Search results for: brain activation

Authors: M. Skibinska, A. Rajewska-Rager, M. Dmitrzak-Weglarz, N. Lepczynska, P. Sibilski, P. Kapelski, J. Pawlak, J. Twarowska-Hauser

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Introduction: Neurotrophic factors have been implicated in neuropsychiatric disorders. Brain-Derived Neurotrophic Factor (BDNF) influences neuron differentiation in development as well as synaptic plasticity and neuron survival in adulthood. BDNF is widely studied in mood disorders and has been proposed as a biomarker for depression. BDNF is synthesized as precursor protein – proBDNF. Both forms are biologically active and exert opposite effects on neurons. Aim: The aim of the study was to examine the serum levels of BDNF and proBDNF in unipolar and bipolar young patients below 24 years old during hypo/manic, depressive episodes and in remission compared to healthy control group. Methods: In a prospective 2 years follow-up study, we investigated alterations in levels of BDNF and proBDNF in 79 patients (23 males, mean age 19.08, SD 3.3 and 56 females, mean age 18.39, SD 3.28) diagnosed with mood disorders: unipolar and bipolar disorder compared with 35 healthy control subjects (7 males, mean age 20.43, SD 4.23 and 28 females, mean age 21.25, SD 2.11). Clinical characteristics including mood, comorbidity, family history, and treatment, were evaluated during control visits and clinical symptoms were rated using the Hamilton Depression Rating Scale and Young Mania Rating Scale. Serum BDNF and proBDNF concentrations were determined by Enzyme-Linked Immunosorbent Assays (ELISA) method. Serum BDNF and proBDNF levels were analysed with covariates: sex, age, age > 18 and < 18 years old, family history of affective disorders, drug-free vs. medicated status. Normality of the data was tested using Shapiro-Wilk test. Levene’s test was used to calculate homogeneity of variance. Non-parametric Tests: Mann-Whitney U test, Kruskal-Wallis ANOVA, Friedman’s ANOVA, Wilcoxon signed rank test, Spearman correlation coefficient were applied in analyses The statistical significance level was set at p < 0.05. Results: BDNF and proBDNF serum levels did not differ between patients at baseline and controls as well as comparing patients in acute episode of depression/hypo/mania at baseline and euthymia (at month 3 or 6). Comparing BDNF and proBDNF levels between patients in euthymia and control group no differences have been found. Increased BDNF level in women compared to men at baseline (p=0.01) have been observed. BDNF level at baseline was negatively correlated with depression and mania occurence at 24 month (p=0.04). BDNF level at 12 month was negatively correlated with depression and mania occurence at 12 month (p=0.01). Correlation of BDNF level with sex have been detected (p=0.01). proBDNF levels at month 3, 6 and 12 negatively correlated with disease status (p=0.02, p=0.008, p=0.009, respectively). No other correlations of BDNF and proBDNF levels with clinical and demographical variables have been detected. Discussion: Our results did not show any differences in BDNF and proBDNF levels between depression, mania, euthymia, and controls. Imbalance in BDNF/proBDNF signalling may be involved in pathogenesis of mood disorders. Further studies on larger groups are recommended. Grant was founded by National Science Center in Poland no 2011/03/D/NZ5/06146.

Keywords: bipolar disorder, Brain-Derived Neurotrophic Factor (BDNF), proBDNF, unipolar depression

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Authors: Majed Al Otaibi, Melissa Lessard-Beaudoin, Amel Loudghi, Raphael Chouinard-Watkins, Melanie Plourde, Frederic Calon, C. Alexandre Castellano, Stephen Cunnane, Helene Payette, Pierrette Gaudreau, Denis Gris, Rona K. Graham

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Introduction: Alzheimer disease (AD) is a chronic disorder that affects millions of individuals worldwide. Symptoms include memory dysfunction, and also alterations in attention, planning, language and overall cognitive function. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Studying the mechanisms underlying the olfactory dysfunction may therefore lead to the discovery of potential biomarkers and/or treatments for neurodegenerative diseases. Objectives: To determine if olfactory dysfunction predicts future cognitive impairment in the aging population and to characterize the olfactory system in a murine model expressing a genetic factor of AD. Method: For the human study, quantitative olfactory tests (UPSIT and OMT) have been done on 93 subjects (aged 80 to 94 years) from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge) cohort accepting to participate in the ORCA secondary study. The telephone Modified Mini Mental State examination (t-MMSE) was used to assess cognition levels, and an olfactory self-report was also collected. In a separate cohort, olfactory cortical volume was calculated using MRI results from healthy old adults (n=25) and patients with AD (n=18) using the AAL single-subject atlas and performed with the PNEURO tool (PMOD 3.7). For the murine study, we are using Western blotting, RT-PCR and immunohistochemistry. Result: Human Study: Based on the self-report, 81% of the participants claimed to not suffer from any problem with olfaction. However, based on the UPSIT, 94% of those subjects showed a poor olfactory performance and different forms of microsmia. Moreover, the results confirm that olfactory function declines with age. We also detected a significant decrease in olfactory cortical volume in AD individuals compared to controls. Murine study: Preliminary data demonstrate there is a significant decrease in expression levels of the proform of caspase-3 and the caspase substrate STK3, in the olfactory bulb of mice expressing human APOE4 compared with controls. In addition, there is a significant decrease in the expression level of the caspase-9 proform and caspase-8 active fragment. Analysis of the mature neuron marker, NeuN, shows decreased expression levels of both isoforms. The data also suggest that Iba-1 immunostaining is increased in the olfactory bulb of APOE4 mice compared to wild type mice. Conclusions: The activation of caspase-3 may be the cause of the decreased levels of STK3 through caspase cleavage and may play role in the inflammation observed. In the clinical study, our results suggest that seniors are unaware of their olfactory function status and therefore it is not sufficient to measure olfaction using the self-report in the elderly. Studying olfactory function and cognitive performance in the aging population will help to discover biomarkers in the early stage of the AD.

Keywords: Alzheimer's disease, APOE4, cognition, caspase, brain atrophy, neurodegenerative, olfactory dysfunction

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Authors: Khushboo Shah

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Categorical bans on the death penalty and life-without-parole sentences for juvenile offenders in a growing number of countries have established a new era in juvenile jurisprudence. This has been brought about by integration of the growing knowledge in cognitive neuroscience and appreciation of the inherent differences between adults and adolescents over the last ten years. This evolving understanding of being a child in the criminal system can be aptly reflected through policies that incorporate the mitigating traits of youth. First, the presentation will delineate the structures in cognitive neuroscience and in particular, focus on the prefrontal cortex, the amygdala, and the basal ganglia. These key anatomical structures in the brain are linked to three mitigating adolescent traits—an underdeveloped sense of responsibility, an increased vulnerability to negative influences, and transitory personality traits—that establish why juveniles have a lessened culpability. The discussion will delve into the details depicting how an underdeveloped prefrontal cortex results in the heightened emotional angst, high-energy and risky behavior characteristic of the adolescent time period or how the amygdala, the emotional center of the brain, governs different emotional expression resulting in why teens are susceptible to negative influences. Based on this greater understanding, it is incumbent that policies adequately reflect the adolescent physiology and psychology in the criminal system. However, it is important to ensure that these views are appropriately weighted while considering the jurisprudence for the treatment of children in the law. To ensure this balance is appropriately stricken, policies must incorporate the distinctive traits of youth in sentencing and legal considerations and yet refrain from the potential fallacies of absolving a juvenile offender of guilt and culpability. Accordingly, three policies will demonstrate how these results can be achieved: (1) eliminate housing of juvenile offenders in the adult prison system, (2) mandate fitness hearings for all transfers of juveniles to adult criminal court, and (3) use the post-disposition review as a type of rehabilitation method for juvenile offenders. Ultimately, this interdisciplinary approach of science and law allows for a better understanding of adolescent psychological and social functioning and can effectuate better legal outcomes for juveniles tried as adults.

Keywords: criminal law, Juvenile Justice, interdisciplinary, neuroscience

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Authors: M. Liebherr, P. Schubert, S. Kersten, C. Dietz, L. Franz, C. T. Haas

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With a long history, dual-task has become one of the most intriguing research fields regarding human brain functioning and cognition. However, findings considering effects of task-interrelations are limited (especially, in combined motor and cognitive tasks). Therefore, we aimed at developing a measurement system in order to analyse interrelation effects of cognitive and motor tasks. On the one hand, the present study demonstrates the applicability of the measurement system and on the other hand first results regarding a systematization of different task combinations are shown. Future investigations should combine imagine technologies and this developed measurement system.

Keywords: dual-task, interference, cognition, measurement

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Authors: H. Namazi, H. T. N. Kuan

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It is known that in humans, the adaptation to a given odor occurs within a quite short span of time (typically one minute) after the odor is presented to the brain. Different models of human olfaction have been developed by scientists but none of these models consider the diffusion phenomenon in olfaction. A novel microscopic model of the human olfaction is presented in this paper. We develop this model by incorporating the transient diffusivity. In fact, the mathematical model is written based on diffusion of the odorant within the mucus layer. By the use of the model developed in this paper, it becomes possible to provide quantification of the objective strength of odor.

Keywords: diffusion, microscopic model, mucus layer, olfaction

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Authors: Vasilij Djackov, Tomas Zapnickas, Evgenii Iamshchikov, Lukas Norkevicius, Rima Mickeviciene, Larisa Vasiljeva

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In this paper, the resistance and pitching values of the test of an electric ferry are presented. The research was carried out in the open flow channel of Klaipėda University with a multi-axis dynamometer. The received model resistance values were recalculated to the real vessel and the preliminary chosen propulsion unit power was compared. After analyzing the results of the pitching of the model, it was concluded that the shape of the hull needs to be further improved, taking into account the possible uneven weight distribution at the ends of the ferry. Further investigation of the hull of the electric ferry is recommended, including experiments with various water depths and activation of propulsion units.

Keywords: electrical ferry, model tests, open flow channel, pitching, resistance

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Authors: Zhen Qin, Yufei Peng, Jianbei Li, Jidong Long

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In order to study the activity of the coated aluminate barium-tungsten cathodes during activation, aging, poisoning and long-term use. Through a set of hot-cathode micro-area emission uniformity study device, we tested the micro-area emission performance of the cathode under different conditions. The change of activity of cathode micro-area was obtained. The influence of micro-area activity on the performance of the cathode was explained by the ageing model of barium-tungsten cathode. This helps to improve the design and process of the cathode and can point the way in finding the factors that affect life in the cathode operation.

Keywords: barium-tungsten cathode, ageing model, micro-area emission, emission uniformity

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Authors: G. S. Ryu, K. T. Koh, H. Y. Kim, G. H. An, D. W. Seo

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Geopolymer mortar is produced by alkaline activation of pozzolanic materials such as fly ground granulated blast-furnace slag (GGBFS) and fly ash (FA). Its unique reaction pathway facilitates rapid strength development in comparison with hydration of ordinary Portland cement (OPC). Geopolymer can be fabricated using various types and dosages of alkali-activator, which effectively gives a wider control over the performance of the final product. The present study investigates the effect of types of precursors and curing conditions on the fresh state and strength development characteristics of geopolymers, thereby comparatively exploring the effect of precursors from various sources of origin. The obtained result showed that the setting time and strength development of the specimens with the identical mix proportion but different precursors displayed significant variations.

Keywords: alkali-activated material, blast furnace slag, fly ash, flowability, strength development

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Authors: Jalil ur Rehman, Ramesh C, Tailor, Isa Khan, Jahanzeeb Ashraf, Muhammad Afzal, Geofferry S. Ibbott

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The purpose of this analysis is to estimate secondary cancer risks after VMAT compared to other modalities of head and neck radiotherapy (IMRT, 3DCRT). Computer tomography (CT) scans of Radiological Physics Center (RPC) head and neck phantom were acquired with CT scanner and exported via DICOM to the treatment planning system (TPS). Treatment planning was done using four arc (182-178 and 180-184, clockwise and anticlockwise) for volumetric modulated arc therapy (VMAT) , Nine fields (200, 240, 280, 320,0,40,80,120 and 160), which has been commonly used at MD Anderson Cancer Center Houston for intensity modulated radiation therapy (IMRT) and four fields for three dimensional radiation therapy (3DCRT) were used. True beam linear accelerator of 6MV photon energy was used for dose delivery, and dose calculation was done with CC convolution algorithm with prescription dose of 6.6 Gy. Primary Target Volume (PTV) coverage, mean and maximal doses, DVHs and volumes receiving more than 2 Gy and 3.8 Gy of OARs were calculated and compared. Absolute point dose and planar dose were measured with thermoluminescent dosimeters (TLDs) and GafChromic EBT2 film, respectively. Quality Assurance of VMAT and IMRT were performed by using ArcCHECK method with gamma index criteria of 3%/3mm dose difference to distance to agreement (DD/DTA). PTV coverage was found 90.80 %, 95.80 % and 95.82 % for 3DCRT, IMRT and VMAT respectively. VMAT delivered the lowest maximal doses to esophagus (2.3 Gy), brain (4.0 Gy) and thyroid (2.3 Gy) compared to all other studied techniques. In comparison, maximal doses for 3DCRT were found higher than VMAT for all studied OARs. Whereas, IMRT delivered maximal higher doses 26%, 5% and 26% for esophagus, normal brain and thyroid, respectively, compared to VMAT. It was noted that esophagus volume receiving more than 2 Gy was 3.6 % for VMAT, 23.6 % for IMRT and up to 100 % for 3DCRT. Good agreement was observed between measured doses and those calculated with TPS. The averages relative standard errors (RSE) of three deliveries within eight TLD capsule locations were, 0.9%, 0.8% and 0.6% for 3DCRT, IMRT and VMAT, respectively. The gamma analysis for all plans met the ±5%/3 mm criteria (over 90% passed) and results of QA were greater than 98%. The calculations for maximal doses and volumes of OARs suggest that the estimated risk of secondary cancer induction after VMAT is considerably lower than IMRT and 3DCRT.

Keywords: RPC, 3DCRT, IMRT, VMAT, EBT2 film, TLD

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Authors: Prateek Rastogi, Jenash Acharya

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Histopathology examination has been a boon to forensic experts all around the world since its implication in autopsy cases. Whenever a case of sudden death is encountered, forensic experts clandestinely focus on cardiovascular, respiratory, gastrointestinal or cranio-cerebral causes. After ruling out poisoning or trauma, they are left with the only option available, histopathology examination. Besides preserving thoracic and abdominal organs, brain tissues are very less frequently subjected for the analysis. Based on provisional diagnosis documented on hospital treatment record files, one hemisphere of grossly unremarkable cerebrum was confirmatively diagnosed by histopathology examination to be a case of cerebral toxoplasmosis.

Keywords: cerebral toxoplasmosis, sudden death, health information, histopathology

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Authors: N. Demertzis, J. L. Bowen

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Sepsis is a complex and rapidly evolving condition, resulting from uncontrolled prolonged activation of host immune system due to pathogenic insult. The aim of this study is the development of a multiplex electrochemical sensing platform, capable of detecting both pathogen associated and host immune markers to enable the rapid and definitive diagnosis of sepsis. A combination of aptamers and molecular imprinting approaches have been employed to generate sensing systems for lipopolysaccharide (LPS), c-reactive protein (CRP) and procalcitonin (PCT). Gold working electrodes were mechanically polished and electrochemically cleaned with 0.1 M sulphuric acid using cyclic voltammetry (CV). Following activation, a self-assembled monolayer (SAM) was generated, by incubating the electrodes with a thiolated anti-LPS aptamer / dithiodibutiric acid (DTBA) mixture (1:20). 3-aminophenylboronic acid (3-APBA) in combination with the anti-LPS aptamer was used for the development of the hybrid molecularly imprinted sensor (apta-MIP). Aptasensors, targeting PCT and CRP were also fabricated, following the same approach as in the case of LPS, with mercaptohexanol (MCH) replacing DTBA. In the case of the CRP aptasensor, the SAM was formed following incubation of a 1:1 aptamer: MCH mixture. However, in the case of PCT, the SAM was formed with the aptamer itself, with subsequent backfilling with 1 μM MCH. The binding performance of all systems has been evaluated using electrochemical impedance spectroscopy. The apta-MIP’s polymer thickness is controlled by varying the number of electropolymerisation cycles. In the ideal number of polymerisation cycles, the polymer must cover the electrode surface and create a binding pocket around LPS and its aptamer binding site. Less polymerisation cycles will create a hybrid system which resembles an aptasensor, while more cycles will be able to cover the complex and demonstrate a bulk polymer-like behaviour. Both aptasensor and apta-MIP were challenged with LPS and compared to conventional imprinted (absence of aptamer from the binding site, polymer formed in presence of LPS) and non-imprinted polymers (NIPS, absence of LPS whilst hybrid polymer is formed). A stable LPS aptasensor, capable of detecting down to 5 pg/ml of LPS was generated. The apparent Kd of the system was estimated at 17 pM, with a Bmax of approximately 50 pM. The aptasensor demonstrated high specificity to LPS. The apta-MIP demonstrated superior recognition properties with a limit of detection of 1 fg/ml and a Bmax of 100 pg/ml. The CRP and PCT aptasensors were both able to detect down to 5 pg/ml. Whilst full binding performance is currently being evaluated, there is none of the sensors demonstrate cross-reactivity towards LPS, CRP or PCT. In conclusion, stable aptasensors capable of detecting LPS, PCT and CRP at low concentrations have been generated. The realisation of a multiplex panel such as described herein, will effectively contribute to the rapid, personalised diagnosis of sepsis.

Keywords: aptamer, electrochemical impedance spectroscopy, molecularly imprinted polymers, sepsis

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Authors: Ana Bermudez de Castro Muela, Xiomara Santos Salas, Silvia Cayon Somacarrera

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The aim of this review is to explain what is the intracranial hypotension and its main causes, and also to approach to the diagnostic management in the different clinical situations, understanding radiological findings, and physiopathological substrate. An approach to the diagnostic management is presented: what are the guidelines to follow, the different tests available, and the typical findings. We review the myelo-CT and myelo-RM studies in patients with suspected CSF fistula or hypotension of unknown cause during the last 10 years in three centers. Signs of intracranial hypotension (subdural hygromas/hematomas, pachymeningeal enhancement, venous sinus engorgement, pituitary hyperemia, and lowering of the brain) that are evident in baseline CT and MRI are also sought. The intracranial hypotension is defined as a lower opening pressure of 6 cmH₂O. It is a relatively rare disorder with an annual incidence of 5 per 100.000, with a female to male ratio 2:1. The clinical features it’s an orthostatic headache, which is defined as development or aggravation of headache when patients move from a supine to an upright position and disappear or typically relieve after lay down. The etiology is a decrease in the amount of cerebrospinal fluid (CSF), usually by loss of it, either spontaneous or secondary (post-traumatic, post-surgical, systemic disease, post-lumbar puncture etc.) and rhinorrhea and/or otorrhea may exist. The pathophysiological mechanisms of hypotension and CSF hypertension are interrelated, as a situation of hypertension may lead to hypotension secondary to spontaneous CSF leakage. The diagnostic management of intracranial hypotension in our center includes, in the case of being spontaneous and without rhinorrhea and/or otorrhea and according to necessity, a range of available tests, which will be performed from less to more complex: cerebral CT, cerebral MRI and spine without contrast and CT/MRI with intrathecal contrast. If we are in a situation of intracranial hypotension with the presence of rhinorrhea/otorrhea, a sample can be obtained for the detection of b2-transferrin, which is found in the CSF physiologically, as well as sinus CT and cerebral MRI including constructive interference steady state (CISS) sequences. If necessary, cisternography studies are performed to locate the exact point of leakage. It is important to emphasize the significance of myelo-CT / MRI to establish the diagnosis and location of CSF leak, which is indispensable for therapeutic planning (whether surgical or not) in patients with more than one lesion or doubts in the baseline tests.

Keywords: cerebrospinal fluid, neuroradiology brain, magnetic resonance imaging, fistula

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Authors: Y. J. Song, Q. S. Xu, X. C. Wang, H. Wang, C. Q. Li

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The catalyst of copper oxide loaded on HZSM-5 was developed for nitrous oxide (N₂O) direct decomposition. The kinetic of nitrous oxide decomposition was studied for CuO/HZSM-5 catalyst prepared by incipient wetness impregnation method. The external and internal diffusion of catalytic reaction were considered in the investigation. Experiment results indicated that the external diffusion was basically eliminated when the reaction gas mixture gas hourly space velocity (GHSV) was higher than 9000h⁻¹ and the influence of the internal diffusion was negligible when the particle size of the catalyst CuO/HZSM-5 was small than 40-60 mesh. The experiment results showed that the kinetic of catalytic decomposition of N₂O was a first-order reaction and the activation energy and the pre-factor of the kinetic equation were 115.15kJ/mol and of 1.6×109, respectively.

Keywords: catalytic decomposition, CuO/HZSM-5, kinetic, nitrous oxide

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Authors: Yahia Massinissa, Melakhessou Med Akram, Mezahdia Mehdi, Marref Salah Eddine

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Cytokines are natural proteins which act as true intercellular communication signals in immune and inflammatory responses. Reverse signaling pathways that activate cytokines help to regulate different functions at the target cell, causing its activation, its proliferation, the differentiation, its survival or death. It was shown that malfunctioning of the cytokine regulation, particularly over-expression, contributes to the onset and development of certain serious diseases such as chronic rheumatoid arthritis, Crohn's disease, psoriasis, lupus. The action mode of Kinoid® technology is based on the principle vaccine: The patient's immune system is activated so that it neutralizes itself and the factor responsible for the disease. When applied specifically to autoimmune diseases, therapeutic vaccination allows the body to neutralize cytokines (proteins) overproduced through a highly targeted stimulation of the immune system.

Keywords: cytokines, Kinoid tech, auto-immune diseases, vaccination

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Authors: Prashant Sharma, Jyotsna Dutta Majumdar

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The present study concerns development of a composite thermal barrier coating consisting of a mixture of La2O3 and YSZ (with 8 wt.%, 32 wt.% and 50 wt.% 50% La2O3) by plasma spray deposition technique on a CoNiCrAlY based bond coat deposited on Inconel 718 substrate by high velocity oxy-fuel deposition (HVOF) technique. The addition of La2O3 in YSZ causes the formation of pyrochlore (La2Zr2O7) phase in the inter splats boundary along with the presence of LaYO3 phase. The coefficient of thermal expansion is significantly reduced from due to the evolution of different phases and structural defects in the sprayed coating. The activation energy for TGO growth under isothermal and cyclic oxidation was increased in the composite coating as compared to YSZ coating.

Keywords: plasma spraying, oxidation resistance, thermal barrier coating, microstructure, X-ray method

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Authors: Vaibhavi Birle

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Posterior reversible encephalopathy syndrome is a rare clinic-radiological syndrome associated with acute changes in blood pressure during pregnancy. It is characterized symptomatically by headache, seizures, altered mental status, and visual blurring with radiological changes of white matter (vasogenic oedema) affecting the posterior occipital and parietal lobes of the brain. It is being increasingly recognized due to increased institutional deliveries and advances in imaging particularly magnetic resonance imaging (MRI). In spite of the increasing diagnosis the prediction of PRES and patient factors affecting susceptibility is still not clear. Hence, we conducted the retrospective study to analyse the factors associated with PRES at our tertiary centre.

Keywords: pres syndrome, eclampsia, maternal outcome, fetal outcome

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Authors: Shahbaa F. Bdewi, Bakhtyar K. Aziz, Ayad A. R. Mutar

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Nano-materials show different surface properties due to their high surface area and active sites. This study investigates the feasibility of using nano-MgO (NMO) for removing Congo red (CR) dye from wastewater. NMO was prepared by molten salt method. Equilibrium experiments show the equilibrium was reached after 120 minutes and maximum adsorption efficiency was obtained in acidic media up to pH 6. Isotherm studies revealed the favorability of the adsorption process. The overall adsorption process was spontaneous and endothermic in nature with a maximum adsorption capacity of 1100 mg g-1 at 40°C as estimated from Langmuir isotherm. The adsorption kinetics was found to follow pseudo second-order rate equation. Relatively high activation energy (180.7 kJ mol-1) was obtained which is consistent with chemisorption mechanism for the adsorption process.

Keywords: adsorption, congo red, magnesium oxide, nanoparticles

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Authors: Sourav Ray, Christoph Stein, Marcus Weber

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A new class of drug candidates, initially derived from mathematical modeling of ligand-receptor interactions, activate the μ-opioid receptor (MOR) preferentially at acidic extracellular pH-levels, as present in injured tissues. This is of commercial interest because it may preclude the adverse effects of conventional MOR agonists like fentanyl, which include but are not limited to addiction, constipation, sedation, and apnea. Animal studies indicate the importance of taking the pH value of the chemical environment of MOR into account when designing new drugs. Hydrogen bonds (HBs) play a crucial role in stabilizing protein secondary structure and molecular interaction, such as ligand-protein interaction. These bonds may depend on the pH value of the chemical environment. For the MOR, antagonist naloxone and agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) form HBs with ionizable residue HIS 297 at physiological pH to modulate signaling. However, such interactions were markedly reduced at acidic pH. Although fentanyl-induced signaling is also diminished at acidic pH, HBs with HIS 297 residue are not observed at either acidic or physiological pH for this strong agonist of the MOR. Molecular dynamics (MD) simulations can provide greater insight into the interaction between the ligand of interest and the HIS 297 residue. Amino acid protonation states are adjusted to the model difference in system acidity. Unbiased and unrestrained MD simulations were performed, with the ligand in the proximity of the HIS 297 residue. Ligand-receptor complexes were embedded in 1-palmitoyl-2-oleoyl-sn glycero-3-phosphatidylcholine (POPC) bilayer to mimic the membrane environment. The occurrence of HBs between the different ligands and the HIS 297 residue of MOR at acidic and physiological pH values were tracked across the various simulation trajectories. No HB formation was observed between fentanyl and HIS 297 residue at either acidic or physiological pH. Naloxone formed some HBs with HIS 297 at pH 5, but no such HBs were noted at pH 7. Interestingly, DAMGO displayed an opposite yet more pronounced HB formation trend compared to naloxone. Whereas a marginal number of HBs could be observed at even pH 5, HBs with HIS 297 were more stable and widely present at pH 7. The HB formation plays no and marginal role in the interaction of fentanyl and naloxone, respectively, with the HIS 297 residue of MOR. However, HBs play a significant role in the DAMGO and HIS 297 interaction. Post DAMGO administration, these HBs might be crucial for the remediation of opioid tolerance and restoration of opioid sensitivity. Although experimental studies concur with our observations regarding the influence of HB formation on the fentanyl and DAMGO interaction with HIS 297, the same could not be conclusively stated for naloxone. Therefore, some other supplementary interactions might be responsible for the modulation of the MOR activity by naloxone binding at pH 7 but not at pH 5. Further elucidation of the mechanism of naloxone action on the MOR could assist in the formulation of cost-effective naloxone-based treatment of opioid overdose or opioid-induced side effects.

Keywords: effect of system acidity, hydrogen bond formation, opioid action, receptor activation

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Authors: Marie-Eve Joret, Marijn Van Vliet, Flavio Camarrone, Marc M. Van Hulle

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Event-related potentials (ERPs) provide evidence that the human brain can process and understand music at a pre-attentive level. Music-specific ERPs include the Early Right Anterior Negativity (ERAN) and a late Negativity (N5). This study aims to further investigate this issue using two types of syntactic manipulations in music: mild violations, containing no out-of-key tones and strong violations, containing out-of-key tones. We will examine whether both manipulations will elicit the same ERPs.

Keywords: ERAN ERPs, Music, N5, P3, ERPs, Music, N5 component, P3 component

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Authors: Palwinder Singh

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Beyond the conventional mode of working with anti-inflammatory agents through enzyme inhibition, herein, an alternate substrate of cyclooxygenase-2 was developed. Proline centered pentapeptide iso-conformational to arachidonic acid exhibited appreciable selectivity for COX-2 overcoming acetic acid and formalin induced pain in rats to almost 80% and was treated as a substrate by the enzyme. Remarkably, COX-2 metabolized the pentapeptide into small fragments consisting mainly of di- and tri-peptides that ensured the safe breakdown of the peptide under in-vivo conditions. The kinetic parameter Kcat/Km for COX-2 mediated metabolism of peptide 6.3 x 105 M-1 s-1 was quite similar to 9.5 x 105 M-1 s-1 for arachidonic acid. Evidenced by the dynamic molecular studies and the use of Y385F COX-2, it was observed that the breakage of the pentapeptide has probably taken place through H-bond activation of the peptide bond by the side chains of Y385 and S530.

Keywords: small peptides, anti-inflammatory agents, cyclooxygenase-2, unnatural substrates

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Authors: Xiaoling Ren, Guidong Yang

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As one of the largest industrial synthetic chemicals in the world, ammonia has the advantages of high energy density, easy liquefaction, and easy transportation, which is widely used in agriculture, chemical industry, energy storage, and other fields. The industrial Haber-Bosch method process for ammonia synthesis is generally conducted under severe conditions. It is essential to develop a green, sustainable strategy for ammonia production to meet the growing demand. In this direction, photocatalytic nitrogen reduction has huge advantages over the traditional, well-established Haber-Bosch process, such as the utilization of natural sun light as the energy source and significantly lower pressure and temperature to affect the reaction process. However, the high activation energy of nitrogen and the low efficiency of photo-generated electron-hole separation in the photocatalyst result in low ammonia production yield. Many researchers focus on improving the catalyst. In addition to modifying the catalyst, improving the dispersion of the catalyst and making full use of active sites are also means to improve the overall catalytic activity. Few studies have been carried out on this, which is the aim of this work. In this work, by making full use of the nitrogen activation ability of WO3-x with defective sites, small size WO3-x photocatalyst with high dispersibility was constructed, while the growth of WO3-x was restricted by using a high specific surface area mesoporous SBA-15 molecular sieve with the regular pore structure as a template. The morphology of pure SBA-15 and WO3-x/SBA-15 was characterized byscanning electron microscopy (SEM). Compared with pure SBA-15, some small particles can be found in the WO3-x/SBA-15 material, which means that WO3-x grows into small particles under the limitation of SBA-15, which is conducive to the exposure of catalytically active sites. To elucidate the chemical nature of the material, the X-ray diffraction (XRD) analysis was conducted. The observed diffraction pattern inWO3-xis in good agreement with that of the JCPDS file no.71-2450. Compared with WO3-x, no new peaks appeared in WO3-x/SBA-15.It can be concluded that WO3-x/SBA-15 was synthesized successfully. In order to provide more active sites, the mass content of WO3-x was optimized. Then the photocatalytic nitrogen reduction performances of above samples were performed with methanol as a hole scavenger. The results show that the overall ammonia production performance of WO3-x/SBA-15 is improved than pure bulk WO3-x. The above results prove that making full use of active sites is also a means to improve overall catalytic activity.This work provides material basis for the design of high-efficiency photocatalytic nitrogen reduction catalysts.

Keywords: ammonia, photocatalytic, nitrogen reduction, WO3-x, high dispersibility

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Authors: Anaelle Gabet, Helene Metivier, Christine De Brauer, Gilles Mailhot, Marcello Brigante

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The presence of micropollutants in surface waters has been widely reported around the world, particularly downstream from wastewater treatment plants (WWTPs). Rural WWTPs constitute more than 90 % of the total WWTPs in France. Like conventional ones, they are not able to fully remove micropollutants. Estrogens are excreted by human beings every day and several studies have highlighted their endocrine disruption properties on river wildlife. They are mainly estrone (E1), 17β-estradiol (E2) and 17α-ethinylestradiol (EE2). Rural WWTPs require cheap and robust tertiary processes. UVC activation of H₂O₂ for HO· generation, a very reactive molecule, has demonstrated its effectiveness. However, UVC rays are dangerous to manipulate and energy-consuming. This is why the ability of UVA rays was investigated in this study. Moreover, the use of S₂O₈²⁻ for SO₄·- generation as an alternative to HO· has emerged in the last few years. Such processes have been widely studied on a lab scale. However, pilot-scale works constitute fewer studies. This study was carried out on a 20-L pilot composed of a 1.12-L UV reactor equipped with a polychromatic UVA lamp or a monochromatic (254 nm) UVC lamp fed in recirculation. Degradation rates of a mixture of spiked E1, E2 and EE2 (5 µM each) were followed by HPLC-UV. Results are expressed in UV dose (mJ.cm-2) received by the compounds of interest to compare UVC and UVA. In every system, estrogen degradation rates followed pseudo-first-order rates. First, experiments were carried out in tap water. All estrogens underwent photolysis under UVC rays, although E1 photolysis is higher. However, only very weak photolysis was observed under UVA rays. Preliminary studies on both oxidants have shown that S₂O₈²⁻ photolysis constants are higher than H₂O₂ under both UVA and UVC rays. Therefore, estrogen degradation rates are about ten times higher in the presence of 1 mM of S₂O₈²⁻ than with one mM of H₂O₂ under both radiations. In the same conditions, the mixture of interest required about 40 times higher UV dose when using UVA rays compared to UVC. However, the UVA/S₂O₈²⁻ system only requires four times more UV dose than the conventional UVC/H₂O₂ system. Further studies were carried out in WWTP effluent with the UVC lamp. When comparing these results to the tap water ones, estrogen degradation rates were more inhibited in the S₂O₈²⁻ system than with H₂O₂. It seems that SO₄·- undergo higher quenching by a real effluent than HO·. Preliminary experiments have shown that natural organic matter is mainly responsible for the radical quenching and that HO and SO₄ both had similar second-order reaction rate constants with dissolved organic matter. However, E1, E2 and EE2 second-order reaction rate constants are about ten times lower with SO₄ than with HO. In conclusion, the UVA/S₂O₈²⁻ system showed encouraging results for the use of UVA rays but further studies in WWTP effluent have to be carried out to confirm this interest. The efficiency of other pollutants in the real matrix also needs to be investigated.

Keywords: AOPs, decontamination, estrogens, radicals, wastewater

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Authors: Judy M. Obliosca, Olivia Vest, Sandra Poulos, Kelsi Smith, Tammy Ferguson, Abigail Powers Lott, Alicia K. Smith, Yang Xu, Christopher K. Tison

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Post-Traumatic Stress Disorder (PTSD) is a mental health problem that people may develop after experiencing traumatic events such as combat, natural disasters, and major emotional challenges. Tragically, the number of military personnel with PTSD correlates directly with the number of veterans who attempt suicide, with the highest rate in the Army. Research has shown epigenetic risks in those who are prone to several psychiatric dysfunctions, particularly PTSD. Once initiated in response to trauma, epigenetic alterations in particular, the DNA methylation in the form of 5-methylcytosine (5mC) alters chromatin structure and represses gene expression. Current methods to detect DNA methylation, such as bisulfite-based genomic sequencing techniques, are laborious and have massive analysis workflow while still having high error rates. A faster and simpler detection method of high sensitivity and precision would be useful in a clinical setting to confirm potential PTSD etiologies, prevent other psychiatric disorders, and improve military health. A nano-enhanced Surface Plasmon Resonance imaging (SPRi)-based assay that simultaneously detects site-specific 5mC base (termed as PTSD base) in methylated genes related to PTSD is being developed. The arrays on a sensing chip were first constructed for parallel detection of PTSD bases using synthetic and genomic DNA (gDNA) samples. For the gDNA sample extracted from the whole blood of a PTSD patient, the sample was first digested using specific restriction enzymes, and fragments were denatured to obtain single-stranded methylated target genes (ssDNA). The resulting mixture of ssDNA was then injected into the assay platform, where targets were captured by specific DNA aptamer probes previously immobilized on the surface of a sensing chip. The PTSD bases in targets were detected by anti-5-methylcytosine antibody (anti-5mC), and the resulting signals were then enhanced by the universal nanoenhancer. Preliminary results showed successful detection of a PTSD base in a gDNA sample. Brighter spot images and higher delta values (control-subtracted reflectivity signal) relative to those of the control were observed. We also implemented the in-house surface activation system for detection and developed SPRi disposable chips. Multiplexed PTSD base detection of target methylated genes in blood DNA from PTSD patients of severity conditions (asymptomatic and severe) was conducted. This diagnostic capability being developed is a platform technology, and upon successful implementation for PTSD, it could be reconfigured for the study of a wide variety of neurological disorders such as traumatic brain injury, Alzheimer’s disease, schizophrenia, and Huntington's disease and can be extended to the analyses of other sample matrices such as urine and saliva.

Keywords: epigenetic assay, DNA methylation, PTSD, whole blood, multiplexing

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Authors: Shereen Ismail Fawaz, Shin-Ichi Izumi, Nouran Mohamed Salah, Heba G. Saber, Ibrahim Mohamed Roushdi

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Background: Multiple sclerosis (MS) is a chronic, inflammatory, mainly demyelinating disease of the central nervous system, more common in young adults. Cerebellar involvement is one of the most disabling lesions in MS and is usually a sign of disease progression. It plays a major role in the planning, initiation, and organization of movement via its influence on the motor cortex and corticospinal outputs. Therefore, it contributes to controlling movement, motor adaptation, and motor learning, in addition to its vast connections with other major pathways controlling balance, such as the cerebellopropriospinal pathways and cerebellovestibular pathways. Hence, trying to stimulate the cerebellum by facilitatory protocols will add to our motor control and balance function. Non-invasive brain stimulation, both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), has recently emerged as effective neuromodulators to influence motor and nonmotor functions of the brain. Anodal tDCS has been shown to improve motor skill learning and motor performance beyond the training period. Similarly, rTMS, when used at high frequency (>5 Hz), has a facilitatory effect on the motor cortex. Objective: Our aim was to determine the effect of high-frequency rTMS over the cerebellum in improving balance and functional ambulation of multiple sclerosis patients with Ataxia. Patients and methods: This was a randomized single-blinded placebo-controlled prospective trial on 40 patients. The active group (N=20) received real rTMS sessions, and the control group (N=20) received Sham rTMS using a placebo program designed for this treatment. Both groups received 12 sessions of high-frequency rTMS over the cerebellum, followed by an intensive exercise training program. Sessions were given three times per week for four weeks. The active group protocol had a frequency of 10 Hz rTMS over the cerebellar vermis, work period 5S, number of trains 25, and intertrain interval 25s. The total number of pulses was 1250 pulses per session. The control group received Sham rTMS using a placebo program designed for this treatment. Both groups of patients received an intensive exercise program, which included generalized strengthening exercises, endurance and aerobic training, trunk abdominal exercises, generalized balance training exercises, and task-oriented training such as Boxing. As a primary outcome measure the Modified ICARS was used. Static Posturography was done with: Patients were tested both with open and closed eyes. Secondary outcome measures included the expanded Disability Status Scale (EDSS) and 8 Meter walk test (8MWT). Results: The active group showed significant improvements in all the functional scales, modified ICARS, EDSS, and 8-meter walk test, in addition to significant differences in static Posturography with open eyes, while the control group did not show such differences. Conclusion: Cerebellar high-frequency rTMS could be effective in the functional improvement of balance in MS patients with ataxia.

Keywords: brain neuromodulation, high frequency rTMS, cerebellar stimulation, multiple sclerosis, balance rehabilitation

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Authors: M. Dasgupta, S. Banerjee

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Content Based Image Retrieval (CBIR) coupled with Case Based Reasoning (CBR) is a paradigm that is becoming increasingly popular in the diagnosis and therapy planning of medical ailments utilizing the digital content of medical images. This paper presents a survey of some of the promising approaches used in the detection of abnormalities in retina images as well in mammographic screening and detection of regions of interest in MRI scans of the brain. We also describe our proposed algorithm to detect hard exudates in fundus images of the retina of Diabetic Retinopathy patients.

Keywords: case based reasoning, exudates, retina image, similarity based retrieval

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Authors: Prangya P. Sahoo, B. S. Murty

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The present study deals with phase evolution of oxide dispersed CoCrFeMnNi high entropy alloy as a function of amount of added Y2O3 during mechanical alloying and analysis of grain growth kinetics of CoCrFeMnNi high entropy alloy without and with oxide dispersion. Mechanical alloying of CoCrFeMnNi resulted in a single FCC phase. However, evolution of chromium carbide was observed after heat treatment between 1073 and 1473 K. Comparison of grain growth time exponents and activation energy barrier is also reported. Micro structural investigations, using electron microscopy and EBSD techniques, were carried out to confirm the enhanced grain growth resistance which is attributed to the presence oxide dispersoids.

Keywords: grain growth kinetics, mechanical alloying, oxide dispersion, phase evolution

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Authors: Kyoungjin Kim

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Nanoscale thermites such as the composite mixture of nano-sized aluminum and molybdenum trioxide powders possess several technical advantages such as much higher reaction rate and shorter ignition delay, when compared to the conventional energetic formulations made of micron-sized metal and oxidizer particles. In this study, the self-propagation of combustion wave in compacted pellets of nanoscale thermite composites is modeled and computationally investigated by utilizing the activation energy reduction of aluminum particles due to nanoscale particle sizes. The present computational model predicts the speed of combustion wave propagation which is good agreement with the corresponding experiments of thermite reaction. Also, several characteristics of thermite reaction in nanoscale composites are discussed including the ignition delay and combustion wave structures.

Keywords: nanoparticles, thermite reaction, combustion wave, numerical modeling

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Authors: Kartik Gupta, Virendra Kumar, Sanjeev Sinha, N. Jagannathan

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Introduction: A significant number of patients having human immunodeficiency virus (HIV) infection show a neurocognitive decline (NCD) ranging from minor cognitive impairment to severe dementia. The possible causes of NCD in HIV-infected patients include brain injury by HIV before cART, neurotoxic viral proteins and metabolic abnormalities. In the present study, we compared the level of NCD in asymptomatic HIV-infected patients with changes in brain metabolites measured by using magnetic resonance spectroscopy (MRS). Methods: 43 HIV-positive patients (30 males and 13 females) coming to ART center of the hospital and HIV-seronegative healthy subjects were recruited for the study. All the participants completed MRI and MRS examination, detailed clinical assessments and a battery of neuropsychological tests. All the MR investigations were carried out at 3.0T MRI scanner (Ingenia/Achieva, Philips, Netherlands). MRI examination protocol included the acquisition of T2-weighted imaging in axial, coronal and sagittal planes, T1-weighted, FLAIR, and DWI images in the axial plane. Patients who showed any apparent lesion on MRI were excluded from the study. T2-weighted images in three orthogonal planes were used to localize the voxel in left frontal lobe white matter (FWM) and left basal ganglia (BG) for single voxel MRS. Single voxel MRS spectra were acquired with a point resolved spectroscopy (PRESS) localization pulse sequence at an echo time (TE) of 35 ms and a repetition time (TR) of 2000 ms with 64 or 128 scans. Automated preprocessing and determination of absolute concentrations of metabolites were estimated using LCModel by water scaling method and the Cramer-Rao lower bounds for all metabolites analyzed in the study were below 15\%. Levels of total N-acetyl aspartate (tNAA), total choline (tCho), glutamate + glutamine (Glx), total creatine (tCr), were measured. Cognition was tested using a battery of tests validated for Indian population. The cognitive domains tested were the memory, attention-information processing, abstraction-executive, simple and complex perceptual motor skills. Z-scores normalized according to age, sex and education standard were used to calculate dysfunction in these individual domains. The NCD was defined as dysfunction with Z-score ≤ 2 in at least two domains. One-way ANOVA was used to compare the difference in brain metabolites between the patients and healthy subjects. Results: NCD was found in 23 (53%) patients. There was no significant difference in age, CD4 count and viral load between the two groups. Maximum impairment was found in the domains of memory and simple motor skills i.e., 19/43 (44%). The prevalence of deficit in attention-information processing, complex perceptual motor skills and abstraction-executive function was 37%, 35%, 33% respectively. Subjects with NCD had a higher level of Glutamate in the Frontal region (8.03 ± 2.30 v/s. 10.26 ± 5.24, p-value 0.001). Conclusion: Among newly diagnosed, ART-naïve retroviral disease patients from India, cognitive decline was found in 53\% patients using tests validated for this population. Those with neurocognitive decline had a significantly higher level of Glutamate in the left frontal region. There was no significant difference in age, CD4 count and viral load at initiation of ART between the two groups.

Keywords: HIV, neurocognitive decline, neurometabolites, magnetic resonance spectroscopy

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Authors: Houneïda Benbouzid, Houria Berrebbah, Mohammed-Réda Djebar

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The toxicological impacts of the increasing number of synthetic compounds present in the aquatic environment are assessed predominantly in laboratory studies where test organisms are exposed to a range of concentrations of single compounds. The bio-indicator Paramecium sp., characterized by a short life cycle, rapid multiplication and normal behavior that may be affected by the presence of pollutants. We therefore investigated the inhibitory effect of a newly synthesized acaricide: the chlorfenapyr tested at concentrations of 250, 300, and 350 µM on a pure culture of Paramecium sp. during 6 day. Paramecia treated with different concentrations of Chlorfenapyr illustrate strong inhibition of cell growth from the second day of treatment. Low levels of glutathione, increased glutathione S-transferase and the decrease in respiratory metabolism, recorded in the presence of different concentrations of Chlorfenapyr, involve the activation of detoxification system.

Keywords: Paramecium sp., chlorfenapyr, oxidative enzymes, detoxification

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Authors: Vishnu Emani, Andreas Escher, Ellen Roche

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Background: Orthostatic hypotension (OH) is an autonomic disorder marked by a sudden drop in blood pressure upon standing resulting from autonomic dysfunction. OH is especially prevalent in elderly populations, affecting more than 30% of Americans over the age of 70. OH is one of the most significant risk factors for accidental falls in elderly populations, making it a crucial focus for medical and device therapies. Pharmacologic therapy with midodrine and fludrocortisone may alleviate hypotension but have significant adverse side effects. Abdominal passive compression devices (binders) are more effective than lower extremity compression stockings at mitigating postural hypotension, by improving venous return to the heart. However, abdominal binders are difficult to don and uncomfortable to wear, leading to poor compliance. A disadvantage of passive compression devices is their inability to selectively compress during the crucial moment of standing. it have recently developed an active compression device that applies external pressure on the abdomen during transition from prone to supine position and conducted initial prototype testing. Methods: An active abdominal compression device was developed utilizing a simple, servo-driven strap-tightening mechanism to supply tension onto foam fabric, which applies pressure to the abdomen. Healthy volunteers (n=5) were utilized for prototype testing and were subjected to three conditions: no compression, passive compression (i.e. standard abdominal binder), and active compression (device prototype). Abdominal applied pressure during device activation was measured by strain-gauge manometer placed between the skin and binder. Systolic (SBP) and mean (MAP) arterial blood pressure was measured by standard blood pressure cuff in supine position followed by repeat measurements at 1 minute intervals for 5 minutes following upright position. A survey tool was administered to determine scores (1-10) for comfort and ease of donning abdominal binders. Results: Abdominal pressure increased from 0 to 15±3 mmHg upon device activation for both passive and active compression devices. During transition from supine to upright position, both active and passive compression devices demonstrated significantly higher MAP compared to the no-compression condition (67±4, 68±5, 62±5 respectively P<0.05), but there was no statistically significant difference in SBP or MAP when comparing active to passive compression. Active compression demonstrated significantly higher comfort scores (8.3±1) compared to passive compression (3.2±2) but lower when compared to no compression (10). Subjects universally reported that active compression device was easier to don compared to passive device. Conclusions: Active or passive abdominal compression prevents hypotension associated with postural changes. Active compression is associated with increased comfort and ease of donning compared to passive compression devices. Future trials are warranted to investigate the efficacy of our device in patients with OH.

Keywords: orthostatic hypotension, compression binder, abdominal binder, active abdominal compression

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