Search results for: induction melting

Authors: Ofelia Loani Elvir Lazo, Roya Yumul, Sevan Komshian, Ruby Wang, Jun Tang

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Background: Monitoring the anti-nociceptive drug effect is useful because a sudden and strong nociceptive stimulus may result in untoward autonomic responses and muscular reflex movements. Monitoring the anti-nociceptive effects of perioperative medications has long been desiredas a way to provide anesthesiologists information regarding a patient’s level of antinociception and preclude any untoward autonomic responses and reflexive muscular movements from painful stimuli intraoperatively.To this end, electroencephalogram (EEG) based tools includingBIS and qCON were designed to provide information about the depth of sedation whileqNOXwas produced to informon the degree of antinociception.The goal of this study was to compare the reliability of qCON/qNOX to BIS asspecific indicators of response to nociceptive stimulation. Methods: Sixty-two patients undergoing general anesthesia with LMA were included in this study. Institutional Review Board(IRB) approval was obtained, and informed consent was acquired prior to patient enrollment. Inclusion criteria included American Society of Anesthesiologists (ASA) class I-III, 18 to 80 years of age, and either gender. Exclusion criteria included the inability to consent. Withdrawal criteria included conversion to endotracheal tube and EEG malfunction. BIS and qCON/qNOX electrodes were simultaneously placed o62n all patientsprior to induction of anesthesia and were monitored throughout the case, along with other perioperative data, including patient response to noxious stimuli. All intraoperative decisions were made by the primary anesthesiologist without influence from qCON/qNOX. Student’s t-distribution, prediction probability (PK), and ANOVA were used to statistically compare the relative ability to detect nociceptive stimuli for each index. Twenty patients were included for the preliminary analysis. Results: A comparison of overall intraoperative BIS, qCON and qNOX indices demonstrated no significant difference between the three measures (N=62, p> 0.05). Meanwhile, index values for qNOX (62±18) were significantly higher than those for BIS (46±14) and qCON (54±19) immediately preceding patient responses to nociceptive stimulation in a preliminary analysis (N=20, * p= 0.0408). Notably, certain hemodynamic measurements demonstrated a significant increase in response to painful stimuli (MAP increased from74±13 mm Hg at baseline to 84± 18 mm Hg during noxious stimuli [p= 0.032] and HR from 76±12 BPM at baseline to 80±13BPM during noxious stimuli[p=0.078] respectively). Conclusion: In this observational study, BIS and qCON/qNOX provided comparable information on patients’ level of sedation throughout the course of an anesthetic. Meanwhile, increases in qNOX values demonstrated a superior correlation to an imminent response to stimulation relative to all other indices.

Keywords: antinociception, bispectral index (BIS), general anesthesia, laryngeal mask airway, qCON/qNOX

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Authors: Jeet Chakraborty, Sanjay Dutta

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Antibiotic resistance by bacteria has proved to be a severe threat to mankind in recent times, and this fortifies an urgency to design and develop potent antibacterial small molecules/compounds with nonconventional mechanisms than the conventional ones. DNA carries the genetic signature of any organism, and bacteria maintain their genomic DNA inside the cell in a well-regulated compact form with the help of various nucleoid associated proteins like HU, HNS, etc. These proteins control various fundamental processes like gene expression, replication, etc., inside the cell. Alteration of the native DNA structure of bacteria can lead to severe consequences in cellular processes inside the bacterial cell that ultimately result in the death of the organism. The change in the global DNA structure by small molecules initiates a plethora of cellular responses that have not been very well investigated. Echinomycin and Triostin-A are biologically active Quinoxaline small molecules that typically consist of a quinoxaline chromophore attached with an octadepsipeptide ring. They bind to double-stranded DNA in a sequence-specific way and have high activity against a wide variety of bacteria, mainly against Gram-positive ones. To date, few synthetic quinoxaline scaffolds were synthesized, displaying antibacterial potential against a broad scale of pathogenic bacteria. QNOs (Quinoxaline N-oxides) are known to target DNA and instigate reactive oxygen species (ROS) production in bacteria, thereby exhibiting antibacterial properties. The divergent role of Quinoxaline small molecules in medicinal research qualifies them for the evaluation of their antimicrobial properties as a potential candidate. The previous study from our lab has given new insights on a 6-nitroquinoxaline derivative 1d as an intercalator of DNA, which induces conformational changes in DNA upon binding.7 The binding event observed was dependent on the presence of a crucial benzyl substituent on the quinoxaline moiety. This was associated with a large induced CD (ICD) appearing in a sigmoidal pattern upon the interaction of 1d with dsDNA. The induction of DNA superstructures by 1d at high Drug:DNA ratios was observed that ultimately led to DNA condensation. Eviction of invitro-assembled nucleosome upon treatment with a high dose of 1d was also observed. In this work, monoquinoxaline derivatives of 1d were synthesized by various modifications of the 1d scaffold. The set of synthesized 6-nitroquinoxaline derivatives along with 1d were all subjected to antibacterial evaluation across five different bacteria species. Among the compound set, 3a displayed potent antibacterial activity against Staphylococcus aureus bacteria. 3a was further subjected to various biophysical studies to check whether the DNA structural alteration potential was still intact. The biological response of S. aureus cells upon treatment with 3a was studied using various cell biology processes, which led to the conclusion that 3d can initiate DNA damage in the S. aureus cells. Finally, the potential of 3a in disrupting preformed S.aureus and S.epidermidis biofilms was also studied.

Keywords: DNA structural change, antibacterial, intercalator, DNA superstructures, biofilms

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Authors: Shaista Suhail

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As cancer populations is increasing sharply, the incidence of oral squamous cell carcinoma (OSCC) has also been expected to increase. Oral carcinogenesis is a highly complex, multistep process which involves accumulation of genetic alterations that lead to the induction of proteins promoting cell growth (encoded by oncogenes), increased enzymatic (telomerase) activity promoting cancer cell proliferation. The global increase in frequency and mortality, as well as the poor prognosis of oral squamous cell carcinoma, has intensified current research efforts in the field of prevention and early detection of this disease. The advances in the understanding of the molecular basis of oral cancer should help in the identification of new markers. The study of the carcinogenic process of the oral cancer, including continued analysis of new genetic alterations, along with their temporal sequencing during initiation, promotion and progression, will allow us to identify new diagnostic and prognostic factors, which will provide a promising basis for the application of more rational and efficient treatments. Telomerase activity has been readily found in most cancer biopsies, in premalignant lesions or germ cells. Activity of telomerase is generally absent in normal tissues. It is known to be induced upon immortalization or malignant transformation of human cells such as in oral cancer cells. Maintenance of telomeres plays an essential role during transformation of precancer to malignant stage. Mammalian telomeres, a specialized nucleoprotein structures are composed of large conctamers of the guanine-rich sequence 5_-TTAGGG-3_. The roles of telomeres in regulating both stability of genome and replicative immortality seem to contribute in essential ways in cancer initiation and progression. It is concluded that activity of telomerase can be used as a biomarker for diagnosis of malignant oral cancer and a target for inactivation in chemotherapy or gene therapy. Its expression will also prove to be an important diagnostic tool as well as a novel target for cancer therapy. The activation of telomerase may be an important step in tumorgenesis which can be controlled by inactivating its activity during chemotherapy. The expression and activity of telomerase are indispensable for cancer development. There are no drugs which can effect extremely to treat oral cancers. There is a general call for new emerging drugs or methods that are highly effective towards cancer treatment, possess low toxicity, and have a minor environment impact. Some novel natural products also offer opportunities for innovation in drug discovery. Natural compounds isolated from medicinal plants, as rich sources of novel anticancer drugs, have been of increasing interest with some enzyme (telomerase) blockage property. The alarming reports of cancer cases increase the awareness amongst the clinicians and researchers pertaining to investigate newer drug with low toxicity.

Keywords: oral carcinoma, telomere, telomerase, blockage

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Authors: Atabaev I. G., Fayziev Sh. A., Irmatova Sh. K.

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Raw materials with high content of Kalium oxide widely used in ceramic technology for prevention or decreasing of deformation of ceramic goods during drying process and under thermal annealing. Becouse to low melting temperature it is also used to decreasing of the temperature of thermal annealing during fabrication of ceramic goods [1,2]. So called “Porceline or China stones” - quartz-sericite (muscovite) minerals is also can be used for prevention of deformation as the content of Kalium oxide in muscovite is rather high (SiO2, + KAl2[AlSi3O10](OH)2). [3] . To estimation of possibility of use of this mineral for ceramic manufacture, in the presented article the influence of thermal processing on phase and a chemical content of this raw material is investigated. As well as to other ceramic raw materials (kaoline, white burning clays) the basic requirements of the industry to quality of "a porcelain stone» are following: small size of particles, relative high uniformity of disrtribution of components and phase, white color after burning, small content of colorant oxides or chromophores (Fe2O3, FeO, TiO2, etc) [4,5]. In the presented work natural minerale from the Boynaksay deposit (Uzbekistan) is investigated. The samples was mechanically polished for investigation by Scanning Electron Microscope. Powder with size of particle up to 63 μm was used to X-ray diffractometry and chemical analysis. The annealing of samples was performed at 900, 1120, 1350oC during 1 hour. Chemical composition of Boynaksay raw material according to chemical analysis presented in the table 1. For comparison the composition of raw materials from Russia and USA are also presented. In the Boynaksay quartz – sericite the average parity of quartz and sericite makes 55-60 and 30-35 % accordingly. The distribution of quartz and sericite phases in raw material was investigated using electron probe scanning electronic microscope «JEOL» JXA-8800R. In the figure 1 the scanning electron microscope (SEM) micrograps of the surface and the distributions of Al, Si and K atoms in the sample are presented. As it seen small granular, white and dense mineral includes quartz, sericite and small content of impurity minerals. Basically, crystals of quartz have the sizes from 80 up to 500 μm. Between quartz crystals the sericite inclusions having a tablet form with radiant structure are located. The size of sericite crystals is ~ 40-250 μm. Using data on interplanar distance [6,7] and ASTM Powder X-ray Diffraction Data it is shown that natural «a porcelain stone» quartz – sericite consists the quartz SiO2, sericite (muscovite type) KAl2[AlSi3O10](OH)2 and kaolinite Al203SiO22Н2О (See Figure 2 and Table 2). As it seen in the figure 3 and table 3a after annealing at 900oC the quartz – sericite contains quartz – SiO2 and muscovite - KAl2[AlSi3O10](OH)2, the peaks related with Kaolinite are absent. After annealing at 1120oC the full disintegration of muscovite and formation of mullite phase Al203 SiO2 is observed (the weak peaks of mullite appears in fig 3b and table 3b). After annealing at 1350oC the samples contains crystal phase of quartz and mullite (figure 3c and table 3с). Well known Mullite gives to ceramics high density, abrasive and chemical stability. Thus the obtained experimental data on formation of various phases during thermal annealing can be used for development of fabrication technology of advanced materials. Conclusion: The influence of thermal annealing in the interval 900-1350oC on phase composition and structure of quartz-sericite minerale is investigated. It is shown that during annealing the phase content of raw material is changed. After annealing at 1350oC the samples contains crystal phase of quartz and mullite (which gives gives to ceramics high density, abrasive and chemical stability).

Keywords: quartz-sericite, kaolinite, mullite, thermal processing

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Authors: Mohamed Habireche, Nacer E. Bacha, Mohamed Djeghdjough

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In the brick industry, smooth double roll crusher is used for medium and fine crushing of soft to medium hard material. Due to opposite inward rotation of the rolls, the feed material is nipped between the rolls and crushed by compression. They are subject to intense wear, known as three-body abrasion, due to the action of abrasive products. The production downtime affecting productivity stems from two sources: the bi-monthly rectification of the roll crushers and their replacement when they are completely worn out. Choosing the right material for the roll crushers should result in longer machine cycles, and reduced repair and maintenance costs. All roll crushers are imported from outside Algeria. This results in sometimes very long delivery times which handicap the brickyards, in particular in respecting delivery times and honored the orders made by customers. The aim of this work is to investigate the effect of alloying additions on microstructure and wear behavior of grey lamellar cast iron for smooth roll crushers in brick industry. The base gray iron was melted in an induction furnace with low frequency at a temperature of 1500 °C, in which return cast iron scrap, new cast iron ingot, and steel scrap were added to the melt to generate the desired composition. The chemical analysis of the bar samples was carried out using Emission Spectrometer Systems PV 8050 Series (Philips) except for the carbon, for which a carbon/sulphur analyser Elementrac CS-i was used. Unetched microstructure was used to evaluate the graphite flake morphology using the image comparison measurement method. At least five different fields were selected for quantitative estimation of phase constituents. The samples were observed under X100 magnification with a Zeiss Axiover T40 MAT optical microscope equipped with a digital camera. SEM microscope equipped with EDS was used to characterize the phases present in the microstructure. The hardness (750 kg load, 5mm diameter ball) was measured with a Brinell testing machine for both treated and as-solidified condition test pieces. The test bars were used for tensile strength and metallographic evaluations. Mechanical properties were evaluated using tensile specimens made as per ASTM E8 standards. Two specimens were tested for each alloy. From each rod, a test piece was made for the tensile test. The results showed that the quenched and tempered alloys had best wear resistance at 400 °C for alloyed grey cast iron (containing 0.62%Mn, 0.68%Cr, and 1.09% Cu) due to fine carbides in the tempered matrix. In quenched and tempered condition, increasing Cu content in cast irons improved its wear resistance moderately. Combined addition of Cu and Cr increases hardness and wear resistance for a quenched and tempered hypoeutectic grey cast iron.

Keywords: casting, cast iron, microstructure, heat treating

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Authors: Lalanthica Yogendran, Manassa Hany, Saira Pasha, Benjamin Chaucer, Simarpreet Kaur, Christopher Janusz

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Children and adolescent patients visit the Psychiatric Emergency Department (ED) for multiple reasons. Visiting the Psychiatric ED itself can be a traumatic experience that can affect an adolescents mental well-being, regardless of a history of mental illness. Despite this, limited research exists in this domain. Prospective studies have correlated adverse psychosocial determinants among adolescents to risk factors for poor well-being and unfavorable behavior outcomes. Studies have also shown that physiological stress is a contributor in the development of health problems and an increase in substance abuse in adolescents. This study aimed to retrospectively determine which psychosocial factors are associated with an increase in psychiatric ED visits. 600 charts of patients who had a psychiatric ED and inpatient admission visit from January 2014 through December 2014 were reviewed. Sociodemographics, diagnoses, ED visits and inpatient admissions were collected. Descriptive statistics, chi-square tests and independent t-test analyses were utilized to examine differences in the sample to determine which factors affected ED visits and admissions. The sample was 50% female, 35.2% self-identified black, and had a mean age of 13 years. The majority, 85%, went to public school and 17% were in special education. Attention Deficit Hyperactivity Disorder was the most common admitting diagnosis, found in 132(23%) responders. Most patients came from single parent household 305 (53%). The mean ages of patients that were sexually active, with legal issues, and reporting marijuana substance abuse were 15, 14.35, and 15 years respectively. Patients from two biological parent households had significantly fewer ED visits (1.2 vs. 1.7, p < 0.01) and admissions (0.09 vs. 0.26, p < 0.01). Among social factors, those who reported sexual, physical or emotional abuse had a significantly greater number of ED visits (2.1 vs. 1.5, p < 0.01) and admissions (0.61 vs. 0.14, p < 0.01) than those who did not. Patients that were sexually active or had legal issues or substance abuse with marijuana had a significantly greater number of admissions (0.43 vs. 0.17, p < 0.01), (0.54 vs. .18, p < 0.01) and (0.46 vs. 0.18, p < 0.01) respectively. This data supports the theory of the stability of a two parent home. Dual parenting plays a role in creating a safe space where a child can develop; this is shown by subsequent decreases in psychiatric ED visits and admissions. This may highlight the psychological protective role of a two parent household. Abuse can exacerbate existing psychiatric illness or initiate the onset of new disease. Substance abuse and legal issues result in early induction to the criminal system. Results show that this causes an increase in frequency of visits and severity of symptoms. Only marijuana, but not other illicit substances, correlated with higher incidence of psychiatric ED visits. This may speak to the psychotropic nature of tetrahydrocannabinols and their role in mental illness. This study demonstrates the array of psychosocial factors that lead to increased ED visits and admissions in children and adolescents.

Keywords: adolescent, child psychiatry, emergency department, substance abuse

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Authors: Faris Mohsin Alabeedi

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Pemphigus Vulgaris (PV) is a life-threatening autoimmune blistering disease characterized by the presence of autoantibodies directed against the epidermis's surface proteins. There are two forms of PV, mucocutaneous and mucosal-dominant PV. Disruption of the cell junctions is a hallmark of PV due to the autoantibodies targeting the desmosomal cadherins, desmoglein-3 (Dsg3) and desmoglein-1, leading to acantholysis in the skin and mucous membrane. Although the pathogenesis of PV is known, the detailed molecular events remain not fully understood. Our recent study has shown that both the PV sera and pathogenic anti-Dsg3 antibody AK23 can induce ROS and cause oxidative stress in cultured keratinocytes. In line with our finding, other independent studies also demonstrate oxidative stress in PV. Since Nrf2 plays a crucial role in cellular anti-oxidative stress response, we hypothesize that the expression of Nrf2 may alter in PV. Thus, treatment of cells with PV sera or AK23 may cause changes in Nrf2 expression and distribution. The purpose of this study was to examine the effect of AK23 and PV sera on Nrf2 in a normal human keratinocyte cell line, such as NTERT cells. Both a time-course and dose-dependent experiments with AK23, alongside the matched isotype control IgG, were performed in keratinocyte cultures and analysed by immunofluorescence for Nrf2 and Dsg3. Additionally, the same approach was conducted with the sera from PV patients and healthy individuals that served as a control in this study. All the fluorescent images were analysed using ImageJ software. Each experiment was repeated twice. In general, variations were observed throughout this study. In the dose-response experiments, although enhanced Dsg3 expression was consistently detected in AK23 treated cells, the expression of Nrf2 showed no consistent findings between the experiments, although changes in its expression were noticeable in cells treated with AK23. In the time-course study, a trend with induction of Nrf2 over time was shown in control cells treated with mouse isotype IgG. Treatment with AK23 showed a reduction of Nrf2 in a time-dependent manner, especially at the 24-hour time point. However, the earlier time points, such as 2 hours and 6 hours with AK23 treatments, detected somewhat variations. Finally, PV sera caused a decrease of Dsg3, but on the other hand, variations were observed in Nrf2 expression in PV sera treated cells. In general, PV sera seemed to cause a reduction of Nrf2 in the majority of PV sera treated samples. In addition, more pronounced cytoplasmic expression of Nrf2 has been observed in PV sera treated cells than those treated with AK23, suggesting that polyclonal and monoclonal IgG might induce a different effect on Nrf2 expression and distribution. Further experimental studies are crucial to obtain a more coincide global view of Nrf2-mediated gene regulation. In particular, Pemphigus Voulgaris studies assessing how the Nrf2-dependent network changes from a physiological to a pathological condition can provide insight into disease mechanisms and perhaps initiate further treatment approaches.

Keywords: pemphigus vulgaris, monoclonal antibody against desmoglein-3, Nrf2 oxidative stress, keratinocyte cultures

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Authors: Alvarez M., Chapela M. J., Balboa E., Rubianes D., Sinde E., Fernandez de Ana C., Rodríguez-Blanco A.

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The gut microbiota plays an important role as gut inflammation could contribute to colorectal cancer development; however, this role is still not fully understood, and tools able to prevent this progression are yet to be developed. The main objective of this study was to monitor the effects of a mushroom extracts formulation in gut microbial community composition of an Azoxymethane (AOM)/Dextran sodium sulfate (DSS) mice model of inflammation-linked carcinogenesis. For the in vivo study, 41 adult male mice of the C57BL / 6 strain were obtained. 36 of them have been induced in a state of colon carcinogenesis by a single intraperitoneal administration of AOM at a dose of 12.5 mg/kg; the control group animals received instead of the same volume of 0.9% saline. DSS is an extremely toxic polysaccharide sulfate that causes chronic inflammation of the colon mucosa, favoring the appearance of severe colitis and the production of tumors induced by AOM. Induction by AOM/DSS is an interesting platform for chemopreventive intervention studies. This time the model was used to monitor gut microbiota changes as a result of supplementation with a specific mushroom extracts formulation previously shown to have prebiotic activity. The animals have been divided into three groups: (i) Cancer + mushroom extracts formulation experimental group: to which the MicoDigest2.0 mushroom extracts formulation developed by Hifas da Terra S.L has been administered dissolved in drinking water at an estimated concentration of 100 mg / ml. (ii) Control group of animals with Cancer: to which normal water has been administered without any type of treatment. (iii) Control group of healthy animals: these are the animals that have not been induced cancer or have not received any treatment in drinking water. This treatment has been maintained for a period of 3 months, after which the animals were sacrificed to obtain tissues that were subsequently analyzed to verify the effects of the mushroom extract formulation. A microbiological analysis has been carried out to compare the microbial communities present in the intestines of the mice belonging to each of the study groups. For this, the methodology of massive sequencing by molecular analysis of the 16S gene has been used (Ion Torrent technology). Initially, DNA extraction and metagenomics libraries were prepared using the 16S Metagenomics kit, always following the manufacturer's instructions. This kit amplifies 7 of the 9 hypervariable regions of the 16S gene that will then be sequenced. Finally, the data obtained will be compared with a database that makes it possible to determine the degree of similarity of the sequences obtained with a wide range of bacterial genomes. Results obtained showed that, similarly to certain natural compounds preventing colorectal tumorigenesis, a mushroom formulation enriched the Firmicutes and Proteobacteria phyla and depleted Bacteroidetes. Therefore, it was demonstrated that the consumption of the mushroom extracts’ formulation developed could promote the recovery of the microbial balance that is disrupted in the mice model of carcinogenesis. More preclinical and clinical studies are needed to validate this promising approach.

Keywords: carcinogenesis, microbiota, mushroom extracts, inflammation

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Authors: E. Poupelloz, S. Gauffinet

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Ettringite Ca₆Al₂(SO₄)₃(OH)₁₂26H₂O is one of the major hydrates formed during cement hydration. Ettringite forms in Portland cement from the reaction between tricalcium aluminate Ca₃Al₂O₆ and calcium sulfate. Ettringite is also present in calcium sulfoaluminate cement in which it is the major hydrate, formed by the reaction between yeelimite Ca₄(AlO₂)₆SO₄ and calcium sulfate. About the formation of ettringite, numerous results are available in the literature even if some issues are still under discussion. However, almost all published work about ettringite was done on cementitious systems. Yet in cement, hydration reactions are very complex, the result of dissolution-precipitation processes and are submitted to various interactions. Understanding the formation process of a phase alone, here ettringite, is the first step to later understand the much more complex reactions happening in cement. This study is crucial for the comprehension of early cement hydration and physical behavior. Indeed formation of hydrates, in particular, ettringite, will have an influence on the rheological properties of the cement paste and on the need for admixtures. To make progress toward the understanding of existing phenomena, a specific study of nucleation and growth processes of ettringite was conducted. First ettringite nucleation was studied in ionic aqueous solutions, with controlled but different experimental conditions, as different supersaturation degrees (β), different pH or presence of exogenous ions. Through induction time measurements, interfacial ettringite crystals solution energies (γ) were determined. Growth of ettringite in supersaturated solutions was also studied through chain crystallization reactions. Specific BET surface area measurements and Scanning Electron Microscopy observations seemed to prove that growth process is favored over the nucleation process when ettringite crystals are initially present in a solution with a low supersaturation degree. The influence of stirring on ettringite formation was also investigated. Observation was made that intensity and nature of stirring have a high influence on the size of ettringite needles formed. Needle sizes vary from less than 10µm long depending on the stirring to almost 100µm long without any stirring. During all previously mentioned experiments, initially present ions are consumed to form ettringite in such a way that the supersaturation degree with regard to ettringite is decreasing over time. To avoid this phenomenon a device compensating the drop of ion concentrations by adding some more solutions, and therefore always have constant ionic concentrations, was used. This constant β recreates the conditions of the beginning of cement paste hydration, when the dissolution of solid reagents compensates the consumption of ions to form hydrates. This device allowed the determination of the ettringite precipitation rate as a function of the supersaturation degree β. Taking samples at different time during ettringite precipitation and doing BET measurements allowed the determination of the interfacial growth rate of ettringite in m²/s. This work will lead to a better understanding and control of ettringite formation alone and thus during cements hydration. This study will also ultimately define the impact of ettringite formation process on the rheology of cement pastes at early age, which is a crucial parameter from a practical point of view.

Keywords: cement hydration, ettringite, morphology of crystals, nucleation-growth process

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Authors: Omar Nouri, Wafa Mnejja, Fatma Dhouib, Syrine Zouari, Wicem Siala, Ilhem Charfeddine, Afef Khanfir, Leila Farhat, Nejla Fourati, Jamel Daoud

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Purpose and Objective: Intensity modulated radiation (IMRT) technique, associated with induction chemotherapy (IC) and/or concomitant chemotherapy (CC), is actually the recommended treatment modality for nasopharyngeal carcinomas (NPC). The aim of this study was to evaluate the therapeutic results and the patterns of relapse with this treatment protocol. Material and methods: A retrospective monocentric study of 145 patients with NPC treated between June 2016 and July 2021. All patients received IMRT with integrated simultaneous boost (SIB) of 33 daily fractions at a dose of 69.96 Gy for high-risk volume, 60 Gy for intermediate risk volume and 54 Gy for low-risk volume. The high-risk volume dose was 66.5 Gy in children. Survival analysis was performed according to the Kaplan-Meier method, and the Log-rank test was used to compare factors that may influence survival. Results: Median age was 48 years (11-80) with a sex ratio of 2.9. One hundred-twenty tumors (82.7%) were classified as stages III-IV according to the 2017 UICC TNM classification. Ten patients (6.9%) were metastatic at diagnosis. One hundred-thirty-five patient (93.1%) received IC, 104 of which (77%) were TPF-based (taxanes, cisplatin and 5 fluoro-uracil). One hundred-thirty-eight patient (95.2%) received CC, mostly cisplatin in 134 cases (97%). After a median follow-up of 50 months [22-82], 46 patients (31.7%) had a relapse: 12 (8.2%) experienced local and/or regional relapse after a median of 18 months [6-43], 29 (20%) experienced distant relapse after a median of 9 months [2-24] and 5 patients (3.4%) had both. Thirty-five patients (24.1%) died, including 5 (3.4%) from a cause other than their cancer. Three-year overall survival (OS), cancer specific survival, disease free survival, metastasis free survival and loco-regional free survival were respectively 78.1%, 81.3%, 67.8%, 74.5% and 88.1%. Anatomo-clinic factors predicting OS were age > 50 years (88.7 vs. 70.5%; p=0.004), diabetes history (81.2 vs. 66.7%; p=0.027), UICC N classification (100 vs. 95 vs. 77.5 vs. 68.8% respectively for N0, N1, N2 and N3; p=0.008), the practice of a lymph node biopsy (84.2 vs. 57%; p=0.05), and UICC TNM stages III-IV (93.8 vs. 73.6% respectively for stage I-II vs. III-IV; p=0.044). Therapeutic factors predicting OS were a number of CC courses (less than 4 courses: 65.8 vs. 86%; p=0.03, less than 5 courses: 71.5 vs. 89%; p=0.041), a weight loss > 10% during treatment (84.1 vs. 60.9%; p=0.021) and a total cumulative cisplatin dose, including IC and CC, < 380 mg/m² (64.4 vs. 87.6%; p=0.003). Radiotherapy delay and total duration did not significantly affect OS. No grade 3-4 late side effects were noted in the evaluable 127 patients (87.6%). The most common toxicity was dry mouth which was grade 2 in 47 cases (37%) and grade 1 in 55 cases (43.3%).Conclusion: IMRT for nasopharyngeal carcinoma granted a high loco-regional control rate for patients during the last five years. However, distant relapses remain frequent and conditionate the prognosis. We identified many anatomo-clinic and therapeutic prognosis factors. Therefore, high-risk patients require a more aggressive therapeutic approach, such as radiotherapy dose escalation or adding adjuvant chemotherapy.

Keywords: therapeutic results, prognostic factors, intensity-modulated radiotherapy, nasopharyngeal carcinoma

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Authors: Maria Fatima Almeida, Rodrigo Calili, George Soares, João Krause, Myrthes Marcele Dos Santos, Anna Carolina Suzano E. Silva, Marcos Alexandre Da

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In Brazil, the building sector accounts for 1/6 of energy consumption and 50% of electricity consumption. A complex sector with several driving actors plays an essential role in the country's economy. Currently, the digitalization readiness in this sector is still low, mainly due to the high investment costs and the difficulty of estimating the benefits of digital technologies in buildings. Nevertheless, the potential contribution of digitalization for increasing energy efficiency in the building sector in Brazil has been pointed out as relevant in the political and sectoral contexts, both in the medium and long-term horizons. To contribute to the debate on the possible evolving trajectories of digitalization in the building sector in Brazil and to subsidize the formulation or revision of current public policies and managerial decisions, three future scenarios were created to anticipate the potential energy efficiency in the building sector in Brazil due to digitalization by 2050. This work aims to present these scenarios as a basis to foresight the potential energy efficiency in this sector, according to different digitalization paces - slow, moderate, or fast in the 2050 horizon. A methodological approach was proposed to create alternative prospective scenarios, combining the Global Business Network (GBN) and the Laboratory for Investigation in Prospective Strategy and Organisation (LIPSOR) methods. This approach consists of seven steps: (i) definition of the question to be foresighted and time horizon to be considered (2050); (ii) definition and classification of a set of key variables, using the prospective structural analysis; (iii) identification of the main actors with an active role in the digital and energy spheres; (iv) characterization of the current situation (2021) and identification of main uncertainties that were considered critical in the development of alternative future scenarios; (v) scanning possible futures using morphological analysis; (vi) selection and description of the most likely scenarios; (vii) foresighting the potential energy efficiency in each of the three scenarios, namely slow digitalization; moderate digitalization, and fast digitalization. Each scenario begins with a core logic and then encompasses potentially related elements, including potential energy efficiency. Then, the first scenario refers to digitalization at a slow pace, with induction by the government limited to public buildings. In the second scenario, digitalization is implemented at a moderate pace, induced by the government in public, commercial, and service buildings, through regulation integrating digitalization and energy efficiency mechanisms. Finally, in the third scenario, digitalization in the building sector is implemented at a fast pace in the country and is strongly induced by the government, but with broad participation of private investments and accelerated adoption of digital technologies. As a result of the slow pace of digitalization in the sector, the potential for energy efficiency stands at levels below 10% of the total of 161TWh by 2050. In the moderate digitalization scenario, the potential reaches 20 to 30% of the total 161TWh by 2050. Furthermore, in the rapid digitalization scenario, it will reach 30 to 40% of the total 161TWh by 2050.

Keywords: building digitalization, energy efficiency, scenario building, prospective structural analysis, morphological analysis

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Authors: Jaden Lu, Olivia Lu

Abstract:

Despite the remarkable advancement of solar cell technology, the challenge of optimizing total solar energy harvest efficiency persists, primarily due to significant heat loss. This excess heat not only diminishes solar panel output efficiency but also curtails its operational lifespan. A promising approach to address this issue is the conversion of surplus heat into electricity. In recent years, there is growing interest in the use of thermoelectric generators (TEG) as a potential solution. The integration of efficient TEG devices holds the promise of augmenting overall energy harvest efficiency while prolonging the longevity of solar panels. While certain research groups have proposed the integration of solar cells and TEG devices, a substantial gap between conceptualization and practical implementation remains, largely attributed to low thermal energy conversion efficiency of TEG devices. To bridge this gap and meet the requisites of practical application, a feasible strategy involves the incorporation of a substantial number of p-n junctions within a confined unit volume. However, the manufacturing of high-density TEG p-n junctions presents a formidable challenge. The prevalent solution often leads to large device sizes to accommodate enough p-n junctions, consequently complicating integration with solar cells. Recently, the adoption of 3D printing technology has emerged as a promising solution to address this challenge by fabricating high-density p-n arrays. Despite this, further developmental efforts are necessary. Presently, the primary focus is on the 3D printing of vertically layered TEG devices, wherein p-n junction density remains constrained by spatial limitations and the constraints of 3D printing techniques. This study proposes a novel device configuration featuring horizontally arrayed p-n junctions of Bi2Te3. The structural design of the device is subjected to simulation through the Finite Element Method (FEM) within COMSOL Multiphysics software. Various device configurations are simulated to identify optimal device structure. Based on the simulation results, a new TEG device is fabricated utilizing 3D Selective laser melting (SLM) printing technology. Fusion 360 facilitates the translation of the COMSOL device structure into a 3D print file. The horizontal design offers a unique advantage, enabling the fabrication of densely packed, three-dimensional p-n junction arrays. The fabrication process entails printing a singular row of horizontal p-n junctions using the 3D SLM printing technique in a single layer. Subsequently, successive rows of p-n junction arrays are printed within the same layer, interconnected by thermally conductive copper. This sequence is replicated across multiple layers, separated by thermal insulating glass. This integration created in a highly compact three-dimensional TEG device with high density p-n junctions. The fabricated TEG device is then attached to the bottom of the solar cell using thermal glue. The whole device is characterized, with output data closely matching with COMSOL simulation results. Future research endeavors will encompass the refinement of thermoelectric materials. This includes the advancement of high-resolution 3D printing techniques tailored to diverse thermoelectric materials, along with the optimization of material microstructures such as porosity and doping. The objective is to achieve an optimal and highly integrated PV-TEG device that can substantially increase the solar energy harvest efficiency.

Keywords: thermoelectric, finite element method, 3d print, energy conversion

Procedia PDF Downloads 35

Authors: María José Carrero, Ana M. Borreguero, Juan F. Rodríguez, María M. Velencoso, Ángel Serrano, María Jesús Ramos

Abstract:

Flame-retardants are incorporated in different materials in order to reduce the risk of fire, either by providing increased resistance to ignition, or by acting to slow down combustion and thereby delay the spread of flames. In this work, polyether polyols with fire retardant properties were synthesized due to their wide application in the polyurethanes formulation. The combustion of polyurethanes is primarily dependent on the thermal properties of the polymer, the presence of impurities and formulation residue in the polymer as well as the supply of oxygen. There are many types of flame retardants, most of them are phosphorous compounds of different nature and functionality. The addition of these compounds is the most common method for the incorporation of flame retardant properties. The employment of glycerol phosphate sodium salt as initiator for the polyol synthesis allows obtaining polyols with phosphate groups in their structure. However, some of the critical points of the use of glycerol phosphate salt are: the lower reactivity of the salt and the necessity of a solvent (dimethyl sulfoxide, DMSO). Thus, the main aim in the present work was to determine the amount of the solvent needed to get a good solubility of the initiator salt. Although the anionic polymerization mechanism of polyether formation is well known, it seems convenient to clarify the role that DMSO plays at the starting point of the polymerization process. Regarding the fact that the catalyst deprotonizes the hydroxyl groups of the initiator and as a result of this, two water molecules and glycerol phosphate alkoxide are formed. This alkoxide, together with DMSO, has to form a homogeneous mixture where the initiator (solid) and the propylene oxide (PO) are soluble enough to mutually interact. The addition rate of PO increased when the solvent/initiator ratios studied were increased, observing that it also made the initiation step shorter. Furthermore, the molecular weight of the polyol decreased when higher solvent/initiator ratios were used, what revealed that more amount of salt was activated, initiating more chains of lower length but allowing to react more phosphate molecules and to increase the percentage of phosphorous in the final polyol. However, the final phosphorous content was lower than the theoretical one because only a percentage of salt was activated. On the other hand, glycerol phosphate disodium salt was still partially insoluble in DMSO studied proportions, thus, the recovery and reuse of this part of the salt for the synthesis of new flame retardant polyols was evaluated. In the recovered salt case, the rate of addition of PO remained the same than in the commercial salt but a shorter induction period was observed, this is because the recovered salt presents a higher amount of deprotonated hydroxyl groups. Besides, according to molecular weight, polydispersity index, FT-IR spectrum and thermal stability, there were no differences between both synthesized polyols. Thus, it is possible to use the recovered glycerol phosphate disodium salt in the same way that the commercial one.

Keywords: DMSO, fire retardants, glycerol phosphate disodium salt, recovered initiator, solvent

Procedia PDF Downloads 249

Authors: Jaden Lu, Olivia Lu

Abstract:

Despite the remarkable advancement of solar cell technology, the challenge of optimizing total solar energy harvest efficiency persists, primarily due to significant heat loss. This excess heat not only diminishes solar panel output efficiency but also curtails its operational lifespan. A promising approach to address this issue is the conversion of surplus heat into electricity. In recent years, there is growing interest in the use of thermoelectric generators (TEG) as a potential solution. The integration of efficient TEG devices holds the promise of augmenting overall energy harvest efficiency while prolonging the longevity of solar panels. While certain research groups have proposed the integration of solar cells and TEG devices, a substantial gap between conceptualization and practical implementation remains, largely attributed to low thermal energy conversion efficiency of TEG devices. To bridge this gap and meet the requisites of practical application, a feasible strategy involves the incorporation of a substantial number of p-n junctions within a confined unit volume. However, the manufacturing of high-density TEG p-n junctions presents a formidable challenge. The prevalent solution often leads to large device sizes to accommodate enough p-n junctions, consequently complicating integration with solar cells. Recently, the adoption of 3D printing technology has emerged as a promising solution to address this challenge by fabricating high-density p-n arrays. Despite this, further developmental efforts are necessary. Presently, the primary focus is on the 3D printing of vertically layered TEG devices, wherein p-n junction density remains constrained by spatial limitations and the constraints of 3D printing techniques. This study proposes a novel device configuration featuring horizontally arrayed p-n junctions of Bi2Te3. The structural design of the device is subjected to simulation through the Finite Element Method (FEM) within COMSOL Multiphysics software. Various device configurations are simulated to identify optimal device structure. Based on the simulation results, a new TEG device is fabricated utilizing 3D Selective laser melting (SLM) printing technology. Fusion 360 facilitates the translation of the COMSOL device structure into a 3D print file. The horizontal design offers a unique advantage, enabling the fabrication of densely packed, three-dimensional p-n junction arrays. The fabrication process entails printing a singular row of horizontal p-n junctions using the 3D SLM printing technique in a single layer. Subsequently, successive rows of p-n junction arrays are printed within the same layer, interconnected by thermally conductive copper. This sequence is replicated across multiple layers, separated by thermal insulating glass. This integration created in a highly compact three-dimensional TEG device with high density p-n junctions. The fabricated TEG device is then attached to the bottom of the solar cell using thermal glue. The whole device is characterized, with output data closely matching with COMSOL simulation results. Future research endeavors will encompass the refinement of thermoelectric materials. This includes the advancement of high-resolution 3D printing techniques tailored to diverse thermoelectric materials, along with the optimization of material microstructures such as porosity and doping. The objective is to achieve an optimal and highly integrated PV-TEG device that can substantially increase the solar energy harvest efficiency.

Keywords: thermoelectric, finite element method, 3d print, energy conversion

Procedia PDF Downloads 35

Authors: Zanele D. Ngwenya, Mustapha Mohammed, Felix D. Dakora

Abstract:

Legumes are a major source of biological nitrogen, and therefore play a crucial role in maintaining soil productivity in smallholder agriculture in southern Africa. Through their ability to fix atmospheric nitrogen in root nodules, legumes are a better option for sustainable nitrogen supply in cropping systems than chemical fertilisers. For decades, farmers have been highly receptive to the use of rhizobial inoculants as a source of nitrogen due mainly to the availability of elite rhizobial strains at a much lower compared to chemical fertilisers. To improve the efficiency of the legume-rhizobia symbiosis in African soils would require the use of highly effective rhizobia capable of nodulating a wide range of host plants. This study assessed the morphogenetic diversity, photosynthetic functioning and relative symbiotic effectiveness (RSE) of groundnut, jack bean and soybean microsymbionts in Eswatini soils as a first step to identifying superior isolates for inoculant production. According to the manufacturer's instructions, rhizobial isolates were cultured in yeast-mannitol (YM) broth until the late log phase and the bacterial genomic DNA was extracted using GenElute bacterial genomic DNA kit. The extracted DNA was subjected to enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR) and a dendrogram constructed from the band patterns to assess rhizobial diversity. To assess the N2-fixing efficiency of the authenticated rhizobia, photosynthetic rates (A), stomatal conductance (gs), and transpiration rates (E) were measured at flowering for plants inoculated with the test isolates. The plants were then harvested for nodulation assessment and measurement of plant growth as shoot biomass. The results of ERIC-PCR fingerprinting revealed the presence of high genetic diversity among the microsymbionts nodulating each of the three test legumes, with many of them showing less than 70% ERIC-PCR relatedness. The dendrogram generated from ERIC-PCR profiles grouped the groundnut isolates into 5 major clusters, while the jack bean and soybean isolates were grouped into 6 and 7 major clusters, respectively. Furthermore, the isolates also elicited variable nodule number per plant, nodule dry matter, shoot biomass and photosynthetic rates in their respective host plants under glasshouse conditions. Of the groundnut isolates tested, 38% recorded high relative symbiotic effectiveness (RSE >80), while 55% of the jack bean isolates and 93% of the soybean isolates recorded high RSE (>80) compared to the commercial Bradyrhizobium strains. About 13%, 27% and 83% of the top N₂-fixing groundnut, jack bean and soybean isolates, respectively, elicited much higher relative symbiotic efficiency (RSE) than the commercial strain, suggesting their potential for use in inoculant production after field testing. There was a tendency for both low and high N₂-fixing isolates to group together in the dendrogram from ERIC-PCR profiles, which suggests that RSE can differ significantly among closely related microsymbionts.

Keywords: genetic diversity, relative symbiotic effectiveness, inoculant, N₂-fixing

Procedia PDF Downloads 183

Authors: Heba M. Saad Eldien, Ola Abdel-Tawab Hussein, Ahmed Yassein Nassar

Abstract:

Background: Indomethacin is a non-steroidal anti inflammatory drug. Indomethacin induces an injury to gastrointestinal mucosa in experimental animals and humans and their use is associated with a significant risk of hemorrhage, erosions and perforation of both gastric and intestinal ulcers. The anti-inflammatory action of copper complexes is an important activity of their anti-ulcer effect achieved by their intermediary role as a transport form of copper that allow activation of the several copper-dependent enzymes. Therefore, several copper complexes were synthesized and investigated as promising alternative anti-ulcer therapy. Aim of the work: The purpose of this study was to evaluate a copper chelating complex consisting of egg albumin and copper as one of the copper peptides that can be used as anti-inflammatory agent and effective in ameliorates the hazards of the indomethacin on the histological structure of the fundus of the stomach that could be added to raise the efficacy of the currently used simple and cheap gastric anti-inflammatory drug mucogel. Material &methods: This study was carried out on 40 adult male albino rats,divided equally into 4 groups;Group I(control group) received distilled water,Group II(indomethacin treated group) received (25 mg/kg body weight, oral intubation) once, Group III (mucogel treated group)2 mL/rat once daily, oral incubation, Group IV(copper complex group) 1 mL /rat of 30 gm of copper albumin complex was mixed uniformly with mucogel to 100 mL. Treatment has been started six hour after Induction of Ulcers and continued till the 3rd day. The animals sacrificed and was processed for light, transmission electron microscopy(TEM) and immunostaining for inducible nitric oxide synthase(iNOS). Results: Fundic mucosa of group II, showed exfoliation of epithelial cells lining the gland, discontinuity of surface epithelial cells (ulcer formation), vacuolation and detachment of cells, eosinophilic infiltration and congestion of blood vessels in the lamina propria and submucosa. There was thickening and disarrangement of mucosa, weak positive reaction for PAS and marked increase in the collagen fibers lamina propria and the submucosa of the fundus. TEM revealed degeneration of cheif and parietal cells.Marked increase positive reactive of iNOS in all cells of the fundic gland. Group III showed reconstruction of gastric gland with cystic dilatation and vacuolation, moderate decrease of collagen fibers, reduced the intensity of iNOS while in Group IV healthy mucosa with normal surface lining epithelium and fundic glands, strong positive reaction for PAS, marked decrease of collagen fibers and positive reaction for iNOS. TEM revealed regeneration of cheif and parietal cells. Conclusion: Co treatment of copper-albumin complex seems to be useful for gastric ulcer treatment and ameliorates most of hazards of indomethacin.

Keywords: copper complex, gastric ulcer, indomethacin, rat

Procedia PDF Downloads 311

Authors: G. Cunningham, E. Cantor, X. Wu, F. Shen, G. Jiang, S. Philips, C. Bales, Y. Xiao, T. R. Cummins, J. C. Fehrenbacher, B. P. Schneider

Abstract:

Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons. Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell Technologiesᵀᴹ); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition, and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin, and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin, and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported the functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient-derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN.

Keywords: chemotherapy, iPSC-derived neurons, peripheral neuropathy, taxane, paclitaxel

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Authors: Farideh Tabatabaee Yazdi, Fereshteh Falah, Alireza Vasiee

Abstract:

Introduction: Gamma-aminobutyric acid (GABA) is a non-protein amino acid that is widely present in organisms. GABA is a kind of pharmacological and biological component and its application is wide and useful. Several important physiological functions of GABA have been characterized, such as neurotransmission and induction of hypotension. GABA is also a strong secretagogue of insulin from the pancreas and effectively inhibits small airway-derived lung adenocarcinoma and tranquilizer. Many microorganisms can produce GABA, and lactic acid bacteria have been a focus of research in recent years because lactic acid bacteria possess special physiological activities and are generally regarded as safe. Among them, the Lb. Brevis produced the highest amount of GABA. The major factors affecting GABA production have been characterized, including carbon sources and glutamate concentration. The use of food industry waste to produce valuable products such as amino acids seems to be a good way to reduce production costs and prevent the waste of food resources. In a dairy factory, a high volume of sludge is produced from a separator that contains useful compounds such as growth factors, carbon, nitrogen, and organic matter that can be used by different microorganisms such as Lb.brevis as carbon and nitrogen sources. Therefore, it is a good source of GABA production. GABA is primarily formed by the irreversible α-decarboxylation reaction of L-glutamic acid or its salts, catalysed by the GAD enzyme. In the present study, this aim was achieved for the fast-growing of Lb.brevis and producing GABA, using the dairy industry sludge as a suitable growth medium. Lactobacillus Brevis strains obtained from Microbial Type Culture Collection (MTCC) were used as model strains. In order to prepare dairy sludge as a medium, sterilization should be done at 121 ° C for 15 minutes. Lb. Brevis was inoculated to the sludge media at pH=6 and incubated for 120 hours at 30 ° C. After fermentation, the supernatant solution is centrifuged and then, the GABA produced was analyzed by the Thin Layer chromatography (TLC) method qualitatively and by the high-performance liquid chromatography (HPLC) method quantitatively. By increasing the percentage of dairy sludge in the culture medium, the amount of GABA increased. Also, evaluated the growth of bacteria in this medium showed the positive effect of dairy sludge on the growth of Lb.brevis, which resulted in the production of more GABA. GABA-producing LAB offers the opportunity of developing naturally fermented health-oriented products. Although some GABA-producing LAB has been isolated to find strains suitable for different fermentations, further screening of various GABA-producing strains from LAB, especially high-yielding strains, is necessary. The production of lactic acid, bacterial gamma-aminobutyric acid, is safe and eco-friendly. The use of dairy industry waste causes enhanced environmental safety. Also provides the possibility of producing valuable compounds such as GABA. In general, dairy sludge is a suitable medium for the growth of Lactic Acid Bacteria and produce this amino acid that can reduce the final cost of it by providing carbon and nitrogen source.

Keywords: GABA, Lactobacillus, HPLC, dairy sludge

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Authors: Pamela Chia, Tay Yoong Chuan

Abstract:

Introduction: Severe pulmonary hypertension (PH) patients requiring non-cardiac surgery risk have increased mortality rates ranging. These patients are plagued with cardiorespiratory failure, dysrhythmias and anticoagulation potentially with concurrent sepsis and renal insufficiency, perioperative morbidity. We present a deaf-mute patient with severe idiopathic PH emergently prepared for ruptured ectopic laparotomy. Case Report: A 20 year-old female, 62kg (BMI 25 kg/m2) with severe idiopathic PH (2DE Ejection Fraction was 41%, Pulmonary Artery Systolic Pressure (PASP) 105 mmHg, Right ventricle strain and hypertrophy) and selective mutism was rushed in for emergency laparotomy after presenting to the emergency department for abdominal pain. The patient had an NYHA Class II with room air SpO2 93-95%. While awaiting lung transplant, the patient takes warfarin, Sildanefil, Macitentan and even Selexipag for rising PASP. At presentation, vital signs: BP 95/63, HR 119 SpO2 88% (room air). Despite decreasing haemoglobin 14 to 10g/dL, INR 2.59 was reversed with prothrombin concentrate, and Vitamin K. ECG revealed Right Bundle Branch Block with right ventricular strain and x-ray showed cardiomegaly, dilated Right Ventricle, Pulmonary Arteries, basal atelectasis. Arterial blood gas showed compensated metabolic acidosis pH 7.4 pCO2 32 pO2 53 HCO3 20 BE -4 SaO2 88%. The cardiothoracic surgeon concluded no role for Extracorporeal Membrane Oxygenation (ECMO). We inserted invasive arterial and central venous lines with blood transfusion via an 18G cannula before the patient underwent a midline laparotomy, haemostasis of ruptured ovarian cyst with 2.4L of clots under general anesthesia and FloTrac cardiac output monitoring. Rapid sequence induction was done with Midazolam/Propofol, remifentanil infusion, and rocuronium. The patient was maintained on Desflurane. Blood products and colloids were transfused for further 1.5L blood loss. Postoperatively, the patient was transferred to the intensive care unit and was extubated uneventfully 7hours later. The patient went home a week later. Discussion: Emergency hemostasis laparotomy in anticoagulated WHO Class I PH patient awaiting lung transplant with no ECMO backup poses tremendous stress on the deaf-mute patient and the anesthesiologist. Balancing hemodynamics avoiding hypotension while awaiting hemostasis in the presence of pulmonary arterial dilators and anticoagulation requires close titration of volatiles, which decreases RV contractility. We review the contraindicated anesthetic agents (ketamine, N2O), choice of vasopressors in hypotension to maintain Aortic-right ventricular pressure gradients and nitric oxide use perioperatively. Conclusion: Interdisciplinary communication with a deaf-mute moribund patient and anesthesia considerations pose many rare challenges worth sharing.

Keywords: pulmonary hypertension, case report, warfarin reversal, emergency surgery

Procedia PDF Downloads 181

Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche

Abstract:

It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.

Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells

Procedia PDF Downloads 97

Authors: Soumia Hammadi, Imane Nouacer, Lamine Hamida, Younes A. Hammadi, Rachid Chaibi

Abstract:

Aims and objective: In the present work, we investigate the impact of both acute and chronic diabetes mellitus induced by streptozotocin (STZ) on the hypothalamus of the small gerbil (Gerbillus gerbillus). In this purpose, we aimed to study the histologic structure of the gerbil’s hypothalamic supraoptic (NSO) and paraventricular nucleus (NPV) at two distinct time points: two days and 30 days after diabetes onset. Methods: We conducted our investigation using 19 adult male gerbils weighing 25 to 28 g, divided into three groups as follow: Group I: Control gerbils (n=6) received an intraperitoneal injection of citrate buffer. Group II: STZ-diabetic gerbils (n=8) received a single intraperitoneal injection of STZ at a dose of 165 mg/kg of body weight. Diabetes onset (D0) is considered with the first hyperglycemia level exceeding 2,5 g/L. This group was further divided into two subgroups: Group II-1: Experimental Gerbils, at acute state of diabetes (n=8) sacrificed after 02 days of diabetes onset, Group II-2: Experimental Gerbils at chronic state of diabetes (n=7) sacrificed after 30 days of diabetes onset. Two and 30 days after diabetes onset, gerbils had blood drawn from the retro-orbital sinus into EDTA tubes. After centrifugation at -4°C, plasma was frozen at -80°C for later measurement of Cortisol, ACTH, and insulin. Afterward, animals were decapitated; their brain was removed, weighed, fixed in aqueous bouin, and processed and stained with Toluidine Bleu stain for histo-stereological analysis. A comparison was done with control gerbils treated with citrate buffer. Results: Compared to control gerbils, at 02 Days post diabetes onset, the neuronal somata of the paraventricular (NPV) and supraoptic nuclei (NSO) expressed numerous vacuoles of various sizes, we distinct also a neuronal juxtaposition and several unidentifiable vacuolated profiles were also seen in the neuropile. At the same time, we revealed the presence of à shrunken and condensed nuclei, which seem to touch the parvocellular neurons ( NPV); this leads us to suggest the presence of an apoptotic process in the early stage of diabetes. At 30 days of diabetes mellitus, the NPV manifests a few neurons with a distant appearance, in addition the magnocellular neurons in both NPV and NSO were hypertrophied with a rich euchromatin nucleus, a well-defined nucleolus, and a granular cytoplasm. Despite the neuronal degeneration at this stage, unexpectedly, ACTH registers a continuous significant high level compared to the early stage of diabetes mellitus and to control gerbils. Conclusion: The results suggest that the induction of diabetes mellitus using STZ in the small gerbils lead to alterations in the structure and morphology of the hypothalamus and hyper-secretion of ACTH and cortisol, possibly indicating hyperactivity of the hypothalamo-pituitary adrenal axis (HPA) during both the early and later stages of the disease. The subsequent quantitative evaluation of CRH, immunehistochemical evaluation of apoptosis, and oxidative stress assessment could corroborate our results.

Keywords: diabetes type 1., streptozotocin., small gerbil., hypothalamus., paraventricular nucleus., supraoptic nucleus.

Procedia PDF Downloads 36

Authors: G. Kontochristopoulos, T. Spiliopoulos, V. Markantoni, E. Platsidaki, A. Kouris, E. Balamoti, C. Bokotas, G. Haidemenos

Abstract:

Introduction: There is a high patient demand for periorbital rejuvenation since the facial area is often the first to show visible signs of aging. With advancing age, there are sometimes marked changes that occur in the skin, fat, muscle and bone of the periorbital region, resulting to wrinkles and skin laxity. These changes are among the easiest areas to correct using several minimally invasive techniques, which have become increasingly popular over the last decade. Lasers, radiofrequency, botulinum toxin, fat grafting and fillers are available treatments sometimes in combination to traditional blepharoplasty. This study attempts to show the benefits of a minimally invasive approach to periorbital wrinkles and skin laxity that combine microneedling and 10% trichloroacetic acid (TCA) peels. Method: Eleven female patients aged 34-72 enrolled in the study. They all gave informed consent after receiving detailed information regarding the treatment procedure. Exclusion criteria in the study were previous treatment for the same condition in the past six months, pregnancy, allergy or hypersensitivity to the components, infection, inflammation and photosensitivity on the affected region. All patients had diffuse periorbital wrinkles and mild to moderate upper or lower eyelid skin laxity. They were treated with Automatic Microneedle Therapy System-Handhold and topical application of 10% trichloroacetic acid solution to each periorbital area for five minutes. Needling at a 0,25 mm depth was performed in both latelar (x-y) directions. Subsequently, the peeling agent was applied to each periorbital area for five minutes. Patients were subjected to the above combination every two weeks for a series of four treatments. Subsequently they were followed up regularly every month for two months. The effect was photo-documented. A Physician's and a Patient's Global Assessment Scale was used to evaluate the efficacy of the treatment (0-25% indicated poor response, 25%-50% fair, 50%-75% good and 75%-100% excellent response). Safety was assessed by monitoring early and delayed adverse events. Results: At the end of the study, almost all patients demonstrated significant aesthetic improvement. Physicians assessed a fair and a good improvement in 9(81.8% of patients) and 2(18.1% of patients) participants respectively. Patients Global Assessment rated a fair and a good response in 6 (54.5%) and 5 (45.4%) participants respectively. The procedure was well tolerated and all patients were satisfied. Mild discomfort and transient erythema were quite common during or immediately after the procedure, however only temporary. During the monthly follow up, no complications or scars were observed. Conclusions: Microneedling is known as a simple, office–based collagen induction therapy. Low concentration TCA solution applied to the epidermis that has been more permeable by microneedling, can reach the dermis more effectively. In the present study, chemical peels with 10% TCA acted as an adjuvant to microneedling, as it causes controlled skin damage, promoting regeneration and rejuvenation of tissues. This combined therapy improved periorbital fine lines, wrinkles, and overall appearance of the skin. Thus it constitutes an alternative treatment of periorbital skin aging, with encouraging results and minor side-effects.

Keywords: chemical peels, microneedling, periorbital wrinkles, skin laxity

Procedia PDF Downloads 324

Authors: Alireza Shams, Ali Zamanian, Atefehe Shamosi, Farnaz Ghorbani

Abstract:

Introduction: Although the application of a new strategy remains a remarkable challenge for treatment of disabilities due to neuronal defects, progress in Nanomedicine and tissue engineering, suggesting the new medical methods. One of the promising strategies for reconstruction and regeneration of nervous tissue is replacing of lost or damaged cells by specific scaffolds after Compressive, ischemic and traumatic injuries of central nervous system. Furthermore, ultrastructure, composition, and arrangement of tissue scaffolds are effective on cell grafts. We followed implantation and differentiation of mesenchyme stem cells to neural cells on Gelatin Polylactic-co-glycolic acid (PLGA) scaffolds coated with iron nanoparticles. The aim of this study was to evaluate the capability of stem cells to differentiate into motor neuron-like cells under topographical cues and morphogenic factors. Methods and Materials: Bone marrow mesenchymal stem cells (BMMSCs) was obtained by primary cell culturing of adult rat bone marrow got from femur bone by flushing method. BMMSCs were incubated with DMEM/F12 (Gibco), 15% FBS and 100 U/ml pen/strep as media. Then, BMMSCs seeded on Gel/PLGA scaffolds and tissue culture (TCP) polystyrene embedded and incorporated by Fe Nano particles (FeNPs) (Fe3o4 oxide (M w= 270.30 gr/mol.). For neuronal differentiation, 2×10 5 BMMSCs were seeded on Gel/PLGA/FeNPs scaffolds was cultured for 7 days and 0.5 µ mol. Retinoic acid, 100 µ mol. Ascorbic acid,10 ng/ml. Basic fibroblast growth factor (Sigma, USA), 250 μM Iso butyl methyl xanthine, 100 μM 2-mercaptoethanol, and 0.2 % B27 (Invitrogen, USA) added to media. Proliferation of BMMSCs was assessed by using MTT assay for cell survival. The morphology of BMMSCs and scaffolds was investigated by scanning electron microscopy analysis. Expression of neuron-specific markers was studied by immunohistochemistry method. Data were analyzed by analysis of variance, and statistical significance was determined by Turkey’s test. Results: Our results revealed that differentiation and survival of BMMSCs into motor neuron-like cells on Gel/PLGA/FeNPs as a biocompatible and biodegradable scaffolds were better than those cultured in Gel/PLGA in absence of FeNPs and TCP scaffolds. FeNPs had raised physical power but decreased capacity absorption of scaffolds. Well defined oriented pores in scaffolds due to FeNPs may activate differentiation and synchronized cells as a mechanoreceptor. Induction effects of magnetic FeNPs by One way flow of channels in scaffolds help to lead the cells and can facilitate direction of their growth processes. Discussion: Progression of biological properties of BMMSCs and the effects of FeNPs spreading under magnetic field was evaluated in this investigation. In vitro study showed that the Gel/PLGA/FeNPs scaffold provided a suitable structure for motor neuron-like cells differentiation. This could be a promising candidate for enhancing repair and regeneration in neural defects. Dynamic and static magnetic field for inducing and construction of cells can provide better results for further experimental studies.

Keywords: differentiation, mesenchymal stem cells, nano particles, neuronal defects, Scaffolds

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Authors: Fernanda Piculo, Giovana Vesentini, Gabriela Marini, Debora Cristina Damasceno, Angelica Mercia Pascon Barbosa, Marilza Vieira Cunha Rudge

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Introduction: Women with previous gestational diabetes mellitus (GDM) were significantly more likely to have urinary incontinence (UI) and pelvic floor muscle dysfunction compared to non-diabetic women two years after a cesarean section. Additional results demonstrated that induced diabetes causes detrimental effects on pregnant rat urethral muscle. These results indicate the need for exploration of the mechanistic role of a recovery factor in female UI. Chemokine ligand 7 (CCL7) was significantly over expressed in rat serum, urethral and vaginal tissues immediately following induction of stress UI in a rat model simulating birth trauma. CCL7 over expression has shown potency for stimulating targeted stem cell migration and provide a translational link (clinical measurement) which further provide opportunities for treatment. The aim of this study was to investigate the CCL7 levels profile in diabetic pregnant women with urinary incontinence during pregnancy over the first year postpartum. Methods: This study was conducted in the Perinatal Diabetes Research Center of the Botucatu Medical School/UNESP, and was approved by the Research Ethics Committee of the Institution (CAAE: 20639813.0.0000.5411). The diagnosis of GDM was established between 24th and 28th gestational weeks, by the 75 g-OGTT test according to ADA’s criteria. Urinary incontinence was defined according to the International Continence Society and the CCL7 levels was measured by ELISA (R&D Systems, Catalog Number DCC700). Two hundred twelve women were classified into four study groups: normoglycemic continent (NC), normoglycemic incontinent (NI), diabetic continent (DC) and diabetic incontinent (DI). They were evaluated at six-time-points: 12-18, 24-28 and 34-38 gestational weeks, 24-48 hours, 6 weeks and 6-12 months postpartum. Results: At 12-18 weeks, it was possible to consider only two groups, continent and incontinent, because at this early gestational period has not yet been the diagnosis of GDM. The group with GDM and UI (DI group) showed lower levels of CCL7 in all time points during pregnancy and postpartum, compared to normoglycemic groups (NC and NI), indicating that these women have not recovered from child birth induced UI during the 6-12 months postpartum compared to their controls, and that the progression of UI and/or lack of recovery throughout the first postpartum year can be related with lower levels of CCL7. Instead, serum CCL7 was significantly increased in the NC group. Taken together, these findings of overexpression of CCL7 in the NC group and decreased levels in the DI group, could confirm that diabetes delays the recovery from child birth induced UI, and that CCL7 could potentially be used as a serum marker of injury. Conclusion: This study demonstrates lower levels of CCL7 in the DI group during pregnancy and postpartum and suggests that the progression of UI in diabetic women and/or lack of recovery throughout the first postpartum year can be related with low levels of CCL7. This provides a translational potential where CCL7 measurement could be used as a surrogate for injury after delivery. Successful controlled CCL7 mediated stem cell homing to the lower urinary tract could one day introduce the potential for non-operative treatment or prevention of stress urinary incontinence.

Keywords: CCL7, gestational diabetes, pregnancy, urinary incontinence

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Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche

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Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.

Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle

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Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali

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A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.

Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles

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Authors: Chang-Hui Shen, Michelle Esposito, Andrew J. Shen, Michael Adejokun, Diana Laterman

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The packaging of DNA into nucleosomes is critical to genomic compaction, yet it can leave gene promoters inaccessible to activator proteins or transcription machinery and thus prevents transcriptional initiation. Both chromatin remodelers and histone acetylases (HATs) are the two main transcription co-activators that can reconfigure chromatin structure for transcriptional activation. Ino80p is the core component of the INO80 remodeling complex. Recently, it was shown that Ino80p dissociates from the yeast INO1 promoter after induction. However, when certain HATs were deleted or mutated, Ino80p accumulated at the promoters during gene activation. This suggests a link between HATs’ presence and Ino80p’s dissociation. However, it has yet to be demonstrated that Ino80p can be acetylated. To determine if Ino80p can be acetylated, wild-type Saccharomyces cerevisiae cells carrying Ino80p engineered with a double FLAG tag (MATa INO80-FLAG his3∆200 leu2∆0 met15∆0 trp1∆63 ura3∆0) were grown to mid log phase, as were non-tagged wild type (WT) (MATa his3∆200 leu2∆0 met15∆0 trp1∆63 ura3∆0) and ino80∆ (MATa ino80∆::TRP1 his3∆200 leu2∆0 met15∆0 trp1∆63 ura3∆0) cells as controls. Cells were harvested, and the cell lysates were subjected to immunoprecipitation (IP) with α-FLAG resin to isolate Ino80p. These eluted IP samples were subjected to SDS-PAGE and Western blot analysis. Subsequently, the blots were probed with the α-FLAG and α-acetyl lysine antibodies, respectively. For the blot probed with α-FLAG, one prominent band was shown in the INO80-FLAG cells, but no band was detected in the IP samples from the WT and ino80∆ cells. For the blot probed with the α-acetyl lysine antibody, we detected acetylated Ino80p in the INO80-FLAG strain while no bands were observed in the control strains. As such, our results showed that Ino80p can be acetylated. This acetylation can explain the co-activator’s recruitment patterns observed in current gene activation models. In yeast INO1, it has been shown that Ino80p is recruited to the promoter during repression, and then dissociates from the promoter once de-repression begins. Histone acetylases, on the other hand, have the opposite pattern of recruitment, as they have an increased presence at the promoter as INO1 de-repression commences. This Ino80p recruitment pattern significantly changes when HAT mutant strains are studied. It was observed that instead of dissociating, Ino80p accumulates at the promoter in the absence of functional HATs, such as Gcn5p or Esa1p, under de-repressing processes. As such, Ino80p acetylation may be required for its proper dissociation from the promoters. The remodelers’ dissociation mechanism may also have a wide range of implications with respect to transcriptional initiation, elongation, or even repression as it allows for increased spatial access to the promoter for the various transcription factors and regulators that need to bind in that region. Our findings here suggest a previously uncharacterized interaction between Ino80p and other co-activators recruited to promoters. As such, further analysis of Ino80p acetylation not only will provide insight into the role of epigenetic modifications in transcriptional activation, but also gives insight into the interactions occurring between co-activators at gene promoters during gene regulation.

Keywords: acetylation, chromatin remodeler, epigenetic modification, Ino80p

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Authors: Natalia Hordynska, Magdalena Szechynska-Hebda, Miroslaw Sobczak, Elzbieta Rozanska, Joanna Troczynska, Zofia Banaszak, Maria Wedzony

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Albinism is a common problem encountered in wheat and triticale breeding programs, which require in vitro culture steps e.g. generation of doubled haploids via androgenesis process. Genetic factor is a major determinant of albinism, however, environmental conditions such as temperature and media composition influence the frequency of albino plant formation. Cold incubation of wheat and triticale spikes induced a switch from gametophytic to sporophytic development. Further, androgenic structures formed from anthers of the genotypes susceptible to androgenesis or treated with cold stress, had a pool of structurally primitive plastids, with small starch granules or swollen thylakoids. High temperature was a factor inducing andro-genesis of wheat and triticale, but at the same time, it was a factor favoring the formation of albino plants. In genotypes susceptible to albinism or after heat stress conditions, cells formed from anthers were vacuolated, and plastids were eliminated. Partial or complete loss of chlorophyll pigments and incomplete differentiation of chloroplast membranes result in formation of tissues or whole plant unable to perform photosynthesis. Indeed, susceptibility to the andro-genesis process was associated with an increase of total concentration of photosynthetic pigments in anthers, spikes and regenerated plants. The proper balance of the synthesis of various pigments, was the starting point for their proper incorporation into photosynthetic membranes. In contrast, genotypes resistant to the androgenesis process and those treated with heat, contained 100 times lower content of photosynthetic pigments. In particular, the synthesis of violaxanthin, zeaxanthin, lutein and chlorophyll b was limited. Furthermore, deregulation of starch and lipids synthesis, which led to the formation of very complex starch granules and an increased number of oleosomes, respectively, correlated with the reduction of the efficiency of androgenesis. The content of other sugars varied depending on the genotype and the type of stress. The highest content of various sugars was found for genotypes susceptible to andro-genesis, and highly reduced for genotypes resistant to androgenesis. The most important sugars seem to be glucose and fructose. They are involved in sugar sensing and signaling pathways, which affect the expression of various genes and regulate plant development. Sucrose, on the other hand, seems to have minor effect at each stage of the androgenesis. The sugar metabolism was related to metabolic activity of microspores. The genotypes susceptible to androgenesis process had much faster mitochondrium- and chloroplast-dependent energy conversion and higher heat production by tissues. Thus, the effectiveness of metabolic processes, their balance and the flexibility under the stress was a factor determining the direction of microspore development, and in the later stages of the androgenesis process, a factor supporting the induction of androgenic structures, chloroplast formation and the regeneration of green plants. The work was financed by Ministry of Agriculture and Rural Development within Program: ‘Biological Progress in Plant Production’, project no HOR.hn.802.15.2018.

Keywords: androgenesis, chloroplast, metabolism, temperature stress

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Authors: Jawaad Saleem, Hannah Wright, Peter Sommerville, Adrian Hopper

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Introduction: Inpatient falls are the most commonly reported patient safety incidents, and carry a significant burden on resources, morbidity, and mortality. Ensuring adequate post falls management of patients by staff is therefore paramount to maintaining patient safety especially in out of hours and resource stretched settings. Aims: This quality improvement project aims to improve the current practice of falls management at Guys St Thomas Hospital, London as compared to our 2016 Quality Improvement Project findings. Furthermore, it looks to increase current junior doctors confidence in managing falls and their use of new guidance protocols. Methods: Multifaceted Interventions implemented included: the development of new trust wide guidelines detailing management pathways for patients post falls, available for intranet access. Furthermore, the production of 2000 lanyard cards distributed amongst junior doctors and staff which summarised these guidelines. Additionally, a ‘safety signal’ email was sent from the Trust chief medical officer to all staff raising awareness of falls and the guidelines. Formal falls teaching was also implemented for new doctors at induction. Using an established incident database, 189 consecutive falls in 2017were retrospectively analysed electronically to assess and compared to the variables measured in 2016 post interventions. A separate serious incident database was used to analyse 50 falls from May 2015 to March 2018 to ascertain the statistical significance of the impact of our interventions on serious incidents. A similar questionnaire for the 2017 cohort of foundation year one (FY1) doctors was performed and compared to 2016 results. Results: Questionnaire data demonstrated improved awareness and utility of guidelines and increased confidence as well as an increase in training. 97% of FY1 trainees felt that the interventions had increased their awareness of the impact of falls on patients in the trust. Data from the incident database demonstrated the time to review patients post fall had decreased from an average of 130 to 86 minutes. Improvement was also demonstrated in the reduced time to order and schedule X-ray and CT imaging, 3 and 5 hours respectively. Data from the serious incident database show that ‘the time from fall until harm was detected’ was statistically significantly lower (P = 0.044) post intervention. We also showed the incidence of significant delays in detecting harm ( > 10 hours) reduced post intervention. Conclusions: Our interventions have helped to significantly reduce the average time to assess, order and schedule appropriate imaging post falls. Delays of over ten hours to detect serious injuries after falls were commonplace; since the intervention, their frequency has markedly reduced. We suggest this will lead to identifying patient harm sooner, reduced clinical incidents relating to falls and thus improve overall patient safety. Our interventions have also helped increase clinical staff confidence, management, and awareness of falls in the trust. Next steps include expanding teaching sessions, improving multidisciplinary team involvement to aid this improvement.

Keywords: patient safety, quality improvement, serious incidents, falls, clinical care

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Authors: N. Reza Pour, S. Chuah, T. Vo

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Background: Vertebral artery dissection (VAD) is a rare complication of pregnancy. It can occur spontaneously or following a traumatic event. The pathogenesis is unclear. Predisposing factors include chronic hypertension, Marfan’s syndrome, fibromuscular dysplasia, vasculitis and cystic medial necrosis. Physiological changes of pregnancy have also been proposed as potential mechanisms of injury to the vessel wall. The clinical presentation varies and it can present as a headache, neck pain, diplopia, transient ischaemic attack, or an ischemic stroke. Isolated cases of VAD in pregnancy and puerperium have been reported in the literature. One case was found to have posterior circulation stroke as a result of bilateral VAD and labour was induced at 37 weeks gestation for preeclampsia. Another patient at 38 weeks with severe neck pain that persisted after induction for elevated blood pressure and arteriography showed right VAD postpartum. A single case of lethal VAD in pregnancy with subsequent massive subarachnoid haemorrhage has been reported which was confirmed by the autopsy. Case Presentation: We report two cases of vertebral artery dissection in pregnancy. The first patient was a 32-year-old primigravida presented at the 38th week of pregnancy with the onset of early labour and blood pressure (BP) of 130/70 on arrival. After 2 hours, the patient developed a severe headache with blurry vision and BP was 238/120. Despite treatment with an intravenous antihypertensive, she had eclamptic fit. Magnesium solfate was started and Emergency Caesarean Section was performed under the general anaesthesia. On the second day after the operation, she developed left-sided neck pain. Magnetic Resonance Imaging (MRI) angiography confirmed a short segment left vertebral artery dissection at the level of C3. The patient was treated with aspirin and remained stable without any neurological deficit. The second patient was a 33-year-old primigavida who was admitted to the hospital at 36 weeks gestation with BP of 155/105, constant headache and visual disturbances. She was medicated with an oral antihypertensive agent. On day 4, she complained of right-sided neck pain. MRI angiogram revealed a short segment dissection of the right vertebral artery at the C2-3 level. Pregnancy was terminated on the same day with emergency Caesarean Section and anticoagulation was started subsequently. Post-operative recovery was complicated by rectus sheath haematoma requiring evacuation. She was discharged home on Aspirin without any neurological sequelae. Conclusion: Because of collateral circulation, unilateral vertebral artery dissections may go unrecognized and may be more common than suspected. The outcome for most patients is benign, reflecting the adequacy of the collateral circulation in young patients. Spontaneous VAD is usually treated with anticoagulation or antiplatelet therapy for a minimum of 3-6 months to prevent future ischaemic events, allowing the dissection to heal on its own. We had two cases of VAD in the context of hypertensive disorders of pregnancy with an acceptable outcome. A high level of vigilance is required particularly with preeclamptic patients presenting with head/neck pain to allow an early diagnosis. This is as we hypothesize, early and aggressive management of vertebral artery dissection may potentially prevent further complications.

Keywords: eclampsia, preeclampsia, pregnancy, Vertebral Artery Dissection

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