Search results for: hereditary breast-ovarian cancer syndrome
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2910

Search results for: hereditary breast-ovarian cancer syndrome

690 Effects of Pressure and Temperature on the Extraction of Benzyl Isothiocyanate by Supercritical Fluids from Tropaeolum majus L. Leaves

Authors: Espinoza S. Clara, Gamarra Q. Flor, Marianela F. Ramos Quispe S. Miguel, Flores R. Omar

Abstract:

Tropaeolum majus L. is a native plant to South and Central America, used since ancient times by our ancestors to combat different diseases. Glucotropaeolonin is one of its main components, which when hydrolyzed, forms benzyl isothiocyanate (BIT) that promotes cellular apoptosis (programmed cell death in cancer cells). Therefore, the present research aims to evaluate the effect of the pressure and temperature of BIT extraction by supercritical CO2 from Tropaeolum majus L. The extraction was carried out in a supercritical fluid extractor equipment Speed SFE BASIC Brand: Poly science, the leaves of Tropaeolum majus L. were ground for one hour and lyophilized until obtaining a humidity of 6%. The extraction with supercritical CO2 was carried out with pressures of 200 bar and 300 bar, temperatures of 50°C, 60°C and 70°C, obtained by the conjugation of these six treatments. BIT was identified by thin layer chromatography using 98% BIT as the standard, and as the mobile phase hexane: dichloromethane (4:2). Subsequently, BIT quantification was performed by high performance liquid chromatography (HPLC). The highest yield of oleoresin by supercritical CO2 extraction was obtained pressure 300 bar and temperature at 60°C; and the higher content of BIT at pressure 200 bar and 70°C for 30 minutes to obtain 113.615 ± 0.03 mg BIT/100 g dry matter was obtained.

Keywords: solvent extraction, Tropaeolum majus L., supercritical fluids, benzyl isothiocyanate

Procedia PDF Downloads 438
689 Controlled Size Synthesis of ZnO and PEG-ZnO NPs and Their Biological Evaluation

Authors: Mahnoor Khan, Bashir Ahmad, Khizar Hayat, Saad Ahmad Khan, Laiba Ahmad, Shumaila Bashir, Abid Ali Khan

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The objective of this study was to synthesize the smallest possible size of ZnO NPs using a modified wet chemical synthesis method and to prepare core shell using polyethylene glycol (PEG) as shell material. Advanced and sophisticated techniques were used to confirm the synthesis, size, and shape of these NPs. Rounded, clustered NPs of size 5.343 nm were formed. Both the plain and core shell NPs were tested against MDR bacteria (E. cloacae, E. amnigenus, Shigella, S. odorifacae, Citrobacter, and E. coli). Both of the NPs showed excellent antibacterial properties, whereas E. cloacae showed maximum zone of inhibition of 16 mm, 27 mm, and 32 mm for 500 μg/ml, 1000 μg/ml, and 1500 μg/ml, respectively for plain ZnO NPs and 18 mm, 28 mm and 35 mm for 500 μg/ml, 1000 μg/ml and 1500 μg/ml for core shell NPs. These NPs were also biocompatible on human red blood cells showing little hemolysis of only 4% for 70 μg/ml for plain NPs and 1.5% for 70 μg/ml for core shell NPs. Core shell NPs were highly biocompatible because of the PEG. Their therapeutic effect as photosensitizers in photodynamic therapy (PDT) for cancer treatment was also monitored. The cytotoxicity of ZnO and PEG-ZnO was evaluated using MTT assay. Our results demonstrated that these NPs could generate ROS inside tumor cells after irradiation which in turn initiates an apoptotic pathway leading to cell death hence proving to be an effective candidate for PDT.

Keywords: ZnO, hemolysis, cytotoxiciy assay, photodynamic therapy, antibacterial

Procedia PDF Downloads 140
688 Sheathless, Viscoelastic Circulating Tumor Cell Separation Using Closed-Loop Microfluidics

Authors: Hyunjung Lim, Jeonghun Nam, Hyuk Choi

Abstract:

High-throughput separation is an essential technique for cancer research and diagnosis. Here, we propose a viscoelastic microfluidic device for sheathless, high-throughput isolation of circulating tumor cells (CTCs) from white blood cells. Here, we demonstrate a viscoelastic method for separation and concentration of CTCs using closed-loop microfluidics. Our device is a rectangular straight channel with a low aspect ratio. Also, to achieve high-efficiency, high-throughput processing, we used a polymer solution with low viscosity. At the inlet, CTCs and white blood cells (WBCs) were randomly injected into the microchannel. Due to the viscoelasticity-induced lateral migration to the equilibrium positions, large CTCs could be collected from the side outlet while small WBCs were removed at the center outlet. By recirculating the collected CTCs from the side outlet back to the sample reservoir, continuous separation and concentration of CTCs could be achieved with high separation efficiency (~ 99%). We believe that our device has the potential to be applied in resource-limited clinical settings.

Keywords: circulating tumor cell, closed-loop microfluidics, concentration, separation, viscoelastic fluid

Procedia PDF Downloads 153
687 Comparison of Maternal and Perinatal Outcomes of Obstetric Population Diagnosed with Covid-19 in Reference to Influenza A/H1N1: A Systematic Review and Meta-Analysis

Authors: Maria Vargas Hernandez, Jose Rojas Suarez, Carmelo Dueñas Castell, Sandra Contreras, Camilo Bello, Diana Borre, Walter Anichiarico, Harold Vasquez, Eduard Perez, Jose Santacruz

Abstract:

In the last two decades, there have been outbreaks of emerging infectious diseases, with an impact on both the general population and the obstetric population. These infections, which affect the general population, pose a high risk for adverse maternal and perinatal outcomes, taking into account that physiological and immunological changes that occur during pregnancy can increase their risk or severity. Among these, the pandemics of viral infections, Influenza A/H1N1 and SARS-CoV-2/COVID-19, stand out. In 2009, Influenza A/H1N1 infection (H1N1 2009pdm) affected approximately 3,110 obstetric patients, with data reported from 29 countries, including 1,625 (52.3%) cases that were hospitalized, 378 (23.3%) admissions to ICU and 130 (8%) deaths; and since the end of 2019, the Severe Acute Respiratory Syndrome - 2 (SARS-CoV-2) has been identified, causing the COVID-19 pandemic, with global mortality that is around 2-4% for the general population, and higher mortality in patients requiring admission to the intensive care unit. Its impact on the obstetric population is still unknown. Objectives: To evaluate the impact on maternal and perinatal outcomes of COVID-19 infection in reference to influenza A/H1N1 infection in the obstetric population. Methodology: Systematic review of the literature and meta-analysis. Results: Mortality from maternal infection with influenza A/H1N1 appears to be higher (8%) than mortality due to maternal infection with COVID-19 (3%). The rates of ICU admission, hospitalization, the requirement for invasive mechanical ventilation, and fetal death also appear to be higher in the maternal population with A/H1N1 infection, in reference to the maternal population with COVID-19 infection. Within perinatal outcomes, the admission to the neonatal ICU appears to be higher in the infants born to mothers with COVID-19 infection (28% vs. 15% for COVID-19 and A/H1N1, respectively). Conclusion: A/H1N1 infection in the obstetric population seems to be associated with a higher proportion of adverse outcomes in relation to COVID-19 infection. The actual impact of maternal influenza A/H1N1 infection on perinatal outcomes is unknown. More COVID-19 studies are needed to understand the impact of maternal infection on perinatal outcomes in this population.

Keywords: A/H1N1, COVID-19, maternal outcomes, perinatal outcomes

Procedia PDF Downloads 224
686 Health Impacts of Size Segregated Particulate Matter and Black Carbon in Industrial Area of Firozabad

Authors: Kalpana Rajouriya, Ajay Taneja

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Particulates are ubiquitous in the air environment and cause serious threats to human beings, such as lung cancer, Chronic obstructive pulmonary disease (COPD), and Asthma. Particulates mainly arise from industrial effluent, vehicular emission, and other anthropogenic activities. In the glass industrial city Firozabad, real-time monitoring (mass as well as a number) of size segregated Particulate Matter (PM) and black carbon was done by Aerosol Black Carbon Detector (ABCD) and GRIMM portable aerosol Spectrometer at two different sites in which one site is urban, and another is rural. The average mass concentration of size segregated PM during the study period (March & April 2022) was recorded as PM₁₀ (223.73 g/m-³), PM₅.₀ (44.955 g/m-³), PM₂.₅ (59.275 g/m-³), PM₁.₀ (33.02 g/m-³), PM₀.₅ (2.05 g/m-³), and PM₀.₂₅ (2.99 g/m- ³). In number mode, PM concentration was found as PM₁₀ (27.46g/m-³), PM₅.₀ (233.48g/m-³), PM₂.₅ (646.61g/m-³), PM₁.₀ (1134.94 g/m-³), PM₀.₅ (14056.04g/m-³), and PM₀.₂₅ (182906.4 g/m-³). The highest concentration of BC was found in Urban due to the emissions from diesel engines and wood burning while NO2 was highest at the rural sites. The concentrations of PM₁₀ and PM₂.₅ exceeded the NAAQS and WHO guidelines. The sensitive, exposed population may be at risk of developing health-related problems from exposure to size-segregated PM and BC.

Keywords: particulate matter, black carbon, NO2, health risk

Procedia PDF Downloads 39
685 Fungal Profile and Antifungal Susceptibility Patterns among Symptomatic Pediatrics Patients Attending Aboozar Children’s Hospital, Ahvaz, Iran

Authors: Nasrin Amirrajab, Yasaman Razavi Ghahfarokhi, Zahra Tootak, Maryam Hadian, Fatemeh Abooali Shamshiri

Abstract:

Urinary tract infections (UTIs) have been reported in children with nephrotic syndrome. However, the only causes for the infection reported to date are bacteria, but not many prior reported occurrences of fungi or yeast as causative organisms. Hence, the present study aimed to describe the epidemiology of urinary tract fungal infections in a tertiary care pediatric. A single-center cross-sectional study was conducted at the nephrology ward of Aboozar Pediatric Hospital between March 21, 2021, and April 28, 2022. Urine was collected aseptically from children, inoculated onto culture media, and incubated at 37 °C for 18–48 hours. Yeast was identified following standard procedures. Antifungal susceptibility testing was determined by the disk diffusion method according to the CLSI guideline. Descriptive statistics and logistical regressions were used to estimate the crude ratio with a 95% confidence interval. P-value < 0.05 was considered significant. Among 68 individuals referred to the mycology lab, the result of direct examination and culture of all patients approved for C.albicans. Of these, 38 individuals (55.8%) were male, and 30 (44.2%) were female. The patients' age ranges were between one month and an 18-year-old. In the study of infection intensity, the patients were classified into three levels such as few (73.5%), moderate (20.6%), and many (5.9%). In the present study, all the patients were sensitive to Posaconazole. Also, the eagle effect was found in Amphotericin B, Voriconazole, and Fluconazole with frequencies of 91.7%, 91.7%, and 83%, respectively. In addition, just 8.3% of isolates were resistant to Itraconazole. It has not shown resistance in other mentioned medicine. The patients showed an intermediate response to Itraconazole (91.7%), Fluconazole (17%), Voriconazole (8.3%), and Amphotericin B (8.3%). There is a high prevalence of yeast infections in children with suspected UTIs. Also, boys are more likely to get yeast infections, and the severity of the infection is higher than girls. The present study demonstrated the importance of diagnosing and selecting the appropriate drug for urinary tract fungal infections in hospitalized children.

Keywords: urinary tract infections, children, fungal infections, yeast, antifungal susceptibility

Procedia PDF Downloads 98
684 Alteration of Placental Development and Vascular Dysfunction in Gestational Diabetes Mellitus Has Impact on Maternal and Infant Health

Authors: Sadia Munir

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The aim of this study is to investigate changes in placental development and vascular dysfunction which subsequently affect feto-maternal health in pregnancies complicated by gestational diabetes mellitus (GDM). Fetal and postnatal adverse health outcomes of GDM are shown to be associated with disturbances in placental structure and function. Children of women with GDM are more likely to be obese and diabetic in childhood and adulthood. GDM also increases the risk of adverse pregnancy outcomes, including preeclampsia, birth injuries, macrosomia and neonatal hypoglycemia, respiratory distress syndrome, neonatal cardiac dysfunction and stillbirth. Incidences of type 2 diabetes in the MENA region are growing at an alarming rate which is estimated to become more than double by 2030. Five of the top 10 countries for diabetes prevalence in 2010 were in the Gulf region. GDM also increases the risk of development of type 2 diabetes. Interestingly, more than half of the women with GDM develop diabetes later in their life. The human placenta is a temporary organ located at the interface between mother and fetal blood circulation. Placenta has a central role as both a producer as well as a target of several molecules that are involved in placental development and function. We have investigated performed a Pubmed search with key words placenta, GDM, placental villi, vascularization, cytokines, growth factors, inflammation, hypoxia, oxidative stress and pathophysiology. We have investigated differences in the development and vascularization of placenta, their underlying causes and impact on feto-maternal health through literature review. We have also identified gaps in the literature and research questions that need to be answered to completely understand the central role of placenta in the GDM. This study is important in understanding the pathophysiology of placenta due to changes in the vascularization of villi, surface area and diameter of villous capillaries in pregnancies complicated by GDM. It is necessary to understand these mechanisms in order to develop treatments to reverse their effects on placental malfunctioning, which in turn, will result in improved mother and child health.

Keywords: gestational diabetes mellitus, placenta, vasculature, villi

Procedia PDF Downloads 318
683 Nutraceutical Potential of Mushroom Bioactive Metabolites and Their Food Functionality

Authors: Jackson Ishara, Ariel Buzera, Gustave N. Mushagalusa, Ahmed R. A. Hammam, Judith Munga, Paul Karanja, John Kinyuru

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Numerous mushroom bioactive metabolites, including polysaccharides, eritadenine, lignin, chitosan, mevinolin, and astrakurkurone have been studied in life-threatening conditions and diseases such as diabetes, cardiovascular, hypertension, cancer, DNA damage, hypercholesterolemia, and obesity attempting to identify natural therapies. These bioactive metabolites have shown potential as antiviral and immune system strengthener natural agents through diverse cellular and physiological pathways modulation with no toxicity evidence, widely available, and affordable. In light of the emerging literature, this paper compiles the most recent information describing the molecular mechanisms that underlie the nutraceutical potentials of these mushroom metabolites suggesting their effectiveness if combined with existing drug therapies. The findings raise hope that these mushroom bioactive metabolites may be utilized as natural therapies considering their therapeutic potential while anticipating further research designing clinical trials and developing new drug therapies while encouraging their consumption as a natural adjuvant in preventing and controlling life-threatening conditions and diseases.

Keywords: bioactive metabolites, food functionality, health-threatening conditions, mushrooms, nutraceutical

Procedia PDF Downloads 103
682 Social and Cognitive Stress Impact on Neuroscience and PTSD

Authors: Sadra Abbasi

Abstract:

The complex connection between psychological stress and the onset of different diseases has been an ongoing issue in the mental health field for a long time. Multiple studies have demonstrated that long-term stress can greatly heighten the likelihood of developing health issues like heart disease, cancer, arthritis, and severe depression. Recent research in cognitive science has provided insight into the intricate processes involved in posttraumatic stress disorder (PTSD), suggesting that distinct memory systems are accountable for both vivid reliving and normal autobiographical memories of traumatic incidents, as proposed by dual representation theory. This theory has important consequences for our comprehension of the neural mechanisms involved in fear and behavior related to threats, highlighting the amygdala-hippocampus-medial prefrontal cortex circuit as a crucial component in this process. This particular circuit, extensively researched in behavioral neuroscience, is essential for regulating the body's reactions to stress and trauma. This review will examine how incorporating a modern neuroscience viewpoint into an integrative case formulation offers a current way to comprehend the intricate connections among psychological stress, trauma, and disease.

Keywords: social, cognitive, stress, neuroscience, behavior, PTSD

Procedia PDF Downloads 36
681 Hydroclean Smartbin Solution for Plastic Pollution Crisis

Authors: Anish Bhargava

Abstract:

By 2050, there will be more plastic than fish in our oceans. 51 trillion micro-plastics pollute our waters and contaminate the food on our plates, increasing the risk of tumours and diseases such as cancer. Our product is a solution to the ever-growing problem of plastic pollution. We call it the SmartBin. The SmartBin is a cylindrical device which will float just below the surface of the water, able to move with the aid of 4 water thrusters situated on the sides. As it floats, our SmartBin will suck water into itself and pump it out through the bottom. All waste is collected into a reusable filter including microplastics measuring down to 1.5mm. A speaker emitting sound at a frequency of 9 hertz ensures marine life stays away from the SmartBin. Featured along with our product is a smartphone app which will enable the user to designate an area for the SmartBin to cover on a satellite image. The SmartBin will then return to its start position near the shore, configured through the app. As global pressure to tackle water pollution continues to increase, environmental spending increases too. As our product provides an effective solution to this issue, we can seize the opportunity and scale our company. Our product is unparalleled. It can move at a high speed, covering a wide area rather than being restricted to one position. We target not only oceans and sea-shores, but also rivers, lakes, reservoirs and canals, as they are much easier to access and control.

Keywords: water, plastic, pollution, solution, hydroclean, smartbin, cleanup

Procedia PDF Downloads 206
680 An Overview of Posterior Fossa Associated Pathologies and Segmentation

Authors: Samuel J. Ahmad, Michael Zhu, Andrew J. Kobets

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Segmentation tools continue to advance, evolving from manual methods to automated contouring technologies utilizing convolutional neural networks. These techniques have evaluated ventricular and hemorrhagic volumes in the past but may be applied in novel ways to assess posterior fossa-associated pathologies such as Chiari malformations. Herein, we summarize literature pertaining to segmentation in the context of this and other posterior fossa-based diseases such as trigeminal neuralgia, hemifacial spasm, and posterior fossa syndrome. A literature search for volumetric analysis of the posterior fossa identified 27 papers where semi-automated, automated, manual segmentation, linear measurement-based formulas, and the Cavalieri estimator were utilized. These studies produced superior data than older methods utilizing formulas for rough volumetric estimations. The most commonly used segmentation technique was semi-automated segmentation (12 studies). Manual segmentation was the second most common technique (7 studies). Automated segmentation techniques (4 studies) and the Cavalieri estimator (3 studies), a point-counting method that uses a grid of points to estimate the volume of a region, were the next most commonly used techniques. The least commonly utilized segmentation technique was linear measurement-based formulas (1 study). Semi-automated segmentation produced accurate, reproducible results. However, it is apparent that there does not exist a single semi-automated software, open source or otherwise, that has been widely applied to the posterior fossa. Fully-automated segmentation via such open source software as FSL and Freesurfer produced highly accurate posterior fossa segmentations. Various forms of segmentation have been used to assess posterior fossa pathologies and each has its advantages and disadvantages. According to our results, semi-automated segmentation is the predominant method. However, atlas-based automated segmentation is an extremely promising method that produces accurate results. Future evolution of segmentation technologies will undoubtedly yield superior results, which may be applied to posterior fossa related pathologies. Medical professionals will save time and effort analyzing large sets of data due to these advances.

Keywords: chiari, posterior fossa, segmentation, volumetric

Procedia PDF Downloads 106
679 Assessment of Airborne PM0.5 Mutagenic and Genotoxic Effects in Five Different Italian Cities: The MAPEC_LIFE Project

Authors: T. Schilirò, S. Bonetta, S. Bonetta, E. Ceretti, D. Feretti, I. Zerbini, V. Romanazzi, S. Levorato, T. Salvatori, S. Vannini, M. Verani, C. Pignata, F. Bagordo, G. Gilli, S. Bonizzoni, A. Bonetti, E. Carraro, U. Gelatti

Abstract:

Air pollution is one of the most important worldwide health concern. In the last years, in both the US and Europe, new directives and regulations supporting more restrictive pollution limits were published. However, the early effects of air pollution occur, especially for the urban population. Several epidemiological and toxicological studies have documented the remarkable effect of particulate matter (PM) in increasing morbidity and mortality for cardiovascular disease, lung cancer and natural cause mortality. The finest fractions of PM (PM with aerodynamic diameter <2.5 µm and less) play a major role in causing chronic diseases. The International Agency for Research on Cancer (IARC) has recently classified air pollution and fine PM as carcinogenic to human (1 Group). The structure and composition of PM influence the biological properties of particles. The chemical composition varies with season and region of sampling, photochemical-meteorological conditions and sources of emissions. The aim of the MAPEC (Monitoring Air Pollution Effects on Children for supporting public health policy) study is to evaluate the associations between air pollution and biomarkers of early biological effects in oral mucosa cells of 6-8 year old children recruited from first grade schools. The study was performed in five Italian towns (Brescia, Torino, Lecce, Perugia and Pisa) characterized by different levels of airborne PM (PM10 annual average from 44 µg/m3 measured in Torino to 20 µg/m3 measured in Lecce). Two to five schools for each town were chosen to evaluate the variability of pollution within the same town. Child exposure to urban air pollution was evaluated by collecting ultrafine PM (PM0.5) in the school area, on the same day of biological sampling. PM samples were collected for 72h using a high-volume gravimetric air sampler and glass fiber filters in two different seasons (winter and spring). Gravimetric analysis of the collected filters was performed; PM0.5 organic extracts were chemically analyzed (PAH, Nitro-PAH) and tested on A549 by the Comet assay and Micronucleus test and on Salmonella strains (TA100, TA98, TA98NR and YG1021) by Ames test. Results showed that PM0.5 represents a high variable PM10 percentage (range 19.6-63%). PM10 concentration were generally lower than 50µg/m3 (EU daily limit). All PM0.5 extracts showed a mutagenic effect with TA98 strain (net revertant/m3 range 0.3-1.5) and suggested the presence of indirect mutagens, while lower effect was observed with TA100 strain. The results with the TA98NR and YG1021 strains showed the presence of nitroaromatic compounds as confirmed by the chemical analysis. No genotoxic or oxidative effect of PM0.5 extracts was observed using the comet assay (with/without Fpg enzyme) and micronucleus test except for some sporadic samples. The low biological effect observed could be related to the low level of air pollution observed in this winter sampling associated to a high atmospheric instability. For a greater understanding of the relationship between PM size, composition and biological effects the results obtained in this study suggest to investigate the biological effect of the other PM fractions and in particular of the PM0.5-1 fraction.

Keywords: airborne PM, ames test, comet assay, micronucleus test

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678 A Deep-Learning Based Prediction of Pancreatic Adenocarcinoma with Electronic Health Records from the State of Maine

Authors: Xiaodong Li, Peng Gao, Chao-Jung Huang, Shiying Hao, Xuefeng B. Ling, Yongxia Han, Yaqi Zhang, Le Zheng, Chengyin Ye, Modi Liu, Minjie Xia, Changlin Fu, Bo Jin, Karl G. Sylvester, Eric Widen

Abstract:

Predicting the risk of Pancreatic Adenocarcinoma (PA) in advance can benefit the quality of care and potentially reduce population mortality and morbidity. The aim of this study was to develop and prospectively validate a risk prediction model to identify patients at risk of new incident PA as early as 3 months before the onset of PA in a statewide, general population in Maine. The PA prediction model was developed using Deep Neural Networks, a deep learning algorithm, with a 2-year electronic-health-record (EHR) cohort. Prospective results showed that our model identified 54.35% of all inpatient episodes of PA, and 91.20% of all PA that required subsequent chemoradiotherapy, with a lead-time of up to 3 months and a true alert of 67.62%. The risk assessment tool has attained an improved discriminative ability. It can be immediately deployed to the health system to provide automatic early warnings to adults at risk of PA. It has potential to identify personalized risk factors to facilitate customized PA interventions.

Keywords: cancer prediction, deep learning, electronic health records, pancreatic adenocarcinoma

Procedia PDF Downloads 155
677 Development of a Device for Detecting Fluids in the Esophagus

Authors: F. J. Puertas, M. Castro, A. Tebar, P. J. Fito, R. Gadea, J. M. Monzó, R. J. Colom

Abstract:

There is a great diversity of diseases that affect the integrity of the walls of the esophagus, generally of a digestive nature. Among them, gastroesophageal reflux is a common disease in the general population, affecting the patient's quality of life; however, there are still unmet diagnostic and therapeutic issues. The consequences of untreated or asymptomatic acid reflux on the esophageal mucosa are not only pain, heartburn, and acid regurgitation but also an increased risk of esophageal cancer. Currently, the diagnostic methods to detect problems in the esophageal tract are invasive and annoying, as 24-hour impedance-pH monitoring forces the patient to be uncomfortable for hours to be able to make a correct diagnosis. In this work, the development of a sensor able to measure in depth is proposed, allowing the detection of liquids circulating in the esophageal tract. The multisensor detection system is based on radiofrequency photospectrometry. At an experimental level, consumers representative of the population in terms of sex and age have been used, placing the sensors between the trachea and the diaphragm analyzing the measurements in vacuum, water, orange juice and saline medium. The results obtained have allowed us to detect the appearance of different liquid media in the esophagus, segregating them based on their ionic content.

Keywords: bioimpedance, dielectric spectroscopy, gastroesophageal reflux, GERD

Procedia PDF Downloads 102
676 Inflammatory Cytokine (Interleukin-8): A Diagnostic Marker in Leukemia

Authors: Sandeep Pandey, Nimra Habib, Ranjana Singh, Abbas Ali Mahdi

Abstract:

Leukemia is a malignancy of blood that mainly affects children and young adults; while advancement in the early diagnosis will have the potential to improve the outcome of diseases. A wide range of disease including leukemia shows inflammatory signals in their pathogenesis. In a pilot study conducted in our laboratory, 52 people were screened, of which 26 had leukemia and 26 were free from any kind of malignancy. We performed the estimation of the inflammatory cytokine Interleukin-8 and it was found significantly raised in all the leukemia patients concerning healthy volunteers who participated in the study. Flow cytometry had been performed for the confirmation of leukemia and further genomic, and proteomic, analyses of the sample revealed that IL-8 levels showed a positive correlation in patients with leukemia. The results had shown constitutive secretion of interleukin-8 by leukemia cells. So, our finding demonstrated that IL-8 is considered to have a role in the pathogenesis of leukemia, and quantification of IL-8 levels in leukemia conditions might be more useful and feasible in the clinical setting for the prediction of drug responses where it may represent a putative target for innovative diagnostic toward effective therapeutic approaches. However, further research explorations in this area are needed that include a greater number of patients with all different forms of leukemia, and estimating their IL-8 levels may hold the key for the additional predictive values on the recurrence of leukemia and its prognosis.

Keywords: T-ALL, IL-8, leukemia pathogenesis, cancer therapeutics

Procedia PDF Downloads 72
675 Kinematic Analysis of Human Gait for Typical Postures of Walking, Running and Cart Pulling

Authors: Nupur Karmaker, Hasin Aupama Azhari, Abdul Al Mortuza, Abhijit Chanda, Golam Abu Zakaria

Abstract:

Purpose: The purpose of gait analysis is to determine the biomechanics of the joint, phases of gait cycle, graphical and analytical analysis of degree of rotation, analysis of the electrical activity of muscles and force exerted on the hip joint at different locomotion during walking, running and cart pulling. Methods and Materials: Visual gait analysis and electromyography method has been used to detect the degree of rotation of joints and electrical activity of muscles. In cinematography method an object is observed from different sides and takes its video. Cart pulling length has been divided into frames with respect to time by using video splitter software. Phases of gait cycle, degree of rotation of joints, EMG profile and force analysis during walking and running has been taken from different papers. Gait cycle and degree of rotation of joints during cart pulling has been prepared by using video camera, stop watch, video splitter software and Microsoft Excel. Results and Discussion: During the cart pulling the force exerted on hip is the resultant of various forces. The force on hip is the vector sum of the force Fg= mg, due the body of weight of the person and Fa= ma, due to the velocity. Maximum stance phase shows during cart pulling and minimum shows during running. During cart pulling shows maximum degree of rotation of hip joint, knee: running, and ankle: cart pulling. During walking, it has been observed minimum degree of rotation of hip, ankle: during running. During cart pulling, dynamic force depends on the walking velocity, body weight and load weight. Conclusions: 80% people suffer gait related disease with increasing their age. Proper care should take during cart pulling. It will be better to establish the gait laboratory to determine the gait related diseases. If the way of cart pulling is changed i.e the design of cart pulling machine, load bearing system is changed then it would possible to reduce the risk of limb loss, flat foot syndrome and varicose vein in lower limb.

Keywords: kinematic, gait, gait lab, phase, force analysis

Procedia PDF Downloads 576
674 Image Segmentation with Deep Learning of Prostate Cancer Bone Metastases on Computed Tomography

Authors: Joseph M. Rich, Vinay A. Duddalwar, Assad A. Oberai

Abstract:

Prostate adenocarcinoma is the most common cancer in males, with osseous metastases as the commonest site of metastatic prostate carcinoma (mPC). Treatment monitoring is based on the evaluation and characterization of lesions on multiple imaging studies, including Computed Tomography (CT). Monitoring of the osseous disease burden, including follow-up of lesions and identification and characterization of new lesions, is a laborious task for radiologists. Deep learning algorithms are increasingly used to perform tasks such as identification and segmentation for osseous metastatic disease and provide accurate information regarding metastatic burden. Here, nnUNet was used to produce a model which can segment CT scan images of prostate adenocarcinoma vertebral bone metastatic lesions. nnUNet is an open-source Python package that adds optimizations to deep learning-based UNet architecture but has not been extensively combined with transfer learning techniques due to the absence of a readily available functionality of this method. The IRB-approved study data set includes imaging studies from patients with mPC who were enrolled in clinical trials at the University of Southern California (USC) Health Science Campus and Los Angeles County (LAC)/USC medical center. Manual segmentation of metastatic lesions was completed by an expert radiologist Dr. Vinay Duddalwar (20+ years in radiology and oncologic imaging), to serve as ground truths for the automated segmentation. Despite nnUNet’s success on some medical segmentation tasks, it only produced an average Dice Similarity Coefficient (DSC) of 0.31 on the USC dataset. DSC results fell in a bimodal distribution, with most scores falling either over 0.66 (reasonably accurate) or at 0 (no lesion detected). Applying more aggressive data augmentation techniques dropped the DSC to 0.15, and reducing the number of epochs reduced the DSC to below 0.1. Datasets have been identified for transfer learning, which involve balancing between size and similarity of the dataset. Identified datasets include the Pancreas data from the Medical Segmentation Decathlon, Pelvic Reference Data, and CT volumes with multiple organ segmentations (CT-ORG). Some of the challenges of producing an accurate model from the USC dataset include small dataset size (115 images), 2D data (as nnUNet generally performs better on 3D data), and the limited amount of public data capturing annotated CT images of bone lesions. Optimizations and improvements will be made by applying transfer learning and generative methods, including incorporating generative adversarial networks and diffusion models in order to augment the dataset. Performance with different libraries, including MONAI and custom architectures with Pytorch, will be compared. In the future, molecular correlations will be tracked with radiologic features for the purpose of multimodal composite biomarker identification. Once validated, these models will be incorporated into evaluation workflows to optimize radiologist evaluation. Our work demonstrates the challenges of applying automated image segmentation to small medical datasets and lays a foundation for techniques to improve performance. As machine learning models become increasingly incorporated into the workflow of radiologists, these findings will help improve the speed and accuracy of vertebral metastatic lesions detection.

Keywords: deep learning, image segmentation, medicine, nnUNet, prostate carcinoma, radiomics

Procedia PDF Downloads 96
673 Measure of Pleasure of Drug Users

Authors: Vano Tsertsvadze, Marina Chavchanidze, Lali Khurtsia

Abstract:

Problem of drug use is often seen as a combination of psychological and social problems, but this problem can be considered as economically rational decision in the process of buying pleasure (looking after children, reading, harvesting fruits in the fall, sex, eating, etc.). Before the adoption of the decisions people face to a trade-off - when someone chooses a delicious meal, she takes a completely rational decision, that the pleasure of eating has a lot more value than the pleasure which she will experience after two months diet on the summer beach showing off her beautiful body. This argument is also true for alcohol, drugs and cigarettes. Smoking has a negative effect on health, but smokers are not afraid of the threat of a lung cancer after 40 years, more valuable moment is a pleasure from smoking. Our hypothesis - unsatisfied pleasure and frustration, probably determines the risk of dependence on drug abuse. The purpose of research: 1- to determine the relative measure unit of pleasure, which will be used to measure and assess the intensity of various human pleasures. 2- to compare the intensity of the pleasure from different kinds of activity, with pleasures received from drug use. 3- Based on the analysis of data, to identify factors affecting the rational decision making. Research method: Respondents will be asked to recall the greatest pleasure of their life, which will be used as a measure of the other pleasures. The study will use focus groups and structured interviews.

Keywords: drug, drug-user, measurement, satisfaction

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672 GABARAPL1 (GEC1) mRNA Expression Levels in Patients with Alzheimer's Disease

Authors: Ali Bayram, Burak Uz, Ilhan Dolasik, Remzi Yiğiter

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The GABARAP (GABAA-receptor-associated protein) family consists of GABARAP, GABARAPL1 (GABARAP-like 1) and GABARAPL2 (GABARAP-like 2). GABARAPL1, like GABARAP, was described to interact with both GABAA receptor and tubulin, and to be involved in intracellular GABAA receptor trafficking and promoting tubulin polymerization. In addition, GABARAPL1 is thought to be involved in various physiological (autophagosome closure, regulation of circadian rhythms) and/or pathological mechanisms (cancer, neurodegeneration). Alzheimer’s disease (AD) is a progressive neuro degenerative disorder characterized with impaired cognitive functions. Disruption of the GABAergic neuro transmission as well as cholinergic and glutamatergic interactions, may also be involved in the pathogenesis of AD. GABARAPL1 presents a regulated tissue expression and is the most expressed gene among the GABARAP family members in the central nervous system. We, herein, conducted a study to investigate the GABARAPL1 mRNA expression levels in patients with AD. 50 patients with AD and 49 control patients were enrolled to the present study. Messenger RNA expression levels of GABARAPL1 were detected by real-time polymerase chain reaction. GABARAPL1 mRNA expression in AD / control patients was 0,495 (95% confidence interval: 0,404-0,607), p= 0,00000002646. Reduced activity of GABARAPL1 gene might play a role, at least partly, in the pathophysiology of AD.

Keywords: Alzheimer’s disease, GABARAPL1, mRNA expression, RT-PCR

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671 Risk Factors for Severe Typhoid Fever in Children: A French Retrospective Study about 78 Cases from 2000-2017 in Six Parisian Hospitals

Authors: Jonathan Soliman, Thomas Cavasino, Virginie Pommelet, Lahouari Amor, Pierre Mornand, Simon Escoda, Nina Droz, Soraya Matczak, Julie Toubiana, François Angoulvant, Etienne Carbonnelle, Albert Faye, Loic de Pontual, Luu-Ly Pham

Abstract:

Background: Typhoid and paratyphoid fever are systemic infections caused by Salmonella enterica serovar Typhi or paratyphi (A, B, C). Children traveling to tropical areas are at risk to contract these diseases which can be complicated. Methods: Clinical, biological and bacteriological data were collected from 78 pediatric cases reported between 2000 and 2017 in six Parisian hospitals. Children aged 0 to 18 years old, with a diagnosis of typhoid or paratyphoid fever confirmed by bacteriological exams, were included. Epidemiologic, clinical, biological features and presence of multidrug-resistant (MDR) bacteria or intermediate susceptibility to ciprofloxacin (nalidixic acid resistant) were examined by univariate analysis and by logistic regression analysis to identify risk factors of severe typhoid in children. Results: 84,6% of the children were imported cases of typhoid fever (n=66/78) and 15,4% were autochthonous cases (n=12/78). 89,7% were caused by S.typhi (n=70/78) and 12,8% by S.paratyphi (n=10/78) including 2 co-infections. 19,2% were intrafamilial cases (n=15/78). Median age at diagnosis was 6,4 years-old [6 months-17,9 years]. 28,2% of the cases were complicated forms (n=22/78): digestive (n=8; 10,3%), neurological (n=7; 9%), pulmonary complications (n=4; 5,1%) and hemophagocytic syndrome (n=4; 5,1%). Only 5% of the children had prior immunization with typhoid non-conjugated vaccine (n=4/78). 28% of the cases (n=22/78) were caused by resistant bacteria. Thrombocytopenia and diagnosis delay was significantly associated with severe infection (p= 0.029 and p=0,01). Complicated forms were more common with MDR (p=0,1) and not statistically associated with a young age or sex in this study. Conclusions: Typhoid and paratyphoid fever are not rare in children back from tropical areas. This multicentric pediatric study seems to show that thrombocytopenia, diagnosis delay, and multidrug resistant bacteria are associated with severe typhoid fever and complicated forms in children.

Keywords: antimicrobial resistance, children, Salmonella enterica typhi and paratyphi, severe typhoid

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670 Clinical Evidence of the Efficacy of ArtiCovid (Artemisia Annua Extract) on Covid-19 Patients in DRC

Authors: Md, MCS, MPH Munyangi Wa Nkola Jerome

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The pandemic of COVID-19, a recently discovered contagious respiratory disease called SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus 2 Majority of people infected with SARS-CoV-2: Asymptomatic or mildly ill 14% of patients will develop severe illness requiring hospitalization and oxygen support, and 5% of these will be transferred to an intensive care unit, Urgent need for new treatments that can be used quickly to avoid transfer of patients to intensive care and death. Objective: To evaluate the clinical activity (efficacy) of ArtiCovid Hypothesis: Administration of 3 times a teaspoon per day by COVID patients (symptomatic, mild, or moderate forms) results in the disappearance of symptoms and improvement of biological parameters (including viral suppression). Clinical efficacy: the disappearance of clinical signs after seven days of treatment; reduction in the rate of patients transferred to intensive care units for mechanical ventilation and a decrease in mortality related to this infection Paraclinical efficacy: improvement of biological parameters (mainly d-dimer, CRP) Virological efficacy: suppression of the viral load after seven days of treatment (control test on the seventh day is negative) Pilot study using a standardized solution based on Artemisia annua (ARTICOVID) Obtaining authorization from the health authorities of the province of Central Kongo Recruitment of volunteer patients, mainly in the Kinkanda HospitalCarrying out tests before and after treatment as well as analyses before and after treatment. The protocol obtained the approval of the ethics committee 50 patients who completed the treatment were aged between 2 and 70 years, with an average age of 36 yearsMore half were male (56%). One in four patients was a health professional (25%) Of the 12 health professionals, 4 were physicians. For those who reported the date of onset of the disease, the average duration between the appearance of the first symptoms and the medical consultation was 5 days. The 50 patients put on ARTICOVID were discharged alive with CRP levels substantially normalizedAfter seven to eight days, the control test came back negative. This pilot study suggests that ARTICOVID may be effective against COVID-19 infection.

Keywords: artiCovid, DRC, Covid-19, SARS_COV_2

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669 Electro-Thermal Imaging of Breast Phantom: An Experimental Study

Authors: H. Feza Carlak, N. G. Gencer

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To increase the temperature contrast in thermal images, the characteristics of the electrical conductivity and thermal imaging modalities can be combined. In this experimental study, it is objected to observe whether the temperature contrast created by the tumor tissue can be improved just due to the current application within medical safety limits. Various thermal breast phantoms are developed to simulate the female breast tissue. In vitro experiments are implemented using a thermal infrared camera in a controlled manner. Since experiments are implemented in vitro, there is no metabolic heat generation and blood perfusion. Only the effects and results of the electrical stimulation are investigated. Experimental study is implemented with two-dimensional models. Temperature contrasts due to the tumor tissues are obtained. Cancerous tissue is determined using the difference and ratio of healthy and tumor images. 1 cm diameter single tumor tissue causes almost 40 °mC temperature contrast on the thermal-breast phantom. Electrode artifacts are reduced by taking the difference and ratio of background (healthy) and tumor images. Ratio of healthy and tumor images show that temperature contrast is increased by the current application.

Keywords: medical diagnostic imaging, breast phantom, active thermography, breast cancer detection

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668 Biosynthesis of Natural and Halogenated Plant Alkaloids in Yeast

Authors: Beata J. Lehka, Samuel A. Bradley, Frederik G. Hansson, Khem B. Adhikari, Daniela Rago, Paulina Rubaszka, Ahmad K. Haidar, Ling Chen, Lea G. Hansen, Olga Gudich, Konstantina Giannakou, Yoko Nakamura, Thomas Dugé de Bernonville, Konstantinos Koudounas, Sarah E. O’Connor, Vincent Courdavault, Jay D. Keasling, Jie Zhang, Michael K. Jensen

Abstract:

Monoterpenoid indole alkaloids (MIAs) represent a large class of natural plant products with marketed pharmaceutical activities against a wide range of applications, including cancer and mental disorders. Halogenated MIAs have shown improved pharmaceutical properties; however, characterisation and synthesis of new-to-nature halogenated MIAs remain a challenge in slow-growing plants with limited genetic tractability. Here, we demonstrate a platform for de novo biosynthesis of two bioactive MIAs, serpentine and alstonine, in baker’s yeast Saccharomyces cerevisiae, reaching titers of 8.85 mg/L and 4.48 mg/L, respectively, when cultivated in fed-batch micro bioreactors. Using this MIA biosynthesis platform, we undertake a systematic exploration of the derivative space surrounding these compounds and produce halogenated MIAs. The aim of the current study is to develop a fermentation process for halogenated MIAs.

Keywords: monoterpenoid indole alkaloids, Saccharomyces cerevisiae, halogenated derivatives, fermentation

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667 Adolescent-Parent Relationship as the Most Important Factor in Preventing Mood Disorders in Adolescents: An Application of Artificial Intelligence to Social Studies

Authors: Elżbieta Turska

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Introduction: One of the most difficult times in a person’s life is adolescence. The experiences in this period may shape the future life of this person to a large extent. This is the reason why many young people experience sadness, dejection, hopelessness, sense of worthlessness, as well as losing interest in various activities and social relationships, all of which are often classified as mood disorders. As many as 15-40% adolescents experience depressed moods and for most of them they resolve and are not carried into adulthood. However, (5-6%) of those affected by mood disorders develop the depressive syndrome and as many as (1-3%) develop full-blown clinical depression. Materials: A large questionnaire was given to 2508 students, aged 13–16 years old, and one of its parts was the Burns checklist, i.e. the standard test for identifying depressed mood. The questionnaire asked about many aspects of the student’s life, it included a total of 53 questions, most of which had subquestions. It is important to note that the data suffered from many problems, the most important of which were missing data and collinearity. Aim: In order to identify the correlates of mood disorders we built predictive models which were then trained and validated. Our aim was not to be able to predict which students suffer from mood disorders but rather to explore the factors influencing mood disorders. Methods: The problems with data described above practically excluded using all classical statistical methods. For this reason, we attempted to use the following Artificial Intelligence (AI) methods: classification trees with surrogate variables, random forests and xgboost. All analyses were carried out with the use of the mlr package for the R programming language. Resuts: The predictive model built by classification trees algorithm outperformed the other algorithms by a large margin. As a result, we were able to rank the variables (questions and subquestions from the questionnaire) from the most to least influential as far as protection against mood disorder is concerned. Thirteen out of twenty most important variables reflect the relationships with parents. This seems to be a really significant result both from the cognitive point of view and also from the practical point of view, i.e. as far as interventions to correct mood disorders are concerned.

Keywords: mood disorders, adolescents, family, artificial intelligence

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666 Mathematical Modelling of Spatial Distribution of Covid-19 Outbreak Using Diffusion Equation

Authors: Kayode Oshinubi, Brice Kammegne, Jacques Demongeot

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The use of mathematical tools like Partial Differential Equations and Ordinary Differential Equations have become very important to predict the evolution of a viral disease in a population in order to take preventive and curative measures. In December 2019, a novel variety of Coronavirus (SARS-CoV-2) was identified in Wuhan, Hubei Province, China causing a severe and potentially fatal respiratory syndrome, i.e., COVID-19. Since then, it has become a pandemic declared by World Health Organization (WHO) on March 11, 2020 which has spread around the globe. A reaction-diffusion system is a mathematical model that describes the evolution of a phenomenon subjected to two processes: a reaction process in which different substances are transformed, and a diffusion process that causes a distribution in space. This article provides a mathematical study of the Susceptible, Exposed, Infected, Recovered, and Vaccinated population model of the COVID-19 pandemic by the bias of reaction-diffusion equations. Both local and global asymptotic stability conditions for disease-free and endemic equilibria are determined using the Lyapunov function are considered and the endemic equilibrium point exists and is stable if it satisfies Routh–Hurwitz criteria. Also, adequate conditions for the existence and uniqueness of the solution of the model have been proved. We showed the spatial distribution of the model compartments when the basic reproduction rate $\mathcal{R}_0 < 1$ and $\mathcal{R}_0 > 1$ and sensitivity analysis is performed in order to determine the most sensitive parameters in the proposed model. We demonstrate the model's effectiveness by performing numerical simulations. We investigate the impact of vaccination and the significance of spatial distribution parameters in the spread of COVID-19. The findings indicate that reducing contact with an infected person and increasing the proportion of susceptible people who receive high-efficacy vaccination will lessen the burden of COVID-19 in the population. To the public health policymakers, we offered a better understanding of the COVID-19 management.

Keywords: COVID-19, SEIRV epidemic model, reaction-diffusion equation, basic reproduction number, vaccination, spatial distribution

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665 Potential Activities of Human Endogenous Retroviral kDNA in Melanoma Pathogenesis and HIV-1 Infection

Authors: Jianli Dong, Fangling Xu, Gengming Huang

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Human endogenous retroviral elements (HERVs) comprise approximately 8% of the human genome. They are thought to be germline-integrated genetic remnants of retroviral infections. Although HERV sequences are highly defective, some, especially the K type (HERV-K), have been shown to be expressed and may have biological activities in the pathogenesis of cancer, chronic inflammation and autoimmune diseases. We found that HERV-K GAG and ENV proteins were strongly expressed in pleomorphic melanoma cells. We also detected a critical role of HERV-K ENV in mediating intercellular fusion and colony formation of melanoma cells. Interestingly, we found that levels of HERV-K GAG and ENV expression correlated with the activation of ERK and loss of p16INK4A in melanoma cells, and inhibition of MEK or CDK4, especially in combination, reduced HERV-K expression in melanoma cells. We also performed a reverse transcription-polymerase chain reaction (RT-PCR) assay using DNase I digestion to remove “contaminating” HERV-K genomic DNA and examined HERV-K RNA expression in plasma samples from HIV-1 infected individuals. We found a covariation between HERV-K RNA expression and CD4 cell counts in HIV-1 positive samples. Although a causal link between HERV-K activation and melanoma development, and between HERV-K activation, HIV-1 infection and CD4 cell count have yet to be determined, existing data support the further research efforts in HERV-K.

Keywords: CD4 cell, HERV-K, HIV-1, melanoma

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664 Compliance Of Dialysis patients With Nutrition Guidelines: Insights From A Questionnaire

Authors: Zeiler M., Stadler D., Schmaderer C.

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Over the years of dialysis treatment, most patients experience significant weight loss. The primary emphasis in earlier research was the underlying mechanism of protein energy wasting and the subsequent malnutrition inflammation syndrome. In the interest to provide an effective and rapid solution for the patients, the aim of this study is identifying individual influences of their assumed reduced dietary intake, such as nausea, appetite loss and taste changes, and to determine whether the patients adhere to their nutrition guidelines. A prospective, controlled study with 38 end-stage renal disease patients was performed using a questionnaire to reflect their diet within the last 12 months. Thereby, the daily intake for the most important macro-and micronutrients was calculated to be compared with the individual KDQOI-guideline value, as well as controls matched in age and gender. The majority of the study population did not report symptoms commonly associated with dialysis, such as nausea or inappetence, and denied any change in dietary behavior since receiving renal replacement therapy. The patients’ daily intake of energy (3080kcal ± 1266) and protein (89,9g [53,4-142,0]) did not differ significantly from the controls (energy intake: 3233kcal ± 1046, p=0,597; protein intake: 103,7g [90,1-125,5], p=0,120). The average difference to the individual calculated KDQOI-guideline was +176,0kcal ± 1156 (p=0,357) for energy intake and -1,75g ± 45,9 (p=0,491) for protein intake. However, there was an observed imbalance in the distribution of macronutrients, with a preference for fats over proteins. The patients’ daily intake of sodium (5,4g [ 2,95-10,1]) was higher than in the controls (4,1g [2,04-5,99], p= 0,058) whereas both values for potassium (3,7g ± 1,84) and phosphorous (1,79g ± 0,91) went significantly below the controls’ values (potassium intake: 4,89g ± 1,74, p=0,014; phosphorous intake: 2,04g ± 0,64, p=0,038). Thus, the values exceeded the calculated KDQOI-recommendation by + 3,3g [0,63-7,90] (p<0,001) for sodium, +1,49g ± 1,84 (p<0,001) for potassium and +0,89g ± 0,91 (p<0,001) for phosphorous. Contrary to the assumption, the patients did not under-eat. Nevertheless, their diets did not align with the recommended values. These findings highlight the need for intervention and education among patients and that regular dietary monitoring could prevent unhealthy nutrition habits. The elaboration of individual references instead of standardized guidelines could increase the compliance to the advised diet so that interdisciplinary comorbidities do not develop or worsen.

Keywords: compliance, dialysis, end-stage renal disease, KDQOI, malnutrition, nutrition guidelines, questionnaire, salt intake

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663 Characterizing and Developing the Clinical Grade Microbiome Assay with a Robust Bioinformatics Pipeline for Supporting Precision Medicine Driven Clinical Development

Authors: Danyi Wang, Andrew Schriefer, Dennis O'Rourke, Brajendra Kumar, Yang Liu, Fei Zhong, Juergen Scheuenpflug, Zheng Feng

Abstract:

Purpose: It has been recognized that the microbiome plays critical roles in disease pathogenesis, including cancer, autoimmune disease, and multiple sclerosis. To develop a clinical-grade assay for exploring microbiome-derived clinical biomarkers across disease areas, a two-phase approach is implemented. 1) Identification of the optimal sample preparation reagents using pre-mixed bacteria and healthy donor stool samples coupled with proprietary Sigma-Aldrich® bioinformatics solution. 2) Exploratory analysis of patient samples for enabling precision medicine. Study Procedure: In phase 1 study, we first compared the 16S sequencing results of two ATCC® microbiome standards (MSA 2002 and MSA 2003) across five different extraction kits (Kit A, B, C, D & E). Both microbiome standards samples were extracted in triplicate across all extraction kits. Following isolation, DNA quantity was determined by Qubit assay. DNA quality was assessed to determine purity and to confirm extracted DNA is of high molecular weight. Bacterial 16S ribosomal ribonucleic acid (rRNA) amplicons were generated via amplification of the V3/V4 hypervariable region of the 16S rRNA. Sequencing was performed using a 2x300 bp paired-end configuration on the Illumina MiSeq. Fastq files were analyzed using the Sigma-Aldrich® Microbiome Platform. The Microbiome Platform is a cloud-based service that offers best-in-class 16S-seq and WGS analysis pipelines and databases. The Platform and its methods have been extensively benchmarked using microbiome standards generated internally by MilliporeSigma and other external providers. Data Summary: The DNA yield using the extraction kit D and E is below the limit of detection (100 pg/µl) of Qubit assay as both extraction kits are intended for samples with low bacterial counts. The pre-mixed bacterial pellets at high concentrations with an input of 2 x106 cells for MSA-2002 and 1 x106 cells from MSA-2003 were not compatible with the kits. Among the remaining 3 extraction kits, kit A produced the greatest yield whereas kit B provided the least yield (Kit-A/MSA-2002: 174.25 ± 34.98; Kit-A/MSA-2003: 179.89 ± 30.18; Kit-B/MSA-2002: 27.86 ± 9.35; Kit-B/MSA-2003: 23.14 ± 6.39; Kit-C/MSA-2002: 55.19 ± 10.18; Kit-C/MSA-2003: 35.80 ± 11.41 (Mean ± SD)). Also, kit A produced the greatest yield, whereas kit B provided the least yield. The PCoA 3D visualization of the Weighted Unifrac beta diversity shows that kits A and C cluster closely together while kit B appears as an outlier. The kit A sequencing samples cluster more closely together than both the other kits. The taxonomic profiles of kit B have lower recall when compared to the known mixture profiles indicating that kit B was inefficient at detecting some of the bacteria. Conclusion: Our data demonstrated that the DNA extraction method impacts DNA concentration, purity, and microbial communities detected by next-generation sequencing analysis. Further microbiome analysis performance comparison of using healthy stool samples is underway; also, colorectal cancer patients' samples will be acquired for further explore the clinical utilities. Collectively, our comprehensive qualification approach, including the evaluation of optimal DNA extraction conditions, the inclusion of positive controls, and the implementation of a robust qualified bioinformatics pipeline, assures accurate characterization of the microbiota in a complex matrix for deciphering the deep biology and enabling precision medicine.

Keywords: 16S rRNA sequencing, analytical validation, bioinformatics pipeline, metagenomics

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662 A Review on the Mechanism Removal of Pesticides and Heavy Metal from Agricultural Runoff in Treatment Train

Authors: N. A. Ahmad Zubairi, H. Takaijudin, K. W. Yusof

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Pesticides have been used widely over the world in agriculture to protect from pests and reduce crop losses. However, it affects the environment with toxic chemicals. Exceed of toxic constituents in the ecosystem will result in bad side effects. The hydrological cycle is related to the existence of pesticides and heavy metal which it can penetrate through varieties of sources into the soil or water bodies, especially runoff. Therefore, proper mechanisms of pesticide and heavy metal removal should be studied to improve the quality of ecosystem free or reduce from unwanted substances. This paper reviews the use of treatment train and its mechanisms to minimize pesticides and heavy metal from agricultural runoff. Organochlorine (OCL) is a common pesticide that was found in the agricultural runoff. OCL is one of the toxic chemicals that can disturb the ecosystem such as inhibiting plants' growth and harm human health by having symptoms as asthma, active cancer cell, vomit, diarrhea, etc. Thus, this unwanted contaminant gives disadvantages to the environment and needs treatment system. Hence, treatment train by bioretention system is suitable because removal efficiency achieves until 90% of pesticide removal with selected vegetated plant and additive.

Keywords: pesticides, heavy metal, agricultural runoff, bioretention, mechanism removal, treatment train

Procedia PDF Downloads 159
661 Mechanistic Structural Insights into the UV Induced Apoptosis via Bcl-2 proteins

Authors: Akash Bera, Suraj Singh, Jacinta Dsouza, Ramakrishna V. Hosur, Pushpa Mishra

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Ultraviolet C (UVC) radiation induces apoptosis in mammalian cells and it is suggested that the mechanism by which this occurs is the mitochondrial pathway of apoptosis through the release of cytochrome c from the mitochondria into the cytosol. The Bcl-2 family of proteins pro-and anti-apoptotic is the regulators of the mitochondrial pathway of apoptosis. Upon UVC irradiation, the proliferation of apoptosis is enhanced through the downregulation of the anti-apoptotic protein Bcl-xl and up-regulation of Bax. Although the participation of the Bcl-2 family of proteins in apoptosis appears responsive to UVC radiation, to the author's best knowledge, it is unknown how the structure and, effectively, the function of these proteins are directly impacted by UVC exposure. In this background, we present here a structural rationale for the effect of UVC irradiation in restoring apoptosis using two of the relevant proteins, namely, Bid-FL and Bcl-xl ΔC, whose solution structures have been reported previously. Using a variety of biophysical tools such as circular dichroism, fluorescence and NMR spectroscopy, we show that following UVC irradiation, the structures of Bcl-xlΔC and Bid-FL are irreversibly altered. Bcl-xLΔC is found to be more sensitive to UV exposure than Bid-FL. From the NMR data, dramatic structural perturbations (α-helix to β-sheet) are seen to occur in the BH3 binding region, a crucial segment of Bcl-xlΔC which impacts the efficacy of its interactions with pro-apoptotic tBid. These results explain the regulation of apoptosis by UVC irradiation. Our results on irradiation dosage dependence of the structural changes have therapeutic potential for the treatment of cancer.

Keywords: Bid, Bcl-xl, UVC, apoptosis

Procedia PDF Downloads 127