Search results for: drug kinetics

Authors: Adnan A. Kadi, Nasser S. Al-Shakliah, Haitham Al-Rabiah

Abstract:

Zorifertinib is a novel, potent, oral, a small molecule used to treat non-small cell lung cancer (NSCLC). zorifertinib is an Epidermal Growth Factor Receptor (EGFR) inhibitor and has good blood–brain barrier permeability for (NSCLC) patients with EGFR mutations. zorifertinibis currently at phase II/III clinical trials. The current research reports the characterization and identification of in vitro, in vivo and reactive intermediates of zorifertinib. Prediction of susceptible sites of metabolism and reactivity pathways (cyanide and GSH) of zorifertinib were performed by the Xenosite web predictor tool. In-vitro metabolites of zorifertinib were performed by incubation with rat liver microsomes (RLMs) and isolated perfused rat liver hepatocytes. Extraction of zorifertinib and it's in vitro metabolites from the incubation mixtures were done by protein precipitation. In vivo metabolism was done by giving a single oral dose of zorifertinib(10 mg/Kg) to Sprague Dawely rats in metabolic cages by using oral gavage. Urine was gathered and filtered at specific time intervals (0, 6, 12, 18, 24, 48, 72,96and 120 hr) from zorifertinib dosing. A similar volume of ACN was added to each collected urine sample. Both layers (organic and aqueous) were injected into liquid chromatography ion trap mass spectrometry(LC-IT-MS) to detect vivozorifertinib metabolites. N-methyl piperizine ring and quinazoline group of zorifertinib undergoe metabolism forming iminium and electro deficient conjugated system respectively, which are very reactive toward nucleophilic macromolecules. Incubation of zorifertinib with RLMs in the presence of 1.0 mM KCN and 1.0 Mm glutathione were made to check reactive metabolites as it is often responsible for toxicities associated with this drug. For in vitro metabolites there were nine in vitro phase I metabolites, four in vitro phase II metabolites, eleven reactive metabolites(three cyano adducts, five GSH conjugates metabolites, and three methoxy metabolites of zorifertinib were detected by LC-IT-MS. For in vivo metabolites, there were eight in vivo phase I, tenin vivo phase II metabolitesofzorifertinib were detected by LC-IT-MS. In vitro and in vivo phase I metabolic pathways wereN- demthylation, O-demethylation, hydroxylation, reduction, defluorination, and dechlorination. In vivo phase II metabolic reaction was direct conjugation of zorifertinib with glucuronic acid and sulphate.

Keywords: in vivo metabolites, in vitro metabolites, cyano adducts, GSH conjugate

Procedia PDF Downloads 171

Authors: Adeline Meriaux, Claire Gaiani, Jennifer Burgain, Frantz Fournier, Lionel Muniglia, Jérémy Petit

Abstract:

Spray-drying process is widely used for the production of dairy powders for food and pharmaceuticals industries. It involves the atomization of a liquid feed into fine droplets, which are subsequently dried through contact with a hot air flow. The resulting powders permit transportation cost reduction and shelf life increase but can also exhibit various interesting functionalities (flowability, solubility, protein modification or acid gelation), depending on operating conditions and milk composition. Indeed, particles porosity, surface composition, lactose crystallization, protein denaturation, protein association or crust formation may change. Links between spray-drying conditions and physicochemical and functional properties of powders were investigated by a design of experiment methodology and analyzed by principal component analysis. Quadratic models were developed, and multicriteria optimization was carried out by the use of genetic algorithm. At the time of abstract submission, verification spray-drying trials are ongoing. To perform experiments, milk from dairy farm was collected, skimmed, froze and spray-dried at different air pressure (between 1 and 3 bars) and outlet temperature (between 75 and 95 °C). Dry matter, minerals content and proteins content were determined by standard method. Solubility index, absorption index and hygroscopicity were determined by method found in literature. Particle size distribution were obtained by laser diffraction granulometry. Location of the powder color in the Cielab color space and water activity were characterized by a colorimeter and an aw-value meter, respectively. Flow properties were characterized with FT4 powder rheometer; in particular compressibility and shearing test were performed. Air pressure and outlet temperature are key factors that directly impact the drying kinetics and powder characteristics during spray-drying process. It was shown that the air pressure affects the particle size distribution by impacting the size of droplet exiting the nozzle. Moreover, small particles lead to more cohesive powder and less saturated color of powders. Higher outlet temperature results in lower moisture level particles which are less sticky and can explain a spray-drying yield increase and the higher cohesiveness; it also leads to particle with low water activity because of the intense evaporation rate. However, it induces a high hygroscopicity, thus, powders tend to get wet rapidly if they are not well stored. On the other hand, high temperature provokes a decrease of native serum proteins which is positively correlated to gelation properties (gel point and firmness). Partial denaturation of serum proteins can improve functional properties of powder. The control of air pressure and outlet temperature during the spray-drying process significantly affects the physicochemical and functional properties of powder. This study permitted to better understand the links between physicochemical and functional properties of powder, to identify correlations between air pressure and outlet temperature. Therefore, mathematical models have been developed and the use of genetic algorithm will allow the optimization of powder functionalities.

Keywords: dairy powders, spray-drying, powders functionalities, design of experiment

Procedia PDF Downloads 51

Authors: Pei-Ru Yang, Yu-Chen Lin, Jia-Min Wu

Abstract:

Background: A 58-year-old man with a history of osteoporosis and diabetes presented with chronic pain in his left knee due to severe knee joint degeneration. The knee replacement surgery was recommended by the doctor. But the patient suffered from low pain tolerance and wondered if virtual reality could relieve acute postoperative wound pain. Methods: We used the PICO (patient, intervention, comparison, and outcome) approach to generate indexed keywords and searched systematic review articles from 2017 to 2021 on the Cochran Library, PubMed, and Clinical Key databases. Results: The initial literature results included 38 articles, including 12 Cochrane library articles and 26 PubMed articles. One article was selected for further analysis after removing duplicates and off-topic articles. The eight trials included in this article were published between 2013 and 2019 and recruited a total of 723 participants. The studies, conducted in India, Lebanon, Iran, South Korea, Spain, and China, included adults who underwent hemorrhoidectomy, dental surgery, craniotomy or spine surgery, episiotomy repair, and knee surgery, with a mean age (24.1 ± 4.1 to 73.3 ± 6.5). Virtual reality is an emerging non-drug postoperative analgesia method. The findings showed that pain control was reduced by a mean of 1.48 points (95% CI: -2.02 to -0.95, p-value < 0.0001) in minor surgery and 0.32 points in major surgery (95% CI: -0.53 to -0.11, p-value < 0.03), and the overall postoperative satisfaction has improved. Discussion: Postoperative pain is a common clinical problem in surgical patients. Research has confirmed that virtual reality can create an immersive interactive environment, communicate with patients, and effectively relieve postoperative pain. However, virtual reality requires the purchase of hardware and software and other related computer equipment, and its high cost is a disadvantage. We selected the best literature based on clinical questions to answer the patient's question and used share decision making (SDM) to help the patient make decisions based on the clinical situation after knee replacement surgery to improve the quality of patient-centered care.

Keywords: knee replacement surgery, postoperative pain, share decision making, virtual reality

Procedia PDF Downloads 40

Authors: Aijing Luo, Zirui Xin, Yifeng Yuan

Abstract:

Background: With the rapid development of the online health community, more and more patients or families are seeking health information on the Internet. Objective: This study aimed to discuss how to fully reveal the health information needs expressed by hypertensive patients in their questions in the online environment. Methods: This study randomly selected 1,000 text records from the question data of hypertensive patients from 2008 to 2018 collected from the website www.haodf.com and constructed a classification system through literature research and content analysis. This paper identified the background characteristics and questioning the intention of each hypertensive patient based on the patient’s question and used co-occurrence network analysis to explore the features of the health information needs of hypertensive patients. Results: The classification system for health information needs of patients with hypertension is composed of 9 parts: 355 kinds of drugs, 395 kinds of symptoms and signs, 545 kinds of tests and examinations , 526 kinds of demographic data, 80 kinds of diseases, 37 kinds of risk factors, 43 kinds of emotions, 6 kinds of lifestyles, 49 kinds of questions. The characteristics of the explored online health information needs of the hypertensive patients include: i)more than 49% of patients describe the features such as drugs, symptoms and signs, tests and examinations, demographic data, diseases, etc. ii) these groups are most concerned about treatment (77.8%), followed by diagnosis (32.3%); iii) 65.8% of hypertensive patients will ask doctors online several questions at the same time. 28.3% of the patients are very concerned about how to adjust the medication, and they will ask other treatment-related questions at the same time, including drug side effects, whether to take drugs, how to treat a disease, etc.; secondly, 17.6% of the patients will consult the doctors online about the causes of the clinical findings, including the relationship between the clinical findings and a disease, the treatment of a disease, medication, and examinations. Conclusion: In the online environment, the health information needs expressed by Chinese hypertensive patients to doctors are personalized; that is, patients with different background features express their questioning intentions to doctors. The classification system constructed in this study can guide health information service providers in the construction of online health resources, to help solve the problem of information asymmetry in communication between doctors and patients.

Keywords: online health community, health information needs, hypertensive patients, doctor-patient communication

Procedia PDF Downloads 97

Authors: Ersumo Tessema, Bogale Girmaye Tamrat, Mohammed Burka

Abstract:

Background: Hyperthyroidism is a common thyroid disorder especially in women and characterized by increased thyroid hormone synthesis and secretion. The disorder manifests predominantly as Graves’ disease in iodine-sufficient areas and has increasing prevalence in iodine-deficient countries in patients with nodular thyroid disease and following iodine fortification. In Ethiopia, the magnitude of the disorder is unknown and, in Africa, due to scarcity of resources, its management remains suboptimal. Objective: The aim of this study was to analyze the pattern and management of patients with hyperthyroidism at the United Vision Medical Services Center, Addis Ababa between August 30, 2013, and February 1, 2018. Patients and methods: The study was a retrospective analysis of medical records of all patients with hyperthyroidism at the United Vision Private Medical Services Center, Addis Ababa. A questionnaire was filled out; the collected data entered into a computer and statistically analyzed using the SPSS package. The results were tabulated and discussed with literature review. Results: A total of 589 patients were included in this study. The median age was 40 years, and the male to female ratio was 1.0:7.9. Most patients (93%) presented with goiter and the associated features of toxic goiter except weight loss, sweating and tachycardia were uncommon. Majority of patients presented more than two years after the onset of their presenting symptoms. The most common physical finding (91%), as well as diagnosis, was toxic nodular goiter. The most frequent (83%) derangement in the thyroid function tests was a low thyroid-stimulating hormone, and the most commonly (94%) used antithyroid drug was a propylthiouracil. The most common (96%) surgical procedure in 213 patients was a near-total thyroidectomy with a postoperative course without incident in 92% of all the patients. Conclusion: The incidence and prevalence of hyperthyroidism are apparently on the increase in Addis Ababa, which may be related to the existing severe iodine-deficiency and or the salt iodation program (iodine-induced hyperthyroidism). Hyperthyroidism predominantly affects women and, in surgical services, toxic nodular goiter is more common than diffuse goiter, and the treatment of choice in experienced hands is a near-total thyroidectomy.

Keywords: Ethiopia, grave’s disease, hyperthyroidism, toxic nodular goiter

Procedia PDF Downloads 152

Authors: Adeline Meriaux, Claire Gaiani, Jennifer Burgain, Frantz Fournier, Lionel Muniglia, Jérémy Petit

Abstract:

Spray-drying process is widely used for the production of dairy powders for food and pharmaceuticals industries. It involves the atomization of a liquid feed into fine droplets, which are subsequently dried through contact with a hot air flow. The resulting powders permit transportation cost reduction and shelf life increase but can also exhibit various interesting functionalities (flowability, solubility, protein modification or acid gelation), depending on operating conditions and milk composition. Indeed, particles porosity, surface composition, lactose crystallization, protein denaturation, protein association or crust formation may change. Links between spray-drying conditions and physicochemical and functional properties of powders were investigated by a design of experiment methodology and analyzed by principal component analysis. Quadratic models were developed, and multicriteria optimization was carried out by the use of genetic algorithm. At the time of abstract submission, verification spray-drying trials are ongoing. To perform experiments, milk from dairy farm was collected, skimmed, froze and spray-dried at different air pressure (between 1 and 3 bars) and outlet temperature (between 75 and 95 °C). Dry matter, minerals content and proteins content were determined by standard method. Solubility index, absorption index and hygroscopicity were determined by method found in literature. Particle size distribution were obtained by laser diffraction granulometry. Location of the powder color in the Cielab color space and water activity were characterized by a colorimeter and an aw-value meter, respectively. Flow properties were characterized with FT4 powder rheometer; in particular, compressibility and shearing test were performed. Air pressure and outlet temperature are key factors that directly impact the drying kinetics and powder characteristics during spray-drying process. It was shown that the air pressure affects the particle size distribution by impacting the size of droplet exiting the nozzle. Moreover, small particles lead to more cohesive powder and less saturated color of powders. Higher outlet temperature results in lower moisture level particles which are less sticky and can explain a spray-drying yield increase and the higher cohesiveness; it also leads to particle with low water activity because of the intense evaporation rate. However, it induces a high hygroscopicity, thus, powders tend to get wet rapidly if they are not well stored. On the other hand, high temperature provokes a decrease of native serum proteins, which is positively correlated to gelation properties (gel point and firmness). Partial denaturation of serum proteins can improve functional properties of powder. The control of air pressure and outlet temperature during the spray-drying process significantly affects the physicochemical and functional properties of powder. This study permitted to better understand the links between physicochemical and functional properties of powder to identify correlations between air pressure and outlet temperature. Therefore, mathematical models have been developed, and the use of genetic algorithm will allow the optimization of powder functionalities.

Keywords: dairy powders, spray-drying, powders functionalities, design of experiment

Procedia PDF Downloads 44

Authors: V. S. Bessa, I. S. Moreira, S. Murgolo, C. Piccirillo, G. Mascolo, P. M. L. Castro

Abstract:

The occurrence of pharmaceuticals in the environment has been a topic of increasing concern. Pharmaceuticals are not completely mineralized in the human body and are released on the sewage systems as the pharmaceutical itself and as their “biologically active” metabolites through excretion, as well as by improper elimination and disposal. Conventional wastewater treatment plants (WWTPs) are not designed to remove these emerging pollutants and they are thus released into the environment. The antiepileptic drug carbamazepine (CBZ) and the non-steroidal anti-inflammatory diclofenac (DCF) are two widely used pharmaceuticals, frequently detected in water bodies, including rivers and groundwater, in concentrations ranging from ng L 1 to mg L 1. These two compounds were classified as medium to high-risk pollutants in WWTP effluents and surface waters. Also, CBZ has been suggested as a molecular marker of wastewater contamination in surface water and groundwater and the European Union included DCF in the watch list of substances Directive to be monitored. In the present study, biodegradation of CBZ and DCF by the bacterial strain Labrys portucalensis F11, a strain able to degrade other pharmaceutical compounds, was assessed; tests were performed with F11 as single carbon and energy source, as well as in presence of 5.9mM of sodium acetate. In assays supplemented with 2.0 and 4.0 µM of CBZ, the compound was no longer detected in the bulk medium after 24hr and 5days, respectively. Complete degradation was achieved in 21 days for 11.0 µM and in 23 days for 21.0 µM. For the highest concentration tested (43.0 µM), 95% of degradation was achieved in 30days. Supplementation with acetate increased the degradation rate of CBZ, for all tested concentrations. In the case of DCF, when supplemented as a single carbon source, approximately 70% of DCF (1.7, 3.3, 8.4, 17.5 and 34.0 µM) was degraded in 30days. Complete degradation was achieved in the presence of acetate for all tested concentrations, at higher degradation rates. The detection of intermediates produced during DCF biodegradation was performed by UPLC-QTOF/MS/MS, which allowed the identification of a range of metabolites. Stoichiometric liberation of chorine occurred and no metabolites were detected at the end of the biodegradation assays suggesting a complete mineralization of DCF. Strain Labrys portucalensis F11 proved to be able to degrade these two top priority environmental contaminants and may be potentially useful for biotechnological applications/environment remediation.

Keywords: biodegradation, carbamazepine, diclofenac, pharmaceuticals

Procedia PDF Downloads 244

Authors: Adil Mustafa, Ahmet Erten, Alper Kiraz, Melikhan Tanyeri

Abstract:

Work presented here is based on a novel experimental technique used to hydrodynamically trap oil microdroplets inside a microfluidic chip at the junction of microchannels known as stagnation point. Hydrodynamic trapping has been recently used to trap and manipulate a number of particles starting from microbeads to DNA and single cells. Benzyl Benzoate (BB) is used as droplet material. The microdroplets are trapped individually at stagnation point and their dissolution was observed. Experiments are performed for two concentrations (10mM or 10µM) of AOT surfactant (Docusate Sodium Salt) and two flow rates for each case. Moreover, experimental data is compared with Zhang-Yang-Mao (ZYM) model which studies dissolution of liquid microdroplets in the presence of a host fluid experiencing extensional creeping flow. Industrial processes like polymer blending systems in which heat or mass transport occurs experience extensional flow and an insight into these phenomena is of significant importance to many industrial processes. The experimental technique exploited here gives an insight into the dissolution of liquid microdroplets under extensional flow regime. The comparison of our experimental results with ZYM model reveals that dissolution of microdroplets at lower surfactant concentration (10µM) fits the ZYM model at saturation concentration (Cs) value reported in literature (Cs = 15×10⁻³Kg\m³) while for higher surfactant concentration (10mM) which is also above the critical micelle concentration (CMC) of surfactant (5mM) the data fits ZYM model at (Cs = 45×10⁻³Kg\m³) which is 3X times the value reported in literature. The difference in Cs value from the literature shows enhancement in dissolution rate of sparingly soluble BB microdroplets at surfactant concentrations higher than CMC. Enhancement in the dissolution of sparingly soluble materials is of great importance in pharmaceutical industry. Enhancement in the dissolution of sparingly soluble drugs is a key research area for drug design industry. The experimental method is also advantageous because it is robust and has no mechanical contact with droplets under study are freely suspended in the fluid as compared existing methods used for testing dissolution of drugs. The experiments also give an insight into CMC measurement for surfactants.

Keywords: extensional flow, hydrodynamic trapping, Zhang-Yang-Mao, CMC

Procedia PDF Downloads 323

Authors: Khadijeh Abhari, Seyed Shahram Shekarforoush, Saeid Hosseinzadeh

Abstract:

Probiotics have been considered as an approach to treat and prevent a wide range of inflammatory diseases. The spore forming probiotic strain Bacillus coagulans has demonstrated anti-inflammatory and immune-modulating effects in both animals and humans. The prebiotic, inulin, also potentially affects the immune system as a result of the change in the composition or fermentation profile of the gastrointestinal microbiota. An in vivo trial was conducted to evaluate the effects of probiotic B. coagulans, and inulin, either separately or in combination, on down regulate immune responses and progression of rheumatoid arthritis using induced arthritis rat model. Forty-eight male Wistar rats were randomly divided into 6 groups and fed as follow: 1) control: Normal healthy rats fed by standard diet, 2) Disease control (RA): Arthritic induced (RA) rats fed by standard diet, 3) Prebiotic (PRE): RA+ 5% w/w long chain inulin, 4) Probiotic (PRO): RA+ 109 spores/day B. coagulans by orogastric gavage, 5) Synbiotic (SYN): RA+ 5% w/w long chain inulin and 109 spores/day B. coagulans and 6) Treatment control: (INDO): RA+ 3 mg/kg/day indomethacin by orogastric gavage. Feeding with mentioned diets started on day 0 and continued to the end of study. On day 14, rats were injected with complete Freund’s adjuvant (CFA) to induce arthritis. Arthritis activity was evaluated by biochemical parameters and paw thickness. Biochemical assay for Fibrinogen (Fn), Serum Amyloid A (SAA), TNF-α and Alpha-1-acid glycoprotein (α1AGp) was performed on day 21, 28 and 35 (1, 2 and 3 weeks post RA induction). Pretreatment with PRE, PRO and SYN diets significantly inhibit SAA and Fn production in arthritic rats (P < 0.001). A significant decrease in production of pro-inflammatory cytokines, TNF-α, was seen in PRE, PRO and SYN groups (P < 0.001) which was similar to the effect of the anti-inflammatory drug Indomethacin. Further, there were no significant anti-inflammatory effects observed following different treatments using α1AGp as a RA indicator. Pretreatment with all supplied diets significantly inhibited the development of paw swelling induced by CFA (P < 0.001). Conclusion: Results of this study support that oral intake of probiotic B. coagulans and inulin are able to improve biochemical and clinical parameters of induced RA in rat.

Keywords: rheumatoid arthritis, bacillus coagulans, inulin, animal model

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Authors: Sergio Celaschi, Henrique Canavarro de Alencar, Claaudecir Biazoli

Abstract:

Effluent quality is of the highest priority for compliance with the permit limits of environmental protection agencies and ensures the protection of their local water system. Of the pollutants monitored, the biochemical oxygen demand (BOD) posed one of the greatest challenges. This work presents a solution for wastewater treatment plants - WWTP’s ability to react to different situations and meet treatment goals. Delayed BOD5 results from the lab take 7 to 8 analysis days, hindered the WWTP’s ability to react to different situations and meet treatment goals. Reducing BOD turnaround time from days to hours is our quest. Such a solution is based on a system of two BOD bioreactors associated with Digital Twin (DT) and Machine Learning (ML) methodologies via an Internet of Things (IoT) platform to monitor and control a WWTP to support decision making. DT is a virtual and dynamic replica of a production process. DT requires the ability to collect and store real-time sensor data related to the operating environment. Furthermore, it integrates and organizes the data on a digital platform and applies analytical models allowing a deeper understanding of the real process to catch sooner anomalies. In our system of continuous time monitoring of the BOD suppressed by the effluent treatment process, the DT algorithm for analyzing the data uses ML on a chemical kinetic parameterized model. The continuous BOD monitoring system, capable of providing results in a fraction of the time required by BOD5 analysis, is composed of two thermally isolated batch bioreactors. Each bioreactor contains input/output access to wastewater sample (influent and effluent), hydraulic conduction tubes, pumps, and valves for batch sample and dilution water, air supply for dissolved oxygen (DO) saturation, cooler/heater for sample thermal stability, optical ODO sensor based on fluorescence quenching, pH, ORP, temperature, and atmospheric pressure sensors, local PLC/CPU for TCP/IP data transmission interface. The dynamic BOD system monitoring range covers 2 mg/L < BOD < 2,000 mg/L. In addition to the BOD monitoring system, there are many other operational WWTP sensors. The CPU data is transmitted/received to/from the digital platform, which in turn performs analyses at periodic intervals, aiming to feed the learning process. BOD bulletins and their credibility intervals are made available in 12-hour intervals to web users. The chemical kinetics ML algorithm is composed of a coupled system of four first-order ordinary differential equations for the molar masses of DO, organic material present in the sample, biomass, and products (CO₂ and H₂O) of the reaction. This system is solved numerically linked to its initial conditions: DO (saturated) and initial products of the kinetic oxidation process; CO₂ = H₂0 = 0. The initial values for organic matter and biomass are estimated by the method of minimization of the mean square deviations. A real case of continuous monitoring of BOD wastewater effluent quality is being conducted by deploying an IoT application on a large wastewater purification system located in S. Paulo, Brazil.

Keywords: effluent treatment, biochemical oxygen demand, continuous monitoring, IoT, machine learning

Procedia PDF Downloads 48

Authors: Shannon Glaspy, Gerald Boon, Jack Lambert

Abstract:

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

Keywords: ARV, adverse events, HAART, pediatric

Procedia PDF Downloads 155

Authors: Evelyn Ilabaca, Ximena Valenzuela, Alejandra Torres, María José Galotto, Abel Guarda

Abstract:

One of the biggest problems in food packaging industry, especially with the plastic materials, is the fact that these materials are usually obtained from non-renewable resources and also remain as waste after its use, causing environmental issues. This is an international concern and particular attention is given to reduction, reuse and recycling strategies for decreasing the waste from plastic packaging industry. In general, polyethylenes represent most plastic waste and recycling process of post-consumer polyethylene terephthalate (PCR-PET) has been studied. US Food and Drug Administration (FDA), European Food Safety Authority (EFSA) and Southern Common Market (MERCOSUR) have generated different legislative documents to control the use of PCR-PET in the production of plastic packaging intended direct food contact in order to ensure the capacity of recycling process to remove possible contaminants that can migrate into food. Consequently, it is necessary to demonstrate by challenge test that the recycling process is able to remove specific contaminants, obtaining a safe recycled plastic to human health. These documents establish that the concentration limit for substitute contaminants in PET is 220 ppb (ug/kg) and the specific migration limit is 10 ppb (ug/kg) for each contaminant, in addition to assure the sensorial characteristics of food are not affected. Moreover, under the Commission Regulation (EU) N°10/2011 on plastic materials and articles intended to come into contact with food, it is established that overall migration limit is 10 mg of substances per 1 dm2 of surface area of the plastic material. Thus, the aim of this work is to determine the safety of PCR-PET-containing food packaging materials in Chile by measuring their overall migration, and their comparison with the established limits at international level. This information will serve as a basis to provide a regulation to control and regulate the use of recycled plastic materials in the manufacture of plastic packaging intended to be in direct contact with food. The methodology used involves a procedure according to EN-1186:2002 with some modifications. The food simulants used were ethanol 10 % (v/v) and acetic acid 3 % (v/v) as aqueous food simulants, and ethanol 95 % (v/v) and isooctane as substitutes of fatty food simulants. In this study, preliminary results showed that Chilean food packaging plastics with different PCR-PET percentages agree with the European Legislation for food aqueous character.

Keywords: contaminants, polyethylene terephthalate, plastic food packaging, recycling

Procedia PDF Downloads 249

Authors: Ramin Mehdiabadi

Abstract:

Background: Breast cancer remains the most prevalent cancer diagnosis and the leading cause of cancer death among women globally, representing 11.7% of new cases and 6.9% of deaths. While the incidence and mortality of major cancers are declining in developed regions like the United States and Western Europe, underdeveloped and developing countries exhibit an increasing trend, attributed to lifestyle factors such as smoking, physical inactivity, and high-calorie diets. Objective: This study explores the intricate relationship between the mammalian transcription factor forkhead box (FoxM1) and the microRNA miR-216b-5p in various subtypes of breast cancer, aiming to deepen the understanding of their roles in tumorigenesis, metastasis, and drug resistance. Methods: Breast cancer subtypes were categorized based on key biomarkers: estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2. These include luminal A, luminal B, HER2 enriched, triple-negative, and normal-like subtypes. We focused on analyzing the expression levels of FoxM1 and miR-216b-5p, given the known role of FoxM1 in cell proliferation and its implications in cancer pathologies such as lung, gastric, and breast cancers. Concurrently, miR-216b-5p's function as a tumor suppressor was evaluated to ascertain its regulatory effects on FoxM1. Results: Preliminary data indicate a nuanced interplay between FoxM1 and miR-216b-5p, suggesting a potential inverse relationship that varies across breast cancer subtypes. This relationship underscores the dual role of these biomarkers in modulating cancer progression and response to treatments. Conclusion: The findings advocate for the potential of miR-216b-5p to serve as a prognostic biomarker and a therapeutic target, particularly in subtypes where FoxM1 is prominently expressed. Understanding these molecular interactions provides crucial insights into the personalized treatment strategies and could lead to more effective therapeutic interventions in breast cancer management. Implications: The study highlights the importance of molecular profiling in breast cancer treatment and emphasizes the need for targeted therapeutic approaches in managing diverse cancer subtypes, particularly in varying global contexts where lifestyle factors significantly impact cancer dynamics.

Keywords: breast cancer, gene expression, FoxM1, microRNA

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Authors: S. D. Kadir

Abstract:

Background: Antibiotics have always been at the centrum of the revolution of modern microbiology. Micro-organisms and its pathogenicity, resistant organisms, inappropriate or over usage of various types of antibiotic agents are fuelled multidrug-resistant pathogenic organisms. Our present time review report mainly focuses on the therapeutic condition of antibiotic resistance and the possible roots behind the development of antibiotic resistance in Bangladesh in 2019. Methodology: The systemic review has progressed through a series of research analyses on various manuscripts published on Google Scholar, PubMed, Research Gate, and collected relevant information from established popular healthcare and diagnostic center and its subdivisions all over Bangladesh. Our research analysis on the possible assurance of antibiotic resistance been ensured by the selective medical reports and on random assay on the extent of individual antibiotic in 2019. Results: 5 research articles, 50 medical report summary, and around 5 patients have been interviewed while going through the estimation process. We have prioritized research articles where the research analysis been performed by the appropriate use of the Kirby-Bauer method. Kirby-Bauer technique is preferred as it provides greater efficiency, ensures lower performance expenditure, and supplies greater convenience and simplification in the application. In most of the reviews, clinical and laboratory standards institute guidelines were strictly followed. Most of our reports indicate significant resistance shown by the Beta-lactam drugs. Specifically by the derivatives of Penicillin's, Cephalosporin's (rare use of the first generation Cephalosporin and overuse of the second and third generation of Cephalosporin and misuse of the fourth generation of Cephalosporin), which are responsible for almost 67 percent of the bacterial resistance. Moreover, approximately 20 percent of the resistance was due to the fact of drug pumping from the bacterial cell by tetracycline and sulphonamides and their derivatives. Conclusion: 90 percent of the approximate antibiotic resistance is due to the usage of relative and true broad-spectrum antibiotics. The environment has been created by the following circumstances where; the excessive usage of broad-spectrum antibiotics had led to a condition where the disruption of native bacteria and a series of anti-microbial resistance causing a disturbance of the surrounding environments in medium, leading to a state of super-infection.

Keywords: antibiotics, antibiotic resistance, Kirby Bauer method, microbiology

Procedia PDF Downloads 104

Authors: Govind Kumar

Abstract:

The concept of ‘e-governance’ that was brought about by the new wave of reforms, namely ‘LPG’ in the early 1990s, has been enabling governments across the globe to digitally transform themselves. Digital transformation is leading the governments with qualitative decisions, optimization in rational use of resources, facilitation of cost-benefit analyses, and elimination of redundancy and corruption with the help of ICT-based applications interface. ICT-based applications/technologies have enormous potential for impacting positive change in the social lives of the global citizenry. Supercomputers test and analyze millions of drug molecules for developing candidate vaccines to combat the global pandemic. Further, e-commerce portals help distribute and supply household items and medicines, while videoconferencing tools provide a visual interface between the clients and hosts. Besides, crop yields are being maximized with the help of drones and machine learning, whereas satellite data, artificial intelligence, and cloud computing help governments with the detection of illegal mining, tackling deforestation, and managing freshwater resources. Such e-applications have the potential to take governance an extra mile by achieving 5 Es (effective, efficient, easy, empower, and equity) of e-governance and six Rs (reduce, reuse, recycle, recover, redesign and remanufacture) of sustainable development. If such digital transformation gains traction within the government framework, it will replace the traditional administration with the digitalization of public administration. On the other hand, it has brought in a new set of challenges, like the digital divide, e-illiteracy, technological divide, etc., and problems like handling e-waste, technological obsolescence, cyber terrorism, e-fraud, hacking, phishing, etc. before the governments. Therefore, it would be essential to bring in a rightful mixture of technological and humanistic interventions for addressing the above issues. This is on account of the reason that technology lacks an emotional quotient, and the administration does not work like technology. Both are self-effacing unless a blend of technology and a humane face are brought in into the administration. The paper will empirically analyze the significance of the technological framework of digital transformation within the government set up for the digitalization of public administration on the basis of the synthesis of two case studies undertaken from two diverse fields of administration and present a future framework of the study.

Keywords: digital transformation, electronic governance, public administration, knowledge framework

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Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

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Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

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Authors: Zainab Dashti, Leila Vali

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Background: The Middle East, in particular Kuwait, contains one of the highest rates of patients with Diabetes in the world. Generally, infections resistant to antibiotics among the diabetic population has been shown to be on the rise. This is the first study in Kuwait to compare the antibiotic resistance profiles and genotypic differences between the resistant isolates of Enterobacteriaceae obtained from diabetic and non-diabetic patients. Material/Methods: In total, 65 isolates were collected from diabetic patients consisting of 34 E. coli, 15 K. pneumoniae and 16 other Enterobacteriaceae species (including Salmonella spp. Serratia spp and Proteus spp.). In our control group, a total of 49 isolates consisting of 37 E. coli, 7 K. pneumoniae and 5 other species (including Salmonella spp. Serratia spp and Proteus spp.) were included. Isolates were identified at the species level and antibiotic resistance profiles, including Colistin, were determined using initially the Vitek system followed by double dilution MIC and E-test assays. Multi drug resistance (MDR) was defined as isolates resistant to a minimum of three antibiotics from three different classes. PCR was performed to detect ESBL genes (blaCTX-M, blaTEM & blaSHV), flouroquinolone resistance genes (qnrA, qnrB, qnrS & aac(6’)-lb-cr) and carbapenem resistance genes (blaOXA, blaVIM, blaGIM, blaKPC, blaIMP, & blaNDM) in both groups. Pulse field gel electrophoresis (PFGE) was performed to compare clonal relatedness of both E. coli and K.pneumonaie isolates. Results: Colistin resistance was determined in three isolates with MICs of 32-128 mg/L. A significant difference in resistance to ampicillin (Diabetes 93.8% vs control 72.5%, P value <0.002), augmentin (80% vs 52.5%, p value < 0.003), cefuroxime (69.2% vs 45%, p value < 0.0014), ceftazadime (73.8% vs 42.5%, p value <0.001) and ciprofloxacin (67.6% vs 40%, p value < 0.005) were determined. Also, a significant difference in MDR rates between the two groups (Diabetes 76.9%, control 57.5%, p value <0.036 were found. All antibiotic resistance genes showed a higher prevalence among the diabetic group, except for blaCTX-M, which was higher among the control group. PFGE showed a high rate of diversity between each group of isolates. Conclusions: Our results suggested an alarming rate of antibiotic resistance, in particular Colistin resistance (1.8%) among K. pneumoniea isolated from diabetic patients in Kuwait. MDR among Enterobacteriaceae infections also seems to be a worrying issue among the diabetics of Kuwait. More efforts are required to limit the issue of antibiotic resistance in Kuwait, especially among patients with diabetes mellitus.

Keywords: antibiotic resistance, diabetes, enterobacreriacae, multi antibiotic resistance

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Authors: Faiz N. K. Yusufi, Aquil Ahmed, Jamal Ahmad

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Predicting the risk of diabetic retinopathy (DR) in Indian type 2 diabetes patients is immensely necessary. India, being the second largest country after China in terms of a number of diabetic patients, to the best of our knowledge not a single risk score for complications has ever been investigated. Diabetic retinopathy is a serious complication and is the topmost reason for visual impairment across countries. Any type or form of DR has been taken as the event of interest, be it mild, back, grade I, II, III, and IV DR. A sample was determined and randomly collected from the Rajiv Gandhi Centre for Diabetes and Endocrinology, J.N.M.C., A.M.U., Aligarh, India. Collected variables include patients data such as sex, age, height, weight, body mass index (BMI), blood sugar fasting (BSF), post prandial sugar (PP), glycosylated haemoglobin (HbA1c), diastolic blood pressure (DBP), systolic blood pressure (SBP), smoking, alcohol habits, total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), physical activity, duration of diabetes, diet control, history of antihypertensive drug treatment, family history of diabetes, waist circumference, hip circumference, medications, central obesity and history of DR. Cox proportional hazard regression is used to design risk scores for the prediction of retinopathy. Model calibration and discrimination are assessed from Hosmer Lemeshow and area under receiver operating characteristic curve (ROC). Overfitting and underfitting of the model are checked by applying regularization techniques and best method is selected between ridge, lasso and elastic net regression. Optimal cut off point is chosen by Youden’s index. Five-year probability of DR is predicted by both survival function, and Markov chain two state model and the better technique is concluded. The risk scores developed can be applied by doctors and patients themselves for self evaluation. Furthermore, the five-year probabilities can be applied as well to forecast and maintain the condition of patients. This provides immense benefit in real application of DR prediction in T2DM.

Keywords: Cox proportional hazard regression, diabetic retinopathy, ROC curve, type 2 diabetes mellitus

Procedia PDF Downloads 153

Authors: Sofia N. Gonçalves, Duarte M. S. Albuquerque, José C. F. Pereira

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Microwave technology has been gaining importance in contributing to decarbonization processes in high energy demand industries. Despite the several numerical models presented in the literature, a proper Verification and Validation exercise is still lacking. This is important and required to evaluate the physical process model accuracy and adequacy. Another issue addresses impedance matching, which is an important mechanism used in microwave experiments to increase electromagnetic efficiency. Such mechanism is not available in current computational tools, thus requiring an external numerical procedure. A numerical model was implemented to study the continuous processing of limestone with microwave heating. This process requires the material to be heated until a certain temperature that will prompt a highly endothermic reaction. Both a 2D and 3D model were built in COMSOL Multiphysics to solve the two-way coupling between Maxwell and Energy equations, along with the coupling between both heat transfer phenomena and limestone endothermic reaction. The 2D model was used to study and evaluate the required numerical procedure, being also a benchmark test, allowing other authors to implement impedance matching procedures. To achieve this goal, a controller built in MATLAB was used to continuously matching the cavity impedance and predicting the required energy for the system, thus successfully avoiding energy inefficiencies. The 3D model reproduces realistic results and therefore supports the main conclusions of this work. Limestone was modeled as a continuous flow under the transport of concentrated species, whose material and kinetics properties were taken from literature. Verification and Validation of the coupled model was taken separately from the chemical kinetic model. The chemical kinetic model was found to correctly describe the chosen kinetic equation by comparing numerical results with experimental data. A solution verification was made for the electromagnetic interface, where second order and fourth order accurate schemes were found for linear and quadratic elements, respectively, with numerical uncertainty lower than 0.03%. Regarding the coupled model, it was demonstrated that the numerical error would diverge for the heat transfer interface with the mapped mesh. Results showed numerical stability for the triangular mesh, and the numerical uncertainty was less than 0.1%. This study evaluated limestone velocity, heat transfer, and load influence on thermal decomposition and overall process efficiency. The velocity and heat transfer coefficient were studied with the 2D model, while different loads of material were studied with the 3D model. Both models demonstrated to be highly unstable when solving non-linear temperature distributions. High velocity flows exhibited propensity to thermal runways, and the thermal efficiency showed the tendency to stabilize for the higher velocities and higher filling ratio. Microwave efficiency denoted an optimal velocity for each heat transfer coefficient, pointing out that electromagnetic efficiency is a consequence of energy distribution uniformity. The 3D results indicated the inefficient development of the electric field for low filling ratios. Thermal efficiencies higher than 90% were found for the higher loads and microwave efficiencies up to 75% were accomplished. The 80% fill ratio was demonstrated to be the optimal load with an associated global efficiency of 70%.

Keywords: multiphysics modeling, microwave heating, verification and validation, endothermic reactions modeling, impedance matching, limestone continuous processing

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Authors: Mohamad Shamsuri Juhari

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Fathers who positively involve themselves in their children’s lives will have had a constructive influence on the latter’s social, behavioural, and psychological development. This paper will share the preliminary findings of an ongoing research project which investigates Singaporean fathers from the nation’s minority Malay-Muslim community who commit the reverse, that is, it intends to study the reasons behind these fathers’ non-involvement during the period of their children’s developing years be it through absence, disinterest or ignorance. For instance, children from homes with absentee fathers are more likely to develop deficiencies in attitude and conduct. A father’s negative show of parental skills can also cause setbacks in the child’s education, economic instability in the latter’s future family life, as well as the likelihood of an ensuing intergenerational transmission of criminal behaviour. In the context of the minority Singaporean Malay-Muslim community, the need to investigate the challenges faced by fathers from the ethnic group in carrying out their parental roles arose due to the perceptible rise in statistics reflecting delinquency among its youths. This has resulted in other associated issues such as teenage pregnancies (and the subsequent cyclical patterns of divorce and single motherhood), over-representation in the data for drug offences, and under-representation in statistics reflecting academic achievement. While other factors are known to be involved, these negative outcomes have also been attributed to the lack of fatherly guidance in the affected Malay families. This still-ongoing research project is being carried out in two phases: The first by means of secondary research as well as exploratory data collection via roundtable and focus group discussions with fathers from diverse socio-economic backgrounds. This sets the way for the second phase in which a survey will be undertaken, followed by a series of in-depth face-to-face interviews. The research findings will then be translated into intervention initiatives to overcome the identified challenges. Based on the results collated from Phase 1 of the research, this paper will share a ‘first look’ on the challenges to effective parenting faced by Malay-Muslim fathers in Singapore specifically those relating to the socio-cultural domains of attitude, knowledge, and practice.

Keywords: Malay fathers, socio-cultural domains, attitude, knowledge, practice

Procedia PDF Downloads 160

Authors: Sara Taghdisi, Mehrosadat Mirmohammadi, Mostafa Mokhtarian, Mohammad Hossein Pazandeh

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Leishmaniasis is one of the 10 most important diseases of the World Health Organization with health problems in more than 90 countries. Over one billion people are at risk of these diseases on almost every continent. The present human study was performed to evaluate the therapeutic effect of cotton plant on cutaneous leishmaniasis leision. firstly, the cotton seeds were cleaned and grinded to smaller particles. In the second step, the seeds were oiled by cold press method. In order to separate bioactive compound, after saponification of the oil, its gossypol was hydrolyzed and crystalized. finally, the therapeutic effect of Cottonseed Oil on cutaneous leishmaniasis was investigated. In the current project, Gossypol was extracted with a liquid-liquid extraction method in 120 minutes in the presence of Phosphoric acid from the cotton seed oil of Golestan beach varieties, then got crystallized in darkness using Acetic acid and isolated as Gossypol Acetic acid. The efficiency of the extracted crystal was obtained at 1.28±0.12. the cotton plant could be efficient in the treatment of Cutaneous leishmaniasis. This double-blind randomized controlled clinical trial was performed on 88 cases of leishmaniasis wounds. Patients were randomly divided into two groups of 44 cases. two groups received conventional treatment. In addition to the usual treatment (glucantime), the first group received cottonseed oil and the control group received placebo. The results of the present study showed that the surface of lesion before the intervention and in the first to fourth weeks after the intervention was not significantly different between the two groups (P-value> 0.05). But the surface of lesion in the Intervention group in the eighth and twelfth weeks was lower than the control group (P-value <0.05). This study showed that the improvement of leishmaniasis lesion using topical cotton plant mark in the eighth and twelfth weeks after the intervention was significantly more than the control group. Considering the most common chemical drugs for Cutaneous leishmaniasis treatment are sodium stibogluconate, and meglumine antimonate, which not only have relatively many side effects, but also some species of the Leishmania genus have become resistant to them. Therefore, a plant base bioactive compound such as cottonseed oil can be useful whit fewer side effects.

Keywords: cottonseed oil, crystallization, gossypol, leishmaniasis

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Authors: Nandhakumar Elumalai, Purushothaman Ayyakannu, Sachidanandam T. Panchanatham

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Background: Understanding the basic mechanisms and factors underlying the tumor growth and invasion has gained attention in recent times. The processes of angiogenesis and apoptosis are known to play a vital role in various stages of cancer. The vascular endothelial growth factor (VEGF) is well established as one of the key regulators of tumor angiogenesis while MMPs are known for their exclusive ability to degrade ECM. Objective: The present study was designed to evaluate the pro apoptotic and anti angiogenic activity of the herbal formulation Shemamruthaa. The anticancer activity of Shemamruthaa was tested in breast cancer cell line (MCF-7). Results of MTT, trypan blue and flow cytometric analysis of apoptotis suggested that Shemamruthaa can induce cytotoxicity in cancer cells, in a concentration- and time dependent manner and induce apoptosis. With these results, we further evaluated the antiangiogenic and pro-apoptotic activities of Shemamruthaa in DMBA induced mammary carcinoma in Sprague Dawley rats. Flavono tumour was induced in 8-week-old Sprague-Dawley rats by gastric intubation of 25 mg DMBA in 1ml olive oil. After 90 days of induction period, the rats were orally administered with Shemamruthaa (400 mg/kg body wt) for 45 days. Treatment with the drug SM significantly modulated the expression of p53, MMP-2, MMP-3, MMP-9 and VEGF by means of its anti angiogenic and protease inhibiting activity. Conclusion: Based on these results, it might be concluded that the formulation, Shemamruthaa, constituted of dried flowers of Hibiscus rosa-sinensis, fruits of Emblica officinalis, and honey has been found to exhibit pronounced antiproliferative and apoptotic effects. This enhanced anticancer effect of Shemamruthaa might be attributed to the synergistic action of polyphenols such as flavonoids, tannins, alkaloids, glycosides, saponins, steroids, terpenoids, vitamin C, niacin, pyrogallol, hydroxymethylfurfural, trilinolein, and other compounds present in the formulation. Collectively, these results demonstrate that Shemamruthaa holds potential to be developed as a potent chemotherapeutic agent against mammary carcinoma.

Keywords: Shemamruthaa, flavonoids, MCF-7 cell line, mammary cancer

Procedia PDF Downloads 226

Authors: Lucie Matricon, Anne Roubaud, Geert Haarlemmer, Christophe Geantet

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Introduction: This case discusses the management of two floor of mouth (FOM) Squamous Cell Carcinomas (SCC) not identified upon initial biopsy. Case Report: A 51 year-old male presented with right FOM erythroleukoplakia. Relevant medical history included alcoholic dependence syndrome and alcoholic liver disease. Relevant drug therapy encompassed acamprosate, folic acid, hydroxocobalamin and thiamine. The patient had a 55.5 pack-year smoking history and alcohol dependence from age 14, drinking 16 units/day. FOM incisional biopsy and histopathological analysis diagnosed Carcinoma in situ. Treatment involved wide local excision. Specimen analysis revealed two separate foci of pT1 moderately differentiated SCCs. Carcinoma staging scans revealed no pathological lymphadenopathy, no local invasion or metastasis. SCCs had been excised in completion with narrow margins. MDT discussion concluded that in view of the field changes it would be difficult to identify specific areas needing further excision, although techniques such as Lugol’s Iodine were considered. Further surgical resection, surgical neck management and sentinel lymph node biopsy was offered. The patient declined intervention, primary management involved close monitoring alongside alcohol and smoking cessation referral. Discussion: Narrow excisional margins can increase carcinoma recurrence risk. Biopsy failed to identify SCCs, despite sampling an area of clinical concern. For gross field change multiple incisional biopsies should be considered to increase chance of accurate diagnosis and appropriate treatment. Coupling of tobacco and alcohol has a synergistic effect, exponentially increasing the relative risk of oral carcinoma development. Tobacco and alcoholic control is fundamental in reducing treatment‑related side effects, recurrence risk, and second primary cancer development.

Keywords: microalgae, biofuels, hydrothermal liquefaction, biomass

Procedia PDF Downloads 103

Authors: Ane Escobar, Paula Angelomé, Mihaela Delcea, Marek Grzelczak, Sergio Enrique Moya

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The antibacterial capacity of bone-anchoring implants can be improved by the use of antibiotics that can be delivered to the media after the surgery. Mesoporous films have shown great potential in drug delivery for orthopedic applications, since pore size and thickness can be tuned to produce different surface area and free volume inside the material. This work shows the synthesis of mesoporous titania films (MTF) by sol-gel chemistry and evaporation-induced self-assembly (EISA) on top of glass substrates. Pores with a diameter of 12nm were observed by Transmission Electron Microscopy (TEM). A film thickness of 100 nm was measured by Scanning Electron Microscopy (SEM). Gentamicin was used to study the antibiotic delivery from the film by means of High-performance liquid chromatography (HPLC). The Staphilococcus aureus strand was used to evaluate the effectiveness of the penicillin loaded films toward inhibiting bacterial colonization. MC3T3-E1 pre-osteoblast cell proliferation experiments proved that MTFs have a good biocompatibility and are a suitable surface for MC3T3-E1 cell proliferation. Moreover, images taken by Confocal Fluorescence Microscopy using labeled vinculin, showed good adhesion of the MC3T3-E1 cells to the MTFs, as well as complex actin filaments arrangement. In order to improve cell proliferation Bone Morphogenetic Protein-2 (BMP-2) was adsorbed on top of the mesoporous film. The deposition of the protein was proved by measurements in the contact angle, showing an increment in the hydrophobicity while the protein concentration is higher. By measuring the dehydrogenase activity in MC3T3-E1 cells cultured in dually functionalized mesoporous titatina films with gentamicin and BMP-2 is possible to find an improvement in cell proliferation. For this purpose, the absorption of a yellow-color formazan dye, product of a water-soluble salt (WST-8) reduction by the dehydrogenases, is measured. In summary, this study proves that by means of the surface modification of MTFs with proteins and loading of gentamicin is possible to achieve an antibacterial effect and a cell growth improvement.

Keywords: antibacterial, biocompatibility, bone morphogenetic protein-2, cell proliferation, gentamicin, implants, mesoporous titania films, osteoblasts

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Authors: Magdalena Korytowska, Gunnar Lengstrand, Cecilia Larsson Wexell

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

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

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Authors: Rob Schindler

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Industry-standard methods of mitigating erosion of seabed sediments rely on ‘hard engineering’ approaches which have numerous environmental shortcomings: (1) direct loss of habitat by smothering of benthic species, (2) disruption of sediment transport processes, damaging geomorphic and ecosystem functionality (3) generation of secondary erosion problems, (4) introduction of material that may propagate non-local species, and (5) provision of pathways for the spread of invasive species. Recent studies have also revealed the importance of biological cohesion, the result of naturally occurring extra-cellular polymeric substances (EPS), in stabilizing natural sediments. Mimicking the strong bonding kinetics through the deliberate addition of EPS to sediments – henceforth termed ‘biostabilisation’ - offers a means in which to mitigate against erosion induced by structures or episodic increases in hydrodynamic forcing (e.g. storms and floods) whilst avoiding, or reducing, hard engineering. Here we present unique experiments that systematically examine how biostabilisation reduces scour around a monopile in a current, a first step to realizing the potential of this new method of scouring reduction for a wide range of engineering purposes in aquatic substrates. Experiments were performed in Plymouth University’s recirculating sediment flume which includes a recessed scour pit. The model monopile was 0.048 m in diameter, D. Assuming a prototype monopile diameter of 2.0 m yields a geometric ratio of 41.67. When applied to a 10 m prototype water depth this yields a model depth, d, of 0.24 m. The sediment pit containing the monopile was filled with different biostabilised substrata prepared using a mixture of fine sand (D50 = 230 μm) and EPS (Xanthan gum). Nine sand-EPS mixtures were examined spanning EPS contents of 0.0% < b0 < 0.50%. Scour development was measured using a laser point gauge along a 530 mm centreline at 10 mm increments at regular periods over 5 h. Maximum scour depth and excavated area were determined at different time steps and plotted against time to yield equilibrium values. After 5 hours the current was stopped and a detailed scan of the final scour morphology was taken. Results show that increasing EPS content causes a progressive reduction in the equilibrium depth and lateral extent of scour, and hence excavated material. Very small amounts equating to natural communities (< 0.1% by mass) reduce scour rate, depth and extent of scour around monopiles. Furthermore, the strong linear relationships between EPS content, equilibrium scour depth, excavation area and timescales of scouring offer a simple index on which to modify existing scour prediction methods. We conclude that the biostabilisation of sediments with EPS may offer a simple, cost-effective and ecologically sensitive means of reducing scour in a range of contexts including OWFs, bridge piers, pipeline installation, and void filling in rock armour. Biostabilisation may also reduce economic costs through (1) Use of existing site sediments, or waste dredged sediments (2) Reduced fabrication of materials, (3) Lower transport costs, (4) Less dependence on specialist vessels and precise sub-sea assembly. Further, its potential environmental credentials may allow sensitive use of the seabed in marine protection zones across the globe.

Keywords: biostabilisation, EPS, marine, scour

Procedia PDF Downloads 147

Authors: Ali Showail Ali Alasmari

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Introduction: Cataract is the loss of transparency of the lens inside the eye. It is the most common cause of visual loss and blindness worldwide. This study provides a systemic review of the recent findings on the association of vitamin D, and vitamin B12, and their possible role in preventing cataracts in senile (S) and diabetic mellitus (DM) patient groups. Objective: This study was intended to establish and investigate if there is any role between vitamin D and vitamin B12? Secondly, the connection between serum level of vitamin D and vitamin B12 in cataract incidence senile (s) vs. diabetic mellitus (DM) cataract patient groups. Furthermore, to evaluate and analyze cataract occurrence regarding vitamin D and vitamin B12 levels with other risk factors. Finally, to evaluate lens opacities pre and post treatment with vitamin D and vitaminB12 linked to age and visual acuity loss in both senile(S) and diabetic mellitus (DM) cataract patients’ groups. Methods: This study conducted at the ophthalmology clinic at Muhyail General Hospital. Select a prospective case-control to study the effect of vitamin D and Vit B12 on senile(S) cataracts that caused by age and diabetic mellitus (DM)cataract patients; then we compare these two groups. This study prospectively enrolled a total of 50 samples, 25 with senile cataract and 25 with diabetic cataract, from ophthalmology clinic at Muhyail General Hospital. Measuring 25-hydroxy vitamin D and vitamin B12 level concentrations in the assigned samples. Analyses were performed using SAS (statistical analysis software) program. Results: The most important finding in this study was that the senile(s) cataract patients’ group greatly benefited by the combination therapy of vitamin D, and Vitamin B12 reached (28.5±1.50 and 521.1±21.10) respectively; on the contrary, the diabetic cataract patient group hardly shows any significant improvement (21.5 ± 1.00 and 197.2 ± 7.20) respectively. This is because of the Metformin, the first line drug for treating diabetes, has been reported to potentially decrease vitamin B-12 status. This epigenetic modification was correlated with the diabetic mellitus (DM) cataract patients’ group not responding. Vitamin B12 deficiency also leads to an impairment of the conversion of methylmalonyl-CoA to succinyl-CoA, which has been associated with insulin resistance. There was no significant difference between the age, body mass index (BMI), the mean of Vit-D pre-treatments, and the mean values of Hemoglobin A1C of both senile (S) and diabetic mellitus (DM) cataract patient groups. On other hand, there was a highly significant difference between the mean values of glucose levels in both senile (S) and diabetic mellitus (DM) cataract patient groups. Conclusion: Here we conclude that diabetic mellitus (DM) cataract patient group hardly benefited from this combination therapy vitamin D and vitamin B12; on the other hand senile patient group (s) benefited a lot from the therapy.

Keywords: cataract patients, senile, diabetes mellitus, vitamin B12, vitamin D, Muhyail General Hospital, Saudi Arabia

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Authors: Joshua Fogel, Rivka Herzog

Abstract:

Although direct-to-consumer prescription medication advertisements (DTCA) are viewed or heard in many venues, there does not appear to be any research for internet social media DTCA. We study the association of traditional media DTCA and digital media DTCA including internet social media of YouTube, Facebook, and Twitter with three different outcomes. There was one intentions outcome and two different behavior outcomes. The intentions outcome was the agreement level for seeking additional information about a prescription medication after seeing a DTCA. One behavior outcome was the agreement level for obtaining additional information about a prescription medication after seeing a DTCA. The other behavior outcome was the frequency level for obtaining additional information about a prescription medication after seeing a DTCA. Surveys were completed by 635 college students. Predictors included demographic variables, theory of planned behavior variables, health variables, and advertisements seen or heard. Also, in the behavior analyses, additional predictors of intentions and sources for seeking additional prescription drug information were included. Multivariate linear regression analyses were conducted. We found that increased age was associated with increased behavior, women were associated with increased intentions, and Hispanic race/ethnicity was associated with decreased behavior. For the theory of planned behavior variables, increased attitudes were associated with increased intentions, increased social norms were associated with increased intentions and behavior, and increased intentions were associated with increased behavior. Very good perceived health was associated with increased intentions. Advertisements seen in spam mail were associated with decreased intentions. Advertisements seen on traditional or cable television were associated with decreased behavior. Advertisements seen on television watched on the internet were associated with increased behavior. The source of seeking additional information of reading internet print content was associated with increased behavior. No internet social media advertisements were associated with either intentions or behavior. In conclusion, pharmaceutical brand managers and marketers should consider these findings when tailoring their DTCA advertising campaigns and directing their DTCA advertising budget towards young adults such as college students. They need to reconsider the current approach for traditional television DTCA and also consider dedicating a larger advertising budget toward internet television DTCA. Although internet social media is a popular place to advertise, the financial expenditures do not appear worthwhile for DTCA when targeting young adults such as college students.

Keywords: brand managers, direct-to-consumer advertising, internet, social media

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Authors: Angelika Dierolf, K. Rischer, A. Gonzalez-Roldan, P. Montoya, F. Anton, M. Van der Meulen

Abstract:

Placebo analgesia is a powerful cognitive endogenous pain modulation mechanism with high relevance in pain treatment. Older people would benefit, especially from non-pharmacologic pain interventions, since this age group is disproportionately affected by acute and chronic pain, while pharmacological treatments are less suitable due to polypharmacy and age-related changes in drug metabolism. Although aging is known to affect neurobiological and physiological aspects of pain perception, as for example, changes in pain threshold and pain tolerance, its effects on cognitive pain modulation strategies, including placebo analgesia, have hardly been investigated so far. In the present study, we are assessing placebo analgesia in 35 older adults (60 years and older) and 35 younger adults (between 18 and 35 years). Acute pain was induced with short transdermal electrical pulses to the inner forearm, using a concentric stimulating electrode. Stimulation intensities were individually adjusted to the participant’s threshold. Next to the stimulation site, we applied sham transcutaneous electrical nerve stimulation (TENS). Participants were informed that sometimes the TENS device would be switched on (placebo condition), and sometimes it would be switched off (control condition). In reality, it was always switched off. Participants received alternating blocks of painful stimuli in the placebo and control condition and were asked to rate the intensity and unpleasantness of each stimulus on a visual analog scale (VAS). Pain-related evoked potentials were recorded with a 64-channel EEG. Preliminary results show a reduced placebo effect in older compared to younger adults in both behavioral and neurophysiological data. Older people experienced less subjective pain reduction under sham TENS treatment compared to younger adults, as evidenced by the VAS ratings. The N1 and P2 event-related potential components were generally reduced in the older group. While younger adults showed a reduced N1 and P2 under sham TENS treatment, this reduction was considerably smaller in older people. This reduced placebo effect in the older group suggests that cognitive pain modulation is altered in aging and may at least partly explain why older adults experience more pain. Our results highlight the need for a better understanding of the efficacy of non-pharmacological pain treatments in older adults and how these can be optimized to meet the specific requirements of this population.

Keywords: placebo analgesia, aging, acute pain, TENS, EEG

Procedia PDF Downloads 115

Authors: Farzana Esmailkassam, Usakorn Kunanuvat, Zahraa Mohammed Ali

Abstract:

Objective: The key barrier in Clozapine treatment of treatment-resistant schizophrenia (TRS) includes frequent bloods draws to monitor neutropenia, the main drug side effect. WBC and ANC monitoring must occur throughout treatment. Accurate WBC and ANC counts are necessary for clinical decisions to halt, modify or continue clozapine treatment. The CSAN Pronto point-of-care (POC) analyzer generates white blood cells (WBC) and absolute neutrophils (ANC) through image analysis of capillary blood. POC monitoring offers significant advantages over central laboratory testing. This study evaluated the performance of the CSAN Pronto against the Beckman DxH900 Hematology laboratory analyzer. Methods: Forty venous samples (EDTA whole blood) with varying concentrations of WBC and ANC as established on the DxH900 analyzer were tested in duplicates on three CSAN Pronto analyzers. Additionally, both venous and capillary samples were concomitantly collected from 20 volunteers and assessed on the CSAN Pronto and the DxH900 analyzer. The analytical performance including precision using liquid quality controls (QCs) as well as patient samples near the medical decision points, and linearity using a mix of high and low patient samples to create five concentrations was also evaluated. Results: In the precision study for QCs and whole blood, WBC and ANC showed CV inside the limits established according to manufacturer and laboratory acceptability standards. WBC and ANC were found to be linear across the measurement range with a correlation of 0.99. WBC and ANC from all analyzers correlated well in venous samples on the DxH900 across the tested sample ranges with a correlation of > 0.95. Mean bias in ANC obtained on the CSAN pronto versus the DxH900 was 0.07× 109 cells/L (95% L.O.A -0.25 to 0.49) for concentrations <4.0 × 109 cells/L, which includes decision-making cut-offs for continuing clozapine treatment. Mean bias in WBC obtained on the CSAN pronto versus the DxH900 was 0.34× 109 cells/L (95% L.O.A -0.13 to 0.72) for concentrations <5.0 × 109 cells/L. The mean bias was higher (-11% for ANC, 5% for WBC) at higher concentrations. The correlations between capillary and venous samples showed more variability with mean bias of 0.20 × 109 cells/L for the ANC. Conclusions: The CSAN pronto showed acceptable performance in WBC and ANC measurements from venous and capillary samples and was approved for clinical use. This testing will facilitate treatment decisions and improve clozapine uptake and compliance.

Keywords: absolute neutrophil counts, clozapine, point of care, white blood cells

Procedia PDF Downloads 60