invasion and metastasis culminating in outcome of therapy. Tumor stroma consists of multiple cell types that are in constant cross-talk with the tumor cells to favour a pro-tumorigenic environment. Not much is known about the existence of tumor microenvironment in the pediatric intraocular malignancy, Retinoblastoma (RB). In the present study, we aim to understand the multiple stromal cellular subtypes and tumor stromal interactions expressed in RB tumors. Materials and Methods: Immunohistochemistry for stromal cell markers CD31, CD68, alpha-smooth muscle (α-SMA), vimentin and glial fibrillary acidic protein (GFAP) was performed on formalin fixed paraffin embedded tissues sections of RB (n=12). The differential expression of stromal target molecules; fibroblast activation protein (FAP), tenascin-C (TNC), osteopontin (SPP1), bone marrow stromal antigen 2 (BST2), stromal derived factor 2 and 4 (SDF2 and SDF4) in primary RB tumors (n=20) and normal retina (n=5) was studied by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. The differential expression was correlated with the histopathological features of RB. The interaction between RB cell lines (Weri-Rb-1, NCC-RbC-51) and Bone marrow stromal cells (BMSC) was also studied using direct co-culture and indirect co-culture methods. The functional effect of the co-culture methods on the RB cells was evaluated by invasion and proliferation assays. Global gene expression was studied by using Affymetrix 3’ IVT microarray. Pathway prediction was performed using KEGG and the key molecules were validated using qRT-PCR. Results: The immunohistochemistry revealed the presence of several stromal cell types such as endothelial cells (CD31+;Vim+/-); macrophages (CD68+;Vim+/-); Fibroblasts (Vim+; CD31-;CD68- );myofibroblasts (α-SMA+/ Vim+) and invading retinal astrocytes/ differentiated retinal glia (GFAP+; Vim+). A characteristic distribution of these stromal cell types was observed in the tumor microenvironment, with endothelial cells predominantly seen in blood vessels and macrophages near actively proliferating tumor or necrotic areas. Retinal astrocytes and glia were predominant near the optic nerve regions in invasive tumors with sparse distribution in tumor foci. Fibroblasts were widely distributed with rare evidence of myofibroblasts in the tumor. Both gene and protein expression revealed statistically significant (P<0.05) up-regulation of FAP, TNC and BST2 in primary RB tumors compared to the normal retina. Co-culture of BMSC with RB cells promoted invasion and proliferation of RB cells in direct and indirect contact methods respectively. Direct co-culture of RB cell lines with BMSC resulted in gene expression changes in ECM-receptor interaction, focal adhesion, IL-8 and TGF-β signaling pathways associated with cancer. In contrast, various metabolic pathways such a glucose, fructose and amino acid metabolism were significantly altered under the indirect co-culture condition. Conclusion: The study suggests that the close interaction between RB cells and the stroma might be involved in RB tumor invasion and progression which is likely to be mediated by ECM-receptor interactions and secretory factors. Targeting the tumor stroma would be an attractive option for redesigning treatment strategies for RB.

Keywords: gene expression profiles, retinoblastoma, stromal cells, tumor microenvironment

Procedia PDF Downloads 357

Authors: Adewale Tolulope Irewale, Elias Emeka Elemike, Christian O. Dimkpa, Emeka Emmanuel Oguzie

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As the global population steadily approaches the 10billion mark, the world is currently faced with two major challenges among others – accessing sustainable and clean energy, and food security. Accessing cleaner and sustainable energy sources to drive global economy and technological advancement, and feeding the teeming human population require sustainable, innovative, and smart solutions. To solve the food production problem, producers have relied on fertilizers as a way of improving crop productivity. Commercial inorganic fertilizers, which is employed to boost agricultural food production, however, pose significant ecological sustainability and economic problems including soil and water pollution, reduced input efficiency, development of highly resistant weeds, micronutrient deficiency, soil degradation, and increased soil toxicity. These ecological and sustainability concerns have raised uncertainties about the continued effectiveness of conventional fertilizers. With the application of nanotechnology, plant biomass upcycling offers several advantages in greener energy production and sustainable agriculture through reduction of environmental pollution, increasing soil microbial activity, recycling carbon thereby reducing GHG emission, and so forth. This innovative technology has the potential for a circular economy and creating a sustainable agricultural practice. Nanomaterials have the potential to greatly enhance the quality and nutrient composition of organic biomass which in turn, allows for the conversion of biomass into nanofertilizers that are potentially more efficient. Water hyacinth plant harvested from an inland water at Warri, Delta State Nigeria were air-dried and milled into powder form. The dry biomass were used to prepare biochar at a pre-determined temperature in an oxygen deficient atmosphere. Physicochemical analysis of the resulting biochar was carried out to determine its porosity and general morphology using the Scanning Transmission Electron Microscopy (STEM). The functional groups (-COOH, -OH, -NH2, -CN, -C=O) were assessed using the Fourier Transform InfraRed Spectroscopy (FTIR) while the heavy metals (Cr, Cu, Fe, Pb, Mg, Mn) were analyzed using Inductively Coupled Plasma – Optical Emission Spectrometry (ICP-OES). Impregnation of the biochar with nanonutrients were achieved under varied conditions of pH, temperature, nanonutrient concentrations and resident time to achieve optimum adsorption. Adsorption and desorption studies were carried out on the resulting nanofertilizer to determine kinetics for the potential nutrients’ bio-availability to plants when used as green fertilizers. Water hyacinth (Eichhornia crassipes) which is an aggressively invasive aquatic plant known for its rapid growth and profusion is being examined in this research to harness its biomass as a sustainable feedstock to formulate functionalized nano-biochar fertilizers, offering various benefits including water hyacinth biomass upcycling, improved nutrient delivery to crops and aquatic ecosystem remediation. Altogether, this work aims to create output values in the three dimensions of environmental, economic, and social benefits.

Keywords: biochar-based nanofertilizers, eichhornia crassipes, greener agriculture, sustainable ecosystem, water hyacinth

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Authors: Manuel I. Capel, Antonio Tomeu, Alberto Salguero

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Tumor growth from a transformed cancer-cell up to a clinically apparent mass spans through a range of spatial and temporal magnitudes. Through computer simulations, Cellular Automata (CA) can accurately describe the complexity of the development of tumors. Tumor development prognosis can now be made -without making patients undergo through annoying medical examinations or painful invasive procedures- if we develop appropriate CA-based software tools. In silico testing mainly refers to Computational Biology research studies of application to clinical actions in Medicine. To establish sound computer-based models of cellular behavior, certainly reduces costs and saves precious time with respect to carrying out experiments in vitro at labs or in vivo with living cells and organisms. These aim to produce scientifically relevant results compared to traditional in vitro testing, which is slow, expensive, and does not generally have acceptable reproducibility under the same conditions. For speeding up computer simulations of cellular models, specific literature shows recent proposals based on the CA approach that include advanced techniques, such the clever use of supporting efficient data structures when modeling with deterministic stochastic cellular automata. Multiparadigm and multiscale simulation of tumor dynamics is just beginning to be developed by the concerned research community. The use of stochastic cellular automata (SCA), whose parallel programming implementations are open to yield a high computational performance, are of much interest to be explored up to their computational limits. There have been some approaches based on optimizations to advance in multiparadigm models of tumor growth, which mainly pursuit to improve performance of these models through efficient memory accesses guarantee, or considering the dynamic evolution of the memory space (grids, trees,…) that holds crucial data in simulations. In our opinion, the different optimizations mentioned above are not decisive enough to achieve the high performance computing power that cell-behavior simulation programs actually need. The possibility of using multicore and GPU parallelism as a promising multiplatform and framework to develop new programming techniques to speed-up the computation time of simulations is just starting to be explored in the few last years. This paper presents a model that incorporates parallel processing, identifying the synchronization necessary for speeding up tumor growth simulations implemented in Java and C++ programming environments. The speed up improvement that specific parallel syntactic constructs, such as executors (thread pools) in Java, are studied. The new tumor growth parallel model is proved using implementations with Java and C++ languages on two different platforms: chipset Intel core i-X and a HPC cluster of processors at our university. The parallelization of Polesczuk and Enderling model (normally used by researchers in mathematical oncology) proposed here is analyzed with respect to performance gain. We intend to apply the model and overall parallelization technique presented here to solid tumors of specific affiliation such as prostate, breast, or colon. Our final objective is to set up a multiparadigm model capable of modelling angiogenesis, or the growth inhibition induced by chemotaxis, as well as the effect of therapies based on the presence of cytotoxic/cytostatic drugs.

Keywords: cellular automaton, tumor growth model, simulation, multicore and manycore programming, parallel programming, high performance computing, speed up

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Authors: Wiam El Kheir, Anais Dumais, Maude Beaudoin, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux, Marc-Antoine Lauzon

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The high infiltrative pattern of glioblastoma multiforme cells (GBM) is the main cause responsible for the actual standard treatments failure. The tumor high heterogeneity, the interstitial fluid flow (IFF) and chemokines guides GBM cells migration in the brain parenchyma resulting in tumor recurrence. Drug delivery systems emerged as an alternative approach to develop effective treatments for the disease. Some recent studies have proposed to harness the effect CXC-lchemokine-ligand-12 to direct and control the cancer cell migration through delivery system. However, the dynamics of the brain environment on the delivery system remains poorly understood. Nanoparticles (NPs) and hydrogels are known as good carriers for the encapsulation of different agents and control their release. We studied the release of CXCL12 (free or loaded into NPs) from an alginate-based hydrogel under static and indirect perfusion (IP) conditions. Under static conditions, the main phenomena driving CXCL12 release from the hydrogel was diffusion with the presence of strong interactions between the positively charged CXCL12 and the negatively charge alginate. CXCL12 release profiles were independent from the initial mass loadings. Afterwards, we demonstrated that the release could tuned by loading CXCL12 into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded them into alginate-hydrogel. The initial burst release was substantially attenuated and the overall cumulative release percentages of 21%, 16% and 7% were observed for initial mass loadings of 0.07, 0.13 and 0.26 µg, respectively, suggesting stronger electrostatic interactions. Results were mathematically modeled based on Fick’s second law of diffusion framework developed previously to estimate the effective diffusion coefficient (Deff) and the mass transfer coefficient. Embedding the CXCL12 into NPs decreased the Deff an order of magnitude, which was coherent with experimental data. Thereafter, we developed an in-vitro 3D model that takes into consideration the convective contribution of the brain IFF to study CXCL12 release in an in-vitro microenvironment that mimics as faithfully as possible the human brain. From is unique design, the model also allowed us to understand the effect of IP on CXCL12 release in respect to time and space. Four flow rates (0.5, 3, 6.5 and 10 µL/min) which may increase CXCL12 release in-vivo depending on the tumor location were assessed. Under IP, cumulative percentages varying between 4.5-7.3%, 23-58.5%, 77.8-92.5% and 89.2-95.9% were released for the three initial mass loadings of 0.08, 0.16 and 0.33 µg, respectively. As the flow rate increase, IP culture conditions resulted in a higher release of CXCL12 compared to static conditions as the convection contribution became the main driving mass transport phenomena. Further, depending on the flow rate, IP had a direct impact on CXCL12 distribution within the simulated brain tissue, which illustrates the importance of developing such 3D in-vitro models to assess the efficiency of a delivery system targeting the brain. In future work, using this very model, we aim to understand the impact of the different phenomenon occurring on GBM cell behaviors in response to the resulting chemokine gradient subjected to various flow while allowing them to express their invasive characteristics in an in-vitro microenvironment that mimics the in-vivo brain parenchyma.

Keywords: 3D culture system, chemokines gradient, glioblastoma multiforme, kinetic release, mathematical modeling

Procedia PDF Downloads 54

Authors: A. Calabrese, V. F. Uricchio, D. di Noia, S. Favale, C. Caiati, G. P. Maggi, G. Donvito, D. Diacono, S. Tangaro, A. Italiano, E. Riezzo, M. Zippitelli, M. Toriello, E. Celiberti, D. Festa, A. Colaianni

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Climate change has a severe impact on human health. There is a vast literature demonstrating temperature increase is causally related to cardiovascular problem and represents a high risk for human health, but there are not study that improve a solution. In this work, it is studied how the clime influenced the human parameter through the analysis of climatic conditions in an area of the Apulia Region: Capurso Municipality. At the same time, medical personnel involved identified a set of variables useful to define an index describing health condition. These scientific studies are the base of an innovative alert system, IPPOCRATE, whose aim is to asses climate risk and share information to population at risk to support prevention and mitigation actions. IPPOCRATE is an e-health system, it is designed to provide technological support to analysis of health risk related to climate and provide tools for prevention and management of critical events. It is the first integrated system of prevention of human risk caused by climate change. IPPOCRATE calculates risk weighting meteorological data with the vulnerability of monitored subjects and uses mobile and cloud technologies to acquire and share information on different data channels. It is composed of four components: Multichannel Hub. Multichannel Hub is the ICT infrastructure used to feed IPPOCRATE cloud with a different type of data coming from remote monitoring devices, or imported from meteorological databases. Such data are ingested, transformed and elaborated in order to be dispatched towards mobile app and VoIP phone systems. IPPOCRATE Multichannel Hub uses open communication protocols to create a set of APIs useful to interface IPPOCRATE with 3rd party applications. Internally, it uses non-relational paradigm to create flexible and highly scalable database. WeHeart and Smart Application The wearable device WeHeart is equipped with sensors designed to measure following biometric variables: heart rate, systolic blood pressure and diastolic blood pressure, blood oxygen saturation, body temperature and blood glucose for diabetic subjects. WeHeart is designed to be easy of use and non-invasive. For data acquisition, users need only to wear it and connect it to Smart Application by Bluetooth protocol. Easy Box was designed to take advantage from new technologies related to e-health care. EasyBox allows user to fully exploit all IPPOCRATE features. Its name, Easy Box, reveals its purpose of container for various devices that may be included depending on user needs. Territorial Registry is the IPPOCRATE web module reserved to medical personnel for monitoring, research and analysis activities. Territorial Registry allows to access to all information gathered by IPPOCRATE using GIS system in order to execute spatial analysis combining geographical data (climatological information and monitored data) with information regarding the clinical history of users and their personal details. Territorial Registry was designed for different type of users: control rooms managed by wide area health facilities, single health care center or single doctor. Territorial registry manages such hierarchy diversifying the access to system functionalities. IPPOCRATE is the first e-Health system focused on climate risk prevention.

Keywords: climate change, health risk, new technological system

Procedia PDF Downloads 837

Authors: Aidan Ryan, Nahima Miah, Sahaj Kaur, Imogen Sutherland, Mohamed Saleh

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Pulmonary symptoms are a common presentation to the emergency department. Due to a lack of understanding of the underlying pathophysiology, chronic liver disease is not often considered a cause of dyspnea. We present three patients who were admitted with significant respiratory distress secondary to hepatopulmonary syndrome, portopulmonary hypertension, and hepatic hydrothorax. The first is a 27-year-old male with a 6-month history of progressive dyspnea. The patient developed a severe type 1 respiratory failure with a PaO₂ of 6.3kPa and was escalated to critical care, where he was managed with non-invasive ventilation to maintain oxygen saturation. He had an agitated saline contrast echocardiogram, which showed the presence of a possible shunt. A CT angiogram revealed significant liver cirrhosis, portal hypertension, and large para esophageal varices. Ultrasound of the abdomen showed coarse liver echo patter and enlarged spleen. Along with these imaging findings, his biochemistry demonstrated impaired synthetic liver function with an elevated international normalized ratio (INR) of 1.4 and hypoalbuminaemia of 28g/L. The patient was then transferred to a tertiary center for further management. Further investigations confirmed a shunt of 56%, and liver biopsy confirmed cirrhosis suggestive of alpha-1-antitripsyin deficiency. The findings were consistent with a diagnosis of hepatopulmonary syndrome, and the patient is awaiting a liver transplant. The second patient is a 56-year-old male with a 12-month history of worsening dyspnoea, jaundice, confusion. His medical history included liver cirrhosis, portal hypertension, and grade 1 oesophageal varices secondary to significant alcohol excess. On admission, he developed a type 1 respiratory failure with PaO₂ of 6.8kPa requiring 10L of oxygen. CT pulmonary angiogram was negative for pulmonary embolism but showed evidence of chronic pulmonary hypertension, liver cirrhosis, and portal hypertension. An echocardiogram revealed a grossly dilated right heart with reduced function, pulmonary and tricuspid regurgitation, and pulmonary artery pressures estimated at 78mmHg. His biochemical markers showed impaired synthetic liver function with an INR of 3.2, albumin of 29g/L, along with raised bilirubin of 148mg/dL. During his long admission, he was managed with diuretics with little improvement. After three weeks, he was diagnosed with portopulmonary hypertension and was commenced on terlipressin. This resulted in successfully weaning off oxygen, and he was discharged home. The third patient is a 61-year-old male who presented to the local ambulatory care unit for therapeutic paracentesis on a background of decompensated liver cirrhosis. On presenting, he complained of a 2-day history of worsening dyspnoea and a productive cough. Chest x-ray showed a large pleural effusion, increasing in size over the previous eight months, and his abdomen was visibly distended with ascitic fluid. Unfortunately, the patient deteriorated, developing a larger effusion along with an increase in oxygen demand, and passed away. Without underlying cardiorespiratory disease, in the presence of a persistent pleural effusion with underlying decompensated cirrhosis, he was diagnosed with hepatic hydrothorax. While each presented with dyspnoea, the cause and underlying pathophysiology differ significantly from case to case. By describing these complications, we hope to improve awareness and aid prompt and accurate diagnosis, vital for improving outcomes.

Keywords: dyspnea, hepatic hydrothorax, hepatopulmonary syndrome, portopulmonary syndrome

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Authors: Asma Omri, Iheb Sifaoui, Sofiane Sayahi, Hichem Besbes

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Future vehicle systems demand advanced capabilities, notably in-cabin life detection and driver monitoring systems, with a particular emphasis on drowsiness detection. To meet these requirements, several techniques employ artificial intelligence methods based on real-time vital sign measurements. In parallel, Frequency-Modulated Continuous-Wave (FMCW) radar technology has garnered considerable attention in the domains of healthcare and biomedical engineering for non-invasive vital sign monitoring. FMCW radar offers a multitude of advantages, including its non-intrusive nature, continuous monitoring capacity, and its ability to penetrate through clothing. In this paper, we propose a system utilizing the AWR6843AOP radar from Texas Instruments (TI) to extract precise vital sign information. The radar allows us to estimate Ballistocardiogram (BCG) signals, which capture the mechanical movements of the body, particularly the ballistic forces generated by heartbeats and respiration. These signals are rich sources of information about the cardiac cycle, rendering them suitable for heart rate estimation. The process begins with real-time subject positioning, followed by clutter removal, computation of Doppler phase differences, and the use of various filtering methods to accurately capture subtle physiological movements. To address the challenges associated with FMCW radar-based vital sign monitoring, including motion artifacts due to subjects' movement or radar micro-vibrations, Long Short-Term Memory (LSTM) networks are implemented. LSTM's adaptability to different heart rate patterns and ability to handle real-time data make it suitable for continuous monitoring applications. Several crucial steps were taken, including feature extraction (involving amplitude, time intervals, and signal morphology), sequence modeling, heart rate estimation through the analysis of detected cardiac cycles and their temporal relationships, and performance evaluation using metrics such as Root Mean Square Error (RMSE) and correlation with reference heart rate measurements. For dataset construction and LSTM training, a comprehensive data collection system was established, integrating the AWR6843AOP radar, a Heart Rate Belt, and a smart watch for ground truth measurements. Rigorous synchronization of these devices ensured data accuracy. Twenty participants engaged in various scenarios, encompassing indoor and real-world conditions within a moving vehicle equipped with the radar system. Static and dynamic subject’s conditions were considered. The heart rate estimation through LSTM outperforms traditional signal processing techniques that rely on filtering, Fast Fourier Transform (FFT), and thresholding. It delivers an average accuracy of approximately 91% with an RMSE of 1.01 beat per minute (bpm). In conclusion, this paper underscores the promising potential of FMCW radar technology integrated with artificial intelligence algorithms in the context of automotive applications. This innovation not only enhances road safety but also paves the way for its integration into the automotive ecosystem to improve driver well-being and overall vehicular safety.

Keywords: ballistocardiogram, FMCW Radar, vital sign monitoring, LSTM

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Authors: Pei Yi Lin

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Objective: The objective of this study is to use machine learning methods to build an early prediction classifier model for acute delirium to improve the quality of medical care for intensive care patients. Background: Delirium is a common acute and sudden disturbance of consciousness in critically ill patients. After the occurrence, it is easy to prolong the length of hospital stay and increase medical costs and mortality. In 2021, the incidence of delirium in the intensive care unit of internal medicine was as high as 59.78%, which indirectly prolonged the average length of hospital stay by 8.28 days, and the mortality rate is about 2.22% in the past three years. Therefore, it is expected to build a delirium prediction classifier through big data analysis and machine learning methods to detect delirium early. Method: This study is a retrospective study, using the artificial intelligence big data database to extract the characteristic factors related to delirium in intensive care unit patients and let the machine learn. The study included patients aged over 20 years old who were admitted to the intensive care unit between May 1, 2022, and December 31, 2022, excluding GCS assessment <4 points, admission to ICU for less than 24 hours, and CAM-ICU evaluation. The CAMICU delirium assessment results every 8 hours within 30 days of hospitalization are regarded as an event, and the cumulative data from ICU admission to the prediction time point are extracted to predict the possibility of delirium occurring in the next 8 hours, and collect a total of 63,754 research case data, extract 12 feature selections to train the model, including age, sex, average ICU stay hours, visual and auditory abnormalities, RASS assessment score, APACHE-II Score score, number of invasive catheters indwelling, restraint and sedative and hypnotic drugs. Through feature data cleaning, processing and KNN interpolation method supplementation, a total of 54595 research case events were extracted to provide machine learning model analysis, using the research events from May 01 to November 30, 2022, as the model training data, 80% of which is the training set for model training, and 20% for the internal verification of the verification set, and then from December 01 to December 2022 The CU research event on the 31st is an external verification set data, and finally the model inference and performance evaluation are performed, and then the model has trained again by adjusting the model parameters. Results: In this study, XG Boost, Random Forest, Logistic Regression, and Decision Tree were used to analyze and compare four machine learning models. The average accuracy rate of internal verification was highest in Random Forest (AUC=0.86), and the average accuracy rate of external verification was in Random Forest and XG Boost was the highest, AUC was 0.86, and the average accuracy of cross-validation was the highest in Random Forest (ACC=0.77). Conclusion: Clinically, medical staff usually conduct CAM-ICU assessments at the bedside of critically ill patients in clinical practice, but there is a lack of machine learning classification methods to assist ICU patients in real-time assessment, resulting in the inability to provide more objective and continuous monitoring data to assist Clinical staff can more accurately identify and predict the occurrence of delirium in patients. It is hoped that the development and construction of predictive models through machine learning can predict delirium early and immediately, make clinical decisions at the best time, and cooperate with PADIS delirium care measures to provide individualized non-drug interventional care measures to maintain patient safety, and then Improve the quality of care.

Keywords: critically ill patients, machine learning methods, delirium prediction, classifier model

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