Search results for: clinical psychology interns
711 The Association Between CYP2C19 Gene Distribution and Medical Cannabis Treatment
Authors: Vichayada Laohapiboolkul
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Introduction: As the legal use of cannabis is being widely accepted throughout the world, medical cannabis has been explored in order to become an alternative cure for patients. Tetrahydrocannabinol (THC) and Cannabidiol (CBD) are natural cannabinoids found in the Cannabis plant which is proved to have positive treatment for various diseases and symptoms such as chronic pain, neuropathic pain, spasticity resulting from multiple sclerosis, reduce cancer-associated pain, autism spectrum disorders (ASD), dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette's disorder. Regardless of all the medical benefits, THC, if not metabolized, can lead to mild up to severe adverse drug reactions (ADR). The enzyme CYP2C19 was found to be one of the metabolizers of THC. However, the suballele CYP2C19*2 manifests as a poor metabolizer which could lead to higher levels of THC than usual, possibly leading to various ADRs. Objective: The aim of this study was to investigate the distribution of CYP2C19, specifically CYP2C19*2, genes in Thai patients treated with medical cannabis along with adverse drug reactions. Materials and Methods: Clinical data and EDTA whole blood for DNA extraction and genotyping were collected from patients for this study. CYP2C19*2 (681G>A, rs4244285) genotyping was conducted using the Real-time PCR (ABI, Foster City, CA, USA). Results: There were 42 medical cannabis-induced ADRs cases and 18 medical cannabis tolerance controls who were included in this study. A total of 60 patients were observed where 38 (63.3%) patients were female and 22 (36.7%) were male, with a range of age approximately 19 - 87 years. The most apparent ADRs for medical cannabis treatment were dry mouth/dry throat (76.7%), followed by tachycardia (70%), nausea (30%) and a few arrhythmias (10%). In the total of 27 cases, we found a frequency of 18 CYP2C19*1/*1 alleles (normal metabolizers, 66.7%), 8 CYP2C19*1/*2 alleles (intermediate metabolizers, 29.6%) and 1 CYP2C19*2/*2 alleles (poor metabolizers, 3.7%). Meanwhile, 63.6% of CYP2C19*1/*1, 36.3% and 0% of CYP2C19*1/*2 and *2/*2 in the tolerance controls group, respectively. Conclusions: This is the first study to confirm the distribution of CYP2C19*2 allele and the prevalence of poor metabolizer genes in Thai patients who received medical cannabis for treatment. Thus, CYP2C19 allele might serve as a pharmacogenetics marker for screening before initiating treatment.Keywords: medical cannabis, adverse drug reactions, CYP2C19, tetrahydrocannabinol, poor metabolizer
Procedia PDF Downloads 95710 Therapeutic Effect of Indane 1,3-Dione Derivatives in the Restoration of Insulin Resistance in Human Liver Cells and in Db/Db Mice Model: Biochemical, Physiological and Molecular Insights of Investigation
Authors: Gulnaz Khan, Meha F. Aftab, Munazza Murtaza, Rizwana S. Waraich
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Advanced glycation end products (AGEs) precursor and its abnormal accumulation cause damage to various tissues and organs. AGEs have pathogenic implication in several diseases including diabetes. Existing AGEs inhibitors are not in clinical use, and there is a need for development of novel inhibitors. The present investigation aimed at identifying the novel AGEs inhibitors and assessing their mechanism of action for treating insulin resistance in mice model of diabetes. Novel derivatives of benzylidene of indan-1,3-dione were synthesized. The compounds were selected to study their action mechanism in improving insulin resistance, in vitro, in human hepatocytes and murine adipocytes and then, in vivo, in mice genetic model of diabetes (db/db). Mice were treated with novel derivatives of benzylidene of indane 1,3-dione. AGEs mediated ROS production was measured by dihydroethidium fluorescence assay. AGEs level in the serum of treated mice was observed by ELISA. Gene expression of receptor for AGEs (RAGE), PPAR-gamma, TNF-alpha and GLUT-4 was evaluated by RT-PCR. Glucose uptake was measured by fluorescent method. Microscopy was used to analyze glycogen synthesis in muscle. Among several derivatives of benzylidene of indan-1,3-dione, IDD-24, demonstrated highest inhibition of AGESs. IDD-24 significantly reduced AGEs formation and expression of receptor for advanced glycation end products (RAGE) in fat, liver of db/db mice. Suppression of AGEs mediated ROS production was also observed in hepatocytes and fat cell, after treatment with IDD-24. Glycogen synthesis was increased in muscle tissue of mice treated with IDD-24. In adipocytes, IDD-24 prevented AGEs induced reduced glucose uptake. Mice treated with IDD-24 exhibited increased glucose tolerance, serum adiponectin levels and decreased insulin resistance. The result of present study suggested that IDD-24 can be a possible treatment target to address glycotoxins induced insulin resistance.Keywords: advance glycation end product, hyperglycemia, indan-1, 3-dione, insulin resistance
Procedia PDF Downloads 153709 Novel Nickel Complex Compound Reactivates the Apoptotic Network, Cell Cycle Arrest and Cytoskeletal Rearrangement in Human Colon and Breast Cancer Cells
Authors: Nima Samie, Batoul Sadat Haerian, Sekaran Muniandy, M. S. Kanthimathi
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Colon and breast cancers are categorized as the most prevalent types of cancer worldwide. Recently, the broad clinical application of metal complex compounds has led to the discovery of potential therapeutic drugs. The aim of this study was to evaluate the cytotoxic action of a selected nickel complex compound (NCC) against human colon and breast cancer cells. In this context, we determined the potency of the compound in the induction of apoptosis, cell cycle arrest, and cytoskeleton rearrangement. HT-29, WiDr, CCD-18Co, MCF-7 and Hs 190.T cell lines were used to determine the IC50 of the compound using the MTT assay. Analysis of apoptosis was carried out using immunofluorescence, acridine orange/ propidium iodide double staining, Annexin-V-FITC assay, evaluation of the translocation of NF-kB, oxygen radical antioxidant capacity, quenching of reactive oxygen species content , measurement of LDH release, caspase-3/-7, -8 and -9 assays and western blotting. The cell cycle arrest was examined using flowcytometry and gene expression was assessed using qPCR array. Results showed that our nickel complex compound displayed a potent suppressive effect on HT-29, WiDr, MCF-7 and Hs 190.T after 24 h of treatment with IC50 value of 2.02±0.54, 2.13±0.65, 3.76±015 and 3.14±0.45 µM respectively. This cytotoxic effect on normal cells was insignificant. Dipping in the mitochondrial membrane potential and increased release of cytochrome c from the mitochondria indicated induction of the intrinsic apoptosis pathway by the nickel complex compound. Activation of this pathway was further evidenced by significant activation of caspase 9 and 3/7.The nickel complex compound (NCC) was also shown activate the extrinsic pathways of apoptosis by activation of caspase-8 which is linked to the suppression of NF-kB translocation to the nucleus. Cell cycle arrest in the G1 phase and up-regulation of glutathione reductase, based on excessive ROS production were also observed. The results of this study suggest that the nickel complex compound is a potent anti-cancer agent inducing both intrinsic and extrinsic pathways as well as cell cycle arrest in colon and breast cancer cells.Keywords: nickel complex, apoptosis, cytoskeletal rearrangement, colon cancer, breast cancer
Procedia PDF Downloads 306708 Characteristics of Acute Bacterial Prostatitis in Elderly Patients Attended in the Emergency Department
Authors: Carles Ferré, Ferran Llopis, Javier Jacob, Jordi Giol, Xavier Palom, Ignasi Bardés
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Objective: To analyze the characteristics of acute bacterial prostatitis (ABP) in elderly patients attended in the emergency department (ED). Methods: Observational and cohort study with prospective follow-up including patients with ABP presenting to the ED from January-December 2012. Data were collected for demographic variables, comorbidities, clinical and microbiological findings, treatment, outcome, and reconsultation at 30 days follow up. Findings were compared between patients ≥ 75 years (study group) and < 75 years (control group). Results: During the study period 241 episodes of ABP were included for analysis. Mean age was 62,9 ± 16 years, and 64 (26.5%) were ≥ 75 years old. A history of prostate adenoma was reported in 54 cases (22,4%), diabetes mellitus in 47 patients (19,5%) and prior manipulation of the lower urinary tract in 40 (17%). Mean symptoms duration was 3.38 ± 4.04 days, voiding symptoms were present in 176 cases (73%) and fever in 154 (64%). From 216 urine cultures, 128 were positive (59%) and 24 (17,6%) out of 136 blood cultures. Escherichia coli was the main pathogen in 58.6% of urine cultures and 64% of blood cultures (with resistant strains to fluoroquinolones in 27,7%, cotrimoxazole in 22,9% and amoxicillin/clavulanic in 27.7% of cases). Seventy patients (29%) were admitted to the hospital, and 3 died. At 30-day follow-up, 29 patients (12%) returned to the ED. In the bivariate analysis previous manipulation of the urinary tract, history of cancer, previous antibiotic treatment, resistant E. coli strains to amoxicillin-clavulanate and ciprofloxacin and extended spectrum beta-lactamase (ESBL) producers, renal impairment, and admission to the hospital were significantly more frequent (p < 0.05) among patients ≥ 75 years compared to those younger than 75 years. Conclusions: Ciprofloxacin and amoxicillin-clavulanate appear not to be good options for the empiric treatment of ABP for patients ≥ 75 years given the drug-resistance pattern in our series, and the proportion of ESBL-producing strains of E. coli should be taken into account. Awaiting bacteria identification and antibiogram from urine and/or blood cultures, treatment on an inpatient basis should be considered in older patients with ABP.Keywords: acute bacterial prostatitits, antibiotic resistance, elderly patients, emergency
Procedia PDF Downloads 369707 Reflections of Narrative Architecture in Transformational Representations on the Architectural Design Studio
Authors: M. Mortas, H. Asar, P. Dursun Cebi
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The visionary works of architectural representation in the 21st century's present situation, are practiced through the methodologies which try to expose the intellectual and theoretical essences of futurologist positions that are revealed with this era's interactions. Expansions of conceptual and contextual inputs related to one architectural design representation, depend on its deepness of critical attitudes, its interactions with the concepts such as experience, meaning, affection, psychology, perception and aura, as well as its communication with spatial, cultural and environmental factors. The purpose of this research study is to be able to offer methodological application areas for the design dimensions of experiential practices into architectural design studios, by focusing on the architectural representative narrations of 'transformation,' 'metamorphosis,' 'morphogenesis,' 'in-betweenness', 'superposition' and 'intertwine’ in which they affect and are affected by the today’s spatiotemporal hybridizations of architecture. The narrative representations and the visual theory paradigms of the designers are chosen under the main title of 'transformation' for the investigation of these visionary and critical representations' dismantlings and decodings. Case studies of this research area are chosen from Neil Spiller, Bryan Cantley, Perry Kulper and Dan Slavinsky’s transformative, morphogenetic representations. The theoretical dismantlings and decodings which are obtained from these artists’ contemporary architectural representations are tried to utilize and practice in the structural design studios as alternative methodologies when to approach architectural design processes, for enriching, differentiating, diversifying and 'transforming' the applications of so far used design process precedents. The research aims to indicate architectural students about how they can reproduce, rethink and reimagine their own representative lexicons and so languages of their architectural imaginations, regarding the newly perceived tectonics of prosthetic, biotechnology, synchronicity, nanotechnology or machinery into various experiential design workshops. The methodology of this work can be thought as revealing the technical and theoretical tools, lexicons and meanings of contemporary-visionary architectural representations of our decade, with the essential contents and components of hermeneutics, etymology, existentialism, post-humanism, phenomenology and avant-gardism disciplines to re-give meanings the architectural visual theorists’ transformative representations of our decade. The value of this study may be to emerge the superposed and overlapped atmospheres of futurologist architectural representations for the students who need to rethink on the transcultural, deterritorialized and post-humanist critical theories to create and use the representative visual lexicons of themselves for their architectural soft machines and beings by criticizing the now, to be imaginative for the future of architecture.Keywords: architectural design studio, visionary lexicon, narrative architecture, transformative representation
Procedia PDF Downloads 134706 Early Outcomes and Lessons from the Implementation of a Geriatric Hip Fracture Protocol at a Level 1 Trauma Center
Authors: Peter Park, Alfonso Ayala, Douglas Saeks, Jordan Miller, Carmen Flores, Karen Nelson
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Introduction Hip fractures account for more than 300,000 hospital admissions every year. Many present as fragility fractures in geriatric patients with multiple medical comorbidities. Standardized protocols for the multidisciplinary management of this patient population have been shown to improve patient outcomes. A hip fracture protocol was implemented at a Level I Trauma center with a focus on pre-operative medical optimization and early surgical care. This study evaluates the efficacy of that protocol, including the early transition period. Methods A retrospective review was performed of all patients ages 60 and older with isolated hip fractures who were managed surgically between 2020 and 2022. This included patients 1 year prior and 1 year following the implementation of a hip fracture protocol at a Level I Trauma center. Results 530 patients were identified: 249 patients were treated before, and 281 patients were treated after the protocol was instituted. There was no difference in mean age (p=0.35), gender (p=0.3), or Charlson Comorbidity Index (p=0.38) between the cohorts. Following the implementation of the protocol, there were observed increases in time to surgery (27.5h vs. 33.8h, p=0.01), hospital length of stay (6.3d vs. 9.7d, p<0.001), and ED LOS (5.1h vs. 6.2h, p<0.001). There were no differences in in-hospital mortality (2.01% pre vs. 3.20% post, p=0.39) and complication rates (25% pre vs 26% post, p=0.76). A trend towards improved outcomes was seen after the early transition period but failed to yield statistical significance. Conclusion Early medical management and surgical intervention are key determining factors affecting outcomes following fragility hip fractures. The implementation of a hip fracture protocol at this institution has not yet significantly affected these parameters. This could in part be due to the restrictions placed at this institution during the COVID-19 pandemic. Despite this, the time to OR pre-and post-implementation was quicker than figures reported elsewhere in literature. Further longitudinal data will be collected to determine the final influence of this protocol. Significance/Clinical Relevance Given the increasing number of elderly people and the high morbidity and mortality associated with hip fractures in this population finding cost effective ways to improve outcomes in the management of these injuries has the potential to have enormous positive impact for both patients and hospital systems.Keywords: hip fracture, geriatric, treatment algorithm, preoperative optimization
Procedia PDF Downloads 69705 Adaptive Training Methods Designed to Improve a Shorter Resident Curriculum in Obstetrics and Gynecology
Authors: Philippe Judlin, Olivier Morel
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Background: In France, the resident curriculum (RC) in Obstetrics and Gynecology (OBGYN) takes five years. In the course of the last 15 years, this RC has undergone major changes, characterized mainly by successive reductions of work hours. The program used to comprise long and frequent shifts, huge workload, poor supervision and erratic theoretical teaching. A decade ago, the French Ministry of Heath recommended a limitation of shift duration up to 24 hours and a minimum of 11 hours off duty between shifts. Last year, in order to comply with European Union directives, new recommendations have further limited residents’ work hours to 48 hours per week. Methods: Assessment of the residency program adjustments recently made to accommodate the recommendations while improving the training quality in resorting to new methods. Results: The challenge facing program directors was to provide an all-encompassing curriculum to OBGYN residents despite fewer work hours. Program has been dramatically redesigned, and several measures have been put in place: -The resident rotation system has been redesigned. Residents used to make 6-month rotations between 10-12 Departments of OBGYN or Surgery. Fewer Departments, those providing the best teaching, have been kept in the new RC. -Extensive inhouse supervision has been implemented for all kinds of clinical activities. Effectual supervision of residents has proved to be an effective tool to improve the quality of training. -The tutorship system, with academic members individually overseeing residents during their curriculum, has been perfected. It allows a better follow-up of residents’ progresses during the 5-year program. -The set up of an extensive program of lectures encompassing all maters in Obstetrics & Gynecology. These mandatory lectures are available online in a dedicated website. Therefore, face-to-face lectures have been limited in order to fit in the 48-hour limit. -The use of simulation has been significantly increased in obstetrics, materno-fetal medicine and surgery (stressing especially laparoscopic training). -Residents’ feedback has been taken into account in the setup of the new RC. Conclusion: This extensive overhaul of the Obstetrics and Gynecology RC has been in place since last year only. Nevertheless, the new program seems to adequately take into account the new recommendations while providing a better and more consistent teaching to the OBGYN residents.Keywords: education, laparoscopy, residency, simulation
Procedia PDF Downloads 183704 A Survey Proposal towards Holistic Management of Schizophrenia
Authors: Pronab Ganguly, Ahmed A. Moustafa
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Holistic management of schizophrenia involves mainstream pharmacological intervention, complimentary medicine intervention, therapeutic intervention and other psychosocial factors such as accommodation, education, job training, employment, relationship, friendship, exercise, overall well-being, smoking, substance abuse, suicide prevention, stigmatisation, recreation, entertainment, violent behaviour, arrangement of public trusteeship and guardianship, day-day-living skill, integration with community, and management of overweight due to medications and other health complications related to medications amongst others. Our review shows that there is no integrated survey by combining all these factors. An international web-based survey was conducted to evaluate the significance of all these factors and present them in a unified manner. It is believed this investigation will contribute positively towards holistic management of schizophrenia. There will be two surveys. In the pharmacological intervention survey, five popular drugs for schizophrenia will be chosen and their efficacy as well as harmful side effects will be evaluated on a scale of 0 -10. This survey will be done by psychiatrists. In the second survey, each element of therapeutic intervention and psychosocial factors will be evaluated according to their significance on a scale of 0 - 10. This survey will be done by care givers, psychologists, case managers and case workers. For the first survey, professional bodies of psychiatrists in English speaking countries will be contacted to request them to ask their members to participate in the survey. For the second survey, professional bodies of clinical psychologist and care givers in English speaking countries will be contacted to request them to ask their members to participate in the survey. Additionally, for both the surveys, relevant professionals will be contacted through personal contact networks. For both the surveys, mean, mode, median, standard deviation and net promoter score will be calculated for each factor and then presented in a statistically significant manner. Subsequently each factor will be ranked according to their statistical significance. Additionally, country specific variation will be highlighted to identify the variation pattern. The results of these surveys will identify the relative significance of each type of pharmacological intervention, each type of therapeutic intervention and each type of psychosocial factor. The determination of this relative importance will definitely contribute to the improvement in quality of life for individuals with schizophrenia.Keywords: schizophrenia, holistic management, antipsychotics, quality of life
Procedia PDF Downloads 138703 Fastidious Enteric Pathogens in HIV
Authors: S. Pathak, R. Lazarus
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A 25-year-old male HIV patient (CD4 cells 20/µL and HIV viral load 14200000 copies/ml) with a past medical history of duodenal ulcer, pneumocystis carinii pneumonia, oesophageal candidiasis presented with fever and a seizure to hospital. The only recent travel had been a religious pilgrimage from Singapore to Malaysia 5 days prior; during the trip he sustained skin abrasions. The patient had recently started highly active antiretroviral therapy 2 months prior. Clinical examination was unremarkable other than a temperature of 38.8°C and perianal warts. Laboratory tests showed a leukocyte count 12.5x109 cells/L, haemoglobin 9.4 g/dL, normal biochemistry and a C-reactive protein 121 mg/L. CT head and MRI head were unremarkable and cerebrospinal fluid analysis performed after a delay (due to technical difficulties) of 11 days was unremarkable. Blood cultures (three sets) taken on admission showed Gram-negative rods in the anaerobic bottles only at the end of incubation with culture result confirmed by molecular sequencing showing Helicobacter cinaedi. The patient was treated empirically with ceftriaxone for seven days and this was converted to oral co-amoxiclav for a further seven days after the blood cultures became positive. A Transthoracic echocardiogram was unremarkable. The patient made a full recovery. Helicobacter cinaedi is a gram-negative anaerobic fastidious organism affecting patients with comorbidity. Infection may manifest as cellulitius, colitis or as in this case as bloodstream infection – the latter is often attributed to faeco-oral infection. Laboratory identification requires prolonged culture. Therapeutic options may be limited by resistance to macrolides and fluoroquinolones. The likely pathogen inoculation routes in the case described include gastrointestinal translocation due to proctitis at the site of perianal warts, or breach of the skin via abrasions occurring during the pilgrimage. Such organisms are increasing in prevalence as our patient population ages and patients have multiple comorbidities including HIV. It may be necessary in patients with unexplained fever to prolong incubation of sterile sites including blood in order to identify this unusual fastidious organism.Keywords: fastidious, Helicobacter cinaedi, HIV, immunocompromised
Procedia PDF Downloads 372702 Viability of EBT3 Film in Small Dimensions to Be Use for in-Vivo Dosimetry in Radiation Therapy
Authors: Abdul Qadir Jangda, Khadija Mariam, Usman Ahmed, Sharib Ahmed
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The Gafchromic EBT3 film has the characteristic of high spatial resolution, weak energy dependence and near tissue equivalence which makes them viable to be used for in-vivo dosimetry in External Beam and Brachytherapy applications. The aim of this study is to assess the smallest film dimension that may be feasible for the use in in-vivo dosimetry. To evaluate the viability, the film sizes from 3 x 3 mm to 20 x 20 mm were calibrated with 6 MV Photon and 6 MeV electron beams. The Gafchromic EBT3 (Lot no. A05151201, Make: ISP) film was cut into five different sizes in order to establish the relationship between absorbed dose vs. film dimensions. The film dimension were 3 x 3, 5 x 5, 10 x 10, 15 x 15, and 20 x 20 mm. The films were irradiated on Varian Clinac® 2100C linear accelerator for dose range from 0 to 1000 cGy using PTW solid water phantom. The irradiation was performed as per clinical absolute dose rate calibratin setup, i.e. 100 cm SAD, 5.0 cm depth and field size of 10x10 cm2 and 100 cm SSD, 1.4 cm depth and 15x15 cm2 applicator for photon and electron respectively. The irradiated films were scanned with the landscape orientation and a post development time of 48 hours (minimum). Film scanning accomplished using Epson Expression 10000 XL Flatbed Scanner and quantitative analysis carried out with ImageJ freeware software. Results show that the dose variation with different film dimension ranging from 3 x 3 mm to 20 x 20 mm is very minimal with a maximum standard deviation of 0.0058 in Optical Density for a dose level of 3000 cGy and the the standard deviation increases with the increase in dose level. So the precaution must be taken while using the small dimension films for higher doses. Analysis shows that there is insignificant variation in the absorbed dose with a change in film dimension of EBT3 film. Study concludes that the film dimension upto 3 x 3 mm can safely be used up to a dose level of 3000 cGy without the need of recalibration for particular dimension in use for dosimetric application. However, for higher dose levels, one may need to calibrate the films for a particular dimension in use for higher accuracy. It was also noticed that the crystalline structure of the film got damage at the edges while cutting the film, which can contribute to the wrong dose if the region of interest includes the damage area of the filmKeywords: external beam radiotherapy, film calibration, film dosimetery, in-vivo dosimetery
Procedia PDF Downloads 487701 Expert Supporting System for Diagnosing Lymphoid Neoplasms Using Probabilistic Decision Tree Algorithm and Immunohistochemistry Profile Database
Authors: Yosep Chong, Yejin Kim, Jingyun Choi, Hwanjo Yu, Eun Jung Lee, Chang Suk Kang
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For the past decades, immunohistochemistry (IHC) has been playing an important role in the diagnosis of human neoplasms, by helping pathologists to make a clearer decision on differential diagnosis, subtyping, personalized treatment plan, and finally prognosis prediction. However, the IHC performed in various tumors of daily practice often shows conflicting and very challenging results to interpret. Even comprehensive diagnosis synthesizing clinical, histologic and immunohistochemical findings can be helpless in some twisted cases. Another important issue is that the IHC data is increasing exponentially and more and more information have to be taken into account. For this reason, we reached an idea to develop an expert supporting system to help pathologists to make a better decision in diagnosing human neoplasms with IHC results. We gave probabilistic decision tree algorithm and tested the algorithm with real case data of lymphoid neoplasms, in which the IHC profile is more important to make a proper diagnosis than other human neoplasms. We designed probabilistic decision tree based on Bayesian theorem, program computational process using MATLAB (The MathWorks, Inc., USA) and prepared IHC profile database (about 104 disease category and 88 IHC antibodies) based on WHO classification by reviewing the literature. The initial probability of each neoplasm was set with the epidemiologic data of lymphoid neoplasm in Korea. With the IHC results of 131 patients sequentially selected, top three presumptive diagnoses for each case were made and compared with the original diagnoses. After the review of the data, 124 out of 131 were used for final analysis. As a result, the presumptive diagnoses were concordant with the original diagnoses in 118 cases (93.7%). The major reason of discordant cases was that the similarity of the IHC profile between two or three different neoplasms. The expert supporting system algorithm presented in this study is in its elementary stage and need more optimization using more advanced technology such as deep-learning with data of real cases, especially in differentiating T-cell lymphomas. Although it needs more refinement, it may be used to aid pathological decision making in future. A further application to determine IHC antibodies for a certain subset of differential diagnoses might be possible in near future.Keywords: database, expert supporting system, immunohistochemistry, probabilistic decision tree
Procedia PDF Downloads 216700 Anti-lipidemic and Hematinic Potentials of Moringa Oleifera Leaves: A Clinical Trial on Type 2 Diabetic Subjects in a Rural Nigerian Community
Authors: Ifeoma C. Afiaenyi, Elizabeth K. Ngwu, Rufina N. B. Ayogu
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Diabetes has crept into the rural areas of Nigeria, causing devastating effects on its sufferers; most of them could not afford diabetic medications. Moringa oleifera has been used extensively in animal models to demonstrate its antilipidaemic and haematinic qualities; however, there is a scarcity of data on the effect of graded levels of Moringa oleifera leaves on the lipid profile and hematological parameters in human diabetic subjects. The study determined the effect of Moringa oleifera leaves on the lipid profile and hematological parameters of type 2 diabetic subjects in Ukehe, a rural Nigerian community. Twenty-four adult male and female diabetic subjects were purposively selected for the study. These subjects were shared into four groups of six subjects each. The diets used in the study were isocaloric. A control group (diabetics, group 1) was fed diets without Moringa oleifera leaves. Experimental groups 2, 3 and 4 received 20g, 40g and 60g of Moringa oleifera leaves daily, respectively, in addition to the diets. The subjects' lipid profile and hematological parameters were measured prior to the feeding trial and at the end of the feeding trial. The feeding trial lasted for fourteen days. The data obtained were analyzed using the computer program Statistical Product for Service Solution (SPSS) for windows version 21. A Paired-samples t-test was used to compare the means of values collected before and after the feeding trial within the groups and significance was accepted at p < 0.05. There was a non-significant (p > 0.05) decrease in the mean total cholesterol of the subjects in groups 1, 2 and 3 after the feeding trial. There was a non-significant (p > 0.05) decrease in the mean triglyceride levels of the subjects in group 1 after the feeding trial. Groups 1 and 3 subjects had a non-significant (p > 0.05) decrease in their mean low-density lipoprotein (LDL) cholesterol after the feeding trial. Groups 1, 2 and 4 had a significant (p < 0.05) increase in their mean high-density lipoprotein (HDL) cholesterol after the feeding trial. A significant (p < 0.05) decrease in the mean hemoglobin level was observed only in group 4 subjects. Similarly, there was a significant (p < 0.05) decrease in the mean packed cell volume of group 4 subjects. It was only in group 4 that a significant (p < 0.05) decrease in the mean white blood cells of the subjects was also observed. The changes observed in the parameters assessed were not dose-dependent. Therefore, a similar study of longer duration and more samples is imperative to authenticate these results.Keywords: anemia, diabetic subjects, lipid profile, moringa oleifera
Procedia PDF Downloads 190699 Novel Electrospun Polymeric Nanofibers Loaded Different Medicaments as Drug Delivery Systems for Regenerative Endodontics
Authors: Nura Brimo, Dilek Cokeliler Serdaroglu, Tansel Uyar, Busra Uysal, Elif Bahar Cakici, Miris Dikmen, Zerrin Canturk
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Background: A combination of antibiotics, including metronidazole (MET), ciprofloxacin (CIP), and minocycline (MINO), has been demonstrated to disinfect bacteria in necrotic teeth before regenerative processes. It has been presented clinically that antibiotic pastes may drive to possible stem cell death and difficulties in removing from the canal system, which can limit the regenerative procedure. This study was designed to (1) synthesize nanofibrous webs containing various concentrations of different medicaments (triple, double, and calcium hydroxide,Ca(OH)2), and (2) coat thiselectrospun fibrous gutta-percha (GP) cones. Methods: Poly(vinylpyrrolidone) (PVP)-based electrospun fibrous webs were processed with low medicaments concentrations. Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDX), and X-Ray Photoelectron Spectroscopy (XPS) were carried out to investigate fiber morphology, antibiotic incorporation, and characterized GP-coated fibrous webs, respectively. The chemical and physical properties of dentine were carried out via Fourier Transform Infrared Spectroscopy (FTIR) and Nano-SEM, respectively. The antimicrobial properties of the different fibrous webs were assessed against various bacteria by direct nanofiber/bacteria contact. Cytocompatibility was measured by applying the MTT method. Results: The mean fiber diameter of the experiment groups of medicament-containing fibers ranged in the nm scale and was significantly smaller than PVP fibers. EDX analysis confirmed the presence of medicaments in the nanofibers. XPS analysis presented a complete coating of the fibers with GPs; FTIR and Nano-SEM showed no chemical and physical configuration of intracanal medicaments on the dentine surface. Meanwhile, nanofibrous webs led to a significant reduction in the percentage of viable bacteria compared with the negative control and PVP. Conclusion: Our findings suggest that TA-NFs, DA-NFs, and Cₐ(OH)₂)-NFs coated GP cones have significant potential in eliminating intracanal bacteria, cell-friendly behavior, and clinical usage features.Keywords: drug delivery, drug carrier, electrospinning, nano/microfibers, regenerative endodontic, morphology
Procedia PDF Downloads 105698 Developing a Systemic Monoclonal Antibody Therapy for the Treatment of Large Burn Injuries
Authors: Alireza Hassanshahi, Xanthe Strudwick, Zlatko Kopecki, Allison J Cowin
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Studies have shown that Flightless (Flii) is elevated in human wounds, including burns, and reducing the level of Flii is a promising approach for improving wound repair and reducing scar formation. The most effective approach has been to neutralise Flii activity using localized, intradermal application of function blocking monoclonal antibodies. However, large surface area burns are difficult to treat by intradermal injection of therapeutics, so the aim of this study was to investigate if a systemic injection of a monoclonal antibody against Flii could improve healing in mice following burn injury. Flii neutralizing antibodies (FnAbs) were labelled with Alxa-Fluor-680 for biodistribution studies and the healing effects of systemically administered FnAbs to mice with burn injuries. A partial thickness, 7% (70mm2) total body surface area scald burn injury was created on the dorsal surface of mice (n=10/group), and 100µL of Alexa-Flour-680-labeled FnAbs were injected into the intraperitoneal cavity (IP) at time of injury. The burns were imaged on days 0, 1, 2, 3, 4, and 7 using IVIS Lumina S5 Imaging System, and healing was assessed macroscopically, histologically, and using immunohistochemistry. Fluorescent radiance efficiency measurements showed that IP injected Alexa-Fluor-680-FnAbs localized at the site of burn injury from day 1, remaining there for the whole 7-day study. The burns treated with FnAbs showed a reduction in macroscopic wound area and an increased rate of epithelialization compared to controls. Immunohistochemistry for NIMP-R14 showed a reduction in the inflammatory infiltrate, while CD31/VEGF staining showed improved angiogenesis post-systemic FnAb treatment. These results suggest that systemically administered FnAbs are active within the burn site and can improve healing outcomes. The clinical application of systemically injected Flii monoclonal antibodies could therefore be a potential approach for promoting the healing of large surface area burns immediately after injury.Keywords: biodistribution, burn, flightless, systemic, fnAbs
Procedia PDF Downloads 164697 Incidence and Predictors of Mortality Among HIV Positive Children on Art in Public Hospitals of Harer Town, Enrolled From 2011 to 2021
Authors: Getahun Nigusie
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Background; antiretroviral treatment reduce HIV-related morbidity, and prolonged survival of patients however, there is lack of up-to-date information concerning the treatment long term effect on the survival of HIV positive children especially in the study area. Objective: To assess incidence and predictors of mortality among HIV positive children on ART in public hospitals of Harer town who were enrolled from 2011 to 2021. Methodology: Institution based retrospective cohort study was conducted among 429 HIV positive children enrolled in ART clinic from January 1st 2011 to December30th 2021. Data were collected from medical cards by using a data extraction form, Descriptive analyses were used to Summarized the results, and life table was used to estimate survival probability at specific point of time after introduction of ART. Kaplan Meier survival curve together with log rank test was used to compare survival between different categories of covariates, and Multivariate Cox-proportional hazard regression model was used to estimate adjusted Hazard rate. Variables with p-values ≤0.25 in bivariable analysis were candidates to the multivariable analysis. Finally, variables with p-values < 0.05 were considered as significant variables. Results: The study participants had followed for a total of 2549.6 child-years (30596 child months) with an overall mortality rate of 1.5 (95% CI: 1.1, 2.04) per 100 child-years. Their median survival time was 112 months (95% CI: 101–117). There were 38 children with unknown outcome, 39 deaths, and 55 children transfer out to different facility. The overall survival at 6, 12, 24, 48 months were 98%, 96%, 95%, 94% respectively. being in WHO clinical Stage four (AHR=4.55, 95% CI:1.36, 15.24), having anemia(AHR=2.56, 95% CI:1.11, 5.93), baseline low absolute CD4 count (AHR=2.95, 95% CI: 1.22, 7.12), stunting (AHR=4.1, 95% CI: 1.11, 15.42), wasting (AHR=4.93, 95% CI: 1.31, 18.76), poor adherence to treatment (AHR=3.37, 95% CI: 1.25, 9.11), having TB infection at enrollment (AHR=3.26, 95% CI: 1.25, 8.49),and no history of change their regimen(AHR=7.1, 95% CI: 2.74, 18.24), were independent predictors of death. Conclusion: more than half of death occurs within 2 years. Prevalent tuberculosis, anemia, wasting, and stunting nutritional status, socioeconomic factors, and baseline opportunistic infection were independent predictors of death. Increasing early screening and managing those predictors are required.Keywords: human immunodeficiency virus-positive children, anti-retroviral therapy, survival, Ethiopia
Procedia PDF Downloads 4696 The Routine Use of a Negative Pressure Incision Management System in Vascular Surgery: A Case Series
Authors: Hansraj Bookun, Angela Tan, Rachel Xuan, Linheng Zhao, Kejia Wang, Animesh Singla, David Kim, Christopher Loupos
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Introduction: Incisional wound complications in vascular surgery patients represent a significant clinical and econometric burden of morbidity and mortality. The objective of this study was to trial the feasibility of applying the Prevena negative pressure incision management system as a routine dressing in patients who had undergone arterial surgery. Conventionally, Prevena has been applied to groin incisions, but this study features applications on multiple wound sites such as the thigh or major amputation stumps. Method: This was a cross-sectional observational, single-centre case series of 12 patients who had undergone major vascular surgery. Their wounds were managed with the Prevena system being applied either intra-operatively or on the first post-operative day. Demographic and operative details were collated as well as the length of stay and complication rates. Results: There were 9 males (75%) with mean age of 66 years and the comorbid burden was as follows: ischaemic heart disease (92%), diabetes (42%), hypertension (100%), stage 4 or greater kidney impairment (17%) and current or ex-smoking (83%). The main indications were acute ischaemia (33%), claudication (25%), and gangrene (17%). There were single instances of an occluded popliteal artery aneurysm, diabetic foot infection, and rest pain. The majority of patients (50%) had hybrid operations with iliofemoral endarterectomies, patch arterioplasties, and further peripheral endovascular treatment. There were 4 complex arterial bypass operations and 2 major amputations. The mean length of stay was 17 ± 10 days, with a range of 4 to 35 days. A single complication, in the form of a lymphocoele, was encountered in the context of an iliofemoral endarterectomy and patch arterioplasty. This was managed conservatively. There were no deaths. Discussion: The Prevena wound management system shows that in conjunction with safe vascular surgery, absolute wound complication rates remain low and that it remains a valuable adjunct in the treatment of vasculopaths.Keywords: wound care, negative pressure, vascular surgery, closed incision
Procedia PDF Downloads 121695 Development and Validation of an Instrument Measuring the Coping Strategies in Situations of Stress
Authors: Lucie Côté, Martin Lauzier, Guy Beauchamp, France Guertin
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Stress causes deleterious effects to the physical, psychological and organizational levels, which highlight the need to use effective coping strategies to deal with it. Several coping models exist, but they don’t integrate the different strategies in a coherent way nor do they take into account the new research on the emotional coping and acceptance of the stressful situation. To fill these gaps, an integrative model incorporating the main coping strategies was developed. This model arises from the review of the scientific literature on coping and from a qualitative study carried out among workers with low or high levels of stress, as well as from an analysis of clinical cases. The model allows one to understand under what circumstances the strategies are effective or ineffective and to learn how one might use them more wisely. It includes Specific Strategies in controllable situations (the Modification of the Situation and the Resignation-Disempowerment), Specific Strategies in non-controllable situations (Acceptance and Stubborn Relentlessness) as well as so-called General Strategies (Wellbeing and Avoidance). This study is intended to undertake and present the process of development and validation of an instrument to measure coping strategies based on this model. An initial pool of items has been generated from the conceptual definitions and three expert judges have validated the content. Of these, 18 items have been selected for a short form questionnaire. A sample of 300 students and employees from a Quebec university was used for the validation of the questionnaire. Concerning the reliability of the instrument, the indices observed following the inter-rater agreement (Krippendorff’s alpha) and the calculation of the coefficients for internal consistency (Cronbach's alpha) are satisfactory. To evaluate the construct validity, a confirmatory factor analysis using MPlus supports the existence of a model with six factors. The results of this analysis suggest also that this configuration is superior to other alternative models. The correlations show that the factors are only loosely related to each other. Overall, the analyses carried out suggest that the instrument has good psychometric qualities and demonstrates the relevance of further work to establish predictive validity and reconfirm its structure. This instrument will help researchers and clinicians better understand and assess coping strategies to cope with stress and thus prevent mental health issues.Keywords: acceptance, coping strategies, stress, validation process
Procedia PDF Downloads 333694 Development of Electrochemical Biosensor Based on Dendrimer-Magnetic Nanoparticles for Detection of Alpha-Fetoprotein
Authors: Priyal Chikhaliwala, Sudeshna Chandra
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Liver cancer is one of the most common malignant tumors with poor prognosis. This is because liver cancer does not exhibit any symptoms in early stage of disease. Increased serum level of AFP is clinically considered as a diagnostic marker for liver malignancy. The present diagnostic modalities include various types of immunoassays, radiological studies, and biopsy. However, these tests undergo slow response times, require significant sample volumes, achieve limited sensitivity and ultimately become expensive and burdensome to patients. Considering all these aspects, electrochemical biosensors based on dendrimer-magnetic nanoparticles (MNPs) was designed. Dendrimers are novel nano-sized, three-dimensional molecules with monodispersed structures. Poly-amidoamine (PAMAM) dendrimers with eight –NH₂ groups using ethylenediamine as a core molecule were synthesized using Michael addition reaction. Dendrimers provide added the advantage of not only stabilizing Fe₃O₄ NPs but also displays capability of performing multiple electron redox events and binding multiple biological ligands to its dendritic end-surface. Fe₃O₄ NPs due to its superparamagnetic behavior can be exploited for magneto-separation process. Fe₃O₄ NPs were stabilized with PAMAM dendrimer by in situ co-precipitation method. The surface coating was examined by FT-IR, XRD, VSM, and TGA analysis. Electrochemical behavior and kinetic studies were evaluated using CV which revealed that the dendrimer-Fe₃O₄ NPs can be looked upon as electrochemically active materials. Electrochemical immunosensor was designed by immobilizing anti-AFP onto dendrimer-MNPs by gluteraldehyde conjugation reaction. The bioconjugates were then incubated with AFP antigen. The immunosensor was characterized electrochemically indicating successful immuno-binding events. The binding events were also further studied using magnetic particle imaging (MPI) which is a novel imaging modality in which Fe₃O₄ NPs are used as tracer molecules with positive contrast. Multicolor MPI was able to clearly localize AFP antigen and antibody and its binding successfully. Results demonstrate immense potential in terms of biosensing and enabling MPI of AFP in clinical diagnosis.Keywords: alpha-fetoprotein, dendrimers, electrochemical biosensors, magnetic nanoparticles
Procedia PDF Downloads 130693 The Effect of an Occupational Therapy Programme on Sewing Machine Operators
Authors: N. Dunleavy, E. Lovemore, K. Siljeur, D. Jackson, M. Hendricks, M. Hoosain, N. Plastow, S. Marais
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Background: The work requirements of sewing machine operators cause physical and emotional strain. Past ergonomic interventions have been provided to alleviate physical concerns; however, a holistic, multimodal intervention was needed to improve these factors. Aim: The study aimed to examine the effect of an occupational therapy programme on sewing machine operators’ pain, mental health, and productivity within a factory in the South African context. Methods: A pilot randomised control trial was conducted with 22 sewing machine operators within a single factory. Stratified randomisation was used to determine the experimental (EG) and control groups (CG), using measures for pain intensity, level of depression (mental health), and productivity rates as stratification variables. The EG received the multimodal intervention, incorporating education, seating adaptations, and mental health intervention. In three months, the CG will receive the same intervention. Pre- and post-intervention testing have occurred with upcoming three- and six-month follow-ups. Results: Immediate results indicate a statistically significant decrease in pain in both experimental and control groups; no change in productivity scores and depression between the two groups. This may be attributed to external factors. The values for depression further showed no statistical significance between the two groups and within pre-and post-test results. The Statistical Program for Social Sciences (SPSS) version-24 was used as the data analysis testing, where all the tests will be evaluated at a 5% significance level. Contribution of research: The research adds to the body of knowledge informing the Occupational Therapy role in work settings, providing evidence on the effectiveness of workplace-based multimodal interventions. Conclusion: The study provides initial data on the effectiveness of a pilot randomised control trial on pain and mental health in South Africa. Results indicated no quantitative change between the experimental and control groups; however, qualitative data suggest a clinical significance of the findings.Keywords: ergonomics programme, occupational therapy, sewing machine operators, workplace-based multimodal interventions
Procedia PDF Downloads 78692 Effect of Labisia pumila var. alata with a Structured Exercise Program in Women with Polycystic Ovarian Syndrome
Authors: D. Maryama AG. Daud, Zuliana Bacho, Stephanie Chok, DG. Mashitah PG. Baharuddin, Mohd Hatta Tarmizi, Nathira Abdul Majeed, Helen Lasimbang
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Lifestyle, physical activity, food intake, genetics and medication are contributing factors for people getting obese. Which in some of the obese people were a low or non-responder to exercise. And obesity is very common clinical feature in women affected by Polycystic Ovarian Syndrome (PCOS). Labisia pumila var. alata (LP) is a local herb which had been widely used by Malay women in treating menstrual irregularities, painful menstruation and postpartum well-being. Therefore, this study was carried out to investigate the effect of LP with a structured exercise program on anthropometric, body composition and physical fitness performance of PCOS patients. By using a single blind and parallel study design, where by subjects were assigned into a 16-wk structured exercise program (3 times a week) interventions; (LP and exercise; LPE, and exercise only; E). All subjects in the LPE group were prescribed 200mg LP; once a day, for 16 weeks. The training heart rate (HR) was monitored based on a percentage of the maximum HR (HRmax) achieved during submaximal exercise test that was conducted at wk-0 and wk-8. The progression of aerobic exercise intensity from 25–30 min at 60 – 65% HRmax during the first week to 45 min at 75–80% HRmax by the end of this study. Anthropometric (body weight, Wt; waist circumference, WC; and hip circumference, HC), body composition (fat mass, FM; percentage body fat, %BF; Fat Free Mass, FFM) and physical fitness performance (push up to failure, PU; 1-minute Sit Up, SU; and aerobic step test, PVO2max) were measured at wk-0, wk-4, wk-8, wk-12, and wk-16. This study found that LP does not have a significant effect on body composition, anthropometric and physical fitness performance of PCOS patients underwent a structured exercise program. It means LP does not improve exercise responses of PCOS patients towards anthropometric, body composition and physical fitness performance. The overall data shows exercise responses of PCOS patients is by increasing their aerobic endurance and muscle endurance performances, there is a significant reduction in FM, PBF, HC, and Wt significantly. Therefore, exercise program for PCOS patients have to focus on aerobic fitness, and muscle endurance.Keywords: polycystic ovarian syndrome, Labisia pumila var. alata, body composition, aerobic endurance, muscle endurance, anthropometric
Procedia PDF Downloads 205691 Investigating Homicide Offender Typologies Based on Their Clinical Histories and Crime Scene Behaviour Patterns
Authors: Valeria Abreu Minero, Edward Barker, Hannah Dickson, Francois Husson, Sandra Flynn, Jennifer Shaw
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Purpose – The purpose of this paper is to identify offender typologies based on aspects of the offenders’ psychopathology and their associations with crime scene behaviours using data derived from the National Confidential Enquiry into Suicide and Safety in Mental Health concerning homicides in England and Wales committed by offenders in contact with mental health services in the year preceding the offence (n=759). Design/methodology/approach – The authors used multiple correspondence analysis to investigate the interrelationships between the variables and hierarchical agglomerative clustering to identify offender typologies. Variables describing: the offender’s mental health history; the offenders’ mental state at the time of offence; characteristics useful for police investigations; and patterns of crime scene behaviours were included. Findings – Results showed differences in the offender’s histories in relation to their crime scene behaviours. Further, analyses revealed three homicide typologies: externalising, psychosis and depression. Analyses revealed three homicide typologies: externalising, psychotic and depressive. Practical implications – These typologies may assist the police during homicide investigations by: furthering their understanding of the crime or likely suspect; offering insights into crime patterns; provide advice as to what an offender’s offence behaviour might signify about his/her mental health background; findings suggest information concerning offender psychopathology may be useful for offender profiling purposes in cases of homicide offenders with schizophrenia, depression and comorbid diagnosis of personality disorder and alcohol/drug dependence. Originality/value – Empirical studies with an emphasis on offender profiling have almost exclusively focussed on the inference of offender demographic characteristics. This study provides a first step in the exploration of offender psychopathology and its integration to the multivariate analysis of offence information for the purposes of investigative profiling of homicide by identifying the dominant patterns of mental illness within homicidal behaviour.Keywords: offender profiling, mental illness, psychopathology, multivariate analysis, homicide, crime scene analysis, crime scene behviours, investigative advice
Procedia PDF Downloads 122690 35 MHz Coherent Plane Wave Compounding High Frequency Ultrasound Imaging
Authors: Chih-Chung Huang, Po-Hsun Peng
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Ultrasound transient elastography has become a valuable tool for many clinical diagnoses, such as liver diseases and breast cancer. The pathological tissue can be distinguished by elastography due to its stiffness is different from surrounding normal tissues. An ultrafast frame rate of ultrasound imaging is needed for transient elastography modality. The elastography obtained in the ultrafast system suffers from a low quality for resolution, and affects the robustness of the transient elastography. In order to overcome these problems, a coherent plane wave compounding technique has been proposed for conventional ultrasound system which the operating frequency is around 3-15 MHz. The purpose of this study is to develop a novel beamforming technique for high frequency ultrasound coherent plane-wave compounding imaging and the simulated results will provide the standards for hardware developments. Plane-wave compounding imaging produces a series of low-resolution images, which fires whole elements of an array transducer in one shot with different inclination angles and receives the echoes by conventional beamforming, and compounds them coherently. Simulations of plane-wave compounding image and focused transmit image were performed using Field II. All images were produced by point spread functions (PSFs) and cyst phantoms with a 64-element linear array working at 35MHz center frequency, 55% bandwidth, and pitch of 0.05 mm. The F number is 1.55 in all the simulations. The simulated results of PSFs and cyst phantom which were obtained using single, 17, 43 angles plane wave transmission (angle of each plane wave is separated by 0.75 degree), and focused transmission. The resolution and contrast of image were improved with the number of angles of firing plane wave. The lateral resolutions for different methods were measured by -10 dB lateral beam width. Comparison of the plane-wave compounding image and focused transmit image, both images exhibited the same lateral resolution of 70 um as 37 angles were performed. The lateral resolution can reach 55 um as the plane-wave was compounded 47 angles. All the results show the potential of using high-frequency plane-wave compound imaging for realizing the elastic properties of the microstructure tissue, such as eye, skin and vessel walls in the future.Keywords: plane wave imaging, high frequency ultrasound, elastography, beamforming
Procedia PDF Downloads 524689 Identification and Characterization of in Vivo, in Vitro and Reactive Metabolites of Zorifertinib Using Liquid Chromatography Lon Trap Mass Spectrometry
Authors: Adnan A. Kadi, Nasser S. Al-Shakliah, Haitham Al-Rabiah
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Zorifertinib is a novel, potent, oral, a small molecule used to treat non-small cell lung cancer (NSCLC). zorifertinib is an Epidermal Growth Factor Receptor (EGFR) inhibitor and has good blood–brain barrier permeability for (NSCLC) patients with EGFR mutations. zorifertinibis currently at phase II/III clinical trials. The current research reports the characterization and identification of in vitro, in vivo and reactive intermediates of zorifertinib. Prediction of susceptible sites of metabolism and reactivity pathways (cyanide and GSH) of zorifertinib were performed by the Xenosite web predictor tool. In-vitro metabolites of zorifertinib were performed by incubation with rat liver microsomes (RLMs) and isolated perfused rat liver hepatocytes. Extraction of zorifertinib and it's in vitro metabolites from the incubation mixtures were done by protein precipitation. In vivo metabolism was done by giving a single oral dose of zorifertinib(10 mg/Kg) to Sprague Dawely rats in metabolic cages by using oral gavage. Urine was gathered and filtered at specific time intervals (0, 6, 12, 18, 24, 48, 72,96and 120 hr) from zorifertinib dosing. A similar volume of ACN was added to each collected urine sample. Both layers (organic and aqueous) were injected into liquid chromatography ion trap mass spectrometry(LC-IT-MS) to detect vivozorifertinib metabolites. N-methyl piperizine ring and quinazoline group of zorifertinib undergoe metabolism forming iminium and electro deficient conjugated system respectively, which are very reactive toward nucleophilic macromolecules. Incubation of zorifertinib with RLMs in the presence of 1.0 mM KCN and 1.0 Mm glutathione were made to check reactive metabolites as it is often responsible for toxicities associated with this drug. For in vitro metabolites there were nine in vitro phase I metabolites, four in vitro phase II metabolites, eleven reactive metabolites(three cyano adducts, five GSH conjugates metabolites, and three methoxy metabolites of zorifertinib were detected by LC-IT-MS. For in vivo metabolites, there were eight in vivo phase I, tenin vivo phase II metabolitesofzorifertinib were detected by LC-IT-MS. In vitro and in vivo phase I metabolic pathways wereN- demthylation, O-demethylation, hydroxylation, reduction, defluorination, and dechlorination. In vivo phase II metabolic reaction was direct conjugation of zorifertinib with glucuronic acid and sulphate.Keywords: in vivo metabolites, in vitro metabolites, cyano adducts, GSH conjugate
Procedia PDF Downloads 191688 Effect of Psychosocial, Behavioural and Disease Characteristics on Health-Related Quality of Life after Breast Cancer Surgery: A Cross-Sectional Study of a Regional Australian Population
Authors: Lakmali Anthony, Madeline Gillies
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Background Breast cancer (BC) is usually managed with surgical resection. Many outcomes traditionally used to define successful operative management, such as resection margin, do not adequately reflect patients’ experience. Patient-reported outcomes (PRO) such as Health-Related Quality of life (HRQoL) provide a means by which the impact of surgery for cancer can be reported in a patient-centered way. This exploratory cross-sectional study aims to; (1) describe postoperative HRQoL in patients who underwent primary resection in a regional Australian hospital; (2) describe the prevalence of anxiety, depression and clinically significant fear of cancer recurrence (FCR) in this population; and (3) identify demographic, psychosocial, disease and treatment factors associated with poorer self-reported HRQoL. Methods Patients who had resection of BC in a regional Australian hospital between 2015 and 2022 were eligible. Participants were asked to complete a survey designed to assess HRQoL, as well as validated instruments that assess several other psychosocial PROs hypothesized to be associated with HRQoL; emotional distress, fear of cancer recurrence, social support, dispositional optimism, body image and spirituality. Results Forty-six patients completed the survey. Clinically significant levels of FCR and emotional distress were present in this group. Many domains of HRQoL were significantly worse than an Australian reference population for BC. Demographic and disease factors associated with poor HRQoL included smoking and ongoing adjuvant systemic therapy. The primary operation was not associated with HRQoL for breast cancer. All psychosocial factors measured were associated with HRQoL. Conclusion HRQoL is an important outcome in surgery for both research and clinical practice. This study provides an overview of the quality of life in a regional Australian population of postoperative breast cancer patients and the factors that affect it. Understanding HRQoL and awareness of patients particularly vulnerable to poor outcomes should be used to aid the informed consent and shared decision-making process between surgeon and patient.Keywords: breast cancer, surgery, quality of life, regional population
Procedia PDF Downloads 62687 Adding a Degree of Freedom to Opinion Dynamics Models
Authors: Dino Carpentras, Alejandro Dinkelberg, Michael Quayle
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Within agent-based modeling, opinion dynamics is the field that focuses on modeling people's opinions. In this prolific field, most of the literature is dedicated to the exploration of the two 'degrees of freedom' and how they impact the model’s properties (e.g., the average final opinion, the number of final clusters, etc.). These degrees of freedom are (1) the interaction rule, which determines how agents update their own opinion, and (2) the network topology, which defines the possible interaction among agents. In this work, we show that the third degree of freedom exists. This can be used to change a model's output up to 100% of its initial value or to transform two models (both from the literature) into each other. Since opinion dynamics models are representations of the real world, it is fundamental to understand how people’s opinions can be measured. Even for abstract models (i.e., not intended for the fitting of real-world data), it is important to understand if the way of numerically representing opinions is unique; and, if this is not the case, how the model dynamics would change by using different representations. The process of measuring opinions is non-trivial as it requires transforming real-world opinion (e.g., supporting most of the liberal ideals) to a number. Such a process is usually not discussed in opinion dynamics literature, but it has been intensively studied in a subfield of psychology called psychometrics. In psychometrics, opinion scales can be converted into each other, similarly to how meters can be converted to feet. Indeed, psychometrics routinely uses both linear and non-linear transformations of opinion scales. Here, we analyze how this transformation affects opinion dynamics models. We analyze this effect by using mathematical modeling and then validating our analysis with agent-based simulations. Firstly, we study the case of perfect scales. In this way, we show that scale transformations affect the model’s dynamics up to a qualitative level. This means that if two researchers use the same opinion dynamics model and even the same dataset, they could make totally different predictions just because they followed different renormalization processes. A similar situation appears if two different scales are used to measure opinions even on the same population. This effect may be as strong as providing an uncertainty of 100% on the simulation’s output (i.e., all results are possible). Still, by using perfect scales, we show that scales transformations can be used to perfectly transform one model to another. We test this using two models from the standard literature. Finally, we test the effect of scale transformation in the case of finite precision using a 7-points Likert scale. In this way, we show how a relatively small-scale transformation introduces both changes at the qualitative level (i.e., the most shared opinion at the end of the simulation) and in the number of opinion clusters. Thus, scale transformation appears to be a third degree of freedom of opinion dynamics models. This result deeply impacts both theoretical research on models' properties and on the application of models on real-world data.Keywords: degrees of freedom, empirical validation, opinion scale, opinion dynamics
Procedia PDF Downloads 117686 Discrepant Views of Social Competence and Links with Social Phobia
Authors: Pamela-Zoe Topalli, Niina Junttila, Päivi M. Niemi, Klaus Ranta
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Adolescents’ biased perceptions about their social competence (SC), whether negatively or positively, serve to influence their socioemotional adjustment such as early feelings of social phobia (nowadays referred to as Social Anxiety Disorder-SAD). Despite the importance of biased self-perceptions in adolescents’ psychosocial adjustment, the extent to which discrepancies between self- and others’ evaluations of one’s SC are linked to social phobic symptoms remains unclear in the literature. This study examined the perceptual discrepancy profiles between self- and peers’ as well as between self- and teachers’ evaluations of adolescents’ SC and the interrelations of these profiles with self-reported social phobic symptoms. The participants were 390 3rd graders (15 years old) of Finnish lower secondary school (50.8% boys, 49.2% girls). In contrast with variable-centered approaches that have mainly been used by previous studies when focusing on this subject, this study used latent profile analysis (LPA), a person-centered approach which can provide information regarding risk profiles by capturing the heterogeneity within a population and classifying individuals into groups. LPA revealed the following five classes of discrepancy profiles: i) extremely negatively biased perceptions of SC, ii) negatively biased perceptions of SC, iii) quite realistic perceptions of SC, iv) positively biased perceptions of SC, and v) extremely positively biased perceptions of SC. Adolescents with extremely negatively biased perceptions and negatively biased perceptions of their own SC reported the highest number of social phobic symptoms. Adolescents with quite realistic, positively biased and extremely positively biased perceptions reported the lowest number of socio-phobic symptoms. The results point out the negatively and the extremely negatively biased perceptions as possible contributors to social phobic symptoms. Moreover, the association of quite realistic perceptions with low number of social phobic symptoms indicates its potential protective power against social phobia. Finally, positively and extremely positively biased perceptions of SC are negatively associated with social phobic symptoms in this study. However, the profile of extremely positively biased perceptions might be linked as well with the existence of externalizing problems such as antisocial behavior (e.g. disruptive impulsivity). The current findings highlight the importance of considering discrepancies between self- and others’ perceptions of one’s SC in clinical and research efforts. Interventions designed to prevent or moderate social phobic symptoms need to take into account individual needs rather than aiming for uniform treatment. Implications and future directions are discussed.Keywords: adolescence, latent profile analysis, perceptual discrepancies, social competence, social phobia
Procedia PDF Downloads 234685 Improving Collective Health and Social Care through a Better Consideration of Sex and Gender: Analytical Report by the French National Authority for Health
Authors: Thomas Suarez, Anne-Sophie Grenouilleau, Erwan Autin, Alexandre Biosse-Duplan, Emmanuelle Blondet, Laurence Chazalette, Marie Coniel, Agnes Dessaigne, Sylvie Lascols, Andrea Lasserre, Candice Legris, Pierre Liot, Aline Metais, Karine Petitprez, Christophe Varlet, Christian Saout
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Background: The role of biological sex and gender identity -whether assigned or chosen- as health determinants are far from a recent discovery: several reports have stressed out how being a woman or a man could affect health on various scales. However, taking it into consideration beyond stereotypes and rigid binary assumptions still seems to be a work in progress. Method: The report is a synthesis on a variety of specific topics, each of which was studied by a specialist from the French National Authority for Health (HAS), through an analysis of existing literature on both healthcare policy construction process and instruments (norms, data analysis, clinical trials, guidelines, and professional practices). This work also implied a policy analysis of French recent public health laws and a retrospective study of guidelines with a gender mainstreaming approach. Results: The analysis showed that though sex and gender were well-known determinants of health, their consideration by both public policy and health operators was often incomplete, as it does not incorporate how sex and gender interact, as well as how they interact with other factors. As a result, the health and social care systems and their professionals tend to reproduce some stereotypical and inadequate habits. Though the data available often allows to take sex and gender into consideration, such data is often underused in practice guidelines and policy formulation. Another consequence is a lack of inclusiveness towards transgender or intersex persons. Conclusions: This report first urges for raising awareness of all the actors of health, in its broadest definition, that sex and gender matter beyond first-look conclusions. It makes a series of recommendations in order to reshape policy construction in the health sector on the one hand and to design public health instruments to make them more inclusive regarding sex and gender on the other hand. The HAS finally committed to integrate sex and gender preoccupations in its workings methods, to be a driving force in the spread of these concerns.Keywords: biological sex, determinants of health, gender, healthcare policy instruments, social accompaniment
Procedia PDF Downloads 119684 Mathematical Modeling on Capturing of Magnetic Nanoparticles in an Implant Assisted Channel for Magnetic Drug Targeting
Authors: Shashi Sharma, V. K. Katiyar, Uaday Singh
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The ability to manipulate magnetic particles in fluid flows by means of inhomogeneous magnetic fields is used in a wide range of biomedical applications including magnetic drug targeting (MDT). In MDT, magnetic carrier particles bounded with drug molecules are injected into the vascular system up-stream from the malignant tissue and attracted or retained at the specific region in the body with the help of an external magnetic field. Although the concept of MDT has been around for many years, however, wide spread acceptance of the technique is still looming despite the fact that it has shown some promise in both in vivo and clinical studies. This is because traditional MDT has some inherent limitations. Typically, the magnetic force is not very strong and it is also very short ranged. Since the magnetic force must overcome rather large hydrodynamic forces in the body, MDT applications have been limited to sites located close to the surface of the skin. Even in this most favorable situation, studies have shown that it is difficult to collect appreciable amounts of the MDCPs at the target site. To overcome these limitations of the traditional MDT approach, Ritter and co-workers reported the implant assisted magnetic drug targeting (IA-MDT). In IA-MDT, the magnetic implants are placed strategically at the target site to greatly and locally increase the magnetic force on MDCPs and help to attract and retain the MDCPs at the targeted region. In the present work, we develop a mathematical model to study the capturing of magnetic nanoparticles flowing in a fluid in an implant assisted cylindrical channel under the magnetic field. A coil of ferromagnetic SS 430 has been implanted inside the cylindrical channel to enhance the capturing of magnetic nanoparticles under the magnetic field. The dominant magnetic and drag forces, which significantly affect the capturing of nanoparticles, are incorporated in the model. It is observed through model results that capture efficiency increases from 23 to 51 % as we increase the magnetic field from 0.1 to 0.5 T, respectively. The increase in capture efficiency by increase in magnetic field is because as the magnetic field increases, the magnetization force, which is attractive in nature and responsible to attract or capture the magnetic particles, increases and results the capturing of large number of magnetic particles due to high strength of attractive magnetic force.Keywords: capture efficiency, implant assisted-magnetic drug targeting (IA-MDT), magnetic nanoparticles, modelling
Procedia PDF Downloads 456683 Youth Conflict-Related Trauma through Generations: An Ethnography on the Relationship between Health and Society in Post-Conflict Northern Ireland
Authors: Chiara Magliacane
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This project aims to analyse the relationship between the post-conflict Northern Irish environment and youth trauma in deprived areas. Using an anthropological perspective and methodology, the study investigates the possible contribution that a socio-cultural perspective can give to the current research on the field, with a special focus on the role of transgenerational trauma. The recognition of the role that socio-economic determinants have on health is usually a challenge for social researchers. In post-conflict Northern Ireland, the overall lack of research about connections between the social context and youth trauma opens the way to the present project. Anthropological studies on social implications of mental disorders have achieved impressive results in many societies; they show how conditions of sufferance and poverty are not intrinsically given, but are the products of historical processes and events. The continuum of violence and the politics of victimhood sustains a culture of silence and fear in deprived areas; this implies the need of investigating the structural and symbolic violence that lies behind the diffusion of mental suffering. The project refers to these concepts from Medical Anthropology and looks at connections between trauma and social, political and economic structures. Accordingly, the study considers factors such as poverty, unemployment, social inequality and gender and class perspectives. At the same time, the project problematises categories such as youth and trauma. 'Trauma' is currently debated within the social sciences since the 'invention' of the Post-Traumatic Stress Disorder (PTSD) in 1980. Current critics made to its clinical conception show how trauma has been mainly analysed as a memory of the past. On the contrary, medical anthropological research focuses on wider perspectives on society and its structures; this is a new and original approach to the study of youth trauma considering that, to author’s best knowledge, there is no research of this kind regarding Northern Ireland. Methods: Qualitative interviews, participant observation. Expected Impact: Local Northern Ireland organizations, i.e. specific charities that provide mental health support. Ongoing and present connections will ensure they will hear about this research.Keywords: health and social inequalities, Northern Ireland, structural violence, youth
Procedia PDF Downloads 197682 Significance of Molecular Autophagic Pathway in Gaucher Disease Pathology
Authors: Ozlem Oral, Emre Taskin, Aysel Yuce, Serap Dokmeci, Devrim Gozuacik
Abstract:
Autophagy is an evolutionary conserved lysosome-dependent catabolic pathway, responsible for the degradation of long-lived proteins, abnormal aggregates and damaged organelles which cannot be degraded by the ubiquitin-proteasome system. Lysosomes degrade the substrates through the activity of lysosomal hydrolases and lysosomal membrane-bound proteins. Mutations in the coding region of these proteins cause malfunctional lysosomes, which contributes to the pathogenesis of lysosomal storage diseases. Gaucher disease is a lysosomal storage disease resulting from the mutation of a lysosomal membrane-associated glycoprotein called glucocerebrosidase and its cofactor saposin C. The disease leads to intracellular accumulation of glucosylceramide and other glycolipids. Because of the essential role of lysosomes in autophagic degradation, Gaucher disease may directly be linked to this pathway. In this study, we investigated the expression of autophagy and/or lysosome-related genes and proteins in fibroblast cells isolated from patients with different mutations. We carried out confocal microscopy analysis and examined autophagic flux by utilizing the differential pH sensitivities of RFP and GFP in mRFP-GFP-LC3 probe. We also evaluated lysosomal pH by active lysosome staining and lysosomal enzyme activity. Beside lysosomes, we also performed proteasomal activity and cell death analysis in patient samples. Our data showed significant attenuation in the expression of key autophagy-related genes and accumulation of their proteins in mutant cells. We found decreased the ability of autophagosomes to fuse with lysosomes, associated with elevated lysosomal pH and reduced lysosomal enzyme activity. Proteasomal degradation and cell death analysis showed reduced proteolytic activity of the proteasome, which consequently leads to increased susceptibility to cell death. Our data indicate that the major degradation pathways are affected by multifunctional lysosomes in mutant patient cells and may underlie in the mechanism of clinical severity of Gaucher patients. (This project is supported by TUBITAK-3501-National Young Researchers Career Development Program, Project No: 112T130).Keywords: autophagy, Gaucher's disease, glucocerebrosidase, mutant fibroblasts
Procedia PDF Downloads 321