Search results for: inflammatory pain
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1853

Search results for: inflammatory pain

83 Broad Host Range Bacteriophage Cocktail for Reduction of Staphylococcus aureus as Potential Therapy for Atopic Dermatitis

Authors: Tamar Lin, Nufar Buchshtab, Yifat Elharar, Julian Nicenboim, Rotem Edgar, Iddo Weiner, Lior Zelcbuch, Ariel Cohen, Sharon Kredo-Russo, Inbar Gahali-Sass, Naomi Zak, Sailaja Puttagunta, Merav Bassan

Abstract:

Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder that is characterized by dry skin and flares of eczematous lesions and intense pruritus. Multiple lines of evidence suggest that AD is associated with increased colonization by Staphylococcus aureus, which contributes to disease pathogenesis through the release of virulence factors that affect both keratinocytes and immune cells, leading to disruption of the skin barrier and immune cell dysfunction. The aim of the current study is to develop a bacteriophage-based product that specifically targets S. aureus. Methods: For the discovery of phage, environmental samples were screened on 118 S. aureus strains isolated from skin samples, followed by multiple enrichment steps. Natural phages were isolated, subjected to Next-generation Sequencing (NGS), and analyzed using proprietary bioinformatics tools for undesirable genes (toxins, antibiotic resistance genes, lysogeny potential), taxonomic classification, and purity. Phage host range was determined by an efficiency of plating (EOP) value above 0.1 and the ability of the cocktail to completely lyse liquid bacterial culture under different growth conditions (e.g., temperature, bacterial stage). Results: Sequencing analysis demonstrated that the 118 S. aureus clinical strains were distributed across the phylogenetic tree of all available Refseq S. aureus (~10,750 strains). Screening environmental samples on the S. aureus isolates resulted in the isolation of 50 lytic phages from different genera, including Silviavirus, Kayvirus, Podoviridae, and a novel unidentified phage. NGS sequencing confirmed the absence of toxic elements in the phages’ genomes. The host range of the individual phages, as measured by the efficiency of plating (EOP), ranged between 41% (48/118) to 79% (93/118). Host range studies in liquid culture revealed that a subset of the phages can infect a broad range of S. aureus strains in different metabolic states, including stationary state. Combining the single-phage EOP results of selected phages resulted in a broad host range cocktail which infected 92% (109/118) of the strains. When tested in vitro in a liquid infection assay, clearance was achieved in 87% (103/118) of the strains, with no evidence of phage resistance throughout the study (24 hours). A S. aureus host was identified that can be used for the production of all the phages in the cocktail at high titers suitable for large-scale manufacturing. This host was validated for the absence of contaminating prophages using advanced NGS methods combined with multiple production cycles. The phages are produced under optimized scale-up conditions and are being used for the development of a topical formulation (BX005) that may be administered to subjects with atopic dermatitis. Conclusions: A cocktail of natural phages targeting S. aureus was effective in reducing bacterial burden across multiple assays. Phage products may offer safe and effective steroid-sparing options for atopic dermatitis.

Keywords: atopic dermatitis, bacteriophage cocktail, host range, Staphylococcus aureus

Procedia PDF Downloads 131
82 Auto Surgical-Emissive Hand

Authors: Abhit Kumar

Abstract:

The world is full of master slave Telemanipulator where the doctor’s masters the console and the surgical arm perform the operations, i.e. these robots are passive robots, what the world needs to focus is that in use of these passive robots we are acquiring doctors for operating these console hence the utilization of the concept of robotics is still not fully utilized ,hence the focus should be on active robots, Auto Surgical-Emissive Hand use the similar concept of active robotics where this anthropomorphic hand focuses on the autonomous surgical, emissive and scanning operation, enabled with the vision of 3 way emission of Laser Beam/-5°C < ICY Steam < 5°C/ TIC embedded in palm of the anthropomorphic hand and structured in a form of 3 way disc. Fingers of AS-EH (Auto Surgical-Emissive Hand) as called, will have tactile, force, pressure sensor rooted to it so that the mechanical mechanism of force, pressure and physical presence on the external subject can be maintained, conversely our main focus is on the concept of “emission” the question arises how all the 3 non related methods will work together that to merged in a single programmed hand, all the 3 methods will be utilized according to the need of the external subject, the laser if considered will be emitted via a pin sized outlet, this radiation is channelized via a thin channel which further connect to the palm of the surgical hand internally leading to the pin sized outlet, here the laser is used to emit radiation enough to cut open the skin for removal of metal scrap or any other foreign material while the patient is in under anesthesia, keeping the complexity of the operation very low, at the same time the TIC fitted with accurate temperature compensator will be providing us the real time feed of the surgery in the form of heat image, this gives us the chance to analyze the level, also ATC will help us to determine the elevated body temperature while the operation is being proceeded, the thermal imaging camera in rooted internally in the AS-EH while also being connected to the real time software externally to provide us live feedback. The ICY steam will provide the cooling effect before and after the operation, however for more utilization of this concept we can understand the working of simple procedure in which If a finger remain in icy water for a long time it freezes the blood flow stops and the portion become numb and isolated hence even if you try to pinch it will not provide any sensation as the nerve impulse did not coordinated with the brain hence sensory receptor did not got active which means no sense of touch was observed utilizing the same concept we can use the icy stem to be emitted via a pin sized hole on the area of concern ,temperature below 273K which will frost the area after which operation can be done, this steam can also be use to desensitized the pain while the operation in under process. The mathematical calculation, algorithm, programming of working and movement of this hand will be installed in the system prior to the procedure, since this AS-EH is a programmable hand it comes with the limitation hence this AS-EH robot will perform surgical process of low complexity only.

Keywords: active robots, algorithm, emission, icy steam, TIC, laser

Procedia PDF Downloads 338
81 Managing Human-Wildlife Conflicts Compensation Claims Data Collection and Payments Using a Scheme Administrator

Authors: Eric Mwenda, Shadrack Ngene

Abstract:

Human-wildlife conflicts (HWCs) are the main threat to conservation in Africa. This is because wildlife needs overlap with those of humans. In Kenya, about 70% of wildlife occurs outside protected areas. As a result, wildlife and human range overlap, causing HWCs. The HWCs in Kenya occur in the drylands adjacent to protected areas. The top five counties with the highest incidences of HWC are Taita Taveta, Narok, Lamu, Kajiado, and Laikipia. The common wildlife species responsible for HWCs are elephants, buffaloes, hyenas, hippos, leopards, baboons, monkeys, snakes, and crocodiles. To ensure individuals affected by the conflicts are compensated, Kenya has developed a model of HWC compensation claims data collection and payment. We collected data on HWC from all eight Kenya Wildlife Service (KWS) Conservation Areas from 2009 to 2019. Additional data was collected from stakeholders' consultative workshops held in the Conservation Areas and a literature review regarding payment of injuries and ongoing insurance schemes being practiced in areas. This was followed by the description of the claims administration process and calculation of the pricing of the compensation claims. We further developed a digital platform for data capture and processing of all reported conflict cases and payments. Our product recognized four categories of HWC (i.e., human death and injury, property damage, crop destruction, and livestock predation). Personal bodily injury and human death were provided based on the Continental Scale of Benefits. We proposed a maximum of Kenya Shillings (KES) 3,000,000 for death. Medical, pharmaceutical, and hospital expenses were capped at a maximum of KES 150,000, as well as funeral costs at KES 50,000. Pain and suffering were proposed to be paid for 12 months at the rate of KES 13,500 per month. Crop damage was to be based on farm input costs at a maximum of KES 150,000 per claim. Livestock predation leading to death was based on Tropical Livestock Unit (TLU), which is equivalent to KES 30,000, whick includes Cattle (1 TLU = KES 30,000), Camel (1.4 TLU = KES 42,000), Goat (0.15 TLU = 4,500), Sheep (0.15 TLU = 4,500), and Donkey (0.5 TLU = KES 15,000). Property destruction (buildings, outside structures and harvested crops) was capped at KES 150,000 per any one claim. We conclude that it is possible to use an administrator to collect data on HWC compensation claims and make payments using technology. The success of the new approach will depend on a piloting program. We recommended that a pilot scheme be initiated for eight months in Taita Taveta, Kajiado, Baringo, Laikipia, Narok, and Meru Counties. This will test the claims administration process as well as harmonize data collection methods. The results of this pilot will be crucial in adjusting the scheme before country-wide roll out.

Keywords: human-wildlife conflicts, compensation, human death and injury, crop destruction, predation, property destruction

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80 Diagnostic Yield of CT PA and Value of Pre Test Assessments in Predicting the Probability of Pulmonary Embolism

Authors: Shanza Akram, Sameen Toor, Heba Harb Abu Alkass, Zainab Abdulsalam Altaha, Sara Taha Abdulla, Saleem Imran

Abstract:

Acute pulmonary embolism (PE) is a common disease and can be fatal. The clinical presentation is variable and nonspecific, making accurate diagnosis difficult. Testing patients with suspected acute PE has increased dramatically. However, the overuse of some tests, particularly CT and D-dimer measurement, may not improve care while potentially leading to patient harm and unnecessary expense. CTPA is the investigation of choice for PE. Its easy availability, accuracy and ability to provide alternative diagnosis has lowered the threshold for performing it, resulting in its overuse. Guidelines have recommended the use of clinical pretest probability tools such as ‘Wells score’ to assess risk of suspected PE. Unfortunately, implementation of guidelines in clinical practice is inconsistent. This has led to low risk patients being subjected to unnecessary imaging, exposure to radiation and possible contrast related complications. Aim: To study the diagnostic yield of CT PA, clinical pretest probability of patients according to wells score and to determine whether or not there was an overuse of CTPA in our service. Methods: CT scans done on patients with suspected P.E in our hospital from 1st January 2014 to 31st December 2014 were retrospectively reviewed. Medical records were reviewed to study demographics, clinical presentation, final diagnosis, and to establish if Wells score and D-Dimer were used correctly in predicting the probability of PE and the need for subsequent CTPA. Results: 100 patients (51male) underwent CT PA in the time period. Mean age was 57 years (24-91 years). Majority of patients presented with shortness of breath (52%). Other presenting symptoms included chest pain 34%, palpitations 6%, collapse 5% and haemoptysis 5%. D Dimer test was done in 69%. Overall Wells score was low (<2) in 28 %, moderate (>2 - < 6) in 47% and high (> 6) in 15% of patients. Wells score was documented in medical notes of only 20% patients. PE was confirmed in 12% (8 male) patients. 4 had bilateral PE’s. In high-risk group (Wells > 6) (n=15), there were 5 diagnosed PEs. In moderate risk group (Wells >2 - < 6) (n=47), there were 6 and in low risk group (Wells <2) (n=28), one case of PE was confirmed. CT scans negative for PE showed pleural effusion in 30, Consolidation in 20, atelactasis in 15 and pulmonary nodule in 4 patients. 31 scans were completely normal. Conclusion: Yield of CT for pulmonary embolism was low in our cohort at 12%. A significant number of our patients who underwent CT PA had low Wells score. This suggests that CT PA is over utilized in our institution. Wells score was poorly documented in medical notes. CT-PA was able to detect alternative pulmonary abnormalities explaining the patient's clinical presentation. CT-PA requires concomitant pretest clinical probability assessment to be an effective diagnostic tool for confirming or excluding PE. . Clinicians should use validated clinical prediction rules to estimate pretest probability in patients in whom acute PE is being considered. Combining Wells scores with clinical and laboratory assessment may reduce the need for CTPA.

Keywords: CT PA, D dimer, pulmonary embolism, wells score

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79 Fresh Amnion Membrane Grafting for the Regeneration of Skin in Full Thickness Burn in Newborn - Case Report

Authors: Priyanka Yadav, Umesh Bnasal, Yashvinder Kumar

Abstract:

The placenta is an important structure that provides oxygen and nutrients to the growing fetus in utero. It is usually thrown away after birth, but it has a therapeutic role in the regeneration of tissue. It is covered by the amniotic membrane, which can be easily separated into the amnion layer and the chorion layer—the amnion layer act as a biofilm for the healing of burn wound and non-healing ulcers. The freshly collected membrane has stem cells, cytokines, growth factors, and anti-inflammatory properties, which act as a biofilm for the healing of wounds. It functions as a barrier and prevents heat and water loss and also protects from bacterial contamination, thus supporting the healing process. The application of Amnion membranes has been successfully used for wound and reconstructive purposes for decades. It is a very cheap and easy process and has shown superior results to allograft and xenograft. However, there are very few case reports of amnion membrane grafting in newborns; we intend to highlight its therapeutic importance in burn injuries in newborns. We present a case of 9 days old male neonate who presented to the neonatal unit of Maulana Azad Medical College with a complaint of fluid-filled blisters and burns wound on the body for six days. He was born outside the hospital at 38 weeks of gestation to a 24-year-old primigravida mother by vaginal delivery. The presentation was cephalic and the amniotic fluid was clear. His birth weight was 2800 gm and APGAR scores were 7 and 8 at 1 and 5 minutes, respectively. His anthropometry was appropriate for gestational age. He developed respiratory distress after birth requiring oxygen support by nasal prongs for three days. On the day of life three, he developed blisters on his body, starting from than face then over the back and perineal region. At a presentation on the day of life nine, he had blisters and necrotic wound on the right side of the face, back, right shoulder and genitalia, affecting 60% of body surface area with full-thickness loss of skin. He was started on intravenous antibiotics and fluid therapy. Pus culture grew Pseudomonas aeuroginosa, for which culture-specific antibiotics were started. Plastic surgery reference was taken and regular wound dressing was done with antiseptics. He had a storming course during the hospital stay. On the day of life 35 when the baby was hemodynamically stable, amnion membrane grafting was done on the wound site; for the grafting, fresh amnion membrane was removed under sterile conditions from the placenta obtained by caesarean section. It was then transported to the plastic surgery unit in half an hour in a sterile fluid where the graft was applied over the infant’s wound. The amnion membrane grafting was done twice in two weeks for covering the whole wound area. After successful uptake of amnion membrane, skin from the thigh region was autografted over the whole wound area by Meek technique in a single setting. The uptake of autograft was excellent and most of the areas were healed. In some areas, there was patchy regeneration of skin so dressing was continued. The infant was discharged after three months of hospital stay and was later followed up in the plastic surgery unit of the hospital.

Keywords: amnion membrane grafting, autograft, meek technique, newborn, regeneration of skin

Procedia PDF Downloads 149
78 Raman Spectral Fingerprints of Healthy and Cancerous Human Colorectal Tissues

Authors: Maria Karnachoriti, Ellas Spyratou, Dimitrios Lykidis, Maria Lambropoulou, Yiannis S. Raptis, Ioannis Seimenis, Efstathios P. Efstathopoulos, Athanassios G. Kontos

Abstract:

Colorectal cancer is the third most common cancer diagnosed in Europe, according to the latest incidence data provided by the World Health Organization (WHO), and early diagnosis has proved to be the key in reducing cancer-related mortality. In cases where surgical interventions are required for cancer treatment, the accurate discrimination between healthy and cancerous tissues is critical for the postoperative care of the patient. The current study focuses on the ex vivo handling of surgically excised colorectal specimens and the acquisition of their spectral fingerprints using Raman spectroscopy. Acquired data were analyzed in an effort to discriminate, in microscopic scale, between healthy and malignant margins. Raman spectroscopy is a spectroscopic technique with high detection sensitivity and spatial resolution of few micrometers. The spectral fingerprint which is produced during laser-tissue interaction is unique and characterizes the biostructure and its inflammatory or cancer state. Numerous published studies have demonstrated the potential of the technique as a tool for the discrimination between healthy and malignant tissues/cells either ex vivo or in vivo. However, the handling of the excised human specimens and the Raman measurement conditions remain challenging, unavoidably affecting measurement reliability and repeatability, as well as the technique’s overall accuracy and sensitivity. Therefore, tissue handling has to be optimized and standardized to ensure preservation of cell integrity and hydration level. Various strategies have been implemented in the past, including the use of balanced salt solutions, small humidifiers or pump-reservoir-pipette systems. In the current study, human colorectal specimens of 10X5 mm were collected from 5 patients up to now who underwent open surgery for colorectal cancer. A novel, non-toxic zinc-based fixative (Z7) was used for tissue preservation. Z7 demonstrates excellent protein preservation and protection against tissue autolysis. Micro-Raman spectra were recorded with a Renishaw Invia spectrometer from successive random 2 micrometers spots upon excitation at 785 nm to decrease fluorescent background and secure avoidance of tissue photodegradation. A temperature-controlled approach was adopted to stabilize the tissue at 2 °C, thus minimizing dehydration effects and consequent focus drift during measurement. A broad spectral range, 500-3200 cm-1,was covered with five consecutive full scans that lasted for 20 minutes in total. The average spectra were used for least square fitting analysis of the Raman modes.Subtle Raman differences were observed between normal and cancerous colorectal tissues mainly in the intensities of the 1556 cm-1 and 1628 cm-1 Raman modes which correspond to v(C=C) vibrations in porphyrins, as well as in the range of 2800-3000 cm-1 due to CH2 stretching of lipids and CH3 stretching of proteins. Raman spectra evaluation was supported by histological findings from twin specimens. This study demonstrates that Raman spectroscopy may constitute a promising tool for real-time verification of clear margins in colorectal cancer open surgery.

Keywords: colorectal cancer, Raman spectroscopy, malignant margins, spectral fingerprints

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77 Study of the Biological Activity of a Ganglioside-Containing Drug (Cronassil) in an Experimental Model of Multiple Sclerosis

Authors: Hasmik V. Zanginyan, Gayane S. Ghazaryan, Laura M. Hovsepyan

Abstract:

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system that is induced in laboratory animals by developing an immune response against myelin epitopes. The typical clinical course is ascending palsy, which correlates with inflammation and tissue damage in the thoracolumbar spinal cord, although the optic nerves and brain (especially the subpial white matter and brainstem) are also often affected. With multiple sclerosis, there is a violation of lipid metabolism in myelin. When membrane lipids (glycosphingolipids, phospholipids) are disturbed, metabolites not only play a structural role in membranes but are also sources of secondary mediators that transmit multiple cellular signals. The purpose of this study was to investigate the effect of ganglioside as a therapeutic agent in experimental multiple sclerosis. The biological activity of a ganglioside-containing medicinal preparation (Cronassial) was evaluated in an experimental model of multiple sclerosis in laboratory animals. An experimental model of multiple sclerosis in rats was obtained by immunization with myelin basic protein (MBP), as well as homogenization of the spinal cord or brain. EAE was induced by administering a mixture of an encephalitogenic mixture (EGM) with Complete Freund’s Adjuvant. Mitochondrial fraction was isolated in a medium containing 0,25 M saccharose and 0, 01 M tris buffer, pH - 7,4, by a method of differential centrifugation on a K-24 centrifuge. Glutathione peroxidase activity was assessed by reduction reactions of hydrogen peroxide (H₂O₂) and lipid hydroperoxides (ROOH) in the presence of GSH. LPO activity was assessed by the amount of malondialdehyde (MDA) in the total homogenate and mitochondrial fraction of the spinal cord and brain of control and experimental autoimmune encephalomyelitis rats. MDA was assessed by a reaction with Thiobarbituric acid. For statistical data analysis on PNP, SPSS (Statistical Package for Social Science) package was used. The nature of the distribution of the obtained data was determined by the Kolmogorov-Smirnov criterion. The comparative analysis was performed using a nonparametric Mann-Whitney test. The differences were statistically significant when р ≤ 0,05 or р ≤ 0,01. Correlational analysis was conducted using a nonparametric Spearman test. In the work, refrigeratory centrifuge, spectrophotometer LKB Biochrom ULTROSPECII (Sweden), pH-meter PL-600 mrc (Israel), guanosine, and ATP (Sigma). The study of the process of lipid peroxidation in the total homogenate of the brain and spinal cord in experimental animals revealed an increase in the content of malonic dialdehyde. When applied, Cronassial observed normalization of lipid peroxidation processes. Reactive oxygen species, causing lipid peroxidation processes, can be toxic both for neurons and for oligodendrocytes that form myelin, causing a violation of their lipid composition. The high content of lipids in the brain and the uniqueness of their structure determines the nature of the development of LPO processes. The lipid layer of cellular and intracellular membranes performs two main functions -barrier and matrix (structural). Damage to the barrier leads to dysregulation of intracellular processes and severe disorders of cellular functions.

Keywords: experimental autoimmune encephalomyelitis, multiple sclerosis, neuroinflammation, therapy

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76 The Effects of the Interaction between Prenatal Stress and Diet on Maternal Insulin Resistance and Inflammatory Profile

Authors: Karen L. Lindsay, Sonja Entringer, Claudia Buss, Pathik D. Wadhwa

Abstract:

Maternal nutrition and stress are independently recognized as among the most important factors that influence prenatal biology, with implications for fetal development and poor pregnancy outcomes. While there is substantial evidence from non-pregnancy human and animal studies that a complex, bi-directional relationship exists between nutrition and stress, to the author’s best knowledge, their interaction in the context of pregnancy has been significantly understudied. The aim of this study is to assess the interaction between maternal psychological stress and diet quality across pregnancy and its effects on biomarkers of prenatal insulin resistance and inflammation. This is a prospective longitudinal study of N=235 women carrying a healthy, singleton pregnancy, recruited from prenatal clinics of the University of California, Irvine Medical Center. Participants completed a 4-day ambulatory assessment in early, middle and late pregnancy, which included multiple daily electronic diary entries using Ecological Momentary Assessment (EMA) technology on a dedicated study smartphone. The EMA diaries gathered moment-level data on maternal perceived stress, negative mood, positive mood and quality of social interactions. The numerical scores for these variables were averaged across each study time-point and converted to Z-scores. A single composite variable for 'STRESS' was computed as follows: (Negative mood+Perceived stress)–(Positive mood+Social interaction quality). Dietary intakes were assessed by three 24-hour dietary recalls conducted within two weeks of each 4-day assessment. Daily nutrient and food group intakes were averaged across each study time-point. The Alternative Healthy Eating Index adapted for pregnancy (AHEI-P) was computed for early, middle and late pregnancy as a validated summary measure of diet quality. At the end of each 4-day ambulatory assessment, women provided a fasting blood sample, which was assayed for levels of glucose, insulin, Interleukin (IL)-6 and Tumor Necrosis Factor (TNF)-α. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was computed. Pearson’s correlation was used to explore the relationship between maternal STRESS and AHEI-P within and between each study time-point. Linear regression was employed to test the association of the stress-diet interaction (STRESS*AHEI-P) with the biological markers HOMA-IR, IL-6 and TNF-α at each study time-point, adjusting for key covariates (pre-pregnancy body mass index, maternal education level, race/ethnicity). Maternal STRESS and AHEI-P were significantly inversely correlated in early (r=-0.164, p=0.018) and mid-pregnancy (-0.160, p=0.019), and AHEI-P from earlier gestational time-points correlated with later STRESS (early AHEI-P x mid STRESS: r=-0.168, p=0.017; mid AHEI-P x late STRESS: r=-0.142, p=0.041). In regression models, the interaction term was not associated with HOMA-IR or IL-6 at any gestational time-point. The stress-diet interaction term was significantly associated with TNF-α according to the following patterns: early AHEI-P*early STRESS vs early TNF-α (p=0.005); early AHEI-P*early STRESS vs mid TNF-α (p=0.002); early AHEI-P*mid STRESS vs mid TNF-α (p=0.005); mid AHEI-P*mid STRESS vs mid TNF-α (p=0.070); mid AHEI-P*late STRESS vs late TNF-α (p=0.011). Poor diet quality is significantly related to higher psychosocial stress levels in pregnant women across gestation, which may promote inflammation via TNF-α. Future prenatal studies should consider the combined effects of maternal stress and diet when evaluating either one of these factors on pregnancy or infant outcomes.

Keywords: diet quality, inflammation, insulin resistance, nutrition, pregnancy, stress, tumor necrosis factor-alpha

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75 The Safe Introduction of Tocilizumab for the Treatment of SARS-CoV-2 Pneumonia at an East London District General Hospital

Authors: Andrew Read, Alice Parry, Kate Woods

Abstract:

Since the advent of the SARS-CoV-2 pandemic, the search for medications that can reduce mortality and morbidity has been a global research priority. Several multi-center trials have recently demonstrated improved mortality associated with the use of Tocilizumab, an interleukin-6 receptor antagonist, in patients with severe SARS-CoV-2 pneumonia. Initial data supported the administration in patients requiring respiratory support (non-invasive or invasive ventilation), but more recent data has shown benefit in all hypoxic patients. At the height of the second wave of COVID-19 infections in London, our hospital introduced the use of Tocilizumab for patients with severe COVID-19. Tocilizumab is licensed for use in chronic inflammatory conditions and has been associated with an increased risk of severe bacterial and fungal infections, as well as reactivation of chronic viral infections (e.g., hepatitis B). It is a specialist drug that suppresses the formation of C-reactive protein (CRP) for 6 – 12 weeks. It is not widely used by the general medical community. We aimed to assess Tocilizumab use in our hospital and to implement changes to the protocol as required to ensure administration was safe and appropriate. A retrospective study design was used to assess prescriptions over an initial 3-week period in both intensive care and on the medical wards. This amounted to a total of 13 patients. The initial data collection identified four key areas of concern: adherence to national and local inclusion & exclusion criteria; a collection of appropriate screening blood prior to administration; documentation of informed consent or best interest decision and documentation of Tocilizumab administration on patient discharge information, to alert future healthcare providers that typical measures of inflammation and infection, such as CRP, are unreliable for up to 3-months. Data were collected from electronic notes, blood results and observation charts, and cross referenced with pharmacy data. Initial results showed that all four key areas were completed in approximately 50% of cases. Of particular concern was adherence to exclusion criteria, such as current evidence of bacterial infection, and ensuring the correct screening blood was sent to exclude infections such as hepatitis. To remedy this and improve patient safety, the initial data was presented to relevant healthcare professionals. Subsequently, three interventions were introduced and education on each provided to hospital staff. An electronic ‘order set’ collating the appropriate screening blood was created simplifying the screening process. Pre-formed electronic documentation which can be inserted into the notes was created to provide a framework for consent discussions and reduce the time needed for junior doctors to complete this task. Additionally, a ‘Tocilizumab’ administration card was created and administered via pharmacy. This was distributed to each patient on discharge to ensure future healthcare professionals were aware of the potential effects of Tocilizumab administration, including suppression of CRP. Following these changes, repeat data collection over two months illustrated that each of the 4 safety aspects was met with a 100% success rate in every patient. Although this demonstrates good progress and effective interventions the challenge will be to maintain this progress. The audit data collection is ongoing

Keywords: education, patient safety , SARS-CoV-2, Tocilizumab

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74 Head and Neck Extranodal Rosai-Dorfman Disease- Utility of immunohistochemistry

Authors: Beverly Wang

Abstract:

Background: Rosai-Dorfman disease (RDD), aka sinus histiocytosis with massive lymphadenopathy, is a rare, idiopathic histiocytic proliferative disorder. Although RDD can be seen involving the head and neck lymph nodes, rarely it can affect other extranodal sites. It present 3 unique cases of RDD affecting the nasal cavity, paranasal sinuses, and ear canal. The initial clinical presentation on two cases mimicked a malignant neoplasm. The 3rd case of RDD co-existed with a cholesteatoma of the ear canal. The clinical presentation, histology and immunohistochemical stains, and radiographic findings are discussed. Design: An overview of 3 cases of RDD affected sinonasal cavity and ear canal from UCI Medical Center was conducted. Case 1: A 61 year old male complaining of breathing difficulty presented with bilateral polypoid sinonasal masses and severe nasal obstruction. The masses elevated the nasal floor, and involved the anterior nasal septum to lateral wall. It was endoscopically excised. At intraoperative consultation, frozen section reported a pleomorphic spindle cell neoplasm with scattered large atypical spindle cells, resembling a high grade sarcoma. Case 2: A 46 year old male presented with recurrent bilateral maxillary chronic sinusitis with mass formation, clinically suspicious for malignant lymphoma. Excisional tissue sample showed large irregular spindled histiocytes with abundant granular and vacuolated cytoplasm. Case 3: A 36 year old female with a history of asthma initially presented with left-sided chronic otalgia, occasional nausea, vertigo, and fluctuating pain exacerbated by head movement and temperature changes. CT scan revealed an external auditory canal mass extending to the middle ear, coexisting with a small cholesteatoma. Results: The morphology of all cases revealed large atypical spindled histiocytes resembling fibrohistiocytic or myofibroblastic proliferative neoplasms. Scattered emperipolesis was seen. All 3 cases were confirmed as extranodal sinus RDD, confirmed by immunohistochemistry. The large atypical cells were positive for S100, CD68, and CD163. No evidence for malignancy was identified. Case 3 showed concurrent RDD co-existing with a cholesteatoma. Conclusion: Due to its rarity and variable clinical presentations, the diagnosis of RDD is seldom clinically considered. Extranodal sinus RDD morphologically can be pitfall as mimicker of spindly neoplasm, especially at intraoperative consultation. It can create diagnostic and therapeutic challenges. Correlation of radiological findings with histologic features will help to reach the diagnosis.

Keywords: head and neck, extranodal, rosai-dorfman disease, mimicker, immunohistochemistry

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73 Benzenepropanamine Analogues as Non-detergent Microbicidal Spermicide for Effective Pre-exposure Prophylaxis

Authors: Veenu Bala, Yashpal S. Chhonker, Bhavana Kushwaha, Rabi S. Bhatta, Gopal Gupta, Vishnu L. Sharma

Abstract:

According to UNAIDS 2013 estimate nearly 52% of all individuals living with HIV are now women of reproductive age (15–44 years). Seventy-five percent cases of HIV acquisition are through heterosexual contacts and sexually transmitted infections (STIs), attributable to unsafe sexual behaviour. Each year, an estimated 500 million people acquire atleast one of four STIs: chlamydia, gonorrhoea, syphilis and trichomoniasis. Trichomonas vaginalis (TV) is exclusively sexually transmitted in adults, accounting for 30% of STI cases and associated with pelvic inflammatory disease (PID), vaginitis and pregnancy complications in women. TV infection resulted in impaired vaginal milieu, eventually favoring HIV transmission. In the absence of an effective prophylactic HIV vaccine, prevention of new infections has become a priority. It was thought worthwhile to integrate HIV prevention and reproductive health services including unintended pregnancy protection for women as both are related with unprotected sex. Initially, nonoxynol-9 (N-9) had been proposed as a spermicidal agent with microbicidal activity but on the contrary it increased HIV susceptibility due to surfactant action. Thus, to accomplish an urgent need of novel woman controlled non-detergent microbicidal spermicides benzenepropanamine analogues have been synthesized. At first, five benzenepropanamine-dithiocarbamate hybrids have been synthesized and evaluated for their spermicidal, anti-Trichomonas and anti-fungal activities along with safety profiling to cervicovaginal cells. In order to further enhance the scope of above study benzenepropanamine was hybridized with thiourea as to introduce anti-HIV potential. The synthesized hybrid molecules were evaluated for their reverse transcriptase (RT) inhibition, spermicidal, anti-Trichomonas and antimicrobial activities as well as their safety against vaginal flora and cervical cells. simulated vaginal fluid (SVF) stability and pharmacokinetics of most potent compound versus N-9 was examined in female Newzealand (NZ) rabbits to observe its absorption into systemic circulation and subsequent exposure in blood plasma through vaginal wall. The study resulted in the most promising compound N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) exhibiting better activity profile than N-9 as it showed RT inhibition (72.30 %), anti-Trichomonas (MIC, 46.72 µM against MTZ susceptible and MIC, 187.68 µM against resistant strain), spermicidal (MEC, 0.01%) and antifungal activity (MIC, 3.12–50 µg/mL) against four fungal strains. The high safety against vaginal epithelium (HeLa cells) and compatibility with vaginal flora (lactobacillus), SVF stability and least vaginal absorption supported its suitability for topical vaginal application. Docking study was performed to gain an insight into the binding mode and interactions of the most promising compound, N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) with HIV-1 Reverse Transcriptase. The docking study has revealed that compound (29) interacted with HIV-1 RT similar to standard drug Nevirapine. It may be concluded that hybridization of benzenepropanamine and thiourea moiety resulted into novel lead with multiple activities including RT inhibition. A further lead optimization may result into effective vaginal microbicides having spermicidal, anti-Trichomonas, antifungal and anti-HIV potential altogether with enhanced safety to cervico-vaginal cells in comparison to Nonoxynol-9.

Keywords: microbicidal, nonoxynol-9, reverse transcriptase, spermicide

Procedia PDF Downloads 329
72 Stromal Vascular Fraction Regenerative Potential in a Muscle Ischemia/Reperfusion Injury Mouse Model

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

Abstract:

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

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

Procedia PDF Downloads 98
71 Angiopermissive Foamed and Fibrillar Scaffolds for Vascular Graft Applications

Authors: Deon Bezuidenhout

Abstract:

Pre-seeding with autologous endothelial cells improves the long-term patency of synthetic vascular grafts levels obtained with autografts, but is limited to a single centre due to resource, time and other constraints. Spontaneous in vivo endothelialization would obviate the need for pre-seeding, but has been shown to be absent in man due to limited transanastomotic and fallout healing, and the lack of transmural ingrowth due to insufficient porosity. Two types of graft scaffolds with increased interconnected porosity for improved tissue ingrowth and healing are thus proposed and described. Foam-type polyurethane (PU) scaffolds with small, medium and large, interconnected pores were made by phase inversion and spherical porogen extraction, with and without additional surface modification with covalently attached heparin and subsequent loading with and delivery of growth factors. Fibrillar scaffolds were made either by standard electrospinning using degradable PU (Degrapol®), or by dual electrospinning using non-degradable PU. The latter process involves sacrificial fibres that are co-spun with structural fibres and subsequently removed to increased porosity and pore size. Degrapol samples were subjected to in vitro degradation, and all scaffold types were evaluated in vivo for tissue ingrowth and vascularization using rat subcutaneous model. The foam scaffolds were additionally evaluated in a circulatory (rat infrarenal aortic interposition) model that allows for the grafts to be anastomotically and/or ablumenally isolated to discern and determine endothelialization mode. Foam-type grafts with large (150 µm) pores showed improved subcutaneous healing in terms of vascularization and inflammatory response over smaller pore sizes (60 and 90µm), and vascularization of the large porosity scaffolds was significantly increased by more than 70% by heparin modification alone, and by 150% to 400% when combined with growth factors. In the circulatory model, extensive transmural endothelialization (95±10% at 12 w) was achieved. Fallout healing was shown to be sporadic and limited in groups that were ablumenally isolated to prevent transmural ingrowth (16±30% wrapped vs. 80±20% control; p<0.002). Heparinization and GF delivery improved both mural vascularization and lumenal endothelialization. Degrapol electrospun scaffolds showed decrease in molecular mass and corresponding tensile strength over the first 2 weeks, but very little decrease in mass over the 4w test period. Studies on the effect of tissue ingrowth with and without concomitant degradation of the scaffolds, are being used to develop material models for the finite element modelling. In the case of the dual-spun scaffolds, the PU fibre fraction could be controlled shown to vary linearly with porosity (P = −0.18FF +93.5, r2=0.91), which in turn showed inverse linear correlation with tensile strength and elastic modulus (r2 > 0.96). Calculated compliance and burst pressures of the scaffolds increased with fibre fraction, and compliances matching the human popliteal artery (5-10 %/100 mmHg), and high burst pressures (> 2000 mmHg) could be achieved. Increasing porosity (76 to 82 and 90%) resulted in increased tissue ingrowth from 33±7 to 77±20 and 98±1% after 28d. Transmural endothelialization of highly porous foamed grafts is achievable in a circulatory model, and the enhancement of porosity and tissue ingrowth may hold the key the development of spontaneously endothelializing electrospun grafts.

Keywords: electrospinning, endothelialization, porosity, scaffold, vascular graft

Procedia PDF Downloads 272
70 Midterm Clinical and Functional Outcomes After Treatment with Ponseti Method for Idiopathic Clubfeet: A Prospective Cohort Study

Authors: Neeraj Vij, Amber Brennan, Jenni Winters, Hadi Salehi, Hamy Temkit, Emily Andrisevic, Mohan V. Belthur

Abstract:

Idiopathic clubfoot is a common lower extremity deformity with an incidence of 1:500. The Ponseti Method is well known as the gold standard of treatment. However, there is limited functional data demonstrating correction of the clubfoot after treatment with the Ponseti method. The purpose of this study was to study the clinical and functional outcomes after the Ponseti method with the Clubfoot Disease-Specific Instrument (CDS) and pedobarography. This IRB-approved prospective study included patients aged 3-18 who were treated for idiopathic clubfoot with the Ponseti method between January 2008 and December 2018. Age-matched controls were identified through siblings of clubfoot patients and other community members. Treatment details were collected through a chart review of the included patients. Laboratory assessment included a physical exam, gait analysis, and pedobarography. The Pediatric Outcomes Data Collection Instrument and the Clubfoot Disease-Specific Instrument were also obtained on clubfoot patients (CF). The Wilcoxson rank-sum test was used to study differences between the CF patients and the typically developing (TD) patients. Statistical significance was set at p < 0.05. There were a total of 37 enrolled patients in our study. 21 were priorly treated for CF and 16 were TD. 94% of the CF patients had bilateral involvement. The age at the start of treatment was 29 days, the average total number of casts was seven to eight, and the average total number of casts after Achilles tenotomy was one. The reoccurrence rate was 25%, tenotomy was required in 94% of patients, and ≥1 tenotomy was required in 25% of patients. There were no significant differences between step length, step width, stride length, force-time integral, maximum peak pressure, foot progression angles, stance phase time, single-limb support time, double limb support time, and gait cycle time between children treated with the Ponseti method and typically developing children. The average post-treatment Pirani and Dimeglio scores were 5.50±0.58 and 15.29±1.58, respectively. The average post-treatment PODCI subscores were: Upper Extremity: 90.28, Transfers: 94.6, Sports: 86.81, Pain: 86.20, Happiness: 89.52, Global: 88.6. The average post-treatment Clubfoot Disease-Specific Instrument scores subscores were: Satisfaction: 73.93, Function: 80.32, Overall: 78.41. The Ponseti Method has a very high success rate and remains to be the gold standard in the treatment of idiopathic clubfoot. Timely management leads to good outcomes and a low need for repeated Achilles tenotomy. Children treated with the Ponseti method demonstrate good functional outcomes as measured through pedobarography. Pedobarography may have clinical utility in studying congenital foot deformities. Objective measures for hours of brace wear could represent an improvement in clubfoot care.

Keywords: functional outcomes, pediatric deformity, patient-reported outcomes, talipes equinovarus

Procedia PDF Downloads 56
69 Examining Gender Bias in the Sport Concussion Assessment Tool 3 (SCAT3): A Differential Item Functioning Analysis in NCAA Sports

Authors: Rachel M. Edelstein, John D. Van Horn, Karen M. Schmidt, Sydney N. Cushing

Abstract:

As a consequence of sports-related concussions, female athletes have been documented as reporting more symptoms than their male counterparts, in addition to incurring longer periods of recovery. However, the role of sex and its potential influence on symptom reporting and recovery outcomes in concussion management has not been completely explored. The present aims to investigate the relationship between female concussion symptom severity and the presence of assessment bias. The Sport Concussion Assessment Tool 3 (SCAT3), collected by the NCAA and DoD CARE Consortium, was quantified at five different time points post-concussion. N= 1,258 NCAA athletes, n= 473 female (soccer, rugby, lacrosse, ice hockey) and n=785 male athletes (football, rugby, lacrosse, ice hockey). A polytomous Item Response Theory (IRT) Graded Response Model (GRM) was used to assess the relationship between sex and symptom reporting. Differential Item Functioning (DIF) and Differential Group Functioning (DGF) were used to examine potential group-level bias. Interactions for DIF were utilized to explore the impact of sex on symptom reporting among NCAA male and female athletes throughout and after their concussion recovery. DIF was significantly detected after B-H corrections displayed in limited items; however, one symptom, “Pressure in Head” (-0.29, p=0.04 vs -0.20, p =0.04), was statistically significant at both < 6 hours and 24-48 hours. Thus, implies that at < 6 hours, males were 29% less likely to indicate “Pressure in the Head” compared to female athletes and 20% less likely at 24-48 hours. Overall, the DGF suggested significant group differences, suggesting that male athletes might be at a higher risk for returning to play prematurely (logits = -0.38, p < 0.001). However, after analyzing the SCAT 3, a clinically relevant trend was discovered. Twelve out of the twenty-two symptoms suggest higher difficulty in female athletes within three or more of the five-time points. These symptoms include Balance Problems, Blurry Vision, Confusion, Dizziness, Don’t Feel Right, Feel in Fog, Feel Slow Down, Low Energy, Neck Pain, Sensitivity to Light, Sensitivity to Noise, Trouble Falling Asleep. Despite a lack of statistical significance, this tendency is contrary to current literature stating that males may be unclear on symptoms, but females may be more honest in reporting symptoms. Further research, which includes possible modifying socioecological factors, is needed to determine whether females may consistently experience more symptoms and require longer recovery times or if, parsimoniously, males tend to present their symptoms and readiness for play differently than females. Such research will help to improve the validity of current assumptions concerning male as compared to female head injuries and optimize individualized treatments for sports-related head injuries.

Keywords: female athlete, sports-related concussion, item response theory, concussion assessment

Procedia PDF Downloads 51
68 Road Map to Health: Palestinian Workers in Israel's Construction Sector

Authors: Maya de Vries Kedem, Abir Jubran, Diana Baron

Abstract:

Employment in Israel offers Palestinian workers an income double what they can earn in the West Bank. The need to support their families leads many educated Palestinians to forgo finding work in their profession in the Palestinian Authority and instead look for employment in those sectors open to them in Israel, particularly the construction, agriculture, and industry sectors. The International Labor Organization estimated that about 1,200 workers in Israel die every year because of occupational diseases (diseases caused by working conditions). Construction workers in Israel are constantly exposed to dust, noise, chemical materials, and work in awkward postures, which require prolonged bending, repetitive motion, and other risk factors that can lead to illnesses and death. Occupational health is vastly neglected in Israel and construction workers are particularly at risk . As of June 2022, the Israeli quota in the construction sector for Palestinian workers stood at 80,000. Kav LaOved released a new study on the state of occupational health among Palestinian workers employed in construction in Israel. The study Roadmap to Health: Palestinian Workers in Israel's Construction Sector reviews the extent to which the health of Palestinian workers is protected at work in Israel. The report includes analysis of a survey administered to 256 workers as well as interviews with 10 workers and with 5 Israeli occupational health experts. Report highlights: • Among survey respondents, 63.9% stated that safety procedures to protect their health are rarely followed in their workplace (e.g., taking breaks, using protective gear, following restrictions on lifting heavy items, and having inspectors regularly on site to monitor safety). • All 256 Palestinian workers who participated to the survey said that their health has been directly or indirectly harmed by working in Israel and reported suffering from the following problems: orthopedic problems such as joint, hand, leg or knee problems (100%); headaches (75%); back problems (36.3%); eye problems (23.8%); breathing problems (17.6%); chronic pain (14.8%); heart problems (7.8%); and skin problems (3.5%). • Workers who are injured or do not feel well often continue working for fear of losing their payment for that day. About half of the 256 survey respondents reported that they pay brokerage fees to find an employer with a work permit, often paying between 2,000 and 3,000 NIS per month. “I have an obligation—I pay about NIS 120 a day for my permit, [and] I have to pay for it whether I work or not" a worker said. • Most Palestinian construction workers suffer from stress and mental health problems. Workers pointed to several issues that greatly affect their mood and mental state: daily crossings at crowded checkpoints where workers stand for hours; lack of sleep due to leaving home daily at 3:00-3:30 am; commuting two to four hours to work in each direction; and abusive work environments. A worker told KLO that the sight of thousands of workers standing together at the checkpoint causes “high blood pressure and the feeling that you are going to be squeezed.” Another said, “I felt that my bones would break.” In the survey workers reported suffering from insomnia (70.1%), breathing difficulties (35.8%), chest pressure (27.6%), or rapid pulse rate (12.2%).

Keywords: construction sector, palestinian workers, occupational health, Israel, occupation

Procedia PDF Downloads 64
67 Encapsulated Bioflavonoids: Nanotechnology Driven Food Waste Utilization

Authors: Niharika Kaushal, Minni Singh

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Citrus fruits fall into the category of those commercially grown fruits that constitute an excellent repository of phytochemicals with health-promoting properties. Fruits belonging to the citrus family, when processed by industries, produce tons of agriculture by-products in the form of peels, pulp, and seeds, which normally have no further usage and are commonly discarded. In spite of this, such residues are of paramount importance due to their richness in valuable compounds; therefore, agro-waste is considered a valuable bioresource for various purposes in the food sector. A range of biological properties, including anti-oxidative, anti-cancerous, anti-inflammatory, anti-allergenicity, and anti-aging activity, have been reported for these bioactive compounds. Taking advantage of these inexpensive residual sources requires special attention to extract bioactive compounds. Mandarin (Citrus nobilis X Citrus deliciosa) is a potential source of bioflavonoids with antioxidant properties, and it is increasingly regarded as a functional food. Despite these benefits, flavonoids suffer from a barrier of pre-systemic metabolism in gastric fluid, which impedes their effectiveness. Therefore, colloidal delivery systems can completely overcome the barrier in question. This study involved the extraction and identification of key flavonoids from mandarin biomass. Using a green chemistry approach, supercritical fluid extraction at 330 bar, temperature 40C, and co-solvent 10% ethanol was employed for extraction, and the identification of flavonoids was made by mass spectrometry. As flavonoids are concerned with a limitation, the obtained extract was encapsulated in polylactic-co-glycolic acid (PLGA) matrix using a solvent evaporation method. Additionally, the antioxidant potential was evaluated by the 2,2-diphenylpicrylhydrazyl (DPPH) assay. A release pattern of flavonoids was observed over time using simulated gastrointestinal fluids. From the results, it was observed that the total flavonoids extracted from the mandarin biomass were estimated to be 47.3 ±1.06 mg/ml rutin equivalents as total flavonoids. In the extract, significantly, polymethoxyflavones (PMFs), tangeretin and nobiletin were identified, followed by hesperetin and naringin. The designed flavonoid-PLGA nanoparticles exhibited a particle size between 200-250nm. In addition, the bioengineered nanoparticles had a high entrapment efficiency of nearly 80.0% and maintained stability for more than a year. Flavonoid nanoparticles showed excellent antioxidant activity with an IC50 of 0.55μg/ml. Morphological studies revealed the smooth and spherical shape of nanoparticles as visualized by Field emission scanning electron microscopy (FE-SEM). Simulated gastrointestinal studies of free extract and nanoencapsulation revealed the degradation of nearly half of the flavonoids under harsh acidic conditions in the case of free extract. After encapsulation, flavonoids exhibited sustained release properties, suggesting that polymeric encapsulates are efficient carriers of flavonoids. Thus, such technology-driven and biomass-derived products form the basis for their use in the development of functional foods with improved therapeutic potential and antioxidant properties. As a result, citrus processing waste can be considered a new resource that has high value and can be used for promoting its utilization.

Keywords: citrus, agrowaste, flavonoids, nanoparticles

Procedia PDF Downloads 96
66 Symptom Burden and Quality of Life in Advanced Lung Cancer Patients

Authors: Ammar Asma, Bouafia Nabiha, Dhahri Meriem, Ben Cheikh Asma, Ezzi Olfa, Chafai Rim, Njah Mansour

Abstract:

Despite recent advances in treatment of the lung cancer patients, the prognosis remains poor. Information is limited regarding health related quality of life (QOL) status of advanced lung cancer patients. The purposes of this study were: to assess patient reported symptom burden, to measure their QOL, and to identify determinant factors associated with QOL. Materials/Methods: A cross sectional study of 60 patients was carried out from over the period of 03 months from February 1st to 30 April 2016. Patients were recruited in two department of health care: Pneumology department in a university hospital in Sousse and an oncology unit in a University Hospital in Kairouan. Patients with advanced stage (III and IV) of lung cancer who were hospitalized or admitted in the day hospital were recruited by convenience sampling. We used a questionnaire administrated and completed by a trained interviewer. This questionnaire is composed of three parts: demographic, clinical and therapeutic information’s, QOL measurements: based on the SF-36 questionnaire, Symptom’s burden measurement using the Lung Cancer Symptom Scale (LCSS). To assess Correlation between symptoms burden and QOL, we compared the scores of two scales two by two using the Pearson correlation. To identify factors influencing QOL in Lung cancer, a univariate statistical analysis then, a stepwise backward approach, wherein the variables with p< 0.2, were carried out to determine the association between SF-36 scores and different variables. Results: During the study period, 60 patients consented to complete symptom and quality of life questionnaires at a single point time (72% were recruited from day hospital). The majority of patients were male (88%), age ranged from 21 to 79 years with a mean of 60.5 years. Among patients, 48 (80%) were diagnosed as having non-small cell lung carcinoma (NSCLC). Approximately, 60 % (n=36) of patients were in stage IV, 25 % in stage IIIa and 15 % in stage IIIb. For symptom burden, the symptom burden index was 43.07 (Standard Deviation, 21.45). Loss of appetite and fatigue were rated as the most severe symptoms with mean scores (SD): 49.6 (25.7) and 58.2 (15.5). The average overall score of SF36 was 39.3 (SD, 15.4). The physical and emotional limitations had the lowest scores. Univariate analysis showed that factors which influence negatively QOL were: married status (p<0.03), smoking cessation after diagnosis (p<0.024), LCSS total score (p<0.001), LCSS symptom burden index (p<0.001), fatigue (p<0.001), loss of appetite (p<0.001), dyspnea (p<0.001), pain (p<0.002), and metastatic stage (p<0.01). In multivariate analysis, unemployment (p<0.014), smoking cessation after diagnosis (p<0.013), consumption of analgesic (p<0.002) and the indication of an analgesic radiotherapy (p<0.001) are revealed as independent determinants of QOL. The result of the correlation analyses between total LCSS scores and the total and individual domain SF36 scores was significant (p<0.001); the higher total LCSS score is, the poorer QOL is. Conclusion: A built in support of lung cancer patients would better control the symptoms and promote the QOL of these patients.

Keywords: quality of life, lung cancer, metastasis, symptoms burden

Procedia PDF Downloads 364
65 Validation of an Educative Manual for Patients with Breast Cancer Submitted to Radiation Therapy

Authors: Flavia Oliveira de A. M. Cruz, Edison Tostes Faria, Paula Elaine D. Reis

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When the breast is submitted to radiation therapy (RT), the most common effects are pain, skin changes, mobility restrictions, local sensory alteration, and fatigue. These effects, if not managed properly, may reduce the quality of life of cancer patients and may lead to the treatment discontinuation. Therefore, promoting knowledge and guidelines for symptom management remain a high priority for patients and a challenge for health professionals, due to the need to handle side effects in a population with a life-threatening disease. Printed materials are important strategies for supporting educative activities since they help the individual to assimilate and understand the amount of information transmitted. Nurses' behavior can be systematized through the use of an educative manual, which may be effective in promoting information regarding the treatment, self-care and how to control the effects of RT at home. In view of the importance of guaranteeing the validity of the material before its use, the objective of this research was to validate the content and appearance of an educative manual for breast cancer patients undergoing RT. The Theory of Psychometrics was used for the validation process in this descriptive methodological research. A minimum agreement rate (AR) of 80% was considered to guarantee the validity of the material. The data were collected from October to December 2017, by means of two assessments tools, constructed in the form of a Likert scale, with five levels of understanding. These instruments addressed different aspects of the evaluation, in view of two different groups of participants; 17 experts in the theme area of the educative manual, and 12 women that received RT previously to treat breast cancer. The manual was titled 'Orientation Manual: radiation therapy in breast', and was focused on breast cancer patients attended at the Department of Oncology of the Brasília University Hospital (UNACON/HUB). The research project was submitted to the Research Ethics Committee at the School of Health Sciences of the University of Brasília (CAAE: 24592213.1.0000.0030). Only two items of the assessment tool for the experts, one related to the manual's ability to promote behavioral and attitude changes and the other related to the extent of its use for other health services, obtained AR < 80% and were reformulated based on the participants' suggestions and in the literature. All other items were considered appropriate and/or complete appropriate in the three blocks proposed for the experts: objectives - 89%, structure and form - 93%, and relevance - 93%; and good and/or very good in the five blocks of analysis proposed for patients: objectives - 100%, organization - 100%, writing style - 100%, appearance - 100%, and motivation. The appearance and content validation of the educative manual proposed were attended to. The educative manual was considered relevant and pertinent and may contribute to the understanding of the therapeutic process by breast cancer patients during RT, as well as support clinical practice through the nursing consultation.

Keywords: oncology nursing, nursing care, validation studies, educational technology

Procedia PDF Downloads 100
64 Targeting Basic Leucine Zipper Transcription Factor ATF-Like Mediated Immune Cells Regulation to Reduce Crohn’s Disease Fistula Incidence

Authors: Mohammadjavad Sotoudeheian, Soroush Nematollahi

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Crohn’s disease (CD) is a chronic gastrointestinal segment inflammation encompassing immune dysregulation in a genetically susceptible individual in response to the environmental triggers and interaction between the microbiome and immune system. Uncontrolled inflammation leads to long-term complications, including fibrotic strictures and enteric fistulae. Increased production of Th1 and Th17-cell cytokines and defects in T-regulatory cells have been associated with CD. Th17-cells are essential for protection against extracellular pathogens, but their atypical activity can cause autoimmunity. Intrinsic defects in the control of programmed cell death in the mucosal T-cell compartment are strongly implicated in the pathogenesis of CD. The apoptosis defect in mucosal T-cells in CD has been endorsed as an imbalance of the Bcl-2 and the Bax. The immune system encounters foreign antigens through microbial colonization of mucosal surfaces or infections. In addition, FOSL downregulated IL-26 expression, a cytokine that marks inflammatory Th17-populations in patients suffering from CD. Furthermore, the expression of IL-23 is associated with the transcription factor primary leucine zipper transcription factor ATF-like (Batf). Batf-deficiency demonstrated the crucial role of Batf in colitis development. Batf and IL-23 mediate their effects by inducing IL-6 production. Strong association of IL-23R, Stat3, and Stat4 with IBD susceptibility point to a critical involvement of T-cells. IL-23R levels in transfer fistula were dependent on the AP-1 transcription factor JunB that additionally controlled levels of RORγt by facilitating DNA binding of Batf. T lymphocytes lacking JunB failed to induce IL-23- and Th17-mediated experimental colitis highlighting the relevance of JunB for the IL-23/ Th17 pathway. The absence of T-bet causes unrestrained Th17-cell differentiation. T-cells are central parts of immune-mediated colon fistula. Especially Th17-cells were highly prevalent in inflamed IBD tissues, as RORγt is effective in preventing colitis. Intraepithelial lymphocytes (IEL) contain unique T-cell subsets, including cells expressing RORγt. Increased activated Th17 and decreased T-regulatory cells in inflamed intestinal tissues had been seen. T-cells differentiate in response to many cytokines, including IL-1β, IL-6, IL-23, and TGF-β, into Th17-cells, a process which is critically dependent on the Batf. IL-23 promotes Th17-cell in the colon. Batf manages the generation of IL-23 induced IL-23R+ Th17-cells. Batf is necessary for TGF-β/IL-6-induced Th17-polarization. Batf-expressing T-cells are the core of T-cell-mediated colitis. The human-specific parts of three AP-1 transcription factors, FOSL1, FOSL2, and BATF, are essential during the early stages of Th17 differentiation. BATF supports the Th17 lineage. FOSL1, FOSL2, and BATF make possession of regulatory loci of genes in the Th17 lineage cascade. The AP1 transcription factor Batf is identified to control intestinal inflammation and seems to regulate pathways within lymphocytes, which could theoretically control the expression of several genes. It shows central regulatory properties over Th17-cell development and is intensely upregulated within IBD-affected tissues. Here, we demonstrated that targeting Batf in IBD appears as a therapeutic approach that reduces colitogenic T-cell activities during fistula formation while aiming to affect inflammation in the gut epithelial cells.

Keywords: immune system, Crohn’s Disease, BATF, T helper cells, Bcl, interleukin, FOSL

Procedia PDF Downloads 123
63 Treatment Outcome Of Corneal Ulcers Using Levofloxacin Hydrate 1.5% Ophthalmic Solution And Adjuvant Oral Ciprofloxacin, A Treatment Strategy Applicable To Primary Healthcare

Authors: Celine Shi Ying Lee, Jong Jian Lee

Abstract:

Background: Infectious keratitis is one of the leading causes of blindness worldwide. Prompt treatment with effective medication will control the infection early, preventing corneal scarring and visual loss. fluoroquinolones ophthalmic medication is used because of its broad-spectrum properties, potency, good intraocular penetration, and low toxicity. The study aims to evaluate the treatment outcome of corneal ulcers using Levofloxacin 1.5% ophthalmic solution (LVFX) with adjuvant oral ciprofloxacin when indicated and apply this treatment strategy in primary health care as first-line treatment. Methods: Patients with infective corneal ulcer treated in an eye center were recruited. Inclusion criteria includes Corneal infection consistent with bacterial keratitis, single or multiple small corneal ulcers. Treatment regime: LVFX hourly for the first 2 days, 2 hourly from the 3rd day, and 3 hourly on the 5th day of review. Adjuvant oral ciprofloxacin 500mg BD was administered for 5 days if there were multiple corneal ulcers or when the location of the cornea ulcer was central or paracentral. Results: 47 subjects were recruited. There were 16 (34%) males and 31 (66%) females. 40 subjects (85%) were contact lens (CL) related to corneal ulcer, and 7 subjects (15%) were non-contact lens related. 42 subjects (89%) presented with one ulcer, of which 20 of them (48%) needed adjuvant therapy. 5 subjects presented with 2 or 3 ulcers, of which 3 needed adjuvant therapy. A total of 23 subjects (49%) was given adjuvant therapy (oral ciprofloxacin 500mg BD for 5 days).21 of them (91%) were CL related. All subjects recovered fully, and the average duration of treatment was 3.7 days, with 49% of the subjects resolved on the 3rd day, 38% on the 5thday of and 13% on the 7thday. All subjects showed symptoms of relief of pain, light-sensitivity, and redness on the 3rd day with full visual recovery post-treatment. No adverse drug reactions were recorded. Conclusion: Our treatment regime demonstrated good clinical outcome as first-line treatment for corneal ulcers. A corneal ulcer is a common eye condition in Singapore, mainly due to CL wear. Pseudomonas aeruginosa is the most frequent and potentially sight-threatening pathogen involved in CL related corneal ulcer. Coagulase-negative Staphylococci, Staphylococcus aureus, and Streptococcus Pneumoniae were seen in non-CL users. All these bacteria exhibit good sensitivity rates to ciprofloxacin and levofloxacin. It is therefore logical in our study to use LVFX Eyedrops and adjuvant ciprofloxacin oral antibiotics when indicated as first line treatment for most corneal ulcers. Our study of patients, both CL related and non-CL related, have shown good clinical response and full recovery using the above treatment strategy. There was also a full restoration of visual acuity in all the patients. Eye-trained primary Healthcare practitioners can consider adopting this treatment strategy as first line treatment in patients with corneal ulcers. This is relevant during the COVID pandemic, where hospitals are overwhelmed with patients and in regions with limited access to specialist eye care. This strategy would enable early treatment with better clinical outcome.

Keywords: corneal ulcer, levofloxacin hydrate, treatment strategy, ciprofloxacin

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62 A Second Chance to Live and Move: Lumbosacral Spinal Cord Ischemia-Infarction after Cardiac Arrest and the Artery of Adamkiewicz

Authors: Anna Demian, Levi Howard, L. Ng, Leslie Simon, Mark Dragon, A. Desai, Timothy Devlantes, W. David Freeman

Abstract:

Introduction: Out-of-hospital cardiac arrest (OHCA) can carry a high mortality. For survivors, the most common complication is hypoxic-ischemic brain injury (HIBI). Rarely, lumbosacral spinal cord and/or other spinal cord artery ischemia can occur due to anatomic variation and variable mean arterial pressure after the return of spontaneous circulation. We present a case of an OHCA survivor who later woke up with bilateral leg weakness with preserved sensation (ASIA grade B, L2 level). Methods: We describe a clinical, radiographic, and laboratory presentation, as well as a National Library of Medicine (NLM) search engine methodology, characterizing incidence/prevalence of this entity is discussed. A 70-year-old male, a longtime smoker, and alcohol user, suddenly collapsed at a bar surrounded by friends. He had complained of chest pain before collapsing. 911 was called. EMS arrived, and the patient was in pulseless electrical activity (PEA), cardiopulmonary resuscitation (CPR) was initiated, and the patient was intubated, and a LUCAS device was applied for continuous, high-quality CPR in the field by EMS. In the ED, central lines were placed, and thrombolysis was administered for a suspected Pulmonary Embolism (PE). It was a prolonged code that lasted 90 minutes. The code continued with the eventual return of spontaneous circulation. The patient was placed on an epinephrine and norepinephrine drip to maintain blood pressure. ECHO was performed and showed a “D-shaped” ventricle worrisome for PE as well as an ejection fraction around 30%. A CT with PE protocol was performed and confirmed bilateral PE. Results: The patient woke up 24 hours later, following commands, and was extubated. He was found paraplegic below L2 with preserved sensation, with hypotonia and areflexia consistent with “spinal shock” or anterior spinal cord syndrome. MRI thoracic and lumbar spine showed a conus medullaris level spinal cord infarction. The patient was given IV steroids upon initial discovery of cord infarct. NLM search using “cardiac arrest” and “spinal cord infarction” revealed 57 results, with only 8 review articles. Risk factors include age, atherosclerotic disease, and intraaortic balloon pump placement. AoA (Artery of Adamkiewicz) anatomic variation along with existing atherosclerotic factors and low perfusion were also known risk factors. Conclusion: Acute paraplegia from anterior spinal cord infarction of the AoA territory after cardiac arrest is rare. Larger prospective, multicenter trials are needed to examine potential interventions of hypothermia, lumbar drains, which are sometimes used in aortic surgery to reduce ischemia and/or other neuroprotectants.

Keywords: cardiac arrest, spinal cord infarction, artery of Adamkiewicz, paraplegia

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61 Double Liposomes Based Dual Drug Delivery System for Effective Eradication of Helicobacter pylori

Authors: Yuvraj Singh Dangi, Brajesh Kumar Tiwari, Ashok Kumar Jain, Kamta Prasad Namdeo

Abstract:

The potential use of liposomes as drug carriers by i.v. injection is limited by their low stability in blood stream. Firstly, phospholipid exchange and transfer to lipoproteins, mainly HDL destabilizes and disintegrates liposomes with subsequent loss of content. To avoid the pain associated with injection and to obtain better patient compliance studies concerning various dosage forms, have been developed. Conventional liposomes (unilamellar and multilamellar) have certain drawbacks like low entrapment efficiency, stability and release of drug after single breach in external membrane, have led to the new type of liposomal systems. The challenge has been successfully met in the form of Double Liposomes (DL). DL is a recently developed type of liposome, consisting of smaller liposomes enveloped in lipid bilayers. The outer lipid layer of DL can protect inner liposomes against various enzymes, therefore DL was thought to be more effective than ordinary liposomes. This concept was also supported by in vitro release characteristics i.e. DL formation inhibited the release of drugs encapsulated in inner liposomes. DL consists of several small liposomes encapsulated in large liposomes, i.e., multivesicular vesicles (MVV), therefore, DL should be discriminated from ordinary classification of multilamellar vesicles (MLV), large unilamellar vesicles (LUV), small unilamellar vesicles (SUV). However, for these liposomes, the volume of inner phase is small and loading volume of water-soluble drugs is low. In the present study, the potential of phosphatidylethanolamine (PE) lipid anchored double liposomes (DL) to incorporate two drugs in a single system is exploited as a tool to augment the H. pylori eradication rate. Preparation of DL involves two steps, first formation of primary (inner) liposomes by thin film hydration method containing one drug, then addition of suspension of inner liposomes on thin film of lipid containing the other drug. The success of formation of DL was characterized by optical and transmission electron microscopy. Quantitation of DL-bacterial interaction was evaluated in terms of percent growth inhibition (%GI) on reference strain of H. pylori ATCC 26695. To confirm specific binding efficacy of DL to H. pylori PE surface receptor we performed an agglutination assay. Agglutination in DL treated H. pylori suspension suggested selectivity of DL towards the PE surface receptor of H. pylori. Monotherapy is generally not recommended for treatment of a H. pylori infection due to the danger of development of resistance and unacceptably low eradication rates. Therefore, combination therapy with amoxicillin trihydrate (AMOX) as anti-H. pylori agent and ranitidine bismuth citrate (RBC) as antisecretory agent were selected for the study with an expectation that this dual-drug delivery approach will exert acceptable anti-H. pylori activity.

Keywords: Helicobacter pylorI, amoxicillin trihydrate, Ranitidine Bismuth citrate, phosphatidylethanolamine, multi vesicular systems

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60 Antibacterial Bioactive Glasses in Orthopedic Surgery and Traumatology

Authors: V. Schmidt, L. Janovák, N. Wiegand, B. Patczai, K. Turzó

Abstract:

Large bone defects are not able to heal spontaneously. Bioactive glasses seem to be appropriate (bio)materials for bone reconstruction. Bioactive glasses are osteoconductive and osteoinductive, therefore, play a useful role in bony regeneration and repair. Because of their not optimal mechanical properties (e.g., brittleness, low bending strength, and fracture toughness), their applications are limited. Bioactive glass can be used as a coating material applied on metal surfaces. In this way -when using them as implants- the excellent mechanical properties of metals and the biocompatibility and bioactivity of glasses will be utilized. Furthermore, ion release effects of bioactive glasses regarding osteogenic and angiogenic responses have been shown. Silicate bioactive glasses (45S5 Bioglass) induce the release and exchange of soluble Si, Ca, P, and Na ions on the material surface. This will lead to special cellular responses inducing bone formation, which is favorable in the biointegration of the orthopedic prosthesis. The incorporation of other additional elements in the silicate network such as fluorine, magnesium, iron, silver, potassium, or zinc has been shown, as the local delivery of these ions is able to enhance specific cell functions. Although hip and knee prostheses present a high success rate, bacterial infections -mainly implant associated- are serious and frequent complications. Infection can also develop after implantation of hip prostheses, the elimination of which means more surgeries for the patient and additional costs for the clinic. Prosthesis-related infection is a severe complication of orthopedic surgery, which often causes prolonged illness, pain, and functional loss. While international efforts are made to reduce the risk of these infections, orthopedic surgical infections (SSIs) continue to occur in high numbers. It is currently estimated that up to 2.5% of primary hip and knee surgeries and up to 20% of revision arthroplasties are complicated by periprosthetic joint infection (PJIs). According to some authors, these numbers are underestimated, and they are also increasing. Staphylococcus aureus is the leading cause of both SSIs and PJIs, and the prevalence of methicillin-resistant S. aureus (MRSA) is on the rise, particularly in the United States. These deep infections lead to implant removal and consequently increase morbidity and mortality. The study targets this clinical problem using our experience so far with the Ag-doped polymer coatings on Titanium implants. Non-modified or modified (e.g., doped with antibacterial agents, like Ag) bioactive glasses could play a role in the prevention of infections or the therapy of infected tissues. Bioactive glasses have excellent biocompatibility, proved by in vitro cell culture studies of human osteoblast-like MG-63 cells. Ag-doped bioactive glass-scaffold has a good antibacterial ability against Escherichia coli and other bacteria. It may be concluded that these scaffolds have great potential in the prevention and therapy of implant-associated bone infection.

Keywords: antibacterial agents, bioactive glass, hip and knee prosthesis, medical implants

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59 Immersive and Non-Immersive Virtual Reality Applied to the Cervical Spine Assessment

Authors: Pawel Kiper, Alfonc Baba, Mahmoud Alhelou, Giorgia Pregnolato, Michela Agostini, Andrea Turolla

Abstract:

Impairment of cervical spine mobility is often related to pain triggered by musculoskeletal disorders or direct traumatic injuries of the spine. To date, these disorders are assessed with goniometers and inclinometers, which are the most popular devices used in clinical settings. Nevertheless, these technologies usually allow measurement of no more than two-dimensional range of motion (ROM) quotes in static conditions. Conversely, the wide use of motion tracking systems able to measure 3 to 6 degrees of freedom dynamically, while performing standard ROM assessment, are limited due to technical complexities in preparing the setup and high costs. Thus, motion tracking systems are primarily used in research. These systems are an integral part of virtual reality (VR) technologies, which can be used for measuring spine mobility. To our knowledge, the accuracy of VR measure has not yet been studied within virtual environments. Thus, the aim of this study was to test the reliability of a protocol for the assessment of sensorimotor function of the cervical spine in a population of healthy subjects and to compare whether using immersive or non-immersive VR for visualization affects the performance. Both VR assessments consisted of the same five exercises and random sequence determined which of the environments (i.e. immersive or non-immersive) was used as first assessment. Subjects were asked to perform head rotation (right and left), flexion, extension and lateral flexion (right and left side bending). Each movement was executed five times. Moreover, the participants were invited to perform head reaching movements i.e. head movements toward 8 targets placed along a circular perimeter each 45°, visualized one-by-one in random order. Finally, head repositioning movement was obtained by head movement toward the same 8 targets as for reaching and following reposition to the start point. Thus, each participant performed 46 tasks during assessment. Main measures were: ROM of rotation, flexion, extension, lateral flexion and complete kinematics of the cervical spine (i.e. number of completed targets, time of execution (seconds), spatial length (cm), angle distance (°), jerk). Thirty-five healthy participants (i.e. 14 males and 21 females, mean age 28.4±6.47) were recruited for the cervical spine assessment with immersive and non-immersive VR environments. Comparison analysis demonstrated that: head right rotation (p=0.027), extension (p=0.047), flexion (p=0.000), time (p=0.001), spatial length (p=0.004), jerk target (p=0.032), trajectory repositioning (p=0.003), and jerk target repositioning (p=0.007) were significantly better in immersive than non-immersive VR. A regression model showed that assessment in immersive VR was influenced by height, trajectory repositioning (p<0.05), and handedness (p<0.05), whereas in non-immersive VR performance was influenced by height, jerk target (p=0.002), head extension, jerk target repositioning (p=0.002), and by age, head flex/ext, trajectory repositioning, and weight (p=0.040). The results of this study showed higher accuracy of cervical spine assessment when executed in immersive VR. The assessment of ROM and kinematics of the cervical spine can be affected by independent and dependent variables in both immersive and non-immersive VR settings.

Keywords: virtual reality, cervical spine, motion analysis, range of motion, measurement validity

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58 Chemical and Biological Studies of Kielmeyera coriacea Mart. (Calophyllaceae) Based on Ethnobotanical Survey of Rural Community from Brazil

Authors: Vanessa G. P. Severino, Eliangela Cristina Candida Costa, Nubia Alves Mariano Teixeira Pires Gomides, Lucilia Kato, Afif Felix Monteiro, Maria Anita Lemos Vasconcelos Ambrosio, Carlos Henrique Gomes Martins

Abstract:

One of the biomes present in Brazil is known as Cerrado, which is a vast tropical savanna ecoregion, particularly in the states of Goiás, Mato Grosso do Sul, Mato Grosso, Tocantins and Minas Gerais. Many species of plants are characterized as endemic and they have therapeutic value for a large part of the population, especially to the rural communities. Given that, the southeastern region of the state of Goiás contains about 21 rural communities, which present a form of organization based on the use of natural resources available. One of these rural communities is named of Coqueiros, where the knowledge about the medicinal plants was very important to this research. Thus, this study focuses on the ethnobotanical survey of this community on the use of Kielmeyera coriacea to treat diseases. From the 37 members interviewed, 76% indicated this species for the treatment of intestinal infection, leukemia, anemia, gastritis, gum pain, toothache, cavity, arthritis, arthrosis, healing, vermifuge, rheumatism, antibiotic, skin problems, mycoses and all kinds of infections. The medicinal properties attributed during the interviews were framed in the body system (disease categories), adapted from ICD 10; thus, 20 indications of use were obtained, among five body systems. Therefore, the root of this species was select to chemical and biological (antioxidant and antimicrobial) studies. From the liquid-liquid extraction of ethanolic extract of root (EER), the hexane (FH), ethyl acetate (FAE), and hydro alcoholic (FHA) fractions were obtained. The chemical profile study of these fractions was performed by LC-MS, identifying major compounds such as δ-tocotrienol, prenylated acylphoroglucinol, 2-hydroxy-1-methoxyxanthone and quercitrin. EER, FH, FAE and FHA were submitted to biological tests. FHA presented the best antioxidant action (EC50 201.53 μg mL-1). EER inhibited the bacterial growth of Streptococcus pyogenes and Pseudomonas aeruginosa, microorganisms associated with rheumatism, at Minimum Inhibitory Concentration (MIC) of 6.25 μg mL-1. In addition, the FH-10 subfraction, obtained from FH fractionation, presented MIC of 1.56 μg mL-1 against S. pneumoniae; EER also inhibited the fungus Candida glabrata (MIC 7.81 μg mL- 1). The FAE-4.7.3 fraction, from the fractionation of FAE, presented MIC of 200 μg mL-1 against Lactobacillus casei, which is one of the causes of caries and oral infections. By the correlation of the chemical and biological data, it is possible to note that the FAE-4.7.3 and FH-10 are constituted 4-hydroxy-2,3-methylenedioxy xanthone, 3-hydroxy-1,2-dimethoxy xanthone, lupeol, prenylated acylphoroglucinol and quercitrin, which could be associated with the biological potential found. Therefore, this study provides an important basis for further investigations regarding the compounds present in the active fractions of K. coriacea, which will permit the establishment of a correlation between ethnobotanical survey and bioactivity.

Keywords: biological activity, ethnobotanical survey, Kielmeyera coriacea Mart., LC-MS profile

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57 Pathophysiological Implications in Immersion Treatment Methods of Icthyophthiriasis Disease in African Catfish (Clarias gariepinus) Using Moringa oleifera Extract

Authors: Ikele Chika Bright, Mgbenka Bernard Obialo, Ikele Chioma Faith

Abstract:

Icthyophthiriasis is a prevalent protozoan (ectoparasite) mostly affecting cultured and aquarium fishes. The majority of the chemotherapeutants lack efficacy for completely eliminating Ich parasite without affecting the environment and they are not safe for human health. The present work is focused on the evaluating different immersion treatments of African catfish (Clarias gariepinus) infected with ichthyophthiriasis and treated with a non-chemical and environmental friendly parasiticides Moringa oleifera. A total number of 800 apparently healthy parasites free (examined) post juvenile catfish were obtained from a reputable farm, disinfected with potassium permanganate in a quarantine tank to remove any possible external parasites. The fish were further challenged with approximately 44,000 infective stages of theronts which were obtained through serial passages by cohabitation. Seven groups (A-G) of post Juvenile were used for the experiment which was carried out into three stages; Dips (60minutes), short term treatment (24-96h) and prolong bath treatment (0-15 days). The concentrations selected were dependent on the outcome of the LC50 of the plant material from which dose-dependent factors were used to select various concentrations of the treatment. In Dips treatment, group D-G were treated with 1,500mg/L, 2500mg/L., 3500mg/L and 4500mg/L, short-term treatment was treated with 150mg/L, 250mg/L, 350mg/L and 450mg/L and prolong bath was treated with 15mg/L, 25mg/L, 35mg/L and 45mg/L of the plant extract whereas group A, B and C were normal control, Ich- infested not treated and Ich- infested treated with standard drug (Acriflavin), respectively. The various types of treatment applied with corresponding concentrations showed almost complete elimination of the adult parasites (trophonts) both in the gills and the body smear, thereby making M. oleifera a potential parasiticides. There were serious pathological alterations in the skin and gills which are usually the main point for Ich parasites invasion but no significant morphological characteristics was noted among the treated groups subjected to different immersion treatment patterns. Epitheliocystis, aneurysm, oedema, hemorrhage, and localization of the adult parasite in the gills were the overall common observations made in the gills whereas degeneration of muscle fibre, dermatitis, hemorrhage, oedema, abscess formation and keratinisation were observed in the skin. However, there are no pathological changes in the control group. Moreover, biochemical parameters such as urea, creatinine, albumin., globulin, total protein, ALT, AST), blood chemistry (sodium, chloride, potassium, bicarbonate), antioxidants (CAT, SOD, GPx, LPO), enzymatic activities (myeloperoxidase, thioreadoxin reductase), Inflammatory response (C-reactive protein), Stress markers (lactate dehydrogenase), heamatological parameters (RBC, PCV, WBC, HB and differential count), lipid profile (total cholesterol, tryglycerides , high density lipoprotein and low density lipoprotein) all showed various significant (P<0.05) and no significant (P>0.05) responses among the Ich-infested fish treated under three immersion treatments. It is suggested that M. oleifera may serve as an alternatives to chemotherapeutants for control of Ichthyophthiriasis in African catfish Clarias gariepinus.

Keywords: Icthyophthirius multifilis, immersion treatment, pathophysiology, African catfish

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56 Evaluation of Correct Usage, Comfort and Fit of Personal Protective Equipment in Construction Work

Authors: Anna-Lisa Osvalder, Jonas Borell

Abstract:

There are several reasons behind the use, non-use, or inadequate use of personal protective equipment (PPE) in the construction industry. Comfort and accurate size support proper use, while discomfort, misfit, and difficulties to understand how the PPEs should be handled inhibit correct usage. The need for several protective equipments simultaneously might also create problems. The purpose of this study was to analyse the correct usage, comfort, and fit of different types of PPEs used for construction work. Correct usage was analysed as guessability, i.e., human perceptions of how to don, adjust, use, and doff the equipment, and if used as intended. The PPEs tested individually or in combinations were a helmet, ear protectors, goggles, respiratory masks, gloves, protective cloths, and safety harnesses. First, an analytical evaluation was performed with ECW (enhanced cognitive walkthrough) and PUEA (predictive use error analysis) to search for usability problems and use errors during handling and use. Then usability tests were conducted to evaluate guessability, comfort, and fit with 10 test subjects of different heights and body constitutions. The tests included observations during donning, five different outdoor work tasks, and doffing. The think-aloud method, short interviews, and subjective estimations were performed. The analytical evaluation showed that some usability problems and use errors arise during donning and doffing, but with minor severity, mostly causing discomfort. A few use errors and usability problems arose for the safety harness, especially for novices, where some could lead to a high risk of severe incidents. The usability tests showed that discomfort arose for all test subjects when using a combination of PPEs, increasing over time. For instance, goggles, together with the face mask, caused pressure, chafing at the nose, and heat rash on the face. This combination also limited sight of vision. The helmet, in combination with the goggles and ear protectors, did not fit well and caused uncomfortable pressure at the temples. No major problems were found with the individual fit of the PPEs. The ear protectors, goggles, and face masks could be adjusted for different head sizes. The guessability for how to don and wear the combination of PPE was moderate, but it took some time to adjust them for a good fit. The guessability was poor for the safety harness; few clues in the design showed how it should be donned, adjusted, or worn on the skeletal bones. Discomfort occurred when the straps were tightened too much. All straps could not be adjusted for somebody's constitutions leading to non-optimal safety. To conclude, if several types of PPEs are used together, discomfort leading to pain is likely to occur over time, which can lead to misuse, non-use, or reduced performance. If people who are not regular users should wear a safety harness correctly, the design needs to be improved for easier interpretation, correct position of the straps, and increased possibilities for individual adjustments. The results from this study can be a base for re-design ideas for PPE, especially when they should be used in combinations.

Keywords: construction work, PPE, personal protective equipment, misuse, guessability, usability

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55 Arisarum Vulgare: Bridging Tradition and Science through Phytochemical Characterization and Exploring Therapeutic Potential via in vitro and in vivo Biological Activities

Authors: Boudjelal Amel

Abstract:

Arisarum vulgare, a member of the Araceae family, is an herbaceous perennial widely distributed in the Mediterranean region. A. vulgare is recognized for its medicinal properties and holds significant traditional importance in Algeria for the treatment of various human ailments, including pain, infections, inflammation, digestive disorders, skin problems, eczema, cancer, wounds, burns and gynecological diseases. Despite its extensive traditional use, scientific exploration of A. vulgare remains limited. The study aims to investigate for the first time the therapeutic potential of A. vulgare ethanolic extract obtained by ultrasound-assisted extraction. The chemical composition of the extract was determined by LC-MS/MS analysis. For in vitro phytopharmacological evaluation, several assays, including DPPH, ABTS, FRAP and reducing power, were employed to evaluate the antioxidant activity. The antibacterial activity was assessed againt Escherichia coli, Salmonella typhimurium, Staphylococus aureus, Enterococcus feacium by disk diffusion and microdilution methods. The possible inhibitory activity of ethanolic extract was analyzed against the cholinesterases enzymes (AChE and BChE). The DNA protection activity of A. vulgare ethanolic extract was estimated using the agarose gel electrophoresis method. The capacities of the extract to protect plasmid DNA (pBR322) from the oxidizing effects of H2O2 and UV treatment were evaluated by their DNA-breaking forms. The in vivo wound healing potential of a traditional ointment containing 5% of A. vulgare ethanolic extract was also investigated. The LC-MS/MS profiling of the extract revealed the presence of various bioactive compounds, including naringenin, chlorogenic, vanillic, cafeic, coumaric acids, trans-cinnamic and trans ferrulic acids. The plant extract presented considerable antioxidant potential, being the most active for Reducing power (0,07326±0.001 mg/ml) and DPPH (0.14±0.004 mg/ml). The extract showed the highest inhibition zone diameter against Enterococcus feacium (36±0.1 mm). The ethanolic extract of A. vulgare suppressed the growth of Staphylococus aureus, Escherichia coli and Salmonella typhimurium according to the MIC values. The extract of the plant significantly inhibited both AChE and BChE enzymes. DNA protection activity of the A. vulgare extract was determined as 90.41% for form I and 51.92% for form II. The in vivo experiments showed that 5% ethanolic extract ointment accelerated the wound healing process. The topical application of the traditional formulation enhanced wound closure (95,36±0,6 %) and improved histological parameters in the treated group compared to the control groups. The promising biological properties of Arisarum vulgare revealed that the plant could be appraised as a potential origin of bioactive molecules having multifunctional medicinal uses.

Keywords: arisarum vulgare, LC-MS/MS, antioxidant activity, antimicrobial activity, cholinesterases enzymes inhibition, dna-damage activity, in vivo wound healing

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54 Effect of Cerebellar High Frequency rTMS on the Balance of Multiple Sclerosis Patients with Ataxia

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

Abstract:

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

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