Search results for: muscle stem cells

Authors: Balakrishna Valluru, Ruth Suckling

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A 16 year old male was found collapsed on the road following stab injuries to the chest and abdomen and was transported to the emergency department by ambulance. On arrival in the emergency department the patient was breathless and appeared pale. He was maintaining his airway with spontaneous breathing and had a heart rate of 122 beats per minute with a blood pressure of 83/63 mmHg. He was resuscitated initially with three units of packed red cells. Clinical examination identified three incisional wounds each measuring 2 cm. These were in the left para-sternal region, right infra-scapular region and left upper quadrant of the abdomen. The chest wound over the left parasternal area at the level of 4tth intercostal space was bleeding intermittently on leaning forwards and was relieving his breathlessness intermittently. CT imaging was performed to characterize his injuries and determine his management. CT scan of chest and abdomen showed moderate size haemopericardium with left sided haemopneumothorax. The patient underwent urgent surgical repair of the left ventricle and left anterior descending artery. He recovered without complications and was discharged from the hospital. This case highlights the fact that the potential to develop a life threatening cardiac tamponade was mitigated by the left parasternal stab wound. This injury fortuitously provided a pericardial window through which the bleeding from the injured left ventricle and left anterior descending artery could drain into the left hemithorax providing an opportunity for timely surgical intervention to repair the cardiac injuries.

Keywords: stab, incisional, haemo-pericardium, haemo-pneumothorax

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Authors: Moataz Medhat, Essam E. Khalil, Hatem Haridy

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In the present study, a numerical simulation study is used to 3-D model the steady-state combustion of a staged natural gas flame in a 300 kW swirl-stabilized burner, using ANSYS solver to find the highest combustion efficiency by changing the inlet air swirl number and burner quarl angle in a furnace and showing the effect of flue gas recirculation, type of fuel and staging. The combustion chamber of the gas turbine is a cylinder of diameter 1006.8 mm, and a height of 1651mm ending with a hood until the exhaust cylinder has been reached, where the exit of combustion products which have a diameter of 300 mm, with a height of 751mm. The model was studied by 15 degree of the circumference due to axisymmetric of the geometry and divided into a mesh of about 1.1 million cells. The numerical simulations were performed by solving the governing equations in a three-dimensional model using realizable K-epsilon equations to express the turbulence and non-premixed flamelet combustion model taking into consideration radiation effect. The validation of the results was done by comparing it with other experimental data to ensure the agreement of the results. The study showed two zones of recirculation. The primary one is at the center of the furnace, and the location of the secondary one varies by changing the quarl angle of the burner. It is found that the increase in temperature in the external recirculation zone is a result of increasing the swirl number of the inlet air stream. Also it was found that recirculating part of the combustion products back to the combustion zone decreases pollutants formation especially nitrogen monoxide.

Keywords: burner selection, natural gas, analysis, recirculation

Procedia PDF Downloads 162

Authors: Huimin Zhao, Xiaoquan Liu, Haochen Liu

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The major challenge facing Alzheimer's Disease (AD) drug development is how to effectively improve cognitive function in clinical practice. Growing evidence indicates that stimulating hippocampal neurogenesis is a strategy for restoring cognition in animal models of AD. The mitogen-activated protein kinase (MAPK) pathway is a crucial factor in neurogenesis, which is negatively regulated by Dual-specificity phosphatase 16 (DUSP16). Transcriptome analysis of post-mortem brain tissue revealed up-regulation of DUSP16 expression in AD patients. Additionally, DUSP16 was involved in regulating the proliferation and neural differentiation of neural progenitor cells (NPCs). Nevertheless, whether the effect of DUSP16 on ameliorating cognitive disorders by influencing NPCs differentiation in AD mice remains unclear. Our study demonstrates an association between DUSP16 SNPs and clinical progression in individuals with mild cognitive impairment (MCI). Besides, we found that increased DUSP16 expression in both 3×Tg and SAMP8 models of AD led to NPC differentiation impairments. By silencing DUSP16, cognitive benefits, the induction of AHN and synaptic plasticity, were observed in AD mice. Furthermore, we found that DUSP16 is involved in the process of NPC differentiation by regulating c-Jun N-terminal kinase (JNK) phosphorylation. Moreover, the increased DUSP16 may be regulated by the ETS transcription factor (ELK1), which binds to the promoter region of DUSP16. Loss of ELK1 resulted in decreased DUSP16 mRNA and protein levels. Our data uncover a potential regulatory role for DUSP16 in adult hippocampal neurogenesis and provide a possibility to find the target of AD intervention.

Keywords: alzheimer's disease, cognitive function, DUSP16, hippocampal neurogenesis

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Authors: Akan C. Offong, E. J. Anthony, Vasilije Manovic

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A modified steady-state numerical model is developed for the electrochemical reduction of CO₂ to formic acid. The numerical model achieves a CD (current density) (~60 mA/cm²), FE-faradaic efficiency (~98%) and conversion (~80%) for CO₂ electro-reduction to formic acid in a microfluidic cell. The model integrates charge and species transport, mass conservation, and momentum with electrochemistry. Specifically, the influences of Bi-Sn based nanoparticle catalyst (on the cathode surface) at different mole fractions and 1-ethyl-3-methyl imidazolium tetra-fluoroborate ([EMIM][BF₄]) electrolyte, on CD, FE and CO₂ conversion to formic acid is studied. The reaction is carried out at a constant concentration of electrolyte (85% v/v., [EMIM][BF₄]). Based on the mass transfer characteristics analysis (concentration contours), mole ratio 0.5:0.5 Bi-Sn catalyst displays the highest CO₂ mole consumption in the cathode gas channel. After validating with experimental data (polarisation curves) from literature, extensive simulations reveal performance measure: CD, FE and CO₂ conversion. Increasing the negative cathode potential increases the current densities for both formic acid and H₂ formations. However, H₂ formations are minimal as a result of insufficient hydrogen ions in the ionic liquid electrolyte. Moreover, the limited hydrogen ions have a negative effect on formic acid CD. As CO₂ flow rate increases, CD, FE and CO₂ conversion increases.

Keywords: carbon dioxide, electro-chemical reduction, ionic liquids, microfluidics, modelling

Procedia PDF Downloads 148

Authors: M. Knezevic, V. Marecic, M. Ozanic, I. Kelava, M. Mihelcic, M. Santic

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Francisella tularensis is a highly infectious, gram-negative intracellular bacterium and the causative agent of tularemia. The bacterium has been isolated from more than 250 wild species, including protozoa cells. Since Francisella is very virulent and persists in the environment for years, the aim of this study was to investigate whether Acanthamoeba castellanii-grown F. novicida exhibits an alteration in the resistance to disinfectants. It has been shown by other intracellular pathogens, including Legionella pneumophila that bacteria grown in amoeba exhibit more resistance to disinfectants. However, there is no data showing Francisella viability behaviour after intracellular life cycle in A. castellani. In this study, the bacterial suspensions of A. castellanii-grown or in vitro-grown Francisella were treated with three different disinfectants, and the bacterial viability after disinfection treatment was determined by a colony-forming unit (CFU) counting method, transmission electron microscopy (TEM), fluorescence microscopy as well as the leakage of intracellular fluid. Our results have shown that didecyldimethylammonium chloride (DDAC) combined with isopropyl alcohol was the most effective in bacterial killing; all in vitro-grown and A. castellanii-grown F. novicida were killed after only 10s. Surprisingly, in comparison to in vitro-grown bacteria, A. castellanii-grown F. novicida was more sensitive to decontamination by the benzalkonium chloride combined with DDAC and formic acid and the polyhexamethylene biguanide (PHMB). We can conclude that the tested disinfectants exhibit antimicrobial activity by causing a loss of structural organization and integrity of the Francisella cell wall and membrane and the subsequent leakage of the intracellular contents. Finally, the results of this study clearly demonstrate that Francisella grown in A. castellanii had become more susceptible to many disinfectants.

Keywords: Acanthamoeba, disinfectant, Francisella, sensitivity

Procedia PDF Downloads 101

Authors: Yassir Abdelrazig, Ren Moses

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Roadway planning and design is a very complex process involving five key phases before a project is completed; planning, project development, final design, right-of-way, and construction. The planning phase for a new roadway transportation project is a very critical phase as it greatly affects all latter phases of the project. A location study is usually performed during the preliminary planning phase in a new roadway project. The objective of the location study is to develop alignment alternatives that are cost efficient considering land acquisition and construction costs. This paper describes a methodology to develop optimal preliminary roadway alignments utilizing spatial-data. Four optimization criteria are taken into consideration; roadway length, land cost, land slope, and environmental impacts. The basic concept of the methodology is to convert the proposed project area into a grid, which represents the search space for an optimal alignment. The aforementioned optimization criteria are represented in each of the grid’s cells. A spatial-data optimization technique is utilized to find the optimal alignment in the search space based on the four optimization criteria. Two case studies for new roadway projects in Duval County in the State of Florida are presented to illustrate the methodology. The optimization output alignments are compared to the proposed Florida Department of Transportation (FDOT) alignments. The comparison is based on right-of-way costs for the alignments. For both case studies, the right-of-way costs for the developed optimal alignments were found to be significantly lower than the FDOT alignments.

Keywords: gemoetric design, optimization, planning, roadway planning, roadway design

Procedia PDF Downloads 339

Authors: Bernard L. Middleton, Susan P. Cosgrove

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There is an immediate need for alternative anti-herpetic treatment options effective for both primary infections and reoccurring reactivations of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Alternatives currently approved for the purposes of clinical administration includes antivirals and a reduced set of nucleoside analogues. The present article tests a treatment based on a systemic understanding of how the herpes virus affects cell inhibition and breakdown and targets different phases of the viral cycle, including the entry stage, reproductive cross mutation, and cell-to-cell infection. The treatment consisted of five immunotherapeutic core compounds (5CC), which were hypothesized to be capable of neutralizing human monoclonal antibodies. The tested 5CC were noted as being functional in the application of eliminating the DNA synthesis of herpes viral interferon (IFN) - induced cellular antiviral response. They were here found to neutralize antiviral reproduction by blocking cell-to-cell infection. The activity of the 5CC was tested on RC-37 in vitro using an assay plaque reduction and in vivo against HSV-1 and HSV-2. The 50% inhibitory concentration (IC50) of 5CC was 0.0009% for HSV-1 plaque formation and 0.0008% for HSV-2 plaque formation. Further tests were performed to evaluate the susceptibility of HSV-1 and HSV-2 to anti-herpetic drugs in Vero cells after virus entry. There were high-level markers of the 5CC virucidal activity in the viral suspension of HSV-1 and HSV-2. These concentrations of the 5CC are nontoxic and reduced plaque formation by 98.2% for HSV-1 and 93.0% for HSV-2. Virus HSV-1 and HSV-2 titers were reduced significantly by 5CC to the point of being negative, ranging 0.01–0.09 in 72%. The results concluded the 5CC as being an effective treatment option for the herpes simplex virus.

Keywords: synergy pharmaceuticals, herpes treatment, herpes cure, synergy pharmaceuticals treatment

Procedia PDF Downloads 241

Authors: Mihai Caramihai, Dan Vasilescu

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The main research objective of the experimental bioprocess analyzed in this paper was to obtain large biomass quantities. The bioprocess is performed in 100 L Bioengineering bioreactor with 42 L cultivation medium made of peptone, meat extract and sodium chloride. The reactor was equipped with pH, temperature, dissolved oxygen, and agitation controllers. The operating parameters were 37 oC, 1.2 atm, 250 rpm and air flow rate of 15 L/min. The main objective of this paper is to present a case study to demonstrate that intelligent control, describing the complexity of the biological process in a qualitative and subjective manner as perceived by human operator, is an efficient control strategy for this kind of bioprocesses. In order to simulate the bioprocess evolution, an intelligent control structure, based on fuzzy logic has been designed. The specific objective is to present a fuzzy control approach, based on human expert’ rules vs. a modeling approach of the cells growth based on bioprocess experimental data. The kinetic modeling may represent only a small number of bioprocesses for overall biosystem behavior while fuzzy control system (FCS) can manipulate incomplete and uncertain information about the process assuring high control performance and provides an alternative solution to non-linear control as it is closer to the real world. Due to the high degree of non-linearity and time variance of bioprocesses, the need of control mechanism arises. BIOSIM, an original developed software package, implements such a control structure. The simulation study has showed that the fuzzy technique is quite appropriate for this non-linear, time-varying system vs. the classical control method based on a priori model.

Keywords: intelligent, control, fuzzy model, bioprocess optimization

Procedia PDF Downloads 327

Authors: Francisco Pedroza-Montero, Jesús Naín Pedroza-Montero, Diego Soto-Puebla, Osiris Alvarez-Bajo, Beatriz Castaneda, Sofía Navarro-Espinoza, Martín Pedroza-Montero

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Nanodiamonds have been widely studied for their physical properties, including chemical inertness, biocompatibility, optical transparency from the ultraviolet to the infrared region, high thermal conductivity, and mechanical strength. In this work, we studied how the fluorescence spectrum of nanodiamonds quenches concerning the concentration in aqueous solutions systematically ranging from 0.1 to 10 mg/mL. Our results demonstrated a non-linear fluorescence quenching as the concentration increases for both of the NV zero-phonon lines; the 5 mg/mL concentration shows the maximum fluorescence emission. Furthermore, this behaviour is theoretically explained as an electronic recombination process that modulates the intensity in the NV centres. Finally, to gain more insight, the FRET methodology is used to determine the fluorescence efficiency in terms of the fluorophores' separation distance. Thus, the concentration level is simulated as follows, a small distance between nanodiamonds would be considered a highly concentrated system, whereas a large distance would mean a low concentrated one. Although the 5 mg/mL concentration shows the maximum intensity, our main interest is focused on the concentration of 0.5 mg/mL, which our studies demonstrate the optimal human cell viability (99%). In this respect, this concentration has the feature of being as biocompatible as water giving the possibility to internalize it in cells without harming the living media. To this end, not only can we track nanodiamonds on the surface or inside the cell with excellent precision due to their fluorescent intensity, but also, we can perform thermometry tests transforming a fluorescence contrast image into a temperature contrast image.

Keywords: nanodiamonds, fluorescence spectroscopy, concentration, bioimaging, thermometry

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Authors: Ana Paula Soares, Alexandrina Lages, Helena Oliveira, Francisco-Javier Gutiérrez-Domínguez, Marisa Lousada

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From an early age, exposure to a spoken language allows us to implicitly capture the structure underlying the succession of the speech sounds in that language and to segment it into meaningful units (words). Statistical learning (SL), i.e., the ability to pick up patterns in the sensory environment even without intention or consciousness of doing it, is thus assumed to play a central role in the acquisition of the rule-governed aspects of language and possibly to lie behind the language difficulties exhibited by children with development language disorder (DLD). The research conducted so far has, however, led to inconsistent results, which might stem from the behavioral tasks used to test SL. In a classic SL experiment, participants are first exposed to a continuous stream (e.g., syllables) in which, unbeknownst to the participants, stimuli are grouped into triplets that always appear together in the stream (e.g., ‘tokibu’, ‘tipolu’), with no pauses between each other (e.g., ‘tokibutipolugopilatokibu’) and without any information regarding the task or the stimuli. Following exposure, SL is assessed by asking participants to discriminate between triplets previously presented (‘tokibu’) from new sequences never presented together during exposure (‘kipopi’), i.e., to perform a two-alternative-forced-choice (2-AFC) task. Despite the widespread use of the 2-AFC to test SL, it has come under increasing criticism as it is an offline post-learning task that only assesses the result of the learning that had occurred during the previous exposure phase and that might be affected by other factors beyond the computation of regularities embedded in the input, typically the likelihood two syllables occurring together, a statistic known as transitional probability (TP). One solution to overcome these limitations is to assess SL as exposure to the stream unfolds using online techniques such as event-related potentials (ERP) that is highly sensitive to the time-course of the learning in the brain. Here we collected ERPs to examine the neurofunctional correlates of SL in preschool children with DLD, and chronological-age typical language development (TLD) controls who were exposed to an auditory stream in which eight three-syllable nonsense words, four of which presenting high-TPs and the other four low-TPs, to further analyze whether the ability of DLD and TLD children to extract-word-like units from the steam was modulated by words’ predictability. Moreover, to ascertain if the previous knowledge of the to-be-learned-regularities affected the neural responses to high- and low-TP words, children performed the auditory SL task, firstly, under implicit, and, subsequently, under explicit conditions. Although behavioral evidence of SL was not obtained in either group, the neural responses elicited during the exposure phases of the SL tasks differentiated children with DLD from children with TLD. Specifically, the results indicated that only children from the TDL group showed neural evidence of SL, particularly in the SL task performed under explicit conditions, firstly, for the low-TP, and, subsequently, for the high-TP ‘words’. Taken together, these findings support the view that children with DLD showed deficits in the extraction of the regularities embedded in the auditory input which might underlie the language difficulties.

Keywords: development language disorder, statistical learning, transitional probabilities, word segmentation

Procedia PDF Downloads 188

Authors: Yamina Boukari, Nashiru Billa, Andrew Morris, Stephen Doughty, Kevin Shakesheff

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Poly (lactic-co-glycolic) acid (PLGA) is a synthetic polymer that can be used in bone tissue engineering with the aim of creating a scaffold in order to support the growth of cells. The formation of microspheres from this polymer is an attractive strategy that would allow for the development of an injectable system, hence avoiding invasive surgical procedures. The aim of this study was to develop a microsphere delivery system for use as an injectable scaffold in bone tissue engineering and evaluate various formulation parameters on its properties. Porous and lysozyme-containing PLGA microspheres were prepared using the double emulsion solvent evaporation method from various molecular weights (MW). Scaffolds were formed by sintering to contain 1 -3mg of lysozyme per gram of scaffold. The mechanical and physical properties of the scaffolds were assessed along with the release of lysozyme, which was used as a model protein. The MW of PLGA was found to have an influence on microsphere size during fabrication, with increased MW leading to an increased microsphere diameter. An inversely proportional relationship was displayed between PLGA MW and mechanical strength of formed scaffolds across loadings for low, intermediate and high MW respectively. Lysozyme release from both microspheres and formed scaffolds showed an initial burst release phase, with both microspheres and scaffolds fabricated using high MW PLGA showing the lowest protein release. Following the initial burst phase, the profiles for each MW followed a similar slow release over 30 days. Overall, the results of this study demonstrate that lysozyme can be successfully incorporated into porous PLGA scaffolds and released over 30 days in vitro, and that varying the MW of the PLGA can be used as a method of altering the physical properties of the resulting scaffolds.

Keywords: bone, microspheres, PLGA, tissue engineering

Procedia PDF Downloads 425

Authors: Okpaneje Onyinye Theresa, Ugwu Laeticia Udodiri, Okereke Ngozi Agatha, Okoli Nonso Livinus

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This work is on the synthesis and study of the optical characterization of polyaniline/nickel sulphide nanocomposite. Polyaniline (PANI) and nickel sulphide (NiS) nanoparticles were synthesized by oxidative chemical polymerization and sol-gel method. The polyaniline nickel sulphide nanocomposites with various concentrations of NiS were synthesized by in-situ polymerization of aniline monomer. In each case, the nickel sulphide nanoparticles were uniformly dispersed in the aniline hydrochloride before the initiation of oxidative chemical polymerization using ammonium persulphate. The samples formed were subjected to optical characterization using an ultraviolet (UV)-visible light (VIS) spectrophotometer (model: 756S UV – VIS). Optical analysis of the synthesized nanoparticles and nanocomposites showed absorption of radiation within VIS regions. The Tauc model was used to obtain the optical band gap. Energy band gap values of PANI and NiS were found to be 2.50 eV and 1.95 eV, respectively. PANI/NiSnanocomposites has an energy band gap that decreased from 2.25 eV to 1.90 eV as the amount of NiS increased (from 0.5g to 2.0g). These optical results showed that these nanocomposites are potential materials to be considered in solar cells and optoelectronics devices. The structural analysis confirmed the formation of polyaniline and hexagonal nickel sulphide with an average crystallite size of 25.521 nm, while average crystallite sizes of PANI/NiSnanocomposites ranged from 19.458 nm to 25.108 nm. Average particle sizes obtained from the SEM images ranged from 23.24 nm to 51.88 nm. Compositional results confirmed the presence of desired elements that made up the nanoparticles and nanocomposites.

Keywords: polyaniline, nickel sulphide, polyaniline-nickel sulphide nanocomposite, optical characterization, structural analysis, morphological properties, compositional properties

Procedia PDF Downloads 116

Authors: Saeed Asiri, Yousuf Z. AL-Zahrani

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A new class of support structures, called periodic structures, is introduced in this paper as a viable means for isolating the vibration transmitted from the sea waves to offshore platform structures through its legs. A passive approach to reduce transmitted vibration generated by waves is presented. The approach utilizes the property of periodic structural components that creates stop and pass bands. The stop band regions can be tailored to correspond to regions of the frequency spectra that contain harmonics of the wave frequency, attenuating the response in those regions. A periodic structural component is comprised of a repeating array of cells, which are themselves an assembly of elements. The elements may have differing material properties as well as geometric variations. For the purpose of this research, only geometric and material variations are considered and each cell is assumed to be identical. A periodic leg is designed in order to reduce transmitted vibration of sea waves. The effectiveness of the periodicity on the vibration levels of platform will be demonstrated theoretically. The theory governing the operation of this class of periodic structures is introduced using the transfer matrix method. The unique filtering characteristics of periodic structures are demonstrated as functions of their design parameters for structures with geometrical and material discontinuities; and determine the propagation factor by using the spectral finite element analysis and the effectiveness of design on the leg structure by changing the ratio of step length and area interface between the materials is demonstrated in order to find the propagation factor and frequency response.

Keywords: vibrations, periodic structures, offshore, platforms, transfer matrix method

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Authors: S. K. M. Basha

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Nallamalas one of the centres of Plant Diversity (CPD) (WWF&IUCN,1995) is located in the central eastern Ghats between latitudes 15.20’-16.30’N and Longitude 78.30-80.10E in Andhra Pradesh, extended to an area of 7640 Sq.Km. No Comprehensive work available for RET Plants in the study area, therefore the objective of the present paper is to document the RET Medicinal Plants of Nallamalias and their uses by the local people of the area. In India, one of the major resources to know about the number of plant species and their medicinal values is the groups who are habituated in near and deep forests. The most common groups in south Indian forests are Yanadis and Yerukulas. These two groups of people are residing in the forest, which is located very far from the modern society, towns and cities. They are following traditional methods obtained from their forefathers in all respects, including medication. They are the only source to know many medicinal plants in the areas where they reside and are also important to record the medicinal properties of various plant species which are not reported. The new reports may help in drug industry in order to develop pharmaceutical herbal medicine for human health. In the present study, nearly 150 rare species have been found to be used for various ailments. Out of these 23 species are critically endangered, over 25 are vulnerable and around 22 comes under the category of near threatened. Some important species like Christella dentate, Careya arborea are used for curing cough and cold. Piper attnuatum, piper nigrum are used for curing skin disease. Ipomoea mauritiana is used against male impotency.Glycosmis cochinensis, Entada perseatha are used as contraceptives. The roots of Andrographis nallamalayana and Acrocephalus indicus are used for leucorrhoea. While the stem barks of Gyrocarpus americanus is given orally for spider bite. Piper hymenophyllum leaves mixed with turmeric and gingerly oil is used externally for mouth ulcers in cattle. Piper nigrum fruits are used for skin diseases. Vernonia anthelmentica seeds are used for indigestion. It was widely distributed in this hills. Due to over exploitation this species was in declined condition. Sterculia urens which is a sorce of gum for tribal, due to over exploitation this species declaimed in these hills. Hence, there is an urgent need to conserve the medicinal plants and prevent their exploitation and extinction with the help of tribals. There is a need to adopt sustainable utilization, cultivation and micro propagation techniques. Medicinal plants are as potent and effective today as they were thousands of years ago. They are natures wonderful gift to mankind and are involved in India as a very rich ancient heritage of traditional systems medicine i.e., ayurveda, siddha and unani. Unfortunately, these traditions have been largely eroded because of lack of support and recognition as well as rapid destruction of natural habitats which has led to shrinkage of medicinal plants therefore the conservation of medicinal plants and the revitalization of local health traditions has been taken up on priority basis.

Keywords: RET plants CPD, IUCN, nallamalas, yanadis, yerukulas

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Authors: Cristina Busuioc, Georgeta Voicu, Sorin-Ion Jinga

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The human bone presents in its dry form piezoelectric properties, which means that a mechanical stress results in electric polarization and an applied electric field causes strain. The immediate consequence was the revealing of piezoelectricity role in bone remodelling, as well as the integration of ceramic materials with piezoelectric behaviour in the composition of unitary or composite biomaterials. Thus, we prepared hydroxyapatite - collagen hybrid materials with barium titanate addition in order to achieve a better osseointegration. Barium titanate powder synthesized by a combined sol-gel-hydrothermal method, commercial hydroxyapatite and laboratory extracted collagen gel were employed as starting materials. Before the composites, fabrication, the powder with piezoelectric features was characterized in detail from the compositional, structural, morphological and electrical point of view. The next step was to elucidate the influence of barium titanate presence especially on the biological properties of the final materials. The biocompatibility of the hybrid supports without or with piezoelectric addition was investigated on mouse osteoblast cells through LDH cytotoxicity assay, LIVE/DEAD cell viability assay, and MTT cell proliferation assay. All results indicated that the analysed materials do not exert cytotoxic effects and present the ability to sustain cell survival and to promote their proliferation. In conclusion, barium titanate nanoparticles exhibit a good biocompatibility and osteoinductive properties, while the derived composite materials based on hydroxyapatite as oxide phase and collagen as polymeric phase can be successfully used for tissue engineering applications.

Keywords: barium titanate, hybrid composites, piezoelectricity, tissue engineering

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Authors: V. Marzal, J. C. Torres, B. Garcia-Camara, Manuel Cano-Garcia, Xabier Quintana, I. Perez Garcilopez, J. M. Sanchez-Pena

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At the present time, the use of nanostructures in complex media, like liquid crystals, is widely extended to manipulate their properties, either electrical or optical. In addition, these media can also be used to control the optical properties of the nanoparticles, for instance when they are resonant. In this work, the change on electrical properties of a liquid crystal cell by adding TiO₂ nanoparticles on one of the alignment layers has been analyzed. These nanoparticles, with a diameter of 100 nm and spherical shape, were deposited in one of the substrates (ITO + polyimide) by spin-coating in order to produce a homogeneous layer. These substrates were checked using an optical microscope (objective x100) to avoid potential agglomerates. The liquid crystal cell is then fabricated, using one of these substrates and another without nanoparticles, and filled with E7. The study of the electrical response was done through impedance measurements in a long range of frequencies (3 Hz- 6 MHz) and at ambient temperature. Different nanoparticle concentrations were considered, as well as pure E7 and an empty cell for comparison purposes. Results about the effective dielectric permittivity and conductivity are presented along with models of equivalent electric circuits and its physical interpretation. As a summary, it has been observed the clear influence of the presence of the nanoparticles, strongly modifying the electric response of the device. In particular, a variation of both the effective permittivity and the conductivity of the device have been observed. This result requires a deep analysis of the effect of these nanoparticles on the trapping of free ions in the device, allowing a controlled manipulation and frequency tuning of the electrical response of these devices.

Keywords: alignment layer, electrical behavior, liquid crystal, TiO₂ nanoparticles

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Authors: Thidathit Prachanukool, Chaiyaporn Yuksen, Welawat Tienpratarn, Sorravit Savatmongkorngul, Panvilai Tangkulpanich, Chetsadakon Jenpanitpong, Yuranan Phootothum, Malivan Phontabtim, Promphet Nuanprom

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Background: Ruptured appendicitis has a high morbidity and mortality and requires immediate surgery. The Alvarado Score is used as a tool to predict the risk of acute appendicitis, but there is no such score for predicting rupture. This study aimed to developed the prediction score to determine the likelihood of ruptured appendicitis in an Asian population. Methods: This study was diagnostic, retrospectively cross-sectional and exploratory model at the Emergency Medicine Department in Ramathibodi Hospital between March 2016 and March 2018. The inclusion criteria were age >15 years and an available pathology report after appendectomy. Clinical factors included gender, age>60 years, right lower quadrant pain, migratory pain, nausea and/or vomiting, diarrhea, anorexia, fever>37.3°C, rebound tenderness, guarding, white blood cell count, polymorphonuclear white blood cells (PMN)>75%, and the pain duration before presentation. The predictive model and prediction score for ruptured appendicitis was developed by multivariable logistic regression analysis. Result: During the study period, 480 patients met the inclusion criteria; of these, 77 (16%) had ruptured appendicitis. Five independent factors were predictive of rupture, age>60 years, fever>37.3°C, guarding, PMN>75%, and duration of pain>24 hours to presentation. A score > 6 increased the likelihood ratio of ruptured appendicitis by 3.88 times. Conclusion: Using the Ramathibodi Welawat Ruptured Appendicitis Score. (RAMA WeRA Score) developed in this study, a score of > 6 was associated with ruptured appendicitis.

Keywords: predictive model, risk score, ruptured appendicitis, emergency room

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Authors: Alli Smith Yemisi Rufina, Adanlawo Isaac Gbadura

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Liver disorders are one of the major problems of the world. Despite its frequent occurrence, high morbidity, and high mortality, its medical management is currently inadequate. This study was designed to evaluate the Hepatoprotective effect of saponin extract of the root of Garcinia kola on the integrity of the liver of paracetamol induced Wistar albino rats. Twenty-five male adult Wistar albino rats were divided into five (5) groups. Group I, was the Control group that received distilled water only, group II was the negative control that received 2 g/kg of paracetamol on the 13th day, and group III, IV, and V were pre-treated with 100, 200 and 400 mg/kg of the saponin extract before inducing the liver damage on the 13th day with 2 g/kg of paracetamol. Twenty-four hours after administration, the rats were sacrificed, and blood samples were collected. The serum Alanine Transaminase (ALT), Aspartate Transaminase (AST), Alkaline Phosphatase (ALP) activities, Bilirubin and Conjugated Bilirubin, Glucose and Protein concentrations were evaluated. The liver was fixed immediately in Formalin and was processed and stained with Haematoxylin and Eosin (H&E). Administration of saponin extract from the root of Garcinia kola significantly decreased paracetamol induced elevated enzymes in the test group. Also, histological observations showed that saponin extract of the root of Garcinia kola exhibited a significant liver protection against the toxicant as evident by the cells trying to return to normal. Saponin extract from the root of Garcinia kola indicated a protection of the structural integrity of the hepatocytic cell membrane and regeneration of the damaged liver.

Keywords: hepatoprotective, liver damage, Garcinia kola, saponin, paracetamol

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Authors: Nalan Kaya, Elif Erdem, Mehmet Ali Kisacam, Gonca Ozan, Enver Ozan

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Tobacco smokers continuously inhale thousands of carcinogens and free radicals. It is estimated that about 1017 oxidant molecules are present in each puff of tobacco smoke. It is known that smoking has adverse effects on the structure and functions of the liver. Ellagic acid (EA) has antioxidant, antiapoptotic, anticarcinogenic, antibacterial and antiinflammatory effects. The aim of our study was to investigate the possible protective effect of ellagic acid against tobacco smoke-mediated oxidative stress in the rat liver. Twenty-four male adult (8 weeks old) Spraque-Dawley rats were divided randomly into 4 equal groups: group I (control), group II (tobacco smoke), group III (tobacco smoke + corn oil) and group IV (tobacco smoke + ellagic acid). The rats in group II, III and IV, were exposed to tobacco smoke 1 hour twice a day for 12 weeks. In addition to tobacco smoke exposure, 12 mg/kg ellagic acid (dissolved in corn oil), was applied to the rats in group IV by oral gavage. An equal amount of corn oil used in solving ellagic acid was applied to the rats by oral gavage in group III. At the end of the experimental period, rats were decapitated, and liver tissues were removed. Histological and biochemical analyzes were performed. Sinusoidal dilatation, inflammatory cell infiltration in portal area, increased Kuppfer cells were examined in tobacco smoke group and tobacco smoke+ corn oil groups. The results, observed in tobacco smoke and tobacco smoke+corn oil groups, were found significantly decreased in tobacco smoke+EA group. Group-II and group-III MDA levels were significantly higher, and GSH activities were not different than group-I. Compared to group-II, group-IV MDA level was decreased, and GSH activities was increased significantly. The results indicate that ellagic acid could protect the liver tissue from the tobacco smoke harmful effects.

Keywords: ellagic acid, liver, rat, tobacco smoke

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Authors: Alina Goldberg Cavalleri, Sara Franco Ortega, Nawaporn Onkokesung, Richard Dale, Melissa Brazier-Hicks, Robert Edwards

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Non-target site based resistance (NTSR) to herbicides in weeds is a polygenic trait associated with the upregulation of proteins involved in xenobiotic detoxification and translocation we have termed the xenome. Among the xenome proteins, ABC transporters play a key role in enhancing herbicide metabolism by effluxing conjugated xenobiotics from the cytoplasm into the vacuole. The importance of ABC transporters is emphasized by the fact that they often contribute to multidrug resistance in human cells and antibiotic resistance in bacteria. They also play a key role in insecticide resistance in major vectors of human diseases and crop pests. By surveying available databases, transcripts encoding ABCs have been identified as being enhanced in populations exhibiting NTSR in several weed species. Based on a transcriptomics data in black grass (Alopecurus myosuroides, Am), we have identified three proteins from the ABC-C subfamily that are upregulated in NTSR populations. ABC-C transporters are poorly characterized proteins in plants, but in Arabidopsis localize to the vacuolar membrane and have functional roles in transporting glutathionylated (GSH)-xenobiotic conjugates. We found that the up-regulation of AmABCs strongly correlates with the up-regulation of a glutathione transferase termed AmGSTU2, which can conjugate GSH to herbicides. The expression profile of the ABC transcripts was profiled in populations of black grass showing different degree of resistance to herbicides. This, together with a phylogenetic analysis, revealed that AmABCs cluster in different groups which might indicate different substrate and roles in the herbicide resistance phenotype in the different populations

Keywords: black grass, herbicide, resistance, transporters

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Authors: Mohammad K. Parvez, Ahmed H. Arbab, Mohammed S. Al-Dosari, Adnan J. Al-Rehaily

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We investigated ex vivo and in vivo antioxidative and hepatoprotective effect of Aerva javanica. Total ethanol extract of A. javanica aerial parts was prepared, and tested on DCFH-toxicated HepG2 cell in CCl4-injured Wistar rats. MTT-assay was used to determine cell viability, and serum biochemical markers of liver injury as well as histopathology were performed. In vitro DPPH and β-carotene free-radical scavenging assay and phytochemical screening of the extract was done. Furthermore, A. javanica total extract was standardized and validated by HPTLC method. While DCFH-injured cells were recovered to about 56.7% by 100 microg/ml of the extract, a 200 microg/ml dose resulted in hepatocytes recovery by about 90.2%. Oral administration of the extract (100 and 200 mg/kg.bw/day) significantly normalized the serum SGOT, SGPT, GGT, ALP, bilirubin, cholesterol, HDL, LDL, VLDL, TG and MDA levels, including tissue NP-SH and TP in CCl4-injured rats. In addition, the histopathology of dissected liver also revealed that A. javanica cured the tissue lesion compared to reference drug, Silymarin. In vitro assays revealed strong free-radical scavenging ability of the extract and presence of alkaloids, flavonoids, tannins, sterols and saponins where Rutin, a well-known antioxidant flavonoid was identified. Our finding therefore, suggests the therapeutic potential of A. javanica in various liver diseases. However, isolation of the active principles, their mechanism of action and other therapeutic contribution remain to be addressed.

Keywords: Aerva javanica, antioxidant, hepatoprotection, rutin

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Authors: Szilvia Várallyay, Béla Kovács, Éva Bódi, Farzeneh Garousi, Szilvia Veres

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Arsenic (As) is a naturally occurring substance that can be present in soil, water and air. Vegetables, fruits, and other plants that grow in contaminated soils which are able to accumulate arsenic. Arsenic when presents in plant cells, has various negative physiological effects and when presents in soil will be inorgaic form, namely arsenite (As(III)) and arsenate (As(V)). These two forms of arsenic disrupt plant metabolism by inhibiting its growth and these arsenic species has negative effect on nutrient uptake. A rhizobox experiment was conducted to investigate the effect of arsenite and arsenate on root growth of sunflower seedlings. Sunflower plants were grown in climatic room under irradiance of 300 µmol m-2 s-1, 16-h day and 8-h night photoperiod, day/night temperature of 25/20°C and relative humidity of 65-75%. We applied arsenic in form of arsenite (NaAsO2) and arsenate (KH2AsO4), respectively. The applied arsenic treatments was 0, 10, 30, 90 mg.kg-1. After disinfection, seeds were germinated between moist filter papers. Seedlings with 2-3 cm coleoptils were placed into rhizoboxes. In the rhizoboxes the growing and daily growing rhythm of roots of sunflower can be followed up, moreover possible phytotoxic symptoms of roots resulting from increasing arsenic can be seen. Weights of rhizoboxes were measured daily and also evaporated water added each day. The lengths of roots were measured daily until seedlings roots get at the end of the rhizoboxes. Negative correlation was observed between the higher concentration of arsenic in the soil and the growth of sunflower seedlings roots. The effect of arsenic toxicity was more considerable in 90 mg.kg-1 arsenic treatment than lower concentration. The same arsenite concentration causes slower growth in case of sunflower plant than the same arsenate concentration produced.

Keywords: arsenic, rhizobox experiment, sunflower, root growth

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Authors: W. S. Barber, S. L. King

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This paper is a qualitative case study analysis of the development of a fully online learning community of graduate students through arts-based community building activities. With increasing numbers and types of online learning spaces, it is incumbent upon educators to continue to push the edge of what best practices look like in digital learning environments. In digital learning spaces, instructors can no longer be seen as purveyors of content knowledge to be examined at the end of a set course by a final test or exam. The rapid and fluid dissemination of information via Web 3.0 demands that we reshape our approach to teaching and learning, from one that is content-focused to one that is process-driven. Rather than having instructors as formal leaders, today’s digital learning environments require us to share expertise, as it is the collective experiences and knowledge of all students together with the instructors that help to create a very different kind of learning community. This paper focuses on innovations pursued in a 36 hour 12 week graduate course in higher education entitled “Critical and Reflective Practice”. The authors chronicle their journey to developing a fully online learning community (FOLC) by emphasizing the elements of social, cognitive, emotional and digital spaces that form a moving interplay through the community. In this way, students embrace anywhere anytime learning and often take the learning, as well as the relationships they build and skills they acquire, beyond the digital class into real world situations. We argue that in order to increase student online engagement, pedagogical approaches need to stem from two primary elements, both creativity and critical reflection, that are essential pillars upon which instructors can co-design learning environments with students. The theoretical framework for the paper is based on the interaction and interdependence of Creativity, Intuition, Critical Reflection, Social Constructivism and FOLCs. By leveraging students’ embedded familiarity with a wide variety of technologies, this case study of a graduate level course on critical reflection in education, examines how relationships, quality of work produced, and student engagement can improve by using creative and imaginative pedagogical strategies. The authors examine their professional pedagogical strategies through the lens that the teacher acts as facilitator, guide and co-designer. In a world where students can easily search for and organize information as self-directed processes, creativity and connection can at times be lost in the digitized course environment. The paper concludes by posing further questions as to how institutions of higher education may be challenged to restructure their credit granting courses into more flexible modules, and how students need to be considered an important part of assessment and evaluation strategies. By introducing creativity and critical reflection as central features of the digital learning spaces, notions of best practices in digital teaching and learning emerge.

Keywords: online, pedagogy, learning, communities

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Authors: Majid Ali, Xinfang Jin, Victor Eniola, Henning Hoene

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The performance of proton exchange membrane (PEM) fuel cells is sensitive to several factors, including power fluctuations, hydrogen utilization, and the quality orientation of the fuel cell stack. In this study, we investigate the impact of these factors on the performance of a PEM fuel cell. We start by analyzing the power fluctuations that are typical in renewable energy systems and their effects on the 50 Watt fuel cell's performance. Next, we examine the hydrogen utilization rate (0-1000 mL/min) and its impact on the cell's efficiency and durability. Finally, we investigate the quality orientation (three different positions) of the fuel cell stack, which can significantly affect the cell's lifetime and overall performance. The basis of our analysis is the utilization of experimental results, which have been further validated by comparing them with simulations and manufacturer results. Our results indicate that power fluctuations can cause significant variations in the fuel cell's voltage and current, leading to a reduction in its performance. Moreover, we show that increasing the hydrogen utilization rate beyond a certain threshold can lead to a decrease in the fuel cell's efficiency. Finally, our analysis demonstrates that the orientation of the fuel cell stack can affect its performance and lifetime due to non-uniform distribution of reactants and products. In summary, our study highlights the importance of considering power fluctuations, hydrogen utilization, and quality orientation in designing and optimizing PEM fuel cell systems. The findings of this study can be useful for researchers and engineers working on the development of fuel cell systems for various applications, including transportation, stationary power generation, and portable devices.

Keywords: fuel cell, proton exchange membrane, renewable energy, power fluctuation, experimental

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Authors: David Dolbow, Daniel Credeur, Mujtaba Rahimi, Dobrivoje Stokic, Jennifer Lemacks, Andrew Courtner

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Introduction: Obesity is at epidemic proportions in the spinal cord injury (SCI) population (66-75%), as individuals who suffer from paralysis undergo a dramatic decrease in muscle mass and a dramatic increase in adipose deposition. Obesity is a major public health concern which includes a doubling of the risk of heart disease, stroke and type II diabetes mellitus. It has been demonstrated that physical activity, and especially HIIT, can promote a healthy body composition and decrease the risk cardiometabolic disease in the able-bodied population. However, SCI typically limits voluntary exercise to the arms, but a high prevalence of shoulder pain in persons with chronic SCI (60-90%) can cause increased arm exercise to be problematic. Functional electrical stimulation (FES) cycling has proven to be a safe and effective way to exercise paralyzed leg muscles in clinical and home settings, saving the often overworked arms. Yet, HIIT-FES cycling had not been investigated prior to the current study. The purpose of this study was to investigate the body composition changes with combined HIIT-FES cycling and nutritional counseling on individuals with SCI. Design: A matched (level of injury, time since injury, body mass index) and controlled trail. Setting: University exercise performance laboratory. Subjects: Ten individuals with chronic SCI (C5-T9) ASIA impairment classification (A & B) were divided into the treatment group (n=5) for 30 minutes of HIIT-FES cycling 3 times per week for 8 weeks and nutritional counseling over the phone for 30 minutes once per week for 8 weeks and the control group (n=5) who received nutritional counseling only. Results: There was a statistically significant difference between the HIIT-FES group and the control group in mean body fat percentage change (-1.14 to +0.24) respectively, p = .030). There was also a statistically significant difference between the HIIT-FES and control groups in mean change in legs lean mass (+0.78 kg to -1.5 kg) respectively, p = 0.004. There was a nominal decrease in weight, BMI, total fat mass and a nominal increase in total lean mass for the HIIT-FES group over the control group. However, these changes were not found to be statistically significant. Additionally, there was a nominal decrease in the mean blood glucose levels for both groups 101.8 to 97.8 mg/dl for the HIIT-FES group and 94.6 to 93 mg/dl for the Nutrition only group, however, neither were found to be statistically significant. Conclusion: HIIT-FES cycling combined with nutritional counseling can provide healthful body composition changes including decreased body fat percentage in just 8 weeks. Future study recommendations include a greater number of participants, a primer electrical stimulation exercise program to better ready participants for HIIT-FES cycling and a greater volume of training above 30 minutes, 3 times per week for 8 weeks.

Keywords: body composition, functional electrical stimulation cycling, high-intensity interval training, spinal cord injury

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Authors: Faezah Shekh Abdullah, Mohd. Azizuddin Mohd. Yussof, Komathy Thiagarajan, Hasnoorina Husin, Noor Azreena Abd Aziz

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Polycystic ovary syndrome has been associated with multiple disorders such as endocrine disorder, metabolic syndrome, infertility, and endometrial cancer. Women with polycystic ovary syndrome (PCOS) are anticipated to develop three times more chances for endometrial cancer than women without PCOS. This study, therefore, was conducted to determine the association between polycystic ovary syndrome and endometrial cancer and to determine the cervical cytology features of PCOS. Patients attending the Subfertility Clinic of the National Population and Family Development Board were recruited and examined physically by medical practitioners. They were categorized into two groups; i) the PCOS group if they met Rotterdam Criteria 2004 and ii) the control group if they did not meet Rotterdam Criteria 2004. Cervical sampling was done on all patients via the Liquid-Based Cytology (LBC) method in the pre-and post-subfertility treatment. A total of 167 patients participated in the study, of which 79 belonged to the PCOS group and 88 to the control group. The findings showed no cervical and endometrial cancer cases in both groups. The Liquid-Based Cytology results in the PCOS group displayed more cases with cellular changes, i.e., benign inflammation, atrophic smear and Candida sp. infection. To conclude, no association was found between polycystic ovary syndrome and endometrial cancer. A more holistic study with a higher number of participants can further determine the association between endometrial cancer and PCOS. Furthermore, a longer duration between LBC pre- and post-subfertility treatment should be implied to observe changes in the cervical cells.

Keywords: endometrial cancer, liquid-based cytology, PCOS, polycystic ovary syndrome

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Authors: Ines Kovacic, Dijana Pavicic-Hamer, Petra Buric, Maja Levak Zorinc, Daniel M. Lyons

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Silver nanoparticles (AgNPs), owing to their unique physical and chemical properties, have become one of the most widely used nanoparticles in consumer products. Despite the increased use of AgNPs in science and industry over the past twenty years, only relatively recently has concern been raised over their entering brackish and marine environments. However, data on their potential impact on marine organisms, especially invertebrates are very limited. This study aimed to examine the effects of 60 nm AgNPs (10, 100, 500 and 1000 µg/l) and silver ions (100, 1000 µg/l) on the Mediterranean green crab Carcinus aestuarii Nardo, 1847. The crab mortality was assessed during seven days of exposure. After the exposure, total haemocytes (THC) and differential haemocytes number (DHC) were counted (immune response), in addition to histological examination of gills stained with haematoxylin and eosin. The effect of AgNPs and silver ions resulted in a dose dependent mortality and destruction of gills epithelium with haemocytes infiltration in the gills lacuna. Total haemocyte count was greater with increasing concentration of AgNPs, at concentrations from 10 to 500 µg/l. Hyalinocytes were the most common immunological cells noted in the crab hemolymph, while granulocytes and semigranulocytes were suppressed with increasing concentration of AgNPs (500 and 1000 µg/l). Thus, as crabs are filter feeders, they are susceptible to uptake of AgNPs by direct accumulation in gills mucus or indirectly via circulation of haemocytes in their open vascular system. Results of this study on crabs add to knowledge of the effects of AgNPs in the marine environment.

Keywords: crab, immune response, histological alteration, silver nanoparticles

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Authors: Mathula Thangarajh

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Duchenne muscular dystrophy (DMD) is a severe form of X-linked muscular dystrophy caused by mutations in the dystrophin gene resulting in progressive skeletal muscle weakness. Boys with DMD also have significant cognitive disabilities. The intelligence quotient of boys with DMD, compared to peers, is approximately one standard deviation below average. Detailed neuropsychological testing has demonstrated that boys with DMD have a global developmental impairment, with verbal memory and visuospatial skills most significantly affected. Furthermore, the total brain volume and gray matter volume are lower in children with DMD compared to age-matched controls. These results are suggestive of a significant structural and functional compromise to the developing brain as a result of absent dystrophin protein expression. There is also some genetic evidence to suggest that mutations in the 3’ end of the DMD gene are associated with more severe neurocognitive problems. Our working hypothesis is that (i) boys with DMD do not make gains in neurodevelopmental skills compared to typically developing children and (ii) women carriers of DMD mutations may have subclinical cognitive deficits. We also hypothesize that there may be an intergenerational vulnerability of cognition, with boys of DMD-carrier mothers being more affected cognitively than boys of non-DMD-carrier mothers. The objectives of this study are: 1. Assess the neurodevelopment in boys with DMD at 4-time points and perform baseline neuroradiological assessment, 2. Assess cognition in biological mothers of DMD participants at baseline, 3. Assess possible correlation between DMD mutation and cognitive measures. This study also explores functional brain abnormalities in people with DMD by exploring how regional and global connectivity of the brain underlies executive function deficits in DMD. Such research can contribute to a better holistic understanding of the cognition alterations due to DMD and could potentially allow clinicians to create better-tailored treatment plans for the DMD population. There are four study visits for each participant (baseline, 2-4 weeks, 1 year, 18 months). At each visit, the participant completes the NIH Toolbox Cognition Battery, a validated psychometric measure that is recommended by NIH Common Data Elements for use in DMD. Visits 1, 3, and 4 also involve the administration of the BRIEF-2, ABAS-3, PROMIS/NeuroQoL, PedsQL Neuromuscular module 3.0, Draw a Clock Test, and an optional fMRI scan with the N-back matching task. We expect to enroll 52 children with DMD, 52 mothers of children with DMD, and 30 healthy control boys. This study began in 2020 during the height of the COVID-19 pandemic. Due to this, there were subsequent delays in recruitment because of travel restrictions. However, we have persevered and continued to recruit new participants for the study. We partnered with the Muscular Dystrophy Association (MDA) and helped advertise the study to interested families. Since then, we have had families from across the country contact us about their interest in the study. We plan to continue to enroll a diverse population of DMD participants to contribute toward a better understanding of Duchenne Muscular Dystrophy.

Keywords: neurology, Duchenne muscular dystrophy, muscular dystrophy, cognition, neurodevelopment, x-linked disorder, DMD, DMD gene

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Authors: Megan L. Srinivas

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Individuals with underlying rheumatologic diseases such as dermatomyositis may not adequately respond to tuberculin (PPD) skin tests, creating false negative results. These illnesses are frequently treated with immunosuppressive therapy making proper identification of TB infection imperative. A 59-year-old Filipino man was diagnosed with dermatomyositis on the basis of rash, electromyography, and muscle biopsy. He was initially treated with IVIG infusions and transitioned to oral prednisone and mycophenolate. The patient’s symptoms improved on this regimen. Six months after starting mycophenolate, the patient began having fevers, night sweats, and productive cough without hemoptysis. He moved from the Philippines 5 years prior to dermatomyositis diagnosis, denied sick contacts, and was PPD negative both at immigration and immediately prior to starting mycophenolate treatment. A third PPD was negative following the onset of these new symptoms. He was treated for community-acquired pneumonia, but symptoms worsened over 10 days and he developed watery diarrhea and a growing non-tender, non-mobile mass on the left side of his neck. A chest x-ray demonstrated a cavitary lesion in right upper lobe suspicious for TB that had not been present one month earlier. Chest CT corroborated this finding also exhibiting necrotic hilar and paratracheal lymphadenopathy. Neck CT demonstrated the left-sided mass as cervical chain lymphadenopathy. Expectorated sputum and stool samples contained acid-fast bacilli (AFB), cultures showing TB bacteria. Fine-needle biopsy of the neck mass (scrofula) also exhibited AFB. An MRI brain showed nodular enhancement suspected to be a tuberculoma. Mycophenolate was discontinued and dermatomyositis treatment was switched to oral prednisone with a 3-day course of IVIG. The patient’s infection showed sensitivity to standard RIPE (rifampin, isoniazid, pyrazinamide, and ethambutol) treatment. Within a week of starting RIPE, the patient’s diarrhea subsided, scrofula diminished, and symptoms significantly improved. By the end of treatment week 3, the patient’s sputum no longer contained AFB; he was removed from isolation, and was discharged to continue RIPE at home. He was discharged on oral prednisone, which effectively addressed his dermatomyositis. This case illustrates the unreliability of PPD tests in patients with long-term inflammatory diseases such as dermatomyositis. Other immunosuppressive therapies (adalimumab, etanercept, and infliximab) have been affiliated with conversion of latent TB to disseminated TB. Mycophenolate is another immunosuppressive agent with similar mechanistic properties. Thus, it is imperative that patients with long-term inflammatory diseases and high-risk TB factors initiating immunosuppressive therapy receive a TB blood test (such as a quantiferon gold assay) prior to the initiation of therapy to ensure that latent TB is unmasked before it can evolve into a disseminated form of the disease.

Keywords: dermatomyositis, immunosuppressant medications, mycophenolate, disseminated tuberculosis

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Authors: Lian Zeng

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Double-Spear 1-H2-1 (DS1-H2-1) is an oncolytic virus and an innovative biological drug candidate. The chemical composition of the drug product is a live attenuated West Nile virus (WNV) containing the human T cell costimulator (CD86) gene. After intratumoral injection, the virus can rapidly self-replicate in the injected site and lyse/kill the tumor by repeated infection among tumor cells. We also established xenograft tumor models in mice to evaluate the drug candidate's efficacy on those tumors. The results from preclinical studies on transplanted tumors in immunodeficient mice showed that DS1-H2-1 had significant oncolytic effects on human-origin cancers: it completely (100%) shrieked human glioma; limited human neuroblastoma growth reached as high as 95% growth inhibition rate (%TGITW). The safety data of preclinical animal experiments confirmed that DS1-H2-1 is safe as a biological drug for clinical use. In the preclinical drug efficacy experiment, virus-drug administration with different doses did not show abnormal signs and disease symptoms in more than 300 tested mice, and no side effects or death occurred through various administration routes. Intravenous administration did not cause acute infectious disease or other side effects. However, the replication capacity of the virus in tumor tissue via intravenous administration is only 1% of that of direct intratumoral administration. The direct intratumoral administration of DS1-H2-1 had a higher rate of viral replication. Therefore, choosing direct intratumoral injection can ensure both efficacy and safety.

Keywords: oncolytic virus, WNV-CD86, immunotherapy drugs, glioma, neuroblastoma

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