Search results for: ultrasound therapy
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2326

Search results for: ultrasound therapy

1216 Bacterial Cellulose/Silver-Doped Hydroxyapatite Composites for Tissue Engineering Application

Authors: Adrian Ionut Nicoara, Denisa Ionela Ene, Alina Maria Holban, Cristina Busuioc

Abstract:

At present, the development of materials with biomedical applications is a domain of interest that will produce a full series of benefits in engineering and medicine. In this sense, it is required to use a natural material, and this paper is focused on the development of a composite material based on bacterial cellulose – hydroxyapatite and silver nanoparticles with applications in hard tissue. Bacterial cellulose own features like biocompatibility, non-toxicity character and flexibility. Moreover, the bacterial cellulose can be conjugated with different forms of active silver to possess antimicrobial activity. Hydroxyapatite is well known that can mimic at a significant level the activity of the initial bone. The material was synthesized by using an ultrasound probe and finally characterized by several methods. Thereby, the morphological properties were analyzed by using Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). Because the synthesized material has medical application in restore the tissue and to fight against microbial invasion, the samples were tested from the biological point of view by evaluating the biodegradability in phosphate-buffered saline (PBS) and simulated body fluid (SBF) and moreover the antimicrobial effect was performed on Gram-positive bacterium Staphylococcus aureus, Gram-negative bacterium Escherichia coli, and fungi Candida albicans. The results reveal that the obtained material has specific characteristics for bone regeneration.

Keywords: bacterial cellulose, biomaterials, hydroxyapatite, scaffolds materials

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1215 Computer-Aided Drug Repurposing for Mycobacterium Tuberculosis by Targeting Tryptophanyl-tRNA Synthetase

Authors: Neslihan Demirci, Serdar Durdağı

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Mycobacterium tuberculosis is still a worldwide disease-causing agent that, according to WHO, led to the death of 1.5 million people from tuberculosis (TB) in 2020. The bacteria reside in macrophages located specifically in the lung. There is a known quadruple drug therapy regimen for TB consisting of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Over the past 60 years, there have been great contributions to treatment options, such as recently approved delamanid (OPC67683) and bedaquiline (TMC207/R207910), targeting mycolic acid and ATP synthesis, respectively. Also, there are natural compounds that can block the tryptophanyl-tRNA synthetase (TrpRS) enzyme, chuangxinmycin, and indolmycin. Yet, already the drug resistance is reported for those agents. In this study, the newly released TrpRS enzyme structure is investigated for potential inhibitor drugs from already synthesized molecules to help the treatment of resistant cases and to propose an alternative drug for the quadruple drug therapy of tuberculosis. Maestro, Schrodinger is used for docking and molecular dynamic simulations. In-house library containing ~8000 compounds among FDA-approved indole-containing compounds, a total of 57 obtained from the ChemBL were used for both ATP and tryptophan binding pocket docking. Best of indole-containing 57 compounds were subjected to hit expansion and compared later with virtual screening workflow (VSW) results. After docking, VSW was done. Glide-XP docking algorithm was chosen. When compared, VSW alone performed better than the hit expansion module. Best scored compounds were kept for ten ns molecular dynamic simulations by Desmond. Further, 100 ns molecular dynamic simulation was performed for elected molecules according to Z-score. The top three MMGBSA-scored compounds were subjected to steered molecular dynamic (SMD) simulations by Gromacs. While SMD simulations are still being conducted, ponesimod (for multiple sclerosis), vilanterol (β₂ adrenoreceptor agonist), and silodosin (for benign prostatic hyperplasia) were found to have a significant affinity for tuberculosis TrpRS, which is the propulsive force for the urge to expand the research with in vitro studies. Interestingly, top-scored ponesimod has been reported to have a side effect that makes the patient prone to upper respiratory tract infections.

Keywords: drug repurposing, molecular dynamics, tryptophanyl-tRNA synthetase, tuberculosis

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1214 Formulation and Evaluation of Curcumin-Zn (II) Microparticulate Drug Delivery System for Antimalarial Activity

Authors: M. R. Aher, R. B. Laware, G. S. Asane, B. S. Kuchekar

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Objective: Studies have shown that a new combination therapy with Artemisinin derivatives and curcumin is unique, with potential advantages over known ACTs. In present study an attempt was made to prepare microparticulate drug delivery system of Curcumin-Zn complex and evaluate it in combination with artemether for antimalarial activity. Material and method: Curcumin Zn complex was prepared and encapsulated using sodium alginate. Microparticles thus obtained are further coated with various enteric polymers at different coating thickness to control the release. Microparticles are evaluated for encapsulation efficiency, drug loading and in vitro drug release. Roentgenographic Studies was conducted in rabbits with BaSO 4 tagged formulation. Optimized formulation was screened for antimalarial activity using P. berghei-infected mice survival test and % paracetemia inhibition, alone (three oral dose of 5mg/day) and in combination with arthemether (i.p. 500, 1000 and 1500µg). Curcumin-Zn(II) was estimated in serum after oral administration to rats by using spectroflurometry. Result: Microparticles coated with Cellulose acetate phthalate showed most satisfactory and controlled release with 479 min time for 60% drug release. X-ray images taken at different time intervals confirmed the retention of formulation in GI tract. Estimation of curcumin in serum by spectroflurometry showed that drug concentration is maintained in the blood for longer time with tmax of 6 hours. The survival time (40 days post treatment) of mice infected with P. berghei was compared to survival after treatment with either Curcumin-Zn(II) microparticles artemether combination, curcumin-Zn complex and artemether. Oral administration of Curcumin-Zn(II)-artemether prolonged the survival of P.berghei-infected mice. All the mice treated with Curcumin-Zn(II) microparticles (5mg/day) artemether (1000µg) survived for more than 40 days and recovered with no detectable parasitemia. Administration of Curcumin-Zn(II) artemether combination reduced the parasitemia in mice by more than 90% compared to that in control mice for the first 3 days after treatment. Conclusion: Antimalarial activity of the curcumin Zn-artemether combination was more pronounced than mono therapy. A single dose of 1000µg of artemether in curcumin-Zn combination gives complete protection in P. berghei-infected mice. This may reduce the chances of drug resistance in malaria management.

Keywords: formulation, microparticulate drug delivery, antimalarial, pharmaceutics

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1213 Siderophore Receptor Protein from Klebsiella pneumoniae as a Promising Immunogen for Serotype-Independent Therapeutic Lead Development

Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri

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Klebsiella pneumoniae causes a wide range of infections, including urinary tract infections, sepsis, bacteremia, pneumonia, and liver abscesses. The emergence of multi-drug resistance in this bacterium led to a major setback for clinical management. WHO also endorsed a need for finding alternative therapy to antibiotics for the treatment of these infections. Development of vaccines and passive antibody therapy has been proven as a potent alternative to antibiotics in the case of MDR, XDR, and PDR Klebsiella infections. Siderophore receptors have been demonstrated to be overexpressed for the internalization of iron siderophore complexes during infections in most Gram-negative bacteria. For the present study, immune response to siderophore receptors to establish this protein as a potential immunogen for the development of therapeutic leads was explored. Clinical strains of Klebsiella pneumoniae were grown in iron-deficient conditions, and the iron-regulated outer membrane proteins were extracted and characterized through mass spectrometry for specific identification. The gene for identified protein was cloned in pET- 28a vector and expressed in E. coli. The native protein and the recombinant protein were isolated and purified and used as antigens for the generation of immune response in BALB/c mice. The native protein of Klebsiella pneumoniae grown in iron-deficient conditions was identified as FepA (Ferrienterobactin receptor) and other siderophore receptors. This 80 kDa protein generated an immune response in BALB/c mice. The antiserum from mice after subsequent booster doses was collected and showed binding with FepA protein in western blot and phagocytic uptake of the K. pneumoniae in the presence antiserum from immunized mice also observed from the animal studies after bacterial challenge post immunisation in mice have shown bacterial clearance. The antiserum from mice showed binding and clearance of the Klebsiella pneumoniae bacteria in vitro and in vivo. These antigens used for generating an active immune response in mice can further be used for therapeutic monoclonal antibody development against Klebsiella pneumoniae infections.

Keywords: antiserum, FepA, Klebsiella pneumoniae, multi drug resistance, siderophore receptor

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1212 Stomach Perforation, due to Chronic External Pressure

Authors: Angelis P. Barlampas

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PURPOSE: The purpose of this paper is to demonstrate the important role of taking an appropriate and detailed history, in order to reach the best possible diagnostic conclusion. MATERIAL: A patient presented to the emergency department due to the sudden onset of continuous abdominal pain, during the last hour and with the clinical symptoms of an acute abdomen. During the clinical examination, signs of peritoneal irritation and diffuse abdominal tenderness were found. The rest of the clinical and laboratory tests did not reveal anything important. From the reported medical history, nothing of note was found, except for the report of a large liver cyst, for which he was advised not to take any further action, except from regular ultrasound examination . METHOD: A computed tomography examination was performed after per os administration of gastrografin, which revealed a hyperdense ascitic effusion, similar in density to that of gastrografin within the intestinal tract. The presence of a large cyst of the left hepatic lobe was confirmed, contacting and pushing against the stomach. In the area of the contact between the liver cyst and the pylorus, there were extraluminal air bubbles and local opacity of the peritoneal fat, with a small hyperdense effusion. Result : The above, as well as the absence of a history of stomach ulcer or recent trauma, or other pathology, argue in favor of acute pyloric perforation, due to mural necrosis, in response to chronic external pressure from the pre-existing large liver cyst.

Keywords: perforation, stomach, large liver cyst, CT abdomen, acute abdominal pain, intraperitoneal leakage, constrast leakage

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1211 Nickel Electroplating in Post Supercritical CO2 Mixed Watts Bath under Different Agitations

Authors: Chun-Ying Lee, Kun-Hsien Lee, Bor-Wei Wang

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The process of post-supercritical CO2 electroplating uses the electrolyte solution after being mixed with supercritical CO2 and released to atmospheric pressure. It utilizes the microbubbles that form when oversaturated CO2 in the electrolyte returns to gaseous state, which gives the similar effect of pulsed electroplating. Under atmospheric pressure, the CO2 bubbles gradually diffuse. Therefore, the introduction of ultrasound and/or other agitation can potentially excite the CO2 microbubbles to achieve an electroplated surface of even higher quality. In this study, during the electroplating process, three different modes of agitation: magnetic stirrer agitation, ultrasonic agitation and a combined mode (magnetic + ultrasonic) were applied, respectively, in order to obtain an optimal surface morphology and mechanical properties for the electroplated Ni coating. It is found that the combined agitation mode at a current density of 40 A/dm2 achieved the smallest grain size, lower surface roughness, and produced an electroplated Ni layer that achieved hardness of 320 HV, much higher when compared with conventional method, which were usually in the range of 160 to 300 HV. However, at the same time, the electroplating with combined agitation developed a higher internal stress of 320 MPa due to the lower current efficiency of the process and finer grain in the coating. Moreover, a new control methodology for tailoring the coating’s mechanical property through its thickness was demonstrated by the timely introduction of ultrasonic agitation during the electroplating process with post supercritical CO2 mixed electrolyte.

Keywords: nickel electroplating, micro-bubbles, supercritical carbon dioxide, ultrasonic agitation

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1210 The Investigation of Endogenous Intoxication and Lipid Peroxidation in Patients with Giardiasis Before and After Treatment

Authors: R. H. Begaydarova, B. Zh. Kultanov, B. T. Esilbaeva, G. E. Nasakaeva, Y. Yukhnevich, G. K. Alshynbekova, A. E. Dyusembaeva

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Background: The level of middle molecules of peptides (MMP) allows to evaluate the severity and prognosis of the disease and is a criterion for the effectiveness of the treatment. The detection the products of lipidperoxidation cascade, such as conjugated dienes, malondialdehyde in biological material, has an important role in the development of pathogenesis, the diagnosis and prognosis in different parasitic diseases. Purpose of the study was to evaluate the state of endogenous intoxication and indicators of lipid peroxidation in patients with giardiasis before and after treatment. Materials and methods: Endogenous intoxication was evaluated in patients with giardiasis in the level of middle molecules of peptides (MMP) in the blood. The amount of MMP and products of lipid peroxidation were determined in the blood of 198 patients with giardiasis, 129 of them were women (65%), 69 were men (35%). The MMP level was detected for comparison in the blood of 84 healthy volunteers. The lipid peroxidation were determined in 40 healthy men and women without giardiasis and history of chronic diseases. Data were processed by conventional methods of variation statistics, we calculated the arithmetic mean (M) and standard dispersion (m). t-test (t) was used to assess differences. Results: The level of MMP in the blood was significantly higher in patients with giardiasis in comparison with group of healthy men and women. MMP concentration in the blood of women with Giardia was 2.5 times greater than that of the comparison groups of women. The level of MMP exceeds more than 6 times in men with giardiasis. The decrease in the intensity of endogenous intoxication was two weeks after antigiardia therapy, both men and women. According to the study, a statistically significant increase in the level of all the studied parameters lipid peroxidation cascade was observed in the blood of men with giardiasis, with the exception of the total primary production (NGN). The treatment of giardiasis helped to stabilize the level of almost all metabolites of lipid peroxidation cascade. The exception was level of malondialdehyde, it was significantly elevated to compare with the control group and after treatment. Conclusion: Thus, the MMP level was significantly higher in blood of patients with giardiasis than in comparison group. This is evidence of severe endogenous intoxication caused by giardia infection. The accumulation of primary and secondary products of lipid peroxidation was observed in the blood of men and women. These processes tend to be more active in men than in women. Antigiardiasis therapy contributed to the normalization of almost all the studied indicators of lipid peroxidation in the blood of participants, except the level malondialdehyde in the blood of men.

Keywords: enzymes of antioxidant protection, giardiasis, blood, treatment

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1209 Applications of AFM in 4D to Optimize the Design of Genetic Nanoparticles

Authors: Hosam Abdelhady

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Filming the behaviors of individual DNA molecules in their environment when they interact with individual medicinal nano-polymers in a molecular scale has opened the door to understand the effect of the molecular shape, size, and incubation time with nanocarriers on optimizing the design of robust genetic Nano molecules able to resist the enzymatic degradation, enter the cell, reach to the nucleus and kill individual cancer cells in their environment. To this end, we will show how we applied the 4D AFM as a guide to finetune the design of genetic nanoparticles and to film the effects of these nanoparticles on the nanomechanical and morphological profiles of individual cancer cells.

Keywords: AFM, dendrimers, nanoparticles, DNA, gene therapy, imaging

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1208 Features of Normative and Pathological Realizations of Sibilant Sounds for Computer-Aided Pronunciation Evaluation in Children

Authors: Zuzanna Miodonska, Michal Krecichwost, Pawel Badura

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Sigmatism (lisping) is a speech disorder in which sibilant consonants are mispronounced. The diagnosis of this phenomenon is usually based on the auditory assessment. However, the progress in speech analysis techniques creates a possibility of developing computer-aided sigmatism diagnosis tools. The aim of the study is to statistically verify whether specific acoustic features of sibilant sounds may be related to pronunciation correctness. Such knowledge can be of great importance while implementing classifiers and designing novel tools for automatic sibilants pronunciation evaluation. The study covers analysis of various speech signal measures, including features proposed in the literature for the description of normative sibilants realization. Amplitudes and frequencies of three fricative formants (FF) are extracted based on local spectral maxima of the friction noise. Skewness, kurtosis, four normalized spectral moments (SM) and 13 mel-frequency cepstral coefficients (MFCC) with their 1st and 2nd derivatives (13 Delta and 13 Delta-Delta MFCC) are included in the analysis as well. The resulting feature vector contains 51 measures. The experiments are performed on the speech corpus containing words with selected sibilant sounds (/ʃ, ʒ/) pronounced by 60 preschool children with proper pronunciation or with natural pathologies. In total, 224 /ʃ/ segments and 191 /ʒ/ segments are employed in the study. The Mann-Whitney U test is employed for the analysis of stigmatism and normative pronunciation. Statistically, significant differences are obtained in most of the proposed features in children divided into these two groups at p < 0.05. All spectral moments and fricative formants appear to be distinctive between pathology and proper pronunciation. These metrics describe the friction noise characteristic for sibilants, which makes them particularly promising for the use in sibilants evaluation tools. Correspondences found between phoneme feature values and an expert evaluation of the pronunciation correctness encourage to involve speech analysis tools in diagnosis and therapy of sigmatism. Proposed feature extraction methods could be used in a computer-assisted stigmatism diagnosis or therapy systems.

Keywords: computer-aided pronunciation evaluation, sigmatism diagnosis, speech signal analysis, statistical verification

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1207 A Biophysical Model of CRISPR/Cas9 on- and off-Target Binding for Rational Design of Guide RNAs

Authors: Iman Farasat, Howard M. Salis

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The CRISPR/Cas9 system has revolutionized genome engineering by enabling site-directed and high-throughput genome editing, genome insertion, and gene knockdowns in several species, including bacteria, yeast, flies, worms, and human cell lines. This technology has the potential to enable human gene therapy to treat genetic diseases and cancer at the molecular level; however, the current CRISPR/Cas9 system suffers from seemingly sporadic off-target genome mutagenesis that prevents its use in gene therapy. A comprehensive mechanistic model that explains how the CRISPR/Cas9 functions would enable the rational design of the guide-RNAs responsible for target site selection while minimizing unexpected genome mutagenesis. Here, we present the first quantitative model of the CRISPR/Cas9 genome mutagenesis system that predicts how guide-RNA sequences (crRNAs) control target site selection and cleavage activity. We used statistical thermodynamics and law of mass action to develop a five-step biophysical model of cas9 cleavage, and examined it in vivo and in vitro. To predict a crRNA's binding specificities and cleavage rates, we then compiled a nearest neighbor (NN) energy model that accounts for all possible base pairings and mismatches between the crRNA and the possible genomic DNA sites. These calculations correctly predicted crRNA specificity across 5518 sites. Our analysis reveals that cas9 activity and specificity are anti-correlated, and, the trade-off between them is the determining factor in performing an RNA-mediated cleavage with minimal off-targets. To find an optimal solution, we first created a scheme of safe-design criteria for Cas9 target selection by systematic analysis of available high throughput measurements. We then used our biophysical model to determine the optimal Cas9 expression levels and timing that maximizes on-target cleavage and minimizes off-target activity. We successfully applied this approach in bacterial and mammalian cell lines to reduce off-target activity to near background mutagenesis level while maintaining high on-target cleavage rate.

Keywords: biophysical model, CRISPR, Cas9, genome editing

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1206 Resistance of Mycobacterium tuberculosis to Daptomycin

Authors: Ji-Chan Jang

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Tuberculosis is still major health problem because there is an increase of multidrug-resistant and extensively drug-resistant forms of the disease. Therefore, the most urgent clinical need is to discover potent agents and develop novel drug combination capable of reducing the duration of MDR and XDR tuberculosis therapy. Three reference strains H37Rv, CDC1551, W-Beijing GC1237 and six clinical isolates of MDRTB were tested to daptomycin in the range of 0.013 to 256 mg/L. Daptomycin is resistant to all tested M. tuberculosis strains not only laboratory strains but also clinical MDR strains that were isolated at different source. Daptomycin will not be an antibiotic of choice for treating infection of Gram positive atypical slowly growing M. tuberculosis.

Keywords: tuberculosis, daptomycin, resistance, Mycobacterium tuberculosis

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1205 Evaluation of Phonophoresis with Dexamethasone in Treatment of Hypertrophic Burn Scar

Authors: Alireza Pishgahi, Mohammad Rahbar, Javad Shokri, Shahla Dareshiri, Yaghoub Salekzamani, Fariba Eslamian

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Background and Objectives: Hypertrophic scars are one of the complications following a burn injury. Intralesional corticosteroid injection is an invasive method for treatment of this complication. We had design a single blinded randomized control trial to deliver dexamethasone by phonophoresis and evaluate its efficacy on hypertrophic burn scars characteristics. Material and Methods: 56 cases of hypertrophic burn scar due to burn injury allocated randomly to dexamethasone and control group. Individuals in case group received 10 sessions of dexamethasone 0.4% phonophoresis. Patients in control group had placebo phonophoresis (ultrasound with normal routine aquatic gel without any dexamethasone) with the same protocol. At the beginning of study and one week after last session, hypertrophic scar characteristics and pruritus were measured by ‘Vancouver Scar Scale’, and ‘5-D Pruritus Scale’ respectively in both groups. Results: Despite mild improvement in Vancouver Scar Scale score one week after intervention in dexamethasone phonophoresis group in comparison to control subjects, but this difference was not significant (p=0.08). Pruritus score perceived subjectively were significantly lower one week after intervention in dexamethasone groups in comparison to control subjects (p=0.00). Conclusion: Dexamethasone phonophoresis is a safe and effective treatment method for burn hypertrophic scar pruritus, but its efficacy for scar characteristics improvement needs to be evaluated by larger studies with long-term follow-up period.

Keywords: dexamethasone, hypertrophic scar, phonophoresis, pruritus

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1204 Effect of Motor Imagery of Truncal Exercises on Trunk Function and Balance in Early Stroke: A Randomized Controlled Trial

Authors: Elsa Reethu, S. Karthik Babu, N. Syed

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Background: Studies in the past focused on the additional benefits of action observation in improving upper and lower limb functions and improving activities of daily living when administered along with conventional therapy. Nevertheless, there is a paucity of literature proving the effects of motor imagery of truncal exercise in improving trunk control in patients with stroke. Aims/purpose: To study the effect of motor imagery of truncal exercises on trunk function and balance in early stroke. Methods: A total of 24 patients were included in the study. 12 were included in the experimental group and 12 were included in control group Trunk function was measured using Trunk Control Test (TCT), Trunk Impairment Scale Verheyden (TIS Verheyden) and Trunk Impairment Scale Fujiwara (TIS Fujiwara). The balance was assessed using Brunel Balance Assessment (BBA) and Tinetti POMA. For the experimental group, each session was for 30 minutes of physical exercises and 15 minutes of motor imagery, once a day, six times a week for 3 weeks and prior to the exercise session, patients viewed a video tape of all the trunk exercises to be performed for 15minutes. The control group practiced the trunk exercises alone for the same duration. Measurements were taken before, after and 4 weeks after intervention. Results: The effect of treatment in motor imagery group showed better improvement when compared with control group when measured after 3 weeks on values of static sitting balance, dynamic balance, total TIS (Verheyden) score, BBA, Tinetti balance and gait with a large effect size of 0.86, 1.99, 1.69, 1.06, 1.63 and 0.97 respectively. The moderate effect size was seen in values of TIS Fujiwara (0.58) and small effect size was seen on TCT (0.12) and TIS coordination component (0.13).at the end of 4 weeks after intervention, the large effect size was identified on values of dynamic balance (2.06), total TIS score (1.59) and Tinetti balance (1.24). The moderate effect size was observed on BBA (0.62) and Tinetti gait (0.72). Conclusion: Trunk motor imagery is effective in improving trunk function and balance in patients with stroke and has a carryover effect in the aspects of mobility. The therapy gain that was observed during the time of discharge was seen to be maintained at the follow-up levels.

Keywords: stroke, trunk rehabilitation, trunk function, balance, motor imagery

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1203 High-Speed Imaging and Acoustic Measurements of Dual-frequency Ultrasonic Processing of Graphite in Water

Authors: Justin Morton, Mohammad Khavari, Abhinav Priyadarshi, Nicole Grobert, Dmitry G. Eskin, Jiawei Mi, Kriakos Porfyrakis, Paul Prentice

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Ultrasonic cavitation is used for various processes and applications. Recently, ultrasonic assisted liquid phase exfoliation has been implemented to produce two dimensional nanomaterials. Depending on parameters such as input transducer power and the operational frequency used to induce the cavitation, bubble dynamics can be controlled and optimised. Using ultra-high-speed imagining and acoustic pressure measurements, a dual-frequency systemand its effect on bubble dynamics was investigated. A high frequency transducer (1.174 MHz) showed that bubble fragments and satellite bubbles induced from a low frequency transducer (24 kHz) were able to extend their lifecycle. In addition, this combination of ultrasonic frequencies generated higher acoustic emissions (∼24%) than the sum of the individual transducers. The dual-frequency system also produced an increase in cavitation zone size of∼3 times compared to the low frequency sonotrode. Furthermore, the high frequency induced cavitation bubbleswere shown to rapidly oscillate, although remained stable and did not transiently collapse, even in the presence of a low pressure field. Finally, the spatial distribution of satellite and fragment bubbles from the sonotrode were shown to increase, extending the active cavitation zone. These observations elucidated the benefits of using a dual-frequency system for generating nanomaterials with the aid of ultrasound, in deionised water.

Keywords: dual-frequency, cavitation, bubble dynamics, graphene

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1202 Development and Evaluation of a Cognitive Behavioural Therapy Based Smartphone App for Low Moods and Anxiety

Authors: David Bakker, Nikki Rickard

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Smartphone apps hold immense potential as mental health and wellbeing tools. Support can be made easily accessible and can be used in real-time while users are experiencing distress. Furthermore, data can be collected to enable machine learning and automated tailoring of support to users. While many apps have been developed for mental health purposes, few have adhered to evidence-based recommendations and even fewer have pursued experimental validation. This paper details the development and experimental evaluation of an app, MoodMission, that aims to provide support for low moods and anxiety, help prevent clinical depression and anxiety disorders, and serve as an adjunct to professional clinical supports. MoodMission was designed to deliver cognitive behavioural therapy for specifically reported problems in real-time, momentary interactions. Users report their low moods or anxious feelings to the app along with a subjective units of distress scale (SUDS) rating. MoodMission then provides a choice of 5-10 short, evidence-based mental health strategies called Missions. Users choose a Mission, complete it, and report their distress again. Automated tailoring, gamification, and in-built data collection for analysis of effectiveness was also included in the app’s design. The development process involved construction of an evidence-based behavioural plan, designing of the app, building and testing procedures, feedback-informed changes, and a public launch. A randomized controlled trial (RCT) was conducted comparing MoodMission to two other apps and a waitlist control condition. Participants completed measures of anxiety, depression, well-being, emotional self-awareness, coping self-efficacy and mental health literacy at the start of their app use and 30 days later. At the time of submission (November 2016) over 300 participants have participated in the RCT. Data analysis will begin in January 2017. At the time of this submission, MoodMission has over 4000 users. A repeated-measures ANOVA of 1390 completed Missions reveals that SUDS (0-10) ratings were significantly reduced between pre-Mission ratings (M=6.20, SD=2.39) and post-Mission ratings (M=4.93, SD=2.25), F(1,1389)=585.86, p < .001, np2=.30. This effect was consistent across both low moods and anxiety. Preliminary analyses of the data from the outcome measures surveys reveal improvements across mental health and wellbeing measures as a result of using the app over 30 days. This includes a significant increase in coping self-efficacy, F(1,22)=5.91, p=.024, np2=.21. Complete results from the RCT in which MoodMission was evaluated will be presented. Results will also be presented from the continuous outcome data being recorded by MoodMission. MoodMission was successfully developed and launched, and preliminary analysis suggest that it is an effective mental health and wellbeing tool. In addition to the clinical applications of MoodMission, the app holds promise as a research tool to conduct component analysis of psychological therapies and overcome restraints of laboratory based studies. The support provided by the app is discrete, tailored, evidence-based, and transcends barriers of stigma, geographic isolation, financial limitations, and low health literacy.

Keywords: anxiety, app, CBT, cognitive behavioural therapy, depression, eHealth, mission, mobile, mood, MoodMission

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1201 Multicellular Cancer Spheroids as an in Vitro Model for Localized Hyperthermia Study

Authors: Kamila Dus-Szachniewicz, Artur Bednarkiewicz, Katarzyna Gdesz-Birula, Slawomir Drobczynski

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In modern oncology hyperthermia (HT) is defined as a controlled tumor heating. HT treatment temperatures range between 40–48 °C and can selectively damage heat-sensitive cancer cells or limit their further growth, usually with minimal injury to healthy tissues. Despite many advantages, conventional whole-body and regional hyperthermia have clinically relevant side effects, including cardiac and vascular disorders. Additionally, the lack of accessibility of deep-seated tumor sites and impaired targeting micrometastases renders HT less effective. It is believed that above disadvantages can significantly overcome by the application of biofunctionalized microparticles, which can specifically target tumor sites and become activated by an external stimulus to provide a sufficient cellular response. In our research, the unique optical tweezers system have enabled capturing the silica microparticles, primary cells and tumor spheroids in highly controllable and reproducible environment to study the impact of localized heat stimulation on normal and pathological cell and within multicellular tumor spheroid. High throughput spheroid model was introduced to better mimic the response to HT treatment on tumors in vivo. Additionally, application of local heating of tumor spheroids was performed in strictly controlled conditions resembling tumor microenvironment (temperature, pH, hypoxia, etc.), in response to localized and nonhomogeneous hyperthermia in the extracellular matrix, which promotes tumor progression and metastatic spread. The lack of precise control over these well- defined parameters in basic research leads to discrepancies in the response of tumor cells to the new treatment strategy in preclinical animal testing. The developed approach enables also sorting out subclasses of cells, which exhibit partial or total resistance to therapy, in order to understand fundamental aspects of the resistance shown by given tumor cells in response to given therapy mode and conditions. This work was funded by the National Science Centre (NCN, Poland) under grant no. UMO-2017/27/B/ST7/01255.

Keywords: cancer spheroids, hyperthermia, microparticles, optical tweezers

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1200 A Cognitive Behavioural Therapy for Post-Traumatic Stress Disorders

Authors: Ryotaro Ishikawa

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INTRODUCTION: Post-traumatic stress disorder (PTSD) is a psychiatric label for a collection of psychological symptoms following a traumatic event. PTSD is as a result of a traumatic experience such as rape or sexual assault. A victim may have PTSD if she/he has experienced the following symptoms for at least a month: a) Stressor, b) Intrusion symptoms, c) Avoidance, d) Negative alterations in cognitions and mood, e) Alterations in arousal and reactivity. Studies on the cognitive theory of PTSD emphasized the roles of (a) negative appraisals of trauma memories in maintaining the symptomatology of PTSD, and (b) disorganized trauma memories in the development of PTSD. Mental contamination is primarily caused by experiences involving humans (e.g. violators or perpetrators) as opposed to substances (e.g. dirt or bodily fluids). Feelings of mental contamination may evoke following experiences of ill-treatment, sexual assault, domination, degradation, manipulation, betrayal, or humiliation. Some studies have demonstrated that traumatic thoughts related to sexual assault are particularly strong predictors of mental contamination. Treatment protocols based on cognitive-behavioral therapy appear to be beneficial in reducing the severity of PTSD and mental contamination. Studies on the cognitive theory of PTSD emphasized the roles of (A) negative appraisals of trauma memories in maintaining the symptomatology of PTSD, and (B) disorganized trauma memories in the development of PTSD. We will demonstrate a feasibility study of individual CBT for PTSD and mental contamination in Japanese clinical settings. METHOD: The single-arm trial is a group setting CBT intervention. The primary outcome is the self-rated Posttraumatic Stress Diagnostic Scale, with secondary measurements of depressive severity and mental pollution questionnaire. Assessments are conducted at baseline, after a waiting period before CBT, during CBT, and after CBT. RESULTS: Participants are eligible for the study and complete the outcome measures at all assessment points. In our hypothesis, receiving CBT would lead to improvements in primary and secondary PTSD severity. CONCLUSION: We will demonstrate a feasibility study of individual CBT for PTSD and mental contamination in Japanese clinical settings. Our treatment would achieve favorable treatment outcomes for PTSD with mental contamination in Japanese clinical settings.

Keywords: CBT, cognitive theory, PTSD, mental pollution

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1199 Ultrasonic Investigation as Tool for Study of Molecular Interaction of 2-Hydroxy Substituted Pyrimidine Derivative at Different Concentrations

Authors: Shradha S. Binani, P. S. Bodke, R. V. Joat

Abstract:

Recent decades have witnessed an exponential growth in the field of acoustical parameters and ultrasound on solid, liquid and gases. Ultrasonic propagation parameters yield valuable information regarding the behavior of liquid systems because intra and intermolecular association, dipolar interaction, complex formation and related structural changes affecting the compressibility of the system which in turn produces variations in the ultrasonic velocity. The acoustic and thermo dynamical parameters obtained in ultrasonic study show that ion-solvation is accompanied by the destruction or enhancement of the solvent structure. In the present paper the ultrasonic velocity (v), density (ρ), viscosity(η) have been measured for the pharmacological important compound 2-hydroxy substituted phenyl pyrimidine derivative (2-hydroxy-4-(4’-methoxy phenyl)-6-(2’-hydroxy-4’-methyl-5’-chlorophenyl)pyrimidine) in ethanol as a solvent by using different concentration at constant room temperature. These experimental data have been used to estimate physical parameter like adiabatic compressibility, intermolecular free length, relaxation time, free volume, specific acoustic impedance, relative association, Wada’s constant, Rao’s constant etc. The above parameters provide information in understanding the structural and molecular interaction between solute-solvent in the drug solution with respect to change in concentration.

Keywords: acoustical parameters, ultrasonic velocity, density, viscosity, 2-hydroxy substituted phenyl pyrimidine derivative

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1198 Acupuncture Reduces Pain Disability, Stress, and Depression in United States Military Veterans with Chronic Pain

Authors: Christine Eickhoff, Alyssa Adams, Alaine Duncan

Abstract:

The Washington, DC Veterans Affairs Medical Center (DC VAMC) offers complementary and integrative health (CIH) services such as acupuncture, yoga, meditation, and nutrition education through a coordinated outpatient clinic. The primary population utilizing CIH services are veterans with chronic pain. Acupuncture is one of the most popular of the CIH services available at the DC VAMC. As interest and availability grows, it is important to measure health outcomes associated with CIH service utilization. The purpose of this study was to investigate pain and mental health outcomes for veterans with chronic pain enrolled in individual acupuncture services in the DC VAMC. Veterans at the DC VAMC with self-identified chronic pain and no prior acupuncture experience were recruited for the study (n=70). Veterans were referred for services by a medical provider and completed baseline assessments at the program orientation prior to participating in any CIH services. Veterans received four individual, full-body acupuncture appointments within four weeks of study enrollment. After the first month, participants were scheduled for six appointments that occurred every two weeks and then eight more sessions that were scheduled one month apart. Follow-up assessments were administered at 2, 4, 6, 8, and 12 months. The findings reported will include completed time points at two and four months. Measures include a demographics survey, the Measure Yourself Medical Outcome Profile-2 (MYMOP-2), The Beck Depression Inventory (BDI-II), the Defense Veterans Pain Rating Scale (DVPRS), and the Pain Disability Questionnaire (PDQ). In this sample, 67% identified a pain condition as their primary health concern. Between baseline and two-month follow-up, there were significant improvements in participants’ primary health concern (MYMOP-2 p=0.010), general wellbeing (MYMOP-2 p=0.011), and a significant decrease in the use of medication (MYMOP-2 p<0.000). Between 2 and 4-month follow-up, pain disability (PDQ p=0.035), pain rating (DVPRS p=0.027), and depression (BDI-II p=0.003) significantly improved. Preliminary findings indicate that individual acupuncture therapy can be effective at improving health outcomes, well-being, and decreasing medication use in U.S. military veterans with chronic pain. Findings also suggest that individual acupuncture therapy can improve pain ratings, pain disability, and depression in veterans with chronic pain.

Keywords: acupuncture, chronic pain, depression, integrative health, medication use, military, pain, veterans, wellbeing

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1197 Wire Localization Procedures in Non-Palpable Breast Cancers: An Audit Report and Review of Literature

Authors: Waqas Ahmad, Eisha Tahir, Shahper Aqeel, Imran Khalid Niazi, Amjad Iqbal

Abstract:

Background: Breast conservation surgery applies a number of techniques for accurate localization of lesions. Wire localization remains the method of choice in non-palpable breast cancers post-neoadjuvant chemotherapy. Objective: The aim of our study was to determine the accuracy of wire localization procedures in our department and compare it with internationally set protocols as per the Royal College of Radiologists. Post wire mammography, as well as the margin status of the postoperative specimen, assessed the accuracy of the procedure. Methods: We retrospectively reviewed the data of 225 patients who presented to our department from May 2014 to June 2015 post neoadjuvant chemotherapy with non-palpable cancers. These patients are candidates for wire localized lumpectomies either under ultrasound or stereotactic guidance. Metallic marker was placed in all the patients at the time of biopsy. Post wire mammogram was performed in all the patients and the distance of the wire tip from the marker was calculated. The presence or absence of the metallic clip in the postoperative specimen, as well as the marginal status of the postoperative specimen, was noted. Results: 157 sonographic and 68 stereotactic wire localization procedures were performed. 95% of the wire tips were within 1 cm of the metallic marker. Marginal status was negative in 94% of the patients in histopathological specimen. Conclusion: Our audit report declares more than 95% accuracy of image guided wire localization in successful excision of non-palpable breast lesions.

Keywords: breast, cancer, non-palpable, wire localization

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1196 Prevalence of Adverse Events in Children and Adolescents on Antiretroviral Therapy: Examining the Pediatric Cohort in the Eastern Cape

Authors: Shannon Glaspy, Gerald Boon, Jack Lambert

Abstract:

Studies on AE of highly active antiretroviral therapy (HAART) in children and adolescents are rare. The aim of this study is to observe the frequency of treatment limiting adverse drug reactions against years on ARVs and specific ARV regimen. Methods: A retrospective cohort study was conducted in East London, South Africa. All patient files in the pediatric (0 – 18 years) ARV cohort were examined, selecting only those patients started on HAART. ARV regimen changes explicitly due to AE, age on ARV treatment onset, age of AE onset, and gender were extrapolated. Eligible subjects were obtained from patient folders, anonymized and cross-referenced with data obtained from electronic records. A total of 1120 patients [592 male (52.9%) and 528 female (47.1%)] were charted by incidence and year. Additional information was extrapolated in cases where the patient experienced lipodystrophy and lipoatrophy to include the number of years on ARVs prior to the onset of the AE. Results: Of the 1120 HIV infected children of the hospital cohort, a total of 105 (9.37%) AE (53.3% male) observed were deemed eligible for the study due to completeness of medical history and agreement between electronic records and paper files. The AE cited were as follows: lipoatrophy 62 (5.53% of all subjects), lipodystrophy 27 (2.41%), neuropathy 9 (0.8%), anemia 2 (0.17%), Steven Johnsons Syndrome 1 (0.08%), elevated LFTs 1 (0.8%), breast hypertrophy (0.08%), gastritis 1 (0.08%) and rash 1 (0.08%). The most prevalence ARV regimens associated with the onset of the AE are: D4T/3TC/EFV 72 cases (64.86% of all AE), D4T/3TC/LOPr 24 cases (21.62%). Lipoatrophy and lipodystrophy combined represent 84.76% (89 cases) of all adverse events documented in this cohort. Within the 60 cases of lipoatrophy, the average number of years on ARVs associated with an AE is 3.54, with 14 cases experiencing an AE between 0-2 years of HAART. Within the 29 cases of lipodystrophy, the average number of years on ARVs associated with an AE is 3.89, with 4 cases experiencing an AE between 0-2 years on HAART. The regimen D4T/3TC/EFV is associated with 43 cases (71.66%) of lipoatrophy and 21 cases (72.41%) of lipodystrophy. D4T/3TC/LOPr is associated with 15 cases (25%) of lipoatrophy and 7 cases (24.14%) of lipodystrophy. The frequency of AE associated with ARV regimens could be misrepresented due to prevalence of different 1st line regimens which were not captured in this study, particularly with the systematic change of 1st line drugs from D4T to ABC in 2010. Conclusion: In this descriptive study we found a 9.37% prevalence of AE were significant enough to be treatment limiting among our cohort. Lipoatrophy accounted for 59.04% of all documented AE. Overall, D4T/3TC/EFV was associated with 64.86% of all AE, 71.66% of lipoatrophy cases and 72.41% of lipodystrophy cases.

Keywords: ARV, adverse events, HAART, pediatric

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1195 Effect of Total Body Irradiation for Metastatic Lymph Node and Lung Metastasis in Early Stage

Authors: Shouta Sora, Shizuki Kuriu, Radhika Mishra, Ariunbuyan Sukhbaatar, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

Abstract:

Lymph node (LN) metastasis accounts for 20 - 30 % of all deaths in patients with head and neck cancer. Therefore, the control of metastatic lymph nodes (MLNs) is necessary to improve the life prognosis of patients with cancer. In a classical metastatic theory, tumor cells are thought to metastasize hematogenously through a bead-like network of lymph nodes. Recently, a lymph node-mediated hematogenous metastasis theory has been proposed, in which sentinel LNs are regarded as a source of distant metastasis. Therefore, the treatment of MLNs at the early stage is essential to prevent distant metastasis. Radiation therapy is one of the primary therapeutic modalities in cancer treatment. In addition, total body irradiation (TBI) has been reported to act as activation of natural killer cells and increase of infiltration of CD4+ T-cells to tumor tissues. However, the treatment effect of TBI for MLNs remains unclear. This study evaluated the possibilities of low-dose total body irradiation (L-TBI) and middle-dose total body irradiation (M-TBI) for the treatment of MLNs. Mouse breast cancer FM3A-Luc cells were injected into subiliac lymph node (SiLN) of MXH10/Mo/LPR mice to induce the metastasis to the proper axillary lymph node (PALN) and lung. Mice were irradiated for the whole body on 4 days after tumor injection. The L-TBI and M-TBI were defined as irradiations to the whole body at 0.2 Gy and 1.0 Gy, respectively. Tumor growth was evaluated by in vivo bioluminescence imaging system. In the non-irradiated group, tumor activities on SiLN and PALN significantly increased over time, and the metastasis to the lung from LNs was confirmed 28 days after tumor injection. The L-TBI led to a tumor growth delay in PALN but did not control tumor growth in SiLN and metastasis to the lung. In contrast, it was found that the M-TBI significantly delayed the tumor growth of both SiLN and PALN and controlled the distant metastasis to the lung compared with non-irradiated and L-TBI groups. These results suggest that the M-TBI is an effective treatment method for MLNs in the early stage and distant metastasis from lymph nodes via blood vessels connected with LNs.

Keywords: metastatic lymph node, lung metastasis, radiation therapy, total body irradiation, lymphatic system

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1194 Near Field Focusing Behaviour of Airborne Ultrasonic Phased Arrays Influenced by Airflows

Authors: D. Sun, T. F. Lu, A. Zander, M. Trinkle

Abstract:

This paper investigates the potential use of airborne ultrasonic phased arrays for imaging in outdoor environments as a means of overcoming the limitations experienced by kinect sensors, which may fail to work in the outdoor environments due to the oversaturation of the infrared photo diodes. Ultrasonic phased arrays have been well studied for static media, yet there appears to be no comparable examination in the literature of the impact of a flowing medium on the focusing behaviour of near field focused ultrasonic arrays. This paper presents a method for predicting the sound pressure fields produced by a single ultrasound element or an ultrasonic phased array influenced by airflows. The approach can be used to determine the actual focal point location of an array exposed in a known flow field. From the presented simulation results based upon this model, it can be concluded that uniform flows in the direction orthogonal to the acoustic propagation have a noticeable influence on the sound pressure field, which is reflected in the twisting of the steering angle of the array. Uniform flows in the same direction as the acoustic propagation have negligible influence on the array. For an array impacted by a turbulent flow, determining the location of the focused sound field becomes difficult due to the irregularity and continuously changing direction and the speed of the turbulent flow. In some circumstances, ultrasonic phased arrays impacted by turbulent flows may not be capable of producing a focused sound field.

Keywords: airborne, airflow, focused sound field, ultrasonic phased array

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1193 Epidemiological and Clinical Profile of Patients with Chorioamnionitis

Authors: Isabel Cristina Ortiz Trujillo, Lina Maria Martinez Sanchez, Felipe Hernández Restrepo, Daniel Gallego Gonzalez, Natalia Vargas Grisales, Camilo Andrés Agudelo Vélez

Abstract:

Chorioamnionitis, is a pregnancy infection, causes different fetal and maternal symptoms. Streptococcus agalactiae present in the normal vaginal microflora of some women, favouring its abnormal multiplication during pregnancy, causing perinatal morbidity and mortality. Objective. Describe the clinical and epidemiological profile of the patients with diagnosis of clinical chorioanmionitis. Methodology. Descriptive, cross-sectional study. The population was patients with diagnosis of clinical chorioanmionitis. The information was taken from the medical records. The research was approved by the Ethics Committee. We used the program SPSS ® version 17.0 (SPSS Inc; Chicago, Illinois, USA) for the information analysis, descriptive statistics were used. Results. 78 patients in total with clinical chorioamnionitis, with a mean age of 26.3 ±5, 8 years old, the 69.2% primigravid women. 2.6% of women had positive culture for Streptococcus agalactiae in urine sample during current pregnancy and 30.7% had received some kind of antibiotics during current pregnancy. The 57.7% had 37 to 40 weeks of gestation in the current pregnancy it was calculated more frequently by ultrasound (66.7% in first quarter, 11.5% in the second and 1.9% in the third). In a 60.3% way of termination of pregnancy was vaginal and a 35.9 percent were caesarean section. Among the women in the study, a 30.8% had premature rupture of membranes. Conclusion. The chorioamnionitis continues to be an important cause of antibiotic use during pregnancy or labour and the decision to do a caesarean, with highest percentage in pregnancies-preterm and preterm premature rupture of membranes.

Keywords: chorioamnionitis, Streptococcus agalactiae, pregnancy complications, infectious

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1192 The Design of a Phase I/II Trial of Neoadjuvant RT with Interdigitated Multiple Fractions of Lattice RT for Large High-grade Soft-Tissue Sarcoma

Authors: Georges F. Hatoum, Thomas H. Temple, Silvio Garcia, Xiaodong Wu

Abstract:

Soft Tissue Sarcomas (STS) represent a diverse group of malignancies with heterogeneous clinical and pathological features. The treatment of extremity STS aims to achieve optimal local tumor control, improved survival, and preservation of limb function. The National Comprehensive Cancer Network guidelines, based on the cumulated clinical data, recommend radiation therapy (RT) in conjunction with limb-sparing surgery for large, high-grade STS measuring greater than 5 cm in size. Such treatment strategy can offer a cure for patients. However, when recurrence occurs (in nearly half of patients), the prognosis is poor, with a median survival of 12 to 15 months and with only palliative treatment options available. The spatially-fractionated-radiotherapy (SFRT), with a long history of treating bulky tumors as a non-mainstream technique, has gained new attention in recent years due to its unconventional therapeutic effects, such as bystander/abscopal effects. Combining single fraction of GRID, the original form of SFRT, with conventional RT was shown to have marginally increased the rate of pathological necrosis, which has been recognized to have a positive correlation to overall survival. In an effort to consistently increase the pathological necrosis rate over 90%, multiple fractions of Lattice RT (LRT), a newer form of 3D SFRT, interdigitated with the standard RT as neoadjuvant therapy was conducted in a preliminary clinical setting. With favorable results of over 95% of necrosis rate in a small cohort of patients, a Phase I/II clinical study was proposed to exam the safety and feasibility of this new strategy. Herein the design of the clinical study is presented. In this single-arm, two-stage phase I/II clinical trial, the primary objectives are >80% of the patients achieving >90% tumor necrosis and to evaluation the toxicity; the secondary objectives are to evaluate the local control, disease free survival and overall survival (OS), as well as the correlation between clinical response and the relevant biomarkers. The study plans to accrue patients over a span of two years. All patient will be treated with the new neoadjuvant RT regimen, in which one of every five fractions of conventional RT is replaced by a LRT fraction with vertices receiving dose ≥10Gy while keeping the tumor periphery at or close to 2 Gy per fraction. Surgical removal of the tumor is planned to occur 6 to 8 weeks following the completion of radiation therapy. The study will employ a Pocock-style early stopping boundary to ensure patient safety. The patients will be followed and monitored for a period of five years. Despite much effort, the rarity of the disease has resulted in limited novel therapeutic breakthroughs. Although a higher rate of treatment-induced tumor necrosis has been associated with improved OS, with the current techniques, only 20% of patients with large, high-grade tumors achieve a tumor necrosis rate exceeding 50%. If this new neoadjuvant strategy is proven effective, an appreciable improvement in clinical outcome without added toxicity can be anticipated. Due to the rarity of the disease, it is hoped that such study could be orchestrated in a multi-institutional setting.

Keywords: lattice RT, necrosis, SFRT, soft tissue sarcoma

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1191 Effects of Renin Angiotensin Pathway Inhibition on Efficacy of Anti-PD-1/PD-L1 Treatment in Metastatic Cancer

Authors: Philip Friedlander, John Rutledge, Jason Suh

Abstract:

Inhibition of programmed death-1 (PD-1) or its ligand PD-L1 confers therapeutic efficacy in a wide range of solid tumor malignancies. Primary or acquired resistance can develop through activation of immunosuppressive immune cells such as tumor-associated macrophages. The renin angiotensin system (RAS) systemically regulates fluid and sodium hemodynamics, but components are expressed on and regulate the activity of immune cells, particularly of myeloid lineage. We hypothesized that inhibition of RAS would improve the efficacy of PD-1/PD-L-1 treatment. A retrospective analysis was performed through a chart review of patients with solid metastatic malignancies treated with a PD-1/PD-L1 inhibitor between 1/2013 and 6/2019 at Valley Hospital, a community hospital in New Jersey, USA. Efficacy was determined by medical oncologist documentation of clinical benefit in visit notes and by the duration of time on immunotherapy treatment. The primary endpoint was the determination of efficacy differences in patients treated with an inhibitor of RAS ( ace inhibitor, ACEi, or angiotensin blocker, ARB) compared to patients not treated with these inhibitors. To control for broader antihypertensive effects, efficacy as a function of treatment with beta blockers was assessed. 173 patients treated with PD-1/PD-L-1 inhibitors were identified of whom 52 were also treated with an ACEi or ARB. Chi-square testing revealed a statistically significant relationship between being on an ACEi or ARB and efficacy to PD-1/PD-L-1 therapy (p=0.001). No statistically significant relationship was seen between patients taking or not taking beta blocker antihypertensives (p= 0.33). Kaplan-Meier analysis showed statistically significant improvement in the duration of therapy favoring patients concomitantly treated with ACEi or ARB compared to patients not exposed to antihypertensives and to those treated with beta blockers. Logistic regression analysis revealed that age, gender, and cancer type did not have significant effects on the odds of experiencing clinical benefit (p=0.74, p=0.75, and p=0.81, respectively). We conclude that retrospective analysis of the treatment of patients with solid metastatic tumors with anti-PD-1/PD-L1 in a community setting demonstrates greater clinical benefit in the context of concomitant ACEi or ARB inhibition, irrespective of gender or age. This data supports the development of prospective assessment through randomized clinical trials.

Keywords: angiotensin, cancer, immunotherapy, PD-1, efficacy

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1190 Efficacy of Single-Dose Azithromycin Therapy for the Treatment of Chlamydia trachomatis in Patients Evaluated for Child Sexual Abuse in an Urban Health Center 2006-16

Authors: Trenton Hubbard, Kenneth Soyemi, Emily Siffermann

Abstract:

Introduction: According to the American Academy of Pediatrics (AAP) there are different weight-based recommendations for the treatment of Chlamydia trachomatis (CT) in patients who are being evaluated for sexual assault. Current AAP Red Book guidelines recommend that uncomplicated C. trachomatis anogenital infection in prepubertal patients weighing less than =<45 kg be treated with oral erythromycin 50 mg/kg/day QID for 14 days with no alternative therapies, and for patients whose weight => 45 kg are Azithromycin 1 gm PO once. Our study objective was to determine the efficacy of single-dose Azithromycin therapy for the treatment of Chlamydia trachomatis in patients weighing less than 50 kg who were evaluated for child sexual abuse in an urban setting. Methods: We conducted a retrospective chart review of historical medical records (paper and electronic) patients weighing less than 50 kg who were evaluated for child sexual abuse and subsequently treated for C. trachomatis infection with Azithromycin (20 mg/kg PO once up to a maximum 1 gm) and received a Test of Cure (TOC) from 2006-2016. Qualitative variables were expressed as percentages. Quantitative variables were expressed as mean values (+/- standard deviation [SD]) if they followed a normal distribution or as median values (interquartile range[IQR]) if they did not. Wilcoxson two-sample test was used to compare means of Azithromycin Dose, mg/kg, and TOC timing between treatment responders and non-responders. Results: We reviewed records of 34 patients, average age (SD) was 5.4 (2.0) years, 33 (97%) were treated for CT and 1(3%) for both GC and CT. 25 (74%) were females. Urine PCR was the most commonly used test at evaluation and as TOC with 13 (38%) patients completing both tests. The average (SD) dose of Azithromycin at treatment was 470 (136) mg and average (SD) mg/kg dose of 20 (1.9) mg/kg for all patients. Median (IQR) timing for TOC testing was 19 (14-26) days. Of the 33 with complete data 25 (74%) had a negative TOC. When compared with treatment non-responders (TOC failures), treatment responders received higher doses (average dose (SD) received 495 (139) vs 401(110), P 0.06)); similar average (SD) weight base dosing received (20.8(2.0) vs 19.7 (1.5), P 0.15)), and earlier average (SD)TOC test timing (18.8 (5.6) vs 32 (28.6) P 0.02)). Conclusion: Azithromycin dosing appears to be efficacious in the treatment of CT post sexual assault as majority of patients responded. Although treatment responders and non-responders received similar weight based doses, there is need for additional studies to understand variances and predictors of response.

Keywords: child sexual abuse, chlmaydia trachmotis infection, single-dose azithromycin, weight less than or equal to 45 kilograms

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1189 A Multidisciplinary Team Approach for Limb Salvage in a Rare Case of Pyoderma Gangrenosum in a Significant Circumferential Lower Extremity Wound Complicated by Diabetes and End-stage Renal Disease

Authors: Jenee Gooden, Kevin Vasquez-monterroso, Lady Paula Dejesus, Sandra Wainwright, Daniel Kim, Mackenzie Walker

Abstract:

Introduction: Pyoderma gangrenosum (PG) is a rare, rapidly progressive, neutrophilic ulcerative colitis condition with an incidence of 3 to 10 cases per year ¹ ². Due to the similar appearance, PG is often misdiagnosed as a diabetic ulcer in diabetic patients. Though they may clinically appear similar in appearance, the treatment protocol and diagnostic criteria differ. Also, end-stage renal disease (ESRD) is often a condition seen in diabetic patients, which can have a significant impact on wound healing due to the wide range of uremic toxins³. This case study demonstrates a multidisciplinary team and multimodal treatment approach by podiatric surgery, general surgery, rheumatology, infectious disease, interventional cardiology, wound care and hyperbaric medicine for an uncontrolled diabetic with pyoderma gangrenosum of a significant circumferential wound, covering almost the entire right lower extremity. Methods:56 y.o male presents with multiple PG ulcerations, including the chest, right posterior lower extremity and sacrum. All ulcerations were previously managed by the same wound care specialist. His chief complaint was worsening PG ulcerations accompanied by a fever of 103 °F . This case study focuses on the wound to his RLE. Past medical history significant for diabetes mellitus type 2 with hemoglobin A1c of 10% and end stage renal disease (ESRD) on hemodialysis. A multidisciplinary team approach by podiatric surgery, general surgery, rheumatology, infectious disease, interventional cardiology, wound care and hyperbaric medicine was successfully used to perform right lower extremity limb salvage. The patient was managed by rheumatology for the continuation of prior medication, as well as the mutual agreement with wound care for the addition of dapsone. A coronary CT angiogram was performed by interventional cardiology, but no significant disease was noted, and no further vascular workup was necessary. Multiple surgical sharp wide excisional debridements with application of allografts and split thickness skin grafts for the circumferential ulceration that encompassed almost the entire right lower extremity were performed by both podiatric surgery and general surgery. Wound cultures and soft tissue biopsies were performed, and infectious disease managed antibiotic therapy. Hyperbaric oxygen therapy and wound vac therapy by wound care were also completed as adjunct management. Results: Prevention of leg amputation by limb salvage of the RLE was accomplished by a multidisciplinary team approach, with the wound size decreasing over a total of 29 weeks from 600 cm² to 12.0 x 3.5 x 0.2 cm. Our multidisciplinary team included podiatric surgery, general surgery, rheumatology, infectious disease, interventional cardiology, wound care and hyperbaric medicine. Discussion: Wound healing, in general, can have its challenges, and those challenges are only magnified when accompanied by multiple systemic illnesses. Though the negative impact of diabetes on wound healing is well known, the compound impact of being a diabetic with ESRD and having pyoderma gangrenosum is not. This case demonstrates the necessity for a multidisciplinary team approach with a wide array of treatment modalities to optimize wound healing and perform limb salvage with prevention of lower extremity amputation.

Keywords: diabetes, podiatry, pyoderma gangrenosum, end stage renal disease

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1188 Prayer Therapy in a Case of Acute Myeloid Leukemia: The Good, the Bad and the Ugly

Authors: Rubai M. Ochieng

Abstract:

Cancer, which accounts for 7 percent of deaths per year in Kenya, is the third highest cause of death after infectious and cardiovascular diseases. Awareness Campaigns have tended to focus on leading cancers including breast and cervical for women as well as prostrate and Esophageal for men. Consequently, less common cancers such as Acute Myeloid Leukemia (AML) are rarely properly understood by the general population and a section of the medical fraternity. Diagnoses of AML in patients who may not have heard about it sometimes results in shock, denial and confusion not just to the diagnosed, but also to their family and friends. The diagnosed and caregivers are bound to receive a lot of contradicting information about prognosis, care and treatment of AML. This information, which often comes from diverse sources including doctors, friends, internet and social media platforms, causes further confusion and panic. The situation is handled differently by different people. Religious people sometimes resort to prayer. This paper, written from the perspective of a care giver, is based on data collected from a case of Acute Myeloid Leukemia diagnosed in a 32 year old male who lost his life within six weeks of diagnosis. The sample constitutes of 16 people who participated in prayers. Out of this total, 5 were males including the diagnosed and 11 were females. All the 16 were Christians of protestant orientation including Anglicans, Quakers and Church of God members. Data was collected by the researcher herself through participant of observation. Findings discuss how the 16 participants prayed individually at different times, together in an overnight prayer meeting and every morning through a group social media platform. They shared songs and words of encouragement from the bible. The group prayed for healing, peace and strength to the diagnosed and family, financial breakthrough and doctors’ work and decisions, among other challenges that came with the situation. The paper reveals the immense benefits of prayer to the diagnosed and his close relatives and friends. They include acceptance of the condition and a positive attitude in handling the challenges that arose from the disease and treatment processes. The challenges arising from the prayer approach of handling the situation are also discussed. The paper concludes that prayer as therapy goes a long way in cancer management.

Keywords: acute myeloid leukemia, Kenya, participant observation, prayer

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1187 Oncological and Antiresorptive Treatment of Breast Cancer: Dental Assessment and Risk of MRONJ Development

Authors: Magdalena Korytowska, Gunnar Lengstrand, Cecilia Larsson Wexell

Abstract:

Background: Breast cancer (BC) is the most common cancer among women worldwide, and cases are continuing to increase in Sweden. Bone is the most common metastatic site in breast cancer patients, where > 65-75% of women with advanced breast cancer develop bone metastases during their disease. To prevent the skeletal-related events of metastases (e.g., pathological fractures, bone loss, cancer-induced bone pain, and hypercalcemia bone), two different classes of antiresorptive medications (AR), bisphosphonate and denosumab are typically administered every 3 to 4 weeks. Since 2015, adjuvant bisphosphonate treatment has been used every six months for three to five years in postmenopausal women for the prevention of skeletal metastases and improved survival. Methods: A case-control study was conducted to test the hypotheses that patients treated with high-dose AR are at higher risk of developing MRONJ than breast cancer patients with adjuvant bisphosphonate treatment at a lower dose. Medical and odontological data was collected between 2015-2020. Assessment of oral health and dental care before and during oncological treatment took place at the specialist clinic for Orofacial medicine linked to the specific hospital. Results: In total, 220 patients were included, 101 patients in the high-dose group and 119 patients in the adjuvant BP-treatment group. MRONJ was diagnosed in 13 patients (14%) in the high-dose group. The mandible was affected in most of the cases (84.6%), with a mean duration of high-dose treatment of 19.7 months. In 46.2% of cases, no dental cause of MRONJ could be identified. Overall, estrogen receptor-positive (ER+) BC was the most representative type in 172 patients (78.2%). However, this was 83.9% in the high-dose cases group. The most used drug was denosumab. Twenty-five patients (26.9%) switched their medication from ZOL to denosumab during their oncological treatment. Patients with ER+ breast cancer were reported in 88 patients (87.8%) in the adjuvant group that was treated with ZOL. Conclusions: MRONJ was diagnosed only in the high-dose AR group. Dental assessment and care of patients in the adjuvant group should be considered, with a recommendation to potentially prolong ZOL treatment from 3 to 5 years, with concomitant use of hormonal therapy in patients diagnosed with ER+ breast cancer to prevent bone loss induced by oncological treatment. A new referral for dental assessment is very important in the case of bone metastases when treatment with high dose AR will be required since it is associated with a higher risk of MRONJ.

Keywords: antiresorptive therapy, breast cancer, dental care, MRONJ

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