Search results for: dementia patients
Commenced in January 2007
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Edition: International
Paper Count: 5443

Search results for: dementia patients

163 The Effect of Clover Honey Supplementation on the Anthropometric Measurements and Lipid Profile of Malnourished Infants and Children

Authors: Bassma A. Abdelhaleem, Mamdouh A. Abdulrhman, Nagwa I. Mohamed

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Malnutrition in children is an increasing problem worldwide which may result in both short and long-term irreversible negative health outcomes. Severe Acute Malnutrition (SAM) affects more than 18 million children each year, mostly living in low-income settings. SAM contributes to 45% of all deaths in children less than five years of age. Honey is a natural sweetener, containing mainly monosaccharides (up to 80%), disaccharides (3–5%), water (17–20%), and a wide range of minor constituents such as vitamins, minerals, proteins, amino acids, enzymes, and phytochemicals, mainly phenolic acids, and flavonoids. Honey has been used in many cultures around the world due to its known nutritional and medicinal benefits including the treatment of hypercholesterolemia. Despite its use since ancient times yet little is known about its potential benefits for malnourished children. Honey has the potential to be an affordable solution for malnourished low-income children as it is nutrient-dense and calorie dense food, easily absorbed, highly palatable, enhances appetite, and boosts immunity. This study assessed the effect of clover honey supplementation on the anthropometric measurements and lipid profile of malnourished infants and children. A prospective interventional clinical trial was conducted between November 2019 to November 2020, on 40 malnourished infants and children divided into two groups: Group A (20 children; 11 males and 9 females) received honey in a dose of 1.75ml/kg/dose, twice weekly for 12 weeks and Group B (20 children; 6 males and 14 females) received placebo. Written informed consent was obtained for parents/guardians. Patients were recruited from the Pediatric Nutrition Clinic at Ain Shams University. Anthropometric measurements (weight, height, body mass index, head circumference, and mid-arm circumference) and fasting serum cholesterol levels were measured at baseline and after 3 months. The 3-month honey consumption had a statistically highly significant effect on increasing weight, height, and body mass index and lowering fasting serum cholesterol levels in primary malnourished infants and children. Weight, height, body mass index, and fasting serum cholesterol level before honey consumption were (9.49 ± 2.03, 81.45 ± 8.31, 14.24 ± 2.15, 178.00 ± 20.91) and after 3 months of honey consumption were (10.91 ± 2.11, 84.80 ± 8.23, 15.07 ± 2.05, 162.45 ± 19.73) respectively with P-value < 0.01. Our results showed a significant desirable effect of honey consumption on changes in nutritional status based on weight, height, and body mass index, and has a favourable effect on lowering fasting serum cholesterol levels. These results propose the use of honey as an affordable solution to improve malnutrition, particularly in low-income countries. However, further research needs to weigh benefits against potential harms including the risk of botulinum toxin that is historically associated with honey consumption in early childhood.

Keywords: clinical trial, dyslipidemia, honey, malnutrition

Procedia PDF Downloads 73
162 Computational Approaches to Study Lineage Plasticity in Human Pancreatic Ductal Adenocarcinoma

Authors: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.

Keywords: deconvolution, imaging, microenvironment, PDAC

Procedia PDF Downloads 97
161 Management of Dysphagia after Supra Glottic Laryngectomy

Authors: Premalatha B. S., Shenoy A. M.

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Background: Rehabilitation of swallowing is as vital as speech in surgically treated head and neck cancer patients to maintain nutritional support, enhance wound healing and improve quality of life. Aspiration following supraglottic laryngectomy is very common, and rehabilitation of the same is crucial which requires involvement of speech therapist in close contact with head and neck surgeon. Objectives: To examine the functions of swallowing outcomes after intensive therapy in supraglottic laryngectomy. Materials: Thirty-nine supra glottic laryngectomees were participated in the study. Of them, 36 subjects were males and 3 were females, in the age range of 32-68 years. Eighteen subjects had undergone standard supra glottis laryngectomy (Group1) for supraglottic lesions where as 21 of them for extended supraglottic laryngectomy (Group 2) for base tongue and lateral pharyngeal wall lesion. Prior to surgery visit by speech pathologist was mandatory to assess the sutability for surgery and rehabilitation. Dysphagia rehabilitation started after decannulation of tracheostoma by focusing on orientation about anatomy, physiological variation before and after surgery, which was tailor made for each individual based on their type and extent of surgery. Supraglottic diet - Soft solid with supraglottic swallow method was advocated to prevent aspiration. The success of intervention was documented as number of sessions taken to swallow different food consistency and also percentage of subjects who achieved satisfactory swallow in terms of number of weeks in both the groups. Results: Statistical data was computed in two ways in both the groups 1) to calculate percentage (%) of subjects who swallowed satisfactorily in the time frame of less than 3 weeks to more than 6 weeks, 2) number of sessions taken to swallow without aspiration as far as food consistency was concerned. The study indicated that in group 1 subjects of standard supraglottic laryngectomy, 61% (n=11) of them were successfully rehabilitated but their swallowing normalcy was delayed by an average 29th post operative day (3-6 weeks). Thirty three percentages (33%) (n=6) of the subjects could swallow satisfactorily without aspiration even before 3 weeks and only 5 % (n=1) of the needed more than 6 weeks to achieve normal swallowing ability. Group 2 subjects of extended SGL only 47 %( n=10) of them could achieved satisfactory swallow by 3-6 weeks and 24% (n=5) of them of them achieved normal swallowing ability before 3 weeks. Around 4% (n=1) needed more than 6 weeks and as high as 24 % (n=5) of them continued to be supplemented with naso gastric feeding even after 8-10 months post operative as they exhibited severe aspiration. As far as type of food consistencies were concerned group 1 subject could able to swallow all types without aspiration much earlier than group 2 subjects. Group 1 needed only 8 swallowing therapy sessions for thickened soft solid and 15 sessions for liquids whereas group 2 required 14 sessions for soft solid and 17 sessions for liquids to achieve swallowing normalcy without aspiration. Conclusion: The study highlights the importance of dysphagia intervention in supraglottic laryngectomees by speech pathologist.

Keywords: dysphagia management, supraglotic diet, supraglottic laryngectomy, supraglottic swallow

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160 A Mother’s Silent Adversary: A Case of Pregnant Woman with Cervical Cancer

Authors: Paola Millare, Nelinda Catherine Pangilinan

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Background and Aim: Cervical cancer is the most commonly diagnosed gynecological malignancy during pregnancy. Owing to the rarity of the disease, and the complexity of all factors that have to be taken into consideration, standardization of treatment is very difficult. Cervical cancer is the second most common malignancy among women. The treatment of cancer during pregnancy is most challenging in the case of cervical cancer, since the pregnant uterus itself is affected. This report aims to present a case of cervical cancer in a pregnant woman and how to manage this case and several issues accompanied with it. Methods: This is a case of a 28 year-old, Gravida 4 Para 2 (1111), who presented with watery to mucoid, whitish, non-foul smelling and increasing in amount. Internal examination revealed normal external genitalia, parous outlet, cervix was transformed into a fungating mass measuring 5x4 cm, with left parametrial involvement, body of uterus was enlarged to 24 weeks size, no adnexal mass or tenderness. She had cervical punch biopsy, which revealed, adenocarcinoma, well-differentiated cervical tissue. Standard management for cases with stage 2B cervical carcinoma was to start radiation or radical hysterectomy. In the case of patients diagnosed with cervical cancer and currently pregnant, these kind of management will result to fetal loss. The patient still declined the said management and opted to delay the treatment and wait for her baby to reach at least term and proceed to cesarean section as route of delivery. Results: The patient underwent an elective cesarean section at 37th weeks age of gestation, with an outcome of a term, live baby boy APGAR score 7,9 birthweight 2600 grams. One month postpartum, the patient followed up and completed radiotherapy, chemotherapy and brachytherapy. She was advised to go back after 6 months for monitoring. On her last check up, an internal examination was done which revealed normal external genitalia, vagina admits 2 fingers with ease, there is a palpable fungating mass at the cervix measuring 2x2 cm. A repeat gynecologic oncologic ultrasound was done revealing cervical mass, endophytic, grade 1 color score with stromal invasion 35% post radiation reactive lymph nodes with intact paracolpium, pericervical, and parametrial involvement. The patient was then advised to undergo pelvic boost and for close monitoring of the cervical mass. Conclusion: Cervical cancer in pregnancy is rare but is a dilemma for women and their physicians. Treatment should be multidisciplinary and individualized following careful counseling. In this case, the treatment was clearly on the side of preventing the progression of cervical cancer while she is pregnant, however due to ethical reasons, the management deviates on the right of the patient to decide for her own health and her unborn child. The collaborative collection of data relating to treatment and outcome is strongly encouraged.

Keywords: cancer, cervical, ethical, pregnancy

Procedia PDF Downloads 213
159 Medical Dressing Induced Digital Ischemia in Patient with Congenital Insensitivity to Pain and Anhidrosis

Authors: Abdulwhab Alotaibi, Abdullah Alzahrani, Ziyad Bokhari, Abdulelah Alghamdi

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First described in 1975 by Dr. Miller, Medical dressings are uncommon but possible cause of hand digital ischemia due the tourniquet-like effect. The incident of this complication has been reported across wide range of age-groups, yet it seems like that the pediatric population are specifically vulnerable. Multiple dressing types were reported to have caused ischemic injury, such as elastic wrap, tubular gauze, and self-adherent dressings. We present a case of medical dressing induced digital ischemia in patient with Congenital insensitivity to pain and anhidrosis (CIPA), which further challenge the discovery of the condition. An 8-year-old girl known case of CIPA. Brought by her mother to the ER after nail bed injury, which she managed by application of elastic wrap that was left for 24 hours. When the mother found out she immediately removed the elastic band, and noticed the fingertip was black and cold with tense bullae. The color then changed later when she arrived to the ER to dark purple with bluish discoloration on the tip. On examination there was well demarcated tense bullae on the distal right fifth finger. Neurovascular intact, pulse oximetry on distal digit 100%, capillary refill time was delayed. She was seen under Plastic surgery and conservative management recommended, and patient was discharged with safety netting. Two days later the patient came as follow-up visit at which her condition demonstrated significant improvement, the bullae has since ruptured leaving behind sloughed skin, capillary refill and pulse oximetry were both within normal limits, sensory function couldn’t be assessed but her motor function and ROM were normal, topical bacitracin and bandage dressings were applied for the eroded skin. Patient was scheduled for a follow-up in 2 weeks. Preventatively it’s advisable to avoid the commonly implicated dressings such as elastic, tubular gauze or self-adherent wraps in hand or digital injuries when possible, but in cases where the use of these dressings is of necessity the appropriate precautions must be taken, Dr. Makarewich proposed the following 5 measures to help minimize the incidence of the injury: 1-Unwrapping 12 inches of the dressing before rolling the injured finger. 2-Wrapping from distal to proximal with minimal tension to avoid vascular embarrassment. 3-The use of 5-25 inch to overlap the entire wrap. 4-Maintaining light pressure over the wrap to allow adherence of the dressing. 5-Minimization of the number of layers used to wrap the affected digit. Also assessing the capillary refill after the application can help in determining the patency of the supplying blood vessels. It’s also important to selectively determine if the patient is a candidate for conservative management, as tailored approach can help in maximizing the positive outcomes for our patients.

Keywords: congenital insensitivity to pain, digital ischemia, medical dressing, conservative management

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158 An Investigation of Tetraspanin Proteins’ Role in UPEC Infection

Authors: Fawzyah Albaldi

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Urinary tract infections (UTIs) are the most prevalent of infectious diseases and > 80% are caused by uropathogenic E. coli (UPEC). Infection occurs following adhesion to urothelial plaques on bladder epithelial cells, whose major protein constituent are the uroplakins (UPs). Two of the four uroplakins (UPIa and UPIb) are members of the tetraspanin superfamily. The UPEC adhesin FimH is known to interact directly with UPIa. Tetraspanins are a diverse family of transmembrane proteins that generally act as “molecular organizers” by binding different proteins and lipids to form tetraspanin enriched microdomains (TEMs). Previous work by our group has shown that TEMs are involved in the adhesion of many pathogenic bacteria to human cells. Adhesion can be blocked by tetraspanin-derived synthetic peptides, suggesting that tetraspanins may be valuable drug targets. In this study, we investigate the role of tetraspanins in UPEC adherence to bladder epithelial cells. Human bladder cancer cell lines (T24, 5637, RT4), commonly used as in-vitro models to investigate UPEC infection, along with primary human bladder cells, were used in this project. The aim was to establish a model for UPEC adhesion/infection with the objective of evaluating the impact of tetraspanin-derived reagents on this process. Such reagents could reduce the progression of UTI, particularly in patients with indwelling catheters. Tetraspanin expression on the bladder cells was investigated by q-PCR and flow cytometry, with CD9 and CD81 generally highly expressed. Interestingly, despite these cell lines being used by other groups to investigate FimH antagonists, uroplakin proteins (UPIa, UPIb and UPIII) were poorly expressed at the cell surface, although some were present intracellularly. Attempts were made to differentiate the cell lines, to induce cell surface expression of these UPs, but these were largely unsuccessful. Pre-treatment of bladder epithelial cells with anti-CD9 monoclonal antibody significantly decreased UPEC infection, whilst anti-CD81 had no effects. A short (15aa) synthetic peptide corresponding to the large extracellular region (EC2) of CD9 also significantly reduced UPEC adherence. Furthermore, we demonstrated specific binding of that fluorescently tagged peptide to the cells. CD9 is known to associate with a number of heparan sulphate proteoglycans (HSPGs) that have also been implicated in bacterial adhesion. Here, we demonstrated that unfractionated heparin (UFH)and heparin analogs significantly inhibited UPEC adhesion to RT4 cells, as did pre-treatment of the cells with heparinases. Pre-treatment with chondroitin sulphate (CS) and chondroitinase also significantly decreased UPEC adherence to RT4 cells. This study may shed light on a common pathogenicity mechanism involving the organisation of HSPGs by tetraspanins. In summary, although we determined that the bladder cell lines were not suitable to investigate the role of uroplakins in UPEC adhesion, we demonstrated roles for CD9 and cell surface proteoglycans in this interaction. Agents that target these may be useful in treating/preventing UTIs.

Keywords: UTIs, tspan, uroplakins, CD9

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157 Current Applications of Artificial Intelligence (AI) in Chest Radiology

Authors: Angelis P. Barlampas

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Learning Objectives: The purpose of this study is to inform briefly the reader about the applications of AI in chest radiology. Background: Currently, there are 190 FDA-approved radiology AI applications, with 42 (22%) pertaining specifically to thoracic radiology. Imaging findings OR Procedure details Aids of AI in chest radiology1: Detects and segments pulmonary nodules. Subtracts bone to provide an unobstructed view of the underlying lung parenchyma and provides further information on nodule characteristics, such as nodule location, nodule two-dimensional size or three dimensional (3D) volume, change in nodule size over time, attenuation data (i.e., mean, minimum, and/or maximum Hounsfield units [HU]), morphological assessments, or combinations of the above. Reclassifies indeterminate pulmonary nodules into low or high risk with higher accuracy than conventional risk models. Detects pleural effusion . Differentiates tension pneumothorax from nontension pneumothorax. Detects cardiomegaly, calcification, consolidation, mediastinal widening, atelectasis, fibrosis and pneumoperitoneum. Localises automatically vertebrae segments, labels ribs and detects rib fractures. Measures the distance from the tube tip to the carina and localizes both endotracheal tubes and central vascular lines. Detects consolidation and progression of parenchymal diseases such as pulmonary fibrosis or chronic obstructive pulmonary disease (COPD).Can evaluate lobar volumes. Identifies and labels pulmonary bronchi and vasculature and quantifies air-trapping. Offers emphysema evaluation. Provides functional respiratory imaging, whereby high-resolution CT images are post-processed to quantify airflow by lung region and may be used to quantify key biomarkers such as airway resistance, air-trapping, ventilation mapping, lung and lobar volume, and blood vessel and airway volume. Assesses the lung parenchyma by way of density evaluation. Provides percentages of tissues within defined attenuation (HU) ranges besides furnishing automated lung segmentation and lung volume information. Improves image quality for noisy images with built-in denoising function. Detects emphysema, a common condition seen in patients with history of smoking and hyperdense or opacified regions, thereby aiding in the diagnosis of certain pathologies, such as COVID-19 pneumonia. It aids in cardiac segmentation and calcium detection, aorta segmentation and diameter measurements, and vertebral body segmentation and density measurements. Conclusion: The future is yet to come, but AI already is a helpful tool for the daily practice in radiology. It is assumed, that the continuing progression of the computerized systems and the improvements in software algorithms , will redder AI into the second hand of the radiologist.

Keywords: artificial intelligence, chest imaging, nodule detection, automated diagnoses

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156 Automated System: Managing the Production and Distribution of Radiopharmaceuticals

Authors: Shayma Mohammed, Adel Trabelsi

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Radiopharmacy is the art of preparing high-quality, radioactive, medicinal products for use in diagnosis and therapy. Radiopharmaceuticals unlike normal medicines, this dual aspect (radioactive, medical) makes their management highly critical. One of the most convincing applications of modern technologies is the ability to delegate the execution of repetitive tasks to programming scripts. Automation has found its way to the most skilled jobs, to improve the company's overall performance by allowing human workers to focus on more important tasks than document filling. This project aims to contribute to implement a comprehensive system to insure rigorous management of radiopharmaceuticals through the use of a platform that links the Nuclear Medicine Service Management System to the Nuclear Radio-pharmacy Management System in accordance with the recommendations of World Health Organization (WHO) and International Atomic Energy Agency (IAEA). In this project we attempt to build a web application that targets radiopharmacies, the platform is built atop the inherently compatible web stack which allows it to work in virtually any environment. Different technologies are used in this project (PHP, Symfony, MySQL Workbench, Bootstrap, Angular 7, Visual Studio Code and TypeScript). The operating principle of the platform is mainly based on two parts: Radiopharmaceutical Backoffice for the Radiopharmacian, who is responsible for the realization of radiopharmaceutical preparations and their delivery and Medical Backoffice for the Doctor, who holds the authorization for the possession and use of radionuclides and he/she is responsible for ordering radioactive products. The application consists of sven modules: Production, Quality Control/Quality Assurance, Release, General Management, References, Transport and Stock Management. It allows 8 classes of users: The Production Manager (PM), Quality Control Manager (QCM), Stock Manager (SM), General Manager (GM), Client (Doctor), Parking and Transport Manager (PTM), Qualified Person (QP) and Technical and Production Staff. Digital platform bringing together all players involved in the use of radiopharmaceuticals and integrating the stages of preparation, production and distribution, Web technologies, in particular, promise to offer all the benefits of automation while requiring no more than a web browser to act as a user client, which is a strength because the web stack is by nature multi-platform. This platform will provide a traceability system for radiopharmaceuticals products to ensure the safety and radioprotection of actors and of patients. The new integrated platform is an alternative to write all the boilerplate paperwork manually, which is a tedious and error-prone task. It would minimize manual human manipulation, which has proven to be the main source of error in nuclear medicine. A codified electronic transfer of information from radiopharmaceutical preparation to delivery will further reduce the risk of maladministration.

Keywords: automated system, management, radiopharmacy, technical papers

Procedia PDF Downloads 128
155 Mood Symptom Severity in Service Members with Posttraumatic Stress Symptoms after Service Dog Training

Authors: Tiffany Riggleman, Andrea Schultheis, Kalyn Jannace, Jerika Taylor, Michelle Nordstrom, Paul F. Pasquina

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Introduction: Posttraumatic Stress (PTS) and Posttraumatic Stress Disorder (PTSD) remain significant problems for military and veteran communities. Symptoms of PTSD often include poor sleep, intrusive thoughts, difficulty concentrating, and trouble with emotional regulation. Unfortunately, despite its high prevalence, service members diagnosed with PTSD often do not seek help, usually because of the perceived stigma surrounding behavioral health care. To help address these challenges, non-pharmacological, therapeutic approaches are being developed to help improve care and enhance compliance. The Service Dog Training Program (SDTP), which involves teaching patients how to train puppies to become mobility service dogs, has been successfully implemented into PTS/PTSD care programs with anecdotal reports of improved outcomes. This study was designed to assess the biopsychosocial effects of SDTP from military beneficiaries with PTS symptoms. Methods: Individuals between the ages of 18 and 65 with PTS symptom were recruited to participate in this prospective study. Each subject completes 4 weeks of baseline testing, followed by 6 weeks of active service dog training (twice per week for one hour sessions) with a professional service dog trainer. Outcome measures included the Posttraumatic Stress Checklist for the DSM-5 (PCL-5), Generalized Anxiety Disorder questionnaire-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), social support/interaction, anthropometrics, blood/serum biomarkers, and qualitative interviews. Preliminary analysis of 17 participants examined mean scores on the GAD-7, PCL-5, and PHQ-9, pre- and post-SDTP, and changes were assessed using Wilcoxon Signed-Rank tests. Results: Post-SDTP, there was a statistically significant mean decrease in PCL-5 scores of 13.5 on an 80-point scale (p=0.03) and a significant mean decrease of 2.2 in PHQ-9 scores on a 27 point scale (p=0.04), suggestive of decreased PTSD and depression symptoms. While there was a decrease in mean GAD-7 scores post-SDTP, the difference was not significant (p=0.20). Recurring themes among results from the qualitative interviews include decreased pain, forgetting about stressors, improved sense of calm, increased confidence, improved communication, and establishing a connection with the service dog. Conclusion: Preliminary results of the first 17 participants in this study suggest that individuals who received SDTP had a statistically significant decrease in PTS symptom, as measured by the PCL-5 and PHQ-9. This ongoing study seeks to enroll a total of 156 military beneficiaries with PTS symptoms. Future analyses will include additional psychological outcomes, pain scores, blood/serum biomarkers, and other measures of the social aspects of PTSD, such as relationship satisfaction and sleep hygiene.

Keywords: post-concussive syndrome, posttraumatic stress, service dog, service dog training program, traumatic brain injury

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154 The Impact of Using Flattening Filter-Free Energies on Treatment Efficiency for Prostate SBRT

Authors: T. Al-Alawi, N. Shorbaji, E. Rashaidi, M.Alidrisi

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Purpose/Objective(s): The main purpose of this study is to analyze the planning of SBRT treatments for localized prostate cancer with 6FFF and 10FFF energies to see if there is a dosimetric difference between the two energies and how we can increase the plan efficiency and reduce its complexity. Also, to introduce a planning method in our department to treat prostate cancer by utilizing high energy photons without increasing patient toxicity and fulfilled all dosimetric constraints for OAR (an organ at risk). Then toevaluate the target 95% coverage PTV95, V5%, V2%, V1%, low dose volume for OAR (V1Gy, V2Gy, V5Gy), monitor unit (beam-on time), and estimate the values of homogeneity index HI, conformity index CI a Gradient index GI for each treatment plan.Materials/Methods: Two treatment plans were generated for15 patients with localized prostate cancer retrospectively using the CT planning image acquired for radiotherapy purposes. Each plan contains two/three complete arcs with two/three different collimator angle sets. The maximum dose rate available is 1400MU/min for the energy 6FFF and 2400MU/min for 10FFF. So in case, we need to avoid changing the gantry speed during the rotation, we tend to use the third arc in the plan with 6FFF to accommodate the high dose per fraction. The clinical target volume (CTV) consists of the entire prostate for organ-confined disease. The planning target volume (PTV) involves a margin of 5 mm. A 3-mm margin is favored posteriorly. Organs at risk identified and contoured include the rectum, bladder, penile bulb, femoral heads, and small bowel. The prescription dose is to deliver 35Gyin five fractions to the PTV and apply constraints for organ at risk (OAR) derived from those reported in references. Results: In terms of CI=0.99, HI=0.7, and GI= 4.1, it was observed that they are all thesame for both energies 6FFF and 10FFF with no differences, but the total delivered MUs are much less for the 10FFF plans (2907 for 6FFF vs.2468 for 10FFF) and the total delivery time is 124Sc for 6FFF vs. 61Sc for 10FFF beams. There were no dosimetric differences between 6FFF and 10FFF in terms of PTV coverage and mean doses; the mean doses for the bladder, rectum, femoral heads, penile bulb, and small bowel were collected, and they were in favor of the 10FFF. Also, we got lower V1Gy, V2Gy, and V5Gy doses for all OAR with 10FFF plans. Integral dosesID in (Gy. L) were recorded for all OAR, and they were lower with the 10FFF plans. Conclusion: High energy 10FFF has lower treatment time and lower delivered MUs; also, 10FFF showed lower integral and meant doses to organs at risk. In this study, we suggest usinga 10FFF beam for SBRTprostate treatment, which has the advantage of lowering the treatment time and that lead to lessplan complexity with respect to 6FFF beams.

Keywords: FFF beam, SBRT prostate, VMAT, prostate cancer

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153 The Potential Impact of Big Data Analytics on Pharmaceutical Supply Chain Management

Authors: Maryam Ziaee, Himanshu Shee, Amrik Sohal

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Big Data Analytics (BDA) in supply chain management has recently drawn the attention of academics and practitioners. Big data refers to a massive amount of data from different sources, in different formats, generated at high speed through transactions in business environments and supply chain networks. Traditional statistical tools and techniques find it difficult to analyse this massive data. BDA can assist organisations to capture, store, and analyse data specifically in the field of supply chain. Currently, there is a paucity of research on BDA in the pharmaceutical supply chain context. In this research, the Australian pharmaceutical supply chain was selected as the case study. This industry is highly significant since the right medicine must reach the right patients, at the right time, in right quantity, in good condition, and at the right price to save lives. However, drug shortages remain a substantial problem for hospitals across Australia with implications on patient care, staff resourcing, and expenditure. Furthermore, a massive volume and variety of data is generated at fast speed from multiple sources in pharmaceutical supply chain, which needs to be captured and analysed to benefit operational decisions at every stage of supply chain processes. As the pharmaceutical industry lags behind other industries in using BDA, it raises the question of whether the use of BDA can improve transparency among pharmaceutical supply chain by enabling the partners to make informed-decisions across their operational activities. This presentation explores the impacts of BDA on supply chain management. An exploratory qualitative approach was adopted to analyse data collected through interviews. This study also explores the BDA potential in the whole pharmaceutical supply chain rather than focusing on a single entity. Twenty semi-structured interviews were undertaken with top managers in fifteen organisations (five pharmaceutical manufacturers, five wholesalers/distributors, and five public hospital pharmacies) to investigate their views on the use of BDA. The findings revealed that BDA can enable pharmaceutical entities to have improved visibility over the whole supply chain and also the market; it enables entities, especially manufacturers, to monitor consumption and the demand rate in real-time and make accurate demand forecasts which reduce drug shortages. Timely and precise decision-making can allow the entities to source and manage their stocks more effectively. This can likely address the drug demand at hospitals and respond to unanticipated issues such as drug shortages. Earlier studies explore BDA in the context of clinical healthcare; however, this presentation investigates the benefits of BDA in the Australian pharmaceutical supply chain. Furthermore, this research enhances managers’ insight into the potentials of BDA at every stage of supply chain processes and helps to improve decision-making in their supply chain operations. The findings will turn the rhetoric of data-driven decision into a reality where the managers may opt for analytics for improved decision-making in the supply chain processes.

Keywords: big data analytics, data-driven decision, pharmaceutical industry, supply chain management

Procedia PDF Downloads 79
152 Detection and Identification of Antibiotic Resistant UPEC Using FTIR-Microscopy and Advanced Multivariate Analysis

Authors: Uraib Sharaha, Ahmad Salman, Eladio Rodriguez-Diaz, Elad Shufan, Klaris Riesenberg, Irving J. Bigio, Mahmoud Huleihel

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Antimicrobial drugs have played an indispensable role in controlling illness and death associated with infectious diseases in animals and humans. However, the increasing resistance of bacteria to a broad spectrum of commonly used antibiotics has become a global healthcare problem. Many antibiotics had lost their effectiveness since the beginning of the antibiotic era because many bacteria have adapted defenses against these antibiotics. Rapid determination of antimicrobial susceptibility of a clinical isolate is often crucial for the optimal antimicrobial therapy of infected patients and in many cases can save lives. The conventional methods for susceptibility testing require the isolation of the pathogen from a clinical specimen by culturing on the appropriate media (this culturing stage lasts 24 h-first culturing). Then, chosen colonies are grown on media containing antibiotic(s), using micro-diffusion discs (second culturing time is also 24 h) in order to determine its bacterial susceptibility. Other methods, genotyping methods, E-test and automated methods were also developed for testing antimicrobial susceptibility. Most of these methods are expensive and time-consuming. Fourier transform infrared (FTIR) microscopy is rapid, safe, effective and low cost method that was widely and successfully used in different studies for the identification of various biological samples including bacteria; nonetheless, its true potential in routine clinical diagnosis has not yet been established. The new modern infrared (IR) spectrometers with high spectral resolution enable measuring unprecedented biochemical information from cells at the molecular level. Moreover, the development of new bioinformatics analyses combined with IR spectroscopy becomes a powerful technique, which enables the detection of structural changes associated with resistivity. The main goal of this study is to evaluate the potential of the FTIR microscopy in tandem with machine learning algorithms for rapid and reliable identification of bacterial susceptibility to antibiotics in time span of few minutes. The UTI E.coli bacterial samples, which were identified at the species level by MALDI-TOF and examined for their susceptibility by the routine assay (micro-diffusion discs), are obtained from the bacteriology laboratories in Soroka University Medical Center (SUMC). These samples were examined by FTIR microscopy and analyzed by advanced statistical methods. Our results, based on 700 E.coli samples, were promising and showed that by using infrared spectroscopic technique together with multivariate analysis, it is possible to classify the tested bacteria into sensitive and resistant with success rate higher than 90% for eight different antibiotics. Based on these preliminary results, it is worthwhile to continue developing the FTIR microscopy technique as a rapid and reliable method for identification antibiotic susceptibility.

Keywords: antibiotics, E.coli, FTIR, multivariate analysis, susceptibility, UTI

Procedia PDF Downloads 152
151 Lived Experiences and Perspectives of Adult Survivors of Incest-Related Childhood Sexual Abuse

Authors: Varsha Puri, Sharon Hudson, Ian Kim

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Background: Incest-related childhood sexual abuse (IRCSA) is challenging to study due to the shame and secrecy experienced by its survivors. Ramifications of IRCSA worsen when it is unidentified, and interventions are not made. IRCSA perspectives are essential for future prevention and intervention strategies. However, there is limited understanding of this population’s experiences, perspectives, and long-term struggles. To date, research for IRCSA has utilized data from treatment programs and qualitative research with cohorts of 10-20 people, much of the data is from 10-40 years prior. Methods. In June 2018, an anonymous online survey was posted to multiple social media sites (e.g., Facebook IRCSA groups) and sexual abuse resource sites. Survey responses were collected for a year. The survey collected non-identifying demographics, IRCSA experiences, and outcomes data. Results: We obtained 1310 completed surveys. Demographics of all ages, racial backgrounds, financial backgrounds, and genders were obtained; the majority identified as white (81%) and female (76%). Childhood sexual abuse (CSA) started before the age of 6 in 49% and was endured for more than one year in 84% of respondents, and 39% reported ten or more years of abuse. CSA by multiple perpetrators occurred in 58%, while 8% had ten or more perpetrators. CSA by perpetrators under 21 years old was reported by 46%. Female perpetrators were reported by 28% of respondents. Fathers were the highest reported sexual abusers at 60%, and mothers were reported at 17%. Only 16% reported that at least one of their perpetrators was prosecuted for sexual abuse of a minor. Respondents confirmed that 54% of the time, they informed an adult of the abuse; only 2% agreed that “an intervention was made by the family that protected me.” A majority reported that IRCSA has negatively impacted their intimate/sexual relationships (96%) and mental health (96%). A majority reported negative impacts on biological family relationships (88%), physical health (73%), finances (59%), educational achievement (57%), and employment (56%). When asked about suffering from addiction, 85% of respondents answered yes. Prevention strategies selected most by respondents include early school education around CSA prevention (67%), removing the statute of limitations for reporting CSA (69%), and improved laws protecting IRCSA survivors (63%). Conclusion: The data document that IRCSA can be pervasive, and the dearth of intervention and support for survivors have major lasting impacts. Survivors have a unique and valuable perspective on what interventions are needed to prevent IRCSA and support survivors; their voice has long been unheard in crafting prevention and intervention policies and services. These results thus provide an important call to action from these critical stakeholders. Pediatricians should recognize that perpetrators can be pediatric patients, women, and parents. Pediatricians can advocate for more early CSA prevention education and policy changes that remove the statute of limitations for reporting CSA.

Keywords: incest, childhood sexual abuse, incest-related childhood sexual abuse, incest survivor

Procedia PDF Downloads 67
150 Single Stage “Fix and Flap” Orthoplastic Approach to Severe Open Tibial Fractures: A Systematic Review of the Outcomes

Authors: Taylor Harris

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Gustilo-anderson grade III tibial fractures are exquisitely difficult injuries to manage as they require extensive soft tissue repair in addition to fracture fixation. These injuries are best managed collaboratively by Orthopedic and Plastic surgeons. While utilizing an Orthoplastics approach has decreased the rates of adverse outcomes in these injuries, there is a large amount of variation in exactly how an Orthoplastics team approaches complex cases such as these. It is sometimes recommended that definitive bone fixation and soft tissue coverage be completed simultaneously in a single-stage manner, but there is a paucity of large scale studies to provide evidence to support this recommendation. It is the aim of this study to report the outcomes of a single-stage "fix-and-flap" approach through a systematic review of the available literature. Hopefully, this better informs an evidence-based Orthoplastics approach to managing open tibial fractures. Systematic review of the literature was performed. Medline and Google Scholar were used and all studies published since 2000, in English were included. 103 studies were initially evaluated for inclusion. Reference lists of all included studies were also examined for potentially eligible studies. Gustilo grade III tibial shaft fractures in adults that were managed with a single-stage Orthoplastics approach were identified and evaluated with regard to outcomes of interest. Exclusion criteria included studies with patients <16 years old, case studies, systemic reviews, meta-analyses. Primary outcomes of interest were the rates of deep infections and rates of limb salvage. Secondary outcomes of interest included time to bone union, rates of non-union, and rates of re-operation. 15 studies were eligible. 11 of these studies reported rates of deep infection as an outcome, with rates ranging from 0.98%-20%. The pooled rate between studies was 7.34%. 7 studies reported rates of limb salvage with a range of 96.25%-100%. The pooled rate of the associated studies was 97.8%. 6 reported rates of non-union with a range of 0%-14%, a pooled rate of 6.6%. 6 reported time to bone union with a range of 24 to 40.3 weeks and a pooled average time of 34.2 weeks, and 4 reported rates of reoperation ranging from 7%-55%, with a pooled rate of 31.1%. A few studies that compared a single stage to a multi stage approach side-by-side unanimously favored the single stage approach. Outcomes of Gustilo grade III open tibial fractures utilizing an Orthoplastics approach that is specifically done in a single-stage produce low rates of adverse outcomes. Large scale studies of Orthoplastic collaboration that were not completed in strictly a single stage, or were completed in multiple stages, have not reported as favorable outcomes. We recommend that not only should Orthopedic surgeons and Plastic surgeons collaborate in the management of severe open tibial fracture, but they should plan to undergo definitive fixation and coverage in a single-stage for improved outcomes.

Keywords: orthoplastic, gustilo grade iii, single-stage, trauma, systematic review

Procedia PDF Downloads 68
149 Innovative Strategies for Chest Wall Reconstruction Following Resection of Recurrent Breast Carcinoma

Authors: Sean Yao Zu Kong, Khong Yik Chew

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Introduction: We described a case report of the successful use of advanced surgical techniques in a patient with recurrent breast cancer who underwent a wide resection including the hemi-sternum, clavicle, multiple ribs, and a lobe of the lung due to tumor involvement. This extensive resection exposed critical structures, requiring a creative approach to reconstruction. To address this complex chest wall reconstruction, a free fibula flap and a 4-zone rectus abdominis musculocutaneous flap were successfully utilized. The use of a free vascularized bone flap allowed for rapid osteointegration and resistance against osteoradionecrosis after adjuvant radiation, while a four-zone tram flap allowed for reconstruction of both the chest wall and breast mound. Although limited recipient vessels made free flaps challenging, the free fibula flap served as both a bony reconstruction and vascular conduit, supercharged with the distal peroneal artery and veins of the peroneal artery from the fibula graft. Our approach highlights the potential of advanced surgical techniques to improve outcomes in complex cases of chest wall reconstruction in patients with recurrent breast cancer, which is becoming increasingly relevant as breast cancer incidence rates increases. Case presentation: This report describes a successful reconstruction of a patient with recurrent breast cancer who required extensive resection, including the anterior chest wall, clavicle, and sternoclavicular joint. Challenges arose due to the loss of accessory muscles and the non-rigid rib cage, which could lead to compromised ventilation and instability. A free fibula osteocutaneous flap and a four-zone TRAM flap with vascular supercharging were utilized to achieve long-term stability and function. The patient has since fully recovered, and during the review, both flaps remained viable, and chest mound reconstruction was satisfactory. A planned nipple/areolar reconstruction was offered pending the patient’s decision after adjuvant radiotherapy. Conclusion: In conclusion, this case report highlights the successful use of innovative surgical techniques in addressing a complex case of recurrent breast cancer requiring extensive resection and radical reconstruction. Our approach, utilized a combination of a free fibula flap and a 4-zone rectus abdominis musculocutaneous flap, demonstrates the potential for advanced techniques in chest wall reconstruction to minimize complications and ensure long-term stability and function. As the incidence of breast cancer continues to rise, it is crucial that healthcare professionals explore and utilize innovative techniques to improve patient outcomes and quality of life.

Keywords: free fibula flap, rectus abdominis musculocutaneous flap, post-adjuvant radiotherapy, reconstructive surgery, malignancy

Procedia PDF Downloads 43
148 Development of a Human Skin Explant Model for Drug Metabolism and Toxicity Studies

Authors: K. K. Balavenkatraman, B. Bertschi, K. Bigot, A. Grevot, A. Doelemeyer, S. D. Chibout, A. Wolf, F. Pognan, N. Manevski, O. Kretz, P. Swart, K. Litherland, J. Ashton-Chess, B. Ling, R. Wettstein, D. J. Schaefer

Abstract:

Skin toxicity is poorly detected during preclinical studies, and drug-induced side effects in humans such as rashes, hyperplasia or more serious events like bullous pemphigus or toxic epidermal necrolysis represent an important hurdle for clinical development. In vitro keratinocyte-based epidermal skin models are suitable for the detection of chemical-induced irritancy, but do not recapitulate the biological complexity of full skin and fail to detect potential serious side-effects. Normal healthy skin explants may represent a valuable complementary tool, having the advantage of retaining the full skin architecture and the resident immune cell diversity. This study investigated several conditions for the maintenance of good morphological structure after several days of culture and the retention of phase II metabolism for 24 hours in skin explants in vitro. Human skin samples were collected with informed consent from patients undergoing plastic surgery and immediately transferred and processed in our laboratory by removing the underlying dermal fat. Punch biopsies of 4 mm diameter were cultured in an air-liquid interface using transwell filters. Different cultural conditions such as the effect of calcium, temperature and cultivation media were tested for a period of 14 days and explants were histologically examined after Hematoxylin and Eosin staining. Our results demonstrated that the use of Williams E Medium at 32°C maintained the physiological integrity of the skin for approximately one week. Upon prolonged incubation, the upper layers of the epidermis become thickened and some dead cells are present. Interestingly, these effects were prevented by addition of EGFR inhibitors such as Afatinib or Erlotinib. Phase II metabolism of the skin such as glucuronidation (4-methyl umbeliferone), sulfation (minoxidil), N-acetyltransferase (p-toluidene), catechol methylation (2,3-dehydroxy naphthalene), and glutathione conjugation (chlorodinitro benzene) were analyzed by using LCMS. Our results demonstrated that the human skin explants possess metabolic activity for a period of at least 24 hours for all the substrates tested. A time course for glucuronidation with 4-methyl umbeliferone was performed and a linear correlation was obtained over a period of 24 hours. Longer-term culture studies will indicate the possible evolution of such metabolic activities. In summary, these results demonstrate that human skin explants maintain a normal structure for several days in vitro and are metabolically active for at least the first 24 hours. Hence, with further characterisation, this model may be suitable for the study of drug-induced toxicity.

Keywords: human skin explant, phase II metabolism, epidermal growth factor receptor, toxicity

Procedia PDF Downloads 257
147 Identification of Hub Genes in the Development of Atherosclerosis

Authors: Jie Lin, Yiwen Pan, Li Zhang, Zhangyong Xia

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Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids, immune cells, and extracellular matrix in the arterial walls. This pathological process can lead to the formation of plaques that can obstruct blood flow and trigger various cardiovascular diseases such as heart attack and stroke. The underlying molecular mechanisms still remain unclear, although many studies revealed the dysfunction of endothelial cells, recruitment and activation of monocytes and macrophages, and the production of pro-inflammatory cytokines and chemokines in atherosclerosis. This study aimed to identify hub genes involved in the progression of atherosclerosis and to analyze their biological function in silico, thereby enhancing our understanding of the disease’s molecular mechanisms. Through the analysis of microarray data, we examined the gene expression in media and neo-intima from plaques, as well as distant macroscopically intact tissue, across a cohort of 32 hypertensive patients. Initially, 112 differentially expressed genes (DEGs) were identified. Subsequent immune infiltration analysis indicated a predominant presence of 27 immune cell types in the atherosclerosis group, particularly noting an increase in monocytes and macrophages. In the Weighted gene co-expression network analysis (WGCNA), 10 modules with a minimum of 30 genes were defined as key modules, with blue, dark, Oliver green and sky-blue modules being the most significant. These modules corresponded respectively to monocyte, activated B cell, and activated CD4 T cell gene patterns, revealing a strong morphological-genetic correlation. From these three gene patterns (modules morphology), a total of 2509 key genes (Gene Significance >0.2, module membership>0.8) were extracted. Six hub genes (CD36, DPP4, HMOX1, PLA2G7, PLN2, and ACADL) were then identified by intersecting 2509 key genes, 102 DEGs with lipid-related genes from the Genecard database. The bio-functional analysis of six hub genes was estimated by a robust classifier with an area under the curve (AUC) of 0.873 in the ROC plot, indicating excellent efficacy in differentiating between the disease and control group. Moreover, PCA visualization demonstrated clear separation between the groups based on these six hub genes, suggesting their potential utility as classification features in predictive models. Protein-protein interaction (PPI) analysis highlighted DPP4 as the most interconnected gene. Within the constructed key gene-drug network, 462 drugs were predicted, with ursodeoxycholic acid (UDCA) being identified as a potential therapeutic agent for modulating DPP4 expression. In summary, our study identified critical hub genes implicated in the progression of atherosclerosis through comprehensive bioinformatic analyses. These findings not only advance our understanding of the disease but also pave the way for applying similar analytical frameworks and predictive models to other diseases, thereby broadening the potential for clinical applications and therapeutic discoveries.

Keywords: atherosclerosis, hub genes, drug prediction, bioinformatics

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146 Influenza Virus Circulation among the Population of Kazakhstan in 2012-2014

Authors: N. G. Klivleyeva, T. I. Glebova, G. V. Lukmanova, S. B. Bayseit, S. Z. Taubaeva, M. K. Kalkozhaeva

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The role of viral diseases in the general infectious disease incidence increases every year and requires special attention to the problem of interpreting the etiology of infectious agents. Influenza and acute respiratory viral infections are one of the most pressing public health issues. In the period 2012-2014, collection of 419 nasal swabs and 150 blood sera has been carried out in the patient care institutions of the various Kazakhstan regions from patients with symptoms of ARVI and pneumonia. Primary identification of biosamples for the presence of influenza viral antigens in enzyme immunoassay on nitrocellulose membrane gave positive results in 125 swabs (29.8%). Biosample screening in immunofluorescence test revealed the presence of influenza viral antigens against A/H1 in 63 samples (15.0%), A/H3 – in 70 samples (16.7%) and type B – in 9 samples (2.1%). As a result of primary infection, and successive passages in chick embryos and MDCK cell cultures, 38 HAAg were isolated from 419 samples with a clear cytopathic effect and hemagglutination titre in MDCK cell culture within 1:2-1:4, in CE - 1:8-1:256. The infectivity of isolates in chicken embryos were 3.5-6.5 lg EID50/0.2, in MDCK cell culture – 2.5-6.5 lg PFU/ml. Identification of 28 isolates was carried out in inhibition reactions of hemagglutinating activity and neuraminidase activity, showed their belonging to the influenza virus: 26 strains to A/H1N1, one - to A/H3N2, and one - to type B. Serological examination of blood sera for the presence of specific antibodies being an indirect evidence of the performed isolation and contributing to the timely interpretation of the disease etiology in the epidemics takes an important place in the comprehensive study of influenza viruses circulating among people. Serological analyzes were carried out in HAI assay using a kit consisting of 12 reference strains obtained from the WHO centre for reference and research on Influenza (CDC, Atlanta, USA) and three Kazakhstan (A/Almaty/347/09 (H1N1v), A/Almaty/462/11 (H3N2) and B/Almaty/414/10) human influenza viruses that are stored in the laboratory collection. The results of serological analysis of 150 blood sera showed that antihaemagglutinins against the A/H3N2 virus serosubtype were found in 46 samples (49.4%) out of 93 sera collected in 2012-2013. The antibody titres were within 1:160-1:320. 19 sera (20.4%) were seropositive against influenza A/H1N1 virus, the antibodies were observed in titres of 1:20-1:40. Six sera (6.4%) were positive against the influenza A/H1N1+A/H3N2 virus (mixed infection); the antibodies were recorded in titres of 1:20-1:40. Antihaemagglutinins against influenza type B virus were detected only in five sera (5.4%). The results of analysis of 57 sera collected in 2014 showed that antihaemagglutinins against A/H3N2 virus subtype were detected in 32 blood sera (56.1%) in titres of 1:160-1:640. Ten sera (17.5%) were seropositive against A/H1N1 virus; antihaemagglutinins against influenza type B virus were not detected. Therefore, virological and serological studies have shown that in Kazakhstan, as well as in the world, the influenza viruses A/H1N1, A/H3N2 and influenza B viruses were actively circulating during the epidemic seasons in 2012-2014.

Keywords: influenza, MDCK cell, serological analysis, virus

Procedia PDF Downloads 151
145 Relationship between Glycated Hemoglobin in Adolescents with Type 1 Diabetes Mellitus and Parental Anxiety and Depression

Authors: Evija Silina, Maris Taube, Maksims Zolovs

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Background: Type 1 diabetes mellitus (T1D) is the most common chronic endocrine pathology in children. The management of type 1 diabetes requires a strong diet, physical activity, lifelong insulin therapy, and proper self-monitoring of blood glucose and is usually complicated and, therefore, may result in a variety of psychosocial problems for children, adolescents, and their families. Metabolic control of the disease is determined by glycated haemoglobin (HbA1c), the main criterion for diabetes compensation. A correlation was observed between anxiety and depression levels and glycaemic control in many previous studies. It is assumed that anxiety and depression symptoms negatively affect glycaemic control. Parental psychological distress was associated with higher child self-report of stress and depressive symptoms, and it had negative effects on diabetes management. Objective: The main objective of this paper is to evaluate the relationship between parental mental health conditions (depression and anxiety) and metabolic control of their adolescents with T1DM. Methods: This cross-sectional study recruited adolescents with T1D (N=251) and their parents (N=251). The respondents completed questionnaires. The 7-item Generalized Anxiety Disorder (GAD-7) scale measured anxiety level; The Patient Health Questionnaire – 9 (PHQ-9) measured depressive symptoms. Glycaemic control of patients was assessed using the last glycated haemoglobin (HbA1c) values. GLM mediation analysis was performed to determine the potential mediating effect of the parent’s mental health conditions (depression and anxiety) on the relationship between the mental health conditions (depression and anxiety) of a child on the level of glycated hemoglobin (HbA1c). To test the significance of the mediated effect (ME) for non-normally distributed data, bootstrapping procedures (10,000 bootstrapped samples) were used. Results: 502 respondents were eligible for screening to detect anxiety and depression symptoms. Mediation analysis was performed to assess the mediating role of parent GAD-7 on the linkage between a dependent variable (HbA1c) and independent variables (child GAD-7 un child PHQ-9). The results revealed that the total effect of child GAD-7 (B = 0.479, z = 4.30, p < 0.001) on HbA1c was significant but the total effect of child PHQ-9 (B = 0.166, z = 1.49, p = 0.135) was not significant. With the inclusion of the mediating variable (parent GAD-7), the impact of child GAD-7 on HbA1c was found insignificant (B = 0.113, z=0.98, p = 0.326), the impact of child PHQ-9 on HbA1c was found also insignificant (B = 0.068, z=0.74, p = 0.458). The indirect effect of child GAD-7 on HbA1c through parent GAD-7 was found significant (B = 0.366, z = 4.31, p < 0.001) and the indirect effect of child PHQ-9 on HbA1c through parent GAD-7 was found also significant (B = 0.098, z = 2.56, p = 0.010). This indicates that the relationship between a dependent variable (HbA1c) and independent variables (child GAD-7 un child PHQ-9) is fully mediated by parent GAD-7. Conclusion: The main result suggests that glycated haemoglobin in adolescents with Type 1 diabetes is related to adolescents’ mental health via parents’ anxiety. It means that parents’ anxiety plays a more significant role in the level of glycated haemoglobin in adolescents than depression and anxiety in the adolescent.

Keywords: type 1 diabetes, adolescents, parental diabetes-specific mental health conditions, glycated haemoglobin, anxiety, depression

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144 Attitudes of Gratitude: An Analysis of 30 Cancer Patient Narratives Published by Leading U.S. Cancer Care Centers

Authors: Maria L. McLeod

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This study examines the ways in which cancer patient narratives are portrayed and framed on the websites of three leading U.S. cancer care centers –The University of Texas MD Anderson Cancer Center in Houston, Memorial Sloan Kettering Cancer Center in New York, and Seattle Cancer Care Alliance. Thirty patient stories, ten from each cancer center website blog, were analyzed using qualitative and quantitative textual analysis of unstructured data, documenting repeated use of specific metaphors and tropes while charting common themes and other elements of story structure and content. Patient narratives were coded using grounded theory as the basis for conducting emergent qualitative research. As part of a systematic, inductive approach to collecting and analyzing data, recurrent and unique themes were examined and compared in terms of positive and negative framing, patient agency, and institutional praise. All three of these cancer care centers are teaching hospitals with university affiliations, that emphasizes an evidence-based scientific approach to treatment that utilizes the latest research and cutting-edge techniques and technology. Thus, the use of anecdotal evidence presented in patient narratives could be perceived as being in conflict with this evidence-based model, as the patient stories are not an accurate representation of scientific outcomes related to developing cancer, cancer reoccurrence, or cancer outcomes. The representative patient narratives tend to exclude or downplay adverse responses to treatment, survival rates, integrative and/or complementary cancer treatments, cancer prevention and causes, and barriers to treatment, such as the limitation of insurance plans, costs of treatment, and/or other issues related to access, potentially contributing to false narratives and inaccurate notions of cancer prevention, cancer care treatment and the potential for a cure. Both quantitative and qualitative findings demonstrate that cancer patient stories featured on the blogsites of the nation’s top cancer care centers deemphasize patient agency and, instead, emphasize deference and gratitude toward the institutions where the featured patients received treatment. Along these lines, language choices reflect positive framing of the cancer experience. Accompanying portrait photos of healthy appearing subjects as well as positive-framed headlines, subheads, and pull quotes function similarly, reflecting hopeful, transformative experiences and outcomes over hardship and suffering. Although patient narratives include real, factual scientific details and descriptions of actual events, the stories lack references to more negative realities of cancer diagnosis and treatment. Instead, they emphasize the triumph of survival by which the cancer care center, in the savior/hero role, enables the patient’s success, represented as a cathartic medical journey.

Keywords: cancer framing, cancer stories, medical gaze, patient narratives

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143 The Development of the Psychosomatic Nursing Model from an Evidence-Based Action Research on Proactive Mental Health Care for Medical Inpatients

Authors: Chia-Yi Wu, Jung-Chen Chang, Wen-Yu Hu, Ming-Been Lee

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In nearly all physical health conditions, suicide risk is increased compared to healthy people even after adjustment for age, gender, mental health, and substance use diagnoses. In order to highlight the importance of suicide risk assessment for the inpatients and early identification and engagement for inpatients’ mental health problems, a study was designed aiming at developing a comprehensive psychosomatic nursing engagement (PSNE) model with standardized operation procedures informing how nurses communicate, assess, and engage with the inpatients with emotional distress. The purpose of the study was to promote the gatekeeping role of clinical nurses in performing brief assessment and interventions to detect depression and anxiety symptoms among the inpatients, particularly in non-psychiatric wards. The study will be carried out in a 2000-bed university hospital in Northern Taiwan in 2019. We will select a ward for trial and develop feasible procedures and in-job training course for the nurses to offer mental health care, which will also be validated through professional consensus meeting. The significance of the study includes the following three points: (1) The study targets at an important but less-researched area of PSNE model in the cultural background of Taiwan, where hospital service is highly accessible, but mental health and suicide risk assessment are hardly provided by non-psychiatric healthcare personnel. (2) The issue of PSNE could be efficient and cost-effective in the identification of suicide risks at an early stage to prevent inpatient suicide or to reduce future suicide risk by early treatment of mental illnesses among the high-risk group of hospitalized patients who are more than three-times lethal to suicide. (3) Utilizing a brief tool with its established APP ('The Five-item Brief Symptom Rating Scale, BSRS-5'), we will invent the standardized procedure of PSNE and referral steps in collaboration with the medical teams across the study hospital. New technological tools nested within nursing assessment/intervention will concurrently be invented to facilitate better care quality. The major outcome measurements will include tools for early identification of common mental distress and suicide risks, i.e., the BSRS-5, revised BSRS-5, and the 9-item Concise Mental Health Checklist (CMHC-9). The main purpose of using the CMHC-9 in clinical suicide risk assessment is mainly to provide care and build-up therapeutic relationship with the client, so it will also be used to nursing training highlighting the skills of supportive care. Through early identification of the inpatients’ depressive symptoms or other mental health care needs such as insomnia, anxiety, or suicide risk, the majority of the nursing clinicians would be able to engage in critical interventions that alleviate the inpatients’ suffering from mental health problems, given a feasible nursing input.

Keywords: mental health care, clinical outcome improvement, clinical nurses, suicide prevention, psychosomatic nursing

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142 Comparison and Validation of a dsDNA biomimetic Quality Control Reference for NGS based BRCA CNV analysis versus MLPA

Authors: A. Delimitsou, C. Gouedard, E. Konstanta, A. Koletis, S. Patera, E. Manou, K. Spaho, S. Murray

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Background: There remains a lack of International Standard Control Reference materials for Next Generation Sequencing-based approaches or device calibration. We have designed and validated dsDNA biomimetic reference materials for targeted such approaches incorporating proprietary motifs (patent pending) for device/test calibration. They enable internal single-sample calibration, alleviating sample comparisons to pooled historical population-based data assembly or statistical modelling approaches. We have validated such an approach for BRCA Copy Number Variation analytics using iQRS™-CNVSUITE versus Mixed Ligation-dependent Probe Amplification. Methods: Standard BRCA Copy Number Variation analysis was compared between mixed ligation-dependent probe amplification and next generation sequencing using a cohort of 198 breast/ovarian cancer patients. Next generation sequencing based copy number variation analysis of samples spiked with iQRS™ dsDNA biomimetics were analysed using proprietary CNVSUITE software. Mixed ligation-dependent probe amplification analyses were performed on an ABI-3130 Sequencer and analysed with Coffalyser software. Results: Concordance of BRCA – copy number variation events for mixed ligation-dependent probe amplification and CNVSUITE indicated an overall sensitivity of 99.88% and specificity of 100% for iQRS™-CNVSUITE. The negative predictive value of iQRS-CNVSUITE™ for BRCA was 100%, allowing for accurate exclusion of any event. The positive predictive value was 99.88%, with no discrepancy between mixed ligation-dependent probe amplification and iQRS™-CNVSUITE. For device calibration purposes, precision was 100%, spiking of patient DNA demonstrated linearity to 1% (±2.5%) and range from 100 copies. Traditional training was supplemented by predefining the calibrator to sample cut-off (lock-down) for amplicon gain or loss based upon a relative ratio threshold, following training of iQRS™-CNVSUITE using spiked iQRS™ calibrator and control mocks. BRCA copy number variation analysis using iQRS™-CNVSUITE™ was successfully validated and ISO15189 accredited and now enters CE-IVD performance evaluation. Conclusions: The inclusion of a reference control competitor (iQRS™ dsDNA mimetic) to next generation sequencing-based sequencing offers a more robust sample-independent approach for the assessment of copy number variation events compared to mixed ligation-dependent probe amplification. The approach simplifies data analyses, improves independent sample data analyses, and allows for direct comparison to an internal reference control for sample-specific quantification. Our iQRS™ biomimetic reference materials allow for single sample copy number variation analytics and further decentralisation of diagnostics to single patient sample assessment.

Keywords: validation, diagnostics, oncology, copy number variation, reference material, calibration

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141 Raman Spectroscopic Detection of the Diminishing Toxic Effect of Renal Waste Creatinine by Its in vitro Reaction with Drugs N-Acetylcysteine and Taurine

Authors: Debraj Gangopadhyay, Moumita Das, Ranjan K. Singh, Poonam Tandon

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Creatinine is a toxic chemical waste generated from muscle metabolism. Abnormally high levels of creatinine in the body fluid indicate possible malfunction or failure of the kidneys. This leads to a condition termed as creatinine induced nephrotoxicity. N-acetylcysteine is an antioxidant drug which is capable of preventing creatinine induced nephrotoxicity and is helpful to treat renal failure in its early stages. Taurine is another antioxidant drug which serves similar purpose. The kidneys have a natural power that whenever reactive oxygen species radicals increase in the human body, the kidneys make an antioxidant shell so that these radicals cannot harm the kidney function. Taurine plays a vital role in increasing the power of that shell such that the glomerular filtration rate can remain in its normal level. Thus taurine protects the kidneys against several diseases. However, taurine also has some negative effects on the body as its chloramine derivative is a weak oxidant by nature. N-acetylcysteine is capable of inhibiting the residual oxidative property of taurine chloramine. Therefore, N-acetylcysteine is given to a patient along with taurine and this combination is capable of suppressing the negative effect of taurine. Both N-acetylcysteine and taurine being affordable, safe, and widely available medicines, knowledge of the mechanism of their combined effect on creatinine, the favored route of administration, and the proper dose may be highly useful in their use for treating renal patients. Raman spectroscopy is a precise technique to observe minor structural changes taking place when two or more molecules interact. The possibility of formation of a complex between a drug molecule and an analyte molecule in solution can be explored by analyzing the changes in the Raman spectra. The formation of a stable complex of creatinine with N-acetylcysteinein vitroin aqueous solution has been observed with the help of Raman spectroscopic technique. From the Raman spectra of the mixtures of aqueous solutions of creatinine and N-acetylcysteinein different molar ratios, it is observed that the most stable complex is formed at 1:1 ratio of creatinine andN-acetylcysteine. Upon drying, the complex obtained is gel-like in appearance and reddish yellow in color. The complex is hygroscopic and has much better water solubility compared to creatinine. This highlights that N-acetylcysteineplays an effective role in reducing the toxic effect of creatinine by forming this water soluble complex which can be removed through urine. Since the drug taurine is also known to be useful in reducing nephrotoxicity caused by creatinine, the aqueous solution of taurine with those of creatinine and N-acetylcysteinewere mixed in different molar ratios and were investigated by Raman spectroscopic technique. It is understood that taurine itself does not undergo complexation with creatinine as no additional changes are observed in the Raman spectra of creatinine when it is mixed with taurine. However, when creatinine, N-acetylcysteine and taurine are mixed in aqueous solution in molar ratio 1:1:3, several changes occurring in the Raman spectra of creatinine suggest the diminishing toxic effect of creatinine in the presence ofantioxidant drugs N-acetylcysteine and taurine.

Keywords: creatinine, creatinine induced nephrotoxicity, N-acetylcysteine, taurine

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140 Major Role of Social Media in Encouraging Public Interaction with Health Awareness: A Case Study of Successful Saudi Diabetes Campaign

Authors: Budur Almutairi

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Introduction: There is an alarming increase in the number of diabetic patients in Saudi Arabia during the last twenty years. The World Health Organization (WHO) reports that the country ranks seventh in the world for the rate of diabetes. It is also estimated that around 7 million of the population are diabetic and almost around 3 million have pre-diabetes. The prevalence is more in urban area than in rural and more in women than in men and it is closely associated with the parallel rise in obesity rates. Diabetes is found to be contributing to the increasing mortality, morbidity and vascular complications and becoming a significant cause of medical complications and even death. The trends shown by the numbers are worrying as the prevalence is steadily doubling every two decades and particularly in Saudi Arabia, this could soon reach 50% in those over 50 years of age. The economic growth and prosperity have shown notable changes in the lifestyle of the people. Most importantly, along with an increased consumption of fast foods and sugar-rich carbonated soft drinks, eating habits became less healthy and the level of physical activity is decreased. The simultaneous technological advancement and the introduction of new mechanical devices like, elevators, escalators, remotes and vehicles pushed people to a situation of leading a more sedentary life. This study is attempting to evaluate the success of the campaign that introduced through popular social media in the country. Methodology: The Ministry of Health (MoH) has initiated a novel method of campaign activity to generate discussion among public about diabetes. There were mythical monsters introduced through popular social media with disguised messages about the condition of diabetes has generated widespread discussions about the disease among the general public. The characters that started appearing in social media About 600 retweets of the original post was testimonial for the success of the Twitter campaign. The second most successful form of campaign was a video that adopted a very popular approach of using Dark Comedy in which, the diabetes was represented through a twisted negative character that talks about his meticulous plans of how he is going to take the common people into his clutches. This fictional character gained more popularity when introduced into twitter and people started interacting with him raising various questions and challenging his anti-social activities. Major findings: The video generated more than 3,200,000 views ranking 9th in You Tube’s most popular video in Saudi Arabia and was shared 7000 times in a single week. Also, the hashtag got over 4,500,000impressions and over one million visits. Conclusion: Diabetes mellitus in Saudi Arabia is emerging as an epidemic of massive proportions, threatening to negate the benefits of modernization and economic revival. It is highly possible that healthy practices connected with the prevention and management of DM can easily be implemented in a manner that does not conflict with the cultural milieu of Saudi Arabia.

Keywords: campaign, diabetes, Saudi, social media

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139 Comparison of Incidence and Risk Factors of Early Onset and Late Onset Preeclampsia: A Population Based Cohort Study

Authors: Sadia Munir, Diana White, Aya Albahri, Pratiwi Hastania, Eltahir Mohamed, Mahmood Khan, Fathima Mohamed, Ayat Kadhi, Haila Saleem

Abstract:

Preeclampsia is a major complication of pregnancy. Prediction and management of preeclampsia is a challenge for obstetricians. To our knowledge, no major progress has been achieved in the prevention and early detection of preeclampsia. There is very little known about the clear treatment path of this disorder. Preeclampsia puts both mother and baby at risk of several short term- and long term-health problems later in life. There is huge health service cost burden in the health care system associated with preeclampsia and its complications. Preeclampsia is divided into two different types. Early onset preeclampsia develops before 34 weeks of gestation, and late onset develops at or after 34 weeks of gestation. Different genetic and environmental factors, prognosis, heritability, biochemical and clinical features are associated with early and late onset preeclampsia. Prevalence of preeclampsia greatly varies all over the world and is dependent on ethnicity of the population and geographic region. To authors best knowledge, no published data on preeclampsia exist in Qatar. In this study, we are reporting the incidence of preeclampsia in Qatar. The purpose of this study is to compare the incidence and risk factors of both early onset and late onset preeclampsia in Qatar. This retrospective longitudinal cohort study was conducted using data from the hospital record of Women’s Hospital, Hamad Medical Corporation (HMC), from May 2014-May 2016. Data collection tool, which was approved by HMC, was a researcher made extraction sheet that included information such as blood pressure during admission, socio demographic characteristics, delivery mode, and new born details. A total of 1929 patients’ files were identified by the hospital information management when they apply codes of preeclampsia. Out of 1929 files, 878 had significant gestational hypertension without proteinuria, 365 had preeclampsia, 364 had severe preeclampsia, and 188 had preexisting hypertension with superimposed proteinuria. In this study, 78% of the data was obtained by hospital electronic system (Cerner) and the remaining 22% was from patient’s paper records. We have gone through detail data extraction from 560 files. Initial data analysis has revealed that 15.02% of pregnancies were complicated with preeclampsia from May 2014-May 2016. We have analyzed difference in the two different disease entities in the ethnicity, maternal age, severity of hypertension, mode of delivery and infant birth weight. We have identified promising differences in the risk factors of early onset and late onset preeclampsia. The data from clinical findings of preeclampsia will contribute to increased knowledge about two different disease entities, their etiology, and similarities/differences. The findings of this study can also be used in predicting health challenges, improving health care system, setting up guidelines, and providing the best care for women suffering from preeclampsia.

Keywords: preeclampsia, incidence, risk factors, maternal

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138 Effects of Tramadol Administration on the Ovary of Adult Rats and the Possible Recovery after Tramadol Withdrawal: A Light and Electron Microscopic Study

Authors: Heba Kamal Mohamed

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Introduction: Tramadol is a weak -opioid receptor agonist with an analgesic effect because of the inhibition of uptake of norepinephrine and serotonin. Nowadays, tramadol hydrochloride is frequently used as a pain reliever. Tramadol is recommended for the management of acute and chronic pain of moderate to severe intensity associated with a variety of diseases or problems, including osteoarthritis, diabetic neuropathy, neuropathic pain, and even perioperative pain in human patients. In obstetrics and gynecology, tramadol is used extensively to treat postoperative pain. Aim of the study: This study was undertaken to investigate the histological (light and electron microscopic) and immunohistochemical effects of long term tramadol treatment on the ovary of adult rats and the possible recovery after tramadol withdrawal. Design: Experimental study. Materials and methods: Thirty adult female albino rats were used in this study. They were classified into three main groups (10 rats each). Group I served as the control group. Group II, rats were subcutaneously injected with tramadol 40 mg/kg three times per week for 8 weeks. Group III, rats were subcutaneously injected with tramadol 40 mg/kg three times per week for 8 weeks then were kept for another 8 weeks without treatment for recovery. At the end of the experiment rats were sacrificed and bilateral oophorectomy was carried out; the ovaries were processed for histological study (light and electron microscopic) and immunohistochemical reaction for caspase-3 (apoptotic protein). Results: Examination of the ovary of tramadol-treated rats (group II) revealed many atretic ovarian follicles, some follicles showed detachment of the oocyte from surrounding granulosa cells and others showed loss of the oocyte. Many follicles revealed degenerated vacuolated oocytes and vacuolated theca folliculi cells. Granulosa cells appeared shrunken, disrupted and loosely attached with vacuolated cytoplasm and pyknotic nuclei. Some follicles showed separation of granulosa cells from the theca folliculi layer. The ultrastructural study revealed the presence of granulosa cells with electron dense indented nuclei, damaged mitochondria and granular vacuolated cytoplasm. Other cells showed accumulation of large amount of lipid droplets in their cytoplasm. Some follicles revealed rarifaction of the cytoplasm of oocytes and absent zona pellucida. Moreover, apoptotic changes were detected by immunohistochemical staining in the form of increased staining intensity to caspase-3 (apoptotic protein). With Masson's Trichrome stain, there was an increased collagen fibre deposition in the ovarian cortical stroma. The wall of blood vessels appeared thickened. In the withdrawal group (group III), there was a little improvement in the histological and immunohistochemical changes. Conclusion: Tramadol had serious deleterious effects on ovarian structure. Thus, it should be used with caution, especially when a long term treatment is indicated. Withdrawal of tramadol led to a little improvement in the structural impairment of the ovary.

Keywords: tramadol, ovary, withdrawal, rats

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137 Atypical Intoxication Due to Fluoxetine Abuse with Symptoms of Amnesia

Authors: Ayse Gul Bilen

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Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants that are used clinically for the treatment of anxiety disorders, obsessive-compulsive disorder (OCD), panic disorders and eating disorders. The first SSRI, fluoxetine (sold under the brand names Prozac and Sarafem among others), had an adverse effect profile better than any other available antidepressant when it was introduced because of its selectivity for serotonin receptors. They have been considered almost free of side effects and have become widely prescribed, however questions about the safety and tolerability of SSRIs have emerged with their continued use. Most SSRI side effects are dose-related and can be attributed to serotonergic effects such as nausea. Continuous use might trigger adverse effects such as hyponatremia, tremor, nausea, weight gain, sleep disturbance and sexual dysfunction. Moderate toxicity can be safely observed in the hospital for 24 hours, and mild cases can be safely discharged (if asymptomatic) from the emergency department once cleared by Psychiatry in cases of intentional overdose and after 6 to 8 hours of observation. Although fluoxetine is relatively safe in terms of overdose, it might still be cardiotoxic and inhibit platelet secretion, aggregation, and plug formation. There have been reported clinical cases of seizures, cardiac conduction abnormalities, and even fatalities associated with fluoxetine ingestions. While the medical literature strongly suggests that most fluoxetine overdoses are benign, emergency physicians need to remain cognizant that intentional, high-dose fluoxetine ingestions may induce seizures and can even be fatal due to cardiac arrhythmia. Our case is a 35-year old female patient who was sent to ER with symptoms of confusion, amnesia and loss of orientation for time and location after being found wandering in the streets unconsciously by police forces that informed 112. Upon laboratory examination, no pathological symptom was found except sinus tachycardia in the EKG and high levels of aspartate transaminase (AST) and alanine transaminase (ALT). Diffusion MRI and computed tomography (CT) of the brain all looked normal. Upon physical and sexual examination, no signs of abuse or trauma were found. Test results for narcotics, stimulants and alcohol were negative as well. There was a presence of dysrhythmia which required admission to the intensive care unit (ICU). The patient gained back her conscience after 24 hours. It was discovered from her story afterward that she had been using fluoxetine due to post-traumatic stress disorder (PTSD) for 6 months and that she had attempted suicide after taking 3 boxes of fluoxetine due to the loss of a parent. She was then transferred to the psychiatric clinic. Our study aims to highlight the need to consider toxicologic drug use, in particular, the abuse of selective serotonin reuptake inhibitors (SSRIs), which have been widely prescribed due to presumed safety and tolerability, for diagnosis of patients applying to the emergency room (ER).

Keywords: abuse, amnesia, fluoxetine, intoxication, SSRI

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136 Foslip Loaded and CEA-Affimer Functionalised Silica Nanoparticles for Fluorescent Imaging of Colorectal Cancer Cells

Authors: Yazan S. Khaled, Shazana Shamsuddin, Jim Tiernan, Mike McPherson, Thomas Hughes, Paul Millner, David G. Jayne

Abstract:

Introduction: There is a need for real-time imaging of colorectal cancer (CRC) to allow tailored surgery to the disease stage. Fluorescence guided laparoscopic imaging of primary colorectal cancer and the draining lymphatics would potentially bring stratified surgery into clinical practice and realign future CRC management to the needs of patients. Fluorescent nanoparticles can offer many advantages in terms of intra-operative imaging and therapy (theranostic) in comparison with traditional soluble reagents. Nanoparticles can be functionalised with diverse reagents and then targeted to the correct tissue using an antibody or Affimer (artificial binding protein). We aimed to develop and test fluorescent silica nanoparticles and targeted against CRC using an anti-carcinoembryonic antigen (CEA) Affimer (Aff). Methods: Anti-CEA and control Myoglobin Affimer binders were subcloned into the expressing vector pET11 followed by transformation into BL21 Star™ (DE3) E.coli. The expression of Affimer binders was induced using 0.1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG). Cells were harvested, lysed and purified using nickle chelating affinity chromatography. The photosensitiser Foslip (soluble analogue of 5,10,15,20-Tetra(m-hydroxyphenyl) chlorin) was incorporated into the core of silica nanoparticles using water-in-oil microemulsion technique. Anti-CEA or control Affs were conjugated to silica nanoparticles surface using sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo SMCC) chemical linker. Binding of CEA-Aff or control nanoparticles to colorectal cancer cells (LoVo, LS174T and HC116) was quantified in vitro using confocal microscopy. Results: The molecular weights of the obtained band of Affimers were ~12.5KDa while the diameter of functionalised silica nanoparticles was ~80nm. CEA-Affimer targeted nanoparticles demonstrated 9.4, 5.8 and 2.5 fold greater fluorescence than control in, LoVo, LS174T and HCT116 cells respectively (p < 0.002) for the single slice analysis. A similar pattern of successful CEA-targeted fluorescence was observed in the maximum image projection analysis, with CEA-targeted nanoparticles demonstrating 4.1, 2.9 and 2.4 fold greater fluorescence than control particles in LoVo, LS174T, and HCT116 cells respectively (p < 0.0002). There was no significant difference in fluorescence for CEA-Affimer vs. CEA-Antibody targeted nanoparticles. Conclusion: We are the first to demonstrate that Foslip-doped silica nanoparticles conjugated to anti-CEA Affimers via SMCC allowed tumour cell-specific fluorescent targeting in vitro, and had shown sufficient promise to justify testing in an animal model of colorectal cancer. CEA-Affimer appears to be a suitable targeting molecule to replace CEA-Antibody. Targeted silica nanoparticles loaded with Foslip photosensitiser is now being optimised to drive photodynamic killing, via reactive oxygen generation.

Keywords: colorectal cancer, silica nanoparticles, Affimers, antibodies, imaging

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135 Proposals for the Practical Implementation of the Biological Monitoring of Occupational Exposure for Antineoplastic Drugs

Authors: Mireille Canal-Raffin, Nadege Lepage, Antoine Villa

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Context: Most antineoplastic drugs (AD) have a potential carcinogenic, mutagenic and/or reprotoxic effect and are classified as 'hazardous to handle' by National Institute for Occupational Safety and Health Their handling increases with the increase of cancer incidence. AD contamination from workers who handle AD and/or care for treated patients is, therefore, a major concern for occupational physicians. As part of the process of evaluation and prevention of chemical risks for professionals exposed to AD, Biological Monitoring of Occupational Exposure (BMOE) is the tool of choice. BMOE allows identification of at-risk groups, monitoring of exposures, assessment of poorly controlled exposures and the effectiveness and/or wearing of protective equipment, and documenting occupational exposure incidents to AD. This work aims to make proposals for the practical implementation of the BMOE for AD. The proposed strategy is based on the French good practice recommendations for BMOE, issued in 2016 by 3 French learned societies. These recommendations have been adapted to occupational exposure to AD. Results: AD contamination of professionals is a sensitive topic, and the BMOE requires the establishment of a working group and information meetings within the concerned health establishment to explain the approach, objectives, and purpose of monitoring. Occupational exposure to AD is often discontinuous and 2 steps are essential upstream: a study of the nature and frequency of AD used to select the Biological Exposure Indice(s) (BEI) most representative of the activity; a study of AD path in the institution to target exposed professionals and to adapt medico-professional information sheet (MPIS). The MPIS is essential to gather the necessary elements for results interpretation. Currently, 28 urinary specific BEIs of AD exposure have been identified, and corresponding analytical methods have been published: 11 BEIs were AD metabolites, and 17 were AD. Results interpretation is performed by groups of homogeneous exposure (GHE). There is no threshold biological limit value of interpretation. Contamination is established when an AD is detected in trace concentration or in a urine concentration equal or greater than the limit of quantification (LOQ) of the analytical method. Results can only be compared to LOQs of these methods, which must be as low as possible. For 8 of the 17 AD BEIs, the LOQ is very low with values between 0.01 to 0.05µg/l. For the other BEIs, the LOQ values were higher between 0.1 to 30µg/l. Results restitution by occupational physicians to workers should be individual and collective. Faced with AD dangerousness, in cases of workers contamination, it is necessary to put in place corrective measures. In addition, the implementation of prevention and awareness measures for those exposed to this risk is a priority. Conclusion: This work is a help for occupational physicians engaging in a process of prevention of occupational risks related to AD exposure. With the current analytical tools, effective and available, the (BMOE) to the AD should now be possible to develop in routine occupational physician practice. The BMOE may be complemented by surface sampling to determine workers' contamination modalities.

Keywords: antineoplastic drugs, urine, occupational exposure, biological monitoring of occupational exposure, biological exposure indice

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134 The Efficiency Analysis in the Health Sector: Marmara Region

Authors: Hale Kirer Silva Lecuna, Beyza Aydin

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Health is one of the main components of human capital and sustainable development, and it is very important for economic growth. Health economics, which is an indisputable part of the science of economics, has five stages in general. These are health and development, financing of health services, economic regulation in the health, allocation of resources and efficiency of health services. A well-developed and efficient health sector plays a major role by increasing the level of development of countries. The most crucial pillars of the health sector are the hospitals that are divided into public and private. The main purpose of the hospitals is to provide more efficient services. Therefore the aim is to meet patients’ satisfaction by increasing the service quality. Health-related studies in Turkey date back to the Ottoman and Seljuk Empires. In the near past, Turkey applied 'Health Sector Transformation Programs' under different titles between 2003 and 2010. Our aim in this paper is to measure how effective these transformation programs are for the health sector, to see how much they can increase the efficiency of hospitals over the years, to see the return of investments, to make comments and suggestions on the results, and to provide a new reference for the literature. Within this framework, the public and private hospitals in Balıkesir, Bilecik, Bursa, Çanakkale, Edirne, Istanbul, Kirklareli, Kocaeli, Sakarya, Tekirdağ, Yalova will be examined by using Data Envelopment Analysis (DEA) for the years between 2000 and 2019. DEA is a linear programming-based technique, which gives relatively good results in multivariate studies. DEA basically estimates an efficiency frontier and make a comparison. Constant returns to scale and variable returns to scale are two most commonly used DEA methods. Both models are divided into two as input and output-oriented. To analyze the data, the number of personnel, number of specialist physicians, number of practitioners, number of beds, number of examinations will be used as input variables; and the number of surgeries, in-patient ratio, and crude mortality rate as output variables. 11 hospitals belonging to the Marmara region were included in the study. It is seen that these hospitals worked effectively only in 7 provinces (Balıkesir, Bilecik, Bursa, Edirne, İstanbul, Kırklareli, Yalova) for the year 2001 when no transformation program was implemented. After the transformation program was implemented, for example, in 2014 and 2016, 10 hospitals (Balıkesir, Bilecik, Bursa, Çanakkale, Edirne, İstanbul, Kocaeli, Kırklareli, Tekirdağ, Yalova) were found to be effective. In 2015, ineffective results were observed for Sakarya, Tekirdağ and Yalova. However, since these values are closer to 1 after the transformation program, we can say that the transformation program has positive effects. For Sakarya alone, no effective results have been achieved in any year. When we look at the results in general, it shows that the transformation program has a positive effect on the effectiveness of hospitals.

Keywords: data envelopment analysis, efficiency, health sector, Marmara region

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