Search results for: drug reaction with eosinophilia and systemic symptoms
2300 Frequency of Hepatitis C Virus in Diagnosed Tuberculosis Cases
Authors: Muhammad Farooq Baig, Saleem Qadeer
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Background: The frequency of hepatitis C virus infection along with tuberculosis has not been widely investigated and very low statistics on rates of hepatitis C virus co-infection in tuberculosis patients. Hepatotoxicity is the major side effect of anti-tuberculosis therapy hepatitis HCVliver disease elevates the chances of hepatotoxicity up-to five folds. Objectives & Aim: To see the frequency of Hepatitis Cvirus infection amongst people with diagnosed Tuberculosis using gene X-pert technique. To evaluate the factors associated with HCVinfection in patients with MTBtuberculosis and to determine sensitivity and specificity of the tests. Study design: Comparative analytical study. Methodology: Three hundred and thirteen patients of tuberculosis diagnosed by Genexpert included while testing hepatitis C virus using immunochromotography rapid test technique, enzyme linked immunosorbent assay method and polymerase chain reaction test for confirmation. Results:Higher frequency of tuberculosis infection in males 57.8%, 42.5% between 20-39 years and 22% of hepatitis C virus infection in tuberculosis patients.The sensitivity of rapid test and enzyme-linked immunosorbent assay was 79% and 96% respectively while the specificity of rapid test and enzyme-linked immunosorbent assay was 91% and 99% respectively.Keywords: Mycobactrium Tuberculosis, PC'R, Gene x pert, Hepatitis C virus
Procedia PDF Downloads 762299 The Protective Effects of Naringenin on Iodoacetamide-Induced Ulcerative Colitis in Rats
Authors: Yomna T. Abdou, Hala F. Zaki, Sanaa A. Kenawy
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Naringenin is a flavanone, a type of flavonoid, found in fruits such as grapefruit, oranges, and tomatoes, was found to possess antioxidant, anti-inflammatory and antitumor effects. The present study was conducted to investigate the protective effect of naringenin on iodoacetamide-induced ulcerative colitis (UC) in rats. Male Wistar rats were pretreated with sulfasalazine (300 mg/kg, p.o.) as standard anti-inflammatory drug or naringenin (50 mg/kg, p.o.) for 7 consecutive days then UC was induced by intracolon administration of 0.1 ml (2%) iodoacetamide dissolved in 1% methylcelluose. One week later, animals were scarificed and the colonic tissues were dissected. Colon inflammation was evident by elevation in colon tumor necrosis factor alpha (TNFα) and interleukin-8 (IL-8) as well as inducible nitric oxide synthase (iNOS) enzyme, prostaglandin- E2 (PG-E2) and myeloperoxidase (MPO) activities. Additionally, oxidative stress was manifested by increased colon lipoperoxidation (MDA), glutathione (GSH) depletion, elevated nitric oxide (NO) content and glutathione peroxidase (GPx) activity. Pretreatment with naringenin largely mitigated these alterations. The present study reinforces the hypothetical use of naringenin as an anti-inflammatory complement to conventional UC treatment and could be considered in the dietary prevention of intestinal inflammation and related disorders.Keywords: iodoacetamide, naringenin, sulfasalazine, ulcerative colitis
Procedia PDF Downloads 5152298 Isotretinoin and Psychiatric Adverse Events: A Review of the Evidence
Authors: Thodoris Tsagkaris, Marios Stavropoulos, Panagiotis Theodosis-Nobelos, Charalampos Triantis
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Isotretinoin is a widely used therapeutic for the treatment of acne vulgaris and various other skin disorders. However, since its approval, many side effects and contraindications have been described, particularly important, such as teratogenicity as well as liver disease and dermal deterioration. In a very important allegation, isotretinoin has been linked with psychiatric symptoms like depression, suicidal ideation, schizophrenia, and hypervitaminosis A syndrome characteristics. These adverse effects have raised significant concerns regarding the safety of isotretinoin. Numerous studies and research have associated isotretinoin with side effects on the mental health of patients and have proposed plausible mechanisms regarding this suspected causative relationship. However, the evidence is still contradicting, and the data disperse, making their validity less valuable. Thus, in the present study, we aim to analyze further the available literature and present a complete analysis of the side effects of isotretinoin, with particular emphasis on the effects it may have on the mental health of patients. The review is based on international articles from broad scientific electronic databases like PubMed and Scopus. This review concludes that although many studies have associated isotretinoin with mental effects like depression, bipolar disorder, schizophrenia, and suicidal ideation, the data are still insufficient and often contradictory. In fact, additional studies with accurate data and larger double-blinded samples, and more analytic systematic reviews are required. It is especially important to monitor the dose and the intervals that isotretinoin has to be administered in order to potentially cause mental health problems, as well as the duration of treatment and the role that the patient's medical and pharmaceutical history may play.Keywords: acne, depression, isotretinoin, mental health
Procedia PDF Downloads 1612297 Investigating the Thermal Characteristics of Reclaimed Solid Waste from a Landfill Site Using Thermogravimetry
Authors: S. M. Al-Salem, G.A. Leeke, H. J. Karam, R. Al-Enzi, A. T. Al-Dhafeeri, J. Wang
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Thermogravimetry has been popularized as a thermal characterization technique since the 1950s. It aims at investigating the weight loss against both reaction time and temperature, whilst being able to characterize the evolved gases from the volatile components of the organic material being tested using an appropriate hyphenated analytical technique. In an effort to characterize and identify the reclaimed waste from an unsanitary landfill site, this approach was initiated. Solid waste (SW) reclaimed from an active landfill site in the State of Kuwait was collected and prepared for characterization in accordance with international protocols. The SW was segregated and its major components were identified after washing and air drying. Shredding and cryomilling was conducted on the plastic solid waste (PSW) component to yield a material that is representative for further testing and characterization. The material was subjected to five heating rates (b) with minimal repeatable weight for high accuracy thermogravimetric analysis (TGA) following the recommendation of the International Confederation for Thermal Analysis and Calorimetry (ICTAC). The TGA yielded thermograms that showed an off-set from typical behavior of commercial grade resin which was attributed to contact of material with soil and thermal/photo-degradation.Keywords: polymer, TGA, pollution, landfill, waste, plastic
Procedia PDF Downloads 1292296 Analysis of Anti-Tuberculosis Immune Response Induced in Lungs by Intranasal Immunization with Mycobacterium indicus pranii
Authors: Ananya Gupta, Sangeeta Bhaskar
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Mycobacterium indicus pranii (MIP) is a saprophytic mycobacterium. It is a predecessor of M. avium complex (MAC). Whole genome analysis and growth kinetics studies have placed MIP in between pathogenic and non-pathogenic species. It shares significant antigenic repertoire with M. tuberculosis and have unique immunomodulatory properties. MIP provides better protection than BCG against pulmonary tuberculosis in animal models. Immunization with MIP by aerosol route provides significantly higher protection as compared to immunization by subcutaneous (s.c.) route. However, mechanism behind differential protection has not been studied. In this study, using mice model we have evaluated and compared the M.tb specific immune response in lung compartments (airway lumen / lung interstitium) as well as spleen following MIP immunization via nasal (i.n.) and s.c. route. MIP i.n. vaccination resulted in increased seeding of memory T cells (CD4+ and CD8+ T-cells) in the airway lumen. Frequency of CD4+ T cells expressing Th1 migratory marker (CXCR3) and activation marker (CD69) were also high in airway lumen of MIP i.n. group. Significantly high ex vivo secretion of cytokines- IFN-, IL-12, IL-17 and TNF- from cells of airway luminal spaces provides evidence of antigen-specific lung immune response, besides generating systemic immunity comparable to MIP s.c. group. Analysis of T cell response on per cell basis revealed that antigen specific T-cells of MIP i.n. group were functionally superior as higher percentage of these cells simultaneously secreted IFN-gamma, IL-2 and TNF-alpha cytokines as compared to MIP s.c. group. T-cells secreting more than one of the cytokines simultaneously are believed to have robust effector response and crucial for protection, compared with single cytokine secreting T-cells. Adoptive transfer of airway luminal T-cells from MIP i.n. group into trachea of naive B6 mice revealed that MIP induced CD8 T-cells play crucial role in providing long term protection. Thus the study demonstrates that MIP intranasal vaccination induces M.tb specific memory T-cells in the airway lumen that results in an early and robust recall response against M.tb infection.Keywords: airway lumen, Mycobacterium indicus pranii, Th1 migratory markers, vaccination
Procedia PDF Downloads 1872295 Metabolic Syndrome and Mental Health in Post Traumatic Stress Disorder Patient
Authors: Hassan Shahmiri Barzoki
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Background: Posttraumatic stress disorder (PTSD) is an abnormal physiologic and psychological reaction in person with severe traumatic history. In recent studies, the relationship between PTSD and some other disease apparently unrelated to psychological situations, such as cardiovascular diseases, diabetes, and metabolic syndrome, has been revealed. Thus, the aim of this study was to survey the prevalence of metabolic syndrome and mental health in PTSD patients. Methods: The research design was retrospective cohort study. Subjects were consisted of 142 Iran-Iraq war veterans with PTSD (age: 40-60 years), and the control group was consisted of 153 veterans without PTSD. Data was collected using questionnaires, physical exams and laboratory tests. Results: Prevalence of metabolic syndrome was 45.1%in PTSD group and 17% in control group. In addition, blood pressure, triglyceride and fasting blood sugar in PTSD group were significantly higher than control group (p<0.05). Also, PTSD patients had significant high rates of psychiatric disorders. Conclusion: PTSD patients are more prone to metabolic syndrome and psychiatric disorders than control group.Keywords: mental health, metabolic syndrome, post traumatic stress disorder, patient
Procedia PDF Downloads 932294 Health Sector Budgetary Allocations and Their Implications on Health Service Delivery and Universal Health Coverage in Uganda
Authors: Richard Ssempala, Francis Kintu, Christine K. Tashobya
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Funding for health remains a key constraint facing many developing countries, Uganda inclusive. Uganda’s health sector budget to the national budgetary allocation has stagnated between 8.2% to 10% over the years. Using data collected from different government documents, we sought to establish the implications of the budget allocation over the period (FY2010/11-2018/19) on health services delivery in Uganda to inform policymakers specifically Members of Parliament who are critical in making sectorial allocation on the steps they can adapt to change the terrain of health financing in Uganda. Findings revealed that the contribution of public funding to the health sector is low (15.7%) with private sources (42.6%) and donors contributing much more, with the bulk of private funds, are out of pocket. The study further revealed that low budget allocation had been manifested in inadequate and poorly motivated health workers, essential drug stock-outs that ultimately contribute to poor access to services, catastrophic health expenditures, and high morbidity rates. We recommend for a substantial and sustained increase in the government health budget, optimizing the available resources by addressing wastages, prioritizing health promotion, prevention and finally, institutionalizing the National Health Insurance Scheme.Keywords: budget allocations, universal health coverage, health service delivery, Uganda
Procedia PDF Downloads 1892293 Functional Characterization of Transcriptional Regulator WhiB Proteins of Mycobacterium Tuberculosis
Authors: Sonam Kumari
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Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, possesses a remarkable feature of entering into and emerging from a persistent state. The mechanism by which Mtb switches from the dormant state to the replicative form is still poorly characterized. Proteome studies have given us an insight into the role of certain proteins in giving stupendous virulence to Mtb, but numerous dotsremain unconnected and unaccounted. The WhiB family of proteins is one such protein that is associated with developmental processes in actinomycetes.Mtb has seven such proteins (WhiB1 to WhiB7).WhiB proteins are transcriptional regulators; their conserved C-terminal HTH motif is involved in DNA binding. They regulate various essential genes of Mtbby binding to their promoter DNA. Biophysical Analysis of the effect of DNA binding on WhiB proteins has not yet been appropriately characterized. Interaction with DNA induces conformational changes in the WhiB proteins, confirmed by steady-state fluorescence and circular dichroism spectroscopy. ITC has deduced thermodynamic parameters and the binding affinity of the interaction. Since these transcription factors are highly unstable in vitro, their stability and solubility were enhanced by the co-expression of molecular chaperones. The present study findings help determine the conditions under which the WhiB proteins interact with their interacting partner and the factors that influence their binding affinity. This is crucial in understanding their role in regulating gene expression in Mtbandin targeting WhiB proteins as a drug target to cure TB.Keywords: tuberculosis, WhiB proteins, mycobacterium tuberculosis, nucleic acid binding
Procedia PDF Downloads 1042292 Photocatalytic Degradation of Naproxen in Water under Solar Irradiation over NiFe₂O₄ Nanoparticle System
Authors: H. Boucheloukh, S. Rouissa, N. Aoun, M. Beloucifa, T. Sehili, F. Parrino, V. Loddo
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To optimize water purification and wastewater treatment by heterogeneous photocatalysis, we used NiFe₂O₄ as a catalyst and solar irradiation as a source of energy. In this concept, an organic substance present in many industrial effluents was chosen: naproxen ((S)-6-methoxy-α-methyl-2-naphthaleneacetic acid or 2-(6-methoxynaphthalenyl) propanoic), a non-steroidal anti-inflammatory drug. The main objective of this study is to degrade naproxen by an iron and nickel catalyst, the degradation of this organic pollutant by nickel ferrite has been studied in a heterogeneous aqueous medium, with the study of the various factors influencing photocatalysis such as the concentration of matter and the acidity of the medium. The photocatalytic activity was followed by HPLC-UV andUV-Vis spectroscopy. A first-order kinetic model appropriately fitted the experimental data. The degradation of naproxen was also studied in the presence of H₂O₂ as well as in an aqueous solution. The new hetero-system NiFe₂O₄/oxalic acid is also discussed. The fastest naproxen degradation was obtained with NiFe₂O₄/H₂O₂. In a first-place, we detailed the characteristics of the material NiFe₂O₄, which was synthesized by the sol-gel methods, using various analytical techniques: visible UV spectrophotometry, X-ray diffraction, FTIR, cyclic voltammetry, luminescent discharge optical emission spectroscopy.Keywords: naproxen, nickelate, photocatalysis, oxalic acid
Procedia PDF Downloads 2102291 Preparation and Characterizations of Hydroxyapatite-Sodium Alginate Nanocomposites for Biomedical Applications
Authors: Friday Godwin Okibe, Christian Chinweuba Onoyima, Edith Bolanle Agbaji, Victor Olatunji Ajibola
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Polymer-inorganic nanocomposites are presently impacting diverse areas, specifically in biomedical sciences. In this research, hydroxyapatite-sodium alginate has been prepared, and characterized, with emphasis on the influence of sodium alginate on its characteristics. In situ wet chemical precipitation method was used in the preparation. The prepared nanocomposite was characterized with Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), with image analysis, and X-Ray Diffraction (XRD). The FTIR study shows peaks characteristics of hydroxyapatite and confirmed formation of the nanocomposite via chemical interaction between sodium alginate and hydroxyapatite. Image analysis shows the nanocomposites to be of irregular morphologies which did not show significant change with increasing sodium alginate addition, while particle size decreased with increase in sodium alginate addition (359.46 nm to 109.98 nm). From the XRD data, both the crystallite size and degree of crystallinity also decreased with increasing sodium alginate composition (32.36 nm to 9.47 nm and 72.87% to 1.82% respectively), while the specific surface area and microstrain increased with increasing sodium alginate composition (0.0041 to 0.0139 and 58.99 m²/g to 201.58 m²/g respectively). The results show that the formulation with 50%wt of sodium alginate (HASA-50%wt), possess exceptional characteristics for biomedical applications such as drug delivery.Keywords: nanocomposite, sodium alginate, hydroxyapatite, biomedical, FTIR, XRD, SEM
Procedia PDF Downloads 3302290 Quality of Life of Patients on Oral Antiplatelet Therapy in Outpatient Cardiac Department Dr. Hasan Sadikin Central General Hospital Bandung
Authors: Andhiani Sharfina Arnellya, Mochammad Indra Permana, Dika Pramita Destiani, Ellin Febrina
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Health Research Data, Ministry of Health of Indonesia in 2007, showed coronary heart disease (CHD) or coronary artery disease (CAD) was the third leading cause of death in Indonesia after hypertension and stroke with 7.2% incidence rate. Antiplatelet is one of the important therapy in management of patients with CHD. In addition to therapeutic effect on patients, quality of life is one aspect of another assessment to see the success of antiplatelet therapy. The purpose of this study was to determine the quality of life of patients on oral antiplatelet therapy in outpatient cardiac department Dr. Hasan Sadikin central general hospital, Bandung, Indonesia. This research is a cross sectional by collecting data through quality of life questionnaire of patients which performed prospectively as primary data and secondary data from medical record of patients. The results of this study showed that 54.3% of patients had a good quality of life, 45% had a moderate quality of life, and 0.7% had a poor quality of life. There are no significant differences in quality of life-based on age, gender, diagnosis, and duration of drug use.Keywords: antiplatelet, quality of life, coronary artery disease, coronary heart disease
Procedia PDF Downloads 3242289 Developing a Culturally Acceptable End of Life Survey (the VOICES-ESRD/Thai Questionnaire) for Evaluation Health Services Provision of Older Persons with End-Stage Renal Disease (ESRD) in Thailand
Authors: W. Pungchompoo, A. Richardson, L. Brindle
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Background: The developing of a culturally acceptable end of life survey (the VOICES-ESRD/Thai questionnaire) is an essential instrument for evaluation health services provision of older persons with ESRD in Thailand. The focus of the questionnaire was on symptoms, symptom control and the health care needs of older people with ESRD who are managed without dialysis. Objective: The objective of this study was to develop and adapt VOICES to make it suitable for use in a population survey in Thailand. Methods: The mixed methods exploratory sequential design was focussed on modifying an instrument. Data collection: A cognitive interviewing technique was implemented, using two cycles of data collection with a sample of 10 bereaved carers and a prototype of the Thai VOICES questionnaire. Qualitative study was used to modify the developing a culturally acceptable end of life survey (the VOICES-ESRD/Thai questionnaire). Data analysis: The data were analysed by using content analysis. Results: The revisions to the prototype questionnaire were made. The results were used to adapt the VOICES questionnaire for use in a population-based survey with older ESRD patients in Thailand. Conclusions: A culturally specific questionnaire was generated during this second phase and issues with questionnaire design were rectified.Keywords: VOICES-ESRD/Thai questionnaire, cognitive interviewing, end of life survey, health services provision, older persons with ESRD
Procedia PDF Downloads 2862288 Smartphone Application for Social Inclusion of Deaf Parents and Children About Sphincter Training
Authors: Júlia Alarcon Pinto, Carlos João Schaffhausser, Gustavo Alarcon Pinto
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Introduction: The deaf people in Brazil communicate through the Brazilian Sign Language (LIBRAS), which is restricted to this minority and people that received training. However, there is a lack of prepared professionals in the health system to deal with these patients. Therefore, effective communication, health education, quality of support and assistance are compromised. It is of utmost importance to develop measures that ensure the inclusion of deaf parents and children since there are frequent doubts about sphincter training and an absence of tools to promote effective communication between doctors and their patients. Objective: Use of an efficient, rapid and cheap communication method to promote social inclusion and patient education of deaf parents and children during pediatrics appointments. Results; The application demonstrates how to express phrases and symptoms within seconds and this allows patients to fully understand the information provided during the appointment and are capable to evaluate the signs of readiness, learn the correct approaches with the child, what are the adequate instruments, possible obstacles and the importance to execute medical orientations in order to achieve success in the process. Consequently, patients feel more satisfied, secured and embraced by professionals in the health system care. Conclusion: It is of utmost importance to use efficient and cheap methods that support patient care and education in order to promote health and social inclusion.Keywords: application, deaf patients, social inclusion, sphincter training
Procedia PDF Downloads 1192287 Whole Coding Genome Inter-Clade Comparison to Predict Global Cancer-Protecting Variants
Authors: Lamis Naddaf, Yuval Tabach
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In this research, we identified the missense genetic variants that have the potential to enhance resistance against cancer. Such field has not been widely explored, as researchers tend to investigate mutations that cause diseases, in response to the suffering of patients, rather than those mutations that protect from them. In conjunction with the genomic revolution, and the advances in genetic engineering and synthetic biology, identifying the protective variants will increase the power of genotype-phenotype predictions and can have significant implications on improved risk estimation, diagnostics, prognosis and even for personalized therapy and drug discovery. To approach our goal, we systematically investigated the sites of the coding genomes and picked up the alleles that showed a correlation with the species’ cancer resistance. We predicted 250 protecting variants (PVs) with a 0.01 false discovery rate and more than 20 thousand PVs with a 0.25 false discovery rate. Cancer resistance in Mammals and reptiles was significantly predicted by the number of PVs a species has. Moreover, Genes enriched with the protecting variants are enriched in pathways relevant to tumor suppression like pathways of Hedgehog signaling and silencing, which its improper activation is associated with the most common form of cancer malignancy. We also showed that the PVs are more abundant in healthy people compared to cancer patients within different human races.Keywords: comparative genomics, machine learning, cancer resistance, cancer-protecting alleles
Procedia PDF Downloads 972286 Identifying the Effects of the COVID-19 Pandemic on Syrian and Congolese Refugees’ Health and Economic Access in Central Pennsylvania
Authors: Mariam Shalaby, Kayla Krause, Raisha Ismail, Daniel George
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Introduction: The Pennsylvania State College of Medicine Refugee Initiative is a student-run organization that works with eleven Syrian and Congolese refugee families. Since 2016, it has used grant funding to make weekly produce purchases at a local market, provide tutoring services, and develop trusting relationships. This case study explains how the Refugee Initiative shifted focus to face new challenges due to the COVID-19 pandemic in 2020. Methodology: When refugees who had previously attained stability found themselves unable to pay the bills, the organization shifted focus from food security to direct assistance such as applying for unemployment compensation since many had recently lost jobs. When refugee families additionally struggled to access hygiene supplies, funding was redirected to purchase them. Funds were also raised from the community to provide financial relief from unpaid rent and bills. Findings: Systemic challenges were encountered in navigating federal/state unemployment and social welfare systems, and there was a conspicuous absence of affordable, language-accessible assistance that could help refugees. Finally, as struggling public schools failed to maintain adequate English as a Second Language (ESL) education, the group’s tutoring services were hindered by social distancing and inconsistent access to distance-learning platforms. Conclusion: Ultimately, the pandemic highlighted that a charity-based arrangement is helpful but not sustainable, and challenges persist for refugee families. Based on the Refugee Initiative's experiences over the past year of the COVID-19 pandemic, several needs must be addressed to aid refugee families at this time, including: increased access to affordable and language-accessible social services, educational resources, and simpler options for grant-based financial assistance. Interventions to increase these resources will aid refugee families in need in Central Pennsylvania and internationallyKeywords: COVID-19, health, pandemic, refugees
Procedia PDF Downloads 1292285 Detection of Muscle Swelling Using the Cnts-Based Poc Wearable Strain Sensor
Authors: Nadeem Qaiser, Sherjeel Munsif Khan, Muhammad Mustafa Hussian, Vincent Tung
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One of the emerging fields in the detection of chronic diseases is based on the point-of-care (POC) early monitoring of the symptoms and thus provides a state-of-the-art personalized healthcare system. Nowadays, wearable and flexible sensors are being used for analyzing sweat, glucose, blood pressure, and other skin conditions. However, localized jaw-bone swelling called parotid-swelling caused by some viruses has never been tracked before. To track physical motion or deformations, strain sensors, especially piezoresistive ones, are widely used. This work, for the first time, reports carbon nanotubes (CNTs)-based piezoresistive sensing patch that is highly flexible and stretchable and can record muscle deformations in real-time. The developed patch offers an excellent gauge factor for in-plane stretching and spatial expansion with low hysteresis. To calibrate the volumetric muscle expansion, we fabricated the pneumatic actuator that experienced volumetric expansion and thus redefined the gauge factor. Moreover, we employ a Bluetooth-low-energy system that can send information about muscle activity in real-time to a smartphone app. We utilized COMSOL calculations to reveal the mechanical robustness of the patch. The experiments showed the sensing patch's greater cyclability, making it a patch for personal healthcare and an excellent choice for monitoring the real-time POC monitoring of the human muscle swelling.Keywords: piezoresistive strain sensor, FEM simulations, CNTs sensor, flexible
Procedia PDF Downloads 882284 The Biology of Persister Cells and Antibiotic Resistance
Authors: Zikora K. G. Anyaegbunam, Annabel A. Nnawuihe, Ngozi J. Anyaegbunam, Emmanuel A. Eze
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The discovery and production of new antibiotics is unavoidable in the fight against drug-resistant bacteria. However, this is only part of the problem; we have never really had medications that could completely eradicate an infection. All pathogens create a limited number of dormant persister cells that are resistant to antibiotic treatment. When the concentration of antibiotics decreases, surviving persisters repopulate the population, resulting in a recurrent chronic infection. Bacterial populations have an alternative survival strategy to withstand harsh conditions or antibiotic exposure, in addition to the well-known methods of antibiotic resistance and biofilm formation. Persister cells are a limited subset of transiently antibiotic-tolerant phenotypic variations capable of surviving high-dose antibiotic therapy. Persisters that flip back to a normal phenotype can restart growth when antibiotic pressure drops, assuring the bacterial population's survival. Persister cells have been found in every major pathogen, and they play a role in antibiotic tolerance in biofilms as well as the recalcitrance of chronic infections. Persister cells has been implicated to play a role in the establishment of antibiotic resistance, according to growing research. Thusthe need to basically elucidate the biology of persisters and how they are linked to antibiotic resistance, and as well it's link to diseases.Keywords: persister cells, phenotypic variations, repopulation, mobile genetic transfers, antibiotic resistance
Procedia PDF Downloads 2092283 Determination of Verapamil Hydrochloride in Tablets and Injection Solutions With the Verapamil-Selective Electrode and Possibilities of Application in Pharmaceutical Analysis
Authors: Faisal A. Salih
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Verapamil hydrochloride (Ver) is a drug used in medicine for arrythmia, angina and hypertension as a calcium channel blocker. For the quantitative determination of Ver in dosage forms, the HPLC method is most often used. A convenient alternative to the chromatographic method is potentiometry using a Verselective electrode, which does not require expensive equipment, can be used without separation from the matrix components, which significantly reduces the analysis time, and does not use toxic organic solvents, being a "green", "environmentally friendly" technique. It has been established in this study that the rational choice of the membrane plasticizer and the preconditioning and measurement algorithms, which prevent nonexchangeable extraction of Ver into the membrane phase, makes it possible to achieve excellent analytical characteristics of Ver-selective electrodes based on commercially available components. In particular, an electrode with the following membrane composition: PVC (32.8 wt %), ortho-nitrophenyloctyl ether (66.6 wt %), and tetrakis-4-chlorophenylborate (0.6 wt % or 0.01 M) have the lower detection limit 4 × 10−8 M and potential reproducibility 0.15–0.22 mV. Both direct potentiometry (DP) and potentiometric titration (PT) methods can be used for the determination of Ver in tablets and injection solutions. Masses of Ver per average tablet weight determined by the methods of DP and PT for the same set of 10 tablets were (80.4±0.2 and80.7±0.2) mg, respectively. The masses of Ver in solutions for injection, determined by DP for two ampoules from one set, were (5.00±0.015 and 5.004±0.006) mg. In all cases, good reproducibility and excellent correspondence with the declared quantities were observed.Keywords: verapamil, potentiometry, ion-selective electrode, pharmaceutical analysis
Procedia PDF Downloads 882282 Early Depression Detection for Young Adults with a Psychiatric and AI Interdisciplinary Multimodal Framework
Authors: Raymond Xu, Ashley Hua, Andrew Wang, Yuru Lin
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During COVID-19, the depression rate has increased dramatically. Young adults are most vulnerable to the mental health effects of the pandemic. Lower-income families have a higher ratio to be diagnosed with depression than the general population, but less access to clinics. This research aims to achieve early depression detection at low cost, large scale, and high accuracy with an interdisciplinary approach by incorporating clinical practices defined by American Psychiatric Association (APA) as well as multimodal AI framework. The proposed approach detected the nine depression symptoms with Natural Language Processing sentiment analysis and a symptom-based Lexicon uniquely designed for young adults. The experiments were conducted on the multimedia survey results from adolescents and young adults and unbiased Twitter communications. The result was further aggregated with the facial emotional cues analyzed by the Convolutional Neural Network on the multimedia survey videos. Five experiments each conducted on 10k data entries reached consistent results with an average accuracy of 88.31%, higher than the existing natural language analysis models. This approach can reach 300+ million daily active Twitter users and is highly accessible by low-income populations to promote early depression detection to raise awareness in adolescents and young adults and reveal complementary cues to assist clinical depression diagnosis.Keywords: artificial intelligence, COVID-19, depression detection, psychiatric disorder
Procedia PDF Downloads 1312281 Assessment of Work Postures and Prevalence of Musculoskeletal Disorders among Diamond Polishers in Botswana: A Case Study
Authors: Oanthata Jester Sealetsa, Richie Moalosi
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Musculoskeletal Disorders (MSDs) are reported to be amongst the leading contributing factors of low productivity in many industries across the world, and the most affected being New Emerging Economies (NEC) such as Botswana. This is due to lack of expertise and resources to deal with existing ergonomics challenges. This study was aimed to evaluate occupational postures and the prevalence of musculoskeletal disorders among diamond polishers in a diamond company in Botswana. A case study was conducted with about 106 diamond polishers in Gaborone, Botswana. A case study was chosen because it can investigate and explore an issue thoroughly and deeply, and record behaviour over time so changes in behaviour can be identified. The Corlett and Bishop Body Map was used to determine frequency of MSDs symptoms in different body parts of the workers. This was then followed by the use of the Rapid Entire Body Assessment (REBA) to evaluate the occupational postural risks of MSDs. Descriptive statistics, chi square, and logistic regression were used for data analysis. The results of the study reveal that workers experienced pain in the upper back, lower back, shoulders, neck, and wrists with the most pain reported in the upper back (44.6%) and lower back (44.2%). However, the mean REBA score of 6.07 suggests that sawing, bruiting and polishing were the most dangerous processes in diamond polishing. The study recommends that a redesign of the diamond polishing workstations is necessary to accommodate the anthropometry characteristic of Batswana (people from Botswana) to prevent the development of MSDs.Keywords: assessment, Botswana, diamond polishing, ergonomics, musculoskeletal disorders, occupational postural risks
Procedia PDF Downloads 1802280 Exploring the Illness Experience of Fibromyalgia Patients Using Identity Boxes
Authors: Nicole Brown
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This study considers the illness experience of fibromyalgia patients by using identity boxes. The results improve health care professionals' understanding of patient experiences. Additionally, the concept of the identity boxes may offer a practical solution for helping patients accept the diagnosis of fibromyalgia. Fibromyalgia research traditionally refers to pain experiences and relies on questionnaires, surveys, interviews and some narrative analysis. However, due to the variability in symptoms, symptom levels, and locations, these methods may not be best suited to provide an insight into the patient experience. On the other hand, lengthy interview processes are not easily accessible for sufferers of fibromyalgia. In addition to timelines and diary extracts, this study uses identity boxes as its main data collection method. Participants are asked to find items in response to specific questions and to arrange them in their box. The objects represent the patients' experiences holistically. Participants provide photographs of their identity box at each stage of the process and explain their chosen items. The photographs of the identity boxes and the patients' explanations of their objects and their boxes are subjected to interpretative phenomenological analysis. Despite the unique forms of the completed boxes, common experiences are described: the need for comfort, the role of spirituality and the impact of fibromyalgia on everyday life, that it plays a significant role but those patients are determined not to let it rule their lives. The work with the identity boxes has shown beneficial impact due to the reflective nature involved in the tasks. Further investigations will be needed to identify the long-term impact of identity work using such boxes.Keywords: biographical disruption, fibromyalgia, illness experience, illness narrative
Procedia PDF Downloads 2352279 Examination of Contaminations in Fabricated Cadmium Selenide Quantum Dots Using Laser Induced Plasma Spectroscopy
Authors: Walid Tawfik, W. Askam Farooq, Sultan F. Alqhtani
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Quantum dots (QDots) are nanometer-sized crystals, less than 10 nm, comprise a semiconductor or metallic materials and contain from 100 - 100,000 atoms in each crystal. QDots play an important role in many applications; light emitting devices (LEDs), solar cells, drug delivery, and optical computers. In the current research, a fundamental wavelength of Nd:YAG laser was applied to analyse the impurities in homemade cadmium selenide (CdSe) QDots through laser-induced plasma (LIPS) technique. The CdSe QDots were fabricated by using hot-solution decomposition method where a mixture of Cd precursor and trioctylphosphine oxide (TOPO) is prepared at concentrations of TOPO under controlled temperatures 200-350ºC. By applying laser energy of 15 mJ, at frequency 10 Hz, and delay time 500 ns, LIPS spectra of CdSe QDots samples were observed. The qualitative LIPS analysis for CdSe QDs revealed that the sample contains Cd, Te, Se, H, P, Ar, O, Ni, C, Al and He impurities. These observed results gave precise details of the impurities present in the QDs sample. These impurities are important for future work at which controlling the impurity contents in the QDs samples may improve the physical, optical and electrical properties of the QDs used for solar cell application.Keywords: cadmium selenide, TOPO, LIPS spectroscopy, quantum dots
Procedia PDF Downloads 1432278 Experimental and Finite Element Analysis of Large Deformation Characteristics of Magnetic Responsive Hydrogel Nanocomposites Membranes
Authors: Mallikarjunachari Gangapuram
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Stimuli-responsive hydrogel nanocomposite membranes are gaining significant attention these days due to their potential applications in various engineering fields. For example, sensors, soft actuators, drug delivery, remote controlled therapy, water treatment, shape morphing, and magnetic refrigeration are few advanced applications of hydrogel nanocomposite membranes. In this work, hydrogel nanocomposite membranes are synthesized by embedding nanometer-sized (diameter - 300 nm) Fe₃O₄ magnetic particles into the polyvinyl alcohol (PVA) polymer. To understand the large deformation characteristics of these membranes, a well-known experimental method ball indentation technique is used. Different designing parameters such as membrane thickness, the concentration of magnetic particles and ball diameter on the viscoelastic properties are studied. All the experiments are carried out without and with a static magnetic field. Finite element simulations are carried out to validate the experimental results. It is observed, the creep response decreases and Young’s modulus increases as the thickness and concentration of magnetic particles increases. Image analysis revealed the hydrogel membranes are undergone global deformation for ball diameter 18 mm and local deformation when the diameter decreases from 18 mm to 0.5 mm.Keywords: ball indentation, hydrogel membranes, nanocomposites, Young's modulus
Procedia PDF Downloads 1282277 Additional Usage of Remdesivir with the Standard of Care in Patients with Moderate And Severe COVID-19: A Tertiary Hospital’s Experience
Authors: Pugazhenthan Thangaraju
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Background: Since the pandemic began, more than millions of people have become infected with COVID-19. Globally, researchers are working for safe and effective treatments for this disease. Remdesivir is a drug that has been approved for the treatment of COVID-19. Many aspects are still being considered that may influence the future use of remdesivir. Aim: To assess the safety and efficacy of Remdesivir in hospitalized adult patients diagnosed with moderate and severe COVID-19. Methods: It was a record-based retrospective cohort study conducted between April 1st, 2020 and June 30th, 2021 at the tertiary care teaching hospital All India Institutes of Medical Sciences (AIIMS), Raipur Results: There were a total of 10,559 medical records of COVID-19 patients of which 1034 records were included in this study. Overall, irrespective of the survival status, there was statistical significant difference observed between the WHO score at the time of admission and discharge. Clinical improvement among the survivors was found to be statistically significant. Conclusion: Remdesivir's potential efficacy against coronaviruses has so far been limited to in vitro studies and animal models. However, information about COVID-19 is rapidly expanding. Several clinical trials for the treatment of COVID-19 with remdesivir are now underway. However, the findings of this study support remdesivir as a promising agent in the fight against SARS-CoV-2.Keywords: Remdesivir, COVID-19, SARS-CoV-2, antiviral, RNA-dependent RNA polymerase, viral pneumonia
Procedia PDF Downloads 652276 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients
Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas
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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib
Procedia PDF Downloads 2012275 Acute Myeloid Leukemia Relapse in an a Rare form After Treating his Tuberculosis TB
Authors: Sheikha Turki Alketbi
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Objectives: 1. Documenting the spontaneous resolution of AML following the initiation of anti-TB therapy. 2. Presenting an uncommon type of relapse in Acute Myeloid Leukemia. 3. Highlighting the role of immune markers in the diagnosis of Leukemia cutis. 4. Exploring and highlighting the possibility of skin relapse as the exclusive manifestation, even when skin involvement is known secondary manifestation in AML. Background: Spontaneous remission of Acute Myeloid Leukemia (AML) is a rare phenomenon that has only been reported in some case reports, usually following severe infections. Some studies have described the occurrence of tuberculosis (TB) infection with AML, usually after starting chemotherapy. Spontaneous resolution of AML after starting anti TB therapy (ATT), without starting chemotherapy has never been described in the literature. Moreover, Leukemia cutis is another rare skin manifestation of Acute Myeloid Leukemia as a result of infiltration of the skin or subcutaneous tissue by leukemic cells, in which can present during, precedes, after or independently of systemic leukemia. Methods: Here, we present a case of a 13-year-old male who presented with fever, weight loss, lethargy, epistaxis, bruising and dry cough and was later diagnosed with AML. Before initiating leukemia treatment, the patient was tested for TB and was found to have active TB infection. His leukemia treatment was postponed to clear the TB infection and he was commenced on ATT. Two months later, repeat blood film and bone marrow biopsy showed resolution of his AML. The patient remained in remission for 1 month, after which he presented with symmetrical blue purple well-defined round indurated plaques on the chest and thighs. Our differentials were leukemia cutis and Kaposi sarcoma. Results: Skin Biopsy with immune markers done, showed a picture of Acute Myeloid Leukemia. Immunohistochemistry (IHC) showed neoplastic cells diffusely and strongly positive for LCA, CD2, CD31, MPO, CD117, Lysozymes and TDT, and moderately positive for CD34, CD99, CD43 and CD6 And patchy for CD68. Ki67 showed 60% proliferation index. They were negative for the remaining markers. This suggested acute myeloid leukemia (AML). Conclusion: In summary, we present a rare case of TB with AML that resolved after treatment of TB with ATT but relapsed later as leukemia cutis. While skin involvement might occur as a secondary manifestation of AML, Skin relapse could be the only one.Keywords: Leukemia cutis, Leukemia relapse, Acute Myeloid Leukemia, spontaneous resolution of AML
Procedia PDF Downloads 602274 Enhancing the Sensitivity of Antigen Based Sandwich ELISA for COVID-19 Diagnosis in Saliva Using Gold Conjugated Nanobodies
Authors: Manal Kamel, Sara Maher
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Development of sensitive non-invasive tests for detection of SARS-CoV-2 antigens is imperative to manage the extent of infection throughout the population, yet, it is still challenging. Here, we designed and optimized a sandwich enzyme-linked immunosorbent assay (ELISA) for SARS-CoV-2 S1 antigen detection in saliva. Both saliva samples and nasopharyngeal swapswere collected from 170 PCR-confirmed positive and negative cases. Gold nanoparticles (AuNPs) were conjugated with S1protein receptor binding domain (RBD) nanobodies. Recombinant S1 monoclonal antibodies (S1mAb) as primery antibody and gold conjugated nanobodies as secondary antibody were employed in sandwich ELISA. Our developed system were optimized to achieve 87.5 % sensitivity and 100% specificity for saliva samples compared to 89 % and 100% for nasopharyngeal swaps, respectively. This means that saliva could be a suitable replacement for nasopharyngeal swaps No cross reaction was detected with other corona virus antigens. These results revealed that our developed ELISAcould be establishedas a new, reliable, sensitive, and non-invasive test for diagnosis of SARS-CoV-2 infection, using the easily collected saliva samples.Keywords: COVID 19, diagnosis, ELISA, nanobodies
Procedia PDF Downloads 1342273 Clinical Implication of Hyper-Intense Signal Thyroid Incidentaloma on Time of Flight Magnetic Resonance Angiography
Authors: Inseon Ryoo, Soo Chin Kim, Hyena Jung, Sangil Suh
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Objectives: The purpose of this study is to evaluate the clinical significance of hyper-intense signal thyroid incidentalomas on the time of flight magnetic resonance angiography (TOF-MRA) using correlation study with ultrasound (US). Methods: We retrospectively reviewed 3,505 non-contrast TOF-MRA performed at an institution between September 2014 and May 2017. Two radiologists correlated the thyroid incidentalomas detected on TOF-MRA with US features which was obtained within three months interval between MRA and US examinations in consensus method. Results: The prevalence of hyper-intense signal thyroid nodules incidentally detected on TOF-MRA was 1.2% (43/3505). Among them, 35 people (81.4%) underwent US examinations, and total 45 hyper-intense signal thyroid nodules were detected on US exams. Of these 45 nodules, 35 nodules (72.9%) were categorized as benign (K-TIRADS category 2) on US exams. Fine needle aspiration was performed on 9 nodules according to the indications recommended by Korean Society of Thyroid Radiology. All except one high-suspicious thyroid nodule were confirmed as benign (Bethesda 2) on cytologic exams. One high-suspicious nodule on US showed a non-diagnostic result (Bethesda 1) on cytologic exam. However, this nodule collapsed after aspiration of thick colloid material. Conclusions: Our study showed that the most hyper-intense signal thyroid nodules detected on TOF-MRA were benign. Therefore, if a hyper-intense signal incidentaloma is found on TOF-MRA, further evaluation, especially invasive biopsy of the nodules could be suspended unless the patient had other symptoms or clinical factors suggesting the need for further evaluation.Keywords: incidentaloma, thyroid nodule, TOF MR angiography, ultrasound
Procedia PDF Downloads 1672272 PD-L1 Expression in Papillary Thyroid Carcinoma Arising Denovo or on Top of Autoimmune Thyroiditis
Authors: Dalia M. Abouelfadl, Noha N. Yassen, Marwa E. Shabana
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Background: The evolution of immune therapy motivated many to study the relation between immune response and progression of cancer. Little is known about expression of PD-L1 (a newly evolving immunotherapeutic drug) in papillary thyroid carcinoma (PTC) arising de-novo and PTC arising on top of autoimmune thyroiditis (Hashimoto's (HT) and lymphocytic thyroiditis (LT)). The aim of this work is to study the alteration of expression of PD-L1 in PTCs arising from de-novo or on top of HT OR LT using immunohistochemistry and image analyser system. Method: 100 paraffin blocks for PTC cases were collected retrospectively for staining using PD-L1 rabbit monoclonal antibody (BIOCARE-ACI 3171 A, C). The antibody expression is measured digitally using Image Analyzer Leica Qwin 3000, and the membranous and cytoplasmic expression of PD-L1 in tumor cells was considered positive. The results were correlated with tumor grade, size, and LN status. Results: The study samples consisted of 41 cases of PTC arising De novo, 36 cases on top of HT, and 23 on top of LT. Expression of PD-L1 was highest among the PTC-HL group (25 case-69%) followed by PTC-TL group (14 case-60.8%) then de-novo PTC (19 case-46%) with P Value < 0.05. PD-L1 expression correlated with nodal metastasis and was not relevant to tumor size or grade. Conclusion: The severity of the immune response in tumor microenvironment directly influences PTC prognosis. The anti PD-L1 Ab can be a very successful therapeutic agent for PTC arising on top of HT.Keywords: carcinoma, Hashimoto's, lymphocytic, papillary, PD-L1, thyroiditis
Procedia PDF Downloads 1792271 Dietary Nutrient Consumption Patterns by the Pregnant Mother in Dhaka City, Bangladesh
Authors: Kazi Muhammad Rezaul Karim, Tasmia Tasnim
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Introduction: Pregnancy is a condition of higher nutrient requirement but in developing countries like Bangladesh most of the pregnant women can not meet their nutrient requirement and sometimes they are neglected in the family. The purpose of the study was to assess the nutritional status and dietary nutrient intake by the pregnant women, in Dhaka city, Bangladesh. Methods: The study population comprised of pregnant women from urban or semi-urban, aged between 18 to 35 and free of pregnancy related complication and other diseases. Under a cross-sectional design, 30 healthy non-pregnant as well as 130 pregnant women, at 3 different trimesters of pregnancy were assessed. A questionnaire was developed to obtain demographic, socio-economic, anthropometric, drug and medical history. Three day consecutive 24-hour food recalls were used to assess food intake and then converted to nutrient intake. Results: The average BMI of the nonpregnant women was 22.89 ± 3.4 kg/m2 and that of pregnant women was 23.52 ± 3.71 kg/m2. The mean dietary nutrient intake of dietary fiber, calorie, protein, fat, carbohydrate, calcium, iron, thiamine, riboflavin, vitamin C, Vitamin A, folate, vitamin B6 and Vitamin B12 of the pregnant mothers were 4.38 g, 1619 kcal, 60.05 g, 30.38 g, 268.79 g, 537.21 mg, 21.53 mg, 1.15 mg, 0.94 mg, 97.36 mg, 647.6 µg, 153.93 µg, 1.41 mg and 4.09 µg respectively. Most of pregnant women (more than 90%) can not meet their energy, calcium and folate requirements. Conclusion: Most of the pregnant mother in Bangladesh can not meet their dietary requirements during pregnancy.Keywords: pregnancy, dietary nutrient, nutritional status, BMI
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