Search results for: programmed cell death protein 1

Authors: Ghirmay Teklemicheal, Samsom Mehari, Sara Tesfay

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Objectives: A total of 1074 suspected chikungunya cases were reported in Tesseney Province, Gash Barka region, Eritrea, during an outbreak. This study was aimed to assess the possible association of chikungunya severity among ABO blood groups and other potential determinants. Methods: A sex-matched and age-matched case-control study was conducted during the outbreak. For each case, one control subject had been selected from the mild Chikungunya cases. Along the same line of argument, a second control subject had also been designated through which neighborhood of cases were analyzed, scrutinized, and appeared to the scheme of comparison. Time is always the most sacrosanct element in pursuance of any study. According to the temporal calculation, this study was pursued from October 15, 2018, to November 15, 2018. Coming to the methodological dependability, calculating odds ratios (ORs) and conditional (fixed-effect) logistic regression methods were being applied. As a consequence of this, the data was analyzed and construed on the basis of the aforementioned methodological systems. Results: In this outbreak, 137 severe suspected chikungunya cases and 137 mild chikungunya suspected patients, and 137 controls free of chikungunya from the neighborhood of cases were analyzed. Non-O individuals compared to those with O blood group indicated as significant with a p-value of 0.002. Separate blood group comparison among A and O blood groups reflected as significant with a p-value of 0.002. However, there was no significant difference in the severity of chikungunya among B, AB, and O blood groups with a p-value of 0.113 and 0.708, respectively, and a strong association of chikungunya severity was found with hypertension and diabetes (p-value of < 0.0001); whereas, there was no association between chikungunya severity and asthma with a p-value of 0.695 and also no association with pregnancy (p-value =0.881), ventilator (p-value =0.181), air conditioner (p-value = 0.247), and didn’t use latrine and pit latrine (p-value = 0.318), among individuals using septic and pit latrine (p-value = 0.567) and also among individuals using flush and pit latrine (p-value = 0.194). Conclusions: Non- O blood groups were found to be at risk more than their counterpart O blood group individuals with severe form of chikungunya disease. By the same token, individuals with chronic disease were more prone to severe forms of the disease in comparison with individuals without chronic disease. Prioritization is recommended for patients with chronic diseases and non-O blood group since they are found to be susceptible to severe chikungunya disease. Identification of human cell surface receptor(s) for CHIKV is quite necessary for further understanding of its pathophysiology in humans. Therefore, molecular and functional studies will necessarily be helpful in disclosing the association of blood group antigens and CHIKV infections.

Keywords: Chikungunya, Chikungunya virus, disease outbreaks, case-control studies, Eritrea

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Authors: Merrick Lopez, Aashish Abraham, Melissa Egge, Marissa Hood, Jui Shah

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A 3 year old male with unknown medical history presented initially with encephalopathy, intubated for respiratory failure, and admitted to the pediatric intensive care unit (PICU) with refractory shock. During resuscitation in the emergency department, he was found to be in severe metabolic acidosis with a pH of 7.03 and escalated on vasopressor drips for hypotension. His initial sodium was 174. He was noted to have burn injuries to his scalp, forehead, right axilla, bilateral arm creases and lower legs. He had rhabdomyolysis (initial creatinine kinase 5,430 U/L with peak levels of 62,340 normal <335 U/L), cardiac injury (initial troponin 88 ng/L with peak at 145 ng/L, normal <15ng/L), hypernatremia (peak 174, normal 140), hypocalcemia, liver injury, acute kidney injury, and neuronal loss on magnetic resonance imaging (MRI). Soft restraints and a shock collar were found in the home. He was critically ill for 8 days, but was gradually weaned off drips, extubated, and started on feeds. Discussion Electrical injury, specifically lightning injury is an uncommon but devastating cause of injury in pediatric patients. This patient with suspected abusive use of a dog shock collar presented similar to a lightning strike. Common entrance points include the hands and head, similar to our patient with linear wounds on his forehead. When current enters, it passes through tissues with the least resistance. Nerves, blood vessels, and muscles, have high fluid and electrolyte content and are commonly affected. Exit points are extremities: our child who had circumferential burns around his arm creases and ankles. Linear burns preferentially follow areas of high sweat concentration, and are thought to be due to vaporization of water on the skin’s surface. The most common cause of death from a lightning strike is due to cardiopulmonary arrest. The massive depolarization of the myocardium can result in arrhythmias and myocardial necrosis. The patient presented in cardiogenic shock with evident cardiac damage. Electricity going through vessels can lead to vaporization of intravascular water. This can explain his severe hypernatremia. He also sustained other internal organ injuries (adrenal glands, pancreas, liver, and kidney). Electrical discharge also leads to direct skeletal muscle injury in addition to prolonged muscular spasm. Rhabdomyolysis, the acute damage of muscle, leads to release of potentially toxic components into the circulation which could lead to acute renal failure. The patient had severe rhabdomyolysis and renal injury. Early hypocalcemia has been consistently demonstrated in patients with rhabdomyolysis. This was present in the patient and led to increased vasopressor needs. Central nervous system injuries are also common which can include encephalopathy, hypoxic injury, and cerebral infarction. The patient had evidence of brain injury as seen on MRI. Conclusion Electrical injuries due to lightning strikes and abusive use of a dog shock collar are rare, but can both present in similar ways with respiratory failure, shock, hypernatremia, rhabdomyolysis, brain injury, and multiorgan damage. Although rare, it is essential for early identification and prompt management for acute and chronic complications in these children.

Keywords: cardiogenic shock, dog shock collar, lightning strike, rhabdomyolysis

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Authors: D. Dixon, J. Nicol, J. A. Coulter, E. Harrison

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The ease with which they can be functionalized, combined with their excellent biocompatibility, make gold nanoparticles (AuNPs) ideal candidates for various applications in nanomedicine. Indeed several promising treatments are currently undergoing human clinical trials (CYT-6091 and Auroshell). A successful nanoparticle treatment must first evade the immune system, then accumulate within the target tissue, before enter the diseased cells and delivering the payload. In order to create a clinically relevant drug delivery system, contrast agent or radiosensitizer, it is generally necessary to functionalize the AuNP surface with multiple groups; e.g. Polyethylene Glycol (PEG) for enhanced stability, targeting groups such as antibodies, peptides for enhanced internalization, and therapeutic agents. Creating and characterizing the biological response of such complex systems remains a challenge. The two commonly used methods to attach multiple groups to the surface of AuNPs are the creation of a mixed monolayer, or by binding groups to the AuNP surface using a bi-functional PEG linker. While some excellent in-vitro and animal results have been reported for both approaches further work is necessary to directly compare the two methods. In this study AuNPs capped with both PEG and a Receptor Mediated Endocytosis (RME) peptide were prepared using both mixed monolayer and PEG linker approaches. The PEG linker used was SH-PEG-SGA which has a thiol at one end for AuNP attachment, and an NHS ester at the other to bind to the peptide. The work builds upon previous studies carried out at the University of Ulster which have investigated AuNP synthesis, the influence of PEG on stability in a range of media and investigated intracellular payload release. 18-19nm citrate capped AuNPs were prepared using the Turkevich method via the sodium citrate reduction of boiling 0.01wt% Chloroauric acid. To produce PEG capped AuNPs, the required amount of PEG-SH (5000Mw) or SH-PEG-SGA (3000Mw Jenkem Technologies) was added, and the solution stirred overnight at room temperature. The RME (sequence: CKKKKKKSEDEYPYVPN, Biomatik) co-functionalised samples were prepared by adding the required amount of peptide to the PEG capped samples and stirring overnight. The appropriate amounts of PEG-SH and RME peptide were added to the AuNP to produce a mixed monolayer consisting of approximately 50% PEG and 50% RME. The PEG linker samples were first fully capped with bi-functional PEG before being capped with RME peptide. An increase in diameter from 18-19mm for the ‘as synthesized’ AuNPs to 40-42nm after PEG capping was observed via DLS. The presence of PEG and RME peptide on both the mixed monolayer and PEG linker co-functionalized samples was confirmed by both FTIR and TGA. Bi-functional PEG linkers allow the entire AuNP surface to be capped with PEG, enabling in-vitro stability to be achieved using a lower molecular weight PEG. The approach also allows the entire outer surface to be coated with peptide or other biologically active groups, whilst also offering the promise of enhanced biological availability. The effect of mixed monolayer versus PEG linker attachment on both stability and non-specific protein corona interactions was also studied.

Keywords: nanomedicine, gold nanoparticles, PEG, biocompatibility

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Authors: Z. Terzopoulou, I. Koliakou, D. Bikiaris

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Tissue engineering offers a new approach to regenerate diseased or damaged tissues such as bone. Great effort is devoted to eliminating the need of removing non-degradable implants at the end of their life span, with biodegradable polymers playing a major part. Poly(ε-caprolactone) (PCL) is one of the best candidates for this purpose due to its high permeability, good biodegradability and exceptional biocompatibility, which has stimulated extensive research into its potential application in the biomedical fields. However, PCL degrades much slower than other known biodegradable polymers and has a total degradation of 2-4 years depending on the initial molecular weight of the device. This is due to its relatively hydrophobic character and high crystallinity. Consequently, much attention has been given to the tunable degradation of PCL to meet the diverse requirements of biomedicine. Poly(ε-caprolactone) (PCL) is a biodegradable polyester that lacks bioactivity, so when used in bone tissue engineering, new bone tissue cannot bond tightly on the polymeric surface. Therefore, it is important to incorporate reinforcing fillers into PCL matrix in order to result in a promising combination of bioactivity, biodegradability, and strength. Natural clay halloysite nanotubes (HNTs) were incorporated into PCL polymeric matrix, via in situ ring-opening polymerization of caprolactone, in concentrations 0.5, 1 and 2.5 wt%. Both unmodified and modified with aminopropyltrimethoxysilane (APTES) HNTs were used in this study. The effect of nanofiller concentration and functionalization with end-amino groups on the physicochemical properties of the prepared nanocomposites was studied. Mechanical properties were found enhanced after the incorporation of nanofillers, while the modification increased further the values of tensile and impact strength. Thermal stability of PCL was not affected by the presence of nanofillers, while the crystallization rate that was studied by Differential Scanning Calorimetry (DSC) and Polarized Light Optical Microscopy (POM) increased. All materials were subjected to enzymatic hydrolysis in phosphate buffer in the presence of lipases. Due to the hydrophilic nature of HNTs, the biodegradation rate of nanocomposites was higher compared to neat PCL. In order to confirm the effect of hydrophilicity, contact angle measurements were also performed. In vitro biomineralization test confirmed that all samples were bioactive as mineral deposits were detected by X-ray diffractometry after incubation in SBF. All scaffolds were tested in relevant cell culture using osteoblast-like cells (MG-63) to demonstrate their biocompatibility

Keywords: biomaterials, nanocomposites, scaffolds, tissue engineering

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Authors: Satoko Fujiwara, Kiyotaka Obunai, Kazuya Okubo

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A skew is one of important problems for designing the conveyor and transmission with frictional flat belt, in which running belt is deviated in width direction due to the transverse force applied to the belt. The skew often not only degrades the stability of the path of belt but also causes some damages of the belt and auxiliary machines. However, the transverse behavior such as the skew has not been discussed quantitatively in detail for frictional belts. The objective of this study is to clarify the transverse behavior of frictional flat belt driven by tapered pulley. Commercially available rubber flat belt reinforced by polyamide film was prepared as the test belt where the thickness and length were 1.25 mm and 630 mm, respectively. Test belt was driven between two pulleys made of aluminum alloy, where diameter and inter-axial length were 50 mm and 150 mm, respectively. Some tapered pulleys were applied where tapered angles were 0 deg (for comparison), 2 deg, 4 deg, and 6 deg. In order to alternatively investigate the transverse behavior, the transverse force applied to the belt was measured when the skew was constrained at the string under driving state. The transverse force was measured by a load cell having free rollers contacting on the side surface of the belt when the displacement in the belt width direction was constrained. The conditions of observed bending stiffness in-plane of the belt were changed by preparing three types of belts (the width of the belt was 20, 30, and 40 mm) where their observed stiffnesses were changed. The contributions of the bending stiffness in-plane of belt and initial inter-axial force to the transverse were discussed in experiments. The inter-axial force was also changed by setting a distance (about 240 mm) between the two pulleys. Influence of observed bending stiffness in-plane of the belt and initial inter-axial force on the transverse force were investigated. The experimental results showed that the transverse force was increased with an increase of observed bending stiffness in-plane of the belt and initial inter-axial force. The transverse force acting on the belt running on the tapered pulley was classified into multiple components. Those were components of forces applied with the deflection of the inter-axial force according to the change of taper angle, the resultant force by the bending moment applied on the belt winding around the tapered pulley, and the reaction force applied due to the shearing deformation. The calculation result of the transverse force was almost agreed with experimental data when those components were formulated. It was also shown that the most contribution was specified to be the shearing deformation, regardless of the test conditions. This study found that transverse behavior of frictional flat belt driven by tapered pulley was explained by the summation of those components of forces.

Keywords: skew, frictional flat belt, transverse force, tapered pulley

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Authors: Alireza Barari, Saeed Shirali, Ahmad Abdi

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Introduction: Exercise has contradictory effects on the immune system. Glutamine supplementation may increase the resistance of the immune system in athletes. The Glutamine is one of the most recognized immune nutrients that as a fuel source, substrate in the synthesis of nucleotides and amino acids and is also known to be part of the antioxidant defense. Several studies have shown that improving glutamine levels in plasma and tissues can have beneficial effects on the function of immune cells such as lymphocytes and neutrophils. This study aimed to investigate the effects of resistance training and training combined with glutamine supplementation to improve the levels of cortisol and immunoglobulin in untrained young men. The research shows that physical training can increase the cytokines in the athlete’s body of course; glutamine can counteract the negative effects of resistance training on immune function and stability of the mast cell membrane. Materials and methods: This semi-experimental study was conducted on 30 male non-athletes. They were randomly divided into three groups: control (no exercise), resistance training, resistance training and glutamine supplementation, respectively. Resistance training for 4 weeks and glutamine supplementation in 0.3 gr/kg/day after practice was applied. The resistance-training program consisted of eight exercises (leg press, lat pull, chest press, squat, seatedrow, abdominal crunch, shoulder press, biceps curl and triceps press down) four times per week. Participants performed 3 sets of 10 repetitions at 60–75% 1-RM. Anthropometry indexes (weight, body mass index, and body fat percentage), oxygen uptake (VO2max) Maximal, cortisol levels of immunoglobulins (IgA, IgG, IgM) were evaluated Pre- and post-test. Results: Results showed four week resistance training with and without glutamine cause significant increase in body weight, BMI and significantly decreased (P < 0/001) in BF. Vo2max also increased in both groups of exercise (P < 0/05) and exercise with glutamine (P < 0/001), such as in both groups significant reduction in IgG (P < 0/05) was observed. But no significant difference observed in levels of cortisol, IgA, IgM in any of the groups. No significant change observed in either parameter in the control group. No significant difference observed between the groups. Discussion: The alterations in the hormonal and immunological parameters can be used in order to assess the effect overload on the body, whether acute or chronically. The plasmatic concentration of glutamine has been associated to the functionality of the immunological system in individuals sub-mitted to intense physical training. resistance training has destructive effects on the immune system and glutamine supplementation cannot neutralize the damaging effects of power exercise on the immune system.

Keywords: glutamine, resistance traning, immuglobulins, cortisol

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Authors: Swati Mishra

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In recent years, there has been an explosion in Gold NanoParticle (GNP) research, with a rapid increase in publications in diverse fields, including imaging, bioengineering, and molecular biology. GNPs exhibit unique physicochemical properties, including surface plasmon resonance (SPR) and bind amine and thiol groups, allowing surface modification and use in biomedical applications. Nanoparticle functionalization is the subject of intense research at present, with rapid progress being made towards developing biocompatible, multi-functional particles. In the present study, the photochemical method has been done to functionalize various-shaped GNPs like nanostars by the molecules like ninhydrin. Ninhydrin is bactericidal, virucidal, fungicidal, antigen-antibody reactive, and used in fingerprint technology in forensics. The GNPs functionalized with ninhydrin efficiently will bind to the amino acids on the target protein, which is of eminent importance during the pandemic, especially where long-term treatments of COVID- 19 bring many side effects of the drugs. The photochemical method is adopted as it provides low thermal load, selective reactivity, selective activation, and controlled radiation in time, space, and energy. The GNPs exhibit their characteristic spectrum, but a distinctly blue or redshift in the peak will be observed after UV irradiation, ensuring efficient ninhydrin binding. Now, the bound ninhydrin in the GNP carrier, upon chemically reacting with any amino acid, will lead to the formation of Rhumann purple. A common method of GNP production includes citrate reduction of Au [III] derivatives such as aurochloric acid (HAuCl4) in water to Au [0] through a one-step synthesis of size-tunable GNPs. The following reagents are prepared to validate the approach. Reagent A solution 1 is0.0175 grams ninhydrin in 5 ml Millipore water Reagent B 30 µl of HAuCl₄.3H₂O in 3 ml of solution 1 Reagent C 1 µl of gold nanostars in 3 ml of solution 1 Reagent D 6 µl of cetrimonium bromide (CTAB) in 3 ml of solution1 ReagentE 1 µl of gold nanostars in 3 ml of ethanol ReagentF 30 µl of HAuCl₄.₃H₂O in 3 ml of ethanol ReagentG 30 µl of HAuCl₄.₃H₂O in 3 ml of solution 2 ReagentH solution 2 is0.0087 grams ninhydrin in 5 ml Millipore water ReagentI 30 µl of HAuCl₄.₃H₂O in 3 ml of water The reagents were irradiated at 254 nm for 15 minutes, followed by their UV Visible spectroscopy. The wavelength was selected based on the one reported for excitation of a similar molecule Pthalimide. It was observed that the solution B and G deviate around 600 nm, while C peaks distinctively at 567.25 nm and 983.9 nm. Though it is tough to say about the chemical reaction happening, butATR-FTIR of reagents will ensure that ninhydrin is not forming Rhumann purple in the absence of amino acids. Therefore, these experiments, we achieved the functionalization of gold nanostars with ninhydrin corroborated by the deviation in the spectrum obtained in a mixture of GNPs and ninhydrin irradiated with UV light. It prepares them as a carrier molecule totake up amino acids for targeted delivery or germicidal action.

Keywords: gold nanostars, ninhydrin, photochemical method, UV visible specgtroscopy

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Authors: Apurva Gupta, Surendra Singh

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Spirulina spp., as a promising source of many commercially valuable products, is grown photo autotrophically in open ponds and raceways on a large scale. However, the economic exploitation in an open system seems to have been limited because of lack of multiple stress-tolerant strains. The present study aims to isolate a stable stress tolerant mutant of Spirulina platensis with improved growth rate and enhanced potential to produce its commercially valuable bioactive compounds. N-methyl-n'-nitro-n-nitrosoguanidine (NTG) at 250 μg/mL (concentration permitted 1% survival) was employed for chemical mutagenesis to generate random mutants and screened against NaCl. In a preliminary experiment, wild type S. platensis was treated with NaCl concentrations from 0.5-1.5 M to calculate its LC₅₀. Mutagenized colonies were then screened for tolerance at 0.8 M NaCl (LC₅₀), and the surviving colonies were designated as NaCl tolerant mutants of S. platensis. The mutant cells exhibited 1.5 times improved growth against NaCl stress as compared to the wild type strain in control conditions. This might be due to the ability of the mutant cells to protect its metabolic machinery against inhibitory effects of salt stress. Salt stress is known to adversely affect the rate of photosynthesis in cyanobacteria by causing degradation of the pigments. Interestingly, the mutant cells were able to protect its photosynthetic machinery and exhibited 4.23 and 1.72 times enhanced accumulation of Chl a and phycobiliproteins, respectively, which resulted in enhanced rate of photosynthesis (2.43 times) and respiration (1.38 times) against salt stress. Phycocyanin production in mutant cells was observed to enhance by 1.63 fold. Nitrogen metabolism plays a vital role in conferring halotolerance to cyanobacterial cells by influx of nitrate and efflux of Na+ ions from the cell. The NaCl tolerant mutant cells took up 2.29 times more nitrate as compared to the wild type and efficiently reduce it. Nitrate reductase and nitrite reductase activity in the mutant cells also improved by 2.45 and 2.31 times, respectively against salt stress. From these preliminary results, it could be deduced that enhanced nitrogen uptake and its efficient reduction might be a reason for adaptive and halotolerant behavior of the S. platensis mutant cells. Also, the NaCl tolerant mutant of S. platensis with significant improved growth and phycocyanin accumulation compared to the wild type can be commercially promising.

Keywords: chemical mutagenesis, NaCl tolerant mutant, nitrogen metabolism, photosynthetic machinery, phycocyanin

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Authors: H. Shahid

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Due to Ozone layer depletion on earth, the incoming ultraviolet (UV) radiation is recorded at its high index levels such as 25 in South Peru (13.5° S, 3360 m a.s.l.) Also, the planning of human inhabitation on Mars is under discussion where UV radiations are quite high. The exposure to UV is health hazardous and is avoided by UV filters. On the other hand, artificial UV sources are in use for water thermolysis to generate Hydrogen and Oxygen, which are later used as fuels. This paper presents the utility of employing UVA (315-400nm) and UVB (280-315nm) electromagnetic radiation from the solar spectrum to design and implement an optically active, Hydrogen and Oxygen generation system via thermolysis of desalinated seawater. The proposed system finds its utility on earth and can be deployed in the future on Mars (UVB). In this system, by using Fresnel lens arrays as an optical filter and via active tracking, the ultraviolet light from the sun is concentrated and then allowed to fall on two sub-systems of the proposed system. The first sub-system generates electrical energy by using UV based tandem photovoltaic cells such as GaAs/GaInP/GaInAs/GaInAsP and the second elevates temperature of water to lower the electric potential required to electrolyze the water. An empirical analysis is performed at 30 atm and an electrical potential is observed to be the main controlling factor for the rate of production of Hydrogen and Oxygen and hence the operating point (Q-Point) of the proposed system. The hydrogen production rate in the case of the commercial system in static mode (650ᵒC, 0.6V) is taken as a reference. The silicon oxide electrolyzer cell (SOEC) is used in the proposed (UV) system for the Hydrogen and Oxygen production. To achieve the same amount of Hydrogen as in the case of the reference system, with minimum chamber operating temperature of 850ᵒC in static mode, the corresponding required electrical potential is calculated as 0.3V. However, practically, the Hydrogen production rate is observed to be low in comparison to the reference system at 850ᵒC at 0.3V. However, it has been shown empirically that the Hydrogen production can be enhanced and by raising the electrical potential to 0.45V. It increases the production rate to the same level as is of the reference system. Therefore, 850ᵒC and 0.45V are assigned as the Q-point of the proposed system which is actively stabilized via proportional integral derivative controllers which adjust the axial position of the lens arrays for both subsystems. The functionality of the controllers is based on maintaining the chamber fixed at 850ᵒC (minimum operating temperature) and 0.45V; Q-Point to realize the same Hydrogen production rate as-is for the reference system.

Keywords: hydrogen, oxygen, thermolysis, ultraviolet

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Authors: H. M. Ferreira, H. Cockings, D. F. Gordon

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Climate change is driving a transition in the energy sector, with low-carbon energy sources such as hydrogen (H2) emerging as an alternative to fossil fuels. However, the successful implementation of a hydrogen economy requires an expansion of hydrogen production, transportation and storage capacity. The costs associated with this transition are high but can be partly mitigated by adapting the current oil and natural gas networks, such as pipeline, an important component of the hydrogen infrastructure, to transport pure or blended hydrogen. Steel pipelines are designed to withstand fatigue, one of the most common causes of pipeline failure. However, it is well established that some materials, such as steel, can fail prematurely in service when exposed to hydrogen-rich environments. Therefore, it is imperative to evaluate how defects (e.g. inclusions, dents, and pre-existing cracks) will interact with hydrogen under cyclic loading and, ultimately, to what extent hydrogen induced failure will limit the service conditions of steel pipelines. This presentation will explore how the exposure of API 5L X65 to a hydrogen-rich environment and cyclic loads will influence its susceptibility to hydrogen induced failure. That evaluation will be performed by a combination of several techniques such as hydrogen permeation testing (ISO 17081:2014), fatigue crack growth (FCG) testing (ISO 12108:2018 and AFGROW modelling), combined with microstructural and fractographic analysis. The development of a FCG test setup coupled with an electrochemical cell will be discussed, along with the advantages and challenges of measuring crack growth rates in electrolytic hydrogen environments. A detailed assessment of several electrolytic charging conditions will also be presented, using hydrogen permeation testing as a method to correlate the different charging settings to equivalent hydrogen concentrations and effective diffusivity coefficients, not only on the base material but also on the heat affected zone and weld of the pipelines. The experimental work is being complemented with AFGROW, a useful FCG modelling software that has helped inform testing parameters and which will also be developed to ultimately help industry experts perform structural integrity analysis and remnant life characterisation of pipeline steels under representative conditions. The results from this research will allow to conclude if there is an acceleration of the crack growth rate of API 5L X65 under the influence of a hydrogen-rich environment, an important aspect that needs to be rectified instandards and codes of practice on pipeline integrity evaluation and maintenance.

Keywords: AFGROW, electrolytic hydrogen charging, fatigue crack growth, hydrogen, pipeline, steel

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Authors: Amer Ait Sidhoum

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Interest in sustainability has gained ground among practitioners, academics and policy-makers due to growing stakeholders’ awareness of environmental and social concerns. This is particularly true for agriculture. However, relatively little research has been conducted on the quantification of social sustainability and the contribution of social issues to the agricultural production efficiency. This research's main objective is to propose a method for evaluating prices of social outputs, more precisely shadow prices, by allowing for the stochastic nature of agricultural production that is to say for production uncertainty. In this article, the assessment of social outputs’ shadow prices is conducted within the methodological framework of nonparametric Data Envelopment Analysis (DEA). An output-oriented directional distance function (DDF) is implemented to represent the technology of a sample of Catalan arable crop farms and derive the efficiency scores the overall production technology of our sample is assumed to be the intersection of two different sub-technologies. The first sub-technology models the production of random desirable agricultural outputs, while the second sub-technology reflects the social outcomes from agricultural activities. Once a nonparametric production technology has been represented, the DDF primal approach can be used for efficiency measurement, while shadow prices are drawn from the dual representation of the DDF. Computing shadow prices is a method to assign an economic value to non-marketed social outcomes. Our research uses cross sectional, farm-level data collected in 2015 from a sample of 180 Catalan arable crop farms specialized in the production of cereals, oilseeds and protein (COP) crops. Our results suggest that our sample farms show high performance scores, from 85% for the bad state of nature to 88% for the normal and ideal crop growing conditions. This suggests that farm performance is increasing with an improvement in crop growth conditions. Results also show that average shadow prices of desirable state-contingent output and social outcomes for efficient and inefficient farms are positive, suggesting that the production of desirable marketable outputs and of non-marketable outputs makes a positive contribution to the farm production efficiency. Results also indicate that social outputs’ shadow prices are contingent upon the growing conditions. The shadow prices follow an upward trend as crop-growing conditions improve. This finding suggests that these efficient farms prefer to allocate more resources in the production of desirable outputs than of social outcomes. To our knowledge, this study represents the first attempt to compute shadow prices of social outcomes while accounting for the stochastic nature of the production technology. Our findings suggest that the decision-making process of the efficient farms in dealing with social issues are stochastic and strongly dependent on the growth conditions. This implies that policy-makers should adjust their instruments according to the stochastic environmental conditions. An optimal redistribution of rural development support, by increasing the public payment with the improvement in crop growth conditions, would likely enhance the effectiveness of public policies.

Keywords: data envelopment analysis, shadow prices, social sustainability, sustainable farming

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Authors: A. Julio, R. Caparica, S. Costa Lima, S. Reis, J. G. Costa, P. Fonte, T. Santos De Almeida

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The Mycobacterium leprae causes a chronic and infectious disease called leprosy, which the most common symptoms are peripheral neuropathy and deformation of several parts of the body. The pharmacological treatment of leprosy is a combined therapy with three different drugs, rifampicin, clofazimine, and dapsone. However, clofazimine and dapsone have poor solubility in water and also low bioavailability. Thus, it is crucial to develop strategies to overcome such drawbacks. The use of ionic liquids (ILs) may be a strategy to overcome the low solubility since they have been used as solubility promoters. ILs are salts, liquid below 100 ºC or even at room temperature, that may be placed in water, oils or hydroalcoholic solutions. Another approach may be the encapsulation of drugs into polymeric nanoparticles, which improves their bioavailability. In this study, two different classes of ILs were used, the imidazole- and the choline-based ionic liquids, as solubility enhancers of the poorly soluble antileprotic drugs. Thus, after the solubility studies, it was developed IL-PLGA nanoparticles hybrid systems to deliver such drugs. First of all, the solubility studies of clofazimine and dapsone were performed in water and in water: IL mixtures, at ILs concentrations where cell viability is maintained, at room temperature for 72 hours. For both drugs, it was observed an improvement on the drug solubility and [Cho][Phe] showed to be the best solubility enhancer, especially for clofazimine, where it was observed a 10-fold improvement. Later, it was produced nanoparticles, with a polymeric matrix of poly(lactic-co-glycolic acid) (PLGA) 75:25, by a modified solvent-evaporation W/O/W double emulsion technique in the presence of [Cho][Phe]. Thus, the inner phase was an aqueous solution of 0.2 % (v/v) of the above IL with each drug to its maximum solubility determined on the previous study. After the production, the nanosystem hybrid was physicochemically characterized. The produced nanoparticles had a diameter of around 580 nm and 640 nm, for clofazimine and dapsone, respectively. Regarding the polydispersity index, it was in agreement of the recommended value of this parameter for drug delivery systems (around 0.3). The association efficiency (AE) of the developed hybrid nanosystems demonstrated promising AE values for both drugs, given their low solubility (64.0 ± 4.0 % for clofazimine and 58.6 ± 10.0 % for dapsone), that prospects the capacity of these delivery systems to enhance the bioavailability and loading of clofazimine and dapsone. Overall, the study achievement may signify an upgrading of the patient’s quality of life, since it may mean a change in the therapeutic scheme, not requiring doses of drug so high to obtain a therapeutic effect. The authors would like to thank Fundação para a Ciência e a Tecnologia, Portugal (FCT/MCTES (PIDDAC), UID/DTP/04567/2016-CBIOS/PRUID/BI2/2018).

Keywords: ionic liquids, ionic liquids-PLGA nanoparticles hybrid systems, leprosy treatment, solubility

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Authors: Hani M. Alothaid, Louise Robson, Richmond Muimo

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Cystic fibrosis (CF) is a disease that affects respiratory function and in EU it affects about 1 in 2,500 live births with an average 40-year life expectancy. This disease caused by mutations within the gene encoding the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) chloride channel leading to dysregulation of epithelial fluid transport and chronic lung inflammation, suggesting functional alterations of immune cells. In airways, CFTR been found to form a functional complex with S100A10 and AnxA2 in a cAMP/PKA dependent manner. The multiprotein complex of AnxA2-S100A10 and CFTR is also regulated by calcineurin. The aim of this study was i) to investigate whether chloride ion (Cl−) channels are activated by Pseudomonas aeruginosa lipopolysaccharide (LPS from PA), ii) if this activation is regulated by cAMP/PKA/calcineurin pathway and iii) to investigate the role of LPS-activated Cl− channels in the release of pro-inflammatory cytokines by immune cells. Human peripheral blood monocytes were used in the study. Whole-cell patch records showed that LPS from PA can activate Cl− channels, including CFTR and outwardly-rectifying Cl− channel (ORCC). This activation appears to require an intact PKA/calcineurin signalling pathway. The Gout in the presence of LPS was significantly inhibited by diisothiocyanatostilbene-disulfonic acid (DIDS), an ORCC blocker (p<0.001). The Gout was further suppressed by CFTR(inh)-172, a specific inhibitor for CFTR channels (p<0.001). Monocytes pre-incubated with PKA inhibitor or calcineurin inhibitor before stimulated with LPS from PA that were resulted in DIDS and CFTR(inh)-172 insensitive currents. Activation of both ORCC and CFTR was however, observed in response to monocytes exposure to LPS. Additionally, ELISA showed that the CFTR and ORCC play a role in mediating the release of pro-inflammatory cytokines such as IL-1β upon exposure of monocytes to LPS. However, this secretion was significantly inhibited due to CFTR and ORCC inhibition. However, Cl− may play a role in IL-1β release independent of cAMP/PKA/calcineurin signalling due to the enhancement of IL-1β secretion even when cAMP/PKA/calcineurin pathway was inhibited. In conclusion, our data confirmed that LPS from PA activates Cl− channels in human peripheral blood monocytes. Our data also confirmed that Cl− channels were involved in IL-1β release in monocytes upon exposure to LPS. However, it has been found that PKA and calcineurin does not seem to influence the Cl− dependent cytokine release.

Keywords: cystic fibrosis, CFTR, Annexin A2, S100A10, PP2B, PKA, outwardly-rectifying Cl− channel, Pseudomonas aeruginosa

Procedia PDF Downloads 153

Authors: Natalia V. Naryzhnaya, Alexandr V. Mukhomedzyanov, Ivan A. Derkachev, Boris K. Kurbatov, Leonid N. Maslov

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Background: Techniques of adaptation to hypoxia and remote postconditioning (RPost) have great prospects for use in the clinic. However, recent studies have shown low efficacy of remote postconditioning in patients with AMI. We hypothesize that the reasons for this inefficiency may be metabolic disorders, which are very common, especially in patients with cardiovascular disease, and age of patients. The purpose of the study was to reveal the effectiveness of adaptation to chronic hypoxia and RPost. To determine the possible relationship between the decrease in the effectiveness of projective impacts and disorders of carbohydrate and lipid metabolism. Design: The study was carried out on Wistar rats 60 day old. MetS was induced by high-carbohydrate, high-fat diet (HСHFD). Modeling MS led to the formation of obesity, hypertension, impaired lipid and carbohydrate metabolism, hyperleptinemia, and moderate stress. Groups with adaptation to chronic hypoxia were subjected to hypoxia for 21 days at 12% O2 and 0.3% CO2 after complete of HСHFD. All animals were subjected to 45 min coronary occlusion and 120 min reperfusion. Groups with RPost, immediately after the end of ischemia, tourniquets were applied to the hind limbs in the area of the hip joint (3 times in the mode of 5 min ischemia, 5 min reperfusion). Results: RPost led to a twofold reduction of infarct size in rats with intact metabolism (р < 0.0001), while in rats with MetS, a decrease in infarct size during RPost was 25 % (p = 0.00003). A direct correlation was found between of infarct size during RPost and the serum leptin level of rats with MetC (r = 0.85). The presented data suggested that a decrease in the efficiency of remote postconditioning in rats with diet-induced metabolic syndrome depends on serum leptin. Chronic hypoxia resulted in a 38% reduced in infarct size in metabolically intact rats. The decrease of cardioprotection was observed in rats with chronic hypoxia and MetS. Infarct size showed a direct correlation with impaired glucose tolerance (AUC, glucose tolerance test, r = 0.034) and serum triglyceride levels (r = 0.39). Our study showed the dependence of cardioprotection in rats with metabolic syndrome during chronic hypoxia and DPost on opioids in the blood serum and myocardium, protein kinase C and NO synthase activity. Conclusion: The results obtained showed that the infarct-limiting efficiency of adaptation to hypoxia and remote postconditioning is reduced or completely absent in animals with metabolic syndrome. The increase in the infarction, in this case, directly depends on the disturbances in carbohydrate. lipid metabolism and opioids signaling. Funding: Investigation of effectiveness of chronic hypoxia at the metabolic syndrome was carried out within the support of Russian Science Foundation Grant 22-15-00048. Studies of the mechanisms of arterial hypertension in induced metabolic syndrome were carried out within the framework of the state assignment (122020300042-4). The work was performed using the Center for Collective Use "Medical Genomics".

Keywords: chronic hypoxia, opioids, remote postconditioning, metabolic syndrome

Procedia PDF Downloads 56

Authors: Jerome Dalphinis, Vishal Patel

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The Bailiwick of Jersey is an island British crown dependency situated off the coast of France. Jersey General Hospital’s emergency department sees approximately 40,000 patients a year. It’s outside the NHS, with secondary care being free at the point of care. Sedation is a continuum which extends from a normal conscious level to being fully unresponsive. Procedural sedation produces a minimally depressed level of consciousness in which the patient retains the ability to maintain an airway, and they respond appropriately to physical stimulation. The goals of it are to improve patient comfort and tolerance of the procedure and alleviate associated anxiety. Indications can be stratified by acuity, emergency (cardioversion for life-threatening dysrhythmia), and urgency (joint reduction). In the emergency department, this is most often achieved using a combination of opioids and benzodiazepines. Some departments also use ketamine to produce dissociative sedation, a cataleptic state of profound analgesia and amnesia. The response to pharmacological agents is highly individual, and the drugs used occasionally have unpredictable pharmacokinetics and pharmacodynamics, which can always result in progression between levels of sedation irrespective of the intention. Therefore, practitioners must be able to ‘rescue’ patients from deeper sedation. These practitioners need to be senior clinicians with advanced airway skills (AAS) training. It can lead to adverse effects such as dangerous hypoxia and unintended loss of consciousness if incorrectly undertaken; studies by the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) have reported avoidable deaths. The Royal College of Emergency Medicine, UK (RCEM) released an updated ‘Safe Sedation of Adults in the Emergency Department’ guidance in 2017 detailing a series of standards for staff competencies, and the required environment and equipment, which are required for each target sedation depth. The emergency department in Jersey undertook audit research in 2018 to assess their current practice. It showed gaps in clinical competency, the need for uniform care, and improved documentation. This spurred the development of a checklist incorporating the above RCEM standards, including contraindication for procedural sedation and difficult airway assessment. This was approved following discussion with the relevant heads of departments and the patient safety directorates. Following this, a second audit research was carried out in 2019 with 17 completed checklists (11 relocation of joints, 6 cardioversions). Data was obtained from looking at the controlled resuscitation drugs book containing documented use of ketamine, alfentanil, and fentanyl. TrakCare, which is the patient electronic record system, was then referenced to obtain further information. The results showed dramatic improvement compared to 2018, and they have been subdivided into six categories; pre-procedure assessment recording of significant medical history and ASA grade (2 fold increase), informed consent (100% documentation), pre-oxygenation (88%), staff (90% were AAS practitioners) and monitoring (92% use of non-invasive blood pressure, pulse oximetry, capnography, and cardiac rhythm monitoring) during procedure, and discharge instructions including the documented return of normal vitals and consciousness (82%). This procedural sedation checklist is a safe intervention that identifies pertinent information about the patient and provides a standardised checklist for the delivery of gold standard of care.

Keywords: advanced airway skills, checklist, procedural sedation, resuscitation

Procedia PDF Downloads 93

Authors: Ali Azam Talukder, Jamsheda Ferdous Tuli, Tanzina Islam Reba, Shuvra Kanti Dey, Mamoru Yamada

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Recent global warming created by various pollutants prompted us to find new energy sources instead of fossil fuels. Fossil fuels are one of the key factors to emit various toxic gases in this planet. To solve this problem, along with the scarcity of the worldwide energy crisis, scientists are looking for various alternative options to mitigate the necessity of required future fuels. In this context, bioethanol can be one of the most suitable alternative energy sources. Bioethanol is a renewable, environment-friendly and carbon-neutral sustainable energy. In our previous study, we identified several bioethanol-producing microbes from the natural fermented sources of Bangladesh. Among them, the strain 4C encoded Saccharomyces cerevisiae produced maximum bioethanol when the fermentation temperature was 25˚C. In this study, we have established high-temperature simultaneous saccharification and fermentation process (HTSSF) by co-culturing of thermally adapted thermosensitive 4C as a fermenting agent and Bacillus amyloliquefaciens (C7), as a saccharifying agent under various physiological conditions or treatments. Conventional methods were applied for cell culture, media preparation and other experimental purposes. High-temperature adaptation of strain 4C was made from 30-42ᵒC, using either YPD or YPS media. In brief, for thermal adaptation, the temperature was periodically increased by 2ᵒC, 1ᵒC and 0.5ᵒC when medium growth temperatures were 30-36ᵒC, 36-40ᵒC, and 40-42ᵒC, respectively, where applicable. Amylase activity and bioethanol content were measured by DNS (3, 5-dinitrosalicylic acid) and solvent extraction and dichromate oxidation method, respectively. Among the various growth parameters like temperatures (30˚C, 37˚C and 42˚C), pHs (5.0, 6.0 and 7.0), carbon sources (5.0-10.0%) and ethanol stress tolerance (0.0-12.0%) etc. were tested, maximum Amylase activity (4.0 IU/ml/min) was recorded for Bacillus amyloliquefaciens (C7) at 42˚C, pH 6.0 and 10% starch. On the other hand, 4.10% bioethanol content was recorded when the thermally adapted strain 4C was co-cultured with C7 at 37ᵒC, pH 6.0 and 10.0% starch for 72 hours at HTSSF process. On the other hand, thermally non-adapted strains gave only 0.5-2.0% bioethanol content under the same physiological conditions. The thermally adapted strain 4C and strain C7, both can tolerate ethanol stress up to 12%. Altogether, a comparative study revealed that our established HTSSF process may be suitable for pilot scale and subsequently at industrial level bioethanol production.

Keywords: bioethanol, co-culture, fermentation, saccharification

Procedia PDF Downloads 61

Authors: N. Perini, M. C. Thaller, F. Mercuri, S. Orlanducci, A. Rubechini, L. Migliore

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The preservation of cultural heritage is one of the major challenges of today’s society, because of the fundamental right of future generations to inherit it as the continuity with their historical and cultural identity. Parchments, consisting of a semi-solid matrix of collagen produced from animal skin (i.e., sheep or goats), are a significant part of the cultural heritage, being used as writing material for many centuries. Due to their animal origin, parchments easily undergo biodeterioration. The most common biological damage is characterized by isolated or coalescent purple spots that often leads to the detachment of the superficial layer and the loss of the written historical content of the document. Although many parchments with the same biodegradative features were analyzed, no common causative agent has been found so far. Very recently, a study was performed on a purple-damaged parchment roll dated back 1244 A.D, the A.A. Arm. I-XVIII 3328, belonging to the oldest collection of the Vatican Secret Archive (Fondo 'Archivum Arcis'), by comparing uncolored undamaged and purple damaged areas of the same document. As a whole, the study gave interesting results to hypothesize a model of biodeterioration, consisting of a microbial succession acting in two main phases: the first one, common to all the damaged parchments, is characterized by halophilic and halotolerant bacteria fostered by the salty environment within the parchment maybe induced by bringing of the hides; the second one, changing with the individual history of each parchment, determines the identity of its colonizers. The design of this model was pivotal to this study, performed by different labs of the Tor Vergata University (Rome, Italy), in collaboration with the Vatican Secret Archive. Three documents, belonging to a collection of dramatically damaged parchments archived as 'Faldone Patrizi A 19' (dated back XVII century A.D.), were analyzed through a multidisciplinary approach, including three updated technologies: (i) Next Generation Sequencing (NGS, Illumina) to describe the microbial communities colonizing the damaged and undamaged areas, (ii) RAMAN spectroscopy to analyze the purple pigments, (iii) Light Transmitted Analysis (LTA) to evaluate the kind and entity of the damage to native collagen. The metagenomic analysis obtained from NGS revealed DNA sequences belonging to Halobacterium salinarum mainly in the undamaged areas. RAMAN spectroscopy detected pigments within the purple spots, mainly bacteriorhodopsine/rhodopsin-like pigments, a purple transmembrane protein containing retinal and present in Halobacteria. The LTA technique revealed extremely damaged collagen structures in both damaged and undamaged areas of the parchments. In the light of these data, the study represents a first confirmation of the microbial succession model described above. The demonstration of this model is pivotal to start any possible new restoration strategy to bring back historical parchments to their original beauty, but also to open opportunities for intervention on a huge amount of documents.

Keywords: biodeterioration, parchments, purple spots, ecological succession

Procedia PDF Downloads 145

Authors: Igor V. Savchenko, Dmitrii A. Samoshkin

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The active study of the properties of lanthanides has begun in the late 50s of the last century, when methods for their purification were developed and metals with a relatively low content of impurities were obtained. Nevertheless, up to date, many properties of the rare earth metals (REM) have not been experimentally investigated, or insufficiently studied. Currently, the thermal conductivity and thermal diffusivity of lanthanides have been studied most thoroughly in the low-temperature region and at moderate temperatures (near 293 K). In the high-temperature region, corresponding to the solid phase, data on the thermophysical characteristics of the REM are fragmentary and in some cases contradictory. Analysis of the literature showed that the data on the thermal conductivity and thermal diffusivity of light REM in the liquid state are few in number, little informative (only one point corresponds to the liquid state region), contradictory (the nature of the thermal conductivity change with temperature is not reproduced), as well as the results of measurements diverge significantly beyond the limits of the total errors. Thereby our experimental results allow to fill this gap and to clarify the existing information on the heat transfer coefficients of neodymium and samarium in a wide temperature range from the melting point up to 1770 K. The measurement of the thermal conductivity of investigated metallic melts was carried out by laser flash technique on an automated experimental setup LFA-427. Neodymium sample of brand NM-1 (99.21 wt % purity) and samarium sample of brand SmM-1 (99.94 wt % purity) were cut from metal ingots and then ones were annealed in a vacuum (1 mPa) at a temperature of 1400 K for 3 hours. Measuring cells of a special design from tantalum were used for experiments. Sealing of the cell with a sample inside it was carried out by argon-arc welding in the protective atmosphere of the glovebox. The glovebox was filled with argon with purity of 99.998 vol. %; argon was additionally cleaned up by continuous running through sponge titanium heated to 900–1000 K. The general systematic error in determining the thermal conductivity of investigated metallic melts was 2–5%. The approximation dependences and the reference tables of the thermal conductivity and thermal diffusivity coefficients were developed. New reliable experimental data on the transport properties of the REM and their changes in phase transitions can serve as a scientific basis for optimizing the industrial processes of production and use of these materials, as well as ones are of interest for the theory of thermophysical properties of substances, physics of metals, liquids and phase transformations.

Keywords: high temperatures, laser flash technique, liquid state, metallic melt, rare earth metals, thermal conductivity, thermal diffusivity

Procedia PDF Downloads 172

Authors: H. I. Obadiah, S. N. Wieser, E. A. Omudu, B. O. Atu, O. Byanet, L. Schnittger, M. Florin-Christensen

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Sarcocystis sp. are Apicomplexan protozoan parasites with a life cycle that involves a predator and a prey as final and intermediate hosts, respectively. In tissues of the intermediate hosts, the parasites produce sarcocysts that vary in size and morphology according to the species. When a suitable predator ingests sarcocyst-containing meat, the parasites are released in the intestine and undergo sexual reproduction producing infective sporocysts, which are excreted with the feces into the environment. The cycle is closed when a prey ingests sporocyst-contaminated water or pasture; the parasites gain access to the circulation, and eventually invade tissues and reproduce asexually yielding sarcocysts. Pig farming is a common practice in Nigeria as well as in many countries around the world. In addition to its importance as protein source, pork is also a source of several pathogens relevant to humans. In the case of Sarcocystis, three species have been described both in domestic and wild pigs, namely, S. miescheriana, S. porcifelis and S. suihominis. Humans can act both as final and aberrant intermediate hosts of S. suihominis, after ingesting undercooked sarcocyst-infested pork. Infections are usually asymptomatic but can be associated with inappetence, nausea, vomiting and diarrhea, or with muscle pain, fever, eosinophilia and bronchospasm, in humans acting as final or intermediate hosts, respectively. Moreover, excretion of infective forms with human feces leads to further dissemination of the infection. In this study, macroscopic sarcocysts of white color, oval shape and a size range of approximately 3-5 mm were observed in the skeletal muscle of a slaughtered pig in an abattoir in Makurdi, Benue State, Nigeria, destined to human consumption. Sarcocysts were excised and washed in distilled water, and genomic DNA was extracted using a commercial kit. The near-complete length of the 18S rRNA gene was analyzed after PCR amplification of two overlapping fragments, each of which were submitted to direct sequencing. In addition, the mitochondrial cytochrome oxidase (cox-1) gene was PCR-amplified and directly sequenced. Two phylogenetic trees containing the obtained sequences along with available relevant 18S rRNA and cox-1 sequences were constructed by neighbor joining after alignment, using the corresponding sequences of Toxoplasma gondii as outgroup. The results showed in both cases that the analyzed sequences grouped with S. suihominis with high bootstrap value, confirming the identity of this macroscopic sarcocyst-forming parasite as S. suihominis. To the best of our knowledge, these results represent the first demonstration of this parasite in pigs of Nigeria and the largest sarcocysts described so far for S. suihominis. The close proximity between pigs and humans in pig farms, and the frequent poor sanitary conditions in human dwellings strongly suggest that the parasite undergoes the sexual stages of its life cycle in humans as final hosts. These findings provide an important reference for the examination and control of Sarcocystis species in pigs of Nigeria.

Keywords: nigeria, pork, sarcocystis suihominis, zoonotic parasite

Procedia PDF Downloads 62

Authors: A. O. Adenaiya, S. F. Curling, O. Y. Ogunsanwo, G . A. Ormondroyd

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Treatment of wood with chemicals in order to prolong its service life may prove difficult in some refractory wood species. This impermeability in wood is usually due to biochemical changes which occur during heartwood formation. Bioincision, which is a short-term, controlled microbial decomposition of wood, is one of the promising approaches capable of improving the amenability of refractory wood to chemical treatments. Gmelina Arborea, a mainstay timber species in Nigeria, has impermeable heartwood due to the excessive tyloses which occlude its vessels. Therefore, the chemical uptake and penetration in Gmelina arborea heartwood bioincised with Inonotus dryophilus fungus was investigated. Five mature Gmelina Arborea trees were harvested at the Departmental plantation in Ajibode, Ibadan, Nigeria and a bolt of 300 cm was obtained from the basal portion of each tree. The heartwood portion of the bolts was extracted and converted into dimensions 20 mm x 20 mm x 60 mm and subsequently conditioned (200C at 65% Relative Humidity). Twenty wood samples each were bioincised with the white-rot fungus Inonotus dryophilus (ID, 999) for 3, 5, 7 and 9 weeks using standard procedure, while a set of sterile control samples were prepared. Ten of each bioincised and control sample were pressure-treated with 5% tanalith preservative, while the other ten of each bioincised and control samples were pressure-treated with a liquid dye for easy traceability of the chemical in the wood, both using a full cell treatment process. The bioincised and control samples were evaluated for their Weight Loss before chemical treatment (WL, %), Preservative Absorption (PA, Kg/m3), Preservative Retention (PR, Kg/m3), Axial Absorption (AA, Kg/m3), Lateral Absorption (LA, Kg/m3), Axial Penetration Depth (APD, mm), Radial Penetration Depth (RPD, mm), and Tangential Penetration Depth (TPD, mm). The data obtained were analyzed using ANOVA at α0.05. Results show that the weight loss was least in the samples bioincised for three weeks (0.09%) and highest after 7 weeks of bioincision (0.48%). The samples bioincised for 3 weeks had the least PA (106.72 Kg/m3) and PR (5.87 Kg/m3), while the highest PA (134.9 Kg/m3) and PR were observed after 7 weeks of bioincision (7.42 Kg/m3). The AA ranged from 27.28 Kg/m3 (3 weeks) to 67.05 Kg/m3 (5 weeks), while the LA was least after 5 weeks of incubation (28.1 Kg/m3) and highest after 9 weeks (71.74 Kg/m3). Significantly lower APD was observed in control samples (6.97 mm) than in the samples bioincised after 9weeks (19.22 mm). The RPD increased from 0.08 mm (control samples) to 3.48 mm (5 weeks), while TPD ranged from 0.38 mm (control samples) to 0.63 mm (9 weeks), implying that liquid flow in the wood was predominantly through the axial pathway. Bioincising G. arborea heartwood with I. dryophilus fungus for 9 weeks is capable of enhancing chemical uptake and deeper penetration of chemicals in the wood through the degradation of the occluding vessel tyloses, which is accompanied by a minimal degradation of the polymeric wood constituents.

Keywords: Bioincision, chemical uptake, penetration depth, refractory wood, tyloses

Procedia PDF Downloads 80

Authors: Abeer Y. Ibrahim, Faten M. Ibrahim, Samah A. El-Newary, Saber F. Hendawy

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Objective: Appreciation of in-vitro anti-inflammatory and antioxidant characters of Vitex agnus-castus berries alcoholic extract and fractions, as well as in-vivo antitumor ability of alcoholic extract and chloroform fraction against Ehrlich ascites carcinoma is the aim of this study. Material and methods: Antioxidant properties of crude alcoholic extract of vitex berries as well as petroleum ether, chloroform, ethyl acetate and butanol fractions were evaluated, in-vitro assessments, as compared with standard materials, l-ascorbic acid (vitamin C) and butylated hydroxyl toluene(BHT). The anti-inflammatory activity was investigated in cyclooxygenase (COX)-1 and COX-2 inhibition assays. Moreover, in-vivo antitumor effect of vitex berries alcoholic and chloroform extracts were evaluated using Ehrlich ascites carcinoma model. Data were presented as mean±SE, and data were analyzed by one-way analysis of variance test. Results and conclusion: Berries crude extract showed potent antioxidant activity followed with its fractions ethyl acetate and chloroform as compared with standard (V.C and BHT). Ethyl acetate fraction showed good reduction capability, metal ion chelation, hydrogen peroxide scavenging, nitric oxide scavenging and superoxide anion scavenging. Meanwhile, chloroform fraction produced the highest free radical scavenging activity and total antioxidant capacity. In respectable of lipid peroxidation inhibition, crude alcoholic extract and its fractions cleared weak inhibition in comparing with standard materials. Anti-inflammatory activity of V. agnus-castus berries chloroform fraction of vitex was best COX-2 inhibitor (IC₅₀, 135.41 µg/ ml) as compared to vitex alcoholic extract or ethyl acetate fraction with weak inhibitory effect on COX-1 (IC50, 778.432 µg/ ml), where the lowest effect on COX-1 was recorded with alcoholic extract. Alcoholic extract and its fractions showed weak COX-1 inhibition activity, whereas COX-2 was inhibited (100%), compared with celecoxib drug (72% at 1000ppm). The crude alcoholic and chloroform extracts of V. agnus-castus barries significantly reduced the viable Ehrlich cell count and increased nonviable count with amelioration of all hematological parameters. This amelioration was reflected on increasing median survival time and significant increase (P < 0.05) in lifespan.

Keywords: anti-inflammatory, antioxidants, ehrlich ascites carcinoma, Vitex agnus-castus

Procedia PDF Downloads 121

Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

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The recent advancements in synthetic chemistry and nanotechnology fostered the development of different nanocarriers for enhanced intracellular delivery of pharmaceutical agents to tumor cells. Polymeric micelles (PMs), characterized by small size, appreciable drug loading capacity (DLC), better accumulation in tumor tissue via enhanced permeability and retention (EPR) effect, and the ability to avoid detection and subsequent clearance by the mononuclear phagocyte (MNP) system, are convenient to improve the poor solubility, slow absorption and non-selective biodistribution of payloads embedded in their hydrophobic cores and hence, enhance the therapeutic efficacy of chemotherapeutic agents. Recently, redox-responsive polymeric micelles have gained significant attention for the delivery and controlled release of anticancer drugs in tumor cells. In this study, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se₂ from mPEG-PLGA, and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. The successful synthesis of the copolymers was verified by different spectroscopic techniques. Above the critical micelle concentration, the amphiphilic copolymer, Bi(mPEG-PLGA)-Se₂, self-assembled into stable micelles. The DLS data indicated that the hydrodynamic diameter of the micelles (123.9 ± 0.85 nm) was suitable for extravasation into the tumor cells through the EPR effect. The drug loading content (DLC) and encapsulation efficiency (EE) of DOX-loaded micelles were found to be 6.61 wt% and 54.9%, respectively. The DOX-loaded micelles showed initial burst release accompanied by sustained release trend where 73.94% and 69.54% of encapsulated DOX was released upon treatment with 6mM GSH and 0.1% H₂O₂, respectively. The biocompatible nature of Bi(mPEG-PLGA)-Se₂ copolymer was confirmed by the cell viability study. In addition, the DOX-loaded micelles exhibited significant inhibition against HeLa cells (44.46%), at a maximum dose of 7.5 µg/mL. The fluorescent microscope images of HeLa cells treated with 3 µg/mL (equivalent DOX concentration) revealed efficient internalization and accumulation of DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles in the cytosol of cancer cells. In conclusion, the intelligent, biocompatible, and the redox stimuli-responsive behavior of Bi(mPEG-PLGA)-Se₂ copolymer marked the potential applications of diselenide-linked mPEG-PLGA micelles for the delivery and on-demand release of chemotherapeutic agents in cancer cells.

Keywords: anticancer drug delivery, diselenide bond, polymeric micelles, redox-responsive

Procedia PDF Downloads 90

Authors: Sabri Serkan Gulluoglu

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The study is aimed at examining the effects of internet marketing with IPTV on human beings. Internet marketing with IPTV is emerging as an integral part of business strategies in today’s technologically advanced world and the business activities all over the world are influences with the emergence of this modern marketing tool. As the population of the Internet and on-line users’ increases, new research issues have arisen concerning the demographics and psychographics of the on-line user and the opportunities for a product or service. In recent years, we have seen a tendency of various services converging to the ubiquitous Internet Protocol based networks. Besides traditional Internet applications such as web browsing, email, file transferring, and so forth, new applications have been developed to replace old communication networks. IPTV is one of the solutions. In the future, we expect a single network, the IP network, to provide services that have been carried by different networks today. For finding some important effects of a video based technology market web site on internet, we determine to apply a questionnaire on university students. Recently some researches shows that in Turkey the age of people 20 to 24 use internet when they buy some electronic devices such as cell phones, computers, etc. In questionnaire there are ten categorized questions to evaluate the effects of IPTV when shopping. There were selected 30 students who are filling the question form after watching an IPTV channel video for 10 minutes. This sample IPTV channel is “buy.com”, it look like an e-commerce site with an integrated IPTV channel on. The questionnaire for the survey is constructed by using the Likert scale that is a bipolar scaling method used to measure either positive or negative response to a statement (Likert, R) it is a common system that is used is the surveys. By following the Likert Scale “the respondents are asked to indicate their degree of agreement with the statement or any kind of subjective or objective evaluation of the statement. Traditionally a five-point scale is used under this methodology”. For this study also the five point scale system is used and the respondents were asked to express their opinions about the given statement by picking the answer from the given 5 options: “Strongly disagree, Disagree, Neither agree Nor disagree, Agree and Strongly agree”. These points were also rates from 1-5 (Strongly disagree, Disagree, Neither disagree Nor agree, Agree, Strongly agree). On the basis of the data gathered from the questionnaire some results are drawn in order to get the figures and graphical representation of the study results that can demonstrate the outcomes of the research clearly.

Keywords: IPTV, internet marketing, online, e-commerce, video based technology

Procedia PDF Downloads 218

Authors: Agnieszka H. Ludwig-Slomczynska, Michal T. Seweryn, Przemyslaw Kapusta, Ewelina Pitera, Katarzyna Cyganek, Urszula Mantaj, Lucja Dobrucka, Ewa Wender-Ozegowska, Maciej T. Malecki, Pawel Wolkow

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Obesity results from an imbalance between energy intake and its expenditure. Genome-Wide Association Study (GWAS) analyses have led to discovery of only about 100 variants influencing body mass index (BMI), which explain only a small portion of genetic variability. Analysis of gene epistasis gives a chance to discover another part. Since it was shown that interaction and communication between nuclear and mitochondrial genome are indispensable for normal cell function, we have looked for epistatic interactions between the two genomes to find their correlation with BMI. Methods: The analysis was performed on 366 T1DM patients using Illumina Infinium OmniExpressExome-8 chip and followed by imputation on Michigan Imputation Server. Only genes which influence mitochondrial functioning (listed in Human MitoCarta 2.0) were included in the analysis – variants of nuclear origin (MAF > 5%) in 1140 genes and 42 mitochondrial variants (MAF > 1%). Gene expression analysis was performed on GTex data. Association analysis between genetic variants and BMI was performed with the use of Linear Mixed Models as implemented in the package 'GENESIS' in R. Analysis of association between mRNA expression and BMI was performed with the use of linear models and standard significance tests in R. Results: Among variants involved in epistasis between mitochondria and nucleus we have identified one in mitochondrial transcription factor, TFB2M (rs6701836). It interacted with mitochondrial variants localized to MT-RNR1 (p=0.0004, MAF=15%), MT-ND2 (p=0.07, MAF=5%) and MT-ND4 (p=0.01, MAF=1.1%). Analysis of the interaction between nuclear variant rs6701836 (nuc) and rs3021088 localized to MT-ND2 mitochondrial gene (mito) has shown that the combination of the two led to BMI decrease (p=0.024). Each of the variants on its own does not correlate with higher BMI [p(nuc)=0.856, p(mito)=0.116)]. Although rs6701836 is intronic, it influences gene expression in the thyroid (p=0.000037). rs3021088 is a missense variant that leads to alanine to threonine substitution in the MT-ND2 gene which belongs to complex I of the electron transport chain. The analysis of the influence of genetic variants on gene expression has confirmed the trend explained above – the interaction of the two genes leads to BMI decrease (p=0.0308). Each of the mRNAs on its own is associated with higher BMI (p(mito)=0.0244 and p(nuc)=0.0269). Conclusıons: Our results show that nuclear-mitochondrial epistasis can influence BMI in T1DM patients. The correlation between transcription factor expression and mitochondrial genetic variants will be subject to further analysis.

Keywords: body mass index, epistasis, mitochondria, type 1 diabetes

Procedia PDF Downloads 152

Authors: Aminu Mohammed, Shahidul Islam

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Aframomum melegueta K.Schum commonly known as Grains of Paradise has been a popularly used spice in most of the African food preparation. Available data have shown that ethyl acetate fraction from crude ethanolic extract exhibited α-amylase and α-glucosidase inhibitory actions, improved pancreatic β-cell damage and ameliorated insulin resistance in diabetic rats. Additionally, 6-gingerol, 6-shogaol, 6-paradol and oleanolic acid are shown to be the compounds responsible for the antidiabetic action of A. melegueta. However, detail antioxidant potential of this spice in a diabetic animal model has not yet been reported. Thus, the present study investigates the effect of oral consumption of A. melegueta fruit on the in vivo antioxidant status of type 2 diabetes (T2D) model of rats. T2D was induced in rats by feeding a 10% fructose solution ad libitum for two weeks followed by a single intraperitoneal injection of streptozotocin (40 mg/kg body weight (bw)). The animals were orally administered with 150 (DAML) or 300 mg/kg bw (DAMH) of the fraction once daily for four weeks. Data were analyzed by using a statistical software package (SPSS for Windows, version 22, IBM Corporation, NY, USA) using Tukey’s-HSD multiple range post-hoc test. Values were considered significantly different at p < 0.05. According to the data, after four weeks of intervention, diabetic untreated animals showed significantly (p < 0.05) elevation of blood glucose levels. The levels of thiobarbituric acid reactive substances (TBARS) were observed to increase with concomitant reduction of reduced glutathione (GSH) levels in the serum and organs (liver, kidney, heart and pancreas) of diabetic untreated animals. The activities of endogenous antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and reductase) were greatly reduced in the serum and organs of diabetic untreated animals compared to the normal animals. These alterations were reverted to near-normal after the treatment of A. melegueta fruit in the treated groups (DAML & DAMH) within the study period, especially at the dose of 300 mg/kg bw. This potent antioxidant action may partly be attributed to the presence of the 6-Gingerol, 6-shogaol and 6-paradol are known to possess antioxidant action. The results of our study showed that A. melegueta intake improved the antioxidant status of T2D rats and therefore could be used to ameliorate the diabetes-induced oxidative damage.

Keywords: Aframomum melegueta, antioxidant, ethyl acetate extract, type 2 diabetes

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Authors: Srijata Mitra, Mobina Parveen, Pranab Roy, Narayan Chandra Chattopadhyay

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Chlorinated hydrocarbon can be a major pollution problem in groundwater as well as soil. Many people interact with these chemicals on daily accidentally or by professionally in the laboratory. One of the most common sources for Chlorinated hydrocarbon contamination of soil and groundwater are industrial effluents. The wide use and discharge of Trichloroethylene (TCE), a volatile chlorohydrocarbon from chemical industry, led to major water pollution in rural areas. TCE is an mainly used as an industrial metal degreaser in industries. Biotransformation of TCE to the potent carcinogen vinyl chloride (VC) by consortia of anaerobic bacteria might have role for the above purpose. For these reasons, the aim of current study was to isolate and characterized the genes involved in TCE metabolism and also to investigate the in silico study of those genes. To our knowledge, only one aromatic dioxygenase system, the toluene dioxygenase in Pseudomonas putida F1 has been shown to be involved in TCE degradation. This is first instance where Bacillus cereus group being used in biodegradation of trichloroethylene. A novel bacterial strain 2479 was isolated from oil depot site at Rajbandh, Durgapur (West Bengal, India) by enrichment culture technique. It was identified based on polyphasic approach and ribotyping. The bacterium was gram positive, rod shaped, endospore forming and capable of degrading trichloroethylene as the sole carbon source. On the basis of phylogenetic data and Fatty Acid Methyl Ester Analysis, strain 2479 should be placed within the genus Bacillus and species cereus. However, the present isolate (strain 2479) is unique and sharply different from the usual Bacillus strains in its biodegrading nature. Fujiwara test was done to estimate that the strain 2479 could degrade TCE efficiently. The gene for TCE biodegradation was PCR amplified from genomic DNA of Bacillus cereus 2479 by using todC1 gene specific primers. The 600bp amplicon was cloned into expression vector pUC I8 in the E. coli host XL1-Blue and expressed under the control of lac promoter and nucleotide sequence was determined. The gene sequence was deposited at NCBI under the Accession no. GU183105. In Silico approach involved predicting the physico-chemical properties of deduced Tce1 protein by using ProtParam tool. The tce1 gene contained 342 bp long ORF encoding 114 amino acids with a predicted molecular weight 12.6 kDa and the theoretical pI value of the polypeptide was 5.17, molecular formula: C559H886N152O165S8, total number of atoms: 1770, aliphatic index: 101.93, instability index: 28.60, Grand Average of Hydropathicity (GRAVY): 0.152. Three differentially expressed proteins (97.1, 40 and 30 kDa) were directly involved in TCE biodegradation, found to react immunologically to the antibodies raised against TCE inducible proteins in Western blot analysis. The present study suggested that cloned gene product (TCE1) was capable of degrading TCE as verified chemically.

Keywords: cloning, Bacillus cereus, in silico analysis, TCE

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Authors: Antonis Elia, Theo Loizou, Gladys Onambele-Pearson, Matthew Barlow, Georgina Stebbings

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Hypoxic conditions have been reported to enhance red blood cell production in both acclimatised low-landers and altitude adapted populations. This process is mediated by the erythropoietin hormone, which is released predominantly by the hypoxic kidney. A higher haemoglobin concentration was previously reported in elite breath-hold divers when compared to elite-skiers and untrained individuals. Therefore, the present study aimed to investigate whether apnoea induced hypoxia could induce a significant increase in serum erythropoietin concentration in recreational breath-hold divers which would provide an explanation to the higher haemoglobin levels observed in elite breath-hold divers. Identifying whether apnoea induced hypoxia induces a significant increase in serum erythropoietin might suggest that apnoea can be used as an alternative acclimatisation method to high altitude exposure. Seven healthy, recreational male breath-hold divers performed two sets of five 180 second breath-holds with a ten-minute supine rest between each set and a two-minute seated rest between each apnoea. During each breath-hold, participant’s heart rate and peripheral oxygen saturation levels were recorded every subsequent 10 seconds until the end of the 180 second breath-hold. After each 180 second breath-hold a capillary blood sample was collected from the finger to identify circulating haemoglobin levels. Following completion of the apnoeic protocol, three blood samples were collected at 30, 90 and 180 minutes to measure circulating erythropoietin levels. A significant interaction between erythropoietin and time was observed (F(3,18)= 4.72, p < 0.001), with significant increases in erythropoietin evident at 30 (t(6)= -5.035, p < 0.0590 (t(6)= -6.162, p < 0.05) and 180 (t(6)= - 7.232, p < 0.001) minutes post the last apnoea when compared to baseline. Corresponding average increases when compared to baseline were 16% at 30, 23% at 90 and 40% at 180 minutes post the last apnoea. A significant interaction between haemoglobin and time was observed (F(78,84)= 20.814, p < 0.001), with significant increases in haemoglobin evident at the fifth (t(29)= -1.124, p < 0.001), ninth (t(29)= -1.357, p < 0.001) and tenth (t(29)= -1.211, p < 0.05) apnoeas when compared to baseline. A significant interaction between peripheral oxygen saturation and time was observed (F(10,60)= 408.23, p < 0.001). The present study demonstrates that a series of ten 180 second breath-holds is sufficient to induce a significant increase in the circulating erythropoietin concentration of recreational breath hold divers. These observations may suggest that apnoea induced hypoxia may be used as an alternative acclimatisation method to high altitude exposure.

Keywords: apnoea, breath-holding, diving reflex, erythropoietin, haemoglobin

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Authors: Susana Gonçalves, Joana Lencart, Anabela Gregório Dias

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Introduction: In combination with chemotherapy, Total Body Irradiation (TBI) is most used as part of the conditioning regimen prior to allogeneic hematopoietic stem cell transplantation. Conventional TBI techniques have a long application time but non-conformality of beam-application with the inability to individually spare organs at risk. Our institution’s intention is to start using Volumetric Modulated Arc Therapy (VMAT) techniques to increase homogeneity of delivered radiation. As a first approach, a dosimetric plan was performed on a computed tomography (CT) scan of a Rando Alderson antropomorfic phantom (head and torso), using a set of six arcs distributed along the phantom. However, a full body anthropomorphic phantom is essential to carry out technique validation and implementation. Our aim is to define the physical and chemical characteristics and the ideal manufacturing procedure of upper and lower limbs to our anthropomorphic phantom, for later validate TBI using VMAT. Materials and Methods: To study the better fit between our phantom and limbs, a CT scan of Rando Alderson anthropomorphic phantom was acquired. CT was performed on GE Healthcare equipment (model Optima CT580 W), with slice thickness of 2.5 mm. This CT was also used to access the electronic density of soft tissue and bone through Hounsfield units (HU) analysis. Results: CT images were analyzed and measures were made for the ideal upper and lower limbs. Upper limbs should be build under the following measures: 43cm length and 7cm diameter (next to the shoulder section). Lower limbs should be build under the following measures: 79cm length and 16.5cm diameter (next to the thigh section). As expected, soft tissue and bone have very different electronic density. This is important to choose and analyze different materials to better represent soft tissue and bone characteristics. The approximate HU values of the soft tissue and for bone shall be 35HU and 250HU, respectively. Conclusion: At the moment, several compounds are being developed based on different types of resins and additives in order to be able to control and mimic the various constituent densities of the tissues. Concurrently, several manufacturing techniques are being explored to make it possible to produce the upper and lower limbs in a simple and non-expensive way, in order to finally carry out a systematic and appropriate study of the total body irradiation. This preliminary study was a good starting point to demonstrate the feasibility of TBI with VMAT.

Keywords: TBI, VMAT, anthropomorphic phantom, tissue equivalent materials

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Authors: Sandy Elsayed, Aya Mohamed, Noha Nassar

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Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behavior. Multiple studies suggest that oxidative stress and neuroinflammation are key factors in the etiology of ASD and often associated with worsening of ASD-related behaviors. Nuclear factor erythroid 2-related factor 2 (NRF-2) is a transcription factor that promotes expression of antioxidant response element genes in oxidative stress. In ASD subjects, decreased expression of NRF-2 in frontal cortex shifted the redox homeostasis towards oxidative stress, and resulted in inflammation evidenced by elevation of nuclear factor kappa B (NF-κB) transcriptional activity. Dimethyl fumarate (DMF) is a NRF-2 activator that is used in the treatment of psoriasis and multiple sclerosis. It participates in the transcriptional control of inflammatory factors via inhibition of NF-κB and its downstream targets. This study aimed to investigate the role of DMF in alleviating the cognitive impairments and behavior deficits associated with ASD through mitigation of oxidative stress and inflammation in prenatal valproic acid (VPA) rat model of autism. Methods: Pregnant female Wistar rats received a single intraperitoneal injection of VPA (600 mg/kg) to induce autistic-like-behavioral and neurobiological alterations in their offspring. Chronic oral gavage of DMF (150mg/kg/day) started from postnatal day (PND) 24 till PND62 (39 days). Prenatal VPA exposure elicited autistic behaviors including decreased social interaction and stereotyped behavior. Social interaction was evaluated using three-chamber sociability test and calculation of sociability index (SI), while stereotyped repetitive behavior and anxiety associated with ASD were assessed using marble burying test (MBT). Biochemical analyses were done on prefrontal cortex homogenates including NRF-2, and NF-κB expression. Moreover, inducible nitric oxide synthase (iNOS) gene expression and tumor necrosis factor (TNF-) protein expression were evaluated as markers of inflammation. Results: Prenatal VPA elicited decreased social interaction shown by decreased SI compared to control group (p < 0.001) and DMF enhanced SI (p < 0.05). In MBT, prenatal injection of VPA manifested stereotyped behavior and enhanced number of buried marbles compared to control (p < 0.05) and DMF reduced the anxiety-related behavior in rats exhibiting ASD-like behaviors (p < 0.05). In prefrontal cortex, NRF-2 expression was downregulated in prenatal VPA model (p < 0.0001) and DMF reversed this effect (p < 0.0001). The inflammatory transcription factor NF-κB was elevated in prenatal VPA model (p < 0.0001) and reduced (p < 0.0001) upon NRF-2 activation by DMF. Prenatal VPA expressed higher levels of proinflammatory cytokine TNF- compared to control group (p < 0.0001) and DMF reduced it (p < 0.0001). Finally, the gene expression of iNOS was downregulated upon NRF-2 activation by DMF (p < 0.01). Conclusion: This study proposes that DMF is a potential agent that can be used to ameliorate autistic-like-changes through NRF-2 activation along with NF-κB downregulation and therefore, it is a promising novel therapy for ASD.

Keywords: autism spectrum disorders, dimethyl fumarate, neuroinflammation, NRF-2

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Authors: B. Atika, S. Lehmann, E. Wimmer

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The defense strategy is very common in the insect world. Defensive substances play a wide variety of functions for beetles, such as repellents, toxicants, insecticides, and antimicrobics. Beetles react to predators, invaders, and parasitic microbes with the release of toxic and repellent substances. Defensive substances are directed against a large array of potential target organisms or may function for boiling bombardment or as surfactants. Usually, Coleoptera biosynthesize and store their defensive compounds in a complex secretory organ, known as odoriferous defensive stink glands. The red flour beetle, Tribolium castaneum (Coleoptera: Tenebrionidae), uses these glands to produce antimicrobial p-benzoquinones and 1-alkenes. In the past, the morphology of stink gland has been studied in detail in tenebrionid beetles; however, very little is known about the genes that are involved in the production of gland secretion. In this study, we studied a subset of genes that are essential for the benzoquinone production in red flour beetle. In the first phase, we selected 74 potential candidate genes from a genome-wide RNA interference (RNAi) knockdown screen named 'iBeetle.' All these 74 candidate genes were functionally characterized by RNAi-mediated gene knockdown. Therefore, they were selected for a subsequent gas chromatography-mass spectrometry (GC-MS) analysis of secretion volatiles in respective RNAi knockdown glands. 33 of them were observed to alter the phenotype of stink gland. In the GC-MS analysis, 7 candidate genes were noted to display a strongly altered gland, in terms of secretion color and chemical composition, upon knockdown, showing their key role in the biosynthesis of gland secretion. Morphologically altered stink glands were found for odorant receptor and protein kinase superfamily. Subsequent GC-MS analysis of secretion volatiles revealed reduced benzoquinone levels in LIM domain, PDZ domain, PBP/GOBP family knockdowns and a complete lack of benzoquinones in the knockdown of sulfatase-modifying factor enzyme 1, sulfate transporter family. Based on stink gland transcriptome data, we analyzed the function of sulfatase-modifying factor enzyme 1 and sulfate transporter family via RNAi-mediated gene knockdowns, GC-MS, in situ hybridization, and enzymatic activity assays. Morphologically altered stink glands were noted in knockdown of both these genes. Furthermore, GC-MS analysis of secretion volatiles showed a complete lack of benzoquinones in the knockdown of these two genes. In situ hybridization showed that these two genes are expressed around the vesicle of certain subgroup of secretory stink gland cells. Enzymatic activity assays on stink gland tissue showed that these genes are involved in p-benzoquinone biosynthesis. These results suggest that sulfatase-modifying factor enzyme 1 and sulfate transporter family play a role specifically in benzoquinone biosynthesis in red flour beetles.

Keywords: Red Flour Beetle, defensive stink gland, benzoquinones, sulfate transporter, sulfatase-modifying factor enzyme 1

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